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BACKGROUND: The hybrid method 18F-FDG PET/ CT has been proven as a method of choice in oncology for diagnostics, staging, restaging of the tumor and evaluation of the therapeutic effect. The aim of the study was to determine the value of 18F-FDG PET/ CT for detection of synchronous tumors and consequently the influence on the patients management. MATERIAL AND METHODS: The examinations were performed on Discovery, GE Healthcare PET/ CT using standard protocol. Among the patients, examined by 18F FDG  PET/ CT for one year (n = 1 408), unsuspected synchronous tumors were detected in 11 cases (0.8%). RESULTS: Five pulmonary carcinomas, four head and neck squamous cell carcinomas (HNSCC), one ovarian carcinoma and one tumor of the sigma were detected as second malignancies. The histology verification was done in five cases (all HNSCC and one sigma carcinoma). In one patient with ovarian carcinoma, histology was obtained after surgery. In the rest of patients, no verification was undertaken because of the patients refusal and the advanced stage of the diseases, demanding systemic chemotherapy. Four patients (three with HNSCC and one with ovarian secondary malignancy) had favorable outcome during the nine  month  follow up. CONCLUSION: The hybrid method PET/ CT, combining the metabolic and morphologic findings, can help detection of synchronous malignancies in a small percentage of cases, but with a positive influence on management of considerable part of such patients.

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PURPOSE: To evaluate post-surgical tumor-metabolic regions outside of the computed tomography (CT)-defined volume for radiation therapy (RT) planning using functional imaging of scintimammography (SMG) ± single photon emission computerized tomography (SPECT) in breast cancer (BC) patients. METHODS: 62 operated high-risk BC females, mean age 50.45 years, underwent SMG±SPECT before RT planning. Twenty-one and twelve patients with stage I and IIa respectively had lumpectomy (LT) with axillary lymph node dissection (ALND), and modified radical mastectomy (Patay) + ALND was realized in 29 stage IIb-III patients. All SMG images, positive for viable tumor tissue (VTT) or metastatically involved lymph nodes (LNs) were verified cytologically/ histologically. Three early planar and delayed images were acquired after i.v. administration of 550-740 MBq 99mTc- MIBI or 99mTc-TF. Uptake values (UV) > 1.65 revealed VTT. RESULTS: Data in 49 (79%) of 62 patients were characterized as true-negative (TN; UV<1.35). In 13 (21%) patients SMG visualized 22 true-positive (TP) malignant lesions: 2 residual VTT in scars, 1 newly defined BC in the contralateral breast and 18 regional LN metastases (6 axillary, 6 parasternal, 1 sub- and 5 supraclavicular). All 22 TP VTT lesions were imaged by scintigraphy using different tumor-seeking radiopharmaceuticals: 99mTc-MIBI - 17 (77%) and 99mTc- TF - 5 (23%) of the TP lesions. One false-positive (FP) (inflammation: UV>1.65) and one false-negative (FN) (UV<1.35) foci were found. Applying SMG±SPECT for BC restaging after surgery, the RT volume was changed in 13 of 62 (21%) patients. CONCLUSION: SMG is a reliable imaging method for evaluating residual VTT, LN metastases or altered biological activity in the scars after BC surgery and could modify the irradiated volume, optimizing the therapeutic effect and minimizing RT side effects.

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The treatment of lymphoproliferative diseases has changed dramatically during the last decades. The improved therapeutic results for this disease group are included among the most important achievements of modern oncohaematology. They are due to better disease staging, use of new markers for risk assessment, patient stratification in separate risk groups, implementation of highly effective chemotherapy (CHT), progress of targeted therapies using monoclonal antibodies, proteasome inhibitors, modern radiation therapy (RT) and supportive care. The achieved progress, especially in the treatment of Hodgkin's disease (HD), is an example of the fundamental dependence of clinical practice on the scientific achievements, mainly in the field of diagnostics and in the two pure anticancer therapeutic modalities: chemo- and radiotherapy. The aim of this article was to discuss the basic variants of RT in the multimodal treatment of HD and the clinical experience accumulated during the last decades. The experience gained in the area of involved field RT (IFRT) and extended field RT (EFRT), both alone or as a part of the combined-therapy protocols, is considered in detail. The role of RT is also discussed as a part of the dose-escalated CHT combined programmes for patients recurring, progressing or partially responding to treatment, carried out mainly as IFRT, total lymphoid irradiation (TLI) or total body irradiation (TBI). Regardless of the already attained achievements of the combined treatment at the present stage of development of oncological knowledge, there is still no consensus with respect to the optimal therapy of HD in children and in adult patients. New trials addressing issues of the best modality, best RT technique, optimal dose of RT, optimal number of cycles and timing of CHT are still needed. The contemporary challenge is to optimize treatment so that it can be accomplished with the least toxicity, lowest cost, and greatest efficiency possible.

