Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma

Ping Yang, Kimary Kulig, Jennifer M. Boland, Michele R. Erickson-Johnson, Andre M. Oliveira, Jason Wampfler, Aminah Jatoi, Claude Deschamps, Randolph Stuart Marks, Connie Fortner, Shawn Stoddard, Francis Nichols, Julian R Molina, Marie Christine Aubry, Hui Tang, Eunhee S. Yi

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Abstract

Introduction: The EML4-anaplastic lymphoma kinase (ALK) translocation is a recognized oncogenic driver in non-small cell lung cancer. We investigated immunohistochemistry (IHC) screening with fluorescence in situ hybridization (FISH) confirmation for ALK detection and estimated the prevalence of ALK positivity in our patient cohort of never-smokers, together with differences in clinical outcomes and prognostic factors for patients with ALK-positive and ALK-negative tumors. Methods: We designed a three-phase study (training, validation, and testing) in 300 never-smokers with lung adenocarcinoma from the observational Mayo Clinic Lung Cancer Cohort. Tumor samples were tested using IHC and FISH, and concordance between the methods was assessed. Clinical outcomes were assessed via 5-year progression- or recurrence-free survival from diagnosis. Prognostic factors for ALK-positive tumors and metastases were also investigated. Results: ALK-positive patients were significantly (p < 0.05) younger and had higher grade tumors than ALK-negative patients. ALK positivity was 12.2% by IHC and confirmed at 8.2% of tumors by FISH, with complete concordance between IHC 3+/0 and FISH+/- assessments, respectively. Five-year risk of progression or recurrence was doubled for patients with ALK-positive compared with ALK-negative tumors; ALK-positive tumors also appeared to be associated with a higher risk of brain and liver metastases. Conclusions: Our findings suggest that ALK positivity is associated with a significantly poor outcome in nonsmoking-related adenocarcinoma and that ALK-positive tumors may be associated with an increased risk of brain and liver metastases compared with ALK-negative disease. Consequently, an unmet medical need exists in ALK-positive lung cancer patients, and effective ALK-specific therapies are needed.

Original languageEnglish (US)
Pages (from-to)90-97
Number of pages8
JournalJournal of Thoracic Oncology
Volume7
Issue number1
DOIs
StatePublished - Jan 2012

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Disease-Free Survival
Fluorescence In Situ Hybridization
Neoplasms
Immunohistochemistry
anaplastic lymphoma kinase
Adenocarcinoma of lung
Neoplasm Metastasis
Lung Neoplasms
Recurrence
Validation Studies
Liver
Brain
Non-Small Cell Lung Carcinoma
Adenocarcinoma

Keywords

  • EML4-anaplastic lymphoma kinase
  • Fluorescence in situ hybridization
  • Immunohistochemistry
  • Non-small cell lung cancer
  • Progression- and recurrence-free survival

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Yang, P., Kulig, K., Boland, J. M., Erickson-Johnson, M. R., Oliveira, A. M., Wampfler, J., ... Yi, E. S. (2012). Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma. Journal of Thoracic Oncology, 7(1), 90-97. https://doi.org/10.1097/JTO.0b013e31823c5c32

Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma. / Yang, Ping; Kulig, Kimary; Boland, Jennifer M.; Erickson-Johnson, Michele R.; Oliveira, Andre M.; Wampfler, Jason; Jatoi, Aminah; Deschamps, Claude; Marks, Randolph Stuart; Fortner, Connie; Stoddard, Shawn; Nichols, Francis; Molina, Julian R; Aubry, Marie Christine; Tang, Hui; Yi, Eunhee S.

In: Journal of Thoracic Oncology, Vol. 7, No. 1, 01.2012, p. 90-97.

Research output: Contribution to journalArticle

Yang, P, Kulig, K, Boland, JM, Erickson-Johnson, MR, Oliveira, AM, Wampfler, J, Jatoi, A, Deschamps, C, Marks, RS, Fortner, C, Stoddard, S, Nichols, F, Molina, JR, Aubry, MC, Tang, H & Yi, ES 2012, 'Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma', Journal of Thoracic Oncology, vol. 7, no. 1, pp. 90-97. https://doi.org/10.1097/JTO.0b013e31823c5c32
Yang, Ping ; Kulig, Kimary ; Boland, Jennifer M. ; Erickson-Johnson, Michele R. ; Oliveira, Andre M. ; Wampfler, Jason ; Jatoi, Aminah ; Deschamps, Claude ; Marks, Randolph Stuart ; Fortner, Connie ; Stoddard, Shawn ; Nichols, Francis ; Molina, Julian R ; Aubry, Marie Christine ; Tang, Hui ; Yi, Eunhee S. / Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma. In: Journal of Thoracic Oncology. 2012 ; Vol. 7, No. 1. pp. 90-97.
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abstract = "Introduction: The EML4-anaplastic lymphoma kinase (ALK) translocation is a recognized oncogenic driver in non-small cell lung cancer. We investigated immunohistochemistry (IHC) screening with fluorescence in situ hybridization (FISH) confirmation for ALK detection and estimated the prevalence of ALK positivity in our patient cohort of never-smokers, together with differences in clinical outcomes and prognostic factors for patients with ALK-positive and ALK-negative tumors. Methods: We designed a three-phase study (training, validation, and testing) in 300 never-smokers with lung adenocarcinoma from the observational Mayo Clinic Lung Cancer Cohort. Tumor samples were tested using IHC and FISH, and concordance between the methods was assessed. Clinical outcomes were assessed via 5-year progression- or recurrence-free survival from diagnosis. Prognostic factors for ALK-positive tumors and metastases were also investigated. Results: ALK-positive patients were significantly (p < 0.05) younger and had higher grade tumors than ALK-negative patients. ALK positivity was 12.2{\%} by IHC and confirmed at 8.2{\%} of tumors by FISH, with complete concordance between IHC 3+/0 and FISH+/- assessments, respectively. Five-year risk of progression or recurrence was doubled for patients with ALK-positive compared with ALK-negative tumors; ALK-positive tumors also appeared to be associated with a higher risk of brain and liver metastases. Conclusions: Our findings suggest that ALK positivity is associated with a significantly poor outcome in nonsmoking-related adenocarcinoma and that ALK-positive tumors may be associated with an increased risk of brain and liver metastases compared with ALK-negative disease. Consequently, an unmet medical need exists in ALK-positive lung cancer patients, and effective ALK-specific therapies are needed.",
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AU - Yang, Ping

