Accounting for <i>EGFR</i> Mutations in Epidemiologic Analyses of Non–Small Cell Lung Cancers: Examples Based on the International Lung Cancer Consortium Data-Reference-Cited by-同舟云学术

Accounting for EGFR Mutations in Epidemiologic Analyses of Non–Small Cell Lung Cancers: Examples Based on the International Lung Cancer Consortium Data

Published:2022-03-01 Issue:3 Volume:31 Page:679-687
ISSN:1055-9965
Container-title:Cancer Epidemiology, Biomarkers & Prevention
language:en
Short-container-title:

Author:

Schmid Sabine¹²,Jiang Mei³^ORCID,Brown M. Catherine¹^ORCID,Fares Aline⁴,Garcia Miguel¹,Soriano Joelle¹⁵,Dong Mei¹⁶^ORCID,Thomas Sera⁷,Kohno Takashi⁸^ORCID,Leal Leticia Ferro⁹,Diao Nancy¹⁰^ORCID,Xie Juntao¹¹,Wang Zhichao¹²¹³^ORCID,Zaridze David¹⁴,Holcatova Ivana¹⁵,Lissowska Jolanta¹⁶,Świątkowska Beata¹⁷^ORCID,Mates Dana¹⁸^ORCID,Savic Milan¹⁹,Wenzlaff Angela S.²⁰^ORCID,Harris Curtis C.²¹,Caporaso Neil E.²²,Ma Hongxia²³,Fernandez-Tardon Guillermo²⁴^ORCID,Barnett Matthew J.²⁵^ORCID,Goodman Gary²⁶,Davies Michael P.A.²⁷^ORCID,Pérez-Ríos Mónica²⁸²⁹,Taylor Fiona³⁰³¹,Duell Eric J.³²³³^ORCID,Schoettker Ben³⁴³⁵,Brenner Hermann³⁴³⁵³⁶³⁷^ORCID,Andrew Angeline³⁸,Cox Angela³⁰^ORCID,Ruano-Ravina Alberto²⁸²⁹^ORCID,Field John K.²⁷^ORCID,Marchand Loic Le³⁹,Wang Ying⁴⁰,Chen Chu⁴¹,Tardon Adonina²⁴^ORCID,Shete Sanjay⁴²,Schabath Matthew B.⁴³^ORCID,Shen Hongbing²³,Landi Maria Teresa²²,Ryan Brid M.²¹,Schwartz Ann G.²⁰^ORCID,Qi Lihong⁴⁴,Sakoda Lori C.⁴⁵^ORCID,Brennan Paul⁴⁶^ORCID,Yang Ping¹²^ORCID,Zhang Jie¹¹,Christiani David C.¹⁰^ORCID,Reis Rui Manuel⁹⁴⁷⁴⁸^ORCID,Shiraishi Kouya⁸,Hung Rayjean J.⁶⁷^ORCID,Xu Wei¹⁶,Liu Geoffrey¹⁶^ORCID

Affiliation:

1. 1The Princess Margaret Cancer Centre and University Health Network, University of Toronto, Toronto, Ontario, Canada.

2. 2Department of Medical Oncology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.

3. 3State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

4. 4Division of Medical Oncology, Hospital de Base de São José do Rio Preto, SP, Brazil.

5. 5University of Ottawa, Ottawa, Ontario, Canada.

6. 6Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

7. 7Lunenfeld-Tanenbaum Research Institute, Sinai Health Systems, Toronto, Ontario, Canada.

8. 8Division of Genome Biology, National Cancer Centre Research Institute, Tokyo, Japan.

9. 9Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.

10. 10Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

11. 11Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

12. 12Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.

13. 13Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

14. 14Russian N.N. Blokhin Cancer Research Centre, Moscow, Russian Federation.

15. 15Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.

16. 16Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.

17. 17The Nofer Institute of Occupational Medicine, Lodz, Poland.

