Immune-based classification of HPV-associated oropharyngeal cancer with implications for biomarker-driven treatment de-intensification.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zeng Peter Y F, Cecchini Matthew J, Barrett John W, Shammas-Toma Matthew, De Cecco Loris, Serafini Mara S, Cavalieri Stefano, Licitra Lisa, Hoebers Frank, Brakenhoff Ruud H, Leemans C René, Scheckenbach Kathrin, Poli Tito, Wang Xiaowei, Liu Xinyi, Laxague Francisco, Prisman Eitan, Poh Catherine, Bose Pinaki, Dort Joseph C, Shaikh Mushfiq H, Ryan Sarah E B, Dawson Alice, Khan Mohammed I, Howlett Christopher J, Stecho William, Plantinga Paul, Daniela da Silva Sabrina, Hier Michael, Khan Halema, MacNeil Danielle, Mendez Adrian, Yoo John, Fung Kevin, Lang Pencilla, Winquist Eric, Palma David A, Ziai Hedyeh, Amelio Antonio L, Li Shawn S-C, Boutros Paul C, Mymryk Joe S, Nichols Anthony C
Аннотация
METHODS: We created an immune score (UWO3) associated with survival outcomes in six independent cohorts comprising 906 patients, including blinded retrospective and prospective external validations. Two aggressive radiation de-escalation cohorts were used to assess the ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 immune class and outcomes.
FINDINGS: A three-gene immune score classified patients into three immune classes (immune rich, mixed, or immune desert) and was strongly associated with disease-free survival in six datasets, including large retrospective and prospective datasets. Pooled analysis demonstrated that the immune rich group had superior disease-free survival compared to the immune desert (HR = 9.0, 95% CI: 3.2-25.5, P = 3.6 × 10-5) and mixed (HR = 6.4, 95% CI: 2.2-18.7, P = 0.006) groups after adjusting for age, sex, smoking status, and AJCC8 clinical stage. Finally, UWO3 was able to identify patients from two small treatment de-escalation cohorts who remain disease-free after aggressive de-escalation to 30 Gy radiation.
INTERPRETATION: With additional prospective validation, the UWO3 score could enable biomarker-driven clinical decision-making for patients with HPV+ OPSCC based on robust outcome prediction across six independent cohorts. Prospective de-escalation and intensification clinical trials are currently being planned.
FUNDING: CIHR, European Union, and the NIH.