Extracerebral Metastases Research Articles

Validity test of small cell lung cancer (SCLC) graded prognostic assessment and proposal of a new index for patients with brain metastases from SCLC

Background and purposeWe performed a validity test of a recently-reported, small cell lung cancer (SCLC) graded prognostic assessment (GPA) system for SCLC patients with brain metastases (BMs). Thereafter, we created a new prognostic index, the SCLC Grade, for such patients. Materials and methodsWe studied 508 SCLC patients selected from among nearly 7000 consecutive patients undergoing gamma knife SRS for BMs since 1998. ResultsIn the SCLC GPA, there were no median survival time (MST) differences among pairs of the neighboring subgroups. Therefore, the 508 patients were randomly divided into the two series, i.e., a test (340 patients) and a validity (168) series. In the test series, five factors were identified by univariable analyses as favoring longer survival (rounded lower 95 % CI of the HR was at least 1.3): Sex, Karnofsky Performance Status, tumor numbers, primary tumor status and extracerebral metastases. This new index is the sum of scores (0 and 1) of these five factors: SCLC-Grade 4–6 (score of 4, 5 or 6), 2–3 (2 or 3), and 0–1 (0 or 1). This new system showed highly statistically significant MST differences among subclasses. Next, this SCLC-Grade was applied to the verification series. Consistent results were obtained, i.e., there were highly statistically significant MST differences among subclasses. ConclusionsOur validity test results for the SCLC GPA demonstrated this system to not precisely reflect the outcomes of SCLC patients with BMs. Our results suggest the herein-proposed SCLC-Grade to have superior prognostic value.

Genomic and tumor microenvironment dynamics of brain metastases in breast cancer.

1018 Background: Brain metastases (BM) in breast cancer (BC) have a poor prognosis, with median survival at 7.2-13 months. Interplay between genomic evolution of cancer cells and development of BM is obscure. We sought to identify genomic aberrations associated with BM. Methods: We included 14095 BC samples: 429 BM, 7858 extra-cerebral metastases (ECM) and 5808 primary tumors (PT) were analyzed by next generation sequencing of DNA (NextSeq, 592 genes and NovaSeq, WES) and RNA (NovaSeq, WTS) (Caris Life Sciences, AZ). Tumor mutational burden-high (TMB-H) was defined as ≥10 mt/MB. Cut-off for PD-L1 immunohistochemistry positivity was ≥2 intensity and >5% staining (SP142). Global loss of heterozygosity (gLOH) used a cut-off of ≥ 16%. PAM50 was evaluable for a subset (n=9724, 69%) with WTS data. Statistical significance determined using chi-square and Mann-Whitney U test and adjusted for multiple comparisons (q<0.05). Results: Median age was lower in BM than ECM and PT (55 vs 62 vs 59 years, q<0.05). BM subtype was triple negative (TNBC, 40.1%), HR+/HER2- (30.5%), or HER2+ (29.4%) vs. ECM primarily HR+/HER2- (65.4%) and PT HER2+ (52.5%). BM were Basal-like (35.3%) or HER2-enriched (35.3%), whereas ECM were Luminal B (47.2%) and PT were Basal-like (34.4%) or Luminal B (34.6%). The Table summarizes molecular findings. In HR+/HER2- BC, BM were associated with TMB-H vs. ECM and PT (q<0.05). BM had higher GATA3-mt and ESR1-mt compared to PT (q<0.05). In HER2+ BC, BM had lower PD-L1+ (11.8% vs 39.3%) and higher ESR1-mt than PT. BM had higher ERBB2-amp (93.5% vs 75.2%) and RARA-amp (27.3% vs 6.7%) than PT (q<0.05). TNBC BM had higher proportion of TMB-H tumors but lower PD-L1+ (20.8% vs 50.7%) than PT. BM had increased gLOH than ECM (59.2% vs 36.2%). PIK3CA was lower in BM vs. ECM. In all subtypes, BM, when compared to ECM and PT respectively, were associated with decreased AR+ (HR+/HER2-: 57.7% vs 80.8% vs 85.7%; HER2+: 54.4% vs 77.1% vs 81%; TNBC: 15.1% vs 27.7% vs 23.1%), increased dendritic cell infiltration (HR+/HER2-: 3.2% vs 2.6% vs 2.5%; HER2+: 3.85% vs 2.41% vs 2.36%; TNBC: 3.96% vs 2.89% vs 3.05%) but lower IFN score (HR+/HER2-: -0.56 vs -0.41 vs-0.35; HER2+: -0.53 vs -0.39 vs -0.30; TNBC: -0.55 vs -0.30 vs -0.28). Conclusions: BM in BC are more frequently associated with TNBC and Basal-like BC phenotypes than ECM or PTs. BM have a higher proportion of ESR1-mut than PTs, highlighting a possible association between endocrine resistance and development of BM. BM had lower IFN score and PDL-1 expression highlighting an immunosuppressed tumor microenvironment. [Table: see text]

