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As the number of radiotherapy and radiology diagnostic procedures increases from year to year, so does the use of general volatile anaesthesia (VA). Although considered safe, VA exposure can cause different adverse effects and, in combination with ionising radiation (IR), can also cause synergistic effects. However, little is known about DNA damage incurred by this combination at doses applied in a single radiotherapy treatment. To learn more about it, we assessed DNA damage and repair response in the liver tissue of Swiss albino male mice following exposure to isoflurane (I), sevoflurane (S), or halothane (H) alone or in combination with 1 or 2 Gy irradiation using the comet assay. Samples were taken immediately (0 h) and 2, 6, and 24 h after exposure. Compared to control, the highest DNA damage was found in mice receiving halothane alone or in combination with 1 or 2 Gy IR treatments. Sevoflurane and isoflurane displayed protective effects against 1 Gy IR, while with 2 Gy IR the first adverse effects appeared at 24 h post-exposure. Although VA effects depend on liver metabolism, the detection of unrepaired DNA damage 24 h after combined exposure with 2 Gy IR indicates that we need to look further into the combined effects of VA and IR on genome stability and include a longer time frame than 24 h for single exposure as well as repeated exposure as a more realistic scenario in radiotherapy treatment.

Patient immobilisation with volatile anaesthetics (VA) during radiotherapy is sometimes unavoidable. Although it is known that both VAs and ionising radiation can have nephrotoxic effects, there are no studies of their combined effects on DNA damage. The aim of this in vivo study was to address this gap by investigating whether 48 groups of healthy Swiss albino mice (totalling 240) would differ in kidney cell DNA damage response (alkaline comet assay) to isoflurane, sevoflurane, or halothane anaesthesia and exposure to 1 Gy or 2 Gy of ionising radiation. We took kidney cortex samples after 0, 2, 6, and 24 h of exposure and measured comet parameters: tail length and tail intensity. To quantify the efficiency of the cells to repair and re-join DNA strand breaks, we also calculated cellular DNA repair index. Exposure to either VA alone increased DNA damage, which was similar between sevoflurane and isoflurane, and the highest with halothane. In combined exposure (VA and irradiation with 1 Gy) DNA damage remained at similar levels for all time points or was even lower than damage caused by radiation alone. Halothane again demonstrated the highest damage. In combined exposure with irradiation of 2 Gy sevoflurane significantly elevated tail intensity over the first three time points, which decreased and was even lower on hour 24 than in samples exposed to the corresponding radiation dose alone. This study confirmed that volatile anaesthetics are capable of damaging DNA, while combined VA and 1 Gy or 2 Gy treatment did not have a synergistic damaging effect on DNA. Further studies on the mechanisms of action are needed to determine the extent of damage in kidney cells after longer periods of observation and how efficiently the cells can recover from exposure to single and multiple doses of volatile anaesthetics and radiotherapy.

Copyright of Acta Chirurgica Iugoslavica is the property of Association of Yugoslav Surgeons and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Chirurgica Iugoslavica is the property of Association of Yugoslav Surgeons and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Chirurgica Iugoslavica is the property of Association of Yugoslav Surgeons and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Chirurgica Iugoslavica is the property of Association of Yugoslav Surgeons and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Chirurgica Iugoslavica is the property of Association of Yugoslav Surgeons and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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.

Although both can cause DNA damage, the combined impact of volatile anesthetics halothane/sevoflurane/isoflurane and radiotherapeutic exposure on sensitive brain cells in vivo has not been previously analyzed. Healthy Swiss albino male mice (240 in total, 48 groups) were exposed to either halothane/sevoflurane/isoflurane therapeutic doses alone (2 h); 1 or 2 gray of gamma radiation alone; or combined exposure. Frontal lobe brain samples from five animals were taken immediately and 2, 6, and 24 h after exposure. DNA damage and cellular repair index were analyzed using the alkaline comet assay and the tail intensity parameter. Elevated tail intensity levels for sevoflurane/halothane were the highest at 6 h and returned to baseline within 24 h for sevoflurane, but not for halothane, while isoflurane treatment caused lower tail intensity than control values. Combined exposure demonstrated a slightly halothane/sevoflurane protective and isoflurane protective effect, which was stronger for 2 than for 1 gray. Cellular repair indices and tail intensity histograms indicated different modes of action in DNA damage creation. Isoflurane/sevoflurane/halothane preconditioning demonstrated protective effects in sensitive brain cells in vivo . Owing to the constant increases in the combined use of radiotherapy and volatile anesthetics, further studies should explore the mechanisms behind these effects, including longer and multiple exposure treatments and in vivo brain tumor models.

