IMPACT OF CLINICAL AND THERAPEUTIC FACTORS ON MAJOR LATE COMPLICATIONS AFTER RADIOTHERAPY WITH OR WITHOUT CONCOMITANT CHEMOTHERAPY FOR ANALCARCINOMA

Purpose: To investigate factors potentially influencing major late mor bidity after sphincter-conserving treatment for anal carcinoma. Method s and Materials: Grade 3-4 complications were retrospectively analysed in 144 evaluable patients (pts), 55 pts after split-course radiothera py (RT), and 89 after concomitant chemo-RT. First sequence RT delivere d a median dose of 39.6 Gy using megavoltage photon beams, Boost treat ment used either Ir-192 implantation or external beam RT (median dose 20 Gy), Chemotherapy started on day 1 and in 83% of pts consisted of M itomycin-C (10 mg/m(2)) and a 5-day infusion of 5-fluorourcil (600-800 mg/m(2)/day), Uni-and multivariate analyses tested the association of following factors with complication rate: age, gender, stage, anatomi c tumor extent, type of biopsy, external RT technique (dose, fraction size, field arrangement), boost type (brachytherapy vs, external), bra chytherapy dose and dose rate, overall treatment time, and addition of chemotherapy. Results: Five-year actuarial complication rate was 16%, Two variables were significantly associated with complication rate: a natomic tumor extent (canal or margin vs. both +/- rectum; 10 vs, 31% complications, p = 0.0004) and first sequence prescribed dose (<39.6 G y vs. greater than or equal to 39.6 Gy; 7 vs, 23% complications, p = 0 .012), confirmed as independent factors by Cox analysis, Grade 4 anal morbidity correlated significantly with prior local excision, All six bone complications were observed in pts treated by chemo-RT using larg e pelvic fields, five occurring in pts older than 66. Conclusion: Pts with tumors involving more than one anatomic subsite or treated with t he higher first sequence RT dose are at greater risk of major complica tions. Prior tumor excision and combined modality therapy in older pts appear to favor major anal and bone complications, respectively. (C) 1997 Elsevier Science Inc.