The aim of the study was to compare the spontaneous and ex vivo radiation-induced chromosomal damage in lymphocytes of untreated prostate cancer patients and age-matched healthy donors, and to evaluate the chromosomal damage, induced by radiotherapy, and its persistence. Blood samples from 102 prostate cancer patients were obtained before radiotherapy to investigate the excess acentric fragments and dicentric chromosomes. In addition, in a subgroup of ten patients, simple exchanges in chromosomes 2 and 4 were evaluated by fluorescent in situ hybridization (FISH), before the onset of therapy, in the middle and at the end of therapy, and 1 year later. Data were compared to blood samples from ten age-matched healthy donors. We found that spontaneous yields of acentric chromosome fragments and simple exchanges were significantly increased in lymphocytes of patients before onset of therapy, indicating chromosomal instability in these patients. Ex vivo radiation-induced aberrations were not significantly increased, indicating proficient repair of radiation-induced DNA double-strand breaks in lymphocytes of these patients. As expected, the yields of dicentric and acentric chromosomes, and the partial yields of simple exchanges, were increased after the onset of therapy. Surprisingly, yields after 1 year were comparable to those directly after radiotherapy, indicating persistence of chromosomal instability over this time. Our results indicate that prostate cancer patients are characterized by increased spontaneous chromosomal instability. This instability seems to result from defects other than a deficient repair of radiation-induced DNA double-strand breaks. Radiotherapy-induced chromosomal damage persists 1 year after treatment.
Ovarian cancer (OC) is associated with the highest cancer-related mortality among gynecological cancers, since nearly 2/3 of patients are diagnosed with advanced stage disease which is caused by an unspecific clinical appearance and the lack of effective early detection methods. So far only histopathological and clinical prognostic factors have clinical relevance from which FIGO-stage and the postoperative residual disease have predominant importance. Early stage OC (FIGO Ia-II) has a good prognosis with survival rates of approximately 90%, provided that the tumor is macroscopically resected and an adequate surgical staging has been performed. Additionally early stage OC patients should receive an adjuvant platinum-based chemotherapy. In advanced stage OC (FIGO IIb-IV) the aim of primary surgery is a maximum cytoreduction. Additionally, postoperative treatment is performed with carboplatin/paclitaxel for six cycles. So far there are no data to support the introduction of non-cross-resistant agents, dose escalation or prolongation of therapy. The majority of advanced stage patients relapse despite optimal primary therapy. Treatment of recurrent disease follows palliative considerations and should serve symptom control and tumor regression and especially quality of life. The prognosis of recurrent disease differs extensively according to the length of the progression-free survival and response to primary platinum-based chemotherapy and is differentiated into platinum-refractory and platinum-sensitive disease. Platinum-refractory OC generally have an extensive chemoresistance against all available cytostatic agents. Various mono-chemotherapies do not exceed response rates of 20%. In contrast, platinum-sensitive recurrent OC have a much more favourable prognosis due to response rates of 30-50% with platinum-based combination therapies. Another operation seems to be only reasonable in case of platinum-sensitive recurrent disease and if the tumor can be macroscopically resected with no residual tumor The aftercare in OC should focus on the detection of recurrent disease and the detection and therapy of maintained treatment related toxicities as well as psycho-oncological aspects.
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