Clinical Outcomes of Proton Beam Therapy for Unresectable Locally Advanced Pancreatic Cancer: A Single-Center Retrospective Study

Abstract

PurposeWe retrospectively researched the treatment outcome of proton beam therapy (PBT) and assessed its efficacy for inoperable locally advanced pancreatic cancer (LAPC) at our institution. Materials and MethodsFifty-four patients (28 males and 26 females, median age 67 years of ranges from 40 to 88 years were diagnosed with unresectable stage III LAPC and administered PBT from April 2009 to March 2020. Either patients who could not complete PBT, or had new distant metastases during the treatment, or did not have enough follow-up time were excluded from this study. All patients were clinically staged based on the International Union of Cancer TNM staging system (UICC 8th edition) using CT, MRI, and PET, and were diagnosed as stage III (histologic type: eighteen adenocarcinoma patients, thirty-six clinically diagnosed patients). PBT was performed using the passive method, with a median total dose of 67.5 GyE (range: 50-77 GyE/25-35 fractions). Chemotherapy was used in combination during PBT in forty-six patients (85.2%). Overall survival (OS), local progression-free survival (LPFS), progression-free survival (PFS), and median overall survival time (MST) were analyzed by Kaplan-Meier and log-rank tests. Univariate and multivariate analyses were performed for the following factors: maximum standardized uptake value (SUVmax), ECOG-performance status (PS), tumor site, total irradiation dose, concurrent chemotherapy, and primary tumor site. Cutoff values for SUVmax and tumor diameter were estimated using receiver operating characteristic (ROC) curves and area under the curve (AUC) based on OS. Multivariate analysis was evaluated using the Cox proportional hazards models. Adverse events were evaluated using CTCAE ver. 5.0. ResultsThe median observation period was 17.4 months of ranges from 4.0 to 89.7 months. The median tumor diameter was 36.5 mm of ranges from 15 to 90 mm, the median SUVmax was 5.85 (range: 2.1-27.6), and their cutoff values were estimated to 37 mm and 4.8 mm, respectively. 1-, 2-year OS were 77.8%, 35.2% with MST 18.2 months, respectively and only one patient survived more than 5 years. 12 patients (22.2%) developed local recurrence, and 1-, 2-year LPFS rate were 89.7% and 74.5%, respectively; PFS at 1-year was 58.8%. PS score, Tumor site and irradiation dose were the prognostic factor related to OS that showed a significant difference. On the other hand, there was a significant difference in factors involved in LPFS, 96.7%/77.9% in the first year and 86.6%/54.4% in the second year in the groups with tumor dose ≥67.5 GyE and <67.5 GyE, respectively (p = 0.015). Treatment-related acute toxicities were neutropenia (Grade1/2/3:3.7%/11.1%/31.5%), leukopenia (Grade 1/2/3:1.8%/7.4%/20.4%), and thrombocytopenia (Grade 1/2:1.8%/7.4%), while the late effects including peptic ulcer were captured only grade2+. The late adverse events of Grade 3 or higher were not observed. ConclusionsPBT achieving 67.5 Gy combined with standard chemotherapy showed the excellent local control for unresectable LAPC. Total irradiation dose, Tumor site and PS score at an initial diagnosis could be important prognostic factors. In this study, the dose-effect relationship was found so an increase in dose should be considered to improve prognosis.