Dose–Volume and Radiobiological Model-Based Comparative Evaluation of the Gastrointestinal Toxicity Risk of Photon and Proton Irradiation Plans in Localized Pancreatic Cancer Without Distant Metastasis

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 NTCP IMRT−PSPBT and NTCP VMAT−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 (D max and V 50 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. Raturi et al. Proton vs. Photon-Modulated Radiotherapy in Pancreas 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.

Investigate the Dosimetric and Potential Clinical Benefits Utilizing Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost Technique for Locally Advanced Pancreatic Cancer: A Comparison Between Photon and Proton Beam Therapy

“…Additionally, Raturi showed that the normal tissue complication probability (NTCP) is not statistically different between photon and proton planning groups. However, these studies did not consider the relationship between the OAR sparing, and the target location since the patient-specific geometry plays a key factor in proton planning ( 15 ). Additionally, the feasibility of proton SBRT-SIB for pancreatic tumor has not been addressed yet.…”

HIF2 Regulates Intestinal Wnt5a Expression

“…Radiation therapy for abdominal and pelvic tumors is challenging because the small intestine is exquisitely radiosensitive, which limits the dose that can be delivered to tumors without major GI toxicity (2)(3)(4)(5)(6). Unfortunately, there are no FDA-approved therapies to prevent GI radiotoxicities.…”

“…This toxicity is especially limiting in the case of abdominal and pelvic cancers, which are surrounded by the exquisitely radiosensitive gastrointestinal (GI) tract, and they require high doses of radiation to achieve tumoricidal effects (2). Multiple studies have highlighted how common GI radiotoxicity is among cancer patients (3)(4)(5). Results from a Phase 3 clinical trial showed that over a third of patients treated with 45 Gy or 50.4 Gy four-field pelvic radiotherapy or pelvic intensitymodulated radiotherapy reported GI symptoms following radiation treatment (6).…”

A novel X‐Ray and γ‐Ray combination strategy for potential dose escalation in patients with locally advanced pancreatic cancer

“…20,21 The model parameters used for calculation of pancreatic adenocarcinoma cell death and the NTCP for failure of kidneys, gastric bleeding, striction or fistula of the small intestine and liver failure were given in Appendix 3. [22][23][24][25][26][27][28] Statistical significance was determined applying the paired sample t-test at the 2-tailed, 0.05 significance level.…”

“…The tumor control probability (TCP) and normal tissue complication probability (NTCP) values, proposed according to the Niemierko's effective uniform dose (EUD) model, were calculated using an open‐source MATLAB programme 20,21 . The model parameters used for calculation of pancreatic adenocarcinoma cell death and the NTCP for failure of kidneys, gastric bleeding, striction or fistula of the small intestine and liver failure were given in Appendix 22–28 . Statistical significance was determined applying the paired sample t‐test at the 2‐tailed, 0.05 significance level.…”