The topic of colorectal cancer screening is discussed with special emphasis on its history and improvement of its methodology. The author’s own results are evaluated in terms of international data published in literature in order to put forward his proposals for a new strategy. The devastating power and endemic character of colorectal cancers is stressed and the development of screening activities is recommended to accomplish within the frame of the complex health service.
For most chronic myeloid leukaemia patients the option of a potentially curative allogeneic stem cell transplantation is not available because of age or lack of donor. Alternative therapy with interferon-alpha appears to prolong survival but is probably not curative. The aim of the study is to analyse the clinical results of the first Hungarian autologous transplantations in CML. METHODS: Seven patients were treated with ICE-based regimen plus G-CSF with the aim of mobilising and collecting Ph-negative peripheral stem cells in the setting of autologous transplant program. Five patients had CML in first chronic phase and two in accelerated phase. All patients have been previously treated with interferon-alpha. RESULTS: Median value and ranges for harvested mononuclear cells, CD34<sup>+</sup> cells and CFU-GM were: 5.65x10<sup>8</sup>/kg (2.61-11.38), 1.48x10<sup>6</sup>/kg (0.216-3.5) and 3.43x10<sup>4</sup>/kg (0.243-11.6), respectively. Four out of seven autologous grafts have been transplanted. Busulfan conditioning was used in one case and TBI/Cy conditioning in three patients. All patients are alive and well post-transplant being on interferon-alpha therapy. CONCLUSIONS: Based on the clinical advantages of autologous transplantation including long-term chronic phase, achievement of second chronic phase and improved response to interferon-alpha therapy, the procedure can offer an alternative treatment in CML in lack of HLA-identical donor.
Chimerism is an exceptional immunogenetic state, characterized by the survival and collaboration of cell populations originated from two different individuals. The prerequisites to induce chimerism are immunosuppression, myeloablation or severe immunodeficiency of the recipients on one side and donor originated immuno-hematopoietic cells in the graft on the other. Special immunogenetic conditions to establish chimerism are combined with bone marrow transplantation, transfusion and various kinds of solid organ grafting. There are various methods to detect the type of chimera state depending on the immunogenetic differences between the donor and recipient. The chimera state seems to be one of the leading factors to influence the course of the post-transplant period, the frequency and severity of graft-versus-host disease (GVHD), and the rate of relapse. However, the most important contribution of the chimeric state is the development of graft versus leukemia (GVL) effect. A new conditioning protocol (DBM/Ara-C/Cy) for allogeneic BMT in CML patients and its consequence on chimera state and GVL effect is demonstrated.
Multiple myeloma (MM) is a haematological malignancy characterised by the clonal expansion of malignant plasma cells within the bone marrow. It accounts for 10% of all haematological malignant diseases and 1% of all malignancies. The median age of patients at the time of the diagnosis is 70 years. The characteristic clinical features of MM are bone marrow failure, susceptibility to infections, bone pain, pathological bone fractures, hypercalcaemia, and renal failure. Though MM is currently incurable, the important progress in chemotherapy has resulted in an improvement in survival from a median of 7 months in the 1950-ies to about 3 years today. Advances in the diagnosis and in supportive treatment of infections, hypercalcaemia, and renal failure also contributed to the prolongation of survival. For decades, the gold standard of treatment had been oral melphalan alone or in combination with prednisolone. Combination chemotherapy has not improved overall survival (OS), but these regimens have led to the prolongation of event-free survival (EFS) and also to a better quality of life. High-dose chemotherapy with haemopoietic stem cell rescue resulted in a great improvement in EFS as well as OS. For those very few who have an HLA-compatible donor and are under 55, allogeneic bone marrow transplantation offers the best hope of survival but comes at a greatly increased risk of toxicity. There are conflicting data in the literature concerning the role of interferon-alpha; it seems to be able to prolong the duration of the plateau phase. Current treatment is moving towards an approach using sequential therapy. This involves induction therapy proceeding to high-dose chemotherapy with some form of stem-cell rescue. Bisphosphonates reduce hypercalcaemia, bone pain and can inhibit bone destruction. They also possess a direct antitumor activity. The better understanding of the pathomechanism of the disease gives the opportunity of the application of new therapeutic modalities such as antagonising the effect of interleukin-6 (IL-6), or idiotypic vaccination.
The European Society of Pathology and the Society for Hematopathology have developed a new World Health Organization (WHO) classification of hematological malignancies. The classification is based on the principle that the classification is a list of entities defined by the combination of morphology, immunophenotype, genetic and clinical features. The WHO classification is a new basis of communications between pathologist and oncologist which will help to understand and treat hematological malignancies
The mucosa-associated lymphoid tissue (MALT) lymphoma is a very indolent disease. Its most common site is the stomach. The lymphoma begins as a reactive lymphocyte accumulation mostly due to an infection of Helicobacter pylori (HP). Through repeated mutations this tissue is transformed into the characteristic MALT lymphoma. At the time of the diagnosis the lymphoma is usually localised, but in one third of the patients the disease has already been disseminated. There are not any commonly accepted guidelines of therapy concerning this primary gastric MALT lymphoma, but certain general tendencies have already been defined. In the early disease the aim of the treatment is curative with the preservation of the stomach as much as possible. In a considerable number of cases, when the surface of the stomach is affected by HP, one can achieve histological and molecular biologic remission after eliminating the bacteria. However, there is no such therapeutic consequence to be expected in case of a deeply invasive tumour. The optimal treatment of patients of this group as well as those whose disease is resistant to HP eradication treatment together with those who are HP negative is radiotherapy or surgery with chemotherapy. In this latter case quality of life becomes worse. In an advanced case cure is impossible and chemotherapy is the most effective to ease the patient’s state.
The authors analyze the progress achieved in the treatment of low-grade as well as of high-grade non-Hodgkin’s lymphomas. The challenging task in the treatment of low-grade or indolent lymphomas still is to decide whether watchful waiting is sufficient or whether chemotherapy is necessary and how aggressive this treatment should be. Among the new chemotherapeutic agents the role of purine analogues should be emphasized, fludarabin is especially important in the treatment of chronic lymphocytic leukemia and follicular lymphoma, while pentostatin and cladribine have revolutionized the treatment of hairy cell leukemia. Treatment with monoclonal antibodies, radioimmunoconjugates as well as autologous or allogeneic stem cell transplantation are potential new therapeutic options in the treatment of low-grade non-Hodgkin’s lymphomas. In the case of aggressive non-Hodgkin’s lymphomas risk-adapted strategies help the choice between standard or more intensive treatment options. In patients with relapsed high-grade lymphomas stem cell transplantation is indicated. In patients with marginal zone lymphoma the combination of hyperCVAD protocol + stem cell transplantation greatly improves prognosis.
As the Human Genome Project hurtles towards completion, DNA microarray technology offers the potential to open wide new windows into the study of genome complexity. DNA chips can be used for many different purposes, most prominently to measure levels of gene expression (messenger RNA abundance) for tens of thousands of genes simultaneously. But how much of this data is useful and is some superfluous? Can array data be used to identify a handful of critical genes that will lead to a more detailed taxonomy of haematological malignancies and can this or similar array data be used to predict clinical outcome? It is still too early to predict what the ultimate impact of DNA chips will be on our understanding of cancer biology. There are many critically important questions about this new field that are yet unaddressed. By the publication of this article, it is hoped that the technology of DNA chips will be opened up and demystified, and that additional opportunities for creative exploration will be catalysed.
Syndecans, transmembrane heparan sulfate proteoglycans, play an important role in cell-cell and cell-matrix interactions, as receptors/co-receptors of matrix elements, cytokines, growth factors. These functions are partly non-specific and due to the heparan sulfate chains attached to the ectodomain, and partly specific related to the transmembrane and cytoplasmic domains of the core protein. In hemopoietic cells syndecan-1 is expressed in certain B cells, in pre-B cells and plasma cells. In lymphoproliferative diseases this normal syndecan-1 expression of plasma cells is retained in myelomas/plasmocytomas, other lymphoplasmocytic NHL subtypes and primary effusional lymphomas. Syndecan-1 expression is probably gained in B-CLL, and lost in other NHLs of pre- or post-follicular origin. These results suggest that the expression of syndecan is essential for some NHLs, probably ensuring the required connections to the microenvironment. From a diagnostic point of view, syndecan-1 is a very useful phenotypic marker to identify cells with plasmocytic differentiation. The importance of syndecan expression in CLL and Hodgkin-lymphoma still requires further studies.
Two metastasis associated proteins, CD44v6 and NM23-H1, are expressed by normal lymphoid cells, the former serving as activation marker and the later as a constitutive protein. CD44v6 is considered as a marker of poor prognosis of various hematological cancers but its expression was not demonstrated in childhood acute lymphoblastic leukemia (ALL). On the other hand, NM23-H1 is considered as a differentiation inhibitory factor in various hematological cancers and as a marker of poor prognosis. Therefore we have analyzed the expression of CD44v6 and NM23-H1 in bone marrow of sixteen pediatric ALL patients using immunocytochemistry. For the first time, we have demonstrated the expression of CD44v6 protein epitopes on leukemic cells in a proportion of ALL cases (6/16), primarily in the medium/high risk group (except one case), suggesting a possible association to an unfavorable outcome. On the other hand, NM23-H1 protein expression was maintained in leukemic cells in 50% of both low and medium/high risk ALL cases. The majority of the pediatric ALL cases expressed only one of the metastasis associated proteins (10/16). This feature is highly similar to the observations made in several adult solid cancers. The potential of CD44v6 expression in leukemic cells as prognosticator in pediatric ALL has to be evaluated in a larger clinical trial.
The morphin-analogue, Durogesic, has robust analgetic effect without repeated side-effects and is suitable for special applications providing it as the first choice for therapy of cancer pain and as an acceptable alternative for CR morphin. Clinical studies not only provided evidences for the pharmacological effectivity of Durogesic but suggested that the quality of life of cancer patients improved significantly as well.
In evaluating the health state of the population one of the most reliable parameter is mortality. The development of statistical and spatial analytical methods gave a tool for evaluating mortality and morbidity in small areas. GIS mapping helps in the assessment of health state of small areas, to investigate causal relationship and create plans of intervention. Within the frames of the National Environmental Health Action Programme (NEHAP, 1996) a spatial statistical information system was elaborated. By the help of this system, mortality from cancer of the lip, oral cavity and pharynx (ICD-X.: C00-C14) was analysed for 1986-1997 and morbidity for 1997-1999 by computing standardised mortality and morbidity ratio. Regions with unfavourable mortality and morbidity were defined, statistical significance was tested. After age and gender stratification, a cluster analysis was also carried out. An international comparison of mortality was done as well. According to our data, mortality - most frequent in both sexes according to the international comparison - as well as morbidity showed a typical spatial distribution. An excess in mortality and morbidity is observable in the central part of the country, as well as in the Northern part and in traditional wine producing areas. The spatial accumulation of mortality is very similar to that of mortality from chronic liver diseases (ICD-X.: K70). In the primary prevention of oral cancer smoking cessation and the decrease of alcohol consumption is of great importance. Screening activity of GPs and dental doctors is of major importance in secondary prevention.
Animal experiments, in vitro studies of mechanisms, biological plausibility and massive epidemiological evidence prove that tobacco – smoked and unsmoked – is the major cause of oral cancer in the world. In Hungary today tobacco is mostly smoked in cigarettes, the smoking prevalence being amongst the highest in Europe: it is no surprise that Hungary has the highest rate of oral cancer in the world today. Tobacco use, however, synergises with heavy alcohol use in a dose dependent manner, the effect being supermultiplicative: most of the rising incidence of oral cancer in Europe is probably due to rising alcohol consumption in recent decades in the presence of continuing high levels of tobacco use. Smaller roles can be ascribed to inherited predisposition, environmental agents, poor diet, infections with viruses and fungi and poor oral hygiene/oral health care. The approach to primary prevention is thus clear, and must emphasise tobacco avoidance and sensible use of alcohol, together with good nutrition and dental care.
Tobacco represents the single most preventable cause of disease and death in the world today. Of 260 million male deaths in the developed world between 1950 and 2000, it is estimated that 50 million will be due to smoking. In the oral and craniofacial region tobacco use has been associated with the occurrence of cleft palate, periodontal disease and tooth loss, and a variety of soft tissue lesions including oral cancer. For example, smoking is estimated to account for 92% of cancers of the lip, oral cavity and pharynx. Few studies have examined relative efficiency of the many different approaches to tobacco control but, in general, legislative approaches such as increasing tobacco taxes and prohibiting advertising are most effective and those based on printed educational materials and cessation groups, the least effective. In all cases, advice or intervention by health care professionals ranked among the most effective non-legislative approaches to control. A very wide range of professionally-based interventions have been described, including pharmacologic interventions, behavioral approaches and group counseling. The dental profession has a unique opportunity to influence tobacco use by their patients. Its use is almost always immediately evident to the dentist or dental assistant in terms of odor, staining, poor oral hygiene or obvious oral disease. There is also a tendency for the length of personal contact with the dentist to be greater than with a physician. Guidelines are now available that provide the dental professional with advice on the best approaches to tobacco control with their patients.
In most Western societies, there is an abundance of information on what needs to be done to control the use of tobacco. This paper presents different strategies for addressing tobacco control. Many of the strategies such as increasing taxes, increasing control over promotion of tobacco, and the restriction of smoking should be made a priority. However, there is still the need to provide help for the smoker to quit. The evidence with regards to effective ways of getting smokers to quit and the effectiveness of different modalities is reviewed. Programs found to be effective include self-help, individual counseling, and group counseling. Counseling programs appear to double the effect of success compared to no program. Nicotine replacement therapy has been demonstrated to be an important adjunct therapy to the behavioral programs. Issues regarding the cessation of tobacco by youth need to be addressed distinctively from adult cessation. Relapse prevention for both youth and adults needs to become a major focus of programs dealing with smokers who want to quit.
This review summarizes empirical evidence for clinical interventions designed to reduce children’s residentia environmental tobacco smoke (ETS) exposure. Legislation prohibiting ETS exposure in public buildings, especially work settings, may decrease ETS exposure in private residences. Media, policy/legal regulations, and brief clinical advice require more study to determine their effectiveness for decreasing ETS exposure in private residences. Three published and two in progress trials found that repeated counseling reduced ETS exposure in asthmatic and healthy children from lower through middle class families. Dentists, physicans, and other clinicians may be strategic supervisors for paraprofessional counseling designed to lower children’s ETS exposure in their home. Research is needed to determine the cultural tailoring needed to be effective in Hungary.
In Hungary today the mortality rate of middle aged (55-64 years old) men is higher than it was in the 1930s. Within these statistics there are considerable socioeconomic differences, the mortality rate of lower secondary or lower educated middle aged men is 1.45 times higher than among those with higher education. About 40% of these socioeconomic mortality differences can be explained by higher prevalence of risk behaviour in lower socioeconomic groups. According to the results of our national representative survey conducted in the Hungarian population with 12640 persons in 1995, the prevalence of smoking was 45.5% among men and 26.6% among women. In the populaton younger than 45 years old the prevalence of smoking among men was 47.9%, among women 31.9%. Among men there is a clear socioeconomic gradient in smoking, in the number of daily cigarettes, the quantity of spirit consumption in one occasion, among women this socioeconomic gradient is not so obvious. The effectiveness of health promotion programmes depends on effective management of the motivational, psychological determinants of risk behaviour.
The dramatic increase in the mortality of lip- and oral cancers in Hungary in the last decades points to the importance of primary and secondary prevention. Stomato-oncological screening examinations belong to the latter category, and might represent useful tools in the early diagnosis and treatment of oral carcinomas and precancerous lesions. The aim of the paper is to review the methods, results and effectivity of stomato-oncological screening examinations in Hungary. Between 1962 and 2000 nine screening examinations were performed: one on a population sample, one in an industrial setting, four connected to X-ray lung-screening examinations (one with the help of a mobile unit), one on voluntary persons, one on high risk people (homeless), one in general medical practice. Among these, in the last five years, in the course of the stomato-oncological examination of 17325 individuals, oral carcinoma has been found in 0.12%, and oral precanceroses in 2.63%. Although the general dentist is obliged by law to perform a stomato-oncological examination on the patients appearing in the practice, unfortunately, about 50-to-90% of the population does not visit a dentist regularly. The regular examination of these - high risk - groups by the help of the above methods, including the help of general medical practitioners is highly recommended.
The aim of our proposal is to suggest selected screening for people, who are the most likely candidates for the development of head and neck cancer. The screening organized by the family physicians on their own database in collaboration with the local dentists or ENT doctors involves examination and health education by effective communication and written information about risk of cancer and early signs and symptoms of the disease.
Search of different biomarkers is one of the most important demands of the national cancer prevention programme. We examined the usefulness of bleomycin sensitivity assay, whether it serves as a biomarker of individual sensitivity and risk for head and neck cancer under our environmental conditions. The test is based on the measurement of the means of chromatid breaks induced by bleomycin in vitro in a single lymphocyte (break/cell=b/c). 156 head and neck cancer patients were matched not only with 295 healthy controls (146 non-smokers and 149 smokers), but also with 51 strong alcoholic and smoking patients with liver disease whose lifestyle did not differ from that of the cancer patients. The aberrant cell frequency of cancer patients (2.85%), alcoholics (2.82%) and healthy smokers (2.81%) was similar and higher (p<0.03) than the values of non-smoker controls (2.25%). Thus, the results of conventional chromosome analysis indicate the effect of exposure to mutagens, derived mainly from smoking. Mutagen sensitivity measured by the bleomycin assay was significantly higher in both the cancer- (1.13 b/c) and the alcoholic patients (1.29 b/c) compared with smoker (1.04 b/c) and non-smoker controls (0.98 b/c). The bleomycin sensitivity assay, therefore, seems to be the biomarker not only for the cancer, but also for a disease of the same aetiology such as alcohol-related liver disease. However, the method is not suitable for the assessment of individual cancer risk due to overlapping of b/c values with those of controls. The proportion of mutagen sensitive persons in the group of Hungarian controls is 42-49%, which is two-fold of those in the US and Western Europe. When we estimate the cancer risk, the results of bleomycin sensitivity assay are equivocal under our experimental conditions, and they must be applied cautiously even in combination with the results of chromosome analysis.
Prognostication of head and neck cancer (HNCC) involves molecular identification of residual tumor cells, prediction of recurrence, distant metastases or secondary tumors and prediction of the sensitvity to therapy. Biomarkers of HNCC are mutations of p53, p16 and amplification of Cyclin D and E2F4. One hundred and fifty-two HNCC cases have been evaluated for p53, hMLH1, Cyclin D and p16 gene alterations using PCR-SSCP and Western blot analysis. P53 mutations of HNCC have been found in 37.5% of cases. However, 11% of the cases showed p53 mutations in the normal peritumoral mucosa suggesting field cancerization process. Mismatch-repair gene mutations (MMR: hMHL1 and hMSH2) occurred with 17 and 8.6% frequency, respectively, while E2F4 mutations were even more frequent (21.4%) in HNCC. Our data suggest that E2F4 overexpression can be caused by the inactivation of the p16 gene in HNCC, while its mutations are most probably associated to the mutations of the MMR genes. These molecular informations can help to predict the biological potential of HNCC as well as the probability of the development of secondary HNCCs.
INTRODUCTION: FDG (fluorine-labeled deoxy-glucose) and 11C-methionine positron emission tomography was evaluated in the diagnostics of head and neck cancer. PET scans were applied for identifying/staging relapse after oncotherapy or searching unknown primary tumor with metastatic lymph nodes of the neck. METHODS: Retrospective analysis of 22 patients examined by 17 <sup>18</sup>FDG and 15 <sup>11</sup>C-methionine PET scan. In 9 cases indication was unknown primary tumor with positive neck, in 13 cases previously treated head and neck cancer patients were examined for recurrence/restaging. RESULTS: In searching for unknown primary tumor not detectable with conventional methods, PET was effective in 22%, however, false positivity and uncertain results were found as well. In restaging PET proved to be very effective (85%) to discover recurrences and to differentiate them from post-treatment (mainly irradiation) effects. In two cases silent distant metastase were detected. CONCLUSION: PET can provide valuable information about unknown primary tumors, recurrences after oncotherapy and distant metastases as well. Simultaneous use of FDG/methionine scans does not improve the results.
