Identifying Oropharyngeal Head and Neck Cancer Patients Who Will Benefit Most From Proton Therapy: Implementation of a Quantitative Clinical Decision-Support Tool


      To use a quantitative decision-support tool we developed for estimating the impact of normal tissue complications (NTCs) after definitive head and neck cancer (HNC) radiation therapy (RT), to identify which oropharyngeal HNC patients would benefit most from receiving proton RT compared to photon IMRT.


      We conducted a systematic literature review of NTCs after HNC RT providing up-to-date dose-response models for dysphagia, esophagitis, hypothyroidism, xerostomia, and oral mucositis. The models were used to estimate NTC probability (NTCP) in a retrospective cohort of 24 oropharyngeal HNC patients previously treated with photon IMRT, with comprehensive nodal RT (CNRT) or unilateral neck RT (UNRT). Comparative proton therapy plans were generated with equal target coverage as the photon IMRT plans using clinical protocols for HNC at a collaborating proton center, with robustness criteria added to the proton therapy optimization. Organ at risk doses from photon and proton RT plans were used to calculate NTCPs, Monte Carlo sampling 10,000 times for each patient to account for uncertainty in model parameters. The latency and duration of each NTC were then modeled based calculated NTCP, accounting for patients’ age-, sex-, and p16-status-specific conditional survival probability. Each NTC was then assigned a quality-adjustment factor based on severity, taken from the online Cost-Effectiveness Analysis Registry and used to calculate the reduction in quality-adjusted life years (QALYs) attributable to each NTC.


      With a median age of 62 y (range: 45-78 y) the average QALY reduction from all HNC RT complications for photon and proton RT was 2.18 y vs. 1.69 y. Long-term NTCs dysphagia and xerostomia contributed 54% and 29% of the QALY reduction, respectively. QALYs spared with proton RT varied considerably between individual patients, from 0.06 to 1.39 QALYs. Eight of 24 patients had an estimated >0.5 QALYs spared with proton RT, and 4 patients >0.75 QALYs spared. Age and p16-status were significantly associated with QALYs spared (p<0.01). For p16-positive patients <62 y old the QALY reduction was 3.57 y vs. 2.78 y for photon and proton RT, with 0.79 QALYs spared using protons.
      Abstract 113; Table
      Average NTCP (%)DysphagiaEsophagitisHypothyroidismXerostomiaOral mucositisAverage QALY reduction (y)
      CNRT (n=15)
      UNRT (n=9)


      Implementing a quantitative decision-support tool we identified p16-positive patients younger than 62 y as those with the greatest estimated benefit from receiving proton RT, given their long life expectancy. These results can help radiation oncologists and proton centers optimize resource allocation and improve patients’ quality of life.


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