Re-Irradiation for Rectal Cancer: A Single Institution Experience Utilizing Photons and Protons

Abstract

Re-irradiation (Re-RT) for rectal cancer (RC) in patients with prior pelvic radiation therapy (RT) has been shown to be effective. However, safety remains a principle concern, particularly with respect late toxicities. Toxicity mitigation is accomplished in a variety of ways, including hyperfractionation and the use of more conformal treatment modalities such as intensity-modulated radiation therapy (IMRT) and proton therapy (PT). Published data on the use of PT for RC is largely limited to dosimetric studies, with little to no published clinical outcomes, especially with Re-RT. We hypothesize that PT may further reduce toxicity seen in these patients. A single institutional retrospective IRB-approved analysis of all RC patients with any prior pelvic RT re-irradiated with any modality from 2006-present was performed. We collected patient and treatment characteristics, including prior diagnosis, re-irradiation records, and acute and late toxicities. Outcomes, including overall Survival (OS) and Local Control (LC), and incidence of Grade 3+ late toxicities (Gr3+T) were estimated using Kaplan-Meier (KM). Forty-six patients (median follow-up 16 months) received Re-RT from 2007-2018, 23 with photons (median follow-up 15 months) and 23 with protons (median follow-up 16 months). Thirty-four patients had recurrent RC [median prior dose 50.4 Gy (43.2-67.2)] and 12 patients de novo RC and variable prior RT (10 for prostate, 1 for seminoma, 1 for ovarian). Median Re-RT dose was 45.3 Gy [(9.6.0-60.0); 34/46 treated BID], median time to Re-RT 35 months (7.2-712), and 40 received concurrent chemotherapy. Twelve underwent surgical resection (10 R0 incl. 2 pCR; 1 R1; 1 R2). Three patients experienced grade 3 acute toxicities, and no acute Grade 4-5 toxicities were observed. Six patients treated with photons had grade 3+ late toxicities, including one grade 5 toxicity, and 2 patients treated with protons had grade 3+ late toxicities, including one grade 5 occurring in a patient with history of significant injury from prior RT. Rates of 1-yr Gr3+ toxicity were 13.8% (95% CI 7.9-19.7%) for the whole cohort, and 23.3% (95%CI 12.7-33.9%) and 4.8% (95%CI 0.2-9.4%) for photons and protons, respectively (p=0.137). One-year LC and 1-year OS for the whole cohort were 78%+/-7.6% and 75%+/-6.5%, respectively Acceptable rates of acute and late toxicity are demonstrated in this series inclusive of patients treated with photons/PT. This is notably the largest reporting of PT results. Though no statistically significant difference in 1-year Gr3+ toxicity between photon and PT was observed, results are early but promising. We await maturation of results with longer follow-up and larger cohort.