AIM: Introduction of a safe and reliable method for reconstruction of soft tissue defects after excision of T1-T2 and borderline carcinomas of the posterior part of the oral cavity and mesopharynx. METHOD: Operation of two male patients suffering from tonsillolingual carcinoma, one with recurrent tumour after irradiation, the other with untreated primary and neck metastasis. After excision of the tumour with mandibular splitting method only a random buccal transposition flap was applied for reconstruction. The flap was adapted anatomically into the defect. It is a modification of previously described methods. RESULTS: Both patients healed primarily with undisturbed blood circulation of the flap. The functional rehabilitation period was short, the flap tolerated the postoperative irradiation, a moderate trismus remained after completion of the treatment, but it was not attributable to the flap. CONCLUSION: The use of the single buccal transposition flap for reconstruction of smaller defects of the posterior part of the oral cavity seems to be a simple, reliable and safe method even after irradiation. The key of the acceptable functional results is the correct adaptation of the flap
The incidence of head and neck cancer has been rapidly increasing in Hungary during the last decade. Most of these tumors are discovered in advanced stage, consequently, surgical removal of the tumor results in large complex defects in the soft tisses and bone elements of the face and neck. For optimal anatomical and functional reconstruction we perform free flap transfer in increasing number of cases. Between December 1993 and March 2001 in the Head and Neck Surgery Department of the National Institute of Oncology the defects after resection of head and neck tumors were reconstructed with free flaps in 85 cases. Radial forearm flap in 64 cases, fibula osteoseptocutaneous flap in 14 cases were used. In 87% of the patients the postoperative period was uneventful, the surgical complications were not more numerous than following traditional reconstructions. The average duration of operations became shorter by 2.5 hours during the last two years than before. In most of the cases we achieved good functional and esthetic results. The quality of life of the patients was excellent in 14%, almost normal in 73% and bad with serious problems of social life in 13%. It is surprising that there was no significant difference between the survival of neck node positive and negative patients. In our practice the replacement of large defects in the head and neck region with free flaps is a reliable and useful method for reconstruction.
AIM: The importance of 3D conformal percutan and brachytherapy treatment planning based on CT and MRI examinations in treatment of oral cavity tumors. Introducing of the planning procedure and the selection aspects. METHOD: We present the treatment planning based on CT and MRI slices of an oral cavity tumor. The percutan or interstitial boost follow the percutan irradiation of the involved regions and lymph nodes, regarding to the target volume and the critical organs. RESULT: Our ADAC 3D planning system gives us the possibility to add the first line and the boost treatment plans, to determine and compare the dose distribution within the planned target volume and the radiation load of the critical organs. CONCLUSION: The comparative 3D radiation planning system allows higher local dose escalation required for the effective radiation treatment of oral cavity tumors with maximal protection of the surrounding healthy tissues.
PURPOSE: To demonstrate a conventional and a new therapeutic method of 3D treatment planning in maxilla tumors, the process of 3D treatment planning and its significance and to compare these two methods. METHOD: We performed 2D and 3D treatment plans. The ADAC planning system was used in the 3D treatment planning. CT and MRI scans were taken on the target volume and on each scan we demarcated the target volume and the critical organs. The irregular fields were obtained by 3D graphic reconstruction provided by the treatment planning programme. RESULTS: Compared to the conventional treatment planning more favourable dose distribution was obtained within the target volume and the radiation burden of the critical organs was kept under their tolerance doses. CONCLUSION: In conformal 3D treatment planning the shape and size of the irradiated volume are in good conformity with those of the target volume. In this way the radiation burden of the critical organs and adjacent intact tissues can be reduced.
AIM: To demonstrate the role, the execution and the importance of the computed tomography (CT) based three-dimensional brachytherapy and conformal percutan radiotherapy in the treatment of the advanced tumour of the base of tongue. METHODS: Between January 1993 and June 2000, 27 patients with stage III-IV squamous cell cancers of the base of tongue were treated after 60 Gy percutan irradiation with interstitial, high dose rate brachytherapy (23 patients) or conformal, multi-fields radiotherapy (4 patients) as a boost. The dose of the boost irradiation varied between 12 and 24 Gy. RESULTS: Boost irradiation was well tolerated by the patients. The local tumour control at the mean follow-up period (39 months) was 52%. Using this two treatment methods in case of percutan conformal irradiation 6%, in case of brachytherapy 1.5% of the mandible received the prescribed boost dose. The spinal cord received a maximum of 15%, and 8% of the boost dose, respectively, depending on the two treatment types. CONCLUSION: With the help of these two radiotherapeutic modalities locally higher cumulative dose and better tumour control can be achieved without the higher risk of radiation injury of the surrounding normal tissues and the two most critical organs (medulla, mandible).
BACKGROUND: Neoadjuvant chemotherapy has an increasing role in multimodality treatment of advanced head and neck cancer. In this paper we summarize our first results with this treatment. METHOD: Thirty-five, previously untreated, mostly inoperable head and neck cancer patients were given two cycles of Cisplatin and 5FU chemotherapy. We continued the therapy only in case of regression until four cycles, then the patients received surgical and/or radiotherapy according to their status. After the treatment patients’ status was regularly evaluated. RESULTS: We detected 4 complete and 20 partial responses after the chemotherapy. Three patients became eligible for a radical operation. At this moment 10 patients are free of tumor, 8 patients died in consequence of the tumor, we have no data in 3 cases, 3 patients are given palliative therapy because of progression, 4 patients are receiving radiotherapy and 7 patients with partial response are candidates for further active oncotherapy. CONCLUSIONS: Although the number of the patients we treated is too small for a statistical analysis, our results are similar to the conclusion of the large randomized studies: after neoadjuvant chemotherapy of advanced head and neck cancer partial response can improve the result of surgical or radiological treatment. Neoadjuvant chemotherapy does not improve survival in advanced head and neck cancer, but it is of great importance because of better quality of life of patients, especially those who had organ preserving therapy.
INTRODUCTION: Combined modality treatment with chemotherapy and radiotherapy in locally advanced head and neck cancers is an effective and often the only treatment with a chance of cure. An alternative is to use chemotherapeutic agents at low doses as radiosensitizers. In this study we examined the radiosensitizing effect of low dose Taxol in locally advanced head and neck cancer. Patients and methods: 26 patients with locally advanced squamous cell carcinoma of the oral cavity and the oropharynx were treated with external beam radiotherapy up to doses of 66-70 Gy and received concomitantly 2 mg/m<sup>2</sup> Taxol intravenously three times a week. Response rates according to WHO criteria, side effects according to the National Cancer Institute Common Toxicity Criteria, overall and progression-free survival were evaluated. RESULTS: All patients completed the therapy. Median radiation dose was 66 Gy, Taxol dose 40 mg/m<sup>2</sup> and treatment duration 54 days. 8 weeks after completion of therapy complete response was 30.8%, partial response 34.6%, stable disease 11.5% and progressive disease 23.1%. The median follow-up time was 25 months (9-36). At the cloes- out date 12 (46,1%) of the patients were alive, 9 without evidence of disease. The estimated median overall survival was 22 months (CI 14.2-34.6), the median progression-free survival 12 months (CI 5.2-18.8). We observed four grade 4, fourteen grade 3 and numerous grade 1-2 side effects. There was no treatment related death. DISCUSSION: Our regimen resulted in a worse response rate than the aggressive chemoradiation protocols treating the same disease. However, the two-year survival was comparable with the results of other studies. The advantages of our schedule are that it is well tolerated, easy to perform on an outpatient basis, resource effective and does not deteriorate the general condition of the patients, therefore successive therapy can be carried out immediately if necessary. We intend to evaluate the effectivity of this treatment in a study comparing radiotherapy with Taxol sensitization versus radiotherapy alone.
AIM: To determine the effect of radiosensitization with Taxol and multimodality treatments on the survival of advanced oral and oropharyngeal cancer. Patients, methods: 56 patients with St. III-IV oral or oropharyngeal cancer were treated with external beam radiotherapy; 26 of them were sensitized by low-dose paxlitaxel and 30 were irradiated traditionally. The median follow up was 23 months (17-36). Endpoints of the study were: response to radiotherapy, progression-free and overall survival and the results of surgery and chemotherapy following radiation. RESULTS: 73.3% (41/56) of treatments resulted in CR or PR with median 10 months (0-33) progression-free and 14 months (4-33) overall survival. There was no significant difference between the radiosensitized and traditional radiotherapy group (p=0.6). The survival was significantly influenced by the stage of tumor and the response to primary radiotherapy. Seven (38.9%) of 16 patients treated also by either surgery or chemotherapy for recurrent or residual disease are free of cancer, 6 (35%) alive with tumor and 5 (26.1%) died with median survivals of 21, 20.5 and 18 months, respectively. Those treated only with radiotherapy with or without sensitization are free of cancer in 31.6%, alive with cancer 5.3%, died 63.2%. CONCLUSION: There were significant correlation between tumor stage, response to radiotherapy and combined modality treatment, and surival. The radiosensitizing effect of Taxol was not obvious so far, it may be apparent in the future by analyzing the long term survival data.
The tumor biological and radiobiological aspects, the mechanism of actions and general considerations of clinical application of radiochemotherapy are discussed. The aims of radiochemotherapy are to prolong the patients survival by improving local tumor control and decreasing distant metastases. The goal of radiochemotherapy is to enhance the therapeutic effect of radiation with tolerable and controllable local and systemic side effects. The mechanism of action of the most frequently used drugs are also discussed.
PURPOSE: the study of the effect of Amifostine in reducing acute mucositis, xerostomia and late xerostomia emerging in the course of locally advanced head and neck cancer radio-chemotherapy. METHODS: Starting in 1999 we have conducted radio-chemotherapy treatment on 7 patients with or without Amifostine protection, each receiving 60 Gy (2 Gy a day/5 fractions a week) loco-regional irradiation. From the first to the fifth day and from the twenty-first to the twenty-fifth day prior to irradiation they were given a 70 mg/m<sup>2</sup> Carboplatin treatment. In the Amifostine group, on days 1-5 and 21-25 300 mg/m<sup>2</sup> and on days 6-20 and 26-30 200 mg/m<sup>2</sup> Amifostine therapy was given prior to the radio- and chemotherapy. RESULTS: In the course of the trial we did not find any haematologic side effects, or side effects directly connected to the Amifostine, which would have required suspension of the therapy. In the active phase, mucositis of Grade 1-2 was detected 1-2 weeks later than in the control group, in contrast to the mucositis of Grade 2-3 in the other arm. Global oral discomfort associated with acute xerostomia was of Grade 4-6 on a linear scale of ten, compared with Grade 7-8 on the active line. We had similar results when testing the symptoms directly connected with late xerostomia. Unstimulated and stimulated saliva production doubled following the Amifostine treatment. CONCLUSION: Despite the small pool of patients we have the impression that Amifostine can effectively reduce the severity of acute mucositis, xerostomia and late xerostomia.
The authors report the results of radiochemotherapy for bladder cancer, both advanced and early with a poor prognosis, on the basis of their own material as well as based on the literature. More than half of the patients received radioprotective madication at the same time. The short follow-up does not allow for far-reaching conclusions, but early results and limited complications appear hopeful. The authors emphasise that, if indicated, radiochemotherapy can serve as an alternative to cystectomy.
The EPI has become available recently in the Oncoradiological Centre of Budapest. The purpose of this paper is to review the construction and operation of the electronic portal imaging devices (EPIDs). The different EPID systems as well the EPID technique vs. portal films are compared. The advantages in patient set-up and the detection of the set-up errors are discussed. The use of the EPID technique in the clinical everyday practice is detailed. Recommendations of the set-up error correction for the most often occurring failures is given.
INTRODUCTION: In this paper the authors have combined different irradiation techniques for breast and adjacent supraclavicular lymph nodes. The aim was to reduce inhomogeneity in the match-line. METHODS: The CadPlan 6.1.5 three-dimensional treatment planning system was applied in this study for CT based plan using a standard medial and lateral wedged tangential breast portals with the adjacent supraclavicular field. Isocenter is placed at depth on the match-line, where asymmetric jaws are used to produce non-divergent field edges. The tangential fields are shaped using multi-leaf collimator (MLC), by following the curvature of the thorax. In this way the cranial vertical match plane is maintaned without using the breast board. The prescribed dose was 50 Gy at the isocentre. RESULTS: The calculated dose distributions were evaluated in three dimension in the match region of supraclavicular field and the two opposing tangential fields. This method produces a more uniform dose distribution in the target volume and in the match-line. Set-up is fast, this is done without the need for table rotation, or vertical cephalad blocks. The average dose to the ipsilateral lung is reduced using the IMRT (intensity modulated radiotherapy) technique by approximately 10% compared with the conventional technique. Furthermore, this new technique has the possibility to improve the field match between the tangential fields and the parasternal field, while maintaning the field match between the tangential fields and the axillary and supraclavicular fields.
PURPOSE: Comparison of the effectiveness of preoperative and sandwich (preoperative and postoperative) radiation therapy in the treatment of midrectum and lower rectum carcinoma, based on a prospective clinical trial. MATERIAL AND METHOD: Over the period between 1990 and 1997, we treated 115 patients suffering from mid-rectum and lower rectum carcinoma at the Budapest Oncoradiological Centre, using sandwich therapy (22.5 Gy preoperative-27.5 Gy postoperative) in the case of 36 patients and 36 Gy preoperative radiation therapy in the case of 79 patients with external-beam megavoltage therapy with mostly telecobalt radiation and to a smaller number of cases 6 MV energy. The external-beam radiation therapy was nearly always applied with a 4-field box technique, and radical surgery was performed within 10 days following the preoperative radiation treatment. Effectiveness was evaluated in terms of a Log-Rank and Peto-Wilcoxon tests and the Kaplan-Meier survival curve. RESULTS: The effectiveness of the different therapies was compared in terms of the percentage of local failure and the rate of disease-free survival. The results show that when using the sandwich radiation therapy local failure is expected to occur in 13.8% of all cases, compared with 17.7%, when only preoperative radiation therapy is used. In terms of five-year disease-free survival, the sandwich therapy seems to be better, but for a higher number of years, namely 7.5, the preoperative radiation therapy yielded better results. CONCLUSION: In terms of local failure, the effectiveness of the preoperative and the sandwich radiation therapies for the treatment of mid-rectum and lower rectum carcinoma was nearly identical, while preoperative radiation therapy provided longer disease-free survival. Further trials using multivariation analysis need to be performed to evaluate the two types of radiation treatments, taking into account other parameters, such as grading, age and lymphatic spread.
The radiation oncologists primary concern is treatment of patients with malignant tumors but sometimes faces on occasion rare, non malignant disorders. The scarcity of disease incidence is reflected by the paucity of references for these diseases in the literature. This minimal exchange of information may make research and analysis difficult, tedious and not easily directed. Even with recognition of the risks of late skin injury, carcinogenesis, leukemogenesis and genetic damage from all ionizing radiation, radiation therapy also continues to be accepted treatment for benign diseases that do not respond to other methods of therapy. The purpose of this paper is to provide a short overview of the radiotherapy of most frequent benign disorders.
The authors review the value of radiotherapy in the multidisciplinary treatment of early (stage 0-II) breast cancer and describe past achievements, current scientific evidences and possible future prospects of clinical research. Results of randomized studies proved that conservative surgery with radiotherapy is equally effective to mastectomy for the treatment of in situ and invasive breast cancer, both in terms of local control and overall survival. In the nineties, findings of prospective clinical trials indicate that the use of irradiation in high-risk patients provides both a significant improvement in loco-regional control and survival rate. The magnitude of survival benefit with appropriate patient selection and radiotherapy technique is similar to that seen with adjuvant systemic therapy. Radiotherapy of early breast cancer is based on level I scientific evidences in the vast majority of cases. Remaining controversial issues are subjects of several ongoing international and Hungarian prospective randomized studies.
The adjuvant use of tamoxifen confers a survival advantage for patients with node-positive and node-negative breast cancer and demonstrated benefit when used alone or in combination with chemotherapy to treat advanced breast cancer.Tamoxifen prevents induced mammary cancer in rats, decreases the contralateral breast cancer incidence in humans, and its safety record in clinical practice is excellent. This finding led to the concept that the drug might play role in breast cancer prevention. In 1986 at the Royal Marsden Hospital a small pilot study was started, which would serve as a feasibility assessment for a larger trial to determine if tamoxifen prevents breast cancer. The trial shows no effect, because the study is too small for accurate results. Similarly, in another tamoxifen prevention study performed in Italy, the incidence of breast cancer did not differ between groups of tamoxifen and placebo. The negative finding of the study is readily explained by the relatively low risk of breast cancer development in the study population, the high drop-out rate and the small number of women who completed 5 years of treatment. In the NSABP P-1 prevention trial tamoxifen reduced the risk of invasive breast cancer by 49% and of noninvasive breast cancer by 50% in the increased risk population of 13.388 healthy women. The article summarizes the recent theoretical and practical data of the chemoprevention of breast cancer.
PURPOSE: To evaluate the effect of tumour bed boost on local tumour control (LTC) after breast conserving surgery in a prospective study. METHODS: Between 1995 and 1998, 207 women with early invasive breast cancer who underwent conservative operation were treated by 50 Gy irradiation to the whole breast and then randomly assigned to receive either no further radiotherapy (n=103) or a boost to the tumour bed (n=104) with either 16 Gy electron (n=52) or 12–14.25 Gy high dose rate brachytherapy (n=52). RESULTS: At a median follow-up of 4.25 years the crude rate of local recurrence was 6.7% with and 13.6% without boost. The respective rates of tumour bed relapse were 3.8% vs. 10.7%. The 4 year probability of LTC, relapse-free survival and breast cancer-specific survival was 94.2% vs. 85.1% (p=0.1176), 82.3% vs. 67.2% (p=0.0438) and 84.8% vs. 90.9% (p=0.1111), respectively, in favour of the boost group. Systemic treatments had no significant impact on LTC (88.9% with and 89.6% without systemic treatment, p=0.8858). CONCLUSION: Tumour bed boost decreased the incidence of local and tumor bed relapses with a reduction of 50% and 64%, respectively. Relapse-free survival was improved significantly with boost. However, the influence of boost treatment on breast cancer-specific survival should be tested in further studies. In spite of the higher incidence of late radiation side effects in the boost arm, boost dose is strongly recommended for patients at high risk for local recurrence. The final results of the EORTC trial and other ongoing studies will help to clarify the indication of boost dose according to prognostic subgroups.
The authors analyzed the epidemiologic and histological characteristics and the management of ovarian carcinoma of low malignant potential (LMP) at a university hospital between 1990 and 2000. The authors carried out a retrospective study reviewing hospital charts. Based on the records experience with 29 such tumors is peresented. Of these 20 (74%) were of the serous variety, 7 (26%) were mucinous. LMP tumors accounted for 16% of proliferating epithelial ovarian tumors. They occured at a mean age of 45 years. The LMP tumors were bilateral in 12% of the cases. The majority of patients (87%) with LMP tumors presented with early stage disease. Tumor markers such as CA-125 were not always elevated as in invasive ovarian carcinoma. Laboratory investigations have not demonstrated that these tumors represent an intermediate step between benign ovarian tumors and carcinoma. The recommended therapy is surgical, consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and tumor debulking. Conservative surgery consisting of unilateral salpingo-oophorectomy is considered to be an appropriate treatment for young women with early stage LMP ovarian tumors who wish to retain their fertility potential. 50 percent of women who underwent conservative surgery subsequently conceived in this study. There were no recurrences in the study group, so the authors conclude that the long term outcome of LMP tumors is extremely favorable.
