Analysis of radiation-induced angiosarcoma of the breast.

Breast angiosarcoma may occur de novo, or as a complication of radiation therapy, or chronic lymphedema secondary to axillary lymph node dissection for mammary carcinoma. Both primary and secondary angiosarcomas may present with bruise like skin discoloration, which may delay the diagnosis. Imaging findings are nonspecific. In case of high-grade tumours, MRI may be used effectively to determine lesion extent by showing rapid enhancement, nevertheless earliest possible diagnostics is crucial therefore any symptoms of angiosarcoma have to be carefully analysed. The case analysed here reports on results of 44-year old premenopausal woman who was treated for a T1N1M0 invasive ductal carcinoma. After a biopsy diagnosis of carcinoma, the patient underwent quadrantectomy with axillary lymph node dissection. She received partial 4 cycles of chemotherapy with adriamycin and cyclophosphamide, followed by radiation treatment. Thereafter, a standard postoperative radiotherapy was applied at our institution four months after chemotherapy (TD 46 Gy in 23 fractions followed by a 10 Gy electron boost to the tumour bed). Adjuvant chemotherapy was finished six months after operation, followed by tamoxifen. Follow up: no further complications were detected during regular check-ups. However, 12-years later, patient reported significant changes at breast region which was exposed to radiation during treatment of original tumour. In this article, we describe the clinical presentation, imaging and pathological findings of secondary angiosarcoma of the breast after radiotherapy (Fig. 2, Ref. 26).

Preoperative radiotherapy of locally advanced rectal cancer: clinical outcome of short-course and long-course treatment with or without concomitant chemotherapy.

BACKGROUND: Preoperative radiotherapy is considered to be standard treatment for locally advanced rectal cancer. The timing and dosage of radiotherapy with or without preoperative chemotherapy remain controversial issues. The objective of this study was to evaluate relevant clinical outcomes of two preoperative radiotherapy regimens - the short-course and -long-course radiotherapy with or without chemotherapy for patients with locally advanced rectal cancer. PATIENTS AND METHODS: 151 patients with stage II-III rectal cancer (103 males and 48 females) treated with preoperative radiotherapy between 01/1999 and 01/2008 were involved in this study. Analysed patterns included sphincter preservation, tumor down-staging, pathological complete remission, frequency of local recurrence, acute and late toxicity, peri-operative complications, overall survival and disease-free survival. RESULTS: Tumor downstaging has been achieved by long-course radiotherapy alone (46%) or in combination with chemotherapy (5-FU or capecitabine, 61%). Pathological complete remission has also been achieved only in the group with long-course radiotherapy (13%). Long-course radiotherapy combined with chemotherapy significantly decreased post treatment local recurrence rates (5% versus 15% in the group after long-course radiotherapy alone, p = 0.0132). Statistically significant difference was confirmed in overall survival of patients treated with long-course radiotherapy combined with chemotherapy vs long-course radiotherapy alone (p = 0.015). Significant difference between the rate of perioperative complications, of acute and late toxicity, 3 and 5 years disease-free survival of treated patients after short-course radiotherapy and long-course radiotherapy was not confirmed. CONCLUSION: Our findings provide convincing evidence that in comparison to preoperative short-course radiotherapy, the preoperative long-course radiotherapy in combination with chemotherapy is the most effective treatment modality for patients with operable locally advanced rectal cancer in terms downstaging and pathologic complete response. Increase in overall survival time as well as lower local recurrence rate makes this modality superior to other preoperative radiotherapy alternatives.

MR imaging of late radiation therapy- and chemotherapy-induced injury: a pictorial essay.

Radiation to the brain and adjuvant chemotherapy may produce late delayed changes from several months to years after treatment of intracranial malignancies with a reported prevalence of 5-24%. The pattern of treatment-related injury may vary from diffuse periventricular white matter lesions to focal or multifocal lesions. Differentiation of treatment-related injury from tumor progression/recurrence may be difficult with conventional MR imaging (MRI). With both disease processes, the characteristic but nonspecific imaging features are vasogenic edema, contrast enhancement, and mass effect. This pictorial essay presents MRI spectra of late therapy-induced injuries in the brain with a particular emphasis on radiation necrosis, the most common and severe form. Novel MRI techniques, such as diffusion-weighted imaging (DWI), proton MR spectroscopy (MRS), and perfusion MRI, improve the possibilities of better characterization of treatment-related changes. Advanced MRI techniques allow for the assessment of metabolism and physiology and may increase specificity for therapy-induced changes.

