Does lung cancer mutation status and targeted therapy predict for outcomes and local control in the setting of brain metastases treated with radiation?

Tony J C Wang, Shumaila Saad, Yasir H. Qureshi, Ashish Jani, Tavish Nanda, Andrew M. Yaeh, Tzlil Rozenblat, Michael B. Sisti, Jeffrey N. Bruce, Guy M. McKhann, Jeraldine Lesser, Balazs Halmos, Mark B. Stoopler, Andrew B. Lassman, Simon K. Cheng, Steven R. Isaacson

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background We investigated effects of genetic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and Kirsten rat sarcoma viral oncogene homolog (KRAS) on overall survival (OS) and local control after stereotactic radiosurgery for brain metastases in non-small cell lung cancer (NSCLC). Methods A cohort of 89 out of 262 NSCLC patients (2003-2013) treated with gamma knife radiosurgery for brain metastases had genotyping available and were selected as our study population. Results Median follow-up was 12 months. Median OS rates for the EGFR, KRAS, echinoderm microtubule-associated protein-like 4 (EML4)-ALK mutated, and wild-type cohorts were 17, 7, 27, and 12 months, respectively (P =. 019), and for targeted versus nontargeted therapy 21 and 11 months, respectively (P =. 071). Targeted therapy was a strong predictor of increased OS on univariate (P =. 037) and multivariate (P =. 022) analysis. Gender, primary tumor controlled status, recursive partitioning analysis class, and graded prognostic assessment score were associated with OS (P <. 05). On multivariate analysis, positive EGFR mutational status was a highly significant predictor for decreased survival (hazard ratio: 8.2; 95% CI: 2.0-33.7; P =. 003). However, when we recategorized EGFR-mutant cases based on whether they received tyrosine kinase inhibitor, OS was no longer significantly shorter (hazard ratio: 1.5; P =. 471). Median OS for patients with and without local failure was 17 and 12 months, respectively (P =. 577). Local failure rates for EGFR, KRAS, EML4-ALK mutated, and wild-type cohorts by lesion were 8.7%, 5.4%, 4.3%, and 5.1%, respectively. Conclusions This study suggests that EGFR tyrosine kinase mutation and ALK translocation results in improved survival to targeted therapies and that mutation status itself does not predict survival and local control in patients with brain metastases from NSCLC.

Original languageEnglish (US)
Pages (from-to)1022-1028
Number of pages7
JournalNeuro-Oncology
Volume17
Issue number7
DOIs
StatePublished - Jul 1 2015
Externally publishedYes

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Lung Neoplasms
Epidermal Growth Factor Receptor
Radiation
Neoplasm Metastasis
Mutation
Survival
Brain
Non-Small Cell Lung Carcinoma
Radiosurgery
Therapeutics
Protein-Tyrosine Kinases
Cetirizine
Oncogenes
Sarcoma
Multivariate Analysis
Survival Rate
anaplastic lymphoma kinase
Population
Neoplasms

Keywords

  • brain metastases
  • mutations
  • non-small cell lung cancer
  • stereotactic radiosurgery
  • targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Does lung cancer mutation status and targeted therapy predict for outcomes and local control in the setting of brain metastases treated with radiation? / Wang, Tony J C; Saad, Shumaila; Qureshi, Yasir H.; Jani, Ashish; Nanda, Tavish; Yaeh, Andrew M.; Rozenblat, Tzlil; Sisti, Michael B.; Bruce, Jeffrey N.; McKhann, Guy M.; Lesser, Jeraldine; Halmos, Balazs; Stoopler, Mark B.; Lassman, Andrew B.; Cheng, Simon K.; Isaacson, Steven R.

In: Neuro-Oncology, Vol. 17, No. 7, 01.07.2015, p. 1022-1028.

Research output: Contribution to journalArticle

Wang, TJC, Saad, S, Qureshi, YH, Jani, A, Nanda, T, Yaeh, AM, Rozenblat, T, Sisti, MB, Bruce, JN, McKhann, GM, Lesser, J, Halmos, B, Stoopler, MB, Lassman, AB, Cheng, SK & Isaacson, SR 2015, 'Does lung cancer mutation status and targeted therapy predict for outcomes and local control in the setting of brain metastases treated with radiation?', Neuro-Oncology, vol. 17, no. 7, pp. 1022-1028. https://doi.org/10.1093/neuonc/nov043
Wang, Tony J C ; Saad, Shumaila ; Qureshi, Yasir H. ; Jani, Ashish ; Nanda, Tavish ; Yaeh, Andrew M. ; Rozenblat, Tzlil ; Sisti, Michael B. ; Bruce, Jeffrey N. ; McKhann, Guy M. ; Lesser, Jeraldine ; Halmos, Balazs ; Stoopler, Mark B. ; Lassman, Andrew B. ; Cheng, Simon K. ; Isaacson, Steven R. / Does lung cancer mutation status and targeted therapy predict for outcomes and local control in the setting of brain metastases treated with radiation?. In: Neuro-Oncology. 2015 ; Vol. 17, No. 7. pp. 1022-1028.
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abstract = "Background We investigated effects of genetic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and Kirsten rat sarcoma viral oncogene homolog (KRAS) on overall survival (OS) and local control after stereotactic radiosurgery for brain metastases in non-small cell lung cancer (NSCLC). Methods A cohort of 89 out of 262 NSCLC patients (2003-2013) treated with gamma knife radiosurgery for brain metastases had genotyping available and were selected as our study population. Results Median follow-up was 12 months. Median OS rates for the EGFR, KRAS, echinoderm microtubule-associated protein-like 4 (EML4)-ALK mutated, and wild-type cohorts were 17, 7, 27, and 12 months, respectively (P =. 019), and for targeted versus nontargeted therapy 21 and 11 months, respectively (P =. 071). Targeted therapy was a strong predictor of increased OS on univariate (P =. 037) and multivariate (P =. 022) analysis. Gender, primary tumor controlled status, recursive partitioning analysis class, and graded prognostic assessment score were associated with OS (P <. 05). On multivariate analysis, positive EGFR mutational status was a highly significant predictor for decreased survival (hazard ratio: 8.2; 95{\%} CI: 2.0-33.7; P =. 003). However, when we recategorized EGFR-mutant cases based on whether they received tyrosine kinase inhibitor, OS was no longer significantly shorter (hazard ratio: 1.5; P =. 471). Median OS for patients with and without local failure was 17 and 12 months, respectively (P =. 577). Local failure rates for EGFR, KRAS, EML4-ALK mutated, and wild-type cohorts by lesion were 8.7{\%}, 5.4{\%}, 4.3{\%}, and 5.1{\%}, respectively. Conclusions This study suggests that EGFR tyrosine kinase mutation and ALK translocation results in improved survival to targeted therapies and that mutation status itself does not predict survival and local control in patients with brain metastases from NSCLC.",
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T1 - Does lung cancer mutation status and targeted therapy predict for outcomes and local control in the setting of brain metastases treated with radiation?

