Basic Score For Brain Metastases Research Articles

Prognosis versus Actual Outcomes in Stereotactic Radiosurgery of Brain Metastases: Reliability of Common Prognostic Parameters and Indices.

This study aims to evaluate the clinical outcome of stereotactic radiosurgery as the sole treatment for brain metastases and to assess prognostic factors influencing survival. A total of 108 consecutive patients with 213 metastases were retrospectively analyzed. Treatment was determined with close-meshed MRI follow-up. Various prognostic factors were assessed, and several prognostic indices were compared regarding their reliability to estimate overall survival. Median overall survival was 15 months; one-year overall survival was 50.5%. Both one- and two-year local controls were 90.9%. The rate of new metastases after SRS was 49.1%. Multivariate analysis of prognostic factors revealed that the presence of extracranial metastases, male sex, lower KPI, and progressive extracranial disease were significant risk factors for decreased survival. Of all evaluated prognostic indices, the Basic Score for Brain Metastases (BSBMs) showed the best correlation with overall survival. A substantial survival advantage was found for female patients after SRS when compared to male patients (18 versus 9 months, p = 0.003). SRS of brain metastasis is a safe and effective treatment option when frequent monitoring for new metastases with MRI is performed. Common prognostic scores lack reliable estimation of survival times. Female sex should be considered as an additional independent positive prognostic factor influencing survival.

Establishment of a prognostic risk prediction modelfor non-small cell lung cancer patients with brainmetastases: a retrospective study.

Patients with non-small cell lung cancer (NSCLC) who develop brain metastases (BM) have a poor prognosis. This study aimed to construct a clinical prediction model to determine the overall survival (OS) of NSCLC patients with BM. A total of 300 NSCLC patients with BM at the Yunnan Cancer Centre were retrospectively analysed. The prediction model was constructed using the least absolute shrinkage and selection operator-Cox regression. The bootstrap sampling method was employed for internal validation. The performance of our prediction model was compared using recursive partitioning analysis (RPA), graded prognostic assessment (GPA), the update of the graded prognostic assessment for lung cancer using molecular markers (Lung-molGPA), the basic score for BM (BSBM), and tumour-lymph node-metastasis (TNM) staging. The prediction models comprising 15 predictors were constructed. The area under the curve (AUC) values for the 1-year, 3-year, and 5-year time-dependent receiver operating characteristic (curves) were 0.746 (0.678-0.814), 0.819 (0.761-0.877), and 0.865 (0.774-0.957), respectively. The bootstrap-corrected AUC values and Brier scores for the prediction model were 0.811 (0.638-0.950) and 0.123 (0.066-0.188), respectively. The time-dependent C-index indicated that our model exhibited significantly greater discrimination compared with RPA, GPA, Lung-molGPA, BSBM, and TNM staging. Similarly, the decision curve analysis demonstrated that our model displayed the widest range of thresholds and yielded the highest net benefit. Furthermore, the net reclassification improvement and integrated discrimination improvement analyses confirmed the enhanced predictive power of our prediction model. Finally, the risk subgroups identified by our prognostic model exhibited superior differentiation of patients' OS. The clinical prediction model constructed by us shows promise in predicting OS for NSCLC patients with BM. Its predictability is superior compared with RPA, GPA, Lung-molGPA, BSBM, and TNM staging.

New prognostic system specific for epidermal growth factor receptor-mutated lung cancer brain metastasis.

Brain metastases (BM) from lung cancer are heterogeneous, and accurate prognosis is required for effective treatment strategies. This study aimed to identify prognostic factors and develop a prognostic system exclusively for epidermal growth factor receptor (EGFR)-mutated lung cancer BM. In total, 173 patients with EGFR-mutated lung cancer from two hospitals who developed BM and received tyrosine kinase inhibitor (TKI) and brain radiation therapy (RT) were included. Univariate and multivariate analyses were performed to identify significant EGFR-mutated BM prognostic factors to construct a new EGFR recursive partitioning analysis (RPA) prognostic index. The predictive discrimination of five prognostic scoring systems including RPA, diagnosis-specific prognostic factors indexes (DS-GPA), basic score for brain metastases (BS-BM), lung cancer using molecular markers (lung-mol GPA) and EGFR-RPA were analyzed using log-rank test, concordance index (C-index), and receiver operating characteristic curve (ROC). The potential predictive factors in the multivariable analysis to construct a prognostic index included Karnofsky performance status, BM at initial lung cancer diagnosis, BM progression after TKI, EGFR mutation type, uncontrolled primary tumors, and number of BM. In the log-rank test, indices of RPA, DS-GPA, lung-mol GPA, BS-BM, and EGFR-RPA were all significant predictors of overall survival (OS) (p ≤ 0.05). The C-indices of each prognostic score were 0.603, 0.569, 0.613, 0.595, and 0.671, respectively; The area under the curve (AUC) values predicting 1-year OS were 0.565 (p=0.215), 0.572 (p=0.174), 0.641 (p=0.007), 0.585 (p=0.106), and 0.781 (p=0.000), respectively. Furthermore, EGFR-RPA performed better in terms of calibration than other prognostic indices.BM progression after TKI and EGFR mutation type were specific prognostic factors for EGFR-mutated lung cancer BM. EGFR-RPA was more precise than other models, and useful for personal treatment.

