Proton therapy delivery method affects dose-averaged linear energy transfer in patients

Abstract

The dosimetric advantages of proton therapy have led to its rapid proliferation in recent decades. This has been accompanied by a shift in technology from older units that deliver protons by passive scattering (PS) to newer units that increasingly use pencil-beam scanning (PBS). The biologic effectiveness of proton physical dose purportedly rises with increasing dose-weighted average linear energy transfer (LETD). The objective of this study was to determine the extent to which proton delivery methods affect LETD. We calculated LETD from simple, dosimetrically matched, and clinical treatment plans with TOPAS Monte-Carlo transport code. Simple treatment plans comprised single fields of PS and PBS protons in a water phantom. We performed simulations of matched and clinical treatment plans by using the treatment and anatomic data obtained from a cohort of children with craniopharyngioma who previously received PS or PBS proton therapy. We compared the distributions of LETD from PS and PBS delivery methods in clinically relevant ROIs. Wilcoxon signed-rank tests comparing single fields in water revealed that the LETD values from PBS were significantly greater than those from PS inside and outside the targeted volume (p < 0.01). Statistical tests comparing LETD-volume histograms from matched and clinical treatment plans showed that LETD was generally greater for PBS treatment plans than for PS treatment plans (p < 0.05). In conclusion, the proton delivery method affects LETD both inside and outside of the target volume. These findings suggest that PBS is more biologically effective than PS. Given the rapid expansion of PBS proton therapy, future studies are needed to confirm the applicability of treatment evaluation methods developed for PS proton therapy to those for modern PBS treatments to ensure their safety and effectiveness for the growing population of patients receiving proton therapy. This study uses data from two clinical trials: NCT01419067 and NCT02792582.

Treatment‐planning approaches to intensity modulated proton therapy and the impact on dose‐weighted linear energy transfer

“… 23 provides the best comparison for our observations when evaluating two versus three beams in treatment plans. Differences between their study and ours are their use of passively scattered proton therapy, a known contributor to differences in LETd, 31 a fixed‐range uncertainty of 3.5%/1 mm rather than scenario‐based robust optimization, and their use of a strategy shooting through the brainstem entirely to avoid track ends within the structure. Their three‐field, dose‐sparing technique (analogous to our three‐beam arrangement with two laterals and a single PA field) showed an increase in mean LETd of 1.0‐keV/μm anterior to the target more than the two‐field plans.…”

“…The increased volume will also occur at a distance further from the target volume, placing it closer to nearby critical structures. (2) The magnitude of high LETd is directly related to the steepness of the dose gradient in a plan, as a prior study demonstrating differences in LETd between pencil‐beam scanning proton therapy and passively scattered proton therapy suggested 31 . As the magnitude of the scenarios is lowered, increasingly conformal doses and steeper dose gradients may be achieved.…”

“…(2) The magnitude of high LETd is directly related to the steepness of the dose gradient in a plan, as a prior study demonstrating differences in LETd between pencil‐beam scanning proton therapy and passively scattered proton therapy suggested. 31 As the magnitude of the scenarios is lowered, increasingly conformal doses and steeper dose gradients may be achieved. In both phantom‐ and patient‐based studies, the scenarios used for robust optimization were increased to ±5%/3 mm and decreased to ±2%/2 mm to assess the trade‐off in the hypotheses.…”

Image-based data mining applies to data collected from children

“…2 ). We selected these levels to span the noise and uncertainty levels representative of out-of-field dose calculations from Monte Carlo simulations [40] to analytical algorithms [41] , [42] . The three test-volume side lengths were = 0.5 cm, 2.0 cm, and 6.0 cm ( Fig.…”