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PURPOSE External beam radiation therapy (EBRT) has gained delayed acceptance as a recommended first-line treatment modality for patients with hepatocellular carcinoma (HCC), given limited evidence that it improves overall survival (OS). We analyzed individual patient data (IPD) from an international cohort to assess OS among patients with HCC treated with EBRT. METHODS We performed a systematic review of publications that assessed EBRT, met prespecified technical standards for HCC, and reported OS (search date December 15, 2022). Corresponding authors were invited to submit IPD for the study. We performed Kaplan-Meier survival analyses to determine OS and restricted mean survival time (RMST) stratified by Barcelona Clinic Liver Cancer (BCLC) stage and treatment status (ie, treatment-naïve and experienced). We performed random effects Cox proportional hazards modeling to assess clinical characteristics associated with OS. RESULTS Data were provided on 4,913 patients treated with EBRT with a median follow-up time of 5.0 years. The median OS was 6.8 years (95% CI, 5.7 to 8.7) for BCLC-0 and 4.6 years (95% CI, 4.1 to 5.1) for BCLC-A. Among treatment-naïve patients, the median OS was not reached (95% CI, 8.6 to not reached) for BCLC-0 and was 5.4 years (95% CI, 4.5 to 6.7) for BCLC-A. In multivariable models, more advanced BCLC stage, higher tumor burden, worse performance status, and Child-Pugh class B or C were associated with a higher risk of mortality. Ablative radiation dose and more recent year of treatment were associated with a reduced risk of death. CONCLUSION To our knowledge, this study represents the largest multinational cohort of patients with HCC treated with EBRT. OS outcomes with EBRT for very early- and early-stage HCC appear to be comparable with resection, thermal ablation, and other ablative locoregional therapies. These data support the inclusion of EBRT in the BCLC HCC clinical decision-making process.

Abstract Background: Recent advances in radiotherapy techniques have allowed ablative doses to be safely delivered to inoperable liver tumors. In this setting, proton beam radiotherapy (PBT) provides the means to escalate radiation dose to the target volume while sparing the uninvolved liver. This study evaluated the safety and efficacy of hypofractionated PBT for liver tumors, predominantly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).Methods: We evaluated the prospective registry of the Proton Collaborative Group for patients undergoing definitive PBT for liver tumors. Demographic, clinicopathologic, toxicity, and dosimetry information were compiled.Results: To date, 63 patients have been treated at 9 institutions between 2013-2019. Thirty (48%) had HCC and 25 (40%) had ICC. The median dose and biological equivalent dose (BED) delivered was 58.05 GyE (range, 32.5-75) and 80.5 GyE (range, 53.6-100), respectively. The median mean liver BED was 13.9 GyE. Three (4.8%) patients experienced at least one grade ³3 toxicity. With median follow-up of 5.1 months (range, 0.1-40.8), the local control (LC) rate at 1 year was 91.2% for HCC and 90.9% for ICC. The 1-year LC was significantly higher (95.7%) for patients receiving BED greater than 75.2 GyE than for patients receiving BED of 75.2 GyE or lower (84.6%, p = 0.029). The overall survival rate at 1 year was 65.6% for HCC and 81.8% for ICC. Conclusions: Hypofractionated PBT results in excellent LC, sparing of the uninvolved liver, and low toxicity, even in the setting of dose-escalation. Higher dose correlates with improved LC, highlighting the importance of PBT especially in patients with recurrent or bulky disease.

Abstract Background: Recent advances in radiotherapy techniques have allowed ablative doses to be safely delivered to inoperable liver tumors. In this setting, proton beam radiotherapy (PBT) provides the means to escalate radiation dose to the target volume while sparing the uninvolved liver. This study evaluated the safety and efficacy of hypofractionated PBT for liver tumors, predominantly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).Methods: We evaluated the prospective registry of the Proton Collaborative Group for patients undergoing definitive PBT for liver tumors. Demographic, clinicopathologic, toxicity, and dosimetry information were compiled.Results: To date, 63 patients have been treated at 9 institutions between 2013-2019. Thirty (48%) had HCC and 25 (40%) had ICC. The median dose and biological equivalent dose (BED) delivered was 58.05 GyE (range, 32.5-75) and 80.5 GyE (range, 53.6-100), respectively. The median mean liver BED was 13.9 GyE. Three (4.8%) patients experienced at least one grade ³3 toxicity. With median follow-up of 5.1 months (range, 0.1-40.8), the local control (LC) rate at 1 year was 91.2% for HCC and 90.9% for ICC. The 1-year LC was significantly higher (95.7%) for patients receiving BED greater than 75.2 GyE than for patients receiving BED of 75.2 GyE or lower (84.6%, p = 0.029). The overall survival rate at 1 year was 65.6% for HCC and 81.8% for ICC. Conclusions: Hypofractionated PBT results in excellent LC, sparing of the uninvolved liver, and low toxicity, even in the setting of dose-escalation. Higher dose correlates with improved LC, highlighting the importance of PBT especially in patients with recurrent or bulky disease.

