International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationEstimating Survival in Melanoma Patients With Brain Metastases: An Update of the Graded Prognostic Assessment for Melanoma Using Molecular Markers (Melanoma-molGPA)
Introduction
Brain metastases are a common and complex conundrum for cancer care. An estimated 300,000 patients receive diagnoses each year of brain metastases in the United States (1), and that incidence is growing because of advances in treatment that result in patients living longer and thus at risk for brain metastases (2). It is a complex problem because of the marked heterogeneity of this patient population and the wide range of prior treatments (none vs extensive) they may have received at the time of diagnosis of the brain metastases. Of all malignancies, melanoma has not only the highest propensity to spread to the brain (3) but also rapidly expanding treatment options (surgery, stereotactic radiosurgery [SRS], whole brain radiation therapy [WBRT], targeted drug therapies, and immunotherapies [4]) resulting in greater heterogeneity. This heterogeneity has long plagued interpretation of clinical trials involving this patient population because it was essentially impossible to sufficiently stratify studies to verify that similar groups of patients were being compared.
This problem led to efforts to better understand prognosis, and progress was made. Gaspar et al (5) published the Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis for brain metastases in 1997. This prognostic index consisted of 3 classes: class I (age <65, Karnovsky performance status [KPS] ≥70, controlled primary tumor, no extracranial metastases [ECM]), class II (all patients not in classes I or III), and class III (KPS <70), which correlated with median survival times of 7.7, 4.5 and 2.3 months, respectively.
Our group published a new more quantitative prognostic index, the Graded Prognostic Assessment (GPA) in 2008 based on age, KPS, ECM, and number of brain metastases (6). Those prognostic factors were weighted by regression coefficients and scaled in such manner that patients with the best/worst prognosis would have a GPA of 4.0/0.0, respectively. In 2010, we refined the GPA to be diagnosis specific when we found that survival varies by diagnosis and diagnosis-specific prognostic factors (7). The Breast-GPA was then further refined using tumor subtype (8) and a summary report was published (9). More recently, the Lung-GPA was updated using molecular factors (EGFR/ALK status) 10, 11, respectively.
The original Melanoma-GPA found that only 2 factors were significant (KPS and the number of brain metastases). We recently published the effect of gene mutations on survival in melanoma patients with brain metastases (12). The purpose of this study was to update the Melanoma-GPA using molecular markers and a larger sample size from the current treatment era.
Section snippets
Methods
A multi-institutional retrospective institutional review board—approved database was created, comprising 823 melanoma patients with newly diagnosed brain metastases from 2006 to 2015. Variables considered included the 4 in the existing GPA: KPS, age, presence of extracranial metastases, and number of brain metastases. Additional variables included gene mutation status (BRAF, CKIT, and NRAS), sex, volume of brain metastases (for those treated with SRS), and time from primary diagnosis to brain
Results
The patient characteristics, survival by gene status (BRAF, CKIT, and NRAS), risk of death by treatment and treatment era, and a summary of drug therapy for this patient cohort have been previously published (13). The treatment breakdown for the 823 patients was as follows: 56% SRS alone, 12% surgery + SRS, 11% WBRT, 9% WBRT + SRS, 4% surgery + WBRT, and 1% surgery + WBRT + SRS.
Table 1 shows the multivariable model used to select and weight factors in the Melanoma-molGPA. Five prognostic
Discussion
A better estimate of survival will facilitate the doctor/patient/family discussion of whether and which treatment is appropriate. A patient with a Melanoma-molGPA of 3.5 to 4.0 can expect to live nearly 3 years, and more aggressive treatment may be indicated. On the other hand, a patient who has a GPA of 0.0 to 1.0 has an expected survival of <5 months and therefore may choose hospice. These decisions are difficult, and the cost of hope can be enormous (13). The QUARTZ trial, a randomized trial
Acknowledgment
The authors thank Susan Lowry, Database Programmer/Analyst and REDCap Administrator, Biostatistical Design and Analysis Center, Clinical and Translational Science Institute, University of Minnesota.
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Note—An online CME test for this article can be taken at https://academy.astro.org.
Supported by National Institutes of Health (NIH) grant No. UL1TR000114 from the National Center for Advancing Translational Sciences (NCATS), and by NIH grant No. P30 CA77598 using the Biostatistics and Bioinformatics Core shared resource of the Masonic Cancer Center, University of Minnesota, and the NCATS. The design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication is solely the responsibility of the authors and does not necessarily represent the official views of the funders or sponsors.
Conflict of interest: J.P.K. has financial connections with Varian; H.A.S. has financial connections with Genentech; D.R. has financial connections with Varian, Siemens, Accuray, BrainLab, and Elekta; and M.P.M. has financial connections with Abbott, Novelos, Phillips, BMS, Celldex, Roche, Elekta, Novocure, Novartis, Cavion, and Pharmacyclics. The other authors report no conflict of interest.