Brain Metastasis Growth Kinetics: A Novel Prognosticator for Stereotactic Radiotherapy

AimsThe rate of size change in brain metastasis may have clinical implications on tumour biology and prognosis for patients who receive stereotactic radiotherapy (SRT). We analysed the prognostic value of brain metastasis size kinetics and propose a model for patients with brain metastases treated with linac-based SRT in predicting overall survival. Materials and methodsWe analysed the patients receiving linac-based SRT between 2010 and 2020. Patient and oncological factors, including the changes in sizes of brain metastasis between the diagnostic and stereotactic magnetic resonance imaging, were collected. The associations between prognostic factors and overall survival were assessed using Cox regression with least absolute selection and shrinkage operator (LASSO) checked by 500 bootstrap replications. Our prognostic score was calculated by evaluating the most statistically significant factors. Patients were grouped and compared according to our proposed score, Score Index for Radiosurgery in Brain Metastases (SIR) and Basic Score for Brain Metastases (BS-BM). ResultsIn total, 85 patients were included. We developed the prognostic model based on the most important predictors of overall survival: growth kinetics, i.e. percentage change in brain metastasis size per day between the diagnostic and stereotactic magnetic resonance imaging (hazard ratio per 1% increase, 1.32; 95% confidence interval 1.06–1.65), extracranial oligometastatic diseases (≤5 involvements) (hazard ratio 0.28; 95% confidence interval 0.16–0.52) and the presence of neurological symptoms (hazard ratio 2.99; 95% confidence interval 1.54–5.81). Patients with scores 0, 1, 2 and 3 had a median overall survival of 44.4 (95% confidence interval 9.6–not reached), 20.4 (95% confidence interval 15.6–40.8), 12.0 (95% confidence interval 7.2–22.8) and 2.4 (95% confidence interval 1.2–not reached) years, respectively. The optimism-corrected c-indices for our proposed model, SIR and BS-BM were 0.65, 0.58 and 0.54, respectively. ConclusionsBrain metastasis growth kinetics is a valuable metric for survival outcomes of SRT. Our model is useful in identifying patients with brain metastasis treated with SRT with different overall survival.

Validation of a novel prognostic index: BMS-Score for patients with brain metastases of small cell lung cancer.

A new disease-specific prognostic score (Disease-specific Prognostic Score for Patients With Brain Metastases From Small-cell Lung Cancer termed BMS-Score) was published to clarify the prognosis of patients with brain metastasis (BM) of small cell lung cancer (SCLC) treated with whole brain radiotherapy (WBRT). The purpose of the present study was to validate the prognostic value of the newly proposed BMS-Score through comparison with three other previously published prognostic indices. In total, 451 patients with BM of SCLC treated with WBRT at the Shanxi Province Cancer Hospital from January 2010 to December 2019 were included. The clinical characteristics of all patients were recorded and follow-up was through April 2020. Overall survival (OS) was calculated by Kaplan-Meier analysis, and univariate and multivariate analyses were used to calculate the prognostic cofactors. The concordance index (C-index) was used to assess the prognostic value of the following four prognostic systems: recursive partitioning analysis (RPA), diagnosis-specific graded prognostic assessment (DS-GPA), basic score for brain metastases (BSBM), and the newly proposed BMS-Score. The independent factors affecting the prognosis of SCLC patients with BM included the Karnofsky performance score (KPS), number of brain metastases, extracranial metastases (ECM) state, and whether treatment had been received before BM. RPA, BSBM, DS-GPA, and BMS-Score log-rank test P values were all less than 0.001 among each group (P<0.001). The C-indices of the four groups were 0.554, 0.584, 0.588, and 0.643, respectively. The four prognostic scoring systems exhibited medium predictive value for SCLC. The BMS-Score had the best applicability compared with the other three prognosis indices.

