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We tried to investigate the outcome and patterns of failure of endometrial cancer patients who were treated with surgery and postoperative radiation therapy (RT).
Eighty-three patients with endometrial cancer who received postoperative RT between May 1979 and August 2000 were included in this retrospective study. Forty-one patients received total abdominal hysterectomy, 41 patients received Wertheim's operation and 1 underwent vaginal hysterectomy. Pelvic lymph node dissection or pelvic lymph node sampling was done in 56 patients and peritoneal cytology was done in 35. All the patients were staged according to 1988 FIGO (International Federation of Gynecology and Obstetrics) staging system; 2 were stage IA, 23 were stage IB, 20 were stage IC, 4 were stage IIA, 5 were stage IIB, 9 were stage IIIA, 2 were stage IIIB and 18 were stage IIIC. The histologic diagnoses were adenocarcinoma in seventy-four patients (89%). The histologic grades were Grade 1, 2 and 3 in 21 (25%), 43 (52%) and 10 (12%) patients, respectively. All the patients received external beam RT (EBRT) with a median dose of 5,040 cGy (range: 4,500~5,075 cGy) to the whole pelvis. Five patients with pathologically confirmed paraaortic lymph node metastasis received 4500 cGy to the paraaortic lymph nodes. Fifteen patients received low-dose intracavitary brachytherapy after their EBRT. A total dose of 7,500~9,540 cGy (median dose: 8511) was prescribed to the vaginal surface.
Overall, 11 patients (13%) experienced disease relapse: 4 with initial stage I or II disease and 7 with initial stage III disease. Among the 54 stage I or II patients, 1 (2%) relapsed in the pelvis only, 2 (4%) relapsed in the vagina and distant organs, and 1 (2%) relapsed in the paraaortic lymph nodes (PANs). Among the 29 stage III patients, 1 (3%) relapsed in the vagina. The most common sites of failure for the stage III patients were the peritoneum (3 patients, 10%), PANs (2 patients, 7%), and lung (2 patients, 7%). With a median follow-up period of 86 months, the overall survival (OS) and disease-free survival (DFS) rates at 5 years were 87% for both. The five-year DFS rate was 93%, 100% and 74% for the stage I, II and III patients, respectively. Three patients experienced severe radiation-related late complications: RTOG (Radiation Therapy Oncology Group) grade 3 radiation cystitis was seen in one patient, and grade 3 bowel obstruction was seen in two patients.
Postoperative RT was useful for controlling pelvic disease. The major patterns of failure for stage III patients were peritoneal seeding and distant metastasis. Selective use of whole abdominal radiotherapy or adjuvant chemotherapy may improve the therapeutic outcome of these patients.
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Histone deacetylase inhibitors (HDIs) are emerging as potentially useful components in anticancer therapy. In this study, we tried to confirm the radiosensitizing effect of trichostatin A (TSA) on a panel of human carcinoma cell lines and elucidate its mechanism of interaction.
A549, HeLa and Caski cells were exposed to TSA for 18 hr prior to irradiation, and the cell survival then measured using a clonogenic assay. Western blot and flow cytometric analyses, for histone acetylation, and cell cycle and apoptosis, respectively, were also performed.
TSA increased the acetylation of histone H3. The pretreatment of TSA consistently radiosensitized all three cell lines. The SF2 (surviving fraction at 2 Gy) of TSA-treated cells was significantly lower than that of mock treated cells. The SER (sensitizer enhancement ratio) increased in all 3 cell lines, in concentration dependent manners. The TSA treated cells showed abrogation of radiation-induced G2/M arrest, in a concentration dependent manner.
The pretreatment of TSA enhanced the radiosensitivity of a panel of human carcinoma cells, which was attributed, in part, to the abrogation of radiation-induced G2/M arrest.
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