Lymphomas are the third most frequent malignancies in childhood. The Hungarian Pediatric Oncology Group was founded in 1971, and since then the same chemotherapeutic protocols have been used in the whole country. In this study we analyzed the data of childhood Hodgkin’s lymphoma in Hungary in the last 11 years (1988-1998). We also compared our results with the international (German) data. The incidence of Hodgkin’s lymphoma (0-15 years) was 7.1/1,000,000 child/year (the same for non-Hodgkin’s lymphoma was 7.5/1,000,000/year); 5.5% of all pediatric malignancies in Hungary). The patients were treated according to the German DAL-HD-82 and 90 protocols. The therapy consisted of 2-6 cytostatic blocks, depending on the stage, followed by involved field irradiation. The overall survival was 94.7±2.0% at 5 years and 91.9±2.7% at 10 years. These results are very similar to the German data: 94% at 5 years and 93% at 10 years. The good results are due to the well organised network and the uniformed treatment. The results may be ameliorated by using autologous bone marrow transplantation.
PURPOSE: The purpose of the study was the evaluation of efficacy and the side effects of irinotecan in treatment of advanced colorectal cancer. METHODS: The authors presented their experiences with irinotecan in the treatment of 10 patients suffering from advanced colorectal cancer. The dose of irinotecan was 350 mg/m<sup>2</sup> every 21 days. Seven out of ten patients have taken oral fluoroquinolon to investigate its effect on the incidence of febrile episodes in case of febrile neutropenia. Three out of ten patients did not receive any antibiotic. The authors have examined the efficacy and safety of the treatment. RESULTS: One complete remission was obtained. Authors describe the observed side effects and the administered supportive care against serious complications. DISCUSSION: Serious diarrhoea has not been found in case of these 10 patients. The diarrhoea caused by irinotecan can be stopped by loperamide. The authors give accounts of early and following results.
STUDY OBJECTIVE: Description and evaluation of radiotherapy of inoperable brain stem tumours. Possibilities of improving therapeutic results. MATERIALS AND METHODS: Between 1987 and 2000 43 patients (23 boys and 20 girls, mean age 8.5±4.4 years) with brain stem tumours were treated with 6 MV and 9 MV X-ray. The doses administered ranged from 30 to 66 Gy; mean 50.41±7.67 Gy. Treatment in each case was performed according to CT- and /or MR-based radiotherapy plan. Since 2000 3D conformal radiotherapy plans have been prepared by using image fusion. RESULTS: All patients were followed. The mean follow-up period was 19.4 months (range: 1 to 112 months). For survival statistics the 2 to 3-year overall and symptom-free survivals were taken into account, the former ones in the function of tumour localisations. The gender of children did not affect the survival (p>0.74). No significant difference was found as to survival in the function of tumour localisation either (p>0.87). CONCLUSION: According to the literature data the results expected were not achieved by hyperfractionation and by delivering an overall focal dose of 72 to 78 Gy. Results can be improved by precise patient fixation and the routine application of 3D conformal radiotherapy plans prepared by CT- and MR-based image fusion. These together can result the correctly reproducible patient fixation, the homogenous radiation delivery in the target volume and the reduction of injury in the surrounding tissues. Irradiation should be performed also in histologically not verified tumours since a 24.6 month transitory improvement could be achieved in 60.5% of our patients.
PURPOSE: Study of thyroid function in Hodgkin’s disease patients in complete remission. PATIENTS AND METHODS: We examined the thyroid function of 160 Hodgkin’s disease patients in complete remission for at least one year, and determined the values of supersensitive thyroid stimulating hormone (sTSH), free T4 (fT4), free T3 (fT3) hormones. RESULTS: Normal values were observed in 117 patients, subclinical change (only elevated sTSH) in 28 patients, clinical hypothyroidism in 14 patients (also low fT4 and/or fT3), hyperthyroidism (Basedow’s disease) in one patient. Hypothyroidism was one and a half times more frequent in females than in males. The normal and low thyroid function group did not differ from each other in mean age, histological subtypes, disease stage, general symptoms, and whether lymphangiography was performed. Hypothyroidism was more frequent in patients who had undergone mantle or neck radiotherapy. The onset of thyroid gland underfunction was more pronounced from six years after neck radiotherapy. The thyroid disease could be controlled using a daily dose of 25–225 mg levothyroxin. CONCLUSIONS: During the care of Hodgkin’s disease patients routine examination of the thyroid function is important for the early recognition and prevention of treatment related late complications. On the other hand in treatment planning phase more attention should be paid to thyroid gland protection when neck radiotherapy is used.
PURPOSE: To study the clinical characteristics of bilateral testicular tumors in the cisplatin era. PATIENTS AND METHODS: Between November 1988 and November 1998 2386 testicular cancer patients were treated in our Department and 72 bilateral germ cell testicular cancer patients were retrospectively explored (3%). The incidence, the clinical and histological characteristics and, in the case of asynchronous tumor, the interval between the two tumors were analyzed. RESULTS: During the 10 years 19 synchronous (26.4%) and 53 asynchronous bilateral germ cell testicular cancers (73.6%) were treated. The incidence of bilateral synchronous seminoma was 68.4%. Among the asynchronous tumors 9 concordant seminomas and 9 concordant nonseminomas were detected. In the first, second and third 5-year follow-up period 39.6, 30.2, and 28.2% of asynchronous tumors were diagnosed. The incidence of seminoma after the first castration in the 5, 10 and 15 years was 19, 37.5, and 60%, respectively. The overall survival rates of synchronous and asynchronous testicular cancer were 84 and 93%. In cases of asynchronous tumor the prevalence of stage I cancer was significantly greater in a regularly controlled population (p=0.014) than in the not regularly followed population, but the survival rate was good in both groups. Nonseminoma showed up earlier as first and second tumor than seminoma (p=0.05, p=0.045). The interval between the two asynchronous tumors was shorter in the case of nonseminoma than in the case of seminoma (p=0.002). CONCLUSION: The prognosis of bilateral germ cell testicular cancer is good because of the high incidence rate of seminoma and the effective treatment. With regular follow-up the early diagnosis of second testicular tumors is probable. The interval between the tumors depends on the patients’ age and the histology of the second tumor, in the case of seminoma it is longer. The effect of the previous treatment on the incidence of seminoma and the interval between the two asynchronous tumors requires further investigations.
AIM: Assessment of occurrence and possible prognostic significance of c-myc and Ha-ras amplification, p53 deletion and overexpression of cyclin D1, p53 and p21 in papillary thyroid cancer. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tumor tissue from 24 patients were investigated. Dot-blot DNA hybridization was used to detect oncogene amplification or deletion. The expression of oncoproteins was determined by immunohistochemical method. RESULTS: In our samples neither Ha-ras amplification nor p53 deletion were found. Low c-myc amplification (mean: 2.55) occured in 4 cases (17%). p53 protein was detected in 16 samples (66.6%), with p21 expression (chi<sup>2</sup>=7.02, p<0.01) in 6 cases (25%). The p53 expression did not influence the tumor fenotype. Cyclin D1 overexpression was found in 12 cases (50%), it was often associated with p21 expression (chi2=10.1, p<0.001) and in inverse relation to the tumor lymphocytic infiltration (chi<sup>2</sup>=5.35, p<0.05). Increased expression of estrogen receptor was shown in 4 cyclin D1 positive samples (17%). CONCLUSIONS: The p53 detected in our study is likely not to be mutant protein in all cases because its presence was associated with p21 expression that the mutant protein cannot induce and also it did not mean more aggressive tumor phenotype. The connection of cyclin D1 overexpression with the lymphocytic infiltration of the tumor suggests that the increased expression of cyclin D1 means poor prognosis. The coexpression of cyclin D1 and p21 raises the modulative character of the p21 protein, thought to be a tumor suppressor originally, but we find a CDK-independent, estrogen receptor mediated effect of cyclin D1 more likely, which has been described in breast cancer and is also proved by the coexpression of cyclin D1 and estrogen receptor detected here.
The clinical importance of tumor-induced cachexia is indicated by the fact that two thirds of the cancer patients suffer from it and it plays an outstanding role in mortality of the disease. The onset of the tumorous anorexia/cachexia syndrome does not depend on tumor burden or the stage of the disease. The syndrome is very complex in nature and cannot be reversed by over-feeding of the patient. The appropriate supply of calories, carbohydrates, proteins and lipids is impossible, therefore administration of nutrients which do not cause volume-load for the patient is justified. Enteral feeding must be the primary aim in cancer patients till the gastrointestinal tract is functioning. To improve appetite and increase body weight specific pharmacological intervention may also be necessary. Understanding the molecular mechanisms of the development of tumorous anorexia/cachexia syndrome opens new ways of treatment.
Patients with cancer frequently develop anaemia. Various factors, including the type of malignancy and the intensity of chemotherapy influence the prevalence of anaemia and need of transfusions. Among the numerous causes of its development, the most frequent type is cancer anaemia, the so-called anaemia of chronic disorders. Anaemia of chronic disorders is diagnosed when neoplastic disease is accompanied by an otherwise unexplained microcytic anaemia with compromised iron utilisation and decreased erythropoietin secretion. In 50-70% of patients with solid tumors or hematological malignancies, mainly with multiple myeloma and malignant lymphomas, transfusion can be avoided, or significantly decreased by the use of recombinant erythropoietin. This review provides tools to decide the best candidates for this treatment and a guideline to monitor its efficacy.
DNA-microarray technology can be used to assess the expression of several thousands of genes at the same time.The identification of the gene expression profiles may help to better characterize human cancer.These studies may reveal subclasses of tumor types with similar histopathologic profile but different clinical courses.Furthermore,such studies could help to define therapeutic sensitivity and to estimate prognosis of various cancers.Identification of gene expression profiles of cancer can identify new therapeutic targets or cancer susceptibility genes.The DNA-microarray technology may write a new chapter in molecular oncology.
HER-2 (c-erbB2, neu) receptor is the molecular marker of ductal breast cancer although it is verexpressed in other adenocarcinoma as well (e.g.endometrial, colorectal and lung cancers). The increased receptor expression is most frequently (90 –97%) due to gene amplification. Detection of the overexpression of HER-2 helps to determine prognosis, to predict chemoresistance and to select for Herceptin therapy. HER-2 overexpression can be estimated either by immunohistochemistry or by fluorescent in situ hybridisation (FISH). Standardization of the immunohistochemical HER-2 tests is the best in HercepTest DAKO), however, the frequent 2+level requires complementary FISH test to verify gene amplification. This combination is not necessary at low (0 –1+) or high (3+) level of immunohistochemical reactions, because the correlation with gene amplification status is acceptably high. Recently several new anti-HER-2 antibodies have been introduced into HER-2 diagnostics in various countries. According to our experiences we recommend to combine rationally the immunohistochemistry and FISH techniques to determine the HER-2 status in breast cancer.
For many years data of cancer research indicated that viruses can cause cancer. Virus infections induce cancer by different mechanisms. To predict the significance of a viral DNA fragment in human cells we have to be aware of the changes the particular virus is able to induce there.However, no matter which mechanisms of viral carcinogenesis are utilized, generally other factors (environmental, chemical, immunodeficiency, etc.) are also needed to induce invasive cancer in human. Before the introduction of nucleic acid based detection technique virus identification was a long and cumbersome process. This has been eliminated by the invention of recombinant gene technology and polymerase chain reaction. Virus nucleic acid can be detected without amplification using Southern, Northern and in situ hybridization. Techniques for target (polymerase chain reaction)or signal (hybrid capture, tyramine) amplification improved the sensitivity of detection.In the meantime, for the successful use of the arsenal of new methods we have to consider the characteristic feature of molecular virus research. A major achievement of molecular virus detection is that it proved the pathological significance of viruses in human cancers even in those where this was not expected. Hopefully these informations will increase the effort for elimination of oncogen virus infections.
For over two decades banding has remained the ’gold standard’ of cytogenetic analysis, providing the first genome-wide screen for abnormalities. However, conventional cytogenetic banding techniques are limited to the detection of rearrangements involving more than 2 Mb of DNA. In addition,the identification of de novo unbalanced chromosome rearrangements provides a particular challenge for chromosome banding to decipher.In recent years a number of techniques based on FISH have evolved, all of which complement the conventional banding approaches and which have steadily increased the accuracy of cytogenetic diagnosis. FISH is now the method of choice because of the increased sensitivity, and speed with which it can be applied to a variety of cellular targets. In this article we try to highlight the technical aspects of FISH and the practical application of this technique on different tumors (soft tissue tumors, breast carcinomas, renal cell carcinomas, bladder tumors and germ cell tumors).
HPVs commonly cause proliferative lesions of squamous epithelium, and infection with certain HPV types carries a high risk of malignant transformation. We used molecular techniques to detect and type HPV in papillomas and carcinomas in the oral cavity and esophagus. DNA was extracted from 150 fresh or paraffin embedded biopsy specimens, and analyzed for HPV by PCR with 15 sets of consensus primers directed to conserved regions of L1 gene, three sets of HPV16E6 primers (specific for the HPV 16 prototype and L83V variant), and sets of primers specific for the E6 gene of other mucosa type HPVs including HPV 6, 11, 16, 18, 52, 58, 66 and 73. Overall, HPV sequences were detected in 61 of 150 specimens. HPV DNA sequences were detected in 16/32 specimens in the oropharyngeal region, in 13/36 specimens in larynx and 32/82 specimens in esophagus. Papillomas contained only the episomal form of HPV 16.In the esophagus, the most common type was HPV 73. In all specimens examined, HPV 6/11 (4/150), HPV 16 (23/150), HPV 35 (1/150), HPV 45 (1/150), HPV 54 (1/150), HPV 58 (1/150), HPV 61 (1/150), HPV 66 (1/150), HPV 68 (2/150), HPV 70 (3/150), HPV 72 (1/150), HPV 73 (16/150), double HPV infection (2/150), and unidentified HPV type (4/150) was detected. Interestingly, HPV was found in all verrucous carcinomas and in 18/22 basaloid squamous cell carcinomas. HPV16E6 T350G mutant were observed only in two of eight carcinomas. Using correspondence analysis, a segregation of specific virus types in specific clinico-pathologic lesions (verrucous carcinoma and basaloid squamous cell carcinoma) was proved. It was shown that the relative rates of the HPV positive tumors were significantly higher in women than in men. The synergic action of mucosal irritation and HPV infection may be necessary for the development of the papillomas and the specific types of carcinomas in the oral cavity and in the esophagus.
We have used semiquantitative and real-time quantitative PCRs to detect n-myc gene-amplification in 21 frozen neuroblastoma biopsies and IMR 32 cell line in order to predict biological behaviour of the tumors. Two primer pairs were used in the semiquantitative method to co-amplify a 520-bp fragment of the beta -globin gene -used as a single copy reference standard -and a 258-bp fragment of the n-myc gene. After 30 cycles the PCR products were electrophoresed through an agarose gel and were compared to each other with use of a gel-densitometer. Real-time quantitative analysis was performed in a LightCycler instrument. A single primer pair was used to amplify a 120-bp fragment of the n-myc oncogene and a LC640-labelled fluorescent probe pair to detect the product. Calibration curve, which was set up from a serial dilution including samples with 1, 2, 10 , 13, 25-fold n-myc oncogene amplification, was employed for quantitative analysis. Semiquantitative method did not show distinct difference between tumor groups with no amplification and less than 10-fold amplification, while quantitative LightCycler analysis was able to detect even 2-fold amplification. In situ PCRs were performed in two cases of differentiated tumor samples which contained n-myc amplification. We used biotinylated ATP labelling and the same primer pair as for the LightCycler analysis.In both cases differentiated cell forms did not show n-myc gene amplification, while considerable amplification was detected in the neuroblasts.
The long-term survival probability for Hungarian lung cancer patients is 10% worse than the best results published in the most highly developed countries (the mean 5-year survival probability in Hungary is 5%, in contrast with the 15% survival probability in the USA). On the basis of the international recommendations and personal experience, an attempt was made to formulate the guidelines for radiotherapy as one of the fundamental non-small cell lung cancer (NSCLC) treatment modalities for national use. An expert panel was set up comprising physicians from 6 radiotherapeutic centers (the National Institute of Oncology / Semmelweis University, Budapest; the Beth Israel Medical Center, New York; the University of Kaposvár; the University of Essen; the University of Debrecen; and the County Hospital of Gyula). Experts in two important medical fields closely related to radiotherapy (surgery and diagnostic imaging) were also engaged in the elaboration of the manuscript. Discussion of the most important principles of the radiotherapy and an overview of the prognostic factors was followed by a critical analysis of the protocols applied in the radiotherapy of Hungarian NSCLC patients during recent decades. The new guidelines suggested for the radiotherapy of NSCLC are presented separately for the postoperative period, marginally resectable tumors, and the aggressive or non-aggressive radiotherapy of inoperable tumors. Detailed accounts are given of the techniques of external irradiation and brachytherapy, and of the acute and late radiation-induced damage of normal tissues. The authors believe that this document may be instrumental in improving the survival index of Hungarian NSCLC patients in the near future.
The development of the surgery of the head and neck tumors seemed to be completed for the end of the seventies by the widespread acceptance of the basic technologies. However, the discovery of two techniques, medical laser and PM-lobe initiated major developments in the surgical oncology of head and neck cancer. Based on our studies, the benefits of use of medical laser in oncology are its fine-tuned topological preciseness, tissue-protection and the lack of bleeding disorders. A special benefit of the medical laser is its ablasticity and the support of tissue repair. The wide-spread use of PM-lobe technique in head and neck surgery was made it possible by the development of various modifications such as the cutan-myocutan and the osteomyocutan ones. By the application of the developed variants we were able to correct the consequences of radical resections and achieved acceptable functional and esthetic status in cancer patients.
In breast cancer the membrane expression of HER2 receptor protein encoded by the HER2 proto-oncogene seems to have an ever growing clinical significance. In tissue cultures and animal experiments it was shown that the HER2 gene amplification induces malignant transformation and intensifies the aggressiveness of the tumour cells. Correlating with the so called pheno-and genotypic prognostic markers, the overexpression of HER2 in breast cancer predicts also poor prognosis and indicates enhanced potential for metastatisation. In some of the so called precancerous proliferations and in situ carcinomas we demonstrated the enhanced membrane staining of the HER2 receptor protein. In these cases we frequently observed DNA aneuploidy,the presence of p53 mutational protein and CD44v6 glycoprotein. The immunohistochemical studies of HER2 protein in invasive carcinomas have revealed, an interrelationship between the grade of differentiation, histological type, aggressiveness and biological behaviour of the in situ and invasive carcinomas. In clinical studies trastuzumab, a humanized monoclonal antibody recognizing extracellular domain of HER2 receptor protein, has proved to be effective in HER2 overexpressing metastatic breast cancer either as monotherapy or in combination with chemotherapeutical agents. The DAKO HercepTest is a semiquantitative, standardised method for the determination of HER2 overexpression.
OBJECTIVES: Characterization of breast cancers by various tumour markers which are appropriate for the identification of high risk groups. Markers related to the metastasis cascade and tumour recurrence have been investigated. MATERIALS AND METHODS: RT-PCR was used to determine the expression of cytokeratin 20 in the bone marrow and sentinel lymph node of breast cancer patients (n=45). The expression of HER2, Cadherin E, Cyclin D, Bcl2 and Bax has been evaluated by Western blot (n=744 invasive ductal carcinomas and 117 invasive lobular carcinomas, 124 recurrent breast cancers). Mutations of p53, APC and ß Catenin genes were detected by PCR-SSCP method. RESULTS: Expression of cytokeratin 20 was found in 30% of the bone marrow samples indicating the presence of micrometastasis. The level of Cyclin D, HER2 and Bcl2 is elevated four-fold in the recurrent breast cancers. The metastasis of invasive ductal carcinomas is accompained by high frequency of p53 mutations (24%) and APC mutations (18%). The invasive lobular carcinomas could be characterized with low frequency of p53 mutation (3%), low level of Cadherin E and high level of catenin ß. CONCLUSIONS: Identification of micrometastasis can promote the development of therapeutic strategy. Evaluation of HER2 level and determination of p53 mutations contribute to the identification of high risk patients. Our results suggest that the progression of invasive ductal carcinomas depends on the APC mutations, while metastasis of invasive lobular carcinomas depends on ß catenin mutations.
