Purpose: To 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).
Methods: We 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 imbalance in clinical factors between VMAT and PBSPT, we formed a 1:1 case-matched patient cohort (335 patients each modality). Dose-volume-histogram indices and their associated critical volumes were extracted from the case-matched cohort for VMAT and PBSPT. 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.
Results: Clinical 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.
Conclusion: Our study suggested that RBEs were larger than 1.1 at moderate doses (40-60 Gy[RBE=1.1]) for mandible ORN. RBEs are underestimated in current clinical practice in PBSPT. The derived constraints can be used for plan evaluation and optimization to minimize the mandible ORN.
Funding Support, Disclosures, and Conflict of Interest: This research was supported by Arizona Biomedical Research Commission Investigator Award (ADHS16-162521), the Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, and the Kemper Marley Foundation.