Purpose: Patient immobilization by general volatile anesthesia (VA) may be necessary during medical radiology treatment, and its use has increased in recent years. Although ionizing radiation (IR) is a well-known genotoxic and cytotoxic agent, and VA exposure has caused a range of side effects among patients and occupationally exposed personnel, there are no studies to date comparing DNA damage effects from combined VA and single fractional IR dose exposure., Material and Methods: We investigate whether there is a difference in white blood cells DNA damage response (by the alkaline comet assay) in vivo in 185 healthy Swiss albino mice divided into 37 groups, anesthetized with isoflurane/sevoflurane/halothane and exposed to 1 or 2 Gy of IR. Blood samples were taken after 0, 2, 6 and 24 h after exposure, and comet parameters were measured: tail length, tail intensity and tail moment. The cellular DNA repair index was calculated to quantify the efficiency of cells in repairing and re-joining DNA strand breaks following different treatments., Results: In combined exposures, halothane caused higher DNA damage levels that were dose-dependent; sevoflurane damage increase did not differ significantly from the initial 1 Gy dose, and isoflurane even demonstrated a protective effect, particularly in the 2 Gy dose combined exposure. Nevertheless, none of the exposures reached control levels even after 24 h., Conclusion: Halothane appears to increase the level of radiation-induced DNA damage, while sevoflurane and isoflurane exhibited a protective effect. DNA damage may have been even greater in target organs such as liver, kidney or even the brain, and this is proposed for future study.

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.

Cell atypia in breast fine needle aspiration (FNA) can introduce some diagnostic difficulties. Molecules reflecting proliferative cell potential, such as Ki-67 and p27(Kip1) , can help in recognizing the true biological nature of a cell. Thus, the objective of the study was to analyze the difference in Ki-67 and p27(Kip1) cell immunoexpression in breast FNA specimens between fibroadenomas, fibrocystic changes (FCC) with atypia, and breast carcinoma. Microscopic analyses of cell cytomorphology and Ki-67 and p27(Kip1) breast cell immunoexpression were done after standard Pappenheim and immunocytochemical staining (labeled streptavidin-biotin, LSAB) method in autostainer DakoCytomation TechMate™. The study included 50 patients with breast carcinoma, 20 patients with fibroadenoma, and 20 patients with FCC with atypia. High Ki-67 and low or absent p27(Kip1) were found in most patients with breast carcinoma, while majority of FCC with atypia were characterized by low Ki-67 and moderate to high p27(Kip1) cell immunoexpression. Majority of fibroadenomas were associated with low Ki-67 and low to moderate p27(Kip1) cell immunoexpression indicating progressive decrease in cell cycle inhibition, but still not so high proliferative activity as in carcinoma. However, although statistically significant difference for Ki-67 and p27(Kip1) was found between breast lesions in our study, the large ranges observed for each marker make them essentially useless for better cytological diagnosis in a single case. Regarding their opposite role in cell cycle, inverse correlation of Ki-67 and p27(Kip1) was noticed. Poorly differentiated carcinoma cells had mostly high Ki-67 and low p27(Kip1) cell immunoexpression., (Copyright © 2010 Wiley-Liss, Inc.)

Breast cancer is the leading cause of mortality among women aged 25 to 44 years in Serbia. The purpose of this study was to determine basic clinical and radiological features of breast cancer in young women. 93 women aged 31.0 +/- 3.5 years with breast cancer were identified. The analysis included clinical characteristics (TNM classification) and radiological features (mammography and breast ultrasound). 53.8% of the patients had locoregional disease. The mean diameter of breast cancer was 2.6 +/- 6 cm. Carcinoma in situ was found in 2.2%. Mammography was performed in 25.8% of the patients and breast ultrasound in 68.8%. The results of our study indicate that the diagnosis of breast cancer in young women is late, in the stage with palpable breast tumor and lymph node metastases. Mammography or breast ultrasound are not routinely used. The implementation of algorithms for breast cancer detection and diagnosis in young women helps in earlier detection of breast cancer and consequently improves outcomes.