OBJECTIVES: The aim of this study is to survey the treatment of bone metastases and hypercalcaemia. MATERIALS AND METHODS: A case of male breast cancer is presented here by the authors. The applied clodronat therapy was beneficial. RESULTS: The diagnostic difficulties of such rare, unusually localised, metastasizing male breast cancer are discussed with the survey of Hungarian and world literature. CONCLUSION: The bisphosphonates - beside treating the hypercalcaemia caused by bone metastasis - provide a better quality of life.
AIM: Parallel measurements of tumour markers in the serum and breast cyst fluid in a high risk group (GCBD) of breast cancer. The identification of individuals belonging to this group and their follow-up. MATERIALS AND METHODS: In the breast cyst fluid of 108 patients with GCBD (mean age 47 years) we measured the levels of CA 15 –3, TPA, CEA and ß HCG completed by PCT determinations. Simultaneously, the serum CA 15 –3 and TPA concentrations were also measured using the Luminescent Immunoassay techniques. RESULTS: Strikingly high TPA values were found in 98% of the patients. The CA 15 –3 levels, however, were pathological only in 24%of them. The CEA and ß HCG levels showed hardly any rise and the PCT concentration remained normal. CONCLUSIONS: The lack of any rise in PCT concentration precludes the inflammatory origin of the cystic fluid and the normal serum arker levels exclude ultrafiltration. The increased TPA concentration in the breast cystic fluid and the occurrence of pathological CA 15 –3 level in the above percentage of the cases suggest that GCBD represents not only a high risk group but possibly a precancerous state, too.
Breast cancer is the most frequent solid tumor in women. Predictive and prognostic factors play an important role in the treatment of this cancer. We focused on high risk and heavily pre-treated metastatic breast cancer patients, trying to find the best combination of cytotoxic drugs with high efficacy and low toxicity. Ifosfamide is chemically related to nitrogen mustard and is a synthetic analogue of cyclophosphamide. Ifosfamide has a wide range of antitumor activity. Since ifosfamide as monotherapy has introduced significant tumor reduction in 1st line chemotherapy for advanced breast cancer, some studies started with high-dose continuous infusion of ifosfamide,or combined with paclitaxel or vinorelbine. Patients with poor prognosis primary breast cancer treated with high-dose chemotherapy supported by peripheral blood progenitor cell (PBSC) transplantation have lower risk for local relapse and longer disease-free-survival. Ifosfamide working in the mobilization regimen has effective anti-tumor activity while mobilizing sufficient PBPCs in the majority of patients. In combination with other cytotoxics showed to be effective in high-dose protocols.
OBJECTIVES: Doxorubicin and taxanes are the most effective agents in the treatment of advanced breast cancer. The aim of the study was to compare the efficacy of Doxorubicin (A) + Docetaxel (T) (AT) and standard Doxorubicin (A) + Cyclophosphamide (C) (AC) chemotherapy. MATERIALS AND METHODS: Results of first-line AT (50/75 mg/m2) and AC (60/600 mg/m2) D 1 q 3 wk, maximum of 8 cycles, were compared. Three Hungarian centers - Petz Aladár County Teaching Hospital, Gyõr, St.Margit Hospital, Budapest, and BAZ County Hospital, Miskolc, with 33 patients participated the international, phase III randomized TAX 306 trial. Between June, 1996 and March, 1998, 429 metastatic breast cancer patients were enrolled in the study. Eligible patients were who had not received prior chemotherapy for advanced disease, and were anthracycline-naive. Objective response rate observed in the AT arm was significantly higher than in the AC arm (ORR: 60% vs. 47%, p=0.008). Time to progression was longer in the AT group (37.1 weeks vs. 31.9 weeks, p=0.0153). Except for higher incidence of neutropenia not requiring dose modification in the AT arm, there were no major differences concerning toxicity. T did not enhance cardiac toxicity induced by A. CONCLUSION: AT results in significantly higher response rate and longer time to progression than AC in advanced breast cancer, even in patients with unfavourable prognosis.
Paclitaxel is among the most effective agents in the treatment of breast cancer. Both as a single agent and in combinations, paclitaxel is effective as first-line therapy and as a salvage therapy in patients with locally advanced or metastatic disease. Paclitaxel also demonstrated efficacy in patients who received prior anthracyclin therapy and those with anthracyclin-resistant disease. In the adjuvant setting, data from randomized study have supported the sequential use of paclitaxel after therapy with doxorubicin / cyclophosphamide for patients with node-positive disease. The drug may be used in combination with other chemotherapeutical agents and immune stymulatory agents. Therapy on weekly and every-three-week schedules has been effective.
Advanced breast cancer remains incurable. For these patients, durable response and minimal toxicity are the main goals of current therapy. The antiestrogen tamoxifen has proved to be a significant advance in the treatment of breast cancer. Due to its partial estrogen activity, long term medication with tamoxifen has been found to cause endometrium proliferation wich can result in cancer in some patients. Reduction of estrogen production identified the aromatase inhibitors. Both steroidal substrate analog, type I inactivator, wich inactivate the enzyme and non-steroidal competitive reversible, type II inhibitors, are now avaiable. Two new 3rd generation aromatase inactivators have recently completed phase III evaluation (anastrozole and letrozole) and we have some results investigating one of the new 3rd generation aromatase inhibitors (exemestane). The 3rd generation aromatase inhibitors and inactivators are better tolerated and more effective than each of our current standard 2nd line endocrin therapies. These agents are being directly compared with standard adjuvant medication, tamoxifen, or are being evaluated in different sequences.
The re-discovery of the tumor cell-lined vascular channels and the possible pathomechanism (vasculogenic mimicry) earned major attention in the literature. This phenomenon is known for 60 years following B.Kellner, later supported by several groups, however its significance is still not known. The two new form of tumor blood supply, the incorporation/apoptotic remodeling of the preexisting vasculature and the latest discovery of endothelial gene expression in tumor cells suggest two alternative mechanisms for the development of tumor sinuses or vascular channels. The existence of these sinuses in malignant tumors and their possible function in the nutrient supply may limit the application of the new anti-angiogenic therapies.
PURPOSE: To introduce the CT based three dimensional (3D) conformal brachytherapy treatment planning for interstitial implants, to compare the conventional X-ray film based planning with the 3D planning from the point of view of reconstruction and dosimetry, to discuss the differences and highlight the advantages. MATERIAL AND METHODS: On 10 patients with breast and 5 with head and neck tumor treated with HDR interstitial implants, following the catheter implantations, CT scans were taken at 5 mm spacing. The images were loaded into the PLATO BPS v14.0 3D planning system for brachytherapy. The contours of the target volume and critical structures were outlined on each slice, the catheter describing points were identified and the anatomical structures and catheter positions were reconstructed in 3D. Having taken into account the target volume, the active lengths were determined in each catheter, and dose optimization on dose points on target was performed. RESULTS: The 3D treatment planning was applied at interstitial breast treatments and head and neck implants. We investigated the dose distribution on axial, reconstructed coronal / sagittal planes and in 3D view with respect to anatomical structures. Dose volume histograms related to the target volume and critical structures were used for quantitative assessment of the plans. We found that the conformal dose distribution might result in increase of dose inhomogeneity within the target volume. CONCLUSIONS: The three dimensional brachytherapy treatment planning can be introduced into the clinical practice under proper technical conditions. A tradeoff between conformality and dose homogeneity results in an acceptable dose plan. The dose inhomogeneity can be decreased with the use of CT scans taken before the implantation. The guidelines and quantitative parameters describing the dose distribution, which can be used for determining the optimal dose distribution in clinical point of view, are still waiting to be established.
PURPOSE: To describe the role, the execution and the importance of interstitial radiotherapy in the irradiation of the base of tongue cancer. MATERIAL AND METHODS: Between January, 1993 and December, 1998 nineteen patients with primary squamous cell cancer of the base of tongue (1 T1N0, 3 T2N0, 2 T3N0, 2 T3N2, 3 T4N0, 6 T4N1, 2 T4N2) were managed with brachytherapy partly with definitive intention combined with teletherapy (60-66 Gy) as a boost, partly as a single postoperative treatment. Irradiation was carried out by HDR after-loading (Ir-192) unit, using rigid needle or flexible plastic catheter. The treatment plan was made by PLATO 3D brachytherapy planning system. In case of boost the mean total dose of brachyherapy was 22 Gy (12-30 Gy), in postoperative treatment it was 27 Gy (24-30 Gy). RESULTS: 6-8 weeks after the definitive radiotherapy the CT/MR showed complete remission in 67% and partial remission in 33% of the patients. Of all treated patients during the mean follow-up period (30 months) the local tumour control was 42%. Five patients (26%) died in local failure. Six patients (32%) are alive with tumour. Osteoradionecrosis and fistula did not occur. CONCLUSIONS: In the oncological treatment of the advanced base of tongue tumour the combination of percutan and interstitial radiotherapy seems to be very advantageous,because it improves not only the curability, but the patients quality of life as well.
OBJECTIVE: Developing a new medical software based on the utilisation of information technology required in 3-dimensional treatment planning and modern radiotherapy. METHODS: The physical dose distribution programs were converted into biological meaning with the insertion of biological equivalence equations based on LQ model. Biological dose distributions and biological dose-volume histograms were generated. The treatment plans of a brain tumour patient were investigated to determine the dose burdening of the normal central nervous system tissues. RESULTS: Employing 3D conformal method, the dose of the vital mid-line structures decreased significantly, which possesses a more meaningful biological importance. Different treatment plans and different fractionation regimens could be compared to each other by utilising this kind of biological model. CONCLUSION: By employing information technology we succeeded in establishing a theoretical biological dose distribution system that could be visualised. The advantages of 3D treatment planning proved unambiguous. In the future this method will probably be suitable to choose the best therapeutic regimens.
Elaboration of such a simple technique for total skin electron irradiation which ensures good dose homogeneity and minimal x-ray background dose. MATERIALS AND METHODS: We started large electron field irradiations with the Neptun 10p linear accelerator in the National Institute of Oncology -Budapest in 1986. After the installation of the Siemens Mevatron KD linear accelerator it was possible to introduce the modified Stanford technique. This technique satisfies better the requirements given in the objective. The required field size of 200x75 cm is produced as a result of two fields with 30° angular separation (dual field) at a source skin distance of 465 cm. The patients body is exposed to six dual electron fields. The electron energy is 6 MeV. Despite the long source skin distance the treatment time is relatively short due to the high dose rate (940 mu/min) capability of our Mevatron KD. The in air dose profiles were measured in miniphantom with semiconductor detector. Depth dose curves were measured in water and in polystyrene phantom with semiconductor detector and with films. RESULTS: The measured dose homogeneity of the 6 MeV energy dual field with 30° angular separation is within +/- 5%in a 200x75cm plane field. The depth of dose maximum of the resulting dose distribution of six dual field irradiation is between 2 mm and 5 mm, while the depth of 80% isodose curve is about 8 mm. The total body x-ray background dose is less than 1% of the skin dose. CONCLUSION: The modified Stanford technique adapted to our Mevatron KD linear accelerator is suitable for total skin electron beam therapy.
PURPOSE: To present medical history of secondary chest wall and breast angiosarcomas (AS) developed after radiotherapy, and to discuss the questions of radiogenic origin, diagnosis and treatment by the review of the literature. METHODS: Report of two cases and MEDLINE search for relevant publications. RESULTS: Secondary AS occured in a previously irradiated field after a long (6 and 8 years) latency period in both cases. Detailed histopathological and immunohistochemical examinations from the biopsy and/or surgical specimens confirmed the diagnosis as AS. The first patient with moderately differentiated AS was treated successfully with radical surgery. The second patient with irresecable AS died of rapid local progression within 4 months. The incidence of chest wall and breast AS is increased after irradiation, however, controversial data exist in the literature. The incidence of chest wall and breast AS after radiotherapy was found to be 0.39 ‰ in our patient population, which means an estimated odds ratio of 2.4 for secondary AS. Stewart-Treves syndrome is not of radiogenic origin, since postoperative lymphoedema has been considered as primary etiological factor. CONCLUSIONS: Patients treated with surgery and/or radiotherapy for primary breast cancer are at higher risk for developing secondary AS, compared to the healthy population. An etiological relationship between radiotherapy and subsequent AS of chest wall and breast is likely, but still controversial. Initial radical surgery is the only effective treatment for achieving long term survival. Further adjuvant radiotherapy is no longer feasible, due to the previous irradiation. Chemotherapy has only palliative effect. These very rare cases deserve special attention due to the atypical clinical appearance, difficulties of differential diagnosis and poor prognosis.
The authors present preliminary experience with preoperative sentinel lymph node biopsy carried out with lymphoscintigraphy in patients with malignant melanoma. PATIENTS AND METHODS: In the present study patients operated for primary cutaneous malignant melanoma of moderate and high severity were included. On the day of surgery isotope labelled colloid was injected intradermally around the tumor to indicate the lymphatics and to obtain basic information about the localization of the sentinel lymph node(s).During surgery the lymph node(s) previously visualized by the injection of patent-blue staining were detected with the aid of a gamma probe. Simultaneously, the excision of the primary tumor was extended. Histologically verified metastasis in the surgically removed lymph node(s) necessitated block dissection possibly within two weeks. RESULTS: The distribution of patients (19) according to tumor localisation: 2 - upper extremities; 9 - lower extremities; 2 - sacral region; 6 - trunk. Tumor thickness ranged from <1.5 mm (6 patients) to 1.5-3 mm (5 patients) and to >3 mm (8 patients). In two cases the identification of the lymph node has failed. Positive sentinel ymph nodes were detected in two patients. It is noteworthy that with one patient the sentinel lymph node was not regional but intransit. This study was aimed at the development of a suitable method. Further on we wish to try it in prospective randomized studies.
OBJECTIVES: Identification and relative incidence of precancerosis and malignancies of the head and neck region and in the oral cavity. MATERIAL AND METHODS: In three counties of the western region of Hungary we physically examined pathological abnormities of healthy volunteers. Computerised examination reports and anamnestic data have been registered on data sheets. RESULTS: During examination of 5054 persons we have found 5 malignant tumours and 3.7% precancerosis (mostly leukoplakia). CONCLUSIONS: Orofacial tumours that are constantly increasing in our country account for the necessity of stomato-oncological screening test. Therefore, screening should be extended as far as possible to persons who live in poor social-economical circumstances. Persons with multiple risk factors are difficult to be reached by this screening test,therefore it is complicated to treat them at an early stage. We have found intense ignorance in connection with oral tumours and precancerosis. Oral hygiene and status are criticisable. Because of the deficiencies of methods in examination the morbidity rate of tumours in oral cavity is undoubtedly higher than the rate of the statistical data.
OBJECTIVES: The authors discuss upon the changes in the two cell types involved in cell mediated immunity (Killer and Natural Killer) as a result of operation in malignant ovarian tumor atients. METHODS: They study the preoperative and postoperative cell mediated immunity of 28 malignant cystadenocarcinoma cases (FIGO stage I/a-III/c). To determine the maximum K and NK cell activity they used the kinetic model of cytotoxicity enzyme. RESULTS AND CONCLUSIONS: They conclude that operation of malignant ovarian tumors had no significant influence on K and NK cell activity. They hypothesize that unchanged cell mediated immunity seems to be independent of malignant tumors, especially in these conditions. We need further information about this change of cell mediated immunity.
SUMMARY: The CD20+ variant of angiocentric T-cell lymphoma is an unusual type of T-cell lymphomas that present cystic changes in organs because of ischaemic necroses. The purpose of this study was to describe a case of CD20+angiocentric T-cell lymphoma, discussing its clinical, histopathological and immunohistochemical features, to analyze its proliferation kinetics and to consider its possible relationship to the Epstein-Barr virus (EBV) to understand better the pathobiological nature of the disease. METHODS: The clinical, histopathological, immunohistochemical and single-cell DNA cytophotometric features of the case were analyzed. In addition in situ hybridization was performed to detect EBV. RESULTS: The 24 years old woman was admitted to our Institute because of pain in the abdominal region and weight loss. There were enlarged lymph nodes on the neck, and biopsy was done. Histological diagnosis: angiocentric T-cell lymphoma, CD20+ variant. CD3, CD43, CD45RA and CD45R0 antigens were positive in the atypic lymphoid cells of the tumour and in cells infiltrating the vascular wall. DNA index was 0.8589 (hypodiploid). Tumour cells in G1 phase: 47%, S phase: 45.4%, G2 phase: 7.6%. Combined chemotherapy was administered because of clinical stadium IV/B of malignant lymphoma (5 CHOP-Bleo, CEPP, CEP, CMVE treatment). The disease showed gradual progression and the patient died 14 months after the first symptoms had appeared. CONCLUSIONS: In the last 13 years there were 5 cases of angiocentric T-cell lymphoma at our Institute. The CD20+ variant is rare, its clinical symptoms are special, the prognosis is unfavourable. The cause why we demonstrate this case is to call attention to a new treatment for these patients by immunotherapy using monoclonal antibodies against CD20 antigen.
In the lack of effective treatment, the role of prevention has increased in the repressing of lung cancer. Smoking being a pathogenetic factor in the development of lung cancer is an accepted fact. Because of this, primer prevention means first of all the reduction of smoking both with the help of preventing smoking and cessation. A bigger - historical - debate has developed around secunder prevention: the effective screening of lung cancer. Although it was observed that staging rate and resecability had been more advantageous in the screened group, the screening of lung cancer was declared ineffective, because mortality did not improve. The change of approach can be felt from the middle of the 90 ’s. Nowadays the creation of a multimodal lung cancer preventional strategy is in the center of researches. The screening of risk groups can mean the solution with the aid of biomarkers, chest X-ray and spiral CT. In Hungary, with the infrastructure of existing lung-screening network the up-to-date screening of risk groups seems to have reality in the near future.
Lung cancer is the most common malignant tumor among male and second among female. The most effective diagnostic tool would be the early detection of the lung cancer. The diagnosis of tumors has to be based on patho-morphological findings. The invasive diagnostic tools can be used if the proved lung process has any therapeutic consequence. Only an experienced team has the chance to examine quickly and effectively the patients.In Hungary there are pulmonological centers where these teams consisting of pneumonologist, radiologists and pathologists are working effectively.
Primary bronchial cancer is the most common cause of cancer death worldwide, and it shows a steadily increasing incidence. Beside classical histological typing and grading, immunohistochemical, cytometric, and molecular biological parameters are highly needed to assist light microscopy investigations to better characterize primary bronchial cancers. In this work the author summarizes the main tumor markers and prognostic factors in lung cancer studied intensively at present. Serum markers as well as different tissue markers, such as cell proliferation markers, oncogenes, growth factors, apoptosis markers and vascularisation markers, tumor suppressor genes and markers of drug resistance are discussed in details. The methods currently used in this field are also mentioned and the data of the literature is often completed with results of the author ’s own investigations. An overview is given about the role of tumor markers in the early detection of lung cancer, in the assessment of tumor aggressiveness, and in therapy of lung cancer. The aim of this work is to create a bridge between the research laboratory in which lung cancer is studied sometimes using very sophisticated techniques and the bedside with all its practical, difficult but very important questions. Getting closer the theory and the practice can be very promising in the establishment of a fruitful collaboration in order to be more effective in the fight against lung cancer.
