scholarly journals Individualized Nomogram for Predicting Survival in Patients with Brain Metastases After Stereotactic Radiosurgery Utilizing Driver Gene Mutations and Volumetric Surrogates

2021 ◽  
Vol 11 ◽  
Author(s):  
Cheng Zhou ◽  
Changguo Shan ◽  
Mingyao Lai ◽  
Zhaoming Zhou ◽  
Junjie Zhen ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Cox Regression ◽  
Mutational Analysis ◽  
Clinical Chemistry ◽  
Personalized Treatment ◽  
Serum Lactate Dehydrogenase ◽  
Driver Gene ◽  
Karnofsky Performance Score

It is well-known that genomic mutational analysis plays a significant role in patients with NSCLC for personalized treatment. Given the increasing use of stereotactic radiosurgery (SRS) for brain metastases (BM), there is an emerging need for more precise assessment of survival outcomes after SRS. Patients with BM and treated by SRS were eligible in this study. The primary endpoint was overall survival (OS). Cox regression models were used to identify independent prognostic factors. A survival predictive nomogram was developed and evaluated by Concordance-index (C-index), area under the curve (AUC), and calibration curve. From January 2016 to December 2019, a total of 356 BM patients were eligible. The median OS was 17.7 months [95% confidence interval (CI) 15.5–19.9] and the actual OS at 1- and 2-years measured 63.2 and 37.6%, respectively. A nomogram for OS was developed by incorporating four independent prognostic factors: Karnofsky Performance Score, cumulative tumor volume, gene mutation status, and serum lactate dehydrogenase. The nomogram was validated in a separate cohort and demonstrated good calibration and good discriminative ability (C-index = 0.780, AUC = 0.784). The prognostic accuracy of the nomogram (0.792) was considerably enhanced when compared with classical prognostic indices, including the Graded Prognostic Assessment (0.708), recursive partitioning analysis (0.587), and the SRS (0.536). Kaplan–Meier curves showed significant differences in OS among the stratified low-, median- and high-risk groups (P < 0.001). In conclusion, we developed and validated an individualized prognostic nomogram by integrating physiological, volumetric, clinical chemistry, and molecular biological surrogates. Although this nomogram should be validated by independent external study, it has a potential to facilitate more precise risk-stratifications to guide personalized treatment for BM.

scholarly journals RADI-07. Individualized Nomogram for Predicting Survival of Patients with Brain Metastases after Stereotactic Radiosurgery

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii19-iii19
Author(s):  
Lei Wen ◽  
Changguo Shan ◽  
Mingyao Lai ◽  
Zhaoming Zhou ◽  
Linbo Cai
Keyword(s):  
Prognostic Factors ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Clinical Chemistry ◽  
Serum Lactate ◽  
Serum Lactate Dehydrogenase ◽  
Driver Gene ◽  
Karnofsky Performance Score ◽  
Discriminative Ability ◽  
Significant Difference

Abstract Background Given the increasing use of stereotactic radiosurgery (SRS) for brain metastases (BM), there is an emerging need for more precise assessment of survival outcomes after SRS, especially in the modern targeted therapy era. Methods Patients with BM and treated by SRS were eligible in this study. Primary endpoint was overall survival (OS). Cox models were used to identify independent prognostic factors. Survival predictive nomogram was developed and evaluated by Concordance-index (C-index), area under the curve (AUC) and calibration curve. Results From January 2016 to December 2019, a total of 356 BM patients were eligible. Median OS was 17.7 months (95%CI 15.5–19.9) and actual OS at 1- and 2-year measured 63.2% and 37.6%, respectively. Nomogram for OS was developed by incorporating four independent prognostic factors: Karnofsky Performance Score, cumulative tumor volume, driver gene mutation status and serum lactate dehydrogenase. The nomogram was validated in a separate cohort demonstrated a well calibration and good discriminative ability (C-index=0.780, AUC=0.784). The prognostic accuracy of the nomogram (0.792) was considerably enhanced compared with classical prognostic indices, i.e., GPA (0.708), RPA (0.587) and SIR (0.536). Kaplan-Meier curves showed significant difference of OS among stratified low-, median- and high-risk groups (P < .001). Conclusion In conclusion, we developed and validated an individualized prognostic nomogram by integrating physiological, volumetric, clinical chemistry and molecular biological surrogates. This nomogram, should be validated by independent external study, has a potential to facilitate more precise risk-stratifications to guide personalized treatment for BM.

scholarly journals RADI-17. Outcomes for patients with triple negative breast cancer treated with upfront stereotactic radiosurgery for brain metastases

