Long-term normal tissue effects of intraoperative electron radiation therapy (IOERT): Late sequelae, tumor recurrence, and second malignancies

Purpose: To evaluate long-term survivors treated with intraoperative electr on radiation therapy (IOERT) as a component, with particular emphasis on an alyzing late normal tissue toxicity, second malignancies, and patterns of d elayed tumor recurrence. Methods and Materials: From September 1984 to December 1991, 739 patients w ere treated with IOERT, One hundred ninety;five patients were alive at leas t 5 years after IOERT (26%), Patient information regarding late complicatio ns related symptoms, incidence of second tumors, and delayed relapses were analyzed, Normal tissue changes were categorized by a modified LENT/SOMA sc ale (Grade 0-1, Grade 2, and Grade 3-4), Risk of late toxicity was grouped by type and number of cancer treatment modalities employed in each patient: surgery + IOERT alone (17 patients, 9%); IOERT + external radiotherapy a c hemosensibilization (90 patients, 46%); IOERT a external radiotherapy a neo adjuvant chemotherapy (+/- previous radiotherapy) (88 patients, 45%). Biolo gic effective doses (BED) were calculated for alpha/beta = 3.5 for late fib rosis, Results: With a mean follow-up time of the surviving patients of 94 months (range: 55-162 months), 99 patients (51%) had Grade 0-1 toxicity, 52 (27%) had Grade 2, and 44 patients (23%) presented Grade 3-4 late normal tissue c omplications. Risk groups by treatment intensity did correlate with severit y of observed toxicity (p < 0.001), BED estimations did not correlate with late normal tissue damage. The tumor type with higher toxicity scores was b one sarcoma (28/46, 60%), in which the estimated BED = 100.5 Gy, Peripheral neuropathy was the dominant IOERT-specific toxicity present in 24 patients (12%), Second malignancies were identified in 8 patients (4%), none inside the IOERT held (3 questionable to be marginal to the external beam radioth erapy volume). In 36 patients (18%), recurrence of the originally treated t umor was detected, including 11(7%)local relapses. Conclusions: The incidence of late normal tissue complications (50%) and se verity (23%) is significant in a cohort of patients surviving more the 5 ye ars after IOERT. The understanding of the contribution of IOERT to late tis sue damage requires specific analysis. Peripheral neuropathy is a character istic finding in IOERT trials. Second malignancies inside the IOERT field w ere not identified during the study period. The risk of recurrences, includ ing local failures, requires an intensive follow-up of long-term survivors from IOERT trials. (C) 2001 Elsevier Science inc.