Post-therapeutical changes in the brain: novel trends in imaging and their infuence on external beam radiotherapy.

UNLABELLED: Presented is the analysis of patients who underwent external beam radiotherapy (EBRT) to the brain in the period from 2003 to 2006 at the department of Radiation Oncology of the St. Elisabeth Cancer Institute.

The aim of our analysis was to identify risk factors of late delayed therapy induced injuries (LDTI) in the brain. The patients were regularly examined with magnetic resonance (MRI), including conventional and advanced techniques: perfusion imaging (pMRI), diffusion weighted imaging (DWI), MRI spectroscopy (MRS). The results from MRI were correlated with 18fluoro-deoxyglucose positron emission tomography (18FDG/PET) scans, as none of the listed method is sufficiently sensitive and specific by itself. Also clinical data records and treatment plans of these patients were analyzed.

In our cohort we found 6 patients with abnormal post-therapeutical changes, 4 of them with MR and 18FDG/PET scans characteristics for LDTI - radiation necrosis. In one patient biopsy was performed and radiation necrosis (RN) was confirmed.

Radiation-induced meningioma with a long latency period: a case report.

Multiple meningiomas were diagnosed in a 43-year-old man previously treated with high-dose craniospinal radiotherapy at the age of 7 years for medulloblastoma. We suggest that surveillance MRI after high-dose craniospinal radiotherapy should be extended to several (3-5) decades.

Radiation-induced meningiomas.

High dose radiation-induced meningiomas are a rare, severe and late complication of craniospinal radiotherapy for brain tumors. Radiation-induced meningiomas are, according to the literature, several times more frequent than radiogenic gliomas and sarcomas. It is suggested that every new case of radiogenic meningioma has to be reported to elucidate this particular pathologic entity with its many grey areas. In addition to high dose radiation-induced meningiomas, intracranial meningiomas were observed in patients who underwent low-dose radiation for tinea capitis in childhood, applied en mass to immigrants coming to Israel from the North Africa and the Middle East during the 1950. Authors summarize the data on radiogenic meningiomas from the literature and, as the previous radiotherapy may confer a low, but life-long risk for meningioma occurrence, they suggest that surveillance MRI after high dose cerebrospinal radiotherapy should be extended to several (3-5) decades after radiotherapy.

Long-term (15 years) results of extended field radiotherapy in Hodgkin's disease.

From 1975 to 1990, 214 patients with the pathological Stage IA, IB, IIA, IIB and IIIA of Hodgkin's disease were treated by supradiaphragmatic and/or infradiaphragmatic mantle technique. Complete remission was achieved in 70 patients (8%) by means of radiotherapy only. Partial remission was achieved in 9 patients (2%). The survival at 10 years was 86% and 15 years it was 66%. The most frequent late complications were hypothyreosis, Lhermitte's syndrome and radiation pneumonitis.

Radiation-induced apoptosis and cell cycle alterations in human carcinoma cell lines with different radiosensitivities.

Radiosensitivity of examined human neoplastic cell lines was assessed with the aid of MTT assay. Differences between radiosensitive and radioresistant human neoplastic cell lines were as follow: a) radiation-induced apoptosis detected by flow cytometry was apparent in the most radiosensitive (i.e. CH-1 ovarian carcinoma cell line), but not in the radioresistant (i.e. SKOV-3 ovarian carcinoma) cell lines, b) radiation-induced G2/M arrest appeared early after irradiation (6 hours) in both the radioresistant SKOV-3 cells and in the radiosensitive CH-1 human ovarian carcinoma cell line, but a different pattern was observed 24 hours after irradiation with 2 Gy dose with G2/M arrest only in radiosensitive cell line. The radiosensitivity and resistance to radiation-induced apoptosis in the radioresistant human breast carcinoma MDA-MB-231 cell line were similar to those observed in SKOV-3 cells. These data suggest that radiation-induced apoptosis and cell cycle alterations can predict radiosensitivity at least in some examined human malignant cells in vitro.

