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
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BACKGROUND: We determined the impact of genetic alterations in EGFR, ALK, or KRAS on survival after radiotherapy for brain metastases in non-small cell lung cancer (NSCLC). METHODS: Of 172 genotyped NSCLC patients treated with radiotherapy for brain metastases in 2005-2012, 54 had cancers with EGFR mutations, 12 had ALK rearrangements, 38 had KRAS mutations, and 68 were wild-type (WT). Overall survival (OS) was determined. RESULTS: Median follow-up was 8.6 months. Median OS was 13.6 months for patients with EGFR mutations and 26.3 months for patients with ALK rearrangements, in contrast to 5.7 months for KRAS-mutant patients and 5.5 months for WT patients (P = .001). On multivariate analysis, adjusting for receipt of targeted therapy after cranial radiotherapy, ALK rearrangements were associated with improved OS (HR, 0.31; 95% CI, 0.13-0.74; P = .008). EGFR mutations were not significantly associated with improved OS on multivariate analysis (HR, 0.71; 95% CI, 0.37-1.38; P = .3). KRAS mutations were also not associated with improved OS (HR, 0.93; 95% CI, 0.59-1.47; P = .8). Receipt of targeted therapy after cranial radiotherapy was independently associated with improved OS (HR, 0.30; 95% CI, 0.17-0.54; P < .001). Receipt of chemotherapy after cranial radiotherapy, number of brain metastases, extracranial metastases, age, and performance status were also associated with OS. CONCLUSIONS: NSCLC patients with genetic alterations in ALK have improved survival outcomes after radiotherapy for brain metastases compared with EGFR, KRAS, or WT. Subsequent receipt of targeted therapy was associated with additional improvement in OS.
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Others did not find any differences in brain and bone metastases development between EGFR-mutated patients and wild type, or significant differences in number, neuroanatomic location or size of brain metastases.
“However, others did not find any differences in brain and bone metastases development between EGFR-mutated patients and wild type [30] or significant differences in number, neuroanatomic location or size of brain metastases [31].”
From A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): Old successes and future perspectives (2015) · cites this paper as [31]
Patients with EGFR-mutant NSCLC who harbor brain metastases have been reported to have median survival times as long as 2 to 3 years.
“patients with EGFR-mutant NSCLC who are harboring brain metastases have been reported as having median survival times as long as 2 to 3 years.108,109”
WBRT improves the duration of intracranial disease control compared with TKIs or stereotactic radiosurgery.
“WBRT improves the duration of intracranial disease control over TKIs or stereotactic radiosurgery (SRS), 108”
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- Authors
- Mak, K. S., Gainor, J. F., Niemierko, A., Oh, K. S., Willers, H., Choi, N. C., Loeffler, J. S., Sequist, L. V., Shaw, A. T., & Shih, H. A.
- Affiliations
- Harvard University (US)
- Corresponding author
- Mak, K. S.
- Venue
- Neuro-Oncology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-07-22
- Volume
- 17
- Issue
- 2
- Pages
- 296-302
- ISSN
- 1522-8517 (ISSN-L)
- 1523-5866
- PMC
- PMC4288518
- OpenAlex
- W2154996469
- Cited by
- 83
- References
- 49
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 6 · 2022: 5 · 2021: 9 · 2020: 6 · 2019: 9 · 2018: 7 · 2017: 10 · 2016: 12 · 2015: 9
- FWCI
- 8.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuro-Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Brain Metastases and Treatment
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- non-small cell lung cancer, brain metastases, cranial irradiation, EGFR mutation, ALK rearrangement, KRAS mutation, targeted therapy, overall survival, genetic alterations, prognostic factors
- MeSH terms
- Anaplastic Lymphoma Kinase, Adult, Aged, Aged, 80 and over, Brain Neoplasms, Carcinoma, Non-Small-Cell Lung, Female, Genotype, Humans, Lung Neoplasms, Male, Middle Aged, Proto-Oncogene Proteins, Retrospective Studies, Survival Rate, Proto-Oncogene Proteins p21(ras), Treatment Outcome, ras Proteins, Receptor Protein-Tyrosine Kinases, Kaplan-Meier Estimate, Young Adult, ErbB Receptors
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