Head and Neck Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Integrated Biology Platform, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
JCO Precis Oncol. 2021 Oct 27;5. doi: 10.1200/PO.21.00094. eCollection 2021.
Under common therapeutic regimens, the prognosis of human papillomavirus (HPV)-positive squamous oropharyngeal carcinomas (OPCs) is more favorable than HPV-negative OPCs. However, the prognosis of some tumors is dismal, and validated prognostic factors are missing in clinical practice. The present work aimed to validate the prognostic significance of our published three-cluster model and to compare its prognostic value with those of the 8 edition of the tumor-node-metastasis staging system (TNM8) and published signatures and clustering models.
Patients with HPV DNA-positive OPCs with locoregionally advanced nonmetastatic disease treated with curative intent (BD2Decide observational study, NCT02832102) were considered as validation cohort. Patients were treated in seven European centers, with expertise in the multidisciplinary management of patients with head and neck cancer. The median follow-up was 46.2 months (95% CI, 41.2 to 50), and data collection was concluded in September 2019. The primary end point of this study was overall survival (OS). Three-clustering models and seven prognostic signatures were compared with our three-cluster model.
The study population consisted of 235 patients. The three-cluster model confirmed its prognostic value. Two-year OS in each cluster was 100% in the low-risk cluster, 96.6% in the intermediate-risk cluster, and 86.3% in the high-risk cluster ( = .00074). For the high-risk cluster, we observed an area under the curve = 0.832 for 2-year OS, significantly outperforming TNM 8th edition (area under the curve = 0.596), and functional and biological differences were identified for each cluster.
The rigorous clinical selection of the cases included in this study confirmed the robustness of our three-cluster model in HPV-positive OPCs. The prognostic value was found to be independent and superior compared with TNM8. The next step includes the translation of the three-cluster model in clinical practice. This could open the way to future exploration of already available therapies in HPV-positive OPCs tailoring de-escalation or intensification according to the three-cluster model.
验证我们发表的三聚类模型的预后意义，并与第 8 版肿瘤-淋巴结-转移（TNM8）分期系统和已发表的签名和聚类模型的预后价值进行比较。
考虑了 235 名接受根治性治疗的 locoregionally 局部晚期非转移性 HPV DNA 阳性口咽鳞癌（BD2Decide 观察性研究，NCT02832102）患者作为验证队列。患者在 7 个欧洲中心接受治疗，这些中心在头颈部癌症患者的多学科管理方面具有专业知识。中位随访时间为 46.2 个月（95%CI，41.2 至 50），数据收集于 2019 年 9 月结束。本研究的主要终点是总生存（OS）。将三聚类模型和七个预后签名与我们的三聚类模型进行比较。
研究人群包括 235 名患者。三聚类模型证实了其预后价值。每个聚类的 2 年 OS 低危聚类为 100%，中危聚类为 96.6%，高危聚类为 86.3%（=0.00074）。对于高危聚类，我们观察到 2 年 OS 的曲线下面积为 0.832，明显优于第 8 版 TNM（曲线下面积为 0.596），并确定了每个聚类的功能和生物学差异。
本研究中纳入病例的严格临床选择证实了我们在 HPV 阳性口咽鳞癌中三聚类模型的稳健性。发现其预后价值独立且优于 TNM8。下一步包括将三聚类模型转化为临床实践。这可能为未来探索 HPV 阳性口咽鳞癌中已经可用的治疗方法开辟道路，根据三聚类模型对其进行降阶梯或强化治疗。