Combined immunotherapy in melanoma patients with brain metastases: A multicenter international study

BackgroundIpilimumab plus nivolumab (COMBO) is the standard treatment in asymptomatic patients with melanoma brain metastases (MBM). We report a retrospective study aiming to assess the outcome of patients with MBM treated with COMBO outside clinical trials. MethodsConsecutive patients treated with COMBO have been included. Demographics, steroid treatment, Central Nervous System (CNS)-related symptoms, BRAF status, radiotherapy or surgery, response rate (RR), progression-free (PFS) and overall survival (OS) have been analyzed. Results376 patients were included: 262 received COMBO as first-line and 114 as a subsequent line of therapy, respectively. In multivariate analysis, Eastern Cooperative Oncology Group (ECOG) (≥1 vs 0) [HR 1.97 (1.46–2.66)], extracerebral metastases [HR 1.92 (1.09–3.40)], steroid use at the start of COMBO [HR 1.59 (1.08–2.38)], CNS-related symptoms [HR 1.59 (1.08–2.34)], SRS (Stereotactic radiosurgery) [HR 0.63 (0.45–0.88)] and surgery [HR 0.63 (0.43–0.91)] were associated with OS. At a median follow-up of 30 months, the median OS (mOS) in the overall population was 21.3 months (18.1–24.5), whilst OS was not yet reached in treatment-naive patients, steroid-free at baseline. In patients receiving COMBO after BRAF/MEK inhibitors(i) PFS at 1-year was 15.7%. The dose of steroids (dexamethasone < vs ≥ 4 mg/day) was not prognostic. SRS alongside COMBO vs COMBO alone in asymptomatic patients prolonged survival. (p = 0.013). Toxicities were consistent with previous studies. An independent validation cohort (n = 51) confirmed the findings. ConclusionsOur results demonstrate remarkable long-term survival in treatment-naïve, asymptomatic, steroid-free patients, as well as in those receiving SRS plus COMBO. PFS and OS were poor in patients receiving COMBO after progressing to BRAF/MEKi.

Central Nervous System Melanoma: Report of two cases

Primary brain melanomas are exceedingly rare, and metastasis outside of the central nervous system is an uncommon occurrence. The patients initially presented with an intraparenchymal hematoma with associated symptoms. Extensive diagnostic tests did not reveal any tumor-related or vascular patterns contributing to these bleedings. A comprehensive surgical resection was conducted, and the diagnosis of Central Nervous System (CNS) melanoma was confirmed through histological examination. Despite the generally poor prognosis associated with malignant melanomas, the combination of complete surgical resection and emerging therapies is extending overall survival and enhancing the quality of life. In cases where primary brain melanoma is suspected, even in the presence of extracerebral metastasis, aggressive treatment may be a viable consideration.

CyberKnife-based stereotactic radiosurgery or fractionated stereotactic radiotherapy in older patients with brain metastases from non-small cell lung cancer.

We analyzed clinical results of CyberKnife (CK)-based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) in older patients (age ≥65 years) affected by brain metastases (BM) from non-small cell lung cancer (NSCLC). Forty-three older patients with 92 BM were treated with CK-based SRS/FSRT at our institution between 2009 and 2019. The end-point was overall survival (OS). Univariate and multivariate analyses were performed to identify the prognostic factors influencing OS. The in-field local control (IFLC) within the SRS/FSRT field was also assessed. During a median follow-up period of 18 months, the median OS was 32 months. NSCLC-specific graded prognostic assessment (GPA) (p = 0.027) was an independent significant factor affecting OS in the multivariate analysis. The median IFLC period was 31 months, and the total BM volume (p = 0.025) appeared to be a significant feature of IFLC. No adverse events >grade 2 were reported after SRS/FSRT. CK-based SRS/FSRT is a safe and efficient option for older patients with BM arising from NSCLC, showing good OS without severe side effects. GPA, which was consisted in age, performance status, extra-cerebral metastasis, and number of BM, seemed to be predictive factors for OS.