In Hungary the incidence of lung cancer is growing further and the proportion of patients undergoing surgery is less than 30%. Some improvement is indicated by the rate of explorations decreasing to less than 10%. On the other hand the number of adenocarcinomas has grown to take over the position of the squamous cell carcinomas among the patients operated on. In the recent few decades only some minor changes have occurred in the surgical treatment. For this reason when operability has been established new perspectives have been reviewed before drawing conclusions on the number of cases qualifying for resection. Phrenic and recurrent nerve lesions and in some cases metastases in some other organs do not mean inoperability in the absolute sense any more. Based on the new TNM system the criteria of the qualification for and the date of resection are identified by staging implemented reliably and in details. Palliative surgery may also be possible in some selected cases. A complex approach to the treatment of lung cancer is clearly coming into the focus of our attention. Though a resection is the most important episode here an adjuvant (post-operative) therapy and most recently added that a neoadjuvant (pre-operative) therapy shall improve the patient’s chances for survival further, enhancing the favorable result caused by the resection itself. Both the limits and the options of he surgical treatment administered in the cases of metastases in the lung, the brain and the solitary suprarenal gland are discussed in details in the cases of NSCLC.
The purpose of the paper is to outline the current treatment strategies in lung cancer focusing on the possibile role of radiotherapy. METHOD: It defines the place of radiotherapy at the main histological types and stadiums proposing indications according to evidence based medicine. CONCLUSIONS: Radiotherapy is mandatory in non-operated NSCLC st. I-II in perioperative or palliative management of superior sulcus tumours; in the combined modality treatment of limited SCLC and in postoperative adjustment of resected single brain metastasis of lung cancer. It is optional after NSCLC segmentectomy; in palliation or postoperative adjuvation of NSCLC st. III Radiotherapy can be chosen as a part of best supportive care at NSCLC st. IV extensive SCLC and in case of multiple brain or localised lytic bone metastases.
The most problematic area in pulmonary oncology is the chemotherapy of non-small cell lung carcinoma and its place in the therapeutic strategy. Chemotherapy based on the earlier alkylating agents worsened survival of NSCLC patients. That was the reason for the nihilistic approach by many colleagues toward chemotherapy in NSCLC. Today this question has been resolved. Platinum based combined chemotherapy significantly prolongs survival and improves quality of life. Other possibilities are to incorporate the new chemotherapeutic agents (taxanes, Gemcitabine, Vinorelbine, Irinotecan) into the chemotherapeutic regimens. These agents improve the response rate and the quality of life and can be safely administered in outpatient bases, although in comparison to the earlier agents the survival gain is moderate. In early stages the role of adjuvant chemotherapy is questionable. Chemotherapy, surgery and postoperative irradiation may all have a role in the case of N2 disease.In locally advanced disease the use of radiochemotherapy is recommended. In advanced NSCLC chemotherapy is suggested in good performance status. The author summarises the role of chemotherapy in NSCLC, based on literature and on his own experience.
The author summarizes the most recent information on small cell lung cancer. Reviews the epidemiology, prognostic markers and stages of small cell lung cancer Details the more frequently used combined therapeutic modalities, the criteria of the optimal therapeutic approaches and the achieved remission rates. Based on the most recent data, summarizes the new chemotherapeutic agents and their most effective combinations, the second line treatment and immunotherapy. Finally tries to answer the most frequently asked questions.
The effectiveness of cancer treatment given to lung cancer patients is indicated by the asymptomatic and non-toxic survival time. The goal is not to prolong the patients’ suffering, but to lengthen the duration of the best quality of life lived (Time Without Symptoms and Toxicity –TWIST). Supportive care is the prevention and management of side effects which occur during therapy (chemotherapy, radiotherapy, surgery) given to patients suffering from cancer. Supportive care is the widespread activity of doctors, nurses and social workers, including psychosocial assistance and rehabilitation through the various stages of illness till death. Though palliative therapy is understood to be the high level and professional treatment of terminally ill patients in those cases where curative measures are not possible anymore, supportive and palliative treatment often overlap (e.g. pain control, cachexia, obstructive syndromes). Palliative care is part of supportive therapy. The goal of supportive care is to reduce the patients’ subjective symptoms to the minimum (well being) during therapy, follow up and consequently until death. The essence of supportive care is to keep the patients’ quality of life on the highest possible level. This article summarizes the pathophysiology, prevention and therapy of the most frequently occuring side effects observed during the management of lung cancer patients.
Complete removal of the tumour or deep invasion can be proven by repeated transurethral resection of bladder wall at the previous tumour site. Six weeks after transurethral resection of bladder tumour (TURB), in all but TaG1 cases repeated resection were performed for the evaluation of radicality in 62 patients, 43 males and 19 females, suffering bladder cancer, from October 1998. In the case of positive histology another resection was performed for security reason. In the case of 38 superficial (Tis, Ta, T1) cancers, repeated resection revealed negative, identical or different T stage compared with previous histology in 28, 5 and 5 cases, respectively. In 7 cases repeated resection was applied as second intervention after the incomplete resection of large tumour mass. Indication of repeated resection was insufficient depth of resection and carcinoma in situ in 13 and 4 cases, respectively. Based on our data, we conclude that repeated resection should be performed when tumour-free status is not justified and biopsy according to Bressel was not taken.
A recent survey of head and neck cancer indicated a sharp difference in survival between cancer of the hypopharyx and cancers formed in other head and neck sites. We have analyzed tumor size relative to clinical stage and vascularization as possible causes for such a difference in a series of 21 patients with cancers of the laryngopharynx (11 glottic and 10 hypopharyngeal). We found that the volume of the smallest cancers of the larynx at stage 2 are significantly larger than the volume of the cancers of the hypopharynx at stage 4 (p<0.05). Next, we have determined by immunohistochemistry and morphometry the microvessel density (MVD), microvessel perimeter (MVP) and VEGF expression of laryngo-hypopharyngeal cancers. Analysis of these data indicates that there is no difference in vascularization and VEGF expression between these two tumor types. These data strongly suggest that the invasive-but not the angiogenic phenotype of hypopharyngeal cancer cells could be responsible for the more aggressive biological behavior of this head and neck cancer subtype.
The Hungarian Pediatric Oncology Study Group treated 362 acute lymphoblastic leukemia patients between 1990 and 1995 using the the ALL-BFM 90 protocol. The modified protocol, ALL-BFM 95, was used later to treat 257 patients. The two protocols were similarly successful to treat low and medium risk cases. However, the ALL-BFM 95 protocoll was more efficient to treat high risk patients and resulted in 10% increase in survival. The Western-European results are superior by 10-15% compared to the Hungarian data mainly due to the relatively high proportion of the early death in Hungary. Improvement of these data can only be expected from the development of the diagnostic potentials and from further improvement of treatment of the high isk patients.
Correlation between different prognostic factors and the overall survival of Ewing’s sarcoma patients has been investigted. In this study data have been selected from the databank of Hungarian Pediatric Oncologist Section (1988-1999) (n=65). Whenever it was possible statistical analysis has been performed. Results: In our patients time interval from the primary symptoms to the diagnosis was 2-16 months. The average event-free survival in patients suffering from Ewing’s sarcoma without metastasis is 0.39. Meanwhile, this value in patients with pulmonary or other metatasis is 0.24 (Kaplan-Meier analysis). Conclusion: Our results show a moderate difference between the Hungarian and the international event-free survival. Late detection is one of the answers of this discrepancy.
PURPOSE: To present the postoperative radiotherapy technique in children with medulloblastoma, and analyse the effectiveness of radiotherapy and the survival data. MATERIALS AND METHODS: 66 consecutive children (45 male and 21 female) received postoperative chemotherapy and radiotherapy between 1986 and 1998. The mean age was 8.3 years. The radiotherapy was performed with linear accelerator 9MV X-ray irradiation. The high risk patients received 36 Gy craniospinal irradiation, the low risk patients recived 30 Gy. The boost irradiation to the posterior fossa was 20 Gy in both patient groups. The patients received multi-drug chemotherapy immediately after the tumor resection. The radiotherapy started 6-8 weeks after the operation. RESULTS: All 66 patients were evaluated. The mean follow-up time was 45.4 months. The chance of cure is higher at age 8 or more, and less favorable under age 8. After 60 months 68.6% of children under age 8 and 75.9% older than 8 are alive. 20 children (64.5%) are alive after radical tumorectomy and 11 died. The 5 year overall survival was 71%. Recurrence was observed in 23/66 cases, it was the most frequent cause of death. Local failure was in posterior fossa in 15 patients (68.2%). CONCLUSION: The radicality of operation had no significant influence to the overall survival. The tumor stage, age of patients, risk group and metastases are important prognostic factors.
Hepatic tumors account for 0.5-2% of all childhood tumors in Hungary, based of the data last ten years. More than half of the cases were histologically malignant. The worldwide incidence of malignant hepatic tumors is 1.6 / 1 million. Here we present two patients with hepatoblastoma. In the first case the size of the initially inoperable tumor diminished following the chemotherapy and total surgical resection became possible. No sign of relapse occurred so far. The second case included a congenital hepatic tumor which was remarkable because of its unusual clinical presentation and histology.
PURPOSE: The authors analyze their 3-year results of the educational and early detection program for testicular cancer. The goals of the program are to reduce the duration of symptoms and to improve early detection. METHODS: Advertisements were placed in the media describing the early signs of testicular cancer, the risks factors, the correct method of self-investigation and the importance of early detection. Between 1 April, 1995 and 1 April, 1998 5056 volunteers were examined. They underwent physical and ultrasound examination of the testicles, and in case of suspicious findings, tumor markers (alpha-fetoprotein, human choriogonadotropin) were checked. RESULTS: Testicular tumors were found in 1.28% of patients with symptoms (testicular enlargement or nodules). No tumor was found in the population that was symptom-free, or in patients with pain, sensitivity to palpation, or unrelated complaints. Of the patients with a palpable lump and swollen testicles, 4.5 and 3.9% were found to have tumors respectively. In total 32 testicular tumors were detected in 30 patients: 15 (2 bilateral) seminomas, 13 non-seminomas and 4 benign tumors. The occurrence of malignant testicular tumors was most frequent, 1.6% in the age group between 15 and 40 years. The stages were as follows: 9 I/A, 9 I/B, 1 I/S, 3 II/A, 1 II/B and 2 III/B. One patient was lost to follow-up after castration. All the other patients achieved complete remission. CONCLUSION: Despite the increasing incidence of testicular cancer screening of asymptomatic men does not lead to detection of tumors. The awareness of the early signs associated with cancer, self-examination, ultrasound examination of the testicle help in establishing an early diagnosis, nevertheless a widescale program for the early detection of testicular cancer is not justifiable. Effective early detection should be based on an educational program for the population at risk, the appropriate training of doctors and staff engaged in the health care of the young, and the initiation and facilitation of early ultrasound examination at the first symptoms. Serum markers play a limited role in early diagnosis.
The atypical teratoid / rhabdoid tumour is a rare type of tumours of central nervous system appearing usually under 2 years of age, bearing a rather bad prognosis and it may cause serious differential diagnostic problem. The tumour is characterized histologically by the presence of the rhabdoid cells, immunohistochemically by vimentin, SMA, EMA positivity, the frequent presence of cytokeratin, GFAP positivity, but germ cell markers: AFP, hCG negativity, cytogenetically by aberrations of chromosome 22. The case of a one and half month old female infant is presented, who died 8 months after the appearance of the first symptoms. The diagnostic possibilities and the unsolved problem of the therapy are discussed.
Neutropenia, resulting from intensive chemotherapy is a common problem. The appearance of fever in neutropenic patients should always raise the suspicion of infection and should be followed by an intensive diagnostic evaluation and start of antibacterial treatment. The authors analyzed the association between isolated bacteria from blood cultures and the clinical background of all febrile episodes that occurred in neutropenic children in a two-year long period. Comparable to the international trends, our results suggest an increased prevalence of the Gram-positive organisms causing bacteriaemia. The clear majority of the isolated bacteria was coagulase-negativ Staphylococcus (cnS), which is a multiresistant strain, and sensitive only to the glycopeptide antibiotics. This latter fact can be a consequence of the frequent use of central venous catheters. The empirical therapy, the therapy used in microbiologically and clinically proved infections, and the supplementary and prophylactic methods of treatment are presented.
Detection of minimal residual disease (MRD) in childhood leukemia is not possible by cytomorphology or Southern blotting due to their low sensitivity. On the other hand, the use of DNA markers and PCR amplification is helpful in a smaller proportion of leukemia cases (20-30%). Since childhood leukemia is characterized by WT1 gene expression in the majority of cases,monitoring of WT1 expression in the peripheral blood was suggested to be a method of choice to detect MRD. We have studied 22 newly diagnosed childhood acute leukemias and 17 cases in remission. As controls, 19 patients with non-leukemic diseases were included. The majority of our acute leukemia cases (80%) were proved to be WT1 expressors using a highly sensitive nested PCR technique. Ten WT1 + cases have been monitored for a year throughout the inicial therapy phase, using peripheral blood tests. We observed that in 20% of the follow-up cases MRD was suggested which was not detectable by any other methods. It is our intention to introduce this new molecular technique into the clinical management of childhood acute leukemia.
We aim at modelling the strategic decision making process in case of devoting resources to a governmental cancer control program. We use a model based on the theory of Analytic Hierarchy Process. In this article we describe the characteristic features of such a decision making process and reveal the complexity of the problem underlying the decisions. A second article will present and discuss the results from the application of the AHP model. Interventions which are capable of decreasing the burden of cancer in a society need strategic approach. Decisions on interventions seem inevitable to be based on and balance between the priorities and the available resources. There is not much doubt about it that the reason for setting the priorities arises on the one hand from the scarcity of resources. On the other hand, priorities evolve on other bases, and are supposed to guide health policy makers devoting the scarce resources. In general, a strategic mode of thought has been based on assumptions, which, in case of cancer control enhance the necessity to assess information on cancer and cancer patients, and to understand the factors contributing towards better health. The capabilities of the NCCP achieving its aims by preventing the development of cancer diseases (primary prevention), by making use of the means of early detection and appropriate therapy (secondary prevention), and by providing modern (comprehensive) tertiary prevention are inevitably affected by the priorities. Health policy should assume a responsibility for enforcing certain priorities and should be aware of the long-term interest of the population. To solve the problem we restrict the model to a simple three level one, representing the goals, the criteria, and the alternatives of the resource allocation. We determine decreasing the burden of cancer as the overall goal. Distributive justice cost-effectiveness, human rights , evidences, and standpoints of a community serve as criteria, while primary prevention, early detection and therapy, both belonging to the secondary prevention, tertiary prevention, research, and education form the alternatives.
In Hungary mortality caused by malignant tumour diseases is very high. It is the second cause of death showing approximately 25% frequency. Statistics on disability has revealed that during the past 25 years the number of patients become invalid because of cancer has nearly doubled.In comparative international statistics cancer mortality and incidence of the Hungarian male population take the first and that of the female population the second place. The alarming public health problems caused by cancer in Hungary have prompted the authors to identify the causes and search for points of outbreak to stop and reverse these unfavourable tendencies. When analysing the current state of this country authors primarily rely on the studies of the European Cancer Centre, Lyon and those of the Hungarian Central Statistical Office (KSH) and National Cancer Registry. By years 2000-2001 the National Cancer Registry has become a reliable well functioning system. Its activities include the registration of all new cancer patients announced in the previous calendar year. Data processing requires information such as: year of diagnosis, tumour localisation and extension, morphological code and therapeutic interventions. It is a promising sign that the first time over the past 25 years cancer mortality decreased in year 2000. The unfavourable cancer mortality and incidence status in Hungary might be improved by the consistent accomplishment of the project For a Healthy Nation, A Public Health Project for years 2001-2010.
PURPOSE: The increasing premature mortality due to cancer has made population based screening programs for cervical,breast and colorectal cancers inevitable in Hungary. However, when confronted with limited resources, the aim is that, within the budget constrain, the greatest possible health gain should be produced. METHODS: The authors made a systematic review of the international literature concerning the cost-effectiveness of screening programs for the above tumours. RESULTS: In case of cervical cancer the Papanicolaou test, in case of breast cancer the mammography meet the WHO criteria for population-based mass screening. The well-designed organised screening programs are more cost-effective than the opportunistic screening. Among sexually active women, according to structure the mobile screening buses, according to age group screening of the 30-39 years old women seems the most favourable. For breast cancer, screening the 60-70 years old population every second year is the reference strategy from a health economic perspective. The cost-effectiveness results of either increasing the frequency of screening, extending the program for other age groups, or selecting a high-risk population are contradictory. In case of colorectal cancer there is no screening method, which would meet the WHO criteria. The two-day FOBT seems the most favourable, followed by colonoscopy for positive results, in the 55-74 years old population every second year. CONCLUSION: In addition to fulfilling requirements for a population-based screening method, the cost-effectiveness perspective should be taken into account.
The authors examined the spatial accumulation of mortality and morbidity of cancer of the prostate of the total as well as age stratified male population of Hungary. Using GIS, a descriptive epidemiological study was carried out examining the spatial differences of mortality on settlement level with 2000 inhabitans by calculating standardized mortality and morbidity ratios. The significance of the difference of mortality and morbidity from the national mean was tested by chi square probe. On the basis of the results a significant excess in mortality was detected in 11 regions of the country. The unfavourable regions cover 11.6% of the territory of the country where 25.6% of the male population live. A significant excess morbidity can be observed in 8 counties. A significant correlation was found between the unfavourable regions of mortality and morbidity (r=0.443, p<0.05). The age-specific analysis of morbidity revealed the highest excess in morbidity in the age group over 70 years accumulating in 3 counties of Transdanubia and in 6 counties of the Great Plain. On the basis of the results of mortality and morbidity analysis according to age and areas the unfavourable regions can be identified where mortality and morbidity from cancer of the prostate accumulates. These studies serve as a basis for intervention strategies.
Despite the unfavourable epidemiological status, the Hungarian breast cancer control is a non-appropriately developed system having considerable geographical inequalities. The study objective was to describe the small-area pattern of breast cancer mortality and of frequency of mammographical examination. The influence of socio-economical status on these patterns was also studied. The standardised mortality ratios and the standardised relative frequency of mammography was determined for settlements, zip code areas and small regions. Their correlations were analysed with education, unemployment ratio, ratio of Gypsy and German ethnic minorities, population size, smoking, distance to the nearest hospital. The South-Transdanubian Region (STR, consisting of three counties, 22 small regions, 444 zip code areas and 643 settlements) with 1 million inhabitants was the study area. All the studied parameters had significant spatial variability at all levels of aggregation. Beyond the relatively low average mortality risk in the STR, mortality clusters and increasing time trend were identified in certain areas. The mortality and the usage of mammography were inversely correlated with the indices of deprivation. These factors explain 64.5 and 17.5% of the whole variability of local mortality risks at the level of settlements and small regions. The explanatory role of these factors was similarly high for usage of mammography as well (40.2 and 52.6% for small regions and zip code areas). The factors having the strongest influence were the population size (in settlement level mortality model), ratio of gypsies (in small region level mortality and mammography usage models) and ratio of Germans (in mammography usage model for zip code areas). Inserting the counties approaches for screening organisation into the model, it revealed that the population based screening organisation applied in Tolna county has the highest influence being 4.4 times stronger than the most important socio-economic factors.Altogether,it seems that the monitoring of spatial inequalities could improve the performance of breast cancer control identifying the populations with special needs, and there is a need to explore the pathways by which the socio-economic factors can exert their profound influence on the epidemiological status. Moreover, since the results clearly demonstrated that it is possible to achieve relatively high screening participation rates in Hungarian economical and legislative circumstances, the application of this successful method should be encouraged in other areas with low performance screening system.
