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Background: The expression of epidermal growth factor receptor (EGF-R) in breast cancer (BC) is generally considered as an unfavorable event during tumor progression. Its predictive role has been fairly well defined: EGF-R expression predicts tamoxifen unresponsiveness. EGF-R role in autocrine growth regulation was confirmed. However, reported results on its prognostic role in BC patients were conflicting. The prognostic role of EGF-R after 15 years of follow-up is analyzed in a group of 70 localized BC patients, presented at diagnosis in clinical stages I-III. Methods: BC patients newly diagnosed from December 1990 until March 1991, treated in accordance to the National Protocol, were selected for EGF-R analysis. Steroid receptors and EGF-R were determined at diagnosis in same frozen tissue samples, using biochemical methods. Except 6 patients who were lost from follow-up in the interval shorter than 60 months, the remaining patients were followed-up from 60-188 months. The total number of events was 32 relapses (46%), and 27 deaths (38.5%). Results: EGF-R expression was found in 28/70 patients (40%), and the EGF-R content higher than 26 fmol - in 15/70 patients (21%). Neither the expression, nor the high content of EGF-R showed any influence on disease-free or overall survival. Levels of EGF-R were similar in relapsing and relapse-free patients. Nodal status had the strongest infuence on prognosis. Conclusion: Our results suggest that the controversial findings, regarding the EGF-R prognostic role, might be the consequence of a genuine weak influence of EGF-R expression on disease outcome. .

BACKGROUND: Breast conserving surgery followed by postoperative radiotherapy, as alternative to radical mastectomy, has been accepted as an optimal method for loco- regional treatment of the majority of women with early stage of breast carcinoma. The aim of the study was to evaluate the results of postoperative radiotherapy after breast conserving surgery in the Institute for oncology and radiology of Serbia. METHODS: During the 3-year period, 109 breast cancer patients with stage I and II were treated with postoperative radiotherapy after breast conserving surgery. Ninety- four patients underwent quadrantectomy with axillary node dissection, and 15 patients underwent only tumorectomy. After surgery all patients received postoperative radiotherapy to the whole breast with tumor dose 50 Gy in 15 fractions every second day. In 52 patients radiotherapy was given to the regional lymphatics with tumor dose 45 Gy in 15 fractions every second day. Twenty-eight patients received a booster dose (10 Gy) to the tumor bed. Adjuvant systemic therapy was administered depending on the nodal involvement and steroid receptors content: 17 patients received adjuvant chemotherapy (CMF or FAC), 18 received adjuvant hormonal therapy (tamoxifen or ovarian ablation), and 6 patients received both chemo- and hormonotherapy. RESULTS: After median follow-up period of 62 months, there was no evidence of loco- regional recurrence in anyone of patients. Distant metastases occurred in 7 patients (6.4%) with median disease free interval of 27.6 months. At last follow-up 91 patients (83.4%) were alive, 4 patients (3.7%) were dead of disease, and the same number was dead of other causes. The 5-year overall survival rate was 92.9% and disease-free survival rate was 92.7%. CONCLUSION: According to our results the combined surgery and radiotherapy approach provides good local control of early breast cancer patients. Postoperative radiotherapy after breast conserving surgery with or without adjuvant systemic therapy has important role in adjuvant treatment of early breast cancer.

BACKGROUND: Radical or modified radical mastectomy was considered for many years the standard therapy for operable patients. Following radical mastectomy, postoperative irradiation of the chest wall and peripheral lymphatics is indicated in selected highrisk patients. Some studies on breast cancer patients who underwent radical mastectomy and received adjuvant chemotherapy tried to find out whether the addition of irradiation treatment to the chest wall and regional lymph nodes increases survival. The hypothesis in favor of irradiation is that chemotherapy can eliminate distant micrometastases, but is less effective against local and regional diseases, which are better controlled by radiotherapy. METHODS: In one year period, 110 patients with early stage of breast cancer were treated with radical mastectomy, and postoperative radiotherapy. Forty one patients had only postoperative radiotherapy, 27 received also adjuvant chemotherapy, 40 received adjuvant hormonal therapy and 2 patients received both adjuvant chemo and hormonotherapy. Postoperative irradiation was given on the regional lymph nodes (supra and infraclavicular, axillary and internal mammary nodes) with the tumor dose 48 Gy in 22 fractions over a period of four and a half weeks. All fields were treated with Cobalt 60. RESULTS After the median follow up of 67 months, 33 patients (30 %) had some kind of failure in form of local recurrence, distant metastases or both Locoregional relapse alone or associated with distant metastases occurred in 10 patients (9.1 %). Only 1.8 % of patients had local recurrence as the first failure. Distant metastases occurred in 32 patients (29.1%). After the end of follow up, 60 % patients are alive without evidence of disease while 16.4 % patients are alive with disease. The 5 year overall survival rate was 78.19% and 5 year disease free survival rate was 67.44%. CONCLUSION: Postoperative radiotherapy after radical mastectomy has important role in adjuvant treatment of early breast cancer in combination with adjuvant chemotherapy and hormonotherapy.