Cumulative Intracranial Tumor Volume as a Prognostic Factor in Patients with Brain Metastases Undergoing Stereotactic Radiosurgery.

Approximately 25-35% of all cancer patients suffer from brain metastases (BM), and many of them-in particular, those with a limited number of intracranial tumors-are treated with stereotactic radiosurgery (SRS). Accurate prediction of survival remains a key clinical challengein this population. Several prognostic scales have been developed to facilitate this prognostication, including the Recursive Partitioning Analysis (RPA) classification, the modified Recursive Partitioning Analysis (mRPA) subclassifications, the Basic Score for Brain Metastases (BS-BM), the Score Index for Radiosurgery (SIR), the Graded Prognostic Assessment (GPA), and the diagnosis-specific Graded Prognostic Assessment (dsGPA). However, none of these scales include consideration of the cumulative intracranial tumor volume (CITV), which is defined as the sum of all intracranial tumor volumes. Since there is mounting evidence that the CITV carries significant prognostic value in SRS-treated patients with BM, this variableshould be consideredduring survival prognostication, along with other pertinent clinical, pathological, and molecular characteristics.

Outcome and prognostic factors for older patients undergoing radiosurgery for brain metastases

PurposeOlder patients with brain metastases (BM) are often excluded from clinical trials. The aim of our study was to investigate the outcomes following Gamma Knife radiosurgery (GKRS) in young old (65–74 years) and very old (≥75 years) patients with BM. MethodsBetween October 2012 and October 2018, we treated 89 patients aged ≥65 years with GKRS. Patients were divided in two group: young old (YO) and very old (VO) patients. At baseline G8, Graded Prognostic Assessment (DS-GPA) and Basic Score for Brain Metastases (BSBM) were assessed for all patients. Survival analysis was estimated using the Kaplan-Meier (KM) method. Cox regression model was used to investigate the influence of significant factors on KM. ResultsMedian age at the time of GKRS was 72.2 years (range 65–87). A mean of 2.52 lesions were treated per patient (range 1–14). Median overall survival (OS) for YO and VO patients was 14.2 and 15.7 months, respectively. At univariate analysis, there were no significant differences in OS between the two age groups. A high BSBM (p ≤ .0001) and a high DS-GPA score (p = .0069) were associated with longer survival. A low DS-GPA score was the most powerful independent factor for predicting short survival (HR 1.76, 95% CI 1.25–2.46, p = .001) at multivariate analysis. ConclusionGKRS is a safe approach to treat BM in elderly patients. DS-GPA score represents an important prognostic factor for survival in elderly patients undergoing GKRS.

Validation of recursive partitioning analysis, graded prognostic assessment and basic score for brain metastases as prognostic indices among patients with brain metastases treated with radiotherapy in Indonesia

AbstractIntroduction:Metastatic brain disease is still a major contributor to cancer treatment failure. Various treatments have improved in the recent decades, which allow for better control of brain metastatic lesions. Various prognostic scoring tools have been developed and used worldwide to stratify patients with brain metastases to determine who will benefit most from aggressive treatment. The three most commonly used prognostic scoring tools are recursive partitioning analysis (RPA), basic score for brain metastases (BSBM) and graded prognostic assessment (GPA). The aim of this study is to validate these scoring tools using an Indonesian cancer patient population.Method:A retrospective analysis of all patients presenting with brain metastases from January 2012 until December 2014, through using hospital medical records, was conducted. All patients receiving whole brain radiotherapy during this period were included in this study. A follow-up with a telephone call was carried out to determine the patient’s health and survival status. Uncontactable patients were excluded from the analysis. Survival analysis was carried out by stratifying patients based on the three prognostic scoring systems.Result:A total of 80 patients were eligible to be included in the study, with 18 excluded due to being uncontactable. The remaining 62 patients’ data were analysed and stratified with all three scoring systems. The RPA was found to confer better stratification than BSBM and GPA in our study population.Conclusion:GPA was non-prognostic in our study population and BSBM was less prognostic, especially in the middle group, class 1 and class 2. Those BSBM class 1 and class 2 did not provide good prognostic stratification in our study population, whereas RPA was proven to be the best in stratifying patients’ prognosis with brain metastases in our study population.

Analysis of Survival of Patients with Brain Metastases According to Prognostic Indexes and Treatment Strategies.

