The effects of continued smoking in head and neck cancer patients treated with radiotherapy: A systematic review and meta-analysis

Smith, Justin; Nastasi, Domenico R.; Tso, Reece; Vangaveti, Venkat; Renison, Bronia; Chilkuri, Madhavi

doi:10.1016/j.radonc.2019.02.021

Cited by 52 publications

(59 citation statements)

References 46 publications

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“…The latter also had non-cancer related mortality causes similar to HPV-negative cases [28]. Therefore, we strongly advocate smoking cessation as a component of the holistic care of head and neck cancer patients to both minimize long term smoking related co-morbidity and mortality as well as to potentially reduce the impact of smoking during radiotherapy which has been prospectively demonstrated to meaningfully influence hypoxia and disease control [44,45]. Another important element to be considered in the changing profile of HNC concerns increasing age in our populations, which was significant for survival in MVA as has been shown by others [27].…”

Section: Discussionmentioning

confidence: 99%

Durable therapeutic gain despite competing mortality in long-term follow-up of a randomized hyperfractionated radiotherapy trial for locally advanced head and neck cancer

O’Sullivan

Huang

Keane

et al. 2020

Clinical and Translational Radiation Oncology

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To examine the therapeutic ratio and mortality profile over time in a radiotherapy randomized trial in stage III-IV larynx/pharynx cancer with long-term follow-up. Materials/methods: From 1988 to 1995, 331 cases were randomized to either hyperfractionated (HF) (58 Gy/40 fractions, twice daily) or conventional (CF) (51 Gy/20 fractions, once daily) radiotherapy. Overall survival (OS), locoregional (LRC), distant control (DC), Grade 3 late toxicity (LT), and relative mortality risk profile over time were compared between both arms. Results: Median follow-up was 13.6 years. HF had a 10% improved OS at 5-years (40% vs 30%, p = 0.04), but the benefit diminished to 3% at 10-years (21% vs 18%). A trend towards higher LRC with HF remained (5-year: 49% vs 40%; 10-year: 49% vs 39%, p = 0.05). DC rates were unchanged (5-year: 87% vs 85%; 10year: 87 vs 84%, p = 0.56). LT rates were similar (HF vs CF: 5-year: 9% vs 12%; 10-year: 11% vs 14%, p = 0.27). Multivariable analysis confirmed that HF reduced mortality risk by 31% [HR 0.69 (0.55-0.88), p < 0.01] and locoregional failure risk by 35% [HR 0.65 (0.48-0.89), p < 0.01]. Index cancer mortality (5-year: 46% vs 51%; 10-year: 49% vs 55%) was lower in the HF arm. Competing mortality (mostly smoking-related) was also numerically lower with HF at 5-years (14% vs 19%) but became similar at 10-years (30% vs 28%). Conclusions: This trial confirms that HF with augmented total dose has a durable 10% effect size on LRC with comparable LT. OS benefit is evident at 5-years (10%) but relative mortality risk profile changes in longer follow-up.

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Section: Discussionmentioning

confidence: 99%

Durable therapeutic gain despite competing mortality in long-term follow-up of a randomized hyperfractionated radiotherapy trial for locally advanced head and neck cancer

O’Sullivan

Huang

Keane

et al. 2020

Clinical and Translational Radiation Oncology

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“…Moreover, data suggests that current smoking status adversely affects LRC and OS in patients with HNSCC. 40,41 This is further exacerbated by the smokinginduced reduction of radiation-induced tumor killing with subsequent worsening of locoregional control. 42,43 The unavailability of smoking status for patients while on-treatment -as is the case with our study-might raise a question on the weight that should be assigned to the carcinogenic effect of smoking compared to its antagonistic impact on radiotherapy e cacy.…”

Section: Discussionmentioning

confidence: 99%

Tobacco exposure as a major modifier of oncologic outcomes in Human PapillomaVirus (HPV) associated oropharyngeal squamous cell carcinoma