Background: The goal of this study was to introduce a new predictive biomarker assay that might improve a clinical irradiation treatment of malignant diseases. Methods: Thirty-two peripheral blood samples obtained from breast cancer patients were analyzed for superoxide dismutase (SOD) after irradiation with gamma rays (60 Co). SOD was measured in subcellular fractions prepared from unirradiated and irradiated blood samples (McCord and Fridovich). The activity of SOD was measured by the method of Misra and Fridovich and protein concentration by the method of Lowry et al. Results Antioxidant radiation response of patients' blood cells was very variable and specific for each individual. The results indicated that the radiation response during radiotherapy directly depends on the initial state of antioxidant activity in the blood of cancer patients. In the blood samples with high level of SOD activity the irradiation decreased enzymatic activity while in the samples with medium or low level of SOD, the SOD activity was preserved or increased by irradiation with 2 Gy of gamma rays. Conclusion We showed that the modulation of SOD activity in blood cells after irradiation in vitro might be used as predictive biomarker in individualization of therapy protocols.

Background: The aim was to investigate the application of radiopotentiation which was initiated by the fact that in patients with locally advanced non-small cell lung cancer there is a high risk of relapse due to failure in local control of the disease and the risk of systemic micrometastases. The other aim was the evaluation of quality of life. Methods: A study group consisted of 67 patients. Patients were first treated with TD30 Gy in 10 fractions during 2 weeks (5 fractions per week) with a potentiation by 20 mg/m 2 of carboplatinol intravenous bolus infusion just prior to each radiotherapy fraction. After a 2-week pause, additional radiation of 25 Gy in 10 fractions was applied during 2 weeks (5 fractions/week) with a potentiation by 20 mg/m 2 of carboplatinol. Total tumor dose (TTD) was 55 Gy (30+25 Gy) in 20 fractions, total duration of the therapy was 6 weeks, and total dose of carboplatinol was 600 mg. A control group consisted of 70 patients and they were treated with a radical radiotherapy with a conventional fractionation (60 Gy in 30 fractions, 2 Gy per day, 5 fractions per week). Quality of life was evaluated by Karnofsky performance scale (KI), at the beginning of the treatment, after the completion of the whole course of treatment, and during follow-up at regular check-ups. Results After the completion of the whole course of treatment most of patients had KI 80%. Analysis made during the last check-up showed statistically significant low KI. In both study and control groups KI was significantly higher at the beginning of the treatment than KI after the completion of the whole course of treatment (p=0.001). However, the analysis of KI at the time of the completion of the whole course of treatment showed significantly better KI in study group (p=0.036) than in control group. Conclusion: These results showed that the combined radiochemotherapy treatment is well tolerated.

Background: Locally advanced breast cancer (LABC) includes a heterogeneous group of breast neoplasms classified from stage IIB, IIIA to IIIB. LABC with ipsilateral supraclavicular adenopathy without evidence of distant disease is included in the stage IV (but regional stage IV). Purpose of this study was to assess the role of radiotherapy (RT) in combined treatment with systemic therapy (chemotherapy and hormonotherapy) in LABC with ipsilateral supraclavicular adenopathy. Methods: In 5-year period 45 patients with LABC and ipsilateral supraclavicular metastases were treated with radiotherapy and chemo- or hormonotherapy depending on the physical condition, age and steroid receptors (ER, PGR) content. Twenty patients received TD 30 Gy in 10 fractions on breast and regional lymph nodes and 25 patients received TD 51 Gy in 15 fractions on the breast and TD 45 Gy in 15 fractions on regional lymph nodes. Twenty-three patients received chemotherapy (CMF or FAC), 10 received hormonotherapy, and 12 received both chemo- and hormonotherapy. Results: After finishing complete treatment the overall response rate was 93.3%. Complete response was 20% and partial response was 73.3%. Locoregional relapse occurred in 5 patients and distant metastases occurred in 10 patients. Conclusion: Treatment of LABC with ipsilateral supraclavicular lymph node involvement should be aggressive, what means combined radiotherapy and systemic chemo-hormonotherapy. Such treatment provides for these patients maximum chance of long-term disease - free and overall survival.