The First Survival Score for Patients Treated with Whole-Brain Radiotherapy Plus Simultaneous Integrated Boost for Brain Metastases.

A modern approach for brain metastases includes whole-brain radiotherapy plus simultaneous boost (WBRT+SIB). We developed a survival score in 128 patients treated with WBRT+SIB. Three models, each including three prognostic groups, were created. Positive predictive values (PPVs) for death ≤6 and survival ≥6 months were calculated. On multivariate analyses, performance score (KPS) and the number of brain metastases were significantly associated with survival. On univariate analyses, age showed a strong trend, and extra-cerebral cranial metastases a trend. In Model 1 (KPS, number of lesions), compared groups had 6-month survival rates of 15%, 38% and 57%. In Model 2 (KPS, lesions, age), rates were 17%, 33% and 75%, and in Model 3 (KPS, lesions, age, extra-cerebral metastases), 14%, 34% and 78%. PPVs for death ≤6 and survival ≥6 months were 85% and 57% (Model 1), 83% and 75% (Model 2), and 86% and 78% (Model 3). Thus, all models were accurate in predicting death ≤ 6 months; poor-prognosis patients may not benefit from SIB. Models 2 and 3 were superior in predicting survival ≥ 6 months. Given that Model 3 requires more data (including extensive staging), Model 2 is considered favorable for many patients. If extra-cerebral metastases are already known or extensive staging has been performed, Model 3 can also be used.

Genomics of Breast Cancer Brain Metastases: A Meta-Analysis and Therapeutic Implications

Breast cancer brain metastases are a challenging daily practice, and the biological link between gene mutations and metastatic spread to the brain remains to be determined. Here, we performed a meta-analysis on genomic data obtained from primary tumors, extracerebral metastases and brain metastases, to identify gene alterations associated with metastatic processes in the brain. Articles with relevant findings were selected using Medline via PubMed, from January 1999 up to February 2022. A critical review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement (PRISMA). Fifty-seven publications were selected for this meta-analysis, including 37,218 patients in all, 11,906 primary tumor samples, 5541 extracerebral metastasis samples, and 1485 brain metastasis samples. We report the overall and sub-group prevalence of gene mutations, including comparisons between primary tumors, extracerebral metastases and brain metastases. In particular, we identified six genes with a higher mutation prevalence in brain metastases than in extracerebral metastases, with a potential role in metastatic processes in the brain: ESR1, ERBB2, EGFR, PTEN, BRCA2 and NOTCH1. We discuss here the therapeutic implications. Our results underline the added value of obtaining biopsies from brain metastases to fully explore their biology, in order to develop personalized treatments.

Preoperative neutrophil-to-lymphocyte ratio (preNLR) for the assessment of tumor characteristics in lung adenocarcinoma patients with brain metastasis

ObjectivesBrain metastases from lung adenocarcinoma cause significant patient mortality. This study aims to evaluate the role of preoperative Neutrophil-to-Lymphocyte ratio (preNLR) in predicting the survival and prognosis of Lung adenocarcinoma (LUAD) patients with brain metastasis (BM) and provide more references for predicting peritumoral edema. MethodsWe retrospectively reviewed 125 LUAD-BM patients who had undergone surgical resection from December 2015 to December 2020. The clinical characteristic, demographic, MRI data, and preNLR within 24–48 h before craniotomy were collected. Patients were divided into two groups based on preNLR (high NLR and low NLR), with cutoff values determined by receiver operating characteristic (ROC) analysis. Association between preoperative NLR and clinical features was determined by using Pearson chi-squared tests. Uni- and multivariate analyzes were performed to compare the overall survival (OS) of clinical features. ResultsThe patients were divided into NLR-low (64 patients) and NLR-high (61 patients) groups based on receiver operating characteristic analysis of NLR area. According to correlation analysis, a high preNLR (NLR≥2.8) is associated with the both supra- and infratentorial location involved (P = 0.017) and a greater incidence of severe peritumoral edema (P = 0.038). By multivariable analysis, age ≥ 65 years (P = 0.011), KPS < 70 (P = 0.043), elevated preNLR (P = 0.013), extracerebral metastases (P = 0.003), EGFR/ALK+ (P = 0.037), postoperative radiotherapy (P = 0.017) and targeted therapy (P = 0.007) were independent prognostic factors. OS nomogram was constructed based on cox model and model performance was examined (AUC = 0.935). ConclusionsPreNLR may serve as a prognosis indicator in LUAD patients with brain metastasis, and high preNLR tends to be positively associate with multiple locations and severe peritumoral edema.

