Data_Sheet_3_Patient Selection in Human Papillomavirus Related Oropharyngeal Cancer: The Added Value of Prognostic Models in the New TNM 8th Edition Era.PDF

Background: With the growing interest in treatment de-intensification trials for human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPC), prognostic models have become essential for patient selection. The aim of this paper is to validate and compare the prognostic ability of the TNM 8th edition and previous published risk group classifications of Ang et al. and Rietbergen et al. and to derive a patient selection classification for de-intensification trials.
Materials: Patients with HPV+ OPC treated with curative (chemo)radiotherapy between 2004 and 2017 were classified according to the TNM 8th edition, the model of Ang et al. and of Rietbergen et al. HPV status was determined by p16 immunohistochemistry staining. Overall survival was estimated using the Kaplan-Meier method and groups were compared using the log-rank test. Harrell's C-index was used as measure of discriminative performance.
Results: A total of 333 OPC were identified of whom 100 were HPV+. The median follow-up was 63.7 months. The 5-year overall survival (5Y-OS) of stage I, II and III were 91.6, 55.2, and 38.0%. There was a significant difference between stage I vs. II and III. The Harrell's C-index for TNM 8th edition stage was 0.67. Including only HPV+ OPC, the Harrell's C-index for the model of Ang and Rietbergen were both 0.62. We combined the main prognostic factors defining the low risk groups in the three models, stage I, low comorbidity and ≤ 10 pack years, into one new low risk group to identify patients who may benefit from de-intensification trials. Intermediate risk was defined as stage I with high comorbidity or >10 pack years, high risk as stage II-III. The 5Y-OS were 100, 85.7, and 51.3%. The Harrell's C-index for the new classification model was 0.67.
Conclusion: Although TNM 8th edition provides better OS stratification than the 7th edition, it is not performant enough for patient selection, neither are the models from Ang et al. and Rietbergen et al. Therefore, we propose a patient selection classification for de-intensification trials based on the new TNM classification 8th edition, comorbidity and smoking pack years. In addition, this study emphasizes the importance of patient selection and personalized treatment for HPV+OPC.

研究背景：随着人乳头瘤病毒阳性（human papillomavirus positive, HPV+）口咽鳞状细胞癌（oropharyngeal squamous cell carcinoma, OPC）治疗降强度试验的研究兴趣日益增长，预后模型已成为患者筛选的核心工具。本研究旨在验证并比较TNM第8版以及Ang等人、Rietbergen等人已发表的风险分组方案的预后能力，并推导适用于降强度试验的患者筛选分类方案。

研究材料与方法：2004年至2017年间接受根治性放化疗的HPV+ OPC患者，依据TNM第8版、Ang等人模型及Rietbergen等人模型进行分组。HPV状态通过p16免疫组化染色确定。总生存期采用Kaplan-Meier法估算，组间比较采用log-rank检验。以Harrell's C指数作为区分性能的评估指标。

研究结果：共纳入333例OPC患者，其中100例为HPV+。中位随访时间为63.7个月。I、II、III期患者的5年总生存期（5-year overall survival, 5Y-OS）分别为91.6%、55.2%和38.0%。I期与II期、I期与III期患者的总生存期存在显著差异。TNM第8版分期的Harrell's C指数为0.67。仅纳入HPV+ OPC患者时，Ang模型与Rietbergen模型的Harrell's C指数均为0.62。本研究将三个模型中定义低风险组的核心预后因素——I期、低合并症状态及吸烟≤10包年，整合为全新的低风险组，用于筛选可能从降强度试验中获益的患者。中风险组定义为I期合并高合并症状态或吸烟>10包年，高风险组定义为II~III期。低、中、高风险组的5Y-OS分别为100%、85.7%和51.3%。全新分组模型的Harrell's C指数为0.67。

研究结论：尽管TNM第8版相较于第7版能实现更优的总生存期分层，但其用于患者筛选的性能仍不足，Ang等人与Rietbergen等人的模型亦如此。因此，本研究提出一种基于TNM第8版、合并症状态及吸烟包年数的患者筛选分组方案，适用于降强度试验。此外，本研究强调了HPV+ OPC患者筛选与个体化治疗的重要性。