Aim To collect cancer epidemiology data in South Eastern European countries as a basis for potential comparison of their performance in cancer care. Methods The South Eastern European Research Oncology Group (SEEROG) collected and analyzed epidemiological data on incidence and mortality that reflect cancer management in 8 countries - Croatia, Czech Republic, Hungary, Romania, Poland, Slovakia, and Serbia and Montenegro in the last 20-40 years. Results The most common cancer type in men in all countries was lung cancer, followed by colorectal and prostate cancer, with the exception of the Czech Republic, where prostate cancer and colorectal cancer were more common. The most frequent cancer in women was breast cancer followed by colorectal cancer, with the exceptions of Romania and Central Serbia where cervical cancer was the second most common. Cancer mortality data from the last 20-40 years revealed two different patterns in men. In Romania and in Serbia and Montenegro, there was a trend toward an increase, while in the other countries mortality was declining, after increasing for a number of years. In women, a steady decline was observed over many years in the Czech Republic, Hungary, and Slovakia, while in the other countries it remained unchanged. Conclusions There are striking variations in the risk of different cancers by geographic area. Most of the international variation is due to exposure to known or suspected risk factors which provides a clear challenge to prevention. There are some differences in incidence and mortality that cannot be explained by exposure to known risk factors or treatment availabilities. [ABSTRACT FROM AUTHOR]

Background: Bevacizumab is an anti-VEGF, humanized mAb that is the most advanced agent of its class in clinical development. Several studies have examined bevacizumab in combination with chemotherapy in the first- and second-line settings in patients with metastatic CRC. Despite of that, there is lack of information concerning the extent to which bevacizumab can be used to treat metastatic CRC. We still need more evidence related to efficacy and safety of bevacizumab in different settings, or sequential treatments. The aim of this study was to investigate efficacy and safety of bevacizumab added to different chemotherapy in patients with metastatic CRC. Methods: This was a controlled, prospective, multicentre, cohort study. Thirty patients with advanced colorectal cancer were enrolled into this study. Bevacizumab was applied with oxaliplatin-, irinotecan-, 5FU- or capecitabine -based chemotherapy in the first-, second- or third-therapy lines. Totally 261 cycles were applied. The median number of applied cycles per patient was 8 (range 2-16). Results: Objective tumor response (RR) was seen in 11 patients 37% (95%CI 19-69%) calculated on an intention-to-treat basis. The median duration of response was 12 months. Three of 11 patients (27%) with PR had secondary surgery. RR was seen in 9 of 16 patients (56%) who received bevacizumab in the first-line treatment and in 2 of 14 patients (14%) who received therapy in the second+ lines (p=0.02). Clinical benefit (PR+SD) was seen in 22 (74%) patients. 75% of patients achieved clinical benefit in the first-line and 74% in the second+ chemotherapy lines. The median time to progression (TTP) of the patients is was 9 + months (95%CI 7 - + ∞) at the moment of this analysis. The median TTP of patients who received bevacizumab in the first line was 11 months (95%CI 8 - + ∞). The median TTP of patients who received bevacizumab in the second+ lines was 5.5 months (95%CI 4 - + ∞) (p=0.015). The median survival time (OS) for all patients was 9 + months (95%CI 7 - + ∞). The median OS at the moment of analysis was 11 months (95%CI 9 - + ∞) for patients receiving bevacizumab in the first line, and 7 months for patients receiving the drug in the second+ lines (95%CI 6 - + ∞) (p=0.024). The incidence of any toxicity grade 3-4 was less than 10%. Bevacizumab associated incidence of grade 3-4 side effects did not exceed 5%. Hypertension 5% and thromboembolism 5% were the most frequent events. Gastrointestinal perforation did not occur. There was one toxic death due to sepsis and not directly associated with bevacizumab toxicity. Conclusion: Bevacizumab can safely be added to different chemotherapeutic regimens in first- and second+ line. The conferred benefit in overall survival, TTP and response rate obviously requires randomized trials. [ABSTRACT FROM AUTHOR]