18. 18National Institute of Public Health, Bucharest, Romania.

19. 19Department of Thoracic Surgery, Clinical Center of Serbia, Belgrade, Serbia.

20. 20Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.

21. 21Laboratory of Human Carcinogenesis, Centre for Cancer Research, National Institutes of Health, Bethesda, Maryland.

22. 22Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

23. 23Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.

24. 24IUOPA, University of Oviedo, and ISPA (Health Research Institute of the Principality of Asturias) and CIBERESP, Asturias, Spain.

25. 25Program in Biostatistics Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.

26. 26Swedish Cancer Institute, Seattle, Washington.

27. 27Roy Castle Lung Cancer Research Programme, The University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Liverpool, United Kingdom.

28. 28Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Galicia, Spain.

29. 29CIBER de Epidemiología y Salud Pública, CIBERESP, Santiago de Compostela, Galicia, Spain.

30. 30Department of Oncology and Metabolism, University of Sheffield Medical School, Sheffield, United Kingdom.

31. 31Sheffield Teaching Hospitals Foundation Trust, Sheffield, United Kingdom.

32. 32Catalan Institute of Oncology (ICO), Barcelona, Spain.

33. 33Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.

34. 34Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

35. 35Network of Aging Research, Heidelberg University, Heidelberg, Germany.

36. 36Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.

37. 37German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

38. 38Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.

39. 39University of Hawaii Cancer Center, Honolulu, Hawaii.

40. 40American Cancer Society, Atlanta, Georgia.

41. 41Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.

42. 42The University of Texas MD Anderson Cancer Center, Houston, Texas.

43. 43Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.

44. 44The University of California Davis Medical Sciences, Davis, California.

45. 45Kaiser Permanente Northern California, Division of Research, Oakland, California.

46. 46International Agency for Research on Cancer, Lyon, France.

47. 47Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, Braga, Portugal.

48. 48ICVS/3B's-PT Government Associate Laboratory, Braga, Portugal.

Abstract

Abstract Background: Somatic EGFR mutations define a subset of non–small cell lung cancers (NSCLC) that have clinical impact on NSCLC risk and outcome. However, EGFR-mutation-status is often missing in epidemiologic datasets. We developed and tested pragmatic approaches to account for EGFR-mutation-status based on variables commonly included in epidemiologic datasets and evaluated the clinical utility of these approaches. Methods: Through analysis of the International Lung Cancer Consortium (ILCCO) epidemiologic datasets, we developed a regression model for EGFR-status; we then applied a clinical-restriction approach using the optimal cut-point, and a second epidemiologic, multiple imputation approach to ILCCO survival analyses that did and did not account for EGFR-status. Results: Of 35,356 ILCCO patients with NSCLC, EGFR-mutation-status was available in 4,231 patients. A model regressing known EGFR-mutation-status on clinical and demographic variables achieved a concordance index of 0.75 (95% CI, 0.74–0.77) in the training and 0.77 (95% CI, 0.74–0.79) in the testing dataset. At an optimal cut-point of probability-score = 0.335, sensitivity = 69% and specificity = 72.5% for determining EGFR-wildtype status. In both restriction-based and imputation-based regression analyses of the individual roles of BMI on overall survival of patients with NSCLC, similar results were observed between overall and EGFR-mutation-negative cohort analyses of patients of all ancestries. However, our approach identified some differences: EGFR-mutated Asian patients did not incur a survival benefit from being obese, as observed in EGFR-wildtype Asian patients. Conclusions: We introduce a pragmatic method to evaluate the potential impact of EGFR-status on epidemiological analyses of NSCLC. Impact: The proposed method is generalizable in the common occurrence in which EGFR-status data are missing.

Funder

NIH NCI

Publisher

American Association for Cancer Research (AACR)

Subject

Oncology,Epidemiology

Link

https://aacrjournals.org/cebp/article-pdf/31/3/679/3052458/679.pdf

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