During the period 1995-2004 we treated 212 patients (pts) with brain tumors. There were 133 boys and 79 girls, aged from 2,5 yrs up to 18 yrs (Me = 9, 7 yrs). The majority of pts were in age group (4-16) yrs-179 pts. Supratentorial tumors were diagnosed in 118 pts vs. infratentorial 94 pts. Therapy involved surgery, postoperative radiotherapy with or without chemotherapy. Survival rates were calculated using Caplan-Meier method and differences between curves with log-rank test. During the follow-up period from 1 to 9 year (Me = 3 yrs) 5-year disease free survival rate was 55.7%. 79 pts failed to therapy. There was no statistically significant difference in survival according to sex (p = 0.123) and age (p = 0.367). Pts with supratentorial tumors had statistically significant better survival (p = 0.036). Pts with histologic type low grade astrocitomas had statistically significant better survival than malignant gliomas, ependymomas and PNET (p = 0.0001). Surgery, postoperative radiotherapy and chemotherapy in selected cases are efficient therapeutic approach for pediatric brain tumors.

The purpose of the study was to evaluate the efficacy of postoperative radiotherapy (RT) and to investigate prognostic factors for early-stage cervical cancer patients. We reviewed the medical records of 162 cervical cancer patients treated by RT during 2003 year. RT included 30-45 Gy of external photons to pelvis in 12-25 fractions. Brachytherapy with 192Ir was delivered in 3-5 fractions to a dose of 27-32 Gy. The mean age was 49 years (range 27-71). Majority of patients 130 had Stage Ib. Radical hysterectomy with lymphadenectomy was performed in 122 pts. and simple hysterectomy in 40 pts. The 5-year actuarial overall survival (OS) for all patients was 92.6% and disease-free survival (DFS) was 90.9%.There was statistically significant differences in OS and DFS in pat. with positive vs. negative pelvic lymph nodes; tumor 4 cm vs. tumor < or = 4 cm; positive vs. negative surgical margin/residual tumor (p < 0.05). Late GIT complications were determined in 35.8% and UT in 12.3%. In conclusion, postoperative radiotherapy has achieved high-satisfactory survival with acceptable complications. The survival benefit was less evident among patients with positive lymph nodes, tumor > 4 cm and positive surgical margin/residual tumor.

Intracavitary brachytherapy has an important roll in developing complications in postoperative radiotherapy of cervical cancer. 3D- CT based brachytherapy gives precisely estimating doses to organ at risk. In this study, we show our preliminary results in implementation of 3D-imaging based postoperative brachytherapy of cervical cancer: treatment technique and dose-volume parameters. During 2009 year, in 6 patients with early stage I-II of cervical cancer, brachytherapy treatment planning was based on the radiographs and CT imaging brachytherapy technique. Mean values of ICRU reference points of rectum was R max 4,2 Gy and bladder B max 4,5 Gy, while estimated volume-dose parameters D0.1 cm3 D1.0 cm D2.0 cm3 were presented with higher dose.Volume of organ at risk reflected the need for better bladder preparation. Our initial experience in performing CT-based brachytherapy, enabled us to introduce the characteristics of the parameters, assessment of their significance from the aspect of mutual relations applicators and organs at risk. Further analysis are needed, for monitoring the effects of 3D planning on complications.

Numerous questions regarding combined hormono-radiotherapy in the treatment of locally advanced prostate cancer still remain open. We present results of combined treatment in 133 our patients with locally advanced prostate cancer. All patients recieved hormonotherapy as neoadjuvant, concomitant with radiotherapy (tumor dose range 65-72 Gy), and adjuvant. In six months follow-up time, complete regression (CR) was noted in 120 patients (90%), partial regression (PR) in 6 (4.5%), stabile disease (SD) in 2 (1.5%) and progression of disease (PD) in 5 patients (4%). In mean follow up time of 17 months (6-77), 13 patients relapsed. Five-year time to progression was 70%. Five-year disease-free interval for CR patients was 70%. At the date of last control CR was noted in 116 patients (87%), PR in 2 patients (2%), SD in 7 patients (5%), and 8 patients (6%) had progressive disease. Second malignancy was noted in 4 patients. Multidisciplinary studies directed towards the optimisation of combined treatment are ongoing. There are no definitive conclusions.

