Diagnosis-specific Graded Prognostic Assessment Research Articles

Use of the Graded Prognostic Assessment (GPA) score in patients with brain metastases from primary tumours not represented in the diagnosis-specific GPA studies

Assessment of prognostic factors might influence treatment decisions in patients with brain metastases. Based on large studies, the diagnosis-specific graded prognostic assessment (GPA) score is a useful tool. However, patients with unknown or rare primary tumours are not represented in this model. A pragmatic approach might be use of the first GPA version which is not limited to specific primary tumours. This retrospective analysis examines for the first time whether the GPA is a valid score in patients not eligible for the diagnosis-specific GPA. It includes 71 patients with unknown primary tumour, bladder cancer, ovarian cancer, thyroid cancer or other uncommon primaries. Survival was evaluated in uni- and multivariate tests. The GPA significantly predicted survival. Moreover, improved survival was seen in patients treated with surgical resection or radiosurgery (SRS) for brain metastases. The older recursive partitioning analysis (RPA) score was significant in univariate analysis. However, the multivariate model with RPA, GPA and surgery or SRS versus none showed that only GPA and type of treatment were independent predictors of survival. Ideally, cooperative research efforts would lead to development of diagnosis-specific scores also for patients with rare or unknown primary tumours. In the meantime, a pragmatic approach of using the general GPA score appears reasonable.

Validity of Three Recently Proposed Prognostic Grading Indexes for Breast Cancer Patients With Radiosurgically Treated Brain Metastases

We tested the validity of 3 recently proposed prognostic indexes for breast cancer patients with brain metastases (METs) treated radiosurgically. The 3 indexes are Diagnosis-Specific Graded Prognostic Assessment (DS-GPA), New Breast Cancer (NBC)-Recursive Partitioning Analysis (RPA), and our index, sub-classification of RPA class II patients into 3 sub-classes (RPA class II-a, II-b and II-c) based on Karnofsky performance status, tumor number, original tumor status, and non-brain METs. This was an institutional review board-approved, retrospective cohort study using our database of 269 consecutive female breast cancer patients (mean age, 55 years; range, 26-86 years) who underwent Gamma Knife radiosurgery (GKRS) alone, without whole-brain radiation therapy, for brain METs during the 15-year period between 1996 and 2011. The Kaplan-Meier method was used to estimate the absolute risk of each event. Kaplan-Meier plots of our patient series showed statistically significant survival differences among patients stratified into 3, 4, or 5 groups based on the 3 systems (P<.001). However, the mean survival time (MST) differences between some pairs of groups failed to reach statistical significance with all 3 systems. Thus, we attempted to regrade our 269 breast cancer patients into 3 groups by modifying our aforementioned index along with the original RPA class I and III, (ie, RPA I+II-a, II-b, and II-c+III). There were statistically significant MST differences among these 3 groups without overlap of 95% confidence intervals (CIs) between any 2 pairs of groups: 18.4 (95% CI = 14.0-29.5) months in I+II-a, 9.2 in II-b (95% CI = 6.8-12.9, P<.001 vs I+II-a) and 5.0 in II-c+III (95% CI = 4.2-6.8, P<.001 vs II-b). As none of the new grading systems, DS-GPS, BC-RPA and our system, was applicable to our set of radiosurgically treated patients for comparing survivals after GKRS, we slightly modified our system for breast cancer patients.

Non-small cell lung cancer histological subtype has prognostic impact in patients with brain metastases

In patients with brain metastases from non-small cell lung cancer, the prognostic impact of primary tumour histology, a feature with increasing implications for choice of systemic therapy, is not well defined. Therefore, a multi-institutional analysis was performed: retrospective uni- and multivariate analyses in 209 patients treated with different approaches including surgery and radiosurgery. While squamous cell and large cell carcinoma patients had comparable survival, those with adenocarcinoma survived significantly longer. In multivariate models, adenocarcinoma histology was confirmed as independent prognostic factor, which complements both recursive partitioning analysis (RPA) classes and diagnosis-specific graded prognostic assessment (GPA). When evaluated together with primary tumour control, extracranial metastases, number of brain metastases, age and performance status as individual covariates rather than RPA or GPA score, adenocarcinoma histology again emerged as significant prognostic factor. A significant but small survival advantage for patients with adenocarcinoma was evident already in the time period before drugs such as pemetrexed and epidermal growth factor receptor tyrosine kinase inhibitors were available. However, the gap has widened in recently treated patients. Comparable to patients without brain metastases, primary tumour histology should be taken into account when assessing patients' prognosis and recommending treatment strategy.

Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): An American Society for Radiation Oncology evidence-based guideline

PurposeTo systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases. Methods and MaterialsKey clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management. ResultsThe choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation).Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3).Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3).Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3).It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis-specific graded prognostic assessment may be helpful. ConclusionsRadiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone).

Diagnosis-specific graded prognostic assessment score is valid in patients with brain metastases treated in routine clinical practice in two European countries

SummaryBackgroundAssessment of cancer- and host-related prognostic factors has a long tradition in patients with brain metastases. In continuation of large-scale studies performed by the Radiation Therapy Oncology Group (RTOG) in the United States, the 4-tiered diagnosis-specific graded prognostic assessment (DS-GPA) score has been developed. It stratifies patients with common primary tumours metastasizing to the brain (malignant melanoma, lung, breast, kidney and gastrointestinal cancers) into subgroups with different prognoses. However, many patients in the DS-GPA study were treated with surgical resection or radiosurgery (SRS). The present multi-institutional analysis examined for the first time whether DS-GPA is a valid score in European patients managed in routine clinical practice.Material/MethodsThis was a retrospective analysis of 412 patients with primary malignant melanoma, lung, breast, kidney or gastrointestinal cancers. Survival was evaluated in uni- and multivariate tests.ResultsDS-GPA significantly predicted survival and outperformed initial GPA, a score that is not diagnosis-specific. Median survival by DS-GPA strata (all 412 patients) was 2.7, 3.6, 7.0 and 11.3 months in the 4 groups with 0–1, 1.5–2, 2.5–3 and 3.5–4 points, respectively. The previously published survival data (median 7.2 months for all patients) could not be replicated in this cohort (median 3.6 months).ConclusionsDS-GPA is a valid prognostic score that might improve shared decision making as well as patient stratification in prospective clinical trials.

Summary Report on the Graded Prognostic Assessment: An Accurate and Facile Diagnosis-Specific Tool to Estimate Survival for Patients With Brain Metastases

Our group has previously published the Graded Prognostic Assessment (GPA), a prognostic index for patients with brain metastases. Updates have been published with refinements to create diagnosis-specific Graded Prognostic Assessment indices. The purpose of this report is to present the updated diagnosis-specific GPA indices in a single, unified, user-friendly report to allow ease of access and use by treating physicians. A multi-institutional retrospective (1985 to 2007) database of 3,940 patients with newly diagnosed brain metastases underwent univariate and multivariate analyses of prognostic factors associated with outcomes by primary site and treatment. Significant prognostic factors were used to define the diagnosis-specific GPA prognostic indices. A GPA of 4.0 correlates with the best prognosis, whereas a GPA of 0.0 corresponds with the worst prognosis. Significant prognostic factors varied by diagnosis. For lung cancer, prognostic factors were Karnofsky performance score, age, presence of extracranial metastases, and number of brain metastases, confirming the original Lung-GPA. For melanoma and renal cell cancer, prognostic factors were Karnofsky performance score and the number of brain metastases. For breast cancer, prognostic factors were tumor subtype, Karnofsky performance score, and age. For GI cancer, the only prognostic factor was the Karnofsky performance score. The median survival times by GPA score and diagnosis were determined. 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.

Predicting survival in women with breast cancer and brain metastasis

Brain metastases (BMs) are a common occurrence in patients with breast cancer, and accurately predicting survival in these patients is critical to appropriate management. A survival nomogram for breast cancer patients with BM was constructed, and its performance is compared to current predictive models of survival. A Cox proportional hazards regression with a nomogram representation was used to model survival in a population of 261 women with breast cancer and BMs treated from 1999 to 2008. The model was validated internally by 10-fold cross-validation and bootstrapping, and concordance (c) indices were calculated. The predictive performance of the nomogram described here is compared to current prognostic models, including recursive partitioning analysis, graded prognostic assessment, and diagnosis-specific graded prognostic assessment. The c-index for the model described here was 0.67. It outperformed recursive partitioning analysis, graded prognostic assessment, and diagnosis-specific graded prognostic assessment, based on c-index comparisons. The nomogram described here outperformed current strategies for survival prediction in breast cancer patients with BMs. Two additional advantages of this nomogram are its ability to predict individualized, 1-, 3-, and 5-year survival for novel patients and its straightforward representations of the relative effects of each of 9 covariates on neurologic survival. This represents a potentially valuable alternative to current models of survival prediction in this patient population.

