Association of Pack-Years of Cigarette Smoking With Survival and Tumor Progression Among Patients Treated With Chemoradiation for Head and Neck Cancer

Abstract

ImportanceAfter 10 pack-years of smoking was initially established as a threshold for risk stratification, subsequent clinical trials incorporated it to identify candidates for treatment deintensification. However, several recent studies were unable to validate this threshold externally, and the threshold for smoking exposure remains unclear.ObjectiveTo estimate the threshold of pack-years of smoking associated with survival and tumor recurrence among patients with head and neck cancer.Design, Setting, and ParticipantsThis single-institution, cohort study included patients with nonmetastatic head and neck cancer receiving chemoradiation from January 2005 to April 2021. Data were analyzed from January to April 2022.ExposuresHeavy vs light smoking using 22 pack-years as a threshold based on maximizing log-rank test statistic.Main Outcomes and MeasuresOverall survival (OS), progression-free survival (PFS), locoregional failure (LRF), and distant failure (DF).ResultsA total of 518 patients (427 male [82.4%]; median [IQR] age, 61 [55-66] years) were included. Median (IQR) follow-up was 44.1 (22.3-72.8) months. A nonlinear Cox regression model using restricted cubic splines showed continuous worsening of OS and PFS outcomes as pack-years of smoking increased. The threshold of pack-years to estimate OS and PFS was 22. Cox multivariable analysis (MVA) showed that more than 22 pack-years was associated with worse OS (adjusted hazard ratio [aHR] 1.57; 95% CI, 1.11-2.22; P = .01) and PFS (aHR, 1.38; 95% CI, 1.00-1.89; P = .048). On Fine-Gray MVA, heavy smokers were associated with DF (aHR, 1.71; 95% CI, 1.02-2.88; P = .04), but not LRF (aHR, 1.07; 95% CI, 0.61-1.87; P = .82). When 10 pack-years of smoking were used as a threshold, there was no association for OS (aHR, 1.23; 95% CI, 0.83-1.81; P = .30), PFS (aHR, 1.11; 95% CI, 0.78-1.57; P = .56), LRF (aHR, 1.19; 95% CI, 0.64-2.21; P = .58), and DF (aHR, 1.45; 95% CI, 0.82-2.56; P = .20). Current smoking was associated with worse OS and PFS only among human papillomavirus (HPV)-positive tumors (OS: aHR, 2.81; 95% CI, 1.26-6.29; P = .01; PFS: aHR, 2.51; 95% CI, 1.22-5.14; P = .01).Conclusions and RelevanceIn this cohort study of patients treated with definitive chemoradiation, 22 pack-years of smoking was associated with survival and distant metastasis outcomes. Current smoking status was associated with adverse outcomes only among patients with HPV-associated head and neck cancer.

Severe Oral Mucositis After Intensity-Modulated Radiation Therapy for Head and Neck Cancer

“…These findings underscore the importance of smoking cessation prior to initiation of RT for HNC. In addition to worsening OM risk, smoking during treatment has also been linked to worse survival . The contribution of chemotherapy to the development of severe OM remains unclear.…”

“…In addition to worsening OM risk, smoking during treatment has also been linked to worse survival. 25 , 26 The contribution of chemotherapy to the development of severe OM remains unclear. While 2 studies 3 , 6 demonstrated concurrent chemotherapy to be associated with OM, our study and others 5 , 20 did not.…”

“…In addition to worsening OM risk, smoking during treatment has also been linked to worse survival. 25,26 The contribution of chemotherapy to the development of severe OM remains unclear.…”

De-Escalated Therapy and Early Treatment of Recurrences in HPV-Associated Head and Neck Cancer: The Potential for Biomarkers to Revolutionize Personalized Therapy

“…The risk categorization based on pack-years has been extensively adopted and continues to be used as a primary tool to identify patients at low risk appropriate for de-escalated therapy; however, emerging retrospective data from multiple groups would seem to indicate that tobacco exposure of 20–25 pack-years is a more accurate prognostic threshold [ 25 ]. Clinical trials have examined a variety of approaches for reducing therapy in HPV+ oropharynx cancer, with the use of chemotherapy to radically reduce radiation dose with a goal of diminishing late swallowing dysfunction, more modest reduction in radiation dose to reduce acute toxicity and duration of therapy, and transoral resection to permit pathology-driven treatment deintensification with the potential to spare chemotherapy and radiation.…”

High‐risk TP53 mutations predict poor primary treatment response of patients with head and neck squamous cell carcinoma

“…Current evidence suggests that there is high variability in the clinical efficacy of different therapeutic modalities (Gavrielatou et al, 2020; Perrotti et al, 2021), however, clinicians lack predictive biomarkers to successfully correlate treatments with clinical response (Bouhaddou et al, 2021; Cohen et al, 2019; Gavrielatou et al, 2020; Ow et al, 2015). To date, smoking status (Ma et al, 2022), age (Stromberger et al, 2020) and HPV infection (Sabatini & Chiocca, 2020) have been shown to influence therapy outcomes in HNSCC. Additionally, mutations in the TP53 gene have been proposed as predictive biomarkers for therapy response, although inconsistent and controversial results have been reported (Basyuni et al, 2022; Ow et al, 2015).…”