Aim: The significance of mammography in detection of nonpalpable breast cancer, Material and Methods: This prospective study was conducted at the Institute for oncology and radiology of Serbia in Belgrade. It involved 198 asymptomatic women with performed screening mammography, 154 specimen mammography, out of wich 38 had stereotaxic mark, "ex tempore" biopsy, while 44 women had "ex tempore" biopsy and adequate surgery., Results: Screening mammography revealed suspect microcalcifications in 148 cases, impaired structural tissue in 59 and focal condensation in 55 cases. Histologic examination verified breast carcinoma in 80 patients with very statistical significance of ductal type, especially comedo subvariant (p < 0.001). Pleomorphic microcalcifications smaller than 0.5 mm of grouped or segmented form are statistically very significant for malignity (p < 0.001) as well as associated microcalcifications with altered architectony and focal tissue condensation (p < 0.001)., Conclusion: Mammography has great significance in detection of occult breast carcinoma which are not only preinvasive, but olso microinvasive and invasive. This fact leads to the neccesity of introduction of legal obligation for mammography screening, especially for women aged between 50 and 70 years.

Irradiation is the conventional treatment modality for cancer patients. However, besides its cytotoxic effects on malignant cells it might also affect the biology of surviving cells. Since overexpression of HER-2 receptors on malignant cells is a prerequisite for the therapeutic efficacy of Herceptin, it seems important to know whether previous irradiation changes their overexpression. The experiments performed in this work were aimed to determine whether X-ray irradiation of MDA-MB-361 and MDA-MB-453 breast carcinoma cell lines, besides its cytotoxic action, affects the overexpression of HER-2 protein. Determination of the cytotoxic effect of X-ray irradiation was done using trypan blue test. The breast carcinoma cell responsiveness to herceptin treatment in the presence of 10% fresh human serum (from healthy volunteer's) in the presence or absence of 25 microg/ml of herceptin, in vitro before and after cell-irradiation, was evaluated by MTT test. The degree of HER-2 overexpression was determined by immunocytochemistry, using DAKO HercepTest. Preliminary results obtained in this work showed that X-ray irradiation, besides its cytotoxic effect on malignant cells, could lead to overexpression of HER-2 receptors on (initially by immunocytochemistry, HER-2 negative) tumor cells, indicating change in biology of treated tumor cells. Further investigation in this direction will probably be helpful to elucidate this task in order to improve the selection of irradiated patients for Herceptin therapy.

The primary treatment of thyroid gland malignoma is surgery. Success of radiotherapy depends of extent of the previous surgery treatment. The types of radiotherapy are: curative (prophylactic and postoperative) and palliative. Tumor dose and radiotherapy tehnique depend on histologica type, extent of the previous surgery treatment, curative or paliative intent and general condition of patient, and they are from 40 Gy to 65 Gy by conventional fractionation. The basis of radiotherapy treatment planning and choice of radiotherapy treatment technique in survey of the region of interest by imaging procedure. On the basis of those data we determine therapeutic volume and structure of risk (spinal cord, lung) and protection of the risky structures is planned.

In the period of Octo. 01, 1987. up to Dec. 31, 1998. retrospective-prospective, non-randomized study was conducted at IORS, which included 36 patients diagnosed with thyroid gland medullar cancer. Our study had the following aims: evaluation of treatment results following probability of total survival, survival without signs of disease and disease-free interval until local recurrence of the disease and influence of parameters of transcutaneous radiotherapy (intensity of total tumor dose and length of disease-free interval from date of performed operation to beginning of radiotherapy). After finished treatment, median of the patient follow-up was 37.75 months (3.5 up to 141 months); probability of total five-year survival was 62.61% and of 10 year survival was 23.48%. Probability of 5-year survival, without signs of disease was 37.13%, and of 10-year survival 18.56%. As to radiotherapy parameters intensity of total therapy dose was statistically insignificant, while time interval to beginning of transcutaneous radiotherapy, shorter than 2 months, was statistically significant in relation to prognosis of disease outcome.