Validation of RPA and DS-GPA in Patients Treated with Upfront Radiosurgery Alone

Brain metastases present a therapeutic challenge given that patients are living longer with more effective systemic therapies that do not penetrate the CNS. As such, we sought to validate Diagnosis Specific Graded Prognostic Assessment (DS-GPA), a new prognostic index that takes into account histology of the primary cancer, and Recursive Partitioning Analysis (RPA) system on a single institution brain metastasis database of patients treated with initial stereotactic radiosurgery (SRS) alone. We propose that if these indices can be validated and applied to SRS treated patients, it may direct patient selection for initial SRS alone versus upfront whole brain irradiation.

The effect of tumor subtype on survival and the graded prognostic assessment (GPA) for patients with breast cancer and brain metastases.

238 Background: The Diagnosis-Specific Graded Prognostic Assessment (DS-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 magnitude of their regression coefficients to define the GPA index. A GPA score of 4.0 represents the best prognosis, 0.0, the worst. 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 &lt; 0.0001). See table. 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. [Table: see text]

Introduction

The RTOG recursive partitioning analysis (RPA) classification is the gold standard for assessing the prognosis of patients with brain metastases (BM). Newer prognostic scoring systems for BM patients have been proposed, but their superiority over RPA needs to be established for patients treated with radiosurgery.380 patients with 1–3 BM were treated at the VUmc with radiosurgery (RS) from 2002 to 2011. Using baseline characteristics, patient scores were calculated for RPA, the Rotterdam-system, the score index for radiosurgery (SIR), the basic score for BM (BSBM), the graded prognostic assessment (GPA), the diagnosis-specific GPA, the Rades score, and the Golden grading system (GGS) for comparison with survival time and survival classification (⩽3 months or ⩾12 months).Median survival after RS was 7.7 months, with 3-month and 1-year overall survival (OS) of 76% and 39%, respectively. Multivariate analysis confirmed the prognostic value of performance status, age, absence of extracranial metastases, primary tumor site, gender, and steroid response for OS. The percentage of patients included within the intermediate prognostic classes ranged from 48% to 77%, and was 64% for the RPA. All scoring systems highly correlated with OS (p < 0.001). The specificity for predicting early death ranged from 85% to 98% (RPA 88%), with the unfavorable classes of Rades, GGS, BSBM and SIR performing best. The sensitivity for predicting long-term survival ranged from 10% to 69% (RPA 29%), and was highest for the favorable classes of Rades and GGS.All prognostic scoring systems correlated very well with OS. All scores shared the limitation of unbalanced proportions of patients within the prognostic classes. As the clinical superiority of more recently developed prognostic scoring systems was only modest in predicting early death and long term survival, the well-known and easy to use RPA system currently remains the standard.

The prognostic utility of LDH and disease-specific graded prognostic assessment for melanoma brain metastases.

8590 Background: A previously described diagnosis-specific graded prognostic assessment (DS-GPA) for melanoma showed that number of brain metastases (BM) and Karnofksy Performance Score (KPS) were significant prognostic factors. The purpose of this study was to test this DS-GPA in our patient population undergoing stereotactic radiosurgery (SRS) and to determine if other prognostic factors could enhance the prognostic accuracy and utility of this index. Methods: All patients who underwent SRS for melanoma BM from 1999 to 2009 were identified. Demographic, disease and survival data were collected. Continuous variables were stratified according to previously published prognostic models (age <50, 51-59, ≥60; number of BM1, 2-3, >3; KPS <70, 70-80, 90-100). The primary endpoint was overall survival (OS), calculated using Kaplan-Meier method with log rank and multivariate (Cox) analysis. Results: 126 patients underwent SRS for newly diagnosed melanoma BM. Median OS was 8.1 months (range 1.0 to 143.0 months). Increasing number of BM (10.7 versus 7.2 versus 4.9, p=0.030), LDH greater than 200 (11.4 versus 5.4, p=0.032) and decreased KPS (12.4 versus 7.1 versus 5.6, p=0.007) correlated with worse survival, but age, extracranial metastases, and treatment with temozolomide, whole brain radiation or resection did not. On multivariate analysis KPS (HR 2.89, CI 1.34-6.25) and LDH (HR 1.71, CI 1.03-2.83) maintained significance. When analyzed with only number of BM and KPS, the two validated DS-GPA prognostic factors, LDH remained a negative prognostic factor (HR 1.73, CI 1.06- 2.83). Conclusions: If confirmed in a large prospective study, the addition of LDH may improve the prognostic accuracy and utility of a previously described prognostic index based on number of BM and KPS for patients with melanoma metastatic to the brain.