Comparing biological effectiveness guided plan optimization strategies for cranial proton therapy: potential and challenges

Abstract

Background To introduce and compare multiple biological effectiveness guided (BG) proton plan optimization strategies minimizing variable relative biological effectiveness (RBE) induced dose burden in organs at risk (OAR) while maintaining plan quality with a constant RBE. Methods Dose-optimized (DOSEopt) proton pencil beam scanning reference treatment plans were generated for ten cranial patients with prescription doses ≥ 54 Gy(RBE) and ≥ 1 OAR close to the clinical target volume (CTV). For each patient, four additional BG plans were created. BG objectives minimized either proton track-ends, dose-averaged linear energy transfer (LETd), energy depositions from high-LET protons or variable RBE-weighted dose (DRBE) in adjacent serially structured OARs. Plan quality (RBE = 1.1) was assessed by CTV dose coverage and robustness (2 mm setup, 3.5% density), dose homogeneity and conformity in the planning target volumes and adherence to OAR tolerance doses. LETd, DRBE (Wedenberg model, α/βCTV = 10 Gy, α/βOAR = 2 Gy) and resulting normal tissue complication probabilities (NTCPs) for blindness and brainstem necrosis were derived. Differences between DOSEopt and BG optimized plans were assessed and statistically tested (Wilcoxon signed rank, α = 0.05). Results All plans were clinically acceptable. DOSEopt and BG optimized plans were comparable in target volume coverage, homogeneity and conformity. For recalculated DRBE in all patients, all BG plans significantly reduced near-maximum DRBE to critical OARs with differences up to 8.2 Gy(RBE) (p < 0.05). Direct DRBE optimization primarily reduced absorbed dose in OARs (average ΔDmean = 2.0 Gy; average ΔLETd,mean = 0.1 keV/µm), while the other strategies reduced LETd (average ΔDmean < 0.3 Gy; average ΔLETd,mean = 0.5 keV/µm). LET-optimizing strategies were more robust against range and setup uncertaintes for high-dose CTVs than DRBE optimization. All BG strategies reduced NTCP for brainstem necrosis and blindness on average by 47% with average and maximum reductions of 5.4 and 18.4 percentage points, respectively. Conclusions All BG strategies reduced variable RBE-induced NTCPs to OARs. Reducing LETd in high-dose voxels may be favourable due to its adherence to current dose reporting and maintenance of clinical plan quality and the availability of reported LETd and dose levels from clinical toxicity reports after cranial proton therapy. These optimization strategies beyond dose may be a first step towards safely translating variable RBE optimization in the clinics.

Investigation on the physical dose filtered by linear energy transfer for treatment plan evaluation in carbon ion therapy

“…The high‐LET‐dose is a quantity that can be utilized for evaluation and biological treatment plan optimization (of tumors and OARs) in particle therapy. The main hindrance in applying this quantity is the lack of reported voxel based LET‐spectra for clinical outcomes which makes the selection of a reasonable LET threshold difficult 31 . The novel evaluation approach introduced in this study in which $$\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$$ and $$\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$$ distributions were evaluated in cTPs with small and large tumors is a first step to overcome this limitation and to facilitate the application of the $$\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$$ quantity in clinical studies.…”

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“…A recent study 27 compared four different strategies, including the optimization of dirty dose, that all achieved a vRBE‐weighted dose reduction in critical OAR while maintaining plan quality regarding the 1.1‐weighted dose. In that study, the choice of only a single dose level and LET threshold value was considered as the limiting factor to fully exploit the potential of DDopt.…”

Novel unconventional radiotherapy techniques: Current status and future perspectives – Report from the 2nd international radiation oncology online seminar

“…To make optimization criteria solely based on LET is questionable, as the combination of intermediate LET values and high dose results in increased RBE. Yet, LET-painting has the potential to reduce the normal tissue complication probability (NTCP) for brainstem necrosis and optical damage [93].…”

“…MRT and MBRT originated at large 3rd generation synchrotrons [93], facilities offering ideal beam features for these techniques: negligible divergence, kilovoltage X-rays beams and enormous dose rates. MRT and MBRT have shown a remarkable normal tissue sparing at very high peak doses (up to 100 Gy in MBRT and 600 Gy in MRT) [95,[102][103][104][105][106][107][108], and tumor control in aggressive tumor models [109][110][111][112], such as gliomas.…”

“…The advancement of MRT has been slowed down due to the need for very high dose rates and kilovoltage X-rays beams to avoid blurring of the characteristic patterns of peak-and-valleys [93]. This has confined the exploration of the technique to a few large synchrotron facilities.…”