The aim of chemoprevention is to delay or prevent the development of pathological conditions, or to correct abnormal regulatory mechanisms and in some cases even reverse the process. For this intervention to succeed, biomarkers must be found that characterize impaired health status in a phase when impairment is still reversible. Genotoxicological parameters may function as biomarkers of this kind, such as inhibition or delay of mitosis, inhibition of apoptosis, increase in the number of chromosomal aberrations, decrease in the capacity of DNA repairing enzymes, or parameters characterizing immunological status (eg. decreased NK activity). With the help of early signs, impending negative changes or illness (which could not be prevented without effective chemoprevention) can be predicted in apparently healthy individuals. Thus, the first and most important step in chemoprevention is risk characterization. Risk characterization is a complex concept, which includes risk analysis, risk assessment and risk management. Chemoprevention is a part of the latter process. Biomarkers, which can be studied mainly by up-to-date molecular biological methods, are used in discovering risk factors and also in the assessment of caused biological effects. Besides avoiding risk factors, it is very important to strengthen the protective mechanisms, to promote the metabolism of toxic substances, and to repair damage (ward off denaturation of macromolecules caused by free oxygen radicals with antioxidants for example). Chemopreventive agents are therefore diverse in their targets. Most of them have antioxidant properties, such as plant-derived substances, like glycosides, flavonoids, various vitamins, carotinoids, and some trace elements such as selenium. Another group of chemopreventive agents inhibit cell proliferation, or induce programmed cell death (apoptosis). Another group influence terminal differentiation, or inhibit angiogenesis. Some chemopreventive agents affect the metabolism or detoxification of xenobiotics, or boost the functions of the immune system. In many cases these effects are mediated by the rate of methylation of DNA molecules.
The ISO 9001 quality assurance of the National Institute of Oncology has been achieved successfully. We give an account of the brief history and the structure of the assurance system of the Institute, the process of setting our goals, and also the experience gained from drafting ISO 9001 handbook and flowcharts. Apart from the bureaucratic nature of quality assurance, it is a good opportunity for us to investigate our everyday work, put it into orderly manner and work more reliably. Experience has shown that the introduction of a quality assurance system increases the level of patient care, the documentation helps the Institute or some of its departments, or even individuals prevent law suits, and serves as a sound basis for proposing promotion, salary increases and bonuses, or even honors.
Selective estrogen receptor modulators (SERMs) represent a growing class of compounds that act as either estrogen receptor gonists or ntagonists in tissue-selective manner. SERMs with the appropriate selectivity profile offer the opportunity to dissociate the favorable bone and cardio-vascular effects of estrogen from its unfavorable stimulatory effects on the breast and uterus. The triphenylethylene drug tamoxifen proved to be invaluable to treat and protect against breast cancer and bone loss, probably reduces cardiovascular risk, but had side effects on uterus similar to natural estrogens. The tamoxifen derivate toremifene is also used to treat breast cancer, but has less effect on bone. The non-steroidal benzothiophene derivate, raloxifene, is the best SERM available thus far. It has the potential to prevent breast cancer (like tamoxifen), but has better profile in its actions on bone and cardiovascular system (produces a rapid reduction of serum cholesterol, decreases fibrinogen and lipoprotein, improves the vascular epithelial function, attenuates vascular intimal thickening, etc.). It does not increase the incidence of endometrial cancer. Compounds of this class are the first step in developing the perfect hormone replacement and other multitargeted therapy. This review summarizes the recent important knowledge about SERMs.
The authors report on a rare manifestation of soft tissue metastasis of operated colorectal cancer. Interestingly, two years after the resection a etastasis with extremely high tumor marker level (CEA, CA 19.9) was detected. Marker elevation preceded the manifestation of metastasis by nearly half a year. After the metastasectomy the disease progressed. The authors briefly refer to the epidemiology of colorectal cancer, the complex therapy and the follow up.
Based on phase II and III trials Taxol administered in the form of three times/week 1 or 3 hr infusion as mono-or combined chemotherapy of breast cancer is an effective treatment option. These studies proved that this form of drug delivery is effective and well tolerated and the overall response rate is around 50%. The 1 hr weekly infusion of Taxol is an effective second-line treatment in metastatic breast cancer and is better than the 3-weekly infusion since the decreased toxicity increases the therapeutic index.
Combined chemotherapy of breast cancer using antracyclins proved to be superior over classical drug combinations. Taxanes are considered even more effective agents against breast cancer than the previously used drugs. Based on these assumptions, multicentric phase III trial was initiated in Europe to compare the AT combination (doxorubicin and paclitaxel) with the classical FAC (5-fluorouracyl, doxorubicin and cyclophosphamid). AT combination proved to be more effective in the treatment of metastatic breast cancer than FAC as far as the overall response rate and the complete responses are concerned. Furthermore, the time to progression increased in the AT-arm too compared to the FAC-arm. Based on these data it is suggested to use AT combination for the first-line treatment of metastatic breast cancer.
Taxol (paclitaxel) and Herceptin (trastuzumab) are two milestones in the treatment of metastatic breast cancer. Accordingly it was feasible to study the combination of these two highly active drugs (with different toxicity profiles and mechanisms of action) in the treatment of metastatic breast cancer. In multicentric phase III trial performed in the US the combination of Herceptin with either taxane or anthracyclin was investigated. It was established that the combination of Herceptin with Taxol treatment significantly improves the overall response rate, increases the time to progression and the overall survival. These effects are more pronounced in patients characterized with HER/2 +++ overexpression. Based on these evidences the Herceptin-Taxol combined treatment protocol was introduced in Hungary for the treatment of Stage IV breast cancer patients.
The authors have reviewed the financial considerations of oncological FDG PET examinations by the guidelines of the Health Care Financing Administration (USA). By critical assessment of large number of clinical investigations,the cost-effectiveness of FDG PET scans has been confirmed in the following cases: differential diagnosis of solitary pulmonary nodule, diagnosis,staging and restaging of non-small cell lung cancer, colorectal cancer, malignant lymphomas, melanoma malignum, esophageal neoplasms and cancers of the head and neck. The role of this method in breast cancer is currently under intensive investigation. Due to the correct staging, PET examinations in these indications enable the clinicians to choose the optimal treatment ensuring the maximum probability of recovery and being cost-effective as unnecessary medical interventions become avoidable.
Bone metastases afflict over 70% of patients with advanced breast cancer, resulting in impaired quality of life and significant clinical problems. Until appearance of the bisphosphonates there was no specific therapeutic treatment available to manage the symptoms of osteolytic bone metastases. Bisphosphonates are stable chemical analogues of pyrophosphate, and inhibit osteoclast-mediated bone resorption, the treatment is effective in reducing skeletal morbidity in breast cancer with fewer skeletal related events, reduced pain and analgesic consumption, and improved quality of life. As a result, bisphosphonates should now be part of the routine management of metastatic bone disease and multiple myeloma. Promising data have resulted in considerable interest in the possible adjuvant use of bisphosphonates. Pamidronate is an easy to use potent inhibitor of osteolysis, given in conjunction with standard anticancer therapies effectively relieves bone pain and improves performance status. Monthly pamidronate infusions for one or two years in addition to standard anticancer therapy reduce by more than one third the yearly frequency of skeletal-related events. The authors report their practice in which 119 breast cancer patients metastatic to bone received 90-120 mg pamidronate infusion/cycle in addition to standard breast cancer therapy every 3-4 weeks.
PURPOSE: To review the application of MRI images in the radiation treatment planning ,to discuss the advantages and disadvantages of MR imaging with respect to treatment planning, and to investigate the geometric distortion. METHODS: Humanoid therapy phantom was used for MRI and CT scanning, and distances between markers inside and on the surface of the phantom were measured in order to quantify the geometric distortion. The procedure of MRI/CT image fusion, which makes it possible to use the data of both imaging modalities for treatment planning, was described. RESULTS: At small volumes (head phantom) the geometric distortion was negligible (<2 mm), but at large volumes (eg. pelvis) remarkable geometric inaccuracies were observed. For example, the width of the pelvis measured in the MRI images was 7 mm less than the real distance, which corresponds to 2% inaccuracy. Geometric distortion was observed not only in the axial, but also in the sagittal and coronal planes. We have found that the geometric error increases with the distance measured from the magnetic isocenter. When the geometric distortion is not significant, the MRI/CT image fusion can be carried out reliably with the use of surface markers. CONCLUSIONS: At small volumes the MRI images can be used for treatment planning after their fusion with CT images. At larger volumes the geometric distortion without any correction may preclude the MRI images from using them in the treatment planning. A detailed assessment of geometric distortion must be carried out before the introduction of MRI images into the radiation treatment planning.
THE AIM OF THE STUDY: to analyse the incidence of second malignant neoplasms (SMN) in patients treated for Hodgkin’s disease. PATIENTS AND METHODS: Since 1st January 1967, 534 patients have received primary treatment for Hodgkin’s disease and 470 cases have proved to be adequate for data analysis as regards to the development of SMN. RESULTS: SMN developed in 34 cases (7.2%), solid neoplasms were diagnosed in 26 cases (5.5%), lung neoplasms had the greatest incidence (11/26), hematologic malignancies were detected in 8 cases (1.7%), and non-Hodgkin’s lymphoma was found in 5/8 cases. The mean age of patients with solid neoplasms was 38.1 years (18-59 years) at the diagnosis of Hodgkin’s disease and the length of time until the diagnosis of SMN was 13.5 years (1-33 years). The mean age of patients with hematologic malignancies was 45 years (17-64 years), the latency period was 3.2 years (9 months-12 years). The therapies employed prior to the development of solid neoplasms involve: irradiation in 6 cases, chemotherapy in 8 and combined therapy in 12 cases. Out of the 20 cases of chemotherapy, CV/O/PP and its variants were used in 17 cases. Prior to the development of hematologic malignancies, 5 patients had received chemotherapy, 3 combined therapy and 7 patients CV/O/PP and its variants. CONCLUSIONS: The incidence of SMN, especially as regards to hematologic malignancies, was found lower in our patients as compared to literary data. This can be explained by the less intensive therapeutic techniques employed earlier as well as by shorter survival periods. As a result of better therapeutic management, the chances of long term survivals have increased and we should make every effort to avoid late complications such as SMN when planning therapeutic strategies.
AIMS OF THE STUDY: In the 214 polymyositis / dermatomyositis patients in our department we studied the association of polymyositis / dermatomyositis with malignant tumors, the clinical specificities and therapeutic response changes in these cases. METHODS: Retrospective analysis of the data available since 1985 of the patients treated at the DEOEC 3rd Department of Internal Medicine. RESULTS: From 60 patients with dermatomyositis 9 were diagnosed with neoplasia. In 5 patients simultaneously with the dematomyositis diagnosis, in the other 4 patients 2-2-3-7 years after the onset of dermatomyositis. In the 154 patients with polymyositis we did not observe development of tumors. CONCLUSIONS: Neoplasm was observed in 15% of patients with dermatomyositis. The patients presented with serious skin involvement which did not respond well to the dermatomyositis treatment. The patients in whom tumors developed simultaneously with the dermatomyositis required more aggressive treatment. After the therapy of the tumor (surgery, radiotherapy), the skin and muscle symptomps responded better to the immunosuppresive therapy.
OBJECTIVE: To report a rare case of tumour-to-tumour metastasis with differential diagnostic considerations. METHODS AND RESULTS: We report the operation of a Sylvian fissure secretory meningioma in a 48 year-old woman. The tumour was suspicious of a metastasis related to a pulmonary adenocarcinoma operated 4 months before. Histopathology confirmed metastatic adenocarcinoma in a secretory meningioma. CONCLUSIONS: Both secretory meningioma and tumour-to-tumour metastasis are rare, and to our knowledge this is the first report of such a rare coincidence. Secretory meningioma can simulate metastases both clinically (extensive oedema, space occupation, carcinoembryonic antigen secretion) and pathologically (secretory inclusions, positivity for cytokeratin 7 and carcinoembryonic antigen and negativity for vimentin), and therefore may cause a special differential diagnostic dilemma.
The authors observed a solid breast carcinoma in a patient aged 70 years. The tumor cells contained lipids, glycogen and neutral glycoproteins. Axillary lymph node metastasis had already existed at the operation.
Juxtacortical osteosarcoma occurred on the right tibia and fibula of a 20-22 years old man found in a medieval period cemetery of Budapest. MACROSCOPIC DESCRIPTION: The tumor is located circumferentially on the midshaft of the tibia and fibula and appears cone-shaped. The lesion measured 160 mm in length and 3-5 mm in height. The surface of the tumor is irregular, rough, in some areas shows spicules. These spicules averaged 2-4 mm in length and 1-2 mm in diameter. The anterior and medial surface of the tibia is completely covered by osseous tumor. RADIOGRAPHY: The X-ray study demonstrates the medullary involvement, with mixed osteolytic and osteoblastic areas. Tumor infiltration of the cortex is also apparent as irregular rarefication and lytic lesions. In some areas a sunburst picture could be seen. The X-ray picture is characteristic for juxtacortical osteosarcoma. MICROSCOPIC EXAMINATION: stereomicroscopy of specimens shows a sponge-like structure of the surface. The cortical bone is completely destroyed and deep cavities are seen between spiculous and gyrificated neoplastic bone. The spiculae are varied in length and thickness. Irregular bulky bone trabeculae demonstrating uncontrolled neoplastic reaction could be detected. By light microscopic examination severe destruction, osteolytic lesions are seen both in the cortical bone and in the cancellous bone in the peripheral parts of the tumors. Within the neoplastic bone only few remnants of the primary (normal) bone structure could be demonstrated. No reparative reactions were seen next to the osteolysis, the collagen fibers and lamellas are destroyed. Beside the destruction of original bone larger structures composed of irregular newly built nepotistic bone trabeculae can be detected. The newly formed trabeculae (spiculae) contain a tumorous ground substance (probably osteoid tissue) with few collagen fibers, and these areas are covered with a thin bony lamella. In some areas the neoplastic structures are in intimate contact with the original cancellous bone remnants. IMMUNOHISTOCHEMISTRY: Both the osteosarcoma and chondrosarcoma show osteoid and bone neoformation while in the chondrosarcoma type II collagen could also detected. By immunohistochemical reactions no type II and III collagen, only type I collagen reaction was positive. This means that no cartilaginous tissues were present in the tumor. Scanning electron microscopy of these specimens shows sponge-like structures. The tumor reveals irregular trabecular and spicular texture,the spicules are various in diameter and in some spiculae rounded deposits attached to the surface.In our case we found typical radiological and histological picture of the juxtacortical osteosarcoma.
The course of cancer mortality in this country between 1975 and 2001 was analysed solely with mathematical methods using the mortality data provided by the Central Statistical Office. Mortality data were studied according to patient’s sex and tumour localisation and in relation to total cancer mortality. The increase and decrease in cancer mortality were found to differ by sex and tumour localisation: e.g. death rate caused by cancers of the oral cavity showed low deviation with an even increase just like the mortality caused by colorectal cancer, the latter, however, was steeper with men. In case of melanoma higher deviation was associated with increased mortality, again at a higher rate with men. Dying of testicular cancer and of gastric cancer in either sex showed decreasing tendencies. Lung cancer mortality assumed different patterns in the two genders: with men it kept increasing at an even pace until 1994 then the increase stopped. With women, however, the increase since 1985 was steeper than earlier. The breast cancer mortality rates can also be divided into two periods. There was an even rise until 1994 followed by stagnation. As to the total cancer mortality values, the authors state that the rhythm of increase during the first 20 years of the study period had changed, the steepness of trends in the last seven years can be expressed in a small positive number not differing from zero at significant level which means that the increase in cancer mortality has stopped.
The project focuses on cancer types with outstanding publich health importance (breast-, colorectalhead and neck cancers and childhood tumors). Epidemiological studies revealed significant regional differences in the mobidity/mortality of these cancer types in Hungary. Molecular epidemiological studies revealed characteristic BRCA1 mutation patterns of familiar breast cancer and DNA repair enzyme polymorphism in head and neck cancer. New methods have been developed for the screening (lactoferrin), prognostication (c-met expression) or the prediction of therapeutic sensitivity (TS expression) of colorectal cancer. In the pediatric oncology program alternative way of MRD monitoring (WT1 expression) and a potential new therapeutic modality (IFN-alpha) of ALL was developed. Experimental studies demonstrated that the tumoral matrix significantly influences the effects of the classic chemotherapeutic agents. We have identified several genes the expression of which could serve efficiently as markers or targets for therapy of the progression of melanoma (alphaIIbbeta3 integrin, CD44v3 and decorin proteoglycans, AMF receptor).
The author summarizes the progress of adjuvant chemotherapy of breast cancer from the classical Bonadonna-type CMF over the anthracyclines to the taxanes. The CMF regimen represented the prototype of combination chemotherapy which significantly improved early and long term results. After 20 years the patients given adjuvant combination chemotherapy with CMF had significantly better rates of relapse-free survival (p<0.001) and overall survival (p=0.03) compared with no chemotherapy. 6 cycles of CMF was the gold standard of adjuvant chemotherapy in breast cancer for decades. The Milan research group decided in the early 1980s to challange this popular CMF combination by introducing doxorubicin within the adjuvant program. Compared with standard CMF, anthracyclin-containing regimens reduced the annual risk of recurrence by 12% and the annual risk of death by 11%, equating to a 3.2% absolute reduction in recurrence and a 2.7% absolute reduction in mortality at 5 years. This small but real difference seen with regimens containing three or more agents (e.g. CEF and CAF, FAC, FEC, etc.), whereas 4 cycles of 2-drug regimens (e.g. AC or EC) appears to be equivalent to 6 cycles of CMF. Among the novel chemotherapeutic drugs introduced in the 1990s the taxanes have emerged as the most powerful compounds in breast cancer. Several large, adjuvant clinical trials are currently ongoing or have recently completed accrual. The available results from innumerable clinical studies are still inconclusive and do not support the routine use of taxanes in the adjuvant setting - with the exception of the BCIRG 001 docetaxel trial, in which significant improvement was documented in disease free survival with 6 x TAC compared with 6 x FAC (82% vs 74%). Studies on the effect of the new trastuzumab (an antibody against the extracellular domain of the HER2) in adjuvant setting was initiated in early 2000. The Herceptin adjuvant trial programme is extensive, involving more than 12,000 patients worldwide. This trials will potentially offer many women with HER2-positive disease the chance of improved survival.
This review deals with results attained by Hungarian authors in the field of sentinel nodes and presents the current status of sentinel lymphadenectomy in Hungary. After a short historical overview, results with melanoma and breast cancer are summarized, and feasibility studies on other possible sites (gastrointestinal tract, thyroid gland) are also mentioned. Pathological aspects are also dealt with in a separate section. The summary of these results suggests that Hungarian authors have investigated several facets of sentinel node biopsy, their results are in keeping with international results. Despite the favourable results, the method still needs time to be more widely accepted and reflected in the literature.
PURPOSE: Delayed breast reconstruction with implant is frequently used after mastectomy. However, given that many breast cancer patients receive adjuvant radiotherapy, the adaptation of this method raises questions concerning possible cumulative complications. In the present study the compatibility of post-mastectomy radiotherapy and delayed breast reconstruction with implant was examined. PATIENTS AND METHODS: We evaluated a consecutive series of 66 invasive breast cancer patients who have received delayed breast reconstruction with implant after modified radical mastectomy between January 1997 and June 1999. The average time was 51 months from primary surgery to reconstruction. The median dose of loco-regional irradiation was 50 Gy. Grade III atrophic dermatitis was observed in none of the irradiated women. We identified two patient groups: 29 patients did not and 37 patients did receive post-mastectomy radiotherapy. The types and time of reconstruction related chronic complications (capsular contracture, defect of implant shell and skin necrosis) were recorded. Incidence of complications was estimated by the Kaplan-Meier method. Cancer related events were also studied. RESULTS: When expander was used, minor discomfort of the patients was common during the filling course. At four (11%) irradiated patients the expansion with expander was incomplete, due to severe pain. At a median follow up time of 53 months the incidence of capsular contracture was 24.1% without and 29.7% with radiotherapy (p=0.4121). The five-year estimated rate of late complications was 40% and 50%, respectively (relative risk: 1.29, 95% confidence interval: 0.58-2.89, p=0.5173). The position of implant had an impact on the incidence of capsular contracture: 46.2% with subcutaneous and 22.6% with submuscular position (p=0.0881). Four patients (6%) developed local relapse (three in the skin and one subcutaneous). All were treated with tumor excision without implant removal. CONCLUSION: Delayed breast reconstruction with implant after post-mastectomy radiotherapy can be offered to patients who are interested in breast reconstruction and had no severe late radiation skin toxicity. Post-mastectomy radiotherapy does not significantly increase the risk of complications. The use of skin expander is less tolerated by irradiated patients. Submuscular position of implants moderates the risk of capsular contracture.