Survival Outcome of Surgical Resection vs. Radiotherapy in Brain Metastasis From Colorectal Cancer: A Meta-Analysis

BackgroundThe incidence of brain metastasis from colorectal cancer (CRC) increases along with the greater survival rate for CRC because of the advances in therapeutic modalities. Local treatment strategies for brain metastasis include surgical resection and radiotherapy. Nevertheless, given the incongruent literature, the optimal therapeutic approach remains to be investigated. This study aims to systematically compare the real-world survival outcome of surgical resection and radiotherapy in patients with brain metastasis from CRC.MethodsFollowing Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines (PROSPERO, ID: CRD42021240200), the Cochrane Library, Embase, and Medline were searched from the inception of the database to August 2021. Meta-analyses were conducted with results pooled using hazard ratios with corresponding 95% CIs to evaluate the overall survival (OS) following local treatment for brain metastasis from CRC. Summary effects were evaluated using a series of random-effect models.ResultsIn this review, 17 retrospective studies comprising 1,438 participants were included. In comparison with radiotherapy, the OS of patients who received brain metastasectomy was generally longer (HR, 0.53; 95% CI, 0.47–0.60). Extracerebral metastases (HR, 1.58; 95% CI, 1.34–1.86) and multiple brain metastases (HR, 1.38; 95% CI, 1.10–1.72) were associated with worse survival outcomes.ConclusionsFor patients with brain metastasis from CRC, the current real-world evidence demonstrated the survival benefit of aggressive neurosurgical management in suitable patients. Additionally, patients with extracerebral metastases and multiple brain metastases had worse survival outcomes.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=240200.

Immune Checkpoints Inhibitors and SRS/SBRT Synergy in Metastatic Non-Small-Cell Lung Cancer and Melanoma: A Systematic Review.

Background: Several immunotherapy (IT) agents are FDA approved for treatment of melanoma and non-small-cell lung cancer (NSCLC). The addition of stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT) to immunotherapy looks promising. A systematic review was conducted to evaluate the possible synergistic effects of immune checkpoints inhibitors (ICIs) and stereotactic radiation therapy in melanoma and NSCLC. Materials and methods: Pubmed databases from January 2010 to December 2020 were reviewed to identify English language studies reporting control of local and abscopal effect of the combination of ICI-SBRT/SRS in metastatic NSCLC and melanoma cancer. The inclusion criteria were followed according to PICO criteria. Results: Thirty-nine articles were included of the 2141 initial results. The reported rates for local control were 16.5–100% and 40–94% in brain and extracerebral metastases, respectively. Distant/abscopal response rates were 1–45% in extracerebral metastases. Abscopal effect could not be evaluated in brain metastases because it was not reported in studies. Treatments were well tolerated with few grade 4 toxicities and no grade 5. Conclusions: The combined treatment of ICI-SBRT/SRS achieves high local control and non-negligible abscopal response in patients with extracerebral metastases, with its benefit in cerebral metastases being more controversial. Clinical trials are needed to better characterize the potential synergism.

A new prognostic score for predicting survival in patients treated with robotic stereotactic radiotherapy for brain metastases

