IASLC Position Statement on the Documentation of Tobacco Use in Cancer Clinical Trials

IASLC Position Statement on the Documentation of Tobacco Use in Cancer Clinical Trials

Press Release
Oct 24, 2023

Contact: Chris Martin, IASLC Media Relations, cmartin@davidjamesgroup.com 

(Denver, Colo.—October 24, 2024) -- In recent years, there has been growing awareness of the negative impact of tobacco use on clinical outcomes for cancer patients. The 2014 US Surgeon General’s report compiled compelling evidence that cigarette smoking by cancer patients and survivors causes adverse outcomes, including increased all-cause mortality, cancer-specific mortality and increased risk of a second primary cancer (1). The report further demonstrated that continued smoking was strongly associated with a greater risk of cancer treatment toxicity and poor quality-of-life. There is now evidence that smoking cessation after a cancer diagnosis is associated with improved survival (2,3).

Tobacco use has effects that are both prognostic (directly harming patients) and predictive (interfering with cancer therapies). Among lung cancer patients undergoing surgery, there is evidence of more frequent postoperative complications and increased perioperative mortality (4,5). For those patients receiving radiotherapy, there is a greater risk of treatment-related toxicity (6), and less therapeutic efficacy as a result of lower tissue oxygen levels (7). For those receiving systemic therapy with either chemotherapy or molecular targeted agents, there is evidence of less myelosuppression (8) and/or decreased tumour response (9) suggesting that the induction of hepatic enzymes by polycyclic aromatic hydrocarbons in tobacco smoke can increase the rate of clearance of these agents making them less effective (10,11). On the other hand, it appears that patients with a smoking history may have a greater benefit with immune checkpoint inhibitor treatment compared with never smokers (12). Studies of the impact of tobacco on clinical outcomes do not comprehensively address the large number of systemic therapy agents in current use today (13). Nonetheless, the available evidence indicates that smoking can be an important predictive factor that should be accounted for when testing the efficacy of novel cancer therapies. Further research is needed to address the impact of continued smoking after a diagnosis of cancer, to provide guidance on how best to manage treatment for those cancer patients who continue to smoke cigarettes, and to determine the magnitude of clinical benefit that is achieved with smoking cessation (14). 

Newer, alternative tobacco products, including electronic cigarettes (e-cigarettes) and heated tobacco products purportedly lower health risks relative to smoking combustible tobacco cigarettes. However, data on their long-term health effects, including the risk of lung cancer, and their impact on treatment outcomes are unavailable. To characterize the potential association between the use of alternative tobacco products on cancer risk and their impact on cancer treatment outcomes, there is a need to collect data on their use in cancer treatment trials (15).

Large reviews of cooperative group clinical trials have shown that smoking status is documented in only approximately 20% of trials at patient registration and very few trials capture information on smoking status over the course of the trial (16,17). Furthermore, definitions of smoking status (current, former, never smoking) are inconsistent and information on the intensity of smoking is rarely captured (18). Even when smoking status has been determined, few trials report analyses of the prognostic and predictive impact on clinical outcomes (19). Smoking clearly affects survival, as well as the toxicity of cancer treatments, and these endpoints serve as the primary or secondary objectives of virtually all clinical trials. As a result, it is critical that smoking information be collected and available for analysis to accurately assess the benefits and harms of cancer treatment in clinical trials (20).

To advance knowledge on the impacts of tobacco smoke in the context of cancer clinical trials, the IASLC recommends the following:

1. Documentation of tobacco use status at cancer diagnosis and at clinical trial registration using standardized definitions from the validated Cancer Patient Tobacco Use Questionnaire (C–TUQ) (21)

  1. Document the use of tobacco products (including electronic cigarettes and heated tobacco products) at regular intervals over the course of the clinical trial for those individuals who have ever used tobacco products.
  2. Document any methods of smoking cessation used by patients over the course of the clinical trial and their effectiveness.
  3. Verify smoking status using biochemical measures, whenever possible.
  4. Analyze the effect of tobacco use on clinical trial outcomes including response rate, progression free and overall survival, treatment-related toxicity, adverse events, compliance with trial procedures, and quality-of-life.