Head and neck squamous cell carcinoma (HNSCC) is diagnosed mainly in male patients (more than 80% of the cases) with a history of smoking and heavy alcohol consumption. However, only a few percent of all alcoholics develop head and neck cancer. OBJECTIVE OF THE STUDY: to investigate the hormonal status in HNSCC patients as compared to healthy controls and alcoholic persons in order to find changes, if any, characteristic for cancer. METHOD: The liver function expressed by gamma-GT levels, the hypophysis gonadotrop hormone (FSH, LH, prolactin) and sex steroid hormone serum levels were examined in 130 male HNSCC patients, in 54 men with alcoholic liver disease but without any known cancer and in 56 healthy men as controls. RESULTS: When compared to the healthy controls, both alcoholics and tumor patients had abnormal liver function, testosterone, sex hormone binding globuline and prolactin levels, reflecting the presence of alcoholic liver disease in tumor patients as well. However, abnormally elevated circulating FSH (p<0.005) and LH (p<0.0003) levels were present only in the tumor patients. CONCLUSION: Sex steroid hormone abnormalities are common among head and neck cancer patients, mainly as results of the chronic alcoholic liver disease. Elevation of FSH and LH levels suggests a potential role of these hormones in the formation of head and neck cancer. The exact role of the hypothalamus-hypophysis-liver axis in the biology of head and neck cancer requires further investigations.
INTRODUCTION: Leukoplakia is the most frequent preblastomatous alteration in the oral cavity. Its potential for malignant transformation is unpredictable. The aim of the present study was to provide data to the prognosis and molecular genetic background of this disease. MATERIALS AND METHODS: Biopsy material from 15 leukoplakia patients and three oral squamous cell carcinoma patients treated at the Department of Periodontology, Semmelweis University were studied with histological and immunohistochemical methods. Hemotoxylin and eosin staining, Apop-Detect kit (for TUNEL reaction), immunohistochemical reactions for Ki-67 and p53 were applied. The severity of dysplasia, mitotic and apoptotic index and expression as well as distribution of Ki-67 and p53 were examined and related to the clinical appearance of leukoplakia. RESULTS: Mitotic and apoptotic index, Ki-67 expression increased significantly in parallel with the severity of dysplasia and also with the clinical stage (homogenous, nodular erythroleukoplakia). Positivity and intracellular localisation of mutant p53 varied according to the clinical forms of leukoplakia. Homogenous and nodular forms showed cytoplasmic while erythroleukoplakia and carcinoma were characterized by nuclear positivity. CONCLUSION: Increased mitotic, apoptotic and Ki-67 index may indicate unfavourable prognosis of leukoplakia. The expression of Ki-67 and p53 in various forms of leukoplakia varies in parallel with the severity of leukoplakia.
Germ cell testicular cancers are well-curable neoplasms, because total remission can be achieved in about 80% of the cases. However, 15-20% of the patients die due to drug resistance (DR). A number of mechanisms of the multidrug resistance phenotype are known, including MDR/P-glycoprotein (P-gp) and the so-called multidrug resistance associated protein (MRP). Lung Resistance Protein (LRP) is an ATP dependent membrane transporter protein associated with MDR. In our present work we studied the expression of LRP in testicular cancers. LRP expression was determined by immunohistochemistry (IH), Western blot (WB) and RT-PCR techniques. Clinical resistance was defined in accordance with the clinical oncologic rules. In 29 (41%) of 70 primary testicular tumours and in 22 (63%) of 35 cases, elevated LRP levels were established by IH and WB, respectively. In the latter 63%, the LRP mRNA levels were elevated as well. Six cases of the 15 seminomas and 23 cases of the nonseminomatous germ cell tumours (NSGCT) proved to be positive. No relationship was demonstrated between LRP expression and the stage of the disease. Despite the LRP positivity of 6 tumour samples, all of the seminomas proved sensitive. Of the 39 sensitive NSGCT, 27 cases were LRP-negative, whereas 11 tumour samples of 16 patients belonging to the resistant group proved LRP-positive (p=0.04). The authors concluded that the expression of LRP is responsible for clinical drug resistance in non-seminomatous testicular cancer patients.
The ectopic thyroid gland occurring in the midline of the base of tongue is a rare developmental anomaly. It may cause differential diagnostic problems with real malignant tumor. Symptoms, if where are any: foreign-body-feeling, swallowing difficulties, dyspnea, articulation disorders, bleeding and hypothyroidism, but in many cases the diagnosis is accidental. We describe two cases of lingual thyroid gland operated in our department, and discuss the present trends of the treatment of this disease. We agree with most of the authors that only cases presenting with symptoms should be operated, and if possible the normal thyroid tissue should be replaced into the body. However, all discovered cases have to be followed to avoid late hormonal disturbances.
PURPOSE: The authors analysed renal and ureter complications in Hodgkin’s disease patients after treatment. PATIENTS AND METHODS: We examined retrospectively 512 primary treated and followed up patients with Hodgkin’s disease. RESULTS: We observed renal, ureter or bladder complications after irradiation in 16 cases (3.125%). Five patients had injured left kidney, out of them only two had pyuria or proteinuria and 4 received radiotherapy and chemotherapy as well. We observed complications of both kidneys in 7 patients. Four patients had pyelonephritis or cystitis. We did not find severe cystitis in patients treated wsith cyclophosphamide. CONCLUSIONS: Acute and chronic irradiation nephropathy are rather anatomic than functional lesions. Planning, dose and period of the radiotherapy, irradiation volume play parts in the development of complications. Prior chemotherapy increases incidence of irradiation nephropathy. These rare complications of Hodgkin’s disease are usually avoided with the use of modern radiotherapy apparatus and the up to date treatment methods.
AIM: To study the occurrence of valvulopathies after treatment in Hodgkin’s disease patients. PATIENTS AND METHODS: 124 Hodgkin’s disease patients in complete remission for at least 1 year were echocardiographically examined. RESULTS: Abnormal finding was observed in 48/124 (38.4%) of patients, all of them presented with regurgitation, no stenosis was observed. Regurgitation of grade I or II was recorded in most cases. We have found single valvulopathy in 25/48 (52.1%) of patients, and multiple valvulopathy in 23/48 (47.9%) of patients. In most cases (78.7%) the valvulopathy was detected in left heart. Among these 48 patients the ratio of females was significantly higher than those of males, and also the ratio of the patients in early phase compared with those in late phase. We could detect vitium mostly in those patients who had mediastinal irradiation. The combined treatment, including anthracycline therapy, did not increase the frequency of vitium. CONCLUSION: The occurrence of valvulopathy is frequent in Hodgkin’s disease patients, particularly in patients treated by radiation. This is the reason why Hodgkin’s disease patients should be examined regularly with echocardiography. These patients with valvulopathy need treatment adjusted to their state of health, and where possible, the complications should be prevented. In the future, when planning of the radiotherapy - mediastinal irradiation of the Hodgkin’s disease patients their heart protection from radiation should be taken into account.
Bisphosphonates are effective against increased bone resorption because they inhibit osteoclast activity. The use of these drugs is well established for the treatment of metastatic breast and other cancers; they reduce skeletal complications, hypercalcemia, bone pain, and metastatic progression and they can improve the overall survival and quality of life. Preclinical observations and early clinical data indicate that early bisphosphonate treatment reduces the incidence and the extent of newly developed metastases in breast cancer. There is considerable interest in determining whether bisphosphonate treatment is to prevent the incidence of bone metastases and associated complications. To date three randomized, controlled clinical trials have examined the effect of long-term use of clodronate (1600 mg/d po.) on the incidence of bone metastases, other metastases, the survival of patients, and the side effects of the study drug as well. All the trials have observed significant reduction of the occurrence of bone metastases, although this reduction was significant only during the medication period. One of the trials mentioned have shown an unexpected reduction in non-osseous metastases, and two of them have revealed significant improvements in the death rates. These promising results need further evaluation by large clinical trials with longer treatment periods to establish the clinical role of adjuvant bisphosphonate treatment of primary breast cancer.
The Hungarian bisphosphonate market has been increasing for years; last year the number of patients was approximately 3200-3500. We decided to start a research among patients having malignant disease with bone metastases, in order to find out how patients evaluate the drugs, how they are informed and what is the role of doctors and nurses in compliance. Nearly 300 patients filled questionnaires and we have made 16 indepth interviews. The average age of patients was 57 years. More than 60% of patients were younger than 60 and the male-female ratio was 1:2. We found that more than one quarter of the patients arrived to their doctor from farther than 50 km and 70% of them meet their doctor at least once a month. The results showed that 95% of patients would prefer oral treatment (tablets or capsules), and 75% of the patients would choose tablets, if they were asked. Most of the patients wanted to be informed primarily by doctors. Nurses were the hostesses of emotional problems. Doctor-patient relationship was characterised by paternalism. Female patients were more open to nurses, they talked over smaller problems emerging during the treatment and the same occured with some male patients, too. Only 5% of patients received the treatment of their choice. Patients want to be involved more actively in the planning of their treatment process than doctors think, they expect that doctors should prefer their interest. Cancer patients are frequently underinformed and they expect more help to solve their psychological problems.
The author stresses, out of the abundant literature of melanoma, those new pieces of information that have changed the conventional therapeutic approach to melanoma. Elements of melanoma progression leading to a rational transformation of the dogmatic radical surgery are described. In addition, the phenomenon of regression, still requiring further investigations, is also dealt with, as well as the hormonal dependence of melanoma, which has practical importance in the management of some problems, e.g. indication of pregnancy interruption, hormonal contraception, and hormon substitution therapy in postmenopausa. The limited effectiveness of conventional complex tumour killing mechanisms (chemotherapy and radiotherapy) necessitates new therapeutic strategies based on tumour biological knowledge. Finally, the fields of application of vaccination and antiangiogenic and gene manipulation techniques are touched upon.
The authors briefly survey general aspects of crucial importance for the proper functioning of the National Cancer Registry, such as legislation, collected data, identification of patients, the completeness and validity of its content in relation to the results and conclusions of a comprehensive, national supervision performed after the Melanoma Consensus Conference. Compared to earlier national controlling attempts, the present supervision was highly successful: doctors of various hospitals did perform the detailed control of diagnosis in 95.81% of 1361 melanoma patients announced in 2001. They checked whether patients given the C43 BNO code had melanoma indeed, searched for those who received a different BNO code and identified those not announced for any reason to the Registry. After correction the Registry included 1117 new cases of melanoma in 2001. The authors state that the conclusions from this supervision may enhance the reliability not only of the data base of the Registry but that of the hospitals as well.
Clinical observations and histological findings support the relationship between pigmented naevi and melanoma. The author describes the morphological characteristics of congenital, acquired and atypical naevi in relation to the appearance of melanoma. On the basis of clinical observations, in harmony with other investigators, the author advises patients to perform self examination and to undergo regular survey of numerous atypical naevi by a dermatologist. In fact, any of the atypical pigmented naevi present in high number may be a precursor lesion. Patients with such lesions are at higher risk of melanoma development.
The histological appearance of benign melanocytic naevi and malignant melanomas can be variable, causing in a significant number of cases severe differential diagnostic problems. The early, thin (less than 1 mm) melanomas have to be differentiated from naevi containing dominant junctional or lentiginous component or pagetoid melanocytosis and from some epithelial tumours, while in cases of thick lesion the diagnosis of thick melanoma, Spitz naevus, deep penetrating naevus or cellular blue naevus should be considered for example. The morphology of the so-called atypical Spitz naevus and atypical pigmented spindle cell naevus show overlapping with malignant melanoma and sometimes in these cases the biological behaviour cannot be assessed. The variable appearance of malignant melanoma is illustrated by the fact that different superficial soft tissue tumours with epithelioid and/or spindle cells or with pigment can mimic it. The rare balloon cell and signet ring cell melanoma is a mimicker of primary or metastatic carcinoma and the desmoplastic variant is often misdiagnosed as benign mesenchymal lesion. Lymph node metastasis of melanoma, when the primary tumour is not known, may raise the possibility of interdigitating reticulum cell tumour or anaplastic large cell lymphoma.
The role of fine needle aspiration biopsy (FNAB) is discussed in the follow up of patients with the diagnosis of malignant melanoma. The review is based on literary data and the author’s own material. The primary role of FNAB is to confirm metastatic or recurrent melanoma lesions. US or CT guided FNAB is valuable in the diagnosis of visceral metastases. FNAB has limited role in the diagnosis of primary melanomas except in cases with unusual clinical presentation (e.g. oral mucosa). In spite of the well-known cytology the diagnosis can be difficult due to the inherent histological variation of malignant melanomas, especially in cases with unusual localisation and amelanotic tumor presentation when immunocytochemistry is needed. The known clinical history of melanoma is very helpful.
The diagnosis of malignant melanoma must be followed by treatment shown to be effective. Therefore a correct diagnosis, including staging, that will permit a meaningful prognosis and treatment, is essential. The usefulness and great specificity of immunological methods is based on the detection of antigens characteristic of neoplastic and reactive cells. In cases of malignant melanoma, immunohistochemistry has limited practical value in the routine diagnosis of melanocytic lesions. The method may be important, however, in the differential diagnosis of, for example, malignant melanoma vs. non-melanocytic anaplastic neoplasia, malignant vs. benign melanocytic lesions, etc. Recent advances in relating the immunostaining of antigens to the development of tumor cells, such as proliferation and apoptosis, metastatic potential, etc. have given considerable importance to the immunomorphological evaluation of malignant melanomas. Likewise, immunotherapy requires the immunophenotyping of the reactive cells of the immune system.
This review summarizes data related to the pathological assessment and interpretation issues of sentinel lymph nodes in melanoma patients. After a short description of conventional nodal staging of melanoma, separate sections deal with detailed analysis of sentinel nodes, the use of immunohistochemistry, molecular analysis of occult metastases and the possibilities and limitations of intraoperative assessment. Possible pitfalls of each method are also discussed. Finally, research areas related to sentinel nodes are highlighted, too.
The identification of increasingly powerful prognostic factors has led to sequential modifications of the cutaneous melanoma staging system. The American Joint Commitee on Cancer (AJCC) recently proposed major revision of tumor-nodemetastasis (TNM) categories and stage groupings for melanoma. The authors summarize the main characteristics of this new TNM classification of malignant melanoma. The importance of the novel technique - sentinel node biopsy - in the management of malignant melanoma is discussed.
Nucleic acid based molecular techniques have been introduced into the diagnosis of malignant melanoma similarly to other cancers. They were applied for refinement of staging and to detect minimal residual disease. There are several good melanocyte-specific genetic markers such as tyrosinase, gp100, Melan-A/MART-1 and MIA. Unlike in the case of the lymph nodes, peripheral blood or bone marrow do not contain melanocytes excluding the possibility of fals positive reactions. Considering the pronounced heterogenity of melanoma cells the most reliable molecular marker is the expression of tyrosinase. Several studies indicate that the quantity of circulating melanoma cells correlates with tumor burden and disease progression and reflects the effect of therapy. On the other hand, molecular techniques detect circulating melanoma cells much more frequently than the clinical manifestation of the disease progression (molecular recurrence), questioning the clinical significance of the detection of a small number of melanoma cells in the circulation. Based on these data molecular diagnostics is not part of the melanoma protocols yet and further studies are necessary to define its diagnostic role.
Surgical interventions have important role in the treatment of all stages of malignant melanoma. Surgery is the primary treatment of localized cutaneous melanoma. Excision of the primary tumor makes it possible to set up the histological diagnosis and to determine pathological prognostic factors. Appropriate surgical margin is important for local disease control. Sentinel lymph node biopsy with detailed histological examination has gained prominent importance for correct histological staging and for determining adjuvant oncological treatment. Surgery is the primary treatment of isolated regional metastases. Surgical methods also have a role in the palliative management of distant metastatic melanoma. In the present review the most important issues of the surgical treatment of malignant melanoma have been discussed in detail.
OBJECTIVES: Report on clinical observations obtained with sentinel lymph node surgery for malignant melanoma and during follow-up at the Department of Dermatology, National Institute of Oncology, Budapest. PATIENTS AND METHOD: In the period from November, 1997 to September, 2002, the above surgical intervention was made with 179 patients having primary tumour, one to two months after primary tumour removal. Staining with patent blue was combined with isotope technique. The primary melanoma and the pertaining sentinel lymph node(s) were removed. Histological evaluation of the sentinel lymph nodes was performed in serial sections. Immunohistochemical detection of S100, HMB-45, or Melan-A was used in the case of suspected micrometastases. Demonstration of positive sentinel lymph nodes was followed, preferably within 2-3 weeks, by regional block dissection. Interferon in low doses or BCG immune therapy were applied as adjuvant therapy. Bimonthly follow-up of the patients included physical examination and the use of imaging techniques as specified in the melanoma protocol. RESULTS: Sentinel lymph node surgery was successful in 177/179 cases (98%). Positive sentinel lymph node was identified in 26/177 patients (14%). In node positive patients the thickness of the primary tumour was significantly greater than that of node negative ones (p<0.0000). Patients with micrometastases had significantly poorer symptom-free and overall survival by the Mantel-Cox test than those of the other group (p=0.0001 and p=0.0007, respectively). In the discriminance analysis of our data, the discriminant function established from tumour thickness yielded 81.7% and the positivity of sentinel lymph nodes 79.9% correct classification rates. CONCLUSION: In good harmony with literature data, positive sentinel lymph node(s) were found in the case of thicker tumours. The involvement of sentinel lymph node indicated a significantly poorer prognosis.
Approximately one third of clinical Stage I melanoma patients will experience disease recurrence. The author reviews the main prognostic factors predicting the outcome of melanoma patients, the incidence, pattern and time of first metastases. Of all recurrences, two third will occur earlier by the lymphatic, and one third later by the hematogenous pathway. 75-80% of recurrences develop in the first 3 years, 3-4% of metastases occur after 10 years of disease-free interval. The data emphasize the value of lifelong follow-up.
Extracellular tumour markers may have potential role in the follow-up of patients with malignant melanoma, in therapy monitoring and in prediction of prognosis. In our article circulating tumour markers in melanoma (melanoma inhibitory activity, lipid bound sialic acid, neuron specific enolase, TA90 immunkomplex, S-100B protein, 5-S-cysteinyldopa, tyrosinase, cytokines, metalloproteinases, LDH) were reviewed. Among laboratory melanoma markers the S-100B protein is the most investigated. S-100B protein has high specificity, appropriate sensitivity and proved to be significant prognostic factor independent from stages. High serum values are associated with shorter survival. However, before S-100B monitoring immunohistochemistry for the detection of S-100B is required. In the case of malignant melanomas with low expression serum S-100B monitoring may not be sensitive enough to follow disease progression. Although the serum concentration of 5-S-cysteinyldopa did not prove to be independent prognostic factor in our previous studies comprising the highest patient number in the literature, the marker was suggested for therapy monitoring. The survival analysis indicated that the elevated 5-S-cysteinyldopa level predicts shorter survival. In spite of the calculated low correlation between the two markers, parallel elevation of S-100B protein and 5-S-cysteinyldopa indicated shorter survival. On the basis of the literature LDH is the most appropiate tumour marker in stage IV to predict prognosis, but its sensitivity and specificity could not achieve that of S-100B protein. S-100B and LDH proved to be similarly reliable in respect to the clinical outcome. Determination of serum concentration of MIA and tyrosinase are also reliable markers in malignant melanoma. The other investigated markers are not well known yet or do not provide useful information to the clinicians.