The study aimed to analyze potential prognostic factors in patients treated with robotic radiosurgery for brain metastases irrespective of primary tumor location and create a simple prognostic score that can be used without a full diagnostic workup. A retrospective analysis of 142 patients with 1–9 brain metastases treated with stereotactic radiosurgery (1–4 fractions) was performed. Volumes of all lesions were calculated using linear dimensions of the tumors (CC, LR, AP) and 4/3*π*(CC/2)*(LR/2)*(AP/2) formula. Kaplan–Meier method and log-rank test were used to analyze survival. Variables significantly associated with overall survival in univariate analysis were included in Cox multivariate analysis. The validity of the model was tested with the bootstrap method. Variables from the final model were used to construct a new prognostic index by assigning points according to the impact of a specific variable on overall survival. In the multivariate analysis, four factors: Karnofsky Performance Status (p = 0.000068), number of brain metastases (p = 0.019), volume of the largest lesion (p = 0.0037), and presence of extracerebral metastases (p = 0.0017), were independent predictors of survival. Total scores ranged from 0 to 12 points, and patients were divided into four groups based on median survival of each subgroup: 0–1 points—18.8 months, 2–3 points—16.9 months, 4–5 points—5.6 months, and ≥ 6 points—4.9 months (p < 0.001). The new prognostic index is simple to calculate. It has a strong prognostic value in a heterogeneous population of patients with a various number of brain metastases, but its value requires confirmation in another cohort.

Phase III randomized study of carboplatin pemetrexed with or without bevacizumab with initial versus "at progression" cerebral radiotherapy in advanced non squamous non-small cell lung cancer with asymptomatic brain metastasis.

Background:The role and timing of whole or stereotaxic brain radiotherapy (BR) in patients with advanced non-small cell lung cancer (aNSCLC) and asymptomatic brain metastases (aBMs) are not well established. This study investigates whether deferring BR until cerebral progression was superior to upfront BR for patients with aNSCLC and aBM.Methods:This open-label, multicenter, phase III trial, randomized (1:1) aNSCLC patients with aBMs to receive upfront BR and chemotherapy: platin–pemetrexed and bevacizumab in eligible patients, followed by maintenance pemetrexed with or without bevacizumab, BR arm, or the same chemotherapy with BR only at cerebral progression, chemotherapy (ChT) arm. Primary endpoint was progression-free survival (PFS), secondary endpoints were overall survival (OS), global, extra-cerebral and cerebral objective response rate (ORR), toxicity, and quality of life [ClinicalTrials.gov identifier: NCT02162537].Results:The trial was stopped early because of slow recruitment. Among 95 included patients, 91 were randomized in 24 centers: 45 to BR and 46 to ChT arms (age: 60 ± 8.1, men: 79%, PS 0/1: 51.7%/48.3%; adenocarcinomas: 92.2%, extra-cerebral metastases: 57.8%, without differences between arms.) Significantly more patients in the BR-arm received BR compare with those in the ChT arm (87% versus 20%; p < 0.001); there were no significant differences between BR and ChT arms for median PFS: 4.7, 95% confidence interval (CI):3.4–7.5 versus 4.8, 95% CI: 2.4–6.5 months, for median OS: 8.5, 95% CI:.6–11.1 versus 8.3, 95% CI:4.5–11.5 months, cerebral and extra-cerebral ORR (27% versus 13%, p = 0.064, and 30% versus 41%, p = 0.245, respectively). The ChT arm had more grade 3/4 neutropenia than the BR arm (13% versus 6%, p = 0.045); others toxicities were comparable.Conclusion:The significant BR rate difference between the two arms suggests that upfront BR is not mandatory in aNSCLC with aBM but this trial failed to show that deferring BR for aBM is superior in terms of PFS from upfront BR.

Development of a multivariable prediction model to estimate the remaining lifespan of elderly patients with cerebral metastases from small-cell lung cancer.

BackgroundPrognostic tools estimating survival of elderly patients with cerebral metastases from small-cell lung cancer (SCLC) improve treatment personalization. A specific tool for these patients was developed and compared to existing instruments.MethodsOne-hundred-and-forty elderly patients (≥65 years) receiving whole-brain irradiation (WBI) for cerebral metastases from SCLC were retrospectively evaluated. WBI-program, age, gender, Karnofsky performance score, number of cerebral lesions, extracerebral metastases, and interval between SCLC-diagnosis and WBI were investigated. Characteristics significantly associated with survival in the multivariate analysis were used for the tool. Scoring points were calculated by dividing 6-month survival rates (%) by 10 and added for patient scores. The tool was compared to existing diagnosis-specific instruments including updated diagnosis-specific graded prognostic assessment (DS-GPA), Rades-SCLC and WBRT-30-SCLC.ResultsIn the multivariate analysis, KPS (P<0.001), number of cerebral lesions (P=0.013) and extracerebral metastases (P=0.049) were significantly associated with survival. Patient scores of 2 (n=37), 5 (n=69), 8 (n=20) and 11 (n=14) points were obtained; 6-month survival rates were 0%, 9%, 50% and 79% (P<0.001). The positive predictive value (PPV) of the worst group (2 points) to identify patients dying ≤6 months was 100%; PPVs of updated DS-GPA, Rades-SCLC and WBRT-30-SCLC were 94%, 100% and 94%. PPV of the best group (11 points) to identify patients surviving ≥6 months was 79%; PPVs of updated DS-GPA, Rades-SCLC and WBRT-30-SCLC were 86%, 79% and 100%.ConclusionsThe most precise instruments were the new tool and Rades-SCLC for identification of patients dying ≤6 months, and the WBRT-30-SCLC to identify patients surviving ≥6 months.

