Abstract
Background: Radiobiological model-based studies of photon-modulated radiotherapy for pancreatic cancer have reported reduced gastrointestinal (GI) toxicity, although the risk is still high. The purpose of this study was to investigate the potential of 3D-passive scattering proton beam therapy (3D-PSPBT) in limiting GI organ at risk (OAR) toxicity in localized pancreatic cancer based on dosimetric data and the normal tissue complication probability (NTCP) model.Methods: The data of 24 pancreatic cancer patients were retrospectively analyzed, and these patients were planned with intensity-modulated radiotherapy (IMRT), volume-modulated arc therapy (VMAT), and 3D-PSPBT. The tumor was targeted without elective nodal coverage. All generated plans consisted of a 50.4-GyE (Gray equivalent) dose in 28 fractions with equivalent OAR constraints, and they were normalized to cover 50% of the planning treatment volume (PTV) with 100% of the prescription dose. Physical dose distributions were evaluated. GI-OAR toxicity risk for different endpoints was estimated by using published NTCP Lyman–Kutcher–Burman (LKB) models. Analysis of variance (ANOVA) was performed to compare the dosimetric data, and ΔNTCPIMRT−PSPBT and ΔNTCPVMAT−PSPBT were also computed.Results: Similar homogeneity and conformity for the clinical target volume (CTV) and PTV were exhibited by all three planning techniques (P > 0.05). 3D-PSPBT resulted in a significant dose reduction for GI-OARs in both the low-intermediate dose range (below 30 GyE) and the highest dose region (Dmax and V50 GyE) in comparison with IMRT and VMAT (P < 0.05). Based on the NTCP evaluation, the NTCP reduction for GI-OARs by 3D-PSPBT was minimal in comparison with IMRT and VMAT.Conclusion: 3D-PSPBT results in minimal NTCP reduction and has less potential to substantially reduce the toxicity risk of upper GI bleeding, ulceration, obstruction, and perforation endpoints compared to IMRT and VMAT. 3D-PSPBT may have the potential to reduce acute dose-limiting toxicity in the form of nausea, vomiting, and diarrhea by reducing the GI-OAR treated volume in the low-to-intermediate dose range. However, this result needs to be further evaluated in future clinical studies.
Highlights
Pancreatic cancer is a lethal malignancy with a high mortality rate
With the approval of the Institutional Research Ethics Committee, we analyzed the data of 24 consecutive patients with borderline resectable (BR) and locally advanced/unresectable pancreatic cancer (LAPC) without distant metastasis treated at a single institution between 2014 and 2018
In our study, based on the normal tissue complication probability (NTCP) calculation and dosimetric assessment, 3D-PSPBT does not result in a decrease in the radiation-related toxicity risk of upper GI bleeding, ulceration, obstruction, and perforation, but it does improve GI-organ at risk (OAR) sparing in the low-intermediate dose range while maintaining appropriate clinical target volume (CTV) and PTV coverage for localized pancreatic cancer without distant metastasis in comparison with intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT)
Summary
Pancreatic cancer is a lethal malignancy with a high mortality rate. In Japan, pancreatic cancer is the fourth primary cause of cancer-related deaths, and the age-standardized (world) mortality rate was 7.8 age-standardized rate (ASR) per 100,000 in 2018 [1, 2]. Localized PDAC has been classified into resectable, borderline resectable (BR), and locally advanced/unresectable pancreatic cancer (LAPC) [4]. Surgical resection can offer a possibility of better survival;
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