Retrospective Clinical Outcomes of Proton Beam Therapy for Unresectable Locally Advanced Pancreatic Cancer

Abstract

<h3>Purpose/Objective(s)</h3> We retrospectively researched on the treatment outcomes and assessed the efficacy of proton beam therapy (PBT) for unresectable locally advanced pancreatic cancer (LAPC). <h3>Materials/Methods</h3> Fifty-four patients who were diagnosed unresectable LAPC and administered PBT between April 2009 to March 2020 at our institution. Patients who could not completed PBT, had new distant metastases during treatment, and did not have enough follow-up time were excluded in this study. Statistical analyses were performed by calculating overall survival rate (OS) and local control rate (LC). Median survival time (MST) was analyzed by several following factors; maximum standardized uptake values (SUV_max) of FDG-PET evaluation, performance status (PS), tumor site, total irradiation dose, and combination use of chemotherapy. Treatment toxicities were evaluated by Common Terminology Criteria for Adverse Events (CTCAE ver.5.0). OS, MST, and LC were analyzed using the Kaplan-Meier method and log-rank test. The cut-off values for SUV_max and tumor diameter were estimated using the receiver operating characteristic (ROC) curve and area under the curve (AUC) based on MST. <h3>Results</h3> This study included 28 men and 26 women whose median age was 67.5 years (range, 40 to 88 years). All patients were clinical stage III LAPC according to the Union for International Cancer Control (UICC) TNM staging system (8th edition). Median follow-up time was 17.4 months (range, 4.0 to 89.7 months). The median total dose was 67.5GyE (range, 50-77 GyE/25-35 fractions). The median tumor diameter was 36.5mm (range, 15 to 90 mm). The median SUV_max was 5.85 (range, 2.1 to 27.6). Chemotherapy regimens during PBT were following; 24 patients were gemcitabine alone, 5 were tegafur-gimeracil-oteracil (TS-1) alone, 17 were paclitaxel and TS-1. Eight patients did not receive chemotherapy because of their poor general condition. The One-year, 2-year, 3-year OS were 74.1%, 33.3%, 10.8%, respectively. The One-year, 2-year, 3-year LC were 89.0%, 84.6%, 84.6%, respectively. The MST was 17.1 months. Only one patient survived longer than 5 years. The cut-off values were estimated for SUV_max: 4.8 and tumor diameter: 37mm. Two-year OS based on PS-score group were following; PS 0/1/2: 26.1/ 13.4/8.0 months, respectively with significant differences (each group P<0.01). Treatment related acute toxicities were neutropenia (Grade1/2/3: 2/6/17 patients), leukopenia (Grade1/2/3: 1/4/11 patients), thrombocytopenia (Grade1/2: 1/4 patients), respectively. Late toxicity was gastrointestinal ulcer (Grade1/2: 2/2 patients). No Grade 3 or higher late adverse events were observed. <h3>Conclusion</h3> PBT combined standard chemotherapy achieved excellent local control. However, it did not control systematic tumor progression. PS score at first visit could be important prognostic factor.