Disease outcome and associated factors after definitive platinum based chemoradiotherapy for advanced stage HPV-negative head and neck cancer

Background: Definitive concomitant cisplatin-based chemoradiotherapy (CRT) is the current gold stan-dard for most patients with advanced stage head and neck squamous cell carcinoma (HNSCC) of the phar-ynx and larynx. Since previous meta-analysis on CRT outcomes in HNSCC have been reported, advances have been made in radiotherapy techniques and clinical management, while HPV-status has been iden-tified as a strong confounding prognostic factor in oropharyngeal cancer. Here, we present real-world outcome data from a large multicenter cohort of HPV-negative advanced stage HNSCC treated with CRT using contemporary IMRT-based techniques. Method: Retrospective data were collected from a multicenter cohort of 513 patients treated with defini-tive concurrent platinum-based CRT with curative intent between January 2009 and August 2017. Only patients with HPV-negative advanced stage (III-IV) HNSCC were included. A prognostic model for out-come was developed based on clinical parameters and compared to TNM.Results: Nearly half of the 513 patients (49%) had an oropharyngeal tumor, often locally advanced (73.3% T3-T4b) and with involvement of the regional lymph nodes (84%). Most patients (84%) received cisplatin as single agent. In total 66% received the planned number of cycles and 75% reached a cumula-tive cisplatin dose of & GE;200 mg/m2. Locoregional control was achieved in 324 (63%) patients during follow-up, and no association with tumor sites was observed (p = 0.48). Overall survival at 5 year follow-up was 47%, with a better survival for laryngeal cancer (p = 0.02) compared to other sites. A model with clinical variables (gender, high pre-treatment weight loss, N2c/N3-stage and < 200 mg/m2 dose of cisplatin) provided a noticeably stronger association with overall survival than TNM-staging (C-index 0.68 vs 0.55). Simultaneous Integrated Boosting (SIB) significantly outperformed Sequential Boosting (SEQ) to reduce the development of distant metastasis (SEQ vs SIB: OR 1.91 (1.11-3.26; p = 0.02). Conclusion: Despite advances in clinical management, more than a third of patients with HPV-negative HNSCC do not complete CRT treatment protocols due to cisplatin toxicity. A model that consists of clinical variables and treatment parameters including cisplatin dose provided the strongest association with overall survival. Since cisplatin toxicity is a major obstacle in completing definitive CRT, the development of alternative and less toxic radiosensitizers is therefore warranted to improve treatment results. The association of RT-boost technique with distant metastasis is an important finding and requires further study.(c) 2022 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 175 (2022) 112-121 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

This study collected real-world outcome data from 513 patients with HPV-negative advanced stage HNSCC treated with CRT and found that clinical variables and treatment parameters had a stronger association with overall survival. The association of RT-boost technique with distant metastasis is an important finding that requires further study.