Abstract

BackgroundNeoadjuvant radio(chemo)therapy of non-metastasized, borderline resectable or unresectable locally advanced pancreatic cancer is complex and prone to cause side-effects, e.g., in gastrointestinal organs. Intensity-modulated proton therapy (IMPT) enables a high conformity to the targets while simultaneously sparing the normal tissue such that dose-escalation strategies come within reach. In this in silico feasibility study, we compared four IMPT planning strategies including robust multi-field optimization (rMFO) and a simultaneous integrated boost (SIB) for dose-escalation in pancreatic cancer patients.MethodsFor six pancreatic cancer patients referred for adjuvant or primary radiochemotherapy, four rMFO-IMPT-SIB treatment plans each, consisting of two or three (non-)coplanar beam arrangements, were optimized. Dose values for both targets, i.e., the elective clinical target volume [CTV, prescribed dose Dpres = 51Gy(RBE)] and the boost target [Dpres = 66Gy(RBE)], for the organs at risk as well as target conformity and homogeneity indexes, derived from the dose volume histograms, were statistically compared.ResultsAll treatment plans of each strategy fulfilled the prescribed doses to the targets (Dpres(GTV,CTV) = 100%, D95%,(GTV,CTV) ≥ 95%, D2%,(GTV,CTV) ≤ 107%). No significant differences for the conformity index were found (p > 0.05), however, treatment plans with a three non-coplanar beam strategy were most homogenous to both targets (p < 0.045). The median value of all dosimetric results of the large and small bowel as well as for the liver and the spinal cord met the dose constraints with all beam arrangements. Irrespective of the planning strategies, the dose constraint for the duodenum and stomach were not met. Using the three-beam arrangements, the dose to the left kidney could be significant decreased when compared to a two-beam strategy (p < 0.045).ConclusionBased on our findings we recommend a three-beam configuration with at least one non-coplanar beam for dose-escalated SIB with rMFO-IMPT in advanced pancreatic cancer patients achieving a homogeneous dose distribution in the target while simultaneously minimizing the dose to the organs at risk. Further treatment planning studies on aspects of breathing and organ motion need to be performed.

Highlights

  • Neoadjuvant radio(chemo)therapy of non-metastasized, borderline resectable or unresectable locally advanced pancreatic cancer is complex and prone to cause side-effects, e.g., in gastrointestinal organs

  • In the era of three-dimensional conformal radiotherapy (3D-CRT), radiotherapy doses for locally advanced pancreatic cancer (LAPC) patients were hampered by radiosensitive organs at risk (OARs) in proximity of the pancreas prohibiting an adequate dose to the target volume

  • The Mean dose (Dmean) and D2% dose constraints were met for the CTVeval, the D2% of the Clinical target volume (CTV)-gross tumor volume (GTV) always exceeded the preset dose value of 107% due to the dose gradient (D2% > 125.9% of 51Gy, Additional file 2)

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Summary

Introduction

Neoadjuvant radio(chemo)therapy of non-metastasized, borderline resectable or unresectable locally advanced pancreatic cancer is complex and prone to cause side-effects, e.g., in gastrointestinal organs. Intensitymodulated proton therapy (IMPT) enables a high conformity to the targets while simultaneously sparing the normal tissue such that dose-escalation strategies come within reach. In this in silico feasibility study, we compared four IMPT planning strategies including robust multi-field optimization (rMFO) and a simultaneous integrated boost (SIB) for dose-escalation in pancreatic cancer patients. In the most recent clinical study on dose-escalation to a total dose of 66Gy to the boost target using an IMRT-SIB technique with Tomotherapy, Zschaeck et al [6] have reported small numbers of patients suffering from acute radiation-induced grade 3 (nausea, abdominal pain and fatigue) or grade 4 (gastrointestinal bleeding) toxicities in a cohort of 28 patients. Results of the prospective phase III PREOPANC study, a randomized, controlled, multicentric superiority trial combining hypofractionated radiotherapy (15 × 2.4Gy) with gemcitabine (1000 mg/m2) on days 1, 8, 15, preceded and followed by a modified course of gemcitabine, are eagerly awaited [9]

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