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Not all sarcomas that arise after RT are induced by irradiation, but it is impossible to differentiate RIS from primary sarcomas. The lower limit of the latency period for establishing the diagnosis of RIS is controversial and ranges from 6 months to 8 years.18-21, 29 In our study, we used the most common latency criteria of 3 to 4 years as reported by Arlen et al.21 The median latency in our series, 9.3 years, was consistent with data from other studies, in which the median latency ranges from 7.6 years to 22 years.3-11, 29 The shorter period of 7.6 years reported by Kuttesch et al26 may be explained by the younger age of their patients. In addition, the administration of chemotherapy may shorten the interval between RT for the first cancer and http://www.selleckchem.com/products/bay-61-3606.html the subsequent presentation of RIS. However, we produced no evidence that chemotherapy or age had an impact on the timing of RIS in our series. In a study by Wiklund et al,30 a total radiation dose >36 Gy resulted in a median latency of 7.4 years, whereas http://www.selleck.cn/products/sunitinib.html a dose http://www.selleckchem.com/products/q-vd-oph.html 30 Our results suggest that this difference may be caused at least in part by the lower dose given to the patients who received orthovoltage radiation. Our study also suggested that the latency of RIS after megavoltage x-ray therapy was not only shorter than that after orthovoltage x-ray therapy but also was shorter than the latency after Cobalt-60 therapy. However, the limited number of patients and the shorter follow-up of patients who received megavoltage x-rays did not permit us to reach a definitive conclusion in this regard. There were significantly fewer patients with cutaneous or subcutaneous RIS in the megavoltage group than in the orthovoltage group, probably because of a larger skin-sparing effect of megavoltage radiation. In addition, soft tissue adjacent to bone receives a greater absorbed dose with megavoltage radiation than with orthovoltage radiation because of the Compton effect.4 Despite the small number of reports, a wide variety of histologic subtypes has been reported. The most frequent histologic subtypes for de novo sarcomas are malignant fibrous histiocytoma, liposarcoma, and leiomyosarcoma, which are different from those commonly classified as RIS.31 In our study, fibrosarcoma was the most frequent histologic type of RIS followed by osteosarcoma and malignant fibrous histiocytoma.