Lower rates of acute gastrointestinal toxicity with pencil beam proton therapy relative to IMRT in neoadjuvant chemoradiation for rectal cancer

696 Background: Preoperative chemoradiotherapy (CRT) is standard treatment for locally advanced rectal cancer (LARC). GI toxicity leading to ED visits, hospitalization, and need for IV hydration remains a management challenge. Previous studies have established volume of bowel receiving low dose radiation (V15) as the strongest predictor of GI toxicity. We have previously shown pencil beam scanned proton therapy (PBSPT) is dosimetrically superior to IMRT in LARC with respect to low dose to the bowel. This studycompares the toxicity of patients treated with PBSPT and IMRT in neoadjuvant treatment of LARC. Methods: A retrospective review was conducted of patients treated at the University of Pennsylvania with neoadjuvant 5-FU or capecitabine CRT. Patient and tumor characteristics, treatment, and toxicity data were collected. PBSPT (50.4 Gy RBE to standard volumes) was delivered using either two opposed lateral fields or posterior oblique fields with a patient supine or prone. These patients were registered on a prospective registry study. IMRT plans were delivered with 7-9 field IMRT or volumetric arc therapy in the supine or prone position. Statistical analysis was performed using STATA v12.0. Results: Between 3/2009 and 6/2014, 39 patients treated with IMRT and 26 patients treated with PBSPT were studied. Continuous-infusion 5-FU was administered in 31 (79%) IMRT patients and 16 (62%) PBSPT patients (p = 0.162); the remainder received capecitabine. PBSPT patients had significantly lower rates of acute Grade ≥ 2 diarrhea, 12% versus 39% with IMRT (p = 0.022). On multivariable analysis incorporating the type of chemotherapy, use of PBSPT remained a significant predictor of lower rate of Grade ≥ 2 diarrhea (OR = 0.20, 95% CI 0.05 - 0.82, p = 0.025). There was also a borderline significant reduction in Grade ≥ 2 fatigue with the use of PBSPT, occurring in 8% versus 29% of IMRT patients, p = 0.057. Conclusions: These preliminary results indicate PBSPT is associated with significant reduction in acute Grade ≥ 2 diarrhea compared to IMRT. PBSPT may play an important role in the treatment of LARC, a disease with high cure rate where radiation toxicity should be minimized.