Proton Beam Therapy for Liver Cancer is Well Tolerated: Outcomes from the Proton Collaborative Group REG001-09 Trial Michael Chuong, M.D.1,2, Smith Apisarnthanarx, M.D. 3, William Hartsell, M.D.4, Gary Larson, M.D. 5, Henry Tsai, M.D.6, Carl Rossi, M.D. 7, Carlos Vargas, M.D.8 1University of Maryland, 2Miami Cancer Institute at Baptist Health South Florida, 3University of Washington, 4Chicago Proton Center, 5ProCure Oklahoma City, 6ProCure New Jersey, 7Scripps Proton Center, 9Mayo Clinic Table 1. Patient and tumor characteristics Table 2. Treatment characteristics Introduction The liver is one of the most radiosensitive organs, making radiation therapy (RT) for liver tumors extremely challenging. RT is appropriate for highly selected liver patients with limited tumor burden and adequate liver function. Dose reduction may be needed to lower the probability of radiation-induced liver disease (RILD), especially in the presence of cirrhosis. Proton beam therapy (PBT) delivers less radiation dose to the normal liver than photon therapy and is expected to reduce toxicity while also permitting safe dose escalation for some patients with liver tumors. Methods The PCG REG001-09 trial (NCT01255748) prospectively collects data for PBT patients for a variety of tumors including liver cancer. To better understand treatment details and outcomes associated with liver PBT, patients enrolled on the PCG registry trial from 5 institutions who received liver PBT for any cancer between 2012 and 2015 were analyzed. Acute toxicity was considered to have occurred during or within 3 months of PBT completion. Liver function test results were not recorded before, during, or after PBT and therefore RILD could not be assessed. Results Forty-three liver cancer patients were included, most with either hepatocellular carcinoma (48.8%) or cholangiocarcinoma (25.6%). The vast majority did not have liver surgery at any time (83.7%). The median prescribed PBT dose was 58.05 Gy(RBE) (range 21.7-67.5). The median prescribed number of fractions was 15 (range 12-37). The liver only was treated in 90.7%; inclusion of lymph nodes was rare. Uniform scanning was used in 26 (72.1%) and pencil beam scanning in 2 patients (4.7%). Median follow up was 4.4 months (range 1.3-17.9). 3 patients (7%) had an intrahepatic recurrence, 2 patients (4.6%) developed distant metastasis, and 10 patients (23.3%) died. The worst acute toxicity was grade 2 in 16 patients (37.2%) consisting primarily of anorexia (n=8), fatigue (n=5), nausea/vomiting (n=4), and dermatitis (n=4). Conclusions Although longer follow up is needed to assess late toxicities as well as disease control, early outcomes from the PCG registry trial for liver cancer patients using predominantly hypofractionated uniform scanning PBT has a favorable acute toxicity profile. N (%) Total patients 43 Enrollment by institution A B C D E 1 (2.3) 3 (7) 4 (9.3) 10 (23.3) 25 (58.1) Histology Hepatocellular carcinoma Cholangiocarcinoma Squamous cell carcinoma Adenocarcinoma Neuroblastoma Unknown 21 (48.8) 11 (25.6) 7 (16.3) 2 (4.6) Clinical T stage 1 2 3 29 (67.4) Clinical N stage Clinical M stage 13 (30.2) N (%) Surgery Prior to PBT Partial hepatectomy Cholecystectomy After PBT No surgery 6 (14) 5 (11.6) 1 (2.3) 36 (83.7) Liver RT Photon Radioembolization Not prior to PBT Unknown 3 (7) 2 (4.6) 37 (86) Chemotherapy Concurrent with PBT None 10 (23.3) 4 (9.3) 33 (76.7) Prescribed PBT dose Median, Gy(RBE) Range <45 Gy(RBE) 45-50.5 Gy(RBE) >50.5 Gy(RBE) 58.05 21.7-67.5 31 (72.1) Prescribed PBT fractions Median number >2 Gy(RBE) per fraction ≤2 Gy(RBE) per fraction 15 12-37 34 (79.1) 9 (20.9) PBT technique Uniform scanning Pencil beam scanning 26 (60.5) 15 (34.9) PBT target Liver only Liver + locoregional nodes Chest wall 39 (90.7) Figure 1. Liver patient enrollment on the REG001-09 trial from 2012-2015 Figure 2. Worse acute toxicity grade