Exploring the advantages of intensity-modulated proton therapy: experimental validation of biological effects using two different beam intensity-modulation patterns

Duo Ma,Changran Geng,Joycelyn Yiu,Mei Chen,Narayan Sahoo,Mary Sobieski,Matthew Kerr,Xiaodong Zhang,Lawrence Bronk,Wenhua Cao,David R Grosshans,Xiaochun Wang,Radhe Mohan,Fada Guan,Clifford Stephan

doi:10.1038/s41598-020-60246-5

Abstract

In current treatment plans of intensity-modulated proton therapy, high-energy beams are usually assigned larger weights than low-energy beams. Using this form of beam delivery strategy cannot effectively use the biological advantages of low-energy and high-linear energy transfer (LET) protons present within the Bragg peak. However, the planning optimizer can be adjusted to alter the intensity of each beamlet, thus maintaining an identical target dose while increasing the weights of low-energy beams to elevate the LET therein. The objective of this study was to experimentally validate the enhanced biological effects using a novel beam delivery strategy with elevated LET. We used Monte Carlo and optimization algorithms to generate two different intensity-modulation patterns, namely to form a downslope and a flat dose field in the target. We spatially mapped the biological effects using high-content automated assays by employing an upgraded biophysical system with improved accuracy and precision of collected data. In vitro results in cancer cells show that using two opposed downslope fields results in a more biologically effective dose, which may have the clinical potential to increase the therapeutic index of proton therapy.

Highlights

Worldwide the number of proton therapy centers has increased dramatically in recent years[1]
The planning optimizer can be adjusted to alter the intensity of each beamlet, maintaining the same target dose delivered from multiple fields while increasing the weights of low-energy beams enhancing the LETd within the target, so that the biological advantages of protons may be exploited
In many charged particle radiobiology experiments, plastic phantoms are used as the range shifters to obtain biological effect data at different spatial locations along the beam path

Summary

Introduction

Worldwide the number of proton therapy centers has increased dramatically in recent years[1]. The report suggests that, for the time being, the use of a constant RBE should continue in clinical practice because the underlying biophysical bases of proton therapy are not well understood This knowledge gap motivated us to investigate the biological characteristics of protons, especially with scanned proton beams, because such beams are used in IMPT. In its current form, this beam delivery strategy cannot effectively make use of the biological advantages of low-energy (high-LET) protons present within the Bragg peak region. The planning optimizer can be adjusted to alter the intensity of each beamlet, maintaining the same target dose delivered from multiple fields while increasing the weights of low-energy beams enhancing the LETd within the target, so that the biological advantages of protons may be exploited. The simplest and most straightforward method is using two opposed fields for dose patching to deliver the uniform target dose

Objectives

Methods

Results

Conclusion