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii21-iii21
Author(s):  
Ran An ◽  
Yan Wang ◽  
Fuchenchu Wang ◽  
Akshara Singareeka Raghavendra ◽  
Chao Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Univariate Analysis ◽  
Karnofsky Performance Score ◽  
Risk Of Death ◽  
Metastatic Sites

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive subtype with high propensity of developing brain metastases (BM). Clinical outcomes and prognostic factors after stereotactic radiosurgery (SRS) for BM were not well defined. Methods We identified 57 consecutive TNBC patients (pts) treated with single fraction SRS for BM during 05/2008–04/2018. Overall survival (OS) from BM diagnosis and freedom from BM progression (FFBMP) after initial SRS were evaluated. BM progression was defined as local and/or distant brain failure (LBF, DBF) after SRS. Kaplan-Meier analyses and Cox proportional hazard regression were used to estimate survival outcomes and identify prognostic factors. Results The median time to BM development from TNBC diagnosis was 23.7 months (mo) (range 0.7‒271.1). Median OS was 13.1 mo (95%CI 8.0‒19.5). On univariate analysis, Karnofsky performance score (KPS) >70 (p=0.03), number of BMs <3 (p=0.016), and BM among the first metastatic sites (p=0.04) were associated with longer OS. On multivariate analysis, KPS ≤70 was associated with higher risk of death (HR 3.0, p=0.03). Of 46 pts with adequate imaging follow-up, 29 (63%) had intracranial progression with a median FFBMP of 7.4 mo (95% CI 5.7–12.7). At 12 mo the estimated cumulative DBF rate was 61.1% (95%CI 40.8%–74.4%) and LBF rate was 17.8% (95%CI 2%–31.1%). Number of BMs (≥3 vs <3) was not associated with FFBMP (p=0.7). Of the 29 pts with BM progression, additional radiation therapy (RT) (vs. no RT) was associated with improved survival (21.7 vs. 7.0 mo, p<0.0001). Conclusions TNBC pts with BM treated with SRS had an OS of 13.1 mo and FFBMP of 7.4 mo. Good KPS was an independent prognostic factor for OS. Further studies with more pts or conducted prospectively are needed to better understand and to improve treatment outcomes in this pt population.

Upfront stereotactic radiosurgery for brain metastases from triple-negative breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14014-e14014
Author(s):  
Ran An ◽  
Yan Wang ◽  
Fuchenchu Wang ◽  
Akshara Singareeka Raghavendra ◽  
Chao Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Univariate Analysis ◽  
Karnofsky Performance Score ◽  
Risk Of Death

e14014 Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with high propensity of brain metastases (BM). Outcomes after upfront stereotactic radiosurgery (SRS) for BM from TNBC patients are not well defined. We evaluated outcomes and identified prognostic factors for such patients. Methods: We reviewed 57 consecutive patients treated with upfront SRS for BM from TNBC in May 2008–April 2018 at a large-volume cancer center. Endpoints were overall survival (OS) from BM diagnosis and freedom from BM progression (FFBMP) after initial SRS. BM progression was defined as local and/or distant brain failure (LBF or DBF) after initial SRS; LBF was radiographic progression of treated lesions, assessed by a neuroradiologist or treating physician excluding post-radiation changes or radiation necrosis. Kaplan-Meier and Cox proportional hazard regression analyses were used to estimate survival outcomes and identify prognostic factors. Results: In this cohort of 57 patients with a median age of 53 y (range 26–82) at BM diagnosis and follow-up time of 12.2 months (mo, range 0.8–97.5), median time to BM development from TNBC diagnosis was 23.7 mo (range 0.7‒271.1). Estimated median OS time from initial BM diagnosis was 13.1 mo (95% CI 8.0‒19.5). In univariate analysis, Karnofsky performance score (KPS) > 70 (p = 0.03), having < 3 BMs (p = 0.016) at BM diagnosis, and BM as first site of metastasis (p = 0.041) were associated with longer OS. On multivariate analysis, KPS ≤70 was associated with higher risk of death (HR 3.0, p = 0.03). Of 46 patients with imaging follow-up for FFBMP assessment, 29 (63%) developed BM progression after initial SRS with an estimated median FFBMP of 7.4 mo (95% CI 5.7–12.7). Median times to LBF and DBF were 10 mo (range 0.3–97) and 5.9 mo (range 0.3–90.8). Estimated cumulative LBF rate was 17.8% (95% CI 2%–31.1%) and DBF 61.1% (95% CI 40.8%–74.4%) at 12 mo. Number of BMs at BM diagnosis (≥3 vs < 3) was not associated with FFBMP (p = 0.7). Of the 29 patients with BM progression, 5 did not receive salvage radiation therapy (RT) and 24 received salvage RT (SRS, whole-brain radiation [WBRT], or both SRS+WBRT). Receipt of salvage RT was associated with longer survival (median 21.7 mo vs. 7.0 mo for no salvage RT, p < 0.0001) and did not differ by type of salvage RT (median OS 18.6 mo for WBRT; 26.2 mo for SRS+WBRT; 35.9 mo for SRS, p = 0.08). Conclusions: We reported a median OS of 13.1 mo and FFBMP of 7.4 mo in TNBC patients with good local control. Good KPS was independent prognostic factor for better OS. FFBMP did not differ by number of SRS-treated brain lesions ( < 3 vs ≥3). Further prospective studies of larger numbers of patients needed for more accurate comparisons of treatment types.

