Long-term follow-up of RTOG 92-10: Cervical cancer with positive para-aortic lymph nodes

Purpose: The purpose of this study was to evaluate the late toxicity and ef ficacy of twice-daily external irradiation to the pelvis and lumbar para-ao rtic region with brachytherapy and concurrent chemotherapy for carcinoma of the cervix with positive para-aortic lymph nodes. Patients and Methods: This study was designed to administer twice-daily rad iation doses of 1.2 Gy to the pelvis and lumbar para-aortic lymph nodes (si multaneously) at 4-6-h intervals, 5 days per week. The total external radia tion doses were 24-48 Gy to the whole pelvis, 12-36 Gy parametrial boost, a nd 48 Gy to the lumbar para-aortic region with an additional boost to a tot al dose 54-58 Gy to the positive para-aortic lymph node(s). One or two intr acavitary implants were performed to deliver a minimum total dose of 85 Gy to point A. Cisplatin (75 mg/m(2); Days 1, 22, and 43) and 5-fluorouracil ( 1,000 mg/m(2)/24 h X 4 consecutive days, beginning on Days 1, 22, and 43) w ere given for two or three cycles. Results: Thirty patients with clinical Stages I-IV carcinoma of the cervix with biopsy-proven para-aortic lymph node metastases were enrolled in this study. Hyperfractionated external irradiation was completed in 87% (26 of 3 0). Brachytherapy was given in two implants to 47% (14 of 30) and in one im plant to 33% (10 of 30); 13% (4 of 30) did not receive brachytherapy, I pat ient had three implants, and I had five high-dose-rate implants. Radiothera py was completed per protocol in 70%. Three cycles of chemotherapy were giv en to 23% (7 of 30); 73% (22 of 30) received two cycles, and I patient did not receive chemotherapy. The acute toxicity from chemotherapy was Grade 1 in 3%, Grade 2 in 17%, Grade 3 in 48%, and Grade 4 in 28%. Acute toxicity f rom radiotherapy was Grade I in 7%, Grade 2 in 34%, Grade 3 in 21%, and Gra de 4 in 28%. Late toxicity was Grade 1 in 10%, Grade 2 in 17%, Grade 3 in 7 %, and Grade 4 in 17%. Grade 5 toxicity occurred in I patient during the co urse of therapy, but none had a late Grade 5 toxicity. The median follow-up time for the 7 patients alive at the time of last follow-up was 57 months. The overall survival estimates were 46% at 2 years and 29% at 4 years. The probability of local-regional failure was 40% at 1 year and 50% at 2 and 3 years. The probability of disease failure at any site was 46% at 1 year, 6 0% at 2 years, and 63% at 3 years. Conclusion: The results suggest that twice-daily external irradiation to th e pelvis and lumbar para-aortic region with brachytherapy and concurrent ch emotherapy resulted in an unacceptably high rate (17%, 5 of 29) of Grade 4 late toxicity. One patient died of acute complications of therapy. The surv ival estimates seem no better than standard fractionation irradiation witho ut chemotherapy. (C) 2001 Elsevier Science Inc.