Elhalawani

Elgohari

et al. 2020

Preprint

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Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the US is rapidly increasing, driven largely by the epidemic of human papillomavirus (HPV)-mediated OPSCC. Although survival for patients with HPV mediated OPSCC (HPV+ OPSCC) is generally better than that of patients with non-viral HPV+ OPSCC, the improvement is not uniform. We hypothesized that tobacco exposure remains a critical modifier of survival for HPV+ OPSCC patients.Methods: We conducted a retrospective analysis of 611 OPSCC patients with concordant p16 and HPV testing treated at a single institute (2002-2013). Survival analysis was performed using Kaplan-Meier analysis and Cox regression. Recursive partitioning analysis (RPA) was used to define tobacco exposure associated with survival (p<0.05). Results: Tobacco exposure impacted overall survival (OS) for HPV+ patients on univariate and multivariate analysis (p=0.002, p=0.003 respectively). RPA identified 30 pack-years (PY) as a threshold at which survival became significantly worse in HPV+ patients. OS and disease-free survival (DFS) for HPV+ >30 PY patients didn’t differ significantly from HPV- group (p= 0.72, p= 0.27, respectively). HPV+ >30 PY patients had substantially lower 5-year OS when compared to their ≤30 PYs counterparts: 78.4% vs 91.6%; p= 0.03, 76% vs 88.3%; p= 0.07, and 52.3% vs 74%; p= 0.05, for stages I, II, and III (AJCC 8th Edition Manual), respectively.Conclusions: Tobacco exposure can eliminate the survival benefit associated with HPV+ status in OPSCC patients. Until this effect can be clearly quantified using prospective datasets, de-escalation of treatment for HPV+OPSCC smokers should be avoided.

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“…Moreover, data suggests that current smoking status adversely affects LRC and OS in patients with HNSCC. 37,38 This is further exacerbated by the smoking-induced reduction of radiation-induced tumor killing with subsequent worsening of locoregional control. 39,40 The unavailability of smoking status for patients while on-treatment -as is the case with our study-might raise a question on the weight that should be assigned to the carcinogenic effect of smoking compared to its antagonistic impact on radiotherapy efficacy.…”

Section: Discussionmentioning

confidence: 99%

Tobacco exposure as a major modifier of oncologic outcomes in Human PapillomaVirus (HPV) associated oropharyngeal squamous cell carcinoma

Elhalawani

Elgohari

et al. 2020

Preprint

View full text Add to dashboard Cite

Background The incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the US is rapidly increasing, driven largely by the epidemic of human papillomavirus (HPV)-mediated OPSCC. Although survival for patients with HPV mediated OPSCC (HPV+ OPSCC) is generally better than that of patients with non-viral HPV+ OPSCC, the improvement is not uniform. We hypothesized that tobacco exposure remains a critical modifier of survival for HPV+ OPSCC patients. Methods We conducted a retrospective analysis of 611 OPSCC patients with concordant p16 and HPV testing treated at a single institute (2002-2013). Survival analysis was performed using Kaplan-Meier analysis and Cox regression. Recursive partitioning analysis (RPA) was used to define tobacco exposure associated with survival (p<0.05). Results Tobacco exposure impacted overall survival (OS) for HPV+ patients on univariate and multivariate analysis (p=0.002, p=0.003 respectively). RPA identified 30 pack-years (PY) as a threshold at which survival became significantly worse in HPV+ patients. OS and disease-free survival (DFS) for HPV+ >30 PY patients didn’t differ significantly from HPV- group (p= 0.72, p= 0.27, respectively). HPV+ >30 PY patients had substantially lower 5-year OS when compared to their ≤30 PYs counterparts: 78.4% vs 91.6%; p= 0.03, 76% vs 88.3%; p= 0.07, and 52.3% vs 74%; p= 0.05, for stages I, II, and III (AJCC 8th Edition Manual), respectively. Conclusions Tobacco exposure can eliminate the survival benefit associated with HPV+ status in OPSCC patients. Until this effect can be clearly quantified using prospective datasets, de-escalation of treatment for HPV+OPSCC smokers should be avoided.

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The effects of continued smoking in head and neck cancer patients treated with radiotherapy: A systematic review and meta-analysis

Cited by 52 publications

References 46 publications

Durable therapeutic gain despite competing mortality in long-term follow-up of a randomized hyperfractionated radiotherapy trial for locally advanced head and neck cancer

Durable therapeutic gain despite competing mortality in long-term follow-up of a randomized hyperfractionated radiotherapy trial for locally advanced head and neck cancer

Tobacco exposure as a major modifier of oncologic outcomes in Human PapillomaVirus (HPV) associated oropharyngeal squamous cell carcinoma

Tobacco exposure as a major modifier of oncologic outcomes in Human PapillomaVirus (HPV) associated oropharyngeal squamous cell carcinoma

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