Effect of Smoking on Treatment Efficacy and Toxicity in Patients with Cancer: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: The impact of smoking on cancer treatment efficacy and toxicity regardless of cancer type was investigated in this meta-analysis. Smoking during radiotherapy/chemoradiotherapy was associated with worse outcomes and a higher risk for toxicity. Smoking during treatment with EGFR tyrosine kinase inhibitors in lung cancer patients was associated with a worse prognosis, whereas smoking was associated with better outcomes in patients treated with checkpoint inhibitors. No association between smoking and treatment efficacy of chemotherapy was observed, though with low certainty of evidence. Our results can be used by oncology and radiotherapy staff to give patients more convincing information on the benefits that can be derived from smoking cessation before cancer treatment. ABSTRACT: Aim: The aim of the present systematic review and meta-analysis was to summarize the current evidence on the potential impact of smoking during cancer treatment on treatment efficacy and toxicity irrespective of cancer type. Methods: A systematic literature search was performed using two electronic databases for potentially eligible studies. Only studies based on multivariable analysis for the association between smoking, compared to non-smokers (never or former), and treatment efficacy or toxicity were included. Pooled Hazard Ratios (HRs) or Odds Ratios (ORs) and corresponding 95% Confidence Intervals (CIs) were estimated through random-effects meta-analyses. Results: In total, 97 eligible studies were identified, of which 79 were eligible for the pooled analyses. Smoking during radiation therapy, with or without chemotherapy, was associated with an increased risk of locoregional recurrence (pooled HR: 1.56; 95% CI: 1.28–1.91 for radiation therapy; pooled HR: 4.28; 95% CI: 2.06–8.90 for chemoradiotherapy) and worse disease-free survival (pooled HR: 1.88; 95% CI: 1.21–2.90 for radiation therapy; pooled HR: 1.92; 95% CI: 1.41–2.62 for chemoradiotherapy) as well as a higher risk for radiation-induced toxicity (pooled OR: 1.84; 95% CI: 1.32–2.56 for radiation therapy; pooled OR: 2.43; 95% CI: 1.43–4.07 for chemoradiotherapy) with low-to-moderate certainty of evidence. Smoking during treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients with lung cancer was associated with worse progression-free survival compared to non-smokers (pooled HR: 1.43; 95% CI: 1.14–1.80; moderate certainty of evidence), whereas smoking was associated with improved progression-free survival in patients treated with checkpoint inhibitors (HR: 0.70; 95% CI: 0.58–0.84; moderate certainty of evidence). No statistically significant associations were observed between smoking and treatment efficacy or toxicity to chemotherapy. Conclusion: The present meta-analysis confirms earlier evidence of the negative impact of smoking during radiation therapy, with or without chemotherapy, on treatment efficacy and radiation-induced toxicity as well as a negative impact of smoking on the efficacy of EGFR-TKIs and a positive impact on the efficacy of checkpoint inhibitors. The evidence is too weak to draw firm conclusions on the potential association between smoking and chemotherapy, whereas there is no evidence for pooled analyses regarding other types of systemic oncological therapy.