Abstract
PurposeTo retrospectively investigate empirical relative biological effectiveness (RBE) for mandible osteoradionecrosis (ORN) in head and neck (H&N) cancer patients treated with pencil-beam-scanning proton therapy (PBSPT).MethodsWe included 1,266 H&N cancer patients, of which, 931 patients were treated with volumetric-modulated arc therapy (VMAT) and 335 were treated with PBSPT. Among them, 26 VMAT and 9 PBSPT patients experienced mandible ORN (ORN group), while all others were included in the control group. To minimize the impact of the possible imbalance in clinical factors between VMAT and PBSPT patients in the dosimetric comparison between these two modalities and the resulting RBE quantification, we formed a 1:1 case-matched patient cohort (335 VMAT patients and 335 PBSPT patients including both the ORN and control groups) using the greedy nearest neighbor matching of propensity scores. Mandible dosimetric metrics were extracted from the case-matched patient cohort and statistically tested to evaluate the association with mandibular ORN to derive dose volume constraints (DVCs) for VMAT and PBSPT, respectively. We sought the equivalent constraint doses for VMAT so that the critical volumes of VMAT were equal to those of PBSPT at different physical doses. Empirical RBEs of PBSPT for ORN were obtained by calculating the ratio between the derived equivalent constraint doses and physical doses of PBSPT. Bootstrapping was further used to get the confidence intervals.ResultsClinical variables of age, gender, tumor stage, prescription dose, chemotherapy, hypertension or diabetes, dental extraction, smoking history, or current smoker were not statistically related to the incidence of ORN in the overall patient cohort. Smoking history was found to be significantly associated with the ORN incidence in PBSPT patients only. V40Gy[RBE], V50Gy[RBE], and V60Gy[RBE] were statistically different (p<0.05) between the ORN and control group for VMAT and PBSPT. Empirical RBEs of 1.58(95%CI: 1.34-1.64), 1.34(95%CI: 1.23-1.40), and 1.24(95%: 1.15-1.26) were obtained for proton dose at 40 Gy[RBE=1.1], 50 Gy[RBE=1.1] and 60 Gy[RBE=1.1], respectively.ConclusionsOur study suggested that RBEs were larger than 1.1 at moderate doses (between 40 and 60 Gy[RBE=1.1]) with high LET for mandible ORN. RBEs are underestimated in current clinical practice in PBSPT. The derived DVCs can be used for PBSPT plan evaluation and optimization to minimize the incidence rate of mandible ORN.
Highlights
Radiotherapy (RT) is a standard treatment option for head and neck (H&N) cancer
Our study suggested that Relative Biological Effectiveness (RBE) were larger than 1.1 at moderate doses with high linear energy transfer (LET) for mandible ORN
As far as we know, our work presents one of the largest and most comprehensive retrospective adverse event studies focusing on mandible ORN for H&N
Summary
Adverse events are frequent after H&N cancer RT as there are a large number of adjacent organs-at-risk (OARs), resulting in significant increase in need for supportive care and subsequent decreased quality of life [1–3]. Osteoradionecrosis (ORN) is one of the most severe adverse events for H&N cancer treatment. Volumetric-modulated arc therapy (VMAT) and pencilbeam-scanning proton therapy (PBSPT) are two advanced modalities for external beam radiation therapy. VMAT is an advanced form of intensity-modulated photon-based RT (IMRT) that can deliver a precisely sculpted dose distribution using a single or multiple arcs [4]. PBSPT is the most advanced generation of proton therapy. Because protons have a finite range (e.g., Bragg Peak) and no dose exists beyond Bragg Peaks, proton therapy provides more conformal target coverage while sparing adjacent OARs [5]
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