Examining the Effect of ALK and EGFR Mutations on Survival Outcomes in Surgical Lung Brain Metastasis Patients

Author:

Mannam Sneha Sai1,Bray David P.2,Nwagwu Chibueze D.3,Zhong Jim4ORCID,Shu Hui-Kuo4,Eaton Bree4,Sudmeier Lisa4,Goyal Subir5,Deibert Christopher6,Nduom Edjah K.6,Olson Jeffrey6,Hoang Kimberly B.6

Affiliation:

1. Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

2. Department of Neurosurgery, Jefferson University Hospital, Philadelphia, PA 19107, USA

3. Department of Neurosurgery, Brigham and Women’s Hospital, Boston, MA 02115, USA

4. Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA

5. Biostatistics Shared Resource, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA

6. Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA

Abstract

In the context of the post-genomic era, where targeted oncological therapies like monoclonal antibodies (mAbs) and tyrosine-kinase inhibitors (TKIs) are gaining prominence, this study investigates whether these therapies can enhance survival for lung carcinoma patients with specific genetic mutations—EGFR-amplified and ALK-rearranged mutations. Prior to this study, no research series had explored how these mutations influence patient survival in cases of surgical lung brain metastases (BMs). Through a multi-site retrospective analysis, the study examined patients who underwent surgical resection for BM arising from primary lung cancer at Emory University Hospital from January 2012 to May 2022. The mutational statuses were determined from brain tissue biopsies, and survival analyses were conducted. Results from 95 patients (average age: 65.8 ± 10.6) showed that while 6.3% had anaplastic lymphoma kinase (ALK)-rearranged mutations and 20.0% had epidermal growth factor receptor (EGFR)-amplified mutations—with 9.5% receiving second-line therapies—these mutations did not significantly correlate with overall survival. Although the sample size of patients receiving targeted therapies was limited, the study highlighted improved overall survival and progression-free survival rates compared to earlier trials, suggesting advancements in systemic lung metastasis treatment. The study suggests that as more targeted therapies emerge, the prospects for increased overall survival and progression-free survival in lung brain metastasis patients will likely improve.

Funder

National Center for Advancing Translational Sciences of the National Institutes of Health

Biostatistics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference63 articles.

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4. Maltsev, N., Rzhetsky, A., and Gilliam, T.C. (2014). Advances in Experimental Medicine and Biology, Springer.

5. Management of Brain Metastases According to Molecular Subtypes;Soffietti;Nat. Rev. Neurol.,2020

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