1 Institut régional du Cancer de Montpellier (ICM), Montpellier, France2 Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France3 Institut Paoli-Calmettes, Marseille, France4 Centre Georges François Leclerc, Dijon, France5 Centre Hospitalier Universitaire de Rouen, Rouen, France6 Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France
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BACKGROUND:Preoperative radiochemotherapy and total mesorectal excision are the standard-of-care for locally advanced rectal carcinoma, but some patients could be over- or undertreated.OBJECTIVE:This study aimed to assess the feasibility of radiochemotherapy tailored based on the tumor response to induction chemotherapy (FOLFIRINOX) to obtain a minimum R0 resection rate of 90% in the 4 arms of the study.DESIGN:This study is a multicenter randomized trial (NCT01333709).SETTING:This study was conducted at 16 French cancer specialty centers.PATIENTS:Two hundred six patients with locally advanced rectal carcinoma were enrolled between 2011 and 2014.INTERVENTIONS:Good responders (≥75% tumor volume reduction) were randomly assigned to immediate surgery (arm A) or standard radiochemotherapy (Cap 50: 50 Gy irradiation and 1600 mg/m2 oral capecitabine daily) plus surgery (arm B). Poor responders were randomly assigned to Cap 50 (arm C) or intensive radiochemotherapy (Cap 60, 60 Gy irradiation, arm D) before surgery.OUTCOME MEASURES:The primary end point was a R0 resection rate (circumferential resection margin >1 mm).STATISTICAL CONSIDERATIONS:The experimental strategies were to be considered effective if at least 28 successes (R0 resection) among 31 patients in each arm of stratum I and 34 successes among 40 patients in each arm of stratum II were reported (Simon 2-stage design).RESULTS:After induction treatment (good compliance), 194 patients were classified as good (n = 30, 15%) or poor (n = 164, 85%) responders who were included in arms A and B (16 and 14 patients) and arms C and D (113 and 51 patients). The trial was prematurely stopped because of low accrual in arms A and B and recruitment completion in arms C and D. Data from 133 randomly assigned patients were analyzed: 11, 19, 52, and 51 patients in arms A, B, C, and D. Good responders had smaller tumors than poor responders (23 cm3 vs 45 cm3; p < 0.001). The surgical procedure was similar among groups. The R0 resection rates [90% CI] were 100% [70–100], 100% [85–100], 83% [72–91], and 88% [77–95]. Among the first 40 patients, 34 successes were reported in arms C and D (85% R0 resection rate). The circumferential resection margin ≤1 rates were 0%, 0%, 12%, and 5% in arms A, B, C, and D. The rate of transformation from positive to negative circumferential resection margin was 93%.LIMITATIONS:There was low accrual in arms A and B.CONCLUSION:Tailoring preoperative radiochemotherapy based on the induction treatment response appears safe for poor responders and promising for good responders. Long-term clinical results are needed to confirm its efficacy. See Video Abstract at http://links.lww.com/DCR/A359.