scholarly journals Salvage Radiosurgery for Selected Patients with Recurrent Malignant Gliomas

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Miguel Martínez-Carrillo ◽  
Isabel Tovar-Martín ◽  
Mercedes Zurita-Herrera ◽  
Rosario Del Moral-Ávila ◽  
Rosario Guerrero-Tejada ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Stereotactic Radiosurgery ◽  
Anaplastic Astrocytoma ◽  
Cox Regression ◽  
Malignant Gliomas ◽  
High Grade Glioma ◽  
Initial Diagnosis ◽  
Karnofsky Performance Score ◽  
High Grade ◽  
Effective Treatment Option

Purpose. To analyse the survival after salvage radiosurgery and to identify prognostic factors.Methods. We retrospectively reviewed 87 consecutive patients, with recurrent high-grade glioma, that underwent stereotactic radiosurgery between 1997 and 2010. We evaluated the survival after initial diagnosis and after reirradiation. The prognostic factors were analysed by bivariate and multivariate Cox regression model.Results. The median age was 48 years old. The primary histology included anaplastic astrocytoma (47%) and glioblastoma (53%). A margin dose of 18 Gy was administered in the majority of cases (74%). The median survival after initial diagnosis was 21 months (39 months for anaplastic astrocytoma and 18.5 months for glioblastoma) and after reirradiation it was 10 months (17 months for anaplastic astrocytoma and 7.5 months for glioblastoma). In the bivariate analyses, the prognostic factors significantly associated with survival after reirradiation were age, tumour and treatment volume at recurrence, recursive partitioning analyses classification, Karnofsky performance score, histology, and margin to the planning target volume. Only the last four showed significant association in the multivariate analyses.Conclusion. stereotactic radiosurgery is a safe and may be an effective treatment option for selected patients diagnosed with recurrent high-grade glioma. The identified prognostic factors could help individualise the treatment.

LINAC-based stereotactic radiosurgery/radiotherapy for brain metastases in patients with breast cancer

2021 ◽  
pp. 1-9
Author(s):  
Ankita Gupta ◽  
Budhi Singh Yadav ◽  
Nagarjun Ballari ◽  
Namrata Das ◽  
Ngangom Robert
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Progression Free Survival ◽  
Rank Test ◽  
Karnofsky Performance Score ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Prior Surgery

Abstract Background: Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer. Methods: Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was >3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions. Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test. Results: Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699). Conclusion: In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.

Evaluation of Prognostic Factors for Early Mortality After Stereotactic Radiosurgery for Brain Metastases: a Single Institutional Retrospective Review

Neurosurgery ◽  
2017 ◽  
Vol 83 (1) ◽  
pp. 128-136 ◽  
Author(s):  
E Emily Bennett ◽  
Michael A Vogelbaum ◽  
Gene H Barnett ◽  
Lilyana Angelov ◽  
Samuel Chao ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Karnofsky Performance Status ◽  
Systemic Disease ◽  
Performance Status ◽  
Early Death ◽  
Tumor Type ◽  
Prognostic Groups ◽  
Prior Surgery