Aim/Objectives/Background: The American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) have jointly developed the following practice parameter for proton beam radiation therapy. Proton radiotherapy is the application of a high-energy proton beam to a patient in a clinical setting with therapeutic intent. Proton radiotherapy may permit improved therapeutic ratios with lower doses to sensitive normal structures and greater dose to target tumor tissues. Methods: A literature search was performed to identify published articles regarding clinical outcomes, reviews, quality assurance methodologies, and guidelines and standards for proton radiation therapy. Selected articles are referenced in the text. The following recommendations are based on firsthand experiences of multiple clinical authorities who employ proton therapy and have been peer reviewed by experts at different practicing institutions. Results: This practice parameter is developed to serve as a tool in the appropriate application of this evolving technology in the care of cancer patients or other patients with conditions where radiation therapy is indicated. It addresses clinical implementation of proton radiation therapy, including personnel qualifications, quality assurance standards, indications, and suggested documentation. Conclusions: This practice parameter is a tool to guide technical use of proton therapy and does not assess the relative clinical indication of proton radiotherapy when compared with other forms of radiotherapy, but to focus on the best practices required to deliver proton therapy safely and effectively, when clinically indicated. Costs of proton treatments are high, and the economic costs of proton radiotherapy may also need to be considered.

513 Background: The PCG registry is a multicenter registry for patients receiving proton therapy for various malignancies. The current abstract reviews the outcomes for patients receiving postoperative proton therapy for resected pancreatic cancer. Methods: From March, 2013 to August,2016 18 patients with resected pancreatic adenocarcinoma received postoperative proton therapy. The current study reviews the pretreatment characteristics and outcomes of these patients. Results: Median age -70 years (range 52 to 79); Males 12, Females 6; pT Stage -T2–4, T3–13, T4–1; N Stage -N1–12, N0–6; Margin Status -Close-8, Positive-4, Negative-6; Surgical approach -open-16, laparoscopic 2; Operations performed: standard pancreaticoduodenectomy-11, pylorus sparing pancreaticoduodenectomy-4, total pancreatectomy-1; Pancreaticoduodenectomy with portal vein reconstruction –1; Pancreaticoduodenectomy with irreversible electroporation. Median lymph nodes taken-16.50 (range 3 to 72); Median lymph nodes positive-1.5 (range 0 to 7); PNI positive-9, PNI negative-2, PNI unknown-4; LVI positive-7, LVI negative-6, LVI unknown-5; Median tumor size –3.1cm (range 2.2 to 6.2); Median dose delivered –50.51Gy(RBE) (range 27.88 to 54.00); Median treatment duration –38 calendar days (range 25 to 48); One patient died during treatment. One additional patient demonstrated grade 3 toxicity (anorexia, nausea, diarrhea). Only one patient’s treatment was protracted by more than 5 days. Median available follow up is 1.1 years (range 0.07 to 3.4 years); 2 year survival 37%. Conclusions: Postoperative proton therapy after pancreatectomy was well tolerated without treatment interruption or severe toxicity.

389 Background: The liver is one of the most radiosensitive organs, making radiation therapy (RT) for liver tumors extremely challenging. RT is appropriate only for a minority of liver patients with limited tumor burden; a reduction in the prescribed radiation dose may be needed to lower the probability of radiation-induced liver disease especially in the presence of cirrhosis. Proton beam therapy (PBT) delivers less dose to the liver than photon therapy and is expected to reduce toxicity while also permitting safe dose escalation for some patients with liver tumors. Methods: The Proton Collaborative Group REG001-09 trial (NCT01255748) prospectively collects data for PBT patients with a variety of cancer types. 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 2016 were analyzed. Results: A total of 43 liver cancer patients were included, most with hepatocellular carcinoma (48.8%) or cholangiocarcinoma (25.6%). The vast majority did not have surgery at any time (86%). Most were treatment naive prior to PBT; 2 previously had RT and 8 had prior chemotherapy (mostly cholangiocarcinoma patients). The median total prescribed PBT dose was 58.05 Gy(RBE) (range 21.7-67.5). The median number of prescribed fractions was 15 (range 12-37). PBT was delivered to only the liver in 90.7% of patients; inclusion of lymph nodes was rare. Uniform scanning was used in 26 (72.1%) and pencil beam scanning in 2 patients (4.7%); the delivery technique used for the remaining patients was unknown (23.2%). With median follow up of 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. No grade 3 or higher toxicity was reported although 17 patients (39.5%) had grade 2 toxicity predominantly fatigue, anorexia, nausea, or vomiting. 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 shows that predominantly hypofractionated PBT has a very favorable acute toxicity profile.