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Does lung cancer mutation status and targeted therapy predict for outcomes and local control in the setting of brain metastases treated with radiation?
Wang TJ
,
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
.
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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.
Antoniu,
Crizotinib for EML4-ALK positive lung adenocarcinoma: a hope for the advanced disease? Evaluation of Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010;363(18):1693-703.
2011, Pubmed,
Echinobase
Antoniu,
Crizotinib for EML4-ALK positive lung adenocarcinoma: a hope for the advanced disease? Evaluation of Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010;363(18):1693-703.
2011,
Pubmed
,
Echinobase
Arrieta,
Long-term survival in patients with non-small cell lung cancer and synchronous brain metastasis treated with whole-brain radiotherapy and thoracic chemoradiation.
2011,
Pubmed
Barnholtz-Sloan,
Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System.
2004,
Pubmed
Bhangoo,
Evidence-based guidelines for the management of brain metastases.
2011,
Pubmed
Cai,
A comparative analysis of EGFR mutation status in association with the efficacy of TKI in combination with WBRT/SRS/surgery plus chemotherapy in brain metastasis from non-small cell lung cancer.
2014,
Pubmed
Cappuzzo,
ZD 1839 in patients with brain metastases from non-small-cell lung cancer (NSCLC): report of four cases.
2003,
Pubmed
Ceresoli,
Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial.
2004,
Pubmed
Eichler,
EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer.
2010,
Pubmed
Gaspar,
Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials.
1997,
Pubmed
Getman,
Prognosis of patients with non-small cell lung cancer with isolated brain metastases undergoing combined surgical treatment.
2004,
Pubmed
Grommes,
"Pulsatile" high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer.
2011,
Pubmed
Herbst,
Lung cancer.
2008,
Pubmed
Hsiao,
Impact of epidermal growth factor receptor mutations on intracranial treatment response and survival after brain metastases in lung adenocarcinoma patients.
2013,
Pubmed
Jamal-Hanjani,
Epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of epidermal growth factor receptor-mutant non-small cell lung cancer metastatic to the brain.
2012,
Pubmed
Johung,
A clinical model for identifying radiosensitive tumor genotypes in non-small cell lung cancer.
2013,
Pubmed
Lee,
Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis.
2013,
Pubmed
Lynch,
Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.
2004,
Pubmed
Mak,
Significance of targeted therapy and genetic alterations in EGFR, ALK, or KRAS on survival in patients with non-small cell lung cancer treated with radiotherapy for brain metastases.
2015,
Pubmed
Mehta,
Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases.
2003,
Pubmed
Mok,
Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.
2009,
Pubmed
Paez,
EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.
2004,
Pubmed
Slebos,
K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung.
1990,
Pubmed
Soda,
Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
2007,
Pubmed
,
Echinobase
Sperduto,
Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients.
2010,
Pubmed
Sperduto,
A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database.
2008,
Pubmed
Sørensen,
Brain metastases in adenocarcinoma of the lung: frequency, risk groups, and prognosis.
1988,
Pubmed