Extra-cerebral Metastasis - An Independent Predictor of Survival in Older Patients With Brain Metastases Receiving a Local Therapy Plus Whole-Brain Radiotherapy (WBRT).

Although omitting whole-brain radiotherapy (WBRT) during the treatment of few brain metastases more popular, many patients receive local therapies plus WBRT. WBRT may be less reasonable for patients with poor overall survival (OS), particularly if they are older. This study aimed to identify predictors of OS in these patients. One-hundred-and-two older patients receiving a local therapy (surgery, radiosurgery, simultaneous integrated boost) and WBRT for 1-3 brain metastases were evaluated. Type of local therapy, WBRT-regimen, age, gender, performance status, primary tumour type, number of brain metastases, extra-cerebral metastasis, and interval from tumour diagnosis to treatment of brain metastases were analysed for OS. Absence of extra-cerebral metastasis was significantly associated with increased OS on univariate analysis (p=0.001) and Cox regression analysis (risk ratio=2.13, p=0.002). Extra-cerebral metastasis is an independent predictor of OS and can be helpful when assigning a treatment to older patients with few brain metastases.

Brain metastases from germ cell tumor: time to reconsider radiotherapy?

The presence of brain metastases (BMs) from germ cell tumor (GCT) remains a rare situation. BMs predominantly occur among patients with testis primary tumor site, and are almost exclusively associated with non-seminomatous (NS) histologies. Two situations must be distinguished, which differ in terms of clinical presentation, overall prognostic and management. At diagnosis, BMs are almost systematically associated with extra-cerebral metastases and the cornerstone of treatment is chemotherapy, while the role of local treatment remains controversial. In the metachronous setting, BMs more frequently constitute an isolated site of relapse, the outcome is poorer, and the role of local treatment is more consensual. However, all these data widely come from old reports, with outdated radiation techniques. The recent advances in radiation oncology, especially the rising use of stereotactic radiotherapy, could lead to the reconsideration of ancient dogmas regarding the "radiosensitivity" of (NS)GCT and the role of radiotherapy among patients with BMs.

An Instrument to Guide Physicians when Estimating the Survival of Elderly Patients With Brain Metastasis from Gynecological Cancer.

For treatment personalization in elderly cancer patients, survival prognoses should be considered. We developed an instrument to estimate survival of elderly patients with brain metastasis from gynecological cancer. In 15 patients, whole-brain radiotherapy regimen, tumor site, age, Karnofsky performance score (KPS), number of brain metastases, extra-cerebral metastases and interval from diagnosis of gynecological cancer until radiotherapy were retrospectively evaluated for survival. Characteristics found significant on multivariate analysis were used for the instrument. In the multivariate analysis, KPS ≥70% (hazard ratio=3.71, p=0.0499) and an interval ≥28 months (hazard ratio=3.71, p=0.030) were significantly associated with better survival. Based on these characteristics, patients received 0 (n=6), 1 (n=3) or 2 points (n=6). Six-month survival rates of the groups 0-1 and 2 points were 0% and 50%, respectively (p=0.007). This instrument helps estimating survival in elderly patients with brain metastases from gynecological cancer and contributes to personalization of their treatment.

Performance Status Is Associated With Survival in Elderly Patients Irradiated for Cerebral Metastases from Prostate Cancer.

