Author(s)
Marco A Mascarella MD MSc1
Sarah Khalife MD1
Agnihotram V Ramanakumar PhD2
Keith Richardson MD FRCSC1
Robert Siegel MD3
Arjun Joshi MD3
Nathaniel Bouganim MD FRCPC1
Reza Taheri MD PhD3
Andrew Fuson MD3
Nader Sadeghi MD FRCSC1
Affiliation(s)
1McGill University; 2Research Institute of McGill University Health Center; 3George Washington University
Abstract:
<p><strong>Background</strong></p> <p>The treatment of HPV positive oropharyngeal squamous cell carcinoma (OPSCC) is evolving. Various de-escalation trials are investigating new strategies to reduce treatment toxicity while maintaining oncologic cure. Neoadjuvant chemotherapy followed by surgery (NAC+S) is under investigation for treatment naïve, p16 positive OPSCC by our group. This paradigm is based on systemic escalation coupled with surgery-based de-escalation to improve both survival and functional outcome. The objective of this study was to compare survival and feeding tube dependency in patients undergoing NAC+S compared to concomitant chemoradiation (CCRT) for locoregionally advanced p16 positive OPSCC.</p> <p><strong>Methods</strong></p> <p>A prospective cohort of patients with locoregionally advanced, non-metastatic, p16 positive, and treatment naive OPSCC enrolled in a clinical trial of neoadjuvant chemotherapy followed by surgery (transoral + neck dissection) was compared to a cohort of similar patients undergoing concomitant chemoradiation (cisplatin and intensity modulated radiotherapy). NAC+S patients underwent three cycles of induction chemotherapy (cisplatin/docetaxel) which was followed by surgery. A pseudo-randomized comparison based on age, smoking status and T stage was performed to balanced confounders among treatment arms. Cox regression and Kaplan-Meier survival curves were used to compare overall survival (OS), progression free survival (PFS) and feeding tube dependency among the treatment arms.</p> <p><strong>Results</strong></p> <p>A total of 55 patients were treated with NAC+S and 142 with CCRT from 2010 to 2017. Median follow-up was 30 months (±23 months). 11 (7.7%) patients undergoing CCRT required salvage surgery and 2 (3.6%) patients in the NAC+S required adjuvant chemoradiotherapy. After pseudo-randomization, the 5-year OS in patients undergoing NAC+S (83.8%) was similar to CCRT (72.9%, p = 0.38). The 5-year PFS was 85.5% in the NAC+S arm compared to 74.7% in patients undergoing CCRT (p = 0.22). Median duration of feeding tubes was 0.2 months (interquartile range, IQR, of 0.4 months) for NAC+S compared to 5.5 months (IQR 1.3 months) with CCRT (p < 0.001). At 12 months from treatment completion, 24.5% of patients undergoing CCRT and 0 patients in the NAC+S were feeding tube dependent after adjusting for prophylactic feeding tube insertion (p < 0.0001) in the CCRT group. Patients undergoing NAC+S showed a trend toward improved overall survival compared to CCRT after adjusting for age, gender, smoking history, alcohol consumption, Charlson Comorbity Index and tumor subsite.</p> <p><strong>Conclusion</strong></p> <p>Neoadjuvant chemotherapy followed by surgery, reserving radiation for salvage, is a novel paradigm for definitive management of p16 positive OPSCC. It provides lower feeding tube dependence and similar survival outcomes compared to concomitant chemoradiation in patients with locoregionally advanced p16 positive OPSCC.</p>