IMRT and Concurrent Chemotherapy for Anal and Perianal Cancer: The Princess Margaret Hospital Experience

Abstract

IMRT and concurrent chemotherapy is standard treatment for anal and perianal cancer at our center. A research ethics board approved prospective cohort study was established to evaluate toxicity, clinical outcomes and quality of life (QoL). From June 2008, patients (pts) with anal and perianal cancer undergoing IMRT were enrolled. IMRT dose was 36 Gy/20f for elective and 54 Gy/30f - 63 Gy/35f for gross targets using standardized contouring, dose prescriptions and dose-volume criteria. Chemotherapy (weeks 1 and 5) consisted of continuous infusion 5-FU 1g/m2/d (max 1.5g/d), d1-4 and MMC 10 mg/m2, d1. Treatment breaks were not planned. Toxicity was graded using NCI CTC v3. Overall survival (OS), disease-free survival (DFS), and colostomy-free survival (CFS) were estimated using the Kaplan-Meier method. Locoregional failure (LRF) was estimated using the cumulative incidence function. QoL was assessed by the EORTC QLQ-C30 and CR29 questionnaires at baseline, treatment end, 3 and 6 months, and then yearly. QoL scores from different time points were compared using the Wilcoxon test. To date, 41 pts have completed treatment: median FU 1 year; median age 57 years; 20 female; 7 (17%) HIV+; 1 (2%) stage 0, 24 (59%) stage II, and 16 (39%) stage III. IMRT doses were 54 Gy - 14 pts (34%) and 63 Gy - 27 pts (66%) to primary; 54 Gy - 1 pt (2%), 58.5 Gy - 10 pts (24%) and 63 Gy - 9 pts (22%) to enlarged nodes. Fifteen (37%) pts required a treatment break (2 - 15d, median 8d) due to acute toxicity, mainly dermatitis (13/15). Acute toxicities were: grade 3 - skin 44%, hematologic 24%, GI 7%, cardiac 2%, pulmonary (MMC toxicity) 2% and GU 0%; grade 4 - skin 2%, hematologic 5% and pulmonary embolism 2%. Thirty-three (89%) pts achieved a complete response; 2 partial responses; 1 stable disease; 1 progressive disease (died); and 4 were not evaluable (1 died of stroke post treatment, 3 assessments pending). One pt developed a contralateral inguinal nodal recurrence 9 months post treatment, and another developed local recurrence at 10 months. Two pts did not complete treatment: 1 died of cardiac cause, and another refused. One-year OS, DFS, CFS, and LRF were 92%, 85%, 86%, and 7%, respectively. Global QoL, pain, skin, and defecation scores were clinically significantly worse at end of treatment compared to baseline (p = 0.001, p = 0.0002, p < 0.0001, and p = 0.04, respectively), but returned to baseline levels 3 months post treatment. At 6 months, pain scores improved significantly compared to baseline (p = 0.005). We report favorable acute grade 3+ hematologic (29%) and GI/GU toxicities (7%) compared to non-IMRT studies (RTOG 9811: 61% and 36%, respectively), but treatment breaks for dermatitis were common. Early clinical outcomes are promising, and there is no persistent negative impact on QoL.