Radiation-induced DNA damage and repair evaluated with 'comet assay' in human ovarian carcinoma cell lines with different radiosensitivities.

Radiation-induced DNA damage and kinetics of DNA repair was evaluated in three human ovarian carcinoma cell lines (i.e. CH-1, A-2780 and SKOV-3) with different sensitivities to ionizing radiation and radiation-induced apoptosis with the aid of single cell gel electrophoresis (SCGE, the comet assay). A good correlation was found between the initial level of DNA breaks and radiation induced apoptosis in CH-1 and SKOV-3 cell lines. While the radiation-sensitive CH-1 cell line manifested the highest level of initial DNA breakage and a significant delay in DNA break rejoining, the inverse correlation was found in the radiation-resistant cell line SKOV-3. Intermediate initial level of breaks was induced in the A-2780 cell line characterized by the intermediate sensitivity to X-ray radiation in comparison to CH-1 and SKOV-3 cells, however, the kinetics of DNA repair was comparable with radiation-resistant cell line SKOV-3. Our data suggest that the comet assay could be a promising tool for prediction of intrinsic cell radiosensitivity. This method might be considered as a supplementary technique to the more reliable but time consuming clonogenic assay.

Resistance of human multidrug-resistant neoplastic cell lines to paclitaxel-induced-radiosensitization is reduced by the non-immunosuppressive cyclosporine analog SDZ PSC 833.

The non-immunosuppressive cyclosporine analog SDZ PSC 833 abolished the resistance of human multidrug resistant (MDR-1, P-gp) human promyelocyte leukemia HL-60/VCR cells in vitro to paclitaxel-induced cell cycle- and viability alterations, as well as resistance to paclitaxel-induced radiosensitization. Furthermore, SDZ PSC 833 abolished also the resistance of human multidrug-resistant ovarian A2780/ADR cells to paclitaxel-induced cell cycle alterations and reduced its resistance to paclitaxel-induced radiosensitization. In these multidrug-resistant ovarian carcinoma cells the supra-additive interaction between paclitaxel and SDZ PSC 833 pre-exposure and subsequent irradiation appeared at slightly higher paclitaxel concentrations (40-100 nM) compared to those required for a similar interaction in the parental drug sensitive A2780 cells (40-80 nM paclitaxel).

Taxol-enhanced cytotoxic effect of radiation in human promyelocytic leukemia cells: relative resistance of multidrug-resistant HL-60 cells in vitro.

Cytotoxic effects of sequential taxol (paclitaxel) and X-irradiation on drug-sensitive human cultured promyelocytic leukemia (HL-60) cell line and its multidrug-resistant sublines were examined using photometric MTT test and flow cytometry. Paclitaxel (at concentrations 1-10 nmol) stimulated the cytotoxic effect of irradiation in HL-60 and to a lesser extent also in HL-60/ADR, but not in HL-60/VCR cells. The stimulation of radiation-induced cytotoxic effect by paclitaxel correlated with its potential to induce cell cycle and viability alterations identified with flow cytometric analysis (i.e. increased propidium iodide staining, increased side scatter, decreased forward angle scatter, accumulation of necrotic cell detritus, apoptotic pre-G0 cells and cells in the G2/M phase of the cell cycle).

T-lymphocyte subsets (CD4/CD8 ratio) in breast cancer patients.

T-lymphocyte subsets (CD4/CD8 antigen positive cells) were determined in peripheral lymphocytes from 48 patients with breast cancer of different stages by flow immunocytometry with the aid of anti-CD4 and CD8 monoclonal antibodies. A broad individual variability of the CD4/CD8 ratio among both healthy donors and breast cancer patients was observed. The average value of CD4/CD8 ratio decreased in groups as follows: Healthy donors and Stage I patients, Stage IIA, IIB and Stage IV breast cancer patients. These differences were generally statistically not significant. The difference between healthy donors and Stage IV breast cancer patients was statistically significant (p < 0.01), if one exceedingly elevated value of the CD4/CD8 ratio was excluded from statistical evaluation. The average CD4/CD8 value in the group of breast cancer patients with lymph node or distant metastases was lower than that of patients without metastases, but their difference was not statistically significant either.