To retrospectively evaluate the overall survival (OS) of patients with brain metastases (BMs) who had been treated with whole brain radiotherapy (WBRT) and Gamma Knife (GK) according to prognostic factors and prognostic index scores. The study included 91 patients with BMs who had been treated with WBRT and/or GK between 2014 and 2017. The patients with BMs were retrospectively evaluated regarding age, sex, Karnofsky Performance Status (KPS), recursive partitioning analysis (RPA) class, basic score for BM (BS-BM), Graded Prognostic Assessment (DS-GPA) index, primary tumour type, extracranial metastases, primary tumour control, number of BMs, and brain metastasectomy. A univariate analysis of the OS was performed using the Kaplan-Meier method, supplemented by the log-rank test. We also applied a multivariate survival analysis using the Cox regression model. The median OS for all patients with BMs was 6 months. Meanwhile, the median OSs for those with WBRT, GK, and WBRT-GK treatment were 6, 4, and 15 months, respectively (p=0.00). In the multivariate analysis, the female sex (p=0.030), brain metastasectomy (p=0.047), treatment with WBRT-GK (p=0.001), and the controlled primary tumour (p=0.007) significantly correlated with the OS. Furthermore, the BS-BM (p=0.022) was closely related with the OS compared to the RPA and DS-GPA in the multivariate analysis. The BS-BM was found to better predict the survival of patients with BMs according to the prognostic index scores in the multivariate analysis. Thus, our data suggest that the BS-BM is the most appropriate prognostic index.

Prognostic grading system specifically for elderly patients with brain metastases after stereotactic radiosurgery: a 2-institution study.

OBJECTIVEWith the aging of the population, increasing numbers of elderly patients with brain metastasis (BM) are undergoing stereotactic radiosurgery (SRS). Among recently reported prognostic grading indexes, only the basic score for brain metastases (BSBM) is applicable to patients 65 years or older. However, the major weakness of this system is that no BM-related factors are graded. This prompted the authors to develop a new grading system, the elderly-specific (ES)-BSBM.METHODSFor this IRB-approved, retrospective cohort study, the authors used their prospectively accumulated database comprising 3267 consecutive patients undergoing Gamma Knife SRS for BMs during the 1998-2016 period at the Mito GammaHouse. Among these 3267 patients, 1789 patients ≥ 65 years of age were studied (Yamamoto series [Y-series]). Another series of 1785 patients ≥ 65 years of age in whom Serizawa and colleagues performed Gamma Knife SRS during the same period (Serizawa series [S-series]) was used for validity testing of the ES-BSBM.RESULTSTwo factors were identified as strongly impacting longer survival after SRS by means of multivariable analysis using the Cox proportional hazard model with a stepwise selection procedure. These factors are the number of tumors (solitary vs multiple: HR 1.450, 95% CI 1.299-1.621; p < 0.0001) and cumulative tumor volume (≤ 15 cm3 vs > 15 cm3: HR 1.311, 95% CI 1.078-1.593; p = 0.0067). The new index is the addition of scores 0 and 1 for these 2 factors to the BSBM. The ES-BSBM system is based on categorization into 3 classes by adding these 2 scores to those of the original BSBM. Each ES-BSBM category has 2 possible scores. For the category ES-BSBM 4-5, the score is either 4 or 5; for ES-BSBM 2-3, the score is either 2 or 3; and for ES-BSBM 0-1, the score is either 0 or 1. In the Y-series, the median survival times (MSTs, months) after SRS were 17.5 (95% CI 15.4-19.3) in ES-BSBM 4-5, 6.9 (95% CI 6.4-7.4) in ES-BSBM 2-3, and 2.8 (95% CI 2.5-3.6) in ES-BSBM 0-1 (p < 0.0001). Also, in the S-series, MSTs were, respectively, 20.4 (95% CI 17.2-23.4), 7.9 (95% CI 7.4-8.5), and 3.2 (95% CI 2.8-3.6) (p < 0.0001). The ES-BSBM system was shown to be applicable to patients with all primary tumor types as well as to those 80 years or older.CONCLUSIONSThe authors found that the addition of the number of tumors and cumulative tumor volume as scoring factors to the BSBM system significantly improved the prognostic value of this index. The present study is strengthened by testing the ES-BSBM in a different patient group.

Comparison of Prognostic Indices in NSCLC Patients with Brain Metastases after Radiosurgery.