Interferon is a pleiotropic antitumor biological agent that elicits its effect in a dose-dependent manner. Interferon has been tested in high, medium, and low doses; controlled studies, however, indicated that only high-dose therapy markedly prolonged the survival rate. Due to its high toxicity, the high-dose treatment modality has not been widely accepted. At present, neither the optimal dose, nor the duration of interferon adjuvant therapy are established. Furthermore, parameters that could predict responders to treatment are not yet identified. Before careful evaluation of the large-scale, controlled, multi-centric studies, the authors recommend strategy that combines intermedier and highdose therapy for adjuvant treatment of patients with melanoma.
The appearence of brain metastases in patients with malignant melanoma predicts poor prognosis. During the last ten years important progress has been made in the treatment of brain metastases providing longer survival and better quality of life for these patients. In this review article the different treatment modalities, surgery, radiosurgery, radiation therapy and chemotherapy are described and the results published in the literature are briefly presented. Emphasis is made to show the effectiveness of a multimodality approach of this group of patients resulting in a better clinical outcome.
Despite their well-documented immunogenicity, malignant melanomas belong to the most aggressive tumor types. A potential explanation for this is the suboptimal activation of tumor infiltrating T cells. In order to boost immune responses against tumors, a variety of treatment modalities have been tested in animal models and in clinical setting. Antigen-nonspecific approaches (e.g., IFN-alpha and IL-2), as well as active specific immunotherapeutical modalities based on the use of autologous or allogeneic tumor cellsave been investigated in clinical trials of melanoma. The identification of melanoma-associated antigens has opened new avenues in antigen-specific immunotherapy. A promising alternative for the delivery of different forms of melanoma antigens is the application of dendritic cells, the most potent antigen presenting cells capable of eliciting efficient T-cell response. Beside active immunotherapy, immune response against melanoma antigens could be increased through the adoptive transfer of tumor infiltrating lymphocytes or antigenspecific T-cell clones. The most important conclusion that can be drawn from the results of published immunotherapy studies is that these modalities are able to induce durable complete tumor regressions,mostly with reasonable toxicity; however, generally only in a minority of patients. This points to the importance of appropriate patient selection, with regard to the expression of the targeted antigens and HLA molecules, as well as to the general immunocompetence of the patients. A crucial and still unsolved question is monitoring immune activation during treatment, although there are promising new tools that could prove useful in this respect. The presence of tumor-reactive CTL in the circulation or in the tumors does not guarantee an efficient immune response. It is important to assess if these T cells are in an activated and functional state. Finally, in several single target antigen-based clinical studies a therapy-induced immunoselection of antigen-negative clones, leading to disease progression, was observed. This could be overcome with the use of antigen cocktails or whole tumor approaches. A better understanding of the mechanisms of action of immunotherapeutical modalities may enhance the success rate of these strategies.
The role of estrogens, including its sources, tissue distribution, metabolism, and mechanism of action, is discussed in this review. The ER alpha and beta are functioning separately, and there is a physiological balance between their activity. Whenever this balance is overthrown due to endogenous or exogenous carcinogenic factors, malignancy develops. Risk factors of breast cancer are listed and evaluated individually. It should be stressed however, that their carcinogenic effect sums up. The knowledge of established risk factors rises the possibility of chemoprevention, which might be highly desirable in case of gene carriers. Special emphasis is attached to the SERM molecules which act as antiestrogens. Their antitumour effect is largely used in the treatment of hormone sensitive advanced breast cancer patients, and their efficacy has been proved in adjuvant therapy as well. Their preventive use might also be justified, especially in gene carriers. Aromatase inhibitors form a special class among the SERM molecules. In Hungary, anastrozole, letrozole and exemestane are widely applied for the therapy of breast cancer patients, while raloxifene has only been introduced recently, mainly in order to prevent osteoporosis. The therapeutic value of fulvestrant is unknown yet and its antitumour effect has to be explored. The therapeutic significance of these molecules lies in the fact that they might be effective after the development of tamoxifen resistance. There are several explanations for this phenomenon offering new targets for the further development of a succesful antitumour chemotherapy.
AIM: The authors present the Hungarian interim analysis and experience with the BCIRG 001 randomized, multicentric, phase III clinical trial comparing TAC (docetaxel, doxorubicin, cyclophosphamide) and FAC (5-fluorouracil, doxorubicin, cyclophosphamide) in the adjuvant treatment of node positive breast cancer patients. The results are presented according to international data. PATIENTS AND METHODS: Three Hungarian centers - St. Margit Hospital, Budapest, National Institute of Oncology, Budapest, Petz Aladár Hospital, Gyôr - participated in the international trial. Between June 1997 and June 1999, 61 patients with node positive breast cancer were enrolled in the study after the surgery. Thirty-four patients were randomized to TAC (75/50/500 mg/m2 6x q3wk) and 27 patients were randomized to FAC (500/50/500 mg/m2 6x q3wk) chemotherapy, with prospective stratification by node (1-3, 4+). In the case of patients with ER and/or PR positive tumours 5 years tamoxifen treatment was started. Radiotherapy was performed after the 6th cycle of chemotherapy. RESULTS: 36 months of follow up was performed. In both arms the hematological toxicity was more frequent. The TAC group showed a higher incidence of neutropenia (76%) compared to the FAC (22%), as well as a higher incidence of febrile neutropenia (26%), without grade 3-4 infection and there were no cases of septic death. Regarding non-hematological toxicity more grade 3-4 nausea and vomiting was observed in the FAC group. At three years follow up, the international results show statistically significant improvement in disease-free survival (82% vs. 74%, p=0.0011) in favour of TAC, and similar tendency was observed in the case of overall survival (92% vs. 87%, p=0.11). This benefit with TAC was seen regardless of hormone receptor status. Due to the low number of Hungarian patients we cannot declare the same results. CONCLUSIONS: Based on the international analysis TAC was superior to FAC chemotherapy. Additional follow up data will evaluate the role of TAC in the adjuvant setting of early breast cancer treatment. The results indicate that TAC has the potential to be incorporated in the new strategies of adjuvant breast cancer treatments.
INTRODUCTION: The organized breast cancer screening programme has started in Hungary at the end of 2001. AIM: To assess the screening rate, the cost of screening and treatment and to calculate the expected epidemiological and economic gain and cost-effectiveness of mass-screening programme. Methods: The data derive from the financial database of the National Health Insurance Fund of Hungary from 2001. To assess the screening rate the authors used the code No. 42400 mammography screening of outpatient care. The cost of treatment includes the cost of outpatient care, the acute and chronic inpatient care, the subsidies of the prices of medicines and the expenditure on disability to work (including sickness-pay). The expected benefits of the screening programme were modeled with changing mortality decrease for a 10 years interval. RESULTS: The screening rates of women aged 45-65 for 2001 and 2002 were 7% and 21.7%, respectively. The cost of treatment of breast cancer was around 8.6 billion Hungarian forints (29,939,868 USD, 33,426,321 EUR) in 2001. In the age-group 45-65 with 10% mortality decline 509 lives (net present value, NPV: 365), with 20% mortality decline 1.074 (NPV: 772) lives and with 30% mortality decline 1.582 (NPV: 1.139) lives can be saved during a 10 years screening programme. The cost of one life saved varies between 5.7 million forints (19,876 USD, 22,190 EUR)/life saved and 17.8 million forints (62,047 USD, 69,273 EUR)/life saved according to the mortality decline. The cost of one life year saved varies between 271,000 forints (946 USD, 1057 EUR)/life year saved and 847,000 forints (2955 USD, 3299 EUR)/life years saved. CONCLUSION: The implementation of organized breast cancer screening can lead to cost savings in Hungary. The cost-effectiveness of breast cancer screening seems to be acceptable for purchaser.
OBJECTIVE OF THE STUDY: to investigate the clinical outcome of HNSCC patients, and their hormonal status. METHOD: The liver function (GGT), hypophysis gonadotrop hormone (FSH, LH, prolactin) and sexsteroid hormone serum levels were examined in 130 male HNSCC patients. Clinical parameters for age, primary tumor site and clinical tumor stage were also recorded. RESULTS: The survival was disadvantageously influenced by the following parameters: age, the presence of lymph node metastasis, advanced tumor stage, the lower than normal testosterone and the higher than normal FSH serum levels. CONCLUSION: Elevated FSH and decreased testosterone serum levels showed significant correlation with the survival of head and neck cancer patients. The better understanding of their exact role in the biology of HNSCC requires further investigations.
AIM: To present a unique case of an early (T1N0M0) adenocarcinoma of the head of the pancreas, which was successfully treated with radiotherapy alone. MATERIAL AND METHOD: After the computer tomography operated histological verification the combination of interstitial high dose rate after-loading brachytherapy (18 Gy, 6 Gy/die) and percutan irradiation (46 Gy) was applied. RESULT: Fifty-two months after completion of the treatment the patient is alive with no evidence of disease. CONCLUSION: The combination of these therapeutic modalities may be an effective tool to deliver curative dose without any significant sequelae in the treatment of operable pancreatic carcinoma, when the patient’s condition contraindicates surgery.
The authors determined serum PSA levels in combination with digital rectal examination (DRE) and evaluated their role in the differential diagnosis of prostate diseases with special reference to cancer. The possible causes of differences between the observed cut-off level of PSA and the standard level PSA were analyzed. In the last few years the PSA determination found its clinical role in the diagnosis of prostate cancer.
In the second half of 2002, IARC for Central and Eastern European countries targeted studies on the relationship between chromosomal aberrations (CAs) and cancer risk. For these purposes we preliminarily investigated, under identical methodological circumstances, the base-line level of CAs in peripheral blood lymphocytes of 1414 healthy Hungarian persons between 1986 and 2001. The age and sex as biological, and smoking habit and residency (Budapest, industrial- and agricultural settlements) as environmental confounding factors were evaluated. Previously, people were not exposed to any known potential mutagens. The overall frequencies of aberrant cells (1.60±0.05%) were not influenced by sex, age and residency, but the smoking habits (1.84±0.09%) had significant impact on the elevation of aberrant cells. Aneuploidy, exchange-type dicentric chromosomes and the total of aberrations increased significantly with the age of the donors. The individual frequency of aberrant cells ranged between 0-12%. No aberrant cells were detected in 35% of individuals, and 1aberrant cell was found in 23% of the total population, while 42% of the examined persons were characterized with aberrant cell rates between 2-12%. The initial value of 0.85% of aberrant cells doubled by the end of the examined 16-year period, following 2-4-fold fluctuations. None of the investigated biological or environmental factors was responsible for the elevation of the CAs. The causes of the elevation of CA-level can be explained more precisely when these data will be compared to cancer registry database of these persons.
BACKGROUND: The environment is source of carcinogen effects, which cannot be monitored as precisely as it would be required. Due to this fact, it is worth to screen for areas with higher than expected number of cancers that is for clusters. The significance of cluster suspicion is highly variable and the investigations for clusters could need significant resources. Therefore step-wise protocols are recommended, which evaluate before proceedings the possibility of exclusion of cluster existence, or of requirement for further epidemiological investigations. Sometimes, the results establish actions to reorganise the environmental control. OBJECTIVES: The relationship between cancer incidence and dangerous waste disposal sites was investigated in Tolna county (Hungary) and the usefulness of cluster studies was demonstrated by the results. METHODS: The incidence data based on histological investigations and the location of 7 dangerous waste disposal sites were analysed by geographical information system. RESULTS: The incidences were not elevated around 6 sites. The cancer risk seemed to be high by site in settlement S., because of high standardised incidence ratio (SIH=1.41) and empirical Bayes adjusted SIH (SIHEB=1.38). The risk increase proved to be significant in z-test and mid-p test by 10% and 15% type I error. Since the risks showed nonhomogeneous spatial distribution in the county and the number of high-risk settlements was 2.3 to 6.6, the cluster in S. cannot be rejected as false positive observation. The chromium contaminated wastes have been stored in S. for several decades at river-side. Assuming that the exposure was spred by the river and the villages in the 5-km vicinity of the river were exposed, the SIHs were aggregated for every 15-km intervals. The distance from S. was inversely related to the aggregated SIHs. CONCLUSIONS: The sites proved to be noncarcinogenic sources apart from the site S. for which the results suggested the high-risk status. The environmental pollution by site in S. could explain the increased incidence. Consequently, additional studies are indicated in S. to improve the reliability of cluster evaluation. The study also demonstrated that the cluster investigation can be inserted into public health practise to improve the efficiency of cancer control.
120 chemotherapy naive patients were treated with gemcitabine 1250 mg/m2 iv. days 1 and 8 and cisplatin 70 mg/m2 iv. on day 1 between May 1999 and June 2001. The treatments were administered in 21 cycles. The median age of the patients was 53.1 years, the male/female ratio 65%-35%. Performance status was: WHO 0: 26%, WHO 1: 74%. The staging of patients were: IIIA-N2 23%, IIIB 37%, IV 40%. By histology the tumors were: 53.3% adenocarcinoma, 40% squamous cell carcinoma, 2.5% adenosquamous carcinoma, 0.8% macrocellular carcinoma and 3% non-small cell carcinoma (not categorised). We evaluated 413 cycles of chemotherapy. The median number of cycles was 3.44. The primary endpoint of the study was the median survival and time to progression, and the response rate. The results are the following: RR 40% (PR 37.5%, CR 2.5%), MR 13.3%, SD 25%, PD 22%. The time to progression (TTP) in the SD+MR group: 29.8 weeks, in the RR group: 34.1 weeks, mean of all patients: 28.1 weeks. The survival time was estimated by Kaplan-Meier curves. The median survival (MS) of all treated patients was: 54.9 weeks, in the PD group: 34.4 weeks, in the SD+MR group: 59.1 weeks, in the PR+CR group: 62.1 weeks. Conclusion: gemcitabine and cisplatin combination is a very well tolerated therapeutic regimen in the 1st line treatment of NSCLC. Furthermore, this treatment improves the RR and the survival of the patients as well.
In our Department we have studied the first line treatment of 90 stage IIIA-IV non-small cell lung cancer patients using gemcitabine/cisplatin combination. Thirteen cases have been unevaluable for various reasons. At the time of evaluation the planned 4 cycles have been delivered to 38% of patients (34/90). The PR was 39% (30/77), the CR was 2.6% (2/77) while the ORR was found to be 41% (32/77). 226 treatment cycles have been evaluated for side effects. There was no treatment-induced death in this series. CTC grade 3-4 neutropenia occurred in 5.7% of the cycles and only in 2 cases combined with fever. CTC grade 3-4 thrombocytopenia occurred in 4.4% of the cycles but only one patient required platelet suspension administration. Grade 3-4 anaemia developed in 3.5% of the cycles where 5 cases have been treated with RBC concentrate while 3 cases with erythropoetin. Complete alopecia occurred in 6 patients but 3 of them received brain irradiation as well. CTC grade 3-4 nausea and vomiting occurred in 4.4 and 3% of the cycles, respectively, but rehydration was only necessary in 3% of the cycles. Delay of the therapy due to hematological toxicity or vomiting occurred in 8% of the cycles but did not last longer than 2 weeks. Severe CTC grade 3-4 nephrotoxicity did not occur in this study while grade 1-2 elevation of serum creatinin level was found in 1.7% of the cycles. We have concluded that the gemcitabine/cisplatin combination is a safe outpatient modality for the first line treatment of advanced non-small cell lung cancer patients.
In the first phase of this study 34 patients with advanced pancreatic cancer have been treated either with gemcitabine/cisplatin or gemcitabine/5-fluorouracil (5FU)/leucovorin combination. (Gemzar: 900 mg/m2, Cisplatin: 20 mg/m2, 5-FU: 750 mg/m2). Treatments were continued till tumor progression. There was no difference observed between the two protocols in the clinical response rates (PR=65%). On the other hand, a significant difference was found between the two protocols regarding the side effects. In the case of gemcitabine/5-FU neutropenia, thrombocytopenia and anaemia (as well as nausea and vomiting) were much less frequent compared to gemcitabine/cisplatin combination. Based on these data the efficacy of gemcitabine/5-FU combination was evaluated in 99 stage III, T1-4, N1 and stage IV, T1-4, N0-1, M1 pancreatic cancer patients throughout 364 treatment cycles. OR was achieved in 10% while stable disease in 52% of the cases. The average survival period was 8.33 months while the time to progression was 5.75 months. Based on these data we recommend gemcitabine/5-FU/leucovorin combination for the treatment of advanced pancreatic cancer.
M-VAC combination chemotherapy was considered as the gold standard of the treatment of advanced and metastatic bladder cancers. Arrival of gemcitabine or taxanes in the 90s attracted attention since their efficacy was combined with low toxicity profiles. Gemcitabine/cisplatin combination became the most frequently studied treatment modality in the past 3 years. Multicentric, multinational randomized phase-III study indicated that in bladder cancer the gemcitabine/cisplatin combination is equal to M-VAC while in the case of the former the risk to benefit ratio is lower. Accordingly, gemcitabine/cisplatin combination is a safer treatment option in advanced and metastatic bladder cancer and is a real alternative to M-VAC. In the case of patients where cisplatin cannot be administered due to poor renal function, the new drugs with better toxicity profiles provide further treatment options.
The authors present data on 13 patients operated on for the treatment of locally advanced colorectal cancer infiltrating the adjacent parts of the urinary tract. Based on prior diagnostic evidences, every surgical intervention has been indicated as an expected curative resection. All patients of this study underwent a curative resection. The origin of the advanced cancer was in 9 cases the sigmoid colon, in 3 cases the rectum and in 1 case the ascending colon. Beside the resection of the tumorous colon or rectum, a resection of the urinary bladder has been performed in 9, a nephrectomy in 3 and the resection of the ureter in 2 cases. An additional gynecological resection was made in 4 cases for tumors infiltrating the female internal genitals. No mortality and no serious complication needing reoperation occurred in these series. Based on their experiences of a series of 13 radically operated cases, the authors suggest extended multiple organ resection for the treatment of advanced colorectal cancer infiltrating the urinary tract.
Gastro-entero-pancreatic (GEP) endocrine tumours can originate from various pancreatic islet cells, from endocrine cells of the gastric and duodenal mucosa, or from APUD cells of neuroectodermal origin in the gastrointestinal tract. They are benign when smaller than 2 cm, but larger tumours are generally malignant. Surgery is the only method for the curative treatment of GEP tumours. A diagnosed and localised tumour is an absolute indication for radical surgery. Conservative medical treatment may be indicated only in an inoperable condition, but in this case tumour reduction surgery is suggested. In the last 15 years 22 patients with pancreatic neuroendocrine tumours were treated without any mortality. Except for two of them, the surgical therapy was curative.
INTRODUCTION: One of the subtypes of pulmonary adenocarcinoma, bronchioloalveolar carcinoma (BAC), is mentioned as the lung cancer of non-smoking women. We have studied the clinical characteristics of BAC and its surgical teatment. METHODS AND PATIENTS: Between 1992 and 2001, lung resections for BAC were performed on 101 patients: 55 men and 46 women, average age 59.7 years. Thirty-two of the patients were non-smokers, and 69 were active smokers. In 1992 the incidence of BAC was 17.5% of all adenocarcinomas, whereas in 2001 it had risen to 51.6%. The operations involved 76 lobectomies, 12 pulmonectomies, 11 wedge resections and 2 explorative thoracotomies. RESULTS: The surgical mortality was 0.9%. The final histologic findings revealed that 82.1% of the tumours were in stages I or II, with 33.7% of the total in stage I/A. The average 5-year survival was 64.3%. Survival for women 75%, was significantly better than that for men, 51% (p=0.045). A significant difference was not found in the 5-year survival rate for multiple tumours or for BAC cases of different histological types. CONCLUSIONS: The incidence of BAC, which occurs relatively frequently among women, and exhibits a relatively favourable course, has tended to increase in recent years. A majority of these tumours are removed in an early stage. The survival is not significantly poorer in the event of multiple tumours.