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Lassen, Pernille; Huang, Shao Hui; Su, Jie; Waldron, John; Andersen, Maria; Primdahl, Hanne; Johansen, Jørgen; Kristensen, Claus Andrup; Andersen, Elo; Eriksen, Jesper Grau; Hansen, Christian Rønn; Alsner, Jan; Lilja‐Fisher, Jacob; Bratman, Scott V.; Ringash, Jolie; Kim, John; Hope, Andrew; Spreafico, Anna; Almeida, John; Xu, Wei; O'Sullivan, Brian; Overgaard, Jens
International journal of cancer, 15 April 2022, Volume: 150, Issue: 8Journal Article
We compare outcomes in two large‐scale contemporaneously treated HPV‐positive (HPV+) oropharynx cancer (OPC) cohorts treated with definitive radiotherapy/chemoradiotherapy (RT/CRT). p16‐confirmed HPV+ OPC treated between 2007 and 2015 at PMH and DAHANCA were identified. Locoregional failure (LRF), distant metastasis (DM), and overall survival (OS) were compared. Multivariable analysis (MVA) calculated adjusted‐hazard‐ratio (aHR) with 95% confidence interval (95% CI), adjusting for cohort, age, gender, performance status, smoking pack‐years, T‐category and N‐category and chemotherapy. Compared to PMH (n = 701), DAHANCA (n = 1174) contained lower TNM‐8T‐categories (T1‐T2: 77% vs 56%), N‐categories (N0‐N1: 77% vs 67%) and stages (stage I: 63% vs 44% (all P < .001). PMH used standard‐fractionation CRT in 69% (481) while 31% (220) received hypofractionated or moderately accelerated RT‐alone. All DAHANCA patients were treated with moderately accelerated RT; 96% (1129) received nimorazole (NIM) and 73% (856) concurrent weekly cisplatin. DAHANCA had shorter overall‐treatment‐time (P < .001), lower gross tumor (66‐68 vs 70 Gy) and elective neck (50 vs 56 Gy) doses. Median follow‐up was 4.8 years. DAHANCA had higher 5‐year LRF (13% vs 7%, aHR = 0.47 0.34‐0.67), comparable DM (7% vs 12%, aHR = 1.32 0.95‐1.82), but better OS (85% vs 80%, aHR = 1.30 1.01‐1.68). CRT patients had a lower risk of LRF (aHR 0.56 0.39‐0.82), DM (aHR 0.70 0.50‐1.00) and death (aHR 0.39 0.29‐0.52) vs RT‐alone. We observed exemplary outcomes for two large‐scale trans‐Atlantic HPV+ OPC cohorts treated in a similar manner. Concurrent chemotherapy was a strong, independent prognostic factor for all endpoints. Our findings underscore the need for a very careful approach to de‐intensification of treatment for this disease. What's new? HPV‐positive oropharyngeal cancer (OPC) represents a unique subgroup which has very different epidemiology, molecular biology, and response to radiotherapy/chemo‐radiotherapy (RT/CRT) than HPV‐negative squamous cell carcinoma of the head and neck (HNSCC). In this study, the authors compared two large cohorts of HPV‐positive OPC, and found significantly better outcomes in patients that routinely received concurrent chemoradiotherapy with cisplatin compared with radiotherapy alone. The authors conclude that these findings underscore the need for a cautious approach to efforts aimed at de‐intensifying treatment for this disease.
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