Prognostic indices are commonly used in the context of brain metastases radiotherapy to guide patient decision-making and clinical trial stratification. This study is to choose an appropriate prognostic index (PI) for non-small cell lung cancer (NSCLC) patients with brain metastases (BM) who underwent radiosurgery. A total of 103 patients with BM from NSCLC receiving radiosurgery were analyzed retrospectively. There are six prognostic factors were analyzed, including age, primary tumor control, extracranial metastasis, KPS score, number of lesions, max lesion volume; and four prognostic indices were compared, include Recursive Partitioning Analysis (RPA),Graded Prognostic Assessment (GPA), Score Index for Radiosurgery (SIR), Basic Score for Brain Metastases (BSBM). Survival curves were estimated with the Kaplan-Meier method and compared with a log-rank test stratified according to the PIs. Univariate and multivariate analysis was performed using the Cox regression analysis. The PI's predictive capacity was compared in terms of Akaike information criterion (AIC), Log-rank × 2, Concordance index (C-index) and calibration curve. The median survival time was 8 months, and the 6-months and 12-months survival rate were 61% and 26% respectively. All four prognostic indices were correlated with prognosis (P<0.005).The AIC for BSBM (686.317) was the minimum in the four PIs(range,686.317-739.113).The Log-rank × 2 value for BSBM (77.62) was the maximum in the four PIs (range,23.32-77.62).The C-index for BSBM (0.758)was superior than the other PIs predictive capacity (range,0.611-0.758). The calibration curve showed that the BSBM was able to predict 6-months and 12-months overall survival accurately. In conclusion, the BSBM may be the most accurate prognostic index for patients with BM from NSCLC who underwent radiosurgery.

Frameless stereotactic radiosurgery for brain metastases: a review of outcomes and prognostic scores evaluation.

Stereotactic brain radiosurgery provides good local control in patients with limited brain metastases. A newly developed frameless system allows pain-free treatment. We reviewed the effectiveness of this frameless stereotactic brain radiosurgery and identified prognostic factors that may aid better patient selection. Medical records of patients with brain metastases treated with linear accelerator-based frameless stereotactic brain radiosurgery between January 2010 and July 2015 in a university affiliated hospital in Hong Kong were reviewed. Outcomes including local and distant brain control rate, progression-free survival, and overall survival were analysed. Prognostic factors were identified by univariable and multivariable analyses. Association of outcomes with four common prognostic scores was performed. In this study, 64 patients with 94 lesions were treated with a median dose of 18 Gy (range, 12-22 Gy) in a single fraction. The median follow-up was 11.5 months. One-year actuarial local and distant brain control rates were 72% and 71%, respectively. The median overall survival was 13.0 months. On multivariable analysis, Karnofsky performance status score (>50 vs ≤50) and number of lesions (1-2 vs ≥3) were found to associate significantly with distinct brain progression-free survival (P=0.022, hazard ratio=0.20, 95% confidence interval 0.05-0.80 and P=0.003, hazard ratio=0.31, 95% confidence interval 0.14-0.68, respectively). Overall survival was associated significantly with Basic Score for Brain Metastases (P=0.031), Score Index for Radiosurgery in Brain Metastases (P=0.007), and Graded Prognostic Assessment (P=0.003). Improvement in overall survival was observed in all groups of different prognostic scores. Frameless stereotactic brain radiosurgery is effective in patients with oligo-metastases of brain and should be increasingly considered in patients with favourable prognostic scoring.

Applicability of graded prognostic assessment of lung cancer using molecular markers to lung adenocarcinoma patients with brain metastases.

Several scoring systems are available to estimate prognosis and assist in selecting treatment methods for non-small cell lung cancer (NSCLC) patients with brain metastasis, including recursive partitioning analysis (RPA), basic score for brain metastases (BS-BM), and diagnosis-specific graded prognostic assessment (DS-GPA). Lung-molGPA is an update of the DS-GPA that incorporates EGFR and/or ALK mutation status. The present study tested the applicability of these four indexes in 361 lung adenocarcinoma patients with brain metastasis. Potential predictive factors in our independent multivariate analysis included patient age, Karnofsky performance status, EGFR and ALK mutation status, and use of targeted therapy. In the log-rank test, all four systems predicted overall survival (OS) (P<0.001). Harrell’s C indexes were 0.732, 0.724, 0.729, and 0.747 for RPA, BS-BM, DS-GPA, and Lung-molGPA, respectively. Our results confirmed that the Lung-molGPA index was useful for estimating OS in our patient cohort, and appeared to provide the most accurate predictions. However, the independent prognostic factors identified in our study were not entirely in agreement with the Lung-molGPA factors. In an era of targeted therapy, Lung-molGPA must be further updated to incorporate more specific prognostic factors based on additional patient data.

