Comparison of the dose escalation potential for two hypofractionated radiotherapy regimens for locally advanced pancreatic cancer

Alex Dunlop,Uwe Oelfke,Katharine Aitken,Arabella Hunt,Robert A. Mitchell,Jenny Bertholet,Thomas Bird,Simeon Nill

doi:10.1016/j.ctro.2019.03.001

Abstract

ObjectivesTo determine the potential for dose escalation to a biological equivalent dose BED10≅100 Gy in hypofractionated radiotherapy for locally advanced pancreatic cancer (LAPC). Materials and methodsTen unselected LAPC patients were retrospectively included in the study. Two fractionation regimens were compared (5 and 15 fractions). The aim was to cover 95% of the Planning Target Volume (PTV) with a BED10 = 54 Gy (base dose = 33 Gy in 5 fractions, 42.5 Gy in 15 fractions) whilst respecting organs-at-risk (OAR) constraints. Once the highest PTV coverage was achieved dose escalation to a BED10≅100 Gy (escalated dose = 50 Gy in 5 fractions, 67.5 Gy in 15 fractions) was attempted, limiting the PTV maximum dose to 130% of the escalated dose. ResultsIn 5 fractions, 95% PTV coverage by both base and escalated doses could be achieved for one patient with PTV more than 1 cm away from OAR. 95% and 90% PTV coverage by the base dose was achieved in one and two patients respectively. In all other patients, coverage even by the base dose had to be compromised to comply with OAR constraints. In 15 fractions, 95% PTV coverage by the base dose was feasible for all patients except one. Dose escalation allowed improvement in target coverage by the base dose in both fractionation regimen whilst covering a sub-volume of the PTV with a BED10≅100 Gy. Both fractionation schemes were equivalent in terms of dose escalation potential. ConclusionLAPC patients with OAR close to the PTV are generally not eligible for hypofractionation with dose escalation. However, this planning study shows that it is possible to cover PTV sub-volumes with a BED10≅100 Gy in addition to delivering a BED10 = 54 Gy to 90–95% of the PTV as commonly prescribed to this population. Combined with an adaptive approach, this may maximize PTV coverage by a high BED on days with favourable anatomy.

Highlights

In 2017, pancreatic cancer was predicted to be the 3rd most common cause of cancer death in the United States (US) with a 5 year survival rate of only 8% [1]
The aim of this study is to investigate the potential for dose escalation using hypofractionated radiotherapy for a group of locally advanced pancreatic cancer (LAPC) patients with a varying degree of organs at risk (OAR) proximity and evaluate if there is a dosimetric benefit of moderate hypofractionation in 15 fractions compared to 5 fractions in achieving a BED10ffi100 Gy
In 5 fractions, 95% Planning Target Volume (PTV) coverage by the base dose was achieved for patient 1 (PTVOAR = 0%) with CIPADDICK = 0.85 (Fig. 1) and for patient 5 (PTVOAR = 0.84%) with CIPADDICK = 0.90 (Fig. 2, top)

Summary

Introduction

In 2017, pancreatic cancer was predicted to be the 3rd most common cause of cancer death in the United States (US) with a 5 year survival rate of only 8% [1]. The optimal treatment for locally advanced pancreatic cancer (LAPC) is controversial with conflicting results from phase 3 clinical trials on the survival benefit of standard fractionation chemoradiation (CRT) compared to chemotherapy alone [3,4,5,6]. Hypofractionation and stereotactic body radiotherapy (SBRT) have been increasingly investigated for the treatment of LAPC.

Objectives

Methods

Results