AU - Wang, Tony J C

AU - Saad, Shumaila

AU - Qureshi, Yasir H.

AU - Jani, Ashish

AU - Nanda, Tavish

AU - Yaeh, Andrew M.

AU - Rozenblat, Tzlil

AU - Sisti, Michael B.

AU - Bruce, Jeffrey N.

AU - McKhann, Guy M.

AU - Lesser, Jeraldine

AU - Halmos, Balazs

AU - Stoopler, Mark B.

AU - Lassman, Andrew B.

AU - Cheng, Simon K.

AU - Isaacson, Steven R.

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N2 - Background We investigated effects of genetic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and Kirsten rat sarcoma viral oncogene homolog (KRAS) on overall survival (OS) and local control after stereotactic radiosurgery for brain metastases in non-small cell lung cancer (NSCLC). Methods A cohort of 89 out of 262 NSCLC patients (2003-2013) treated with gamma knife radiosurgery for brain metastases had genotyping available and were selected as our study population. Results Median follow-up was 12 months. Median OS rates for the EGFR, KRAS, echinoderm microtubule-associated protein-like 4 (EML4)-ALK mutated, and wild-type cohorts were 17, 7, 27, and 12 months, respectively (P =. 019), and for targeted versus nontargeted therapy 21 and 11 months, respectively (P =. 071). Targeted therapy was a strong predictor of increased OS on univariate (P =. 037) and multivariate (P =. 022) analysis. Gender, primary tumor controlled status, recursive partitioning analysis class, and graded prognostic assessment score were associated with OS (P <. 05). On multivariate analysis, positive EGFR mutational status was a highly significant predictor for decreased survival (hazard ratio: 8.2; 95% CI: 2.0-33.7; P =. 003). However, when we recategorized EGFR-mutant cases based on whether they received tyrosine kinase inhibitor, OS was no longer significantly shorter (hazard ratio: 1.5; P =. 471). Median OS for patients with and without local failure was 17 and 12 months, respectively (P =. 577). Local failure rates for EGFR, KRAS, EML4-ALK mutated, and wild-type cohorts by lesion were 8.7%, 5.4%, 4.3%, and 5.1%, respectively. Conclusions This study suggests that EGFR tyrosine kinase mutation and ALK translocation results in improved survival to targeted therapies and that mutation status itself does not predict survival and local control in patients with brain metastases from NSCLC.

AB - Background We investigated effects of genetic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and Kirsten rat sarcoma viral oncogene homolog (KRAS) on overall survival (OS) and local control after stereotactic radiosurgery for brain metastases in non-small cell lung cancer (NSCLC). Methods A cohort of 89 out of 262 NSCLC patients (2003-2013) treated with gamma knife radiosurgery for brain metastases had genotyping available and were selected as our study population. Results Median follow-up was 12 months. Median OS rates for the EGFR, KRAS, echinoderm microtubule-associated protein-like 4 (EML4)-ALK mutated, and wild-type cohorts were 17, 7, 27, and 12 months, respectively (P =. 019), and for targeted versus nontargeted therapy 21 and 11 months, respectively (P =. 071). Targeted therapy was a strong predictor of increased OS on univariate (P =. 037) and multivariate (P =. 022) analysis. Gender, primary tumor controlled status, recursive partitioning analysis class, and graded prognostic assessment score were associated with OS (P <. 05). On multivariate analysis, positive EGFR mutational status was a highly significant predictor for decreased survival (hazard ratio: 8.2; 95% CI: 2.0-33.7; P =. 003). However, when we recategorized EGFR-mutant cases based on whether they received tyrosine kinase inhibitor, OS was no longer significantly shorter (hazard ratio: 1.5; P =. 471). Median OS for patients with and without local failure was 17 and 12 months, respectively (P =. 577). Local failure rates for EGFR, KRAS, EML4-ALK mutated, and wild-type cohorts by lesion were 8.7%, 5.4%, 4.3%, and 5.1%, respectively. Conclusions This study suggests that EGFR tyrosine kinase mutation and ALK translocation results in improved survival to targeted therapies and that mutation status itself does not predict survival and local control in patients with brain metastases from NSCLC.

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