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BACKGROUND: To establish the efficacy of the combined modality treatment (CMT) including curative extended field radiotherapy (EFRT) and chemotherapy (CHT) by examining the long-term outcome in Hodgkin's disease (HD) patients at the Sofia University Hospital "Queen Giovanna-ISUL", with particular focus on second primary malignancy (SPM), and to establish independent factors correlated with treatment outcome. METHODS AND MATERIALS: Between 1982 and 2007, 170 patients with HD with median age of 12 years (range 3-40), (68 females, 102 males), were included in this retrospective study. The clinical stage (CS) distribution was CS I in 1 patient (0.6%), CS II in 86 (50.5%), CS III in 77 (45.3%) and CS IV in 6 (3.5%) patients. Histologic subtypes included lymphocyte predominance 7.6%, mixed cellularity 47.1%, nodular sclerosis 42.9% and lymphocyte depletion 0.6%. B symptoms were observed in 57.6% of the patients, hepatosplenomegaly--in 30.6%, anemia--in 27.1% and elevated serum lactat dehydrogenase (LDH)--in 41.2%. The overall treatment consisted of both EFRT and CHT. In 115 patients (67%) supradiaphragmatic irradiation of lymphatic nodes was carried out, in 3 (2%) patients subdiaphragmatic irradiation was performed and in 52 (31%)--irradiation of the supra- and infra-diaphragmatic lymph nodes basically by subtotal 35 (20.6%), and total lymphoid irradiation--in 4 (2.4%) patients. The daily dose was 1.5-2 Gy, the total dose for EFRT was 20-40 Gy. From the analyzed 170 patients 150 were assessable for long-term outcome and 120 for SPM analyses. RESULTS: Follow-up extended from a minimum of 0,3 years to maximum 25,7 years, with a median observation time 12 years.The 5-, 10-, 15-, and 25-year overall survival (OS) in the whole group was 93% : 86% : 82% : 82%, respectively. A tendency for better survival was found for patients with age < or = 15 than for those with > 15 years, with 5-, 10-, and 15- year OS of 95% : 87% : 84% vs 84% : 84% : 56%, p = 0.09. There was a trend for better survival in males compared with females with 5-, 10- and 15-year OS of 96%: 93%: 91% vs 88% : 73% : 65%, p = 0.001. The OS difference between CS IIB and IIIA turned out to be significant in favor of the patients in CS IIIA with 5- and 10-year OS of 89%: 76% vs 95%: 90%, respectively, p = 0.03. The following factors were analyzed for their prognostic influence: age, gender, stage, histologic subtype at first diagnosis, sites of involvement, number of involved lymph node areas, B symptoms, hepatosplenomegaly, anemia, elevated serum LDH, daily dose, total dose, boost and technique used in EFRT. In univariate analysis, independent risk factors were gender (p < 0.001), stage (IIB: IIIA) (p = 0.03), mediastinal involvement (p = 0.03), daily dose (p = 0.01) and total dose (p = 0.02). In multivariate analysis, independent risk factors age < or = 15 years (p < 0.001), male gender (p = 0.005), daily dose < or = 1.5 Gy (p = 0.009), and total dose 26-30 Gy (p = 0.048) were found to positively affect OS. We investigated a prognostic model, identifying groups of HD patients with particularly responsive disease, combining prognostic factors as age < or = 15 years (p = 0.001), male gender (p = 0.011), and total dose 26-30 Gy (p = 0.012). In the observed 25-year period SPM development was not established in any of the 120 patients subjected to follow-up. CONCLUSION: The performed first Bulgarian study on CMT including EFRT and CHT exhibited a certain therapeutic potential in the treatment of HD patients, expressed in the achievement of high long term outcome and low SPM frequency.

