NRG Oncology Radiation Therapy Oncology Group 0822: A Phase 2 Study of Preoperative Chemoradiation Therapy Using Intensity Modulated Radiation Therapy in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

Abstract

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.

Qualidade de vida de pacientes durante terapia antineoplásica: estudo descritivo

“…Em relação ao tratamento com antineoplá-sico, identificaram-se protocolos combinados das seguintes drogas: oxaliplatina, fluorouracil, irinotecano, bevacizumabe, capecitabina, epirrubicina e ácido folínico; porém a medicação utilizada em todos os protocolos foi o fluorouracil. Os benefícios da quimioterapia antineoplásica para o câncer de cólon e reto, paliativo ou curativo, são mais evidentes com regimes que incluem a oxaliplatina em associação com o fluorouracil, e também com capecitabina e oxaliplatina (12,13) .…”

The Impact of Novel Radiation Treatment Techniques on Toxicity and Clinical Outcomes in Rectal Cancer

“…The NRG Oncology RTOG 0822 trial evaluated the rate of GI toxicity in patients treated with neoadjuvant chemoradiation with concurrent capecitabine/oxaliplatin (CAPOX) for LARC (29). This study was based on the RTOG 0247 phase II randomized trial comparing capecitabine and oxaliplatin with 3DCRT versus capecitabine and irinotecan with 3DCRT.…”

“…Pelvic radiation to a dose of 45 Gy was delivered with IMRT followed by a 3DCRT boost to the gross disease to 50.4 Gy. Grade ≥ 2 GI toxicity and grade ≥ 3 diarrhea were reported in 50% and 17.6 % of patients, respectively (29). Although real-time quality assurance was performed in all patients with only 5 unacceptable variations, the grade ≥ 2 GI toxicity was significantly higher than the target rate of 28% and the reported rate of 40% in RTOG 0247 (30).…”

Bone marrow tolerance during postoperative chemotherapy in colorectal carcinomas

“…Patients were treated with either intensity-modulated radiation therapy (IMRT) (n=20, 57.1%) or 3D-conformal radiation therapy (3D-CRT) (n=15, 42.8%) to a median dose of 50.4 Gy (range: 48.6-54 Gy) in 1.8 Gy/day fractions. Patients receiving Intensity Modulated Radiation Therapy (IMRT) were treated as per RTOG 0822 with additional institutional dose constraints consisting of the iliac bone marrow (IBM) and femoral head volume receiving 30 Gy <50% (17,18). Similarly, the median volume receiving 30 Gy to the IBM for rectal cancer patients in this study was 37%.…”