Low Dose-Averaged Linear Energy Transfer Contributes to Local Recurrence of Pancreatic Cancer Treated With Carbon Ion Radiation Therapy.

Abstract

To evaluate the effects of dose-averaged linear energy transfer (LET_d) profiles on local control (LC) of pancreatic cancer treated with carbon ion radiation therapy (CIRT). Data from patients with inoperable pancreatic cancer, treated with CIRT and concurrent chemotherapy between 2013 and 2021, were analyzed retrospectively. The prescribed dose was 55.2 Gy (relative biological effectiveness), administered in 12 fractions. The LET_d of CIRT plans were calculated using a previously reported in-house pipeline. The association between tumor LET_d profiles and local recurrence (LR) was analyzed. The study analyzed 106 patients. The 2-year cumulative LR rate was 20.2% (95% confidence interval [CI], 12.8%-28.9%). Analysis of LET_d parameters using a Fine-Gray regression model showed that the minimum LET_d (L_min) for the clinical target volume (CTV) had a significant effect on LR (P = .023). According to the cut-off value of 42.2 keV/µm, determined by time-dependent receiver operating characteristic analysis at 18 months, patients with low CTV L_min had a significantly greater cumulative LR rate than those with high CTV L_min (P = .020; 2-year cumulative LR rate, 32.4% [95% CI, 16.6%-49.3%] vs 12.7% [95% CI, 5.8%-22.5%]). Cause-specific proportional hazards models identified CTV L_min as a significant predictor of LR (hazard ratio, 0.83; [95% CI, 0.71-0.98]; P = .030). CTV L_min showed a strong, significant negative correlation with CTV (P < .0001, r = -0.52). This is the largest study investigating the association between tumor LET_d profiles and LC post-CIRT. The results suggest that low LET_d within the CTV is associated with poor LC in patients with pancreatic cancer treated with CIRT.