Hyperfractionation in radiation treatment of advanced head and neck cancer. A preliminary report.

The effects and side-effects of hyperfractionated therapy in advanced head and neck cancer were investigated in a prospective study. The data of 71 patients were available for evaluation and these were compared to a historical control group treated by a standard one-day fractionation schedule; they showed a tendency to local superiority of hyperfractionated irradiation.

The influence of patients age, type of tumor growth, hematocrit, and radiation-induced tumor regression on the prognosis of advanced uterine cervix carcinoma.

The age of patients, type of tumor growth, pretreatment hematocrit, and radiation-induced tumor regression were evaluated as possible prognostic factors in 222 patients with advanced cervical cancer treated at the Institute of Clinical Oncology in Bratislava in the period from 1960 through 1980. The five-year disease-free survival rate for Stage IIb patients was 50%, for Stage III patients 23.1%, and for Stage IV patients 13%. Radiation-induced tumor regression and type of tumor growth were noted to be a significant prognostic factor with regard to the control of disease in the pelvis. Age of the patients and pretreatment hematocrit were found to be a weak prognostic factor.

Prognostic significance of lymphocytic infiltration in radiation-treated uterine cervix carcinoma.

In a retrospective series of 45 patients with uterine cervix carcinoma Stage Ib and IIa who had been treated by radiation, biopsy material obtained prior to treatment was reevaluated for the presence of lymphocytic infiltration. The analysis based on 5 degrees of the intensity of stromal reaction has shown that the presence of lymphocytic infiltration, the intensity of which was significantly related to the proportion of blood vessels in stroma, was connected with a favorable outcome of treatment. The results suggest that vascular density being the determinant factor in oxygenation of the cancer tissue and its radiotherapeutic control may also play an important role in the immunological reaction against the tumor.

Dynamic dose-fractionation combined with oxygen breathing at ambient pressure and high-dose metronidazole in head and neck, and uterine cervix cancer.

The paper summarizes the results of dynamic dose-fractionation combined with oxygen breathing at ambient pressure and metronidazole in head and neck, and uterine cervix cancer. The patients were given high oral doses of metronidazole (5-6 g/m2) three hours before dose fractions (4.5 Gy for two days) initiating the radiation treatment series. After successive daily irradiation with 2 X 1 Gy in 8 hours interval (without metronidazole) to the tumor dose 29 Gy, 5-day radiation free interval was inserted and then the identical treatment series was repeated to the total dose 60 Gy. Nausea and vomiting were the principal toxic symptoms which were rather severe in gynecological patients. The benefit of metronidazole combination was studied in comparison with a group of patients given dynamic dose-fractionation with breathing of oxygen only. Preliminary analysis of the data suggests that the combination with radiosensitizer has not produced an increase in the curability of cancer in these particular sites.

Our experience with the treatment of nasopharyngeal tumors.

An analysis of a group of 78 patients suffering from nasopharyngeal cancer treated during a period of 15 years is discussed. The ratio of males to females was 1.6 : 1, with a maximum incidence in the 4th and 5th decade. There was a predominance of carcinomas (60 patients) over malignant lymphomas (18 patients). With respect to the stage of the carcinomas, the largest group of patients (36 individuals) could be classified as Stage III. At the beginning of the treatment regional metastases were present in 68% of the carcinomas. Nasopharyngeal tumors were treated only by radiotherapy; in the earlier period by conventional roentgenotherapy, recently by telegammatherapy 60Co only. The 5-year survival rate of patients with carcinomas was 25%, of those with malignant lymphomas was 27.7%. Among carcinomas we found better results in lymphoepitheliomas, among the lymphomas in lymphocytic lymphomas. The present study also discusses the significance of some cofactors that may play a role in respect of prognosis, treatment and final clinical evaluation of patients with nasopharyngeal cancer.