AU - Kulig, Kimary

AU - Boland, Jennifer M.

AU - Erickson-Johnson, Michele R.

AU - Oliveira, Andre M.

AU - Wampfler, Jason

AU - Jatoi, Aminah

AU - Deschamps, Claude

AU - Marks, Randolph Stuart

AU - Fortner, Connie

AU - Stoddard, Shawn

AU - Nichols, Francis

AU - Molina, Julian R

AU - Aubry, Marie Christine

AU - Tang, Hui

AU - Yi, Eunhee S.

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N2 - Introduction: The EML4-anaplastic lymphoma kinase (ALK) translocation is a recognized oncogenic driver in non-small cell lung cancer. We investigated immunohistochemistry (IHC) screening with fluorescence in situ hybridization (FISH) confirmation for ALK detection and estimated the prevalence of ALK positivity in our patient cohort of never-smokers, together with differences in clinical outcomes and prognostic factors for patients with ALK-positive and ALK-negative tumors. Methods: We designed a three-phase study (training, validation, and testing) in 300 never-smokers with lung adenocarcinoma from the observational Mayo Clinic Lung Cancer Cohort. Tumor samples were tested using IHC and FISH, and concordance between the methods was assessed. Clinical outcomes were assessed via 5-year progression- or recurrence-free survival from diagnosis. Prognostic factors for ALK-positive tumors and metastases were also investigated. Results: ALK-positive patients were significantly (p < 0.05) younger and had higher grade tumors than ALK-negative patients. ALK positivity was 12.2% by IHC and confirmed at 8.2% of tumors by FISH, with complete concordance between IHC 3+/0 and FISH+/- assessments, respectively. Five-year risk of progression or recurrence was doubled for patients with ALK-positive compared with ALK-negative tumors; ALK-positive tumors also appeared to be associated with a higher risk of brain and liver metastases. Conclusions: Our findings suggest that ALK positivity is associated with a significantly poor outcome in nonsmoking-related adenocarcinoma and that ALK-positive tumors may be associated with an increased risk of brain and liver metastases compared with ALK-negative disease. Consequently, an unmet medical need exists in ALK-positive lung cancer patients, and effective ALK-specific therapies are needed.

AB - Introduction: The EML4-anaplastic lymphoma kinase (ALK) translocation is a recognized oncogenic driver in non-small cell lung cancer. We investigated immunohistochemistry (IHC) screening with fluorescence in situ hybridization (FISH) confirmation for ALK detection and estimated the prevalence of ALK positivity in our patient cohort of never-smokers, together with differences in clinical outcomes and prognostic factors for patients with ALK-positive and ALK-negative tumors. Methods: We designed a three-phase study (training, validation, and testing) in 300 never-smokers with lung adenocarcinoma from the observational Mayo Clinic Lung Cancer Cohort. Tumor samples were tested using IHC and FISH, and concordance between the methods was assessed. Clinical outcomes were assessed via 5-year progression- or recurrence-free survival from diagnosis. Prognostic factors for ALK-positive tumors and metastases were also investigated. Results: ALK-positive patients were significantly (p < 0.05) younger and had higher grade tumors than ALK-negative patients. ALK positivity was 12.2% by IHC and confirmed at 8.2% of tumors by FISH, with complete concordance between IHC 3+/0 and FISH+/- assessments, respectively. Five-year risk of progression or recurrence was doubled for patients with ALK-positive compared with ALK-negative tumors; ALK-positive tumors also appeared to be associated with a higher risk of brain and liver metastases. Conclusions: Our findings suggest that ALK positivity is associated with a significantly poor outcome in nonsmoking-related adenocarcinoma and that ALK-positive tumors may be associated with an increased risk of brain and liver metastases compared with ALK-negative disease. Consequently, an unmet medical need exists in ALK-positive lung cancer patients, and effective ALK-specific therapies are needed.

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KW - Progression- and recurrence-free survival

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