Comparison of prognostic indices in patients who undergo melanoma brain metastasis radiosurgery

OBJECTIVE The goal of this study was to use 4 prognostic indices to compare survival times of patients who underwent Gamma Knife stereotactic radiosurgery (SRS) to treat melanoma brain metastases. METHODS The authors analyzed 422 consecutive patients (1440 brain metastases) who underwent Gamma Knife SRS. The median total brain tumor volume was 4.7 cm3 (range 0.3-69.3 cm3), and the median number of metastases was 2 (range 1-32). One hundred thirty-two patients underwent whole-brain radiation therapy. Survival times were compared using recursive partitioning analysis (RPA), the Score Index for Radiosurgery (SIR), the Basic Score for Brain Metastases (BSBM), and the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA). RESULTS The overall survival times after SRS were compared. With the RPA index, survival times were 2.6 months (Class III, n = 27), 5.5 months (Class II, n = 348), and 13.0 months (Class I, n = 47). With the DS-GPA index, survival times were 2.8 months (Scores 0-1, n = 67), 4.2 months (Scores 1.5-2.0, n = 143), 6.6 months (Scores 2.5-3.0, n = 111), and 9.4 months (Scores 3.5-4.0, n = 101). With the SIR, survival times were 3.2 months (Scores 0-3, n = 56), 5.8 months (Scores 4-7, n = 319), and 12.7 months (Scores 8-10, n = 47). With the BSBM index, survival times were 2.6 months (BSBM0, n = 47), 5.4 months (BSBM1, n = 282), 11.0 months (BSBM2, n = 86), and 8.8 months (BSBM3, n = 7). The DS-GPA index was the most balanced by case numbers in each class and provided the overall best prognostic index for overall survival. CONCLUSIONS The DS-GPA index proved most balanced and predictive of survival for patients with melanoma who underwent SRS as part of management for brain metastases. Patients whose DS-GPA score was ≥ 2.5 had predictably improved survival times after SRS.

P2.05-013 Stereotactic Brain Radiosurgery in Lung Cancer Patients in the Era of Personalized Therapy: A Review of Outcomes and Prognostic Scores Evaluation: Topic: Clinical Outcome

Stereotactic brain radiosurgery (SRS) was demonstrated to provide good local control in patients with oligo-brain metastases (commonly defined as 4 or less). The discovery of different targeted therapies provided significant improvement in survival in the past decade. We reviewed the effectiveness of SRS in lung cancer patients with oligo-brain metastases and identified prognostic factors which potentially can aid better patient selection. Medical records of patients with brain metastases treated with SRS in Prince of Wales Hospital, Hong Kong in Jan 2010-July 2015 were reviewed. Outcomes including local control rate (LCR), distant brain control rate (BCR) and overall survival (OS) were analyzed. Prognostic factors were identified with univariate and multivariate analyses. Correlation with available prognostic scorings including RTOG Recursive Partitioning Analysis, Basic Score for Brain Metastases, the Score Index for Radiosurgery and Graded Prognostic Assessment was evaluated. Forty-eight patients with 66 lesions were treated with LINAC-based SRS with single dose of 12-24Gy (mean dose 18.1Gy). The distribution of different subtypes is as follows: Non-small cell lung cancer (NSCLC)/adenocarcinoma NOS n=18 (37.5%), EGFR mutation n=17 (35.4%), ALK IHC+ n=3 (6.3%), adenocarcinoma of unknown subtype n=2 (4.2%), squamous cell carcinoma n=5 (10.4%), small cell carcinoma n=2 (4.2%) and unknown subtype n=1 (1.8%). The median follow up time was 11.0 months (0.4-71.4 months). Five patients (9.4%) were symptomatic with acute brain edema. Seven patients (14.6%) had delayed seizure after a mean time of 10.1month (2.0-33.5 months). Six patients (12.5%) became steroid dependent. The median OS was 13.0 months. One year actuarial LCR was 73% and distant BCR was 67%. OS correlated significantly with all four scoring systems. Among NSCLC patients, those with activating EGFR mutation (exon 19 deletion or exon 21 L858R mutation) (n=12) had superior OS compared with non-mutational group (p=0.036, HR 2.811 95% CI 1.072-7.369), but there was no statistically significant difference on local or distant brain control. Concomitant whole brain radiotherapy (WBRT) did not significantly affect OS, local and brain control in the whole group and in EGFR activating mutant subgroup. SRS provided good control in patients with primary lung cancer with oligo-brain metastases. Current available prognostic scores provide good estimation of survival. Patients with EGFR activating mutation had superior survival after SRS compared with non-mutational NSCLC group.

Robustness of the neurological prognostic score in brain metastasis patients treated with Gamma Knife radiosurgery.

