O. Yariv1,2, H. Williams3, K. A. Goodman4, F. S. Verheij3, D. M. Omer3, S. T. Lin5, L. X. Qin5, M. J. Gollub6, L. Saltz7, J. Garcia-Aguilar3, and A. J. Wu1; 1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 2Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 3Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, NY, 4Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, 5Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 6Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 7Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Purpose/Objective(s): The OPRA trial was a randomized clinical trial investigating the optimal sequencing of total neoadjuvant therapy (TNT) for rectal cancer patients desiring organ preservation (OP). An optional higher-dose radiation boost was allowed on this trial. We aimed to determine whether higher radiation boost dose was associated with probability of clinical complete response (cCR) and OP. Materials/
Methods: Patients with clinical stage II/III rectal adenocarcinoma were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Radiation therapy (RT) was delivered to the primary tumor and involved nodes to 4500cGy with concurrent chemotherapy. The standard boost dose to the primary tumor was 500-540cGy (total 5000-5040cGy), but the treating physician was allowed to give an optional higher-dose boost of 900-1100cGy (total 5400-5600cGy). Post-TNT tumor assessment was completed by surgeons, stratifying patients across 3 tiers of clinical response using endoscopy and MRI, and patients with a clinical complete or near-complete response were offered organ preservation. Organ preservation and tumor clinical response rates by radiation boost dose (standard vs. high-dose boost) were estimated using the Kaplan-Meier method and proportions, respectively, and tested for statistical significance using the logrank test and Fisher’s exact test, respectively. Results: A total of303 patients were eligible, including 93 patients in the standard-dose (SD) boost group (median age, 57 [50-66]; 56% male) and 210 in the high-dose (HD) boost group (median age, 58 [50-68]; 68% male). Age, gender, ECOG status, tumor distance from anal verge and systemic treatment type and schedule were similar across the two groups. Clinical T3/T4 stage at presentation was more common among HD patients (83% and 10%, respectively) compared to LD patients (62% and 18%, respectively) (p<0.001); otherwise, the two groups were comparable in all other measured aspects. Median follow-up for patients with organ preservation (OP) was 5.14 years (IQR, 3.75-5.67). The 3- and 5- year probability of OP were both 52% (95% CI, 43%-64%) for SD patients, and 47% (95% CI, 41%-54%) and 45% (95% CI, 38%-52%) for HD patients, respectively. Rates of endoscopic cCR and near-complete response (nCR) were similar among SD patients (41% and 44%, respectively) and HD patients (44% and 39%, respectively) (p=0.5). Conclusion: In the randomized OPRA trial of total neoadjuvant therapy for organ preservation in rectal cancer, a higher radiation boost dose was not significantly associated with probability of achieving a complete clinical response or the durability of organ preservation.
