Angela L Mazul1, Katelyn O Stepan2, Thomas F Barrett2, Wade L Thorstad3, Sean Massa2, Douglas R Adkins4, Mackenzie D Daly3, Jason T Rich2, Randal C Paniello2, Patrik Pipkorn2, Jose P Zevallos2, Ryan S Jackson2, Stephen Y Kang5, Sidharth V Puram6. 1. Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, MO, United States; Division of Public Health Sciences, Department of Surgery, Washington University, St Louis, MO, United States. 2. Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, MO, United States. 3. Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO, United States. 4. Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO, United States. 5. Department of Otolaryngology - Head and Neck Surgery, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH, United States. 6. Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, MO, United States; Department of Genetics, Washington University School of Medicine, St Louis, MO, United States. Electronic address: sidpuram@wustl.edu.
Abstract
INTRODUCTION: Delays in radiation are multifactorial, frequent, and associated with poor outcomes. This study investigates the effect of both primary and adjuvant radiation therapy duration and their interaction with other measures of treatment delay on survival in head and neck squamous cell carcinoma (HNSCC). METHODS: We built a retrospective cohort using the National Cancer Database, consisting of primary oral cavity, hypopharynx, larynx and oropharynx squamous cell carcinoma without distant metastasis and with at least six weeks of radiation. The primary exposure was the duration of radiation therapy (DRT), and the primary outcome was death. We estimated the association between DRT and 5-year overall survival (OS) using Kaplan-Meier curves and hazard ratios (HRs) with Cox proportional hazard regression. RESULTS: In both primary (definitive) and adjuvant (post-surgical) radiation settings, increased DRT results in decreased survival. In the primary radiation cohort, 5-year OS was 59.7% [59.1%-60.3%] among those with 47-53 days DRT, which decreased significantly with each subsequent week to completion (81+ days: 38.4% [36.2%-40.7%]). In the surgical cohort, survival decreased 16.5% when DRT extended beyond 75 days (40-46 days: 68.2% [67.3%-69.1%] vs. 75+ days: 53.3% [50.1%-56.7%]). Multivariate analyses showed increased hazard of death with increased DRT (primary radiation: 81+ days HR: 1.69 [1.58-1.81]); surgical: 75+ days HR: 1.61 [1.37-1.88]), with effects intensifying when restricting to those receiving full-dose radiation. CONCLUSION: A prolonged DRT was associated with worse OS in head and neck cancer. Radiation treatment delays of even a week lead to a significant survival disadvantage. DRT had a stronger association with survival than time to initiation of postoperative adjuvant radiotherapy.
INTRODUCTION: Delays in radiation are multifactorial, frequent, and associated with poor outcomes. This study investigates the effect of both primary and adjuvant radiation therapy duration and their interaction with other measures of treatment delay on survival in head and neck squamous cell carcinoma (HNSCC). METHODS: We built a retrospective cohort using the National Cancer Database, consisting of primary oral cavity, hypopharynx, larynx and oropharynx squamous cell carcinoma without distant metastasis and with at least six weeks of radiation. The primary exposure was the duration of radiation therapy (DRT), and the primary outcome was death. We estimated the association between DRT and 5-year overall survival (OS) using Kaplan-Meier curves and hazard ratios (HRs) with Cox proportional hazard regression. RESULTS: In both primary (definitive) and adjuvant (post-surgical) radiation settings, increased DRT results in decreased survival. In the primary radiation cohort, 5-year OS was 59.7% [59.1%-60.3%] among those with 47-53 days DRT, which decreased significantly with each subsequent week to completion (81+ days: 38.4% [36.2%-40.7%]). In the surgical cohort, survival decreased 16.5% when DRT extended beyond 75 days (40-46 days: 68.2% [67.3%-69.1%] vs. 75+ days: 53.3% [50.1%-56.7%]). Multivariate analyses showed increased hazard of death with increased DRT (primary radiation: 81+ days HR: 1.69 [1.58-1.81]); surgical: 75+ days HR: 1.61 [1.37-1.88]), with effects intensifying when restricting to those receiving full-dose radiation. CONCLUSION: A prolonged DRT was associated with worse OS in head and neck cancer. Radiation treatment delays of even a week lead to a significant survival disadvantage. DRT had a stronger association with survival than time to initiation of postoperative adjuvant radiotherapy.
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