Purpose: To evaluate prospectively the combination of radiotherapy with low doses of carboplatin given as radiosensitizer in patients with locally advanced non-small cell lung cancer (NSCLC)., Patients and Methods: Patients enrolled in this trial were randomly allocated in two groups. The study group consisted of 67 patients with stage IIIA/B NSCLC who were treated initially with a tumor dose (TD) of 30 Gy in 10 fractions, 5 fractions per weeks, in 2 weeks. Carboplatin was administered simultaneously as radiosensitizer at a dose of 20 mg/m(2) i.v. bolus just prior to each radiotherapy fraction. After a 2-week rest an additional 25 Gy were given in 10 fractions, with carboplatin as previously described. The total tumor dose (TTD) was 55 Gy (30+25 Gy) in 20 fractions in 6 weeks and the total dose of carboplatin was 600 mg. The study group was compared with a control group of 70 NSCLC patients who were treated with radical conventional radiotherapy (60 Gy in 30 fractions, 2 Gy per fraction, 5 fractions per week)., Results: Haematological toxicity and oesophagitis were statistically more often seen in the study group. There was no statistically significant difference in the response rate between the 2 groups (53.7% versus 62.8%). The 2-year survival was 27% in the study group and 33% in the control group (p >0.05)., Conclusion: The results showed no response and survival benefit of concomitant chemoradiotherapy compared with conventional radiotherapy. We believe that further prospective, multicenter trials are required to evaluate the concurrent combination of new cytotoxic agents used as radiosensitizers with conventional radiotherapy or radiotherapy with different fractionation schedules and high-technology equipment which enables the application of higher tumor doses.

Introduction: Breast cancer is the most frequent cancer in elderly patients (over 65 years). The recent data indicate that in women aged over 72 years the incidence of breast cancer is twice greater than in women aged 45 years. As more and more women are getting older, the total incidence of breast cancer can be expected to increase. The treatment of these patients is complicated by many other diseases including cardiovascular and pulmonary disorders associated with aging, and because chemotherapy and radical surgery are often contraindicated., Material and Methods: In an one year period in the Institute of Oncology and Radiology of Serbia a group of 53 elderly (65 years and more) patients with locally advanced breast cancer were treated. Twenty four patients (group A) were treated with hypofractionated (concentrated) radiotherapy. The irradiation was delivered to the breast with TD24-26 Gy with two tangentional portals and 19 Gy to regional lymphatics with anterior fields owner 8 fractions, breast and lymphatics alternatively. The same treatment plan was repeated after 28 days (split course). Co60 was used. Twenty nine patients (group B) were treated with conventional fractionated radiotherapy. Irradiation was delivered to the breast with 51 Gy tumour dose in 16 fractions and to the lymphatics with 45 Gy in 15 fractions. Breast and lymphatics were irradiated alternatively, during 31 working days. After 51 Gy the whole breast was boosted with 20 Gy tumour dose and axilla with TD 12 Gy. The concentrated radiotherapy is, in fact, an alternative for radical--conventional or protracted radiotherapy according to the so-called hypofractionated split course technique. Both techniques have very similar TDF factors. The aim of such a plan is the achievement of adequate tumour dose adapted to the age of patients (the patients should be treated in a smaller number of fractions). All patients were aged 65 years or were older. The median age in group A was 72 years and in group B 68 years. Also in all patients breast cancer was locally advanced (stadium III). In group A median follow-up was 29.79 months and in group B 23.62 months., Results: All patients had acute skin reactions. In group A (irradiated with concentrated technique) 91.7% of patients had erythema, 8.3% dry desquamation, but moist desquamation was not observed. In group B (irradiated with conventional technique) 27.6% of patients had erythema, 55.2% dry desquamation and 17.2% moist desquamation. Delayed radiation changes manifested as fibrosis of the breast and region of axilla were noted in 29.24% of patients in group A and 13.8% in group B. The relapse in group A was 41.7% with median relapse free interval of 13.9 months and in group B 48.2% with relapse free interval of 15.6 months. There was no significant statistical difference between the two groups according to standard statistical methods (chi 2 = 0.96; DF = 3; p > 0.05). After approximately 30 months of follow-up, 50% of patients in group A are alive without signs of disease; 16.7% are alive with disease, and 16.7% are dead due to primary disease. In group B 24.1% of patients are alive without signs of disease; 24.1% are alive with disease; and 20.7% are dead due to primary disease. There was no significant statistical difference between the two groups (chi 2 = 4.09; DF = 4; p > 0.05). The overall survival rate in group A was 67% after 4 years and 53% in group B. Relapse free survival was 53% in group A after 4 years and 36% in group B. In conclusion, according to our study there was no statistically significant difference in local control between conventional and hypofractionated radiotherapy in the treatment in elderly patients. The main advantage of concentrated schedule is shortening of duration of irradiation, but the main disadvantage is a high incidence of fibrosis which makes difficult the evaluation of local control. Consensus about treatment of breast cancer in elderly women has not yet been clearly established. Our data suggest that hypofractionated schedule is an effective, suitable and comfortable therapeutic approach in the management of breast cancer in elderly women.

