Reduced Acute Toxicity after Proton Versus Photon Chemoradiation for Anal Cancer: Outcomes from the Proton Collaborative Group REG001-09 Trial

Abstract

Most anal cancer (AC) patients experience acute grade 2 or higher (G2+) toxicity from definitive chemoradiation (CRT) with intensity modulated radiation therapy (IMRT) as shown in the Radiation Therapy Oncology Group (RTOG) 0529 phase 2 trial. Although normal organ sparing has been shown to favor proton beam therapy (PBT) over IMRT, particularly with respect to small bowel and bone marrow, clinical outcomes of PBT for AC have never been published. The Proton Collaborative Group (PCG) REG001-09 trial (NCT01255748) is a multi-institutional registry study that prospectively captures outcomes for a variety of cancer types in patients receiving PBT and/or photon therapy. We compared prospectively recorded acute toxicity outcomes (genitourinary (GU), gastrointestinal (GI), proctitis, dermatitis, fatigue) of AC patients enrolled on the PCG trial who received definitive CRT with either PBT or IMRT. Hematologic toxicity outcomes were not available for analysis. Acute toxicity was evaluated according to the CTCAE version 4.0 and defined as having occurred during or within 90 days after completion of CRT. Dosimetric outcomes were not recorded in the PCG study and therefore could not be evaluated with regards to toxicity. Fifty-one AC patients received definitive CRT across 5 institutions from 2010-2018; 33 (64.7%) received PBT while 18 (35.3%) received IMRT. Radiation target volumes were designed according to the RTOG anorectal contouring atlas. PBT patients were older (median 69.5 vs. 60.5 years; p=0.079), more often male (48.5% vs. 11.1%; p=0.008), and had less advanced T stage (p=0.063) and N stage (p=0.043). There was no difference in median total prescribed radiation dose (both 54 Gy in 30 fractions) or in the use of concurrent chemotherapy (most received 5-fluorouracil and mitomycin-C). PBT was typically delivered with pencil beam scanning (69.7%) versus passive scattering. There was no difference in acute grade 2+ GU toxicity, dermatitis, proctitis, or fatigue based on radiation modality although there was a trend towards reduced GI toxicity favoring PBT (Table 1). Acute grade 2+ GI toxicity among PBT patients on the PCG study was significantly reduced versus historical IMRT outcomes from the RTOG 0529 trial. These are the first clinical outcomes of PBT for AC. PBT achieves a meaningful reduction in acute GI toxicity compared to IMRT although we were not able to determine whether this was due to a reduction in small bowel dose. Future studies are warranted to compare acute hematologic toxicity, late toxicities, and long-term survival in AC patients receiving definitive CRT with PBT versus IMRT.Abstract 1093; Table 1Acute grade 2 or higher toxicity from definitive chemoradiation for anal cancerPCG PBT (n=33)PCG IMRT (n=18)RTOG IMRT (n=325)PCG PBT vs. PCG IMRT P valuePCG PBT vs. RTOG IMRT P valueGastrointestinal12 (36.4%)11 (61.1%)237 (73%)0.089<0.001Genitourinary3 (9.1%)2 (11.1%)66 (20%)0.8160.119Dermatitis28 (84.8%)16 (88.9%)271 (83%)0.6880.828 Open table in a new tab