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. 2015 Aug 1;92(5):1008-1015.
doi: 10.1016/j.ijrobp.2015.04.032. Epub 2015 Apr 23.

Competing Risk Analysis of Neurologic versus Nonneurologic Death in Patients Undergoing Radiosurgical Salvage After Whole-Brain Radiation Therapy Failure: Who Actually Dies of Their Brain Metastases?

John T Lucas Jr  1 , Hentry G Colmer 4th  2 , Lance White  2 , Nora Fitzgerald  3 , Scott Isom  3 , John D Bourland  4 , Adrian W Laxton  5 , Stephen B Tatter  6 , Michael D Chan  7
Affiliations

Competing Risk Analysis of Neurologic versus Nonneurologic Death in Patients Undergoing Radiosurgical Salvage After Whole-Brain Radiation Therapy Failure: Who Actually Dies of Their Brain Metastases?

John T Lucas Jr et al. Int J Radiat Oncol Biol Phys. .

Abstract

Purpose: To estimate the hazard for neurologic (central nervous system, CNS) and nonneurologic (non-CNS) death associated with patient, treatment, and systemic disease status in patients receiving stereotactic radiosurgery after whole-brain radiation therapy (WBRT) failure, using a competing risk model.

Patients and methods: Of 757 patients, 293 experienced recurrence or new metastasis following WBRT. Univariate Cox proportional hazards regression identified covariates for consideration in the multivariate model. Competing risks multivariable regression was performed to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for both CNS and non-CNS death after adjusting for patient, disease, and treatment factors. The resultant model was converted into an online calculator for ease of clinical use.

Results: The cumulative incidence of CNS and non-CNS death at 6 and 12 months was 20.6% and 21.6%, and 34.4% and 35%, respectively. Patients with melanoma histology (relative to breast) (aHR 2.7, 95% CI 1.5-5.0), brainstem location (aHR 2.1, 95% CI 1.3-3.5), and number of metastases (aHR 1.09, 95% CI 1.04-1.2) had increased aHR for CNS death. Progressive systemic disease (aHR 0.55, 95% CI 0.4-0.8) and increasing lowest margin dose (aHR 0.97, 95% CI 0.9-0.99) were protective against CNS death. Patients with lung histology (aHR 1.3, 95% CI 1.1-1.9) and progressive systemic disease (aHR 2.14, 95% CI 1.5-3.0) had increased aHR for non-CNS death.

Conclusion: Our nomogram provides individual estimates of neurologic death after salvage stereotactic radiosurgery for patients who have failed prior WBRT, based on histology, neuroanatomical location, age, lowest margin dose, and number of metastases after adjusting for their competing risk of death from other causes.

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Conflict of interest statement

Conflict of interest: none.

Figures

Fig. 1
Fig. 1
Cumulative incidence of central nervous system and non—central nervous system death.
Fig. 2
Fig. 2
Cumulative incidence of central nervous system (CNS) and non-CNS death by patient-, treatment-, and disease-related factors. (a) Histology, (b) brainstem location, (c) in-field failure versus no in-field failure, (d) distant brain failure versus no distant brain failure, (e) disease status—progressive versus no evidence of disease/stable, (f) low margin dose.
Fig. 3
Fig. 3
Nomogram calibration plot.
See this image and copyright information in PMC

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