The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases

Journal Article · Sat Oct 01 00:00:00 EDT 2016 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/J.IJROBP.2016.06.006· OSTI ID:22645658

Yang, T. Jonathan; Beal, Kathryn ^[1]; Pan, Hubert; Brown, Paul D. ^[2]; Bangdiwala, Ananta; Shanley, Ryan ^[3]; Yeh, Norman; Gaspar, Laurie E. ^[4]; Braunstein, Steve; Sneed, Penny ^[5]; Boyle, John; Kirkpatrick, John P. ^[6]; Mak, Kimberley S.; Shih, Helen A. ^[7]; Engelman, Alex ^[8]; Roberge, David ^[9]; Arvold, Nils D.; Alexander, Brian; Awad, Mark M. ^[10]; others, and

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1. Sloan Kettering Cancer Center, New York, New York (United States)
2. MD Anderson Cancer Center, Houston, Texas (United States)
3. University of Minnesota, Masonic Cancer Center, Biostatistics, Minneapolis, Minnesota (United States)
4. University of Colorado–Denver, Denver, Colorado (United States)
5. University of California–San Francisco, San Francisco, California (United States)
6. Duke University, Durham, North Carolina (United States)
7. Massachusetts General Hospital, Boston, Massachusetts (United States)
8. University of Maryland, Baltimore, Maryland (United States)
9. CHUM, University of Montreal, Montreal, Quebec (Canada)
10. Dana Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (United States)

Purpose: Lung cancer remains the most common cause of both cancer mortality and brain metastases (BM). The purpose of this study was to assess the effect of gene alterations and tyrosine kinase inhibition (TKI) on median survival (MS) and cause of death (CoD) in patients with BM from lung adenocarcinoma (L-adeno). Methods: A multi-institutional retrospective database of patients with L-adeno and newly diagnosed BM between 2006 and 2014 was created. Demographics, gene alterations, treatment, MS, and CoD were analyzed. The treatment patterns and outcomes were compared with those in prior trials. Results: Of 1521 L-adeno patients, 816 (54%) had known alteration status. The gene alteration rates were 29%, 10%, and 26% for EGFR, ALK, and KRAS, respectively. The time from primary diagnosis to BM for EGFR−/+ was 10/15 months (P=.02) and for ALK−/+ was 10/20 months (P<.01), respectively. The MS for the group overall (n=1521) was 15 months. The MS from first treatment for BM for EGFR and ALK−, EGFR+, ALK+ were 14, 23 (P<.01), and 45 (P<.0001) months, respectively. The MS after BM for EGFR+ patients who did/did not receive TKI before BM was 17/30 months (P<.01), respectively, but the risk of death was not statistically different between TKI-naïve patients who did/did not receive TKI after the diagnosis of BM (EGFR/ALK hazard ratios: 1.06 [P=.84]/1.60 [P=.45], respectively). The CoD was nonneurologic in 82% of patients with known CoD. Conclusion: EGFR and ALK gene alterations are associated with delayed onset of BM and longer MS relative to patients without these alterations. The CoD was overwhelmingly nonneurologic in patients with known CoD.

• OSTI ID: 22645658
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 96, Issue 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
BRAIN
DEATH
GENES
INHIBITION
LUNGS
PATIENTS
PHOSPHOTRANSFERASES
TYROSINE