OBJECTIVE The neurological prognostic score (NPS) was recently proposed as a means for predicting neurological outcomes, such as the preservation of neurological function and the prevention of neurological death, in brain metastasis patients treated with Gamma Knife radiosurgery (GKRS). NPS consists of 2 groups: Group A patients were expected to have better neurological outcomes, and Group B patients were expected to have poorer outcomes. NPS robustness was tested in various situations. METHODS In total, 3040 patients with brain metastases that were treated with GKRS were analyzed. The cumulative incidence of the loss of neurological function independence (i.e., neurological deterioration) was estimated using competing risk analysis, and NPS was compared between Groups A and B by employing Gray's model. NPS was tested to determine if it can be applied to 5 cancer categories-non-small cell lung cancer, small cell lung cancer, gastrointestinal tract cancer, breast cancer, and other cancers-as well as if it can be incorporated into the 5 major grading systems: recursive partitioning analysis (RPA), score index for stereotactic radiosurgery (SIR), basic score for brain metastases (BSBM), graded prognostic assessment (GPA), and modified-RPA (M-RPA). RESULTS There were 2263 patients in NPS Group A and 777 patients in Group B. Neurological deterioration was observed in 586 patients (19.2%). The cumulative incidences of neurological deterioration were 9.5% versus 21.0%, 14.1% versus 25.4%, and 17.6% versus 27.8% in NPS Groups A and B at 1, 2, and 5 years, respectively. Significant differences were detected between the NPS groups in all cancer categories. There were significant differences between NPS Groups A and B for all classes in terms of the BSBM, GPA, and M-RPA systems, but the differences failed to reach statistical significance in terms of RPA Class I and SIR Class 0 to 3. CONCLUSIONS The NPS was verified as being highly applicable to all cancer categories and almost all classes for the 5 grading systems in terms of neurological function independence. This NPS system appears to be quite robust in various situations for brain metastasis patients treated with GKRS.

Which Prognostic Index Is Most Appropriate in the Setting of Delayed Stereotactic Radiosurgery for Brain Metastases?

To determine if five commonly used prognostic indices (PIs) - recursive partitioning analysis (RPA), Score Index for Radiosurgery (SIR), Basic Score for Brain Metastases (BSBM), graded prognostic assessment (GPA), and the diagnosis-specific GPA - are valid following delay between diagnosis and treatment of brain metastases. In a single-institutional cohort, records of patients who underwent stereotactic radiosurgery (SRS) more than 30 days from diagnosis of brain metastases were collected, and five PI scores were calculated for each patient. For each PI, three score-based groupings were made to examine survival differences by means of adjusted log-rank analysis and area under the curve (AUC). Of 121 patients with sufficient PI information, 72 underwent SRS more than 30 days after diagnosis. Median age and Karnofsky performance status were 60 years and 80, respectively. Forty-three (60%) patients had lung primaries. Prior to SRS, 38 (52.8%) and 12 (16.7%) patients underwent whole brain radiation therapy (WBRT) and surgery, respectively. Two (2.8%) patients underwent both WBRT and surgery prior to SRS. A median of two lesions were treated per SRS course. Median survival of the cohort was 9.0 months. Using adjusted log-rank analysis for pairwise comparison, BSBM and GPA showed significance between two out of the three prognostic groups, while the other scores showed either one or no significant differences on comparison. AUC demonstrated good applicability for BSBM, RPA, and GPA, although SIR was statistically less prognostic than the other PIs. The PIs analyzed in this study were applicable in the setting of delayed SRS. Although these data are hypothesis generating, they serve to encourage further analyses to validate a PI that is most optimal for these patients.

Prognostic scores for brain metastasis patients: use in clinical practice and trial design.

Brain metastases (BM) are the most serious neurological complication of cancer that results in significant morbidity and mortality in these patients. The most common primary malignancies that lead to BM include lung, breast and melanoma. Until recently the outcomes of patients with BM has been dismal. The current therapeutic options include surgery, whole brain radiation therapy (WBRT), stereotactic radiation (SRS), systemic therapy and symptom management only. Prognostic scores, a useful tool for BM patients, as an estimation of a patient's prognosis can guide tailored treatment for these patients. It is appropriate to recommend more aggressive approaches in patients with good performance status and limited disease and focus on symptom control and palliative measures when the disease is more advanced, or comorbidity preclude aggressive therapy. Due to vastly different outcomes, prognostic scores are important to stratify patients in clinical trials. A number of prognostic scoring systems for BM patients have been proposed that include Recursive Partitioning Analysis (RPA), the Score Index For Radiosurgery (SIR), the Basic Score for Brain Metastases (BSBM), the Rotterdam system (ROTTERDAM), the Golden Grading System (GGS), 2 Rades classification (RADES), the Graded Prognostic Assessment (GPA) and the disease specific Graded Prognostic Assessment (ds-GPA). In this article, we will review the important prognostic scoring systems and their utility in clinical decision making and trial design.

