NRG Oncology Radiation Therapy Oncology Group 0822: A phase II study of preoperative chemoradiotherapy utilizing intensity modulated radiation therapy (IMRT) in combination with capecitabine and oxaliplatin for patients with locally advanced rectal cancer
Mené sur 79 patients atteints d'un cancer rectal non métastatique de stade T3 ou T4 (durée médiane de suivi : 4 ans), cet essai de phase II évalue l'intérêt d'une radiothérapie avec modulation d'intensité dans le cadre d'une chimioradiothérapie néoadjuvante à base de capécitabine et d'oxaliplatine pour réduire la toxicité gastro-intestinale
Purpose : To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Materials and Methods : Patients with localized, non-metastatic T3 or T4 rectal cancer < 12 cm from the anal verge were enrolled in a prospective, multi-institutional, single arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3D-conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed in 4-8 weeks following completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint of the study was acute grade 2-5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of 0.10 (1-sided). Results : 79 patients were accrued, of whom 68 were evaluable. 61 patients (89.7%) had cT3 and 37 (54.4%) cN (+) disease. 42/68 patients received post-operative chemotherapy. 58 patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. 35 patients (51.5%) developed grade ≥ 2 GI toxicity. 12 patients (17.6%) developed grade 3 or 4 diarrhea. pCR was achieved in 10 patients (14.7%). With a median follow-up of 3.98 years, the 4-year locoregional failure (LRF) rate was 7.4% (95% CI: 1.0% - 13.7%). 4-year OS and DFS were 82.9% (95% CI: 70.1% - 90.6%) and 60.6% (95% CI: 47.5% - 71.4%), respectively. Conclusion : The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of gastrointestinal toxicity.