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Tumor Histology Predicts Patterns of Failure and Survival in Patients With Brain Metastases From Lung Cancer Treated With Gamma Knife Radiosurgery

Kuremsky, J. Griff MD; Urbanic, James J. MD; Petty, W. Jeff MD§; Lovato, James F. MS; Bourland, J. Daniel PhD; Tatter, Stephen B. MD, PhD; Ellis, Thomas L. MD¶,†; McMullen, Kevin P. MD; Shaw, Edward G. MD, MA; Chan, Michael D. MD

doi: 10.1227/NEU.0000000000000072
Research-Human-Clinical Studies

BACKGROUND: We review our experience with lung cancer patients with newly diagnosed brain metastases treated with Gamma Knife radiosurgery (GKRS).

OBJECTIVE: To determine whether tumor histology predicts patient outcomes.

METHODS: Between July 1, 2000, and December 31, 2010, 271 patients with brain metastases from primary lung cancer were treated with GKRS at our institution. Included in our study were 44 squamous cell carcinoma (SCC), 31 small cell carcinoma (SCLC), and 138 adenocarcinoma (ACA) patients; 47 patients with insufficient pathology to determine subtype were excluded. No non-small cell lung cancer (NSCLC) patients received whole-brain radiation therapy (WBRT) before their GKRS, and SCLC patients were allowed to have prophylactic cranial irradiation, but no previously known brain metastases. A median of 2 lesions were treated per patient with median marginal dose of 20 Gy.

RESULTS: Median survival was 10.2 months for ACA, 5.9 months for SCLC, and 5.3 months for SCC patients (P = .008). The 1-year local control rates were 86%, 86%, and 54% for ACA, SCC, and SCLC, respectively (P = .027). The 1-year distant failure rates were 35%, 63%, and 65% for ACA, SCC, and SCLC, respectively (P = .057). The likelihood of dying of neurological death was 29%, 36%, and 55% for ACA, SCC, and SCLC, respectively (P = .027). The median time to WBRT was 11 months for SCC and 24 months for ACA patients (P = .04). Multivariate analysis confirmed SCLC histology as a significant predictor of worsened local control (hazard ratio [HR]: 6.46, P = .025) and distant failure (HR: 3.32, P = .0027). For NSCLC histologies, SCC predicted for earlier time to salvage WBRT (HR: 2.552, P = .01) and worsened overall survival (HR: 1.77, P < .0121).

CONCLUSION: Histological subtype of lung cancer appears to predict outcomes. Future trials and prognostic indices should take these histology-specific patterns into account.

ABBREVIATIONS: ACA, adenocarcinoma

GKRS, Gamma Knife radiosurgery

NSCLC, non-small cell lung cancer

PCI, prophylactic cranial irradiation

SCC, squamous cell carcinoma

SCLC, small cell carcinoma

WBRT, whole-brain radiotherapy

Departments of Radiation Oncology;

§Internal Medicine, Hematology, and Oncology;

Neurosurgery, and

Public Health Sciences, Wake Forest University, Winston-Salem, North Carolina;


Correspondence: Griff Kuremsky, MD, Medical Center Boulevard, Winston Salem, NC 27157. E-mail:

Received November 05, 2012

Accepted June 24, 2013

Copyright © by the Congress of Neurological Surgeons