A new grading system focusing on neurological outcomes for brain metastases treated with stereotactic radiosurgery: the modified Basic Score for Brain Metastases.

The Basic Score for Brain Metastases (BSBM) proposed by Lorenzoni and colleagues is one of the best grading systems for predicting survival periods after stereotactic radiosurgery (SRS) for brain metastases. However, it includes no brain factors and cannot predict neurological outcomes, such as preservation of neurological function and prevention of neurological death. Herein, the authors propose a modified BSBM, adding 4 brain factors to the original BSBM, enabling prediction of neurological outcomes, as well as of overall survival, in patients undergoing SRS. To serve as neurological prognostic scores (NPSs), the authors scored 4 significant brain factors for both preservation of neurological function (qualitative survival) and prevention of neurological death (neurological survival) as 0 or 1 as described in the following: > 10 brain tumors = 0 or ≤ 10 = 1, total tumor volume > 15 cm(3) = 0 or ≤ 15 cm(3) = 1, MRI findings of localized meningeal dissemination (yes = 0 or no = 1), and neurological symptoms (yes = 0 or no = 1). According to the sum of NPSs, patients were classified into 2 subgroups: Subgroup A with a total NPS of 3 or 4 and Subgroup B with an NPS of 0, 1, or 2. The authors defined the modified BSBM according to the NPS subgroup classification applied to the original BSBM groups. The validity of this modified BSBM in 2838 consecutive patients with brain metastases treated with SRS was verified. Patients included 1868 with cancer of the lung (including 1604 with non-small cell lung cancer), 355 of the gastrointestinal tract, 305 of the breast, 176 of the urogenital tract, and 134 with other cancers. Subgroup A had 2089 patients and Subgroup B 749. Median overall survival times were 2.6 months in BSBM 0 (382 patients), 5.7 in BSBM 1 (1143), 11.4 in BSBM 2 (1011) and 21.7 in BSBM 3 (302), and pairwise differences between the BSBM groups were statistically significant (all p < 0.0001). One-year qualitative survival rates were 64.6% (modified BSBM 0A, 204 patients), 45.0% (0B, 178), 82.5% (1A, 825), 63.3% (1B, 318), 86.4% (2A, 792), 73.7% (2B, 219), 91.4% (3A, 268), and 73.5% (3B, 34). One-year neurological survival rates were 82.6% (0A), 52.4% (0B), 90.5% (1A), 78.1% (1B), 91.1% (2A), 83.2% (2B), 93.9% (3A), and 76.3% (3B), where A and B identify the subgroup. Statistically significant differences in both qualitative and neurological survivals between Subgroups A and B were detected in all BSBM groups. The authors' new index, the modified BSBM, was found to be excellent for predicting neurological outcomes, independently of life expectancy, in SRS-treated patients with brain metastases.

P08.09 * RADIOSURGERY FOR BRAIN METASTASES: PROSPECTIVE VALIDATION OF THE BSBM PROGNOSTIC SCORE

PURPOSE: To prospectively validate our basic score for brain metastases (BSBM) classification in patients treated by Gamma Knife radiosurgery (GKRS) for brain metastases (BM) METHODS AND MATERIALS: Between January 2003 and December 2007, we treated more than 1000 BM in 283 patients by RS. We followed these patients prospectively since January 2003 using the BSBM classification, which is based on 3 prognostic factors: no extracranial metastatic disease (ECMD), KPS ≥80, primary tumor controlled. A score of 0 to 1 point was attributed to each factors, with a total from 0 to 3 points; the patients had a BSBM score 0, 1, 2 and 3 in 2.5%, 13%, 60% and 24%, respectively. RESULTS: The median survival (MS) was 12 months (95% CI, 10-14 months); the 2-years and 5-years survival were respectively 27 and 10 %. The MS was 2.5, 6, 12 and 20.5 months respectively for the BSBM scores 0, 1, 2 and 3 (p < 0.001); the MS was respectively 13 and 11 months with an ECMD absent or present (p < 0.001), 4 and 13 months according a KPS <80 or ≥80 (p < 0.001) and finally, 13 and 7 months with a primary tumor controlled or not (p < 0.001). All 3 prognostic factors used in the BSBM classification were found statistically significant in univariate and multivariate analysis. CONCLUSIONS: We have validated prospectively our BSBM prognostic model which we developed retrospectively in 2004. The strenghts of our classification is the ease to use as we consider only 3 prognostic factors.