Institute for Onco-Physics, Albert Einstein College of Medicine, Bronx, New York; Department of Radiation Oncology, Montefiore Medical Center, Bronx, New York.
Northwestern Medicine Chicago Proton Center, Warrenville, Illinois.
Int J Radiat Oncol Biol Phys. 2019 Jul 1;104(3):540-552. doi: 10.1016/j.ijrobp.2018.11.039. Epub 2018 Nov 26.
Developing a quantitative decision-support strategy estimating the impact of normal tissue complications from definitive radiation therapy (RT) for head and neck cancer (HNC). We developed this strategy to identify patients with oropharyngeal HNC who may benefit most from receiving proton RT.
Recent normal tissue complication probability (NTCP) models for dysphagia, esophagitis, hypothyroidism, xerostomia, and oral mucositis were used to estimate NTCP for 33 patients with oropharyngeal HNC previously treated with photon intensity modulated radiation therapy (IMRT). Comparative proton therapy plans were generated using clinical protocols for HNC RT at a collaborating proton center. Organ-at-risk (OAR) doses from photon and proton RT plans were used to calculate NTCPs; Monte Carlo sampling 10,000 times was used for each patient to account for model parameter uncertainty. The latency and duration of each complication were modeled from calculated NTCP, accounting for age-, sex-, smoking- and p16-specific conditional survival probability. Complications were then assigned quality-adjustment factors based on severity to calculate quality-adjusted life years (QALYs) lost from each complication.
Based on our institutional-delivered photon IMRT doses and the achievable proton therapy doses, the average QALY reduction from all HNC RT complications for photon and proton therapy was 1.52 QALYs versus 1.15 QALYs, with proton therapy sparing 0.37 QALYs on average (composite 95% confidence interval, 0.27-2.53 QALYs). Long-term complications (dysphagia and xerostomia) contributed most to the QALY reduction. The QALYs spared with proton RT varied considerably among patients, ranging from 0.06 to 0.84 QALYs. Younger patients with p16-positive tumors who smoked ≤10 pack-years may benefit most from proton therapy, although this finding should be validated using larger patient series. A sensitivity analysis reducing photon IMRT doses to all OARs by 20% resulted in no overall estimated benefit with proton therapy with -0.02 QALYs spared, although some patients still had an estimated benefit in this scenario, ranging from -0.50 to 0.43 QALYs spared.
This quantitative decision-support strategy allowed us to identify patients with oropharyngeal cancer who might benefit the most from proton RT, although the estimated benefit of proton therapy ultimately depends on the OAR doses achievable with modern photon IMRT solutions. These results can help radiation oncologists and proton therapy centers optimize resource allocation and improve quality of life for patients with HNC.
开发一种定量决策支持策略，以估计头颈部癌症（HNC）根治性放疗（RT）引起的正常组织并发症的影响。我们开发了这种策略，以确定接受质子放疗可能获益最大的口咽 HNC 患者。
使用最近的吞咽困难、食管炎、甲状腺功能减退、口干和口腔粘膜炎的正常组织并发症概率（NTCP）模型，估算 33 例接受光子调强放疗（IMRT）治疗的口咽 HNC 患者的 NTCP。使用合作质子中心的 HNC RT 临床方案生成质子治疗计划。使用光子和质子 RT 计划的危及器官（OAR）剂量计算 NTCP；对每位患者进行 10,000 次蒙特卡罗抽样，以考虑模型参数不确定性。根据计算的 NTCP 对每种并发症的潜伏期和持续时间进行建模，同时考虑年龄、性别、吸烟和 p16 特异性条件生存概率。然后根据严重程度为并发症分配质量调整因素，以计算每种并发症导致的质量调整生命年（QALY）损失。
根据我们机构提供的光子 IMRT 剂量和可实现的质子治疗剂量，光子和质子治疗引起的所有 HNC RT 并发症导致的平均 QALY 减少量为 1.52 QALY 与 1.15 QALY，质子治疗平均节省 0.37 QALY（复合 95%置信区间，0.27-2.53 QALY）。长期并发症（吞咽困难和口干）对 QALY 减少的贡献最大。质子治疗节省的 QALY 在患者之间差异很大，范围为 0.06 至 0.84 QALY。p16 阳性肿瘤且吸烟量≤10 包年的年轻患者可能从质子治疗中获益最大，尽管这一发现需要使用更大的患者系列进行验证。一项敏感性分析将所有 OAR 的光子 IMRT 剂量降低 20%，结果显示质子治疗无总体获益，节省了-0.02 QALY，尽管在这种情况下，一些患者仍有估计的获益，范围为-0.50 至 0.43 QALY。
这种定量决策支持策略使我们能够识别出口咽癌患者，他们可能从质子放疗中获益最大，尽管质子治疗的估计获益最终取决于现代光子调强放疗解决方案所能达到的 OAR 剂量。这些结果可以帮助放射肿瘤学家和质子治疗中心优化资源分配，并提高 HNC 患者的生活质量。
