Stomach and duodenum dose-volume constraints for locally advanced pancreatic cancer patients treated in 15 fractions in combination with chemotherapy

PurposeTo assess dosimetry predictors of gastric and duodenal toxicities for locally advanced pancreatic cancer (LAPC) patients treated with chemo-radiotherapy in 15 fractions. MethodsData from 204 LAPC patients treated with induction+concurrent chemotherapy and radiotherapy (44.25 Gy in 15 fractions) were available. Forty-three patients received a simultaneous integrated boost of 48-58 Gy. Gastric/duodenal Common Terminology Criteria for Adverse Events v. 5 (CTCAEv5) Grade >= 2 toxicities were analyzed. Absolute/% duodenal and stomach dose-volume histograms (DVHs) of patients with/without toxicities were compared: the most predictive DVH points were identified, and their association with toxicity was tested in univariate and multivariate logistic regressions together with near-maximum dose (D-0.03) and selected clinical variables. ResultsToxicity occurred in 18 patients: 3 duodenal (ulcer and duodenitis) and 10 gastric (ulcer and stomatitis); 5/18 experienced both. At univariate analysis, V44cc (duodenum: p = 0.02, OR = 1.07; stomach: p = 0.01, OR = 1.12) and D-0.03 (p = 0.07, OR = 1.19; p = 0.008, OR = 1.12) were found to be the most predictive parameters. Stomach/duodenum V44Gy and stomach D-0.03 were confirmed at multivariate analysis and found to be sufficiently robust at internal, bootstrap-based validation; the results regarding duodenum D-0.03 were less robust. No clinical variables or %DVH was significantly associated with toxicity. The best duodenum cutoff values were V44Gy < 9.1 cc (and D-0.03 < 47.6 Gy); concerning the stomach, they were V44Gy < 2 cc and D-0.03 < 45 Gy. The identified predictors showed a high negative predictive value (>94%). ConclusionIn a large cohort treated with hypofractionated radiotherapy for LAPC, the risk of duodenal/gastric toxicities was associated with duodenum/stomach DVH. Constraining duodenum V44Gy < 9.1 cc, stomach V44Gy < 2 cc, and stomach D-0.03 < 45 Gy should keep the toxicity rate at approximately or below 5%. The association with duodenum D-0.03 was not sufficiently robust due to the limited number of events, although results suggest that a limit of 45-46 Gy should be safe.

Automated summary

The purpose of this study was to assess the dosimetry predictors of gastric and duodenal toxicities in locally advanced pancreatic cancer (LAPC) patients treated with chemo-radiotherapy in 15 fractions. The study found that restricting the dose volume histograms (DVHs) of the stomach and duodenum to specific values (V44Gy < 9.1 cc, D-0.03 < 47.6 Gy) can reduce the toxicity rate, although the correlation with duodenum D-0.03 was not sufficiently robust.