Epidermal growth factor receptor was determined in 106 newly diagnosed breast cancer patients, using the biochemical method. The group consisted of 58 patients in stage I-II, and 48 patients in stage III-IV. Although a significant inverse correlation was found between EGF-R status, and ER or PR status, quantitative content of EGF-R did not correlate either with quantitative ER, or PR levels. The ER/PR content was similar in all clinical stages, suggesting their stability during the clinical course of the disease. EGF-R content was significantly higher in stage IV, compared to stage I, while intermediate clinical stages and all substages did not differ according to the EGF-R content. EGF-R was confirmed as a weak prognostic factor within clinical stages. However, in a whole group, the overall survival was significantly better in patients whose tumors EGF-R content was lower than 26 fmol/mg, compared to those with higher ERF-R content. EGF-R content was highly predictive for the response to systemic endocrine treatment, in metastatic breast cancer patients. In locally advanced breast cancer a trend towards higher levels of EGF-R was found in inflammatory breast cancers, compared to non-inflammatory ones. Slightly higher levels were found in responders to local non-endocrine primary treatments (radiotherapy with or without chemotherapy), compared to non-responders, suggesting the possible predictive role of EGF-R for the response to such treatments. Our results emphasized the usefulness of quantitative receptor determination suggesting the relative stability of EGF-R content during the clinical course of breast cancer, its independence from ER, its significant predictive and weak prognostic values, and a possible correlation with the aggressiveness of the disease, and response to non-endocrine treatments.

It is considered that in 30% of female patients with breast cancer a certain form of evolutive disease occurs within 5 years from documented diagnosis. In these female patients, 58% develop distal metastases. Thus, a great number of these female patients enter the phase when hope for recovery is small. Then supportive therapy is used. It's main task is to alleviate the life of these patients. Palliative radiotherapy is one of the main elements of this therapy. It is directed to decrease the pain, and bleeding, to prevent fractures and decompression of the spinal cord, as well as many other evolution consequences of local or distal disease. The correct and timely definition of indications for radiotherapy, the optimal planning and conduction of the therapy should take into account the patient's characteristics as well as the main postulates on which radiotherapy is based. In this way the satisfying effects on patients with disseminated breast cancer, may be expected.

The rationale preoperative irradiation is expressed by the sound: eradication of sensitive tumour cells at the periphery of a lesion making complete resection more likely and dissemination of tumour cells by operative manipulation less likely. The dose of irradiation required is approximately 80 to 85% of the dose needed to permanently control the palpable disease, a dose which does not interfere with subsequent mastectomy, if 3 to 4 weeks elapse between the termination of irradiation and mastectomy. One hundred fifteen consecutively examined patients with stage IIIa breast cancer were treated over the period from January 1985 to December 1987 at the Institute of Oncology and Radiology, Belgrade, Serbia. We were interested in the local control of preoperatively irradiated and radically operated patients with the median follow-up of 82 months. Fifteen patients had local recidives, the local control was made in 87%, in the interval between 6 and 66 months (median 18 months). We analyzed the correlation between the local control and the grade of malignancy (GM) of the axillary lymph node and the T status of the tumour. GM was more important than T. Based on our results and on those of other authors, we believe that this multimodal regimen, which includes preoperative irradiation, radical mastectomy and adjuvant cheme-hormonotherapy, is satisfactory for patients with stage IIIa primary breast cancer.

Mastitis carcinomatosa or inflammatory breast cancer (IBC) is a very rare form of breast cancer with aggressive progression, as well as rapid dissemination. Though this disease has been for a long time in focus of interest of clinicians, the problem of its treatment is still unsolved. In the Belgrade Institute of Oncology and Radiology IBC has been already treated with combination of chemotherapy and radiotherapy, and results of such treatment are evaluated and presented in this paper. Taking into account results of the above mentioned treatment as well as that reported in literature, we decided to make its modification. Irradiation was carried out by hyperfractionation, preceded and followed by chemotherapy. Hyper-fractionated regime was assessed using LQ model for determination of radiobiological efficiency. The obtained results showed only a percentual, but not statistically significant improvement. The presented treatment was only an attempt after which it could be concluded that the oncologist today, no matter whatsoever he was trying in the treatment of IBC, could not expect extraordinary results, but must be satisfied with the fact that he has given his best help. Nevertheless, we find our attempt valuable since it gives new opportunities for non-conventional radiotherapeutic treatment, as well as new perspectives in the treatment of IBC, but always in combination with systemic therapy.