A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation

Alexander Rühle, Maria Weymann, Max Behrens, Sebastian Marschner, Marlen Haderlein, Alexander Fabian, Carolin Senger, Daniel R. Dickstein, Johannes Kraft, Jens von der Grün, Eric Chen, Todd Aquino-Michaels, Justus Domschikowski, Amanda Bickel, Alev Altay-Langguth, Goda Kalinauskaite, Victor Lewitzki, Marcelo Bonomi, Dukagjin M. Blakaj, Sachin R. JhawarSujith Baliga, Rahul Barve, Konstantinos Ferentinos, Constantinos Zamboglou, Sören Schnellhardt, Erik Haehl, Simon K.B. Spohn, Thomas Kuhnt, Daniela Zöller, Matthias Guckenberger, Volker Budach, Claus Belka, Richard Bakst, Arnulf Mayer, Heinz Schmidberger, Anca Ligia Grosu, Panagiotis Balermpas, Carmen Stromberger, Nils H. Nicolay

Research output: Contribution to journalArticlepeer-review


Purpose: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiation therapy is considered the standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older patients with HNSCC. Methods and Materials: The SENIOR study is an international multicenter cohort study including older patients (≥65 years) with HNSCC treated with definitive radiation therapy at 13 academic centers in the United States and Europe. Patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) via Kaplan-Meier analyses. Fine‐Gray competing risk regressions were performed regarding the incidence of locoregional failures and distant metastases. Results: Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n = 310; 44%), followed by cisplatin plus 5-fluorouracil (n = 137; 20%), carboplatin (n = 73; 10%), and mitomycin C plus 5-fluorouracil (n = 64; 9%). Carboplatin-based regimens were associated with diminished PFS (hazard ratio [HR], 1.39 [1.03-1.89]; P < .05) and a higher incidence of locoregional failures (subdistribution HR, 1.54 [1.00-2.38]; P = .05) compared with single-agent cisplatin, whereas OS (HR, 1.15 [0.80-1.65]; P = .46) was comparable. There were no oncological differences between single-agent and multiagent cisplatin regimens (all P > .05). The median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR, 0.71 [0.53-0.95]; P = .02), increased PFS (HR, 0.66 [0.51-0.87]; P = .003), and lower incidence of locoregional failures (subdistribution HR, 0.50 [0.31-0.80]; P = .004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR, 0.996 [0.993-0.999]; P = .009). Conclusions: Single-agent cisplatin can be considered in the standard chemotherapy regimen for older patients with HNSCC who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant in older patients with HNSCC.

Original languageEnglish
Pages (from-to)1282-1293
Number of pages12
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number5
StatePublished - 1 Apr 2024


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