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Int J Radiat Oncol Biol Phys. 2016 Jun 1;95(2):673-9. doi: 10.1016/j.ijrobp.2016.01.037. Epub 2016 Feb 2.

Impact of Deferring Radiation Therapy in Patients With Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Develop Brain Metastases.

Author information

1
Department of Radiation Oncology, Yale School of Medicine, New Haven, Connecticut. Electronic address: william.magnuson@yale.edu.
2
Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut.
3
Yale School of Medicine, New Haven, Connecticut.
4
Department of Medical Oncology, Yale School of Medicine, New Haven, Connecticut.
5
Department of Radiation Oncology, Yale School of Medicine, New Haven, Connecticut.

Abstract

PURPOSE:

To perform a retrospective analysis of patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma who developed brain metastases (BM) to evaluate our hypothesis that the use of upfront EGFR-tyrosine kinase inhibitors (TKIs), and deferral of radiation therapy (RT), would result in inferior intracranial progression-free survival but similar overall survival (OS).

METHODS AND MATERIALS:

Of 202 patients diagnosed with EGFR-mutant NSCLC between July 1, 2008, and December 31, 2014, 71 developed BM. Twenty-one patients were excluded owing to prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after whole-brain radiation therapy (WBRT)/stereotactic radiosurgery (SRS) or <6 months' follow-up. Of the remaining 50 patients, 17 received upfront EGFR-TKI followed by SRS or WBRT, 17 WBRT then EGFR-TKI, and 16 SRS followed by EGFR-TKI. Disease-specific-graded prognostic assessment was similar among all 3 groups.

RESULTS:

The median OS was longer in the upfront RT group compared with the upfront EGFR-TKI group (34.1 vs 19.4 months; P=.01). On subgroup analysis, the SRS group had longer OS than the upfront EGFR-TKI group (58.4 vs 19.4 months; P=.01), but the WBRT group did not (29.9 vs 19.4 months; P=.09). Intracranial progression-free survival was improved in patients receiving upfront RT compared with those receiving upfront EGFR-TKI (37.9 vs 10.6 months; P<.001).

CONCLUSIONS:

The present study suggests that the use of upfront EGFR-TKI, and the deferral of SRS or WBRT, may result in inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. A prospective, multi-institutional, randomized trial of upfront EGFR-TKI with RT at intracranial progression versus upfront RT followed by EGFR-TKI is urgently needed.

PMID:
27034176
DOI:
10.1016/j.ijrobp.2016.01.037
[Indexed for MEDLINE]

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