Prognostic factors for patients with brain metastases vary by diagnosis, and for each diagnosis, a robust separation into different GPA scores was discerned, implying considerable heterogeneity in outcome, even within a single tumor type. In summary, these indices and related worksheet provide an accurate and facile diagnosis-specific tool to estimate survival, potentially select appropriate treatment, and stratify clinical trials for patients with brain metastases.

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BACKGROUND The diagnosis-specific Graded Prognostic Assessment (GPA) was published to clarify prognosis for patients with brain metastases. This study refines the existing Breast-GPA by analyzing a larger cohort and tumor subtype. METHODS A multi-institutional retrospective database of 400 breast cancer patients treated for newly-diagnosed brain metastases was generated. Prognostic factors significant for survival were analyzed by multivariate Cox regression (MCR) and recursive partitioning analysis (RPA). Factors were weighted by the magnitude of their regression coefficients to define the GPA index. RESULTS Significant prognostic factors by MCR and RPA were Karnofsky Performance Status (KPS), HER2, ER/PR status, and the interaction between ER/PR and HER2. RPA showed age was significant for patients with KPS 60–80. The median survival time (MST) overall was 13.8 months, and for GPA scores of 0–1.0, 1.5–2.0, 2.5–3.0 and 3.5–4.0 was 3.4 (n=23), 7.7 (n=104), 15.1 (n=140) and 25.3 (n=133) months, respectively (p < 0.0001). Among HER2-negative patients, being ER/PR-positive improved MST from 6.4 to 9.7 months whereas in HER2-positive patients, being ER/PR-positive improved MST from 17.9 to 20.7 months. The log-rank statistic (predictive power) was 110 for the Breast-GPA versus 55 for tumor subtype. CONCLUSIONS The Breast-GPA documents wide variation in prognosis and shows clear separation between subgroups of patients with breast cancer and brain metastases. This tool will aid clinical decision-making and stratification of clinical trials. These data confirm the effect of tumor subtype on survival and show the Breast-GPA offers significantly more predictive power than the tumor subtype alone.

Object The purpose of this study was to validate a new prognostic index for patients with brain metastases. This index, the Graded Prognostic Assessment (GPA), is based on an analysis of 1960 patients whose data were extracted from the Radiation Therapy Oncology Group (RTOG) database. The GPA is based on 4 criteria: age, Karnofsky Performance Scale score, number of brain metastases, and the presence/absence of extracranial metastases. Each of the 4 criteria is given a score of 0, 0.5, or 1.0, so the patient with best prognosis would have a GPA score of 4.0. Methods Between April 2005 and December 2006, 140 eligible patients with brain metastases were treated at the Gamma Knife Center at the University of Minnesota. The GPA score was calculated for each patient, and the score was then correlated with survival. Survival duration was calculated from the date treatment began for the brain metastases. Eligibility criteria included patients treated with whole-brain radiation therapy, stereotactic radiosurgery, or both. Results The median survival time in months observed in the RTOG and Minnesota data by GPA score was as follows: GPA 3.5–4.0, 11.0 and 21.7; GPA 3.0, 8.9 and 17.5; GPA 1.5–2.5, 3.8 and 5.9; and GPA 0–1.0, 2.6 and 3.0, respectively. Conclusions The University of Minnesota data correlate well with the RTOG data and validate the use of the GPA as an effective prognostic index for patients with brain metastases. Clearly, not all patients with brain metastases have the same prognosis, and treatment decisions should be individualized accordingly. The GPA score does appear to be as prognostic as the RPA and is less subjective (because the RPA requires assessment of whether the primary disease is controlled), more quantitative, and easier to use and remember. A multiinstitutional validation study of the GPA is ongoing.

Our group has previously published the Diagnosis-Specific Graded Prognostic Assessment (GPA) showing the prognostic factors associated with survival in patients with brain metastases (BM). The purpose of this study is to investigate the relationship of breast cancer subtype to the time interval from primary diagnosis (PD) to development of BM (TPDBM), number of BM at initial BM presentation and survival. We analyzed our previously described multi-institutional retrospective database of 865 breast cancer patients treated for newly-diagnosed BM from 1993 to 2010. Several factors found to be associated with survival were incorporated into the Breast-GPA, including tumor subtype. The GPA database was further analyzed to determine if the subtype correlated with the TPDBM, number of BM, and survival from PD. After exclusions for incomplete data, 383 patients remained eligible for analysis. The subtypes were approximated as follows: Luminal B: triple positive; HER2: HER2 positive/ER/PR negative; Luminal A; ER/PR positive/HER2 negative; Basal: triple negative. Patients with Basal (90), HER2 (119), Luminal B (98) and Luminal A (76) tumor subtypes had a median TPDBM of 27.5, 35.8, 47.4 and 54.4 months (p < 0.01), median survival from PD of 39.6, 66.4, 90.3 and 72.7 months (p < 0.01) and median survival from BM of 7.3, 17.9, 22.9 and 10.0 months (p < 0.01), respectively. Tumor subtype is an important prognostic factor for survival in patients with breast cancer and BM. Although TPDBM is not an independent prognostic factor for survival (and thus not part of the Breast-GPA), the TPDBM does correlate with tumor subtype but does not correlate with the number of BM. Patients with Basal and HER2 tumor subtypes have short TPDBM. Prospective studies are needed to determine if screening brain MRIs are indicated in patients with Basal or HER2 subtypes.