Revised August 19, 2023 

References 

  1. US DHHS. The Health Consequences of Smoking - 50 Years of Progress: A Report of the Surgeon General. Atlanta, GA.: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014.
  2. US DHHS. Smoking Cessation: A Report of the Surgeon General. 2020, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health: Atlanta, GA.
  3. Caini S, Del Riccio M, Vettori V, Scotti V, Martinoli C, Raimondi S, Cammarata G, Palli D, Banini M, Masala G, Gandini S. Quitting smoking at or around diagnosis improves the overall survival of lung cancer patients: a systematic review and meta-analysis. J Thorac Oncol 2022 May; 17 (5):623-636. doi: 10. 1016/j.jtho.2021.12.005. Epub 2022 Jan4. PMID: 34995798. 
  4. Fukui M, Suzuki K, Matsunaga T, Oh S, Takamochi K. Importance of Smoking Cessation on Surgical Outcome in Primary Lung Cancer. Ann Thorac Surg. 2019 Apr;107(4):1005-1009. Doi: 10.1016/j.athoracsur.2018.12.002. Epub 2019 Jan 2. PMID: 30610851.
  5. Jeganathan V, Knight S, Bricknell M, Ridgers A, Wong R, Brazzale DJ, Ruehland WR, Rahman MA, Leong TL, McDonald CF. Impact of smoking status and chronic obstructive pulmonary disease on pulmonary complications post lung cancer surgery. PLoS One. 2022 Mar 29;17(3): e0266052. doi: 10.1371/journal.pone.0266052. PMID: 35349598; PMCID: PMC8963579.
  6. Perdyan, A, Jassem, J. Impact of tobacco smoking on outcomes of radiotherapy: a narrative review. Curr Oncol 2022; 29,2284-2300.  https://doi.org/10.3390/curroncol29040186.
  7. Hoff CM, Grau C, Overgaard J. Effect of smoking on oxygen delivery and outcome in patients treated with radiotherapy for head and neck squamous cell carcinoma--a prospective study. Radiother Oncol 2012 Apr;103(1):38-44. https://doi: 10.1016/j.radonc.2012.01.011. Epub 2012 Mar 3. PMID: 22385797.
  8. O’Malley M, Healy P, Daignault S, Ramnath N. Cigarette smoking and gemcitabine-induced neutropenia in advanced solid tumors. Oncology 2013; 85:216–222.
  9. Shepherd FA, Pereira JR, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabarbara P, Seymour L for the National Cancer Institute of Canada Clinical Trials Group. Erolinib in previously treated non-small cell lung cancer. NEJM 2005; 353: 123-132.
  10. O’Malley M, King AN, Conte M, Ellingrod VL, Ramnath N. Effects of cigarette smoking on metabolism and effectiveness of systemic therapy for lung cancer. J Thorac Oncol 2014; 9:917–926. 
  11. Chellappan S. Smoking cessation after cancer diagnosis and enhanced therapy response: mechanisms and significance. Curr Oncol 2022; 29: 9956-9969. https://doi.org/10.3090/curroncol29120782. 
  12. Corke LK, Li JJN, Leighl NB, Eng L Tobacco use and response to immune checkpoint inhibitor therapy in non-small cell lung cancer. Curr Oncol 2022; 29: 6260-6276.  https://doi.org/10.3390/curroncol29090492.
  13. Land SR, Methodologic barriers to addressing critical questions about tobacco and cancer prognosis. J Clin Oncol, 2012;30(17):2030-2032.

Peters EN, Torres E, Toll BA, Cummings KM, Gritz ER, Hyland A, Herbst RS, 

  1. Marshall JR, Warren GW. Tobacco Assessment in Actively Accruing National Cancer Institute Cooperative Group Program Clinical Trials. J Clin Oncol 2012 Aug 10;30(23):2869-2875. https://doi:10.1200/JCO.2011.40.8815. Epub 2012 Jun 11.
  2. Goniewicz ML. Chapter 6: Alternative Nicotine Delivery System. Pages 157-175. In: Tobacco and Cancer: The Science and the Story. Eds. Hecht SS and Hatsukami DK (University of Minnesota, Twin Cities, USA). World Scientific Publishing. New Jersey, USA [2022]. 
  3. Peters EN, Warren GW, Sloan JA, Marshall JR. Tobacco assessment in completed lung cancer treatment trials. Cancer 2016; 122(21): 3260-3262.
  4. Eng L, Brual J, Nagee A, Mok S, Fazelzad R, Chaiton M, Saunders DP, Mittman N, Truscott R, Liu G, Bradbury PA, Evans WK, Papadakos J, Giuliani ME. Reporting of tobacco use and tobacco-related analyses in cancer cooperative group clinical trials: a systematic scoping review. ESMO Open. 2022 Dec;7(6):100605. Doi: 10.1016/j.esmoop.2022.100605. Epub 2022 Nov 7. PMID: 36356412; PMCID: PMC9646674.
  5. Land SR, Waren GW, Crafts JI, Hatsukami DK, Ostroff JS, Willis GB, Cholette VY, Mitchell SA, Folz JNM, Gulley JL, Szabo E, Brandon TH, Duffy SA, Toll BA. Cognitive testing of tobacco use items for administration to patients with cancer and cancer survivors in clinical research. Cancer 2016; 122(11): 1728-34.
  6. Land SR, Toll BA, Moinpour CM, Mitchell SA, Ostroff JS, Hatsukami DK, Duffy SA, Gritz ER, Rigotti NA, Brandon TH, Prindivilli SA, Sarna LP, Schnoll RA, Herbst RS, Cinciripini PM, Leischow SJ, Dresler CM, Fiore MC, Warren GW. Research Priorities, Measures, and Recommendations for Assessment of Tobacco Use in Clinical Cancer Research. Clin Cancer Res, 2016; 22(8): 1907-13.
  7. Warren GW, Evans WK, Dresler C. Critical Determinants of Cancer Treatment Outcomes: Smoking Must Be Addressed at the Highest Levels in Cancer Care. J Thorac Oncol. 2021 Jun;16(6):891-893. doi: 10.1016/j.jtho.2021.03.010. Epub 2021 Apr 22. PMID: 33895106.

National Cancer institute, Division of Cancer Control and Population Sciences, Behavioural Research Program. Assessing cancer patient tobacco use. Available at: https://cancercontrol.cancer.gov/brp/tcrb/cancer-patient-tobacco-useAbout the IASLC

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The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies. Founded in 1974, the association's membership includes more than 10,000 lung cancer specialists across all disciplines in over 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The association also publishes the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis and treatment of all thoracic malignancies. Visit www.iaslc.org for more information.

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