Survival in Patients with Brain Metastases: Summary Report on the Updated Diagnosis-Specific Graded Prognostic Assessment and Definition of the Eligibility Quotient

Paul W. Sperduto, Shane Mesko, Jing Li, Daniel Cagney, Ayal Aizer, Nancy U. Lin, Eric Nesbit, Tim J. Kruser, Jason Chan, Steve Braunstein, Jessica Lee, John P. Kirkpatrick, Will Breen, Paul D. Brown, Diana Shi, Helen A. Shih, Hany Soliman, Arjun Sahgal, Ryan Shanley, William A. SperdutoEmil Lou, Ashlyn Everett, Drexell H. Boggs, Laura Masucci, David Roberge, Jill Remick, Kristin Plichta, John M. Buatti, Supriya Jain, Laurie E. Gaspar, Cheng Chia Wu, Tony J.C. Wang, John Bryant, Michael Chuong, Yi An, Veronica Chiang, Toshimichi Nakano, Hidefumi Aoyama, Minesh P. Mehta

Research output: Contribution to journalArticlepeer-review

206 Scopus citations

Abstract

PURPOSE Conventional wisdom has rendered patients with brain metastases ineligible for clinical trials for fear that poor survival could mask the benefit of otherwise promising treatments. Our group previously published the diagnosis-specific Graded Prognostic Assessment (GPA). Updates with larger contemporary cohorts using molecular markers and newly identified prognostic factors have been published. The purposes of this work are to present all the updated indices in a single report to guide treatment choice, stratify research, and define an eligibility quotient to expand eligibility. METHODS A multi-institutional database of 6,984 patients with newly diagnosed brain metastases underwent multivariable analyses of prognostic factors and treatments associated with survival for each primary site. Significant factors were used to define the updated GPA. GPAs of 4.0 and 0.0 correlate with the best and worst prognoses, respectively. RESULTS Significant prognostic factors varied by diagnosis and new prognostic factors were identified. Those factors were incorporated into the updated GPA with robust separation (P, .01) between subgroups. Survival has improved, but varies widely by GPA for patients with non–small-cell lung, breast, melanoma, GI, and renal cancer with brain metastases from 7-47 months, 3-36 months, 5-34 months, 3-17 months, and 4-35 months, respectively. CONCLUSION Median survival varies widely and our ability to estimate survival for patients with brain metastases has improved. The updated GPA (available free at brainmetgpa.com) provides an accurate tool with which to estimate survival, individualize treatment, and stratify clinical trials. Instead of excluding patients with brain metastases, enrollment should be encouraged and those trials should be stratified by the GPA to ensure those trials make appropriate comparisons. Furthermore, we recommend the expansion of eligibility to allow for the enrollment of patients with previously treated brain metastases who have a 50% or greater probability of an additional year of survival (eligibility quotient . 0.50).

Original languageEnglish (US)
Pages (from-to)3773-3784
Number of pages12
JournalJournal of Clinical Oncology
Volume38
Issue number32
DOIs
StatePublished - Nov 10 2020

Bibliographical note

Funding Information:
Supported by National Institutes of Health Grants No. UL1TR002494 from the National Center for Advancing Translational Sciences and P30CA77598 utilizing the Biostatistics and Bioinformatics Core shared resource of the Masonic Cancer Center, University of Minnesota and the National Center for Advancing Translational Sciences. No author received support for the work in this manuscript other than R.S. for statistical analyses.

Publisher Copyright:
Copyright © 2020 American Society of Clinical Oncology. All rights reserved.

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