Mutation status and postresection survival of patients with non–small cell lung cancer brain metastasis: implications of biomarker-driven therapy

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  • 1 Departments of Neurosurgery and
  • | 2 Radiation Oncology, Johns Hopkins University School of Medicine; and
  • | 3 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
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OBJECTIVE

Non–small cell lung cancer (NSCLC) is the most common primary tumor to develop brain metastasis. Prognostic markers are needed to better determine survival after neurosurgical resection of intracranial disease. Given the importance of mutation subtyping in determining systemic therapy and overall prognosis of NSCLC, the authors examined the prognostic value of mutation status for postresection survival of patients with NSCLC brain metastasis.

METHODS

The authors retrospectively analyzed all cases of NSCLC brain metastasis with available molecular testing data that were resected by a single surgeon at a single academic center from January 2009 to February 2019. Mutation status, demographic characteristics, clinical factors, and treatments were analyzed. Association between predictive variables and overall survival after neurosurgery was determined with Cox regression.

RESULTS

Of the included patients (n = 84), 40% were male, 76% were smokers, the mean ± SD Karnofsky Performance Status was 85 ± 14, and the mean ± SD age at surgery was 63 ± 11 years. In total, 23%, 26%, and 4% of patients had EGFR, KRAS, and ALK/ROS1 alterations, respectively. On multivariate analysis, survival of patients with EGFR (HR 0.495, p = 0.0672) and KRAS (HR 1.380, p = 0.3617) mutations were not significantly different from survival of patients with wild-type (WT) tumor. However, the subgroup of patients with EGFR mutation who also received tyrosine kinase inhibitor (TKI) therapy had significantly prolonged survival (HR 0.421, p = 0.0471). In addition, postoperative stereotactic radiosurgery (HR 0.409, p = 0.0177) and resected tumor diameter < 3 cm (HR 0.431, p = 0.0146) were also significantly associated with prolonged survival, but Graded Prognostic Assessment score ≤ 1.0 (HR 2.269, p = 0.0364) was significantly associated with shortened survival.

CONCLUSIONS

Patients with EGFR mutation who receive TKI therapy may have better survival after resection of brain metastasis than patients with WT tumor. These results may inform counseling and decision-making regarding the appropriateness of resection of NSCLC brain metastasis.

ABBREVIATIONS

GPA = Graded Prognostic Assessment; KPS = Karnofsky Performance Status; NA = not applicable; NSCLC = non–small cell lung cancer; OS = overall survival; SRS = stereotactic radiosurgery; TKI = tyrosine kinase inhibitor; VIF = variance inflation factor; WBRT = whole-brain radiotherapy; WT = wild type.

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Contributor Notes

Correspondence Michael Lim: The Johns Hopkins University School of Medicine, Baltimore, MD. mlim3@jhmi.edu.

INCLUDE WHEN CITING Published online June 4, 2021; DOI: 10.3171/2020.10.JNS201787.

Disclosures Dr. Ettinger is a consultant for Beyond Spring, Inc., and the Data Safety Monitoring Board of Takeda Pharmaceutical Co. Dr. Forde is a consultant for Amgen, AstraZeneca, BMS, Daiichi Sankyo, and Janssen; receives grants from AstraZeneca, BMS, Corvus, Kyowa, and Novartis; and receives other from the Data Safety Monitoring Board of Polaris and Flame Therapeutics. Dr. Brahmer reports personal fees for advisory/consultant roles from Merck, Bristol Myers Squibb, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Sanofi, Regeneron, Amgen, and AstraZeneca; and grants from AstraZeneca, Bristol Myers Squibb, and Genentech/Roche. Dr. Feliciano is a consultant for AstraZeneca, Genentech, Bristol Myers Squibb, Merck, Eli Lilly, and Takeda; reports personal fees from AstraZeneca, Genentech, Bristol Myers Squibb, Merck, and Eli Lilly; and receives clinical or research support for the study described from AstraZeneca, Bristol Myers Squibb, and Pfizer. Dr. Levy reports personal fees from AstraZeneca, Merck, Eli Lilly, Pfizer, Celgene, Genentech, and Takeda. Dr. Naidoo is a consultant for AstraZeneca, Bristol Myers Squibb, Roche/Genentech, Pfizer, and Takeda; receives clinical or research support for the study described from Merck and AstraZeneca; and receives honoraria from AstraZeneca, Merck, Bristol Myers Squibb, Pfizer, Takeda, and Roche/Genentech. Dr. Redmond reports grants, non–study-related clinical or research support, and nonfinancial support from Elekta AB; receives honoraria, grants, personal fees, and nonfinancial support from Accuray; receives other from BioMimetix; receives other and nonfinancial support from Brainlab; and receives honoraria from the National Comprehensive Cancer Network. Dr. Kleinberg reports grants from Novocure, Novartis, Accuray, and Arbor Pharmaceuticals and personal fees from Novocure. Dr. Lim is a consultant for Tocagen and VBI and receives support of non–study-related clinical or research effort from Arbor, BMS, Accuray, DNAtrix, Tocagen, Biohaven, and Kyrin-Kyowa.

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