Survival Outcomes and Failure Patterns in Patients with Inoperable Non-Metastatic Pancreatic Cancer Treated with Definitive Radiotherapy

SIMPLE SUMMARY: Historically, the only curative option for patients with pancreatic cancer was surgical resection. It is essential to develop nonoperative local treatment options that can provide a similar benefit. With the development of updated radiotherapy techniques that address organ motion, patients with inoperable diseases have been able to receive curative radiation doses. However, based on modern radiotherapy techniques, the survival outcomes and failure patterns of definitive radiotherapy to the primary tumor for inoperable pancreatic cancer remain inadequately reported in a large population. This study was performed to elucidate the effectiveness of contemporary treatment, identify key failure patterns, and determine the late toxicity in patients treated with definitive radiotherapy, according to our institutional data from the last five years. ABSTRACT: This study investigated the long-term results, failure patterns, and prognostic factors of patients with initially inoperable non-metastatic pancreatic cancer (PC) receiving definitive radiotherapy (RT). Between January 2016 and December 2020, a total of 168 non-metastatic PC patients, who were surgically unresectable or medically inoperable, were enrolled to receive definitive RT, with or without chemotherapy. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan–Meier method with a log-rank test. The cumulative incidence of locoregional and distant progression was estimated using the competing risks model. The Cox proportional-hazards model was used to determine the influence of prognostic variables on OS. With a median follow-up of 20.2 months, the median OS (mOS) and median PFS (mPFS) from diagnosis were 18.0 months [95% confidence interval (CI), 16.5–21.7 months] and 12.3 months (95% CI, 10.2–14.3 months), respectively. The mOS and mPFS from RT were 14.3 months (95% CI, 12.7–18.3 months) and 7.7 months (95% CI, 5.5–12.0 months), respectively. The corresponding 1-year, 2-year, and 3-year OS from diagnosis and RT were 72.1%, 36.6%, and 21.5% as well as 59.0%, 28.8%, and 19.0%, respectively. In a multivariate analysis, stage I–II (p = 0.032), pre-RT CA19–9 ≤ 130 U/mL (p = 0.011), receiving chemotherapy (p = 0.003), and a biologically effective dose (BED(10)) > 80 Gy (p = 0.014) showed a significant favorable influence on OS. Among the 59 available patients with definite progression sites, the recurrences of local, regional, and distant progression were 33.9% (20/59), 18.6% (11/59), and 59.3% (35/59), respectively. The 1-year and 2-year cumulative incidences of locoregional progression after RT were 19.5% (95% CI, 11.5–27.5%) and 32.8% (95% CI, 20.8–44.8%), respectively. Definitive RT was associated with long-term primary tumor control, resulting in superior survival in patients with inoperable non-metastatic PC. Further prospective randomized trials are warranted to validate our results in these patients.