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PURPOSE: To examine the use of whole abdominal irradiation (WAI) open field technique in patients with stage III endometrial cancer (EC). METHODS: Between 1993 and 2007, 26 patients (age 39-70 years, median 58) with stage III EC (IIIA 15, IIIB 2, IIIC 8) were treated with WAI after primary surgery. Five (21)) patients had grade 1 disease, 18 (67%) grade 2 and 3 (12%) grade 3. In 2 (8%) patients a second laparotomy was carried out before the radiotherapy (RT) referral. Ascites and positive peritoneal cytology was present in 3 (15%) and 4 (20%) patients, respectively. After surgery, residua < 2 cm in the upper abdomen were left in 2 patients. WAI was delivered using Co 60 anterior-posterior photon fields to encompass the peritoneal cavity. In 84% of the patients WAI consisted of 30 Gy, delivered mainly in daily fractions of 1.5 Gy (81%), 5 fractions per week. For the remaining patients the dose was 25 Gy (8%) and 20 Gy (8%), respectively. After abdominal RT, 85% of the patients were given a pelvic boost to reach 45 - 50 Gy with 1.8 Gy/fraction/day, using a Co 60 unit. In 5 (19%) patients boost to 45-50 Gy with 1.8 Gy/fraction/day to other risk sites was also given. Two (8%) of 26 patients received 2 cycles of platinum-based chemotherapy. The mean follow-up time was 13.41 years. RESULTS: The treatment time ranged from 14-74 days, median 48. The overall survival (OS) rate was 93% at 5, 10 and 14 years. Ten (38.5%) patients received their treatment with no interruption, and in 16 (61.5%) patients RT was transiently interrupted because of acute gastrointestinal and hematological toxicity. Neither grade 4 acute complications nor mortality while receiving treatment were observed. Late side effects (grade 2 gastrointestinal complications) developed in 1 (5%) patient. During the observation period a second primary malignancy was recorded in 1 patient. CONCLUSION: WAI achieves a quite favorable 5- and 14-year survival rate with an acceptable risk of acute and late side effects in properly selected patients with stage III EC. WAI as a sole or a part of combined treatment warrants further investigation in patients with high-risk EC.

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There has been a remarkable growth in the use of bone marrow transplantation (BMT) in the past 30 years. The rapid expansion of BMT reflects its increasingly important role in the treatment of several life-threatening diseases of the hemopoietic system. The first BMT in human patients was performed after conditioning with total body irradiation (TBI). As an important part of BMT protocols, TBI has an established role in many preparative regimens used before BMT in the treatment of hematological diseases. Historically, TBI schedules varied during the last 30-year period with regard to different radiation source used, treatment technique, beam modifiers, actually delivered total dose, dose rate, and fractionation schedule. The aim of this review article is to discuss the 50- year experience in the field of TBI, as well as radiobiological, technical and dosimetric requirements and especially effects of total dose, dose rate and fractionation schedules on the prognosis of transplanted patients. The radiobiological and radio-oncological requirements demand special TBI treatment techniques quite different from usual radiotherapy. The technique needed depends extremely on the prescribed values of treatment parameters and on the local technical possibilities. TBI dosimetry has to account for the physical situation of treatment with very large field sizes at extended distances and should be performed under TBI conditions close to the real treatment situation. The effects of total dose, dose rate, fractionation schedule on the leukemia cell killing, immunosuppression, and sparing of normal tissues are considered in detail. Their effects on overall survival, leukemia recurrence, acute and chronic graft versus host disease (GvHD), late radiation-induced injuries to normal tissues or organs as well as incidence of interstitial pneumonitis, renal dysfunction and cataract development are analyzed. The definition of currently used TBI procedures is so different in different centers that retrospective analyses remain futile, under better definition and normalization of dose, fraction size, and endpoints occur. There are a lot of difficulties to evaluate, compare or understand clinical RESULTS from so different treatment regimens, often with an irregular set of parameters. In order to establish clinical trials and to evaluate clinical RESULTS, we need comparable schedules, uniform specification, and complete reporting of all relevant parameters. After 50-year experience in the field of TBI, we are beginning to understand the relationship of TBI dose, dose rate and fractionation. However, 20 years after Glasgow we will repeat his persuasion that, however, many questions remain unanswered.

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BACKGROUND: Locally advanced breast cancer (LABC) is one of the main causes of cancer death among women in Bulgaria. In 1988, when this study started, there was still controversy about the role of chemotherapy in controlling systemic disease. There were encouraging results from the Radiation Therapy Oncology Group (RTOG) 82-06 study suggesting that half-body irradiation (HBI) should be used earlier in the disease course to prevent the development of metastases. There were many patients with LABC requiring treatment, but there was a problem with obtaining the drugs needed; they were expensive and not consistently available. PROCEDURE: Taking into account the medical contraindications to chemo-therapy treatment, its toxicity, and the possibility of chemoresistance, we initiated this study to look at the effects of HBI given as two fractions of 4 Gy to the upper and then lower parts of the body, after surgery and before local radiotherapy. RESULTS: The acute tolerance of this regimen in 36 patients with LABC was as good as it was in 4 additional LABC patients with M1 disease, and hematologic recovery was satisfactory. CONCLUSIONS: We conclude that systemic treatment with HBI is tolerable. It therefore may be a convenient and cost-effective treatment for LABC, although better treatments are still needed.

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