Treatment of elderly patients with cancer has increasing importance. Since many of these patients may not tolerate standard treatments, they might benefit from personalized approaches. This study was performed to identify characteristics that allow estimation of survival in elderly patients with prostate cancer with cerebral metastases. Data of 21 elderly patients (≥65 years) receiving whole-brain radiotherapy (WBRT) for cerebral metastases from prostate cancer were retrospectively evaluated. Six characteristics were investigated: WBRT program, age, Karnofsky performance score (KPS), number of brain metastases, extra-cerebral metastases, and interval between diagnosis of prostate cancer and WBRT. On univariate analyses, KPS ≥80% resulted in better survival than KPS ≤70% (log-rank p=0.018). Three-month survival was 60% vs. 36%, and 6-month survival 50% vs. 0%, respectively. In the Cox model, KPS maintained significance (hazard ratio=3.18, p=0.031). KPS is a significant prognostic factor of survival in elderly patients with prostate cancer receiving WBRT for cerebral metastases.

Pre-Treatment Seizures in Patients With 1-3 Cerebral Metastases Receiving Local Therapies Plus Whole-brain Radiotherapy

Seizures impair patients' quality of life. The prognostic role of pre-treatment seizures in patients with 1-3 cerebral metastases receiving local therapies plus whole-brain radiotherapy (WBRT) was investigated. In 249 patients, prevalence, risk factors and associations of pre-treatment seizures with survival were retrospectively evaluated. Age, gender, performance score, tumor type, number of lesions, extra-cerebral metastases, and time from tumor diagnosis to treatment of cerebral metastasis were analyzed for associations with seizures. These characteristics and pre-treatment seizures were also analyzed for associations with survival. The prevalence of pre-treatment seizures was 24.1%. Trends for associations were found between seizures and gender or performance score. On multivariate analysis, age (p=0.008), performance score (p=0.004), tumor type (p<0.001) and extra-cerebral metastasis (p<0.001) were significantly associated with survival. Seizures were comparably common prior to local therapies plus WBRT for cerebral metastases. No factor was found to be significantly associated with seizures, and seizures were not associated with survival.

Clinical prognostic factors associated with survival and a survival score for patients with brain metastases.

Aim: To identify prognostic factors of survival in patients with brain metastases (BM) and to devise a prognostic score. Patients & methods: In this single-institution retrospective study, we analyzed potential clinical prognostic factors in 1363 patients with BM. Based on the Cox proportional hazard model, we devised a BM score with three classes (score <5, 5-6 and >6). Results: The 1-year overall survival (OS) was 26%. Independent prognostic factors of OS were: age, gender, Karnofski performance status, number of BM, control of primary, presence of extracerebral metastases and type of primary tumor. The 1-year OS was 56% for score <5; 21% for score 5-6 and 4% for score >6 (p<0.01). Conclusion: The BM score we propose is effective in grouping patients according to their prognosis and can help decision making regarding treatment adjustments.

Comparison of Diagnosis-Specific Survival Scores for Patients with Small-Cell Lung Cancer Irradiated for Brain Metastases.

Diagnosis-specific survival scores including a new score developed in 157 patients with brain metastases from small-cell lung cancer (SCLC) receiving whole-brain radiotherapy (WBRT) with 30 Gy in 10 fractions (WBRT-30-SCLC) were compared. Three prognostic groups were designed based on the 6-month survival probabilities of significant or almost significant factors, (age, performance score, number of brain metastases, extra-cerebral metastasis). Six-month survival rates were 6% (6–11 points), 44% (12–14 points) and 86% (16–19 points). The WBRT-30-SCLC was compared to three disease-specific scores for brain metastasis from SCLC, the original and updated diagnosis-specific graded prognostic assessment DS-GPA classifications and the Rades-SCLC. Positive predictive values (PPVs) used to correctly predict death ≤6 months were 94% (WBRT-30-SCLC), 88% (original DS-GPA), 88% (updated DS-GPA) and 100% (Rades-SCLC). PPVs to predict survival ≥6 months were 86%, 75%, 76% and 100%. For WBRT-30-SCLC and Rades-SCLC, differences between poor and intermediate prognoses groups and between intermediate and favorable prognoses groups were significant. For both DS-GPA classifications, only the difference between poor and intermediate prognoses groups was significant. Of these disease-specific tools, Rades-SCLC appeared to be the most accurate in identifying patients dying ≤6 months and patients surviving ≥6 months after irradiation, followed by the new WBRT-30-SCLC and the DS-GPA classifications.