Abstract BACKGROUND Stereotactic radiosurgery (SRS) is used commonly for patients with brain metastases (BM) to improve intracranial disease control. However, survival of these patients is often dictated by their systemic disease course. The value of SRS becomes less clear in patients with anticipated short survival. OBJECTIVE To evaluate prognostic factors, which may predict early death (within 90 d) after SRS. METHODS A total of 1427 patients with BM were treated with SRS at our institution (2000-2012). There were 1385 cases included in this study; 1057 patients underwent upfront SRS and 328 underwent salvage SRS. The primary endpoint of the study was all-cause mortality within 90 d after first SRS. Multivariate analyses were performed to develop prognostic indices. RESULTS Two hundred sixty-six patients (19%, 95% confidence interval 17%-21%) died within 90 d after SRS. Multivariate analysis of upfront SRS patients showed that Karnofsky Performance Status, primary tumor type, extracranial metastases, age at SRS, boost treatment, total tumor volume, prior surgery, and interval from primary to BM were independent prognostic factors for 90-d mortality. The first 4 factors were also independent predictors in patients treated with salvage SRS. Based on these factors, an index was defined for each group that categorized patients into 3 and 2 prognostic groups, respectively. Ninety-day mortality was 5% to 7% in the most favorable cohort and 36% to 39% in the least favorable. CONCLUSION Indices based on readily available patient, clinical, and treatment factors that are highly predictive of early death in patients treated with upfront or salvage SRS can be calculated and used to define well-separated prognostic groups.

Mortality, Morbidity, and Prognostic Factors in the Surgical Resection of Brain Metastases: A Contemporary Cohort Study

2020 ◽  
Vol 81 (04) ◽  
pp. 279-289
Author(s):  
Helder Picarelli ◽  
Marcelo de Lima Oliveira ◽  
Gustavo Nader Marta ◽  
Davi J. Fontoura Solla ◽  
Manoel Jacobsen Teixeira ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Brain Metastases ◽  
Causes Of Death ◽  
Cox Regression ◽  
Morbidity And Mortality ◽  
Carcinomatous Meningitis ◽  
Primary Tumor Site ◽  
Risk Of Death ◽  
Prognostic Indices ◽  
The Impact

Abstract Objective Despite advances in systemic therapy and radiotherapy (RT), neurosurgical resection (NSR) remains a mainstay of the treatment of brain metastases (BMs). Although it is unequivocal in instances of diagnostic doubt, radioresistance, and risk of death due to neurologic causes, NSR may be controversial in other situations. Many aspects related to NSR have not yet been well established, and the primary prognostic indices were proposed only in the last decade. This study evaluates the survival and the morbidity, causes of death, prognostic factors, and the impact of RT in patients with BMs treated by NSR in the current era. Methods A total of 200 patients with BMs who were treated by NSR were evaluated sequentially and followed prospectively. We used logistic regression and Cox regression models to identify independent factors associated with mortality at 4 weeks and at 1 year, respectively. Clinical features, morbidity, recurrence, and causes of death were also studied. Results Lung cancer was the most prevalent cancer (36.5%); the median Karnofsky Performance Status (KPS) score was 60. Total resection was achieved in 89%, and adjuvant RT was applied in 63% of the cases. The rates of surgical mortality, morbidity, and mortality at 4 weeks were 1.5%, 17%, and 7.5%, respectively. Systemic infections were the leading cause of death in 62.5% of the cases. The median survival was 5 months, and 34.5% of patients lived > 1 year. The postoperative KPS (KPSpo) score remained unchanged or improved in 94.5% of the cases. In the multivariate analysis, a KPSpo score ≥ 80 and the application of adjuvant RT were associated with a lower risk of death at 12 weeks and at 1 year. Interestingly, the variables of primary tumor site, number of BMs, and presence of carcinomatous meningitis were not significant. Conclusion Morbidity and mortality were high, a third of the patients lived > 1 year, and the KPS score improved or remained unchanged in most cases. Prognostic indices and health conditions were important predictive factors, but the KPSpo score and adjuvant RT were independent variables for survival at 12 weeks and at 1 year. Therefore, new studies are needed to assess the influence of new therapies and specific molecular profiles.

scholarly journals CMET-39. DISPARITIES IN STEREOTACTIC RADIOSURGERY USE AND OUTCOMES FOR MELANOMA BRAIN METASTASES – AN AUSTRALIAN POPULATION-BASED STUDY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi60-vi60
Author(s):  
Wee Loon Ong ◽  
Morikatsu Wada ◽  
Farshad Foroudi
Keyword(s):  
Logistic Regression ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Cox Regression ◽  
Population Based ◽  
Mortality Data ◽  
Multivariate Logistic Regression ◽  
Factors Associated ◽  
Significant Difference ◽  
Melanoma Brain Metastases

Abstract INTRODUCTION We aim to evaluate the use of stereotactic radiosurgery (SRS) among patients who received radiotherapy for melanoma brain metastases (MBM), and the associated outcomes. METHODS This is a population-based cohort of patients who received radiotherapy for MBM between 2013 and 2016, as captured in the Victorian Radiotherapy Minimum Dataset. Brain radiotherapy was classified as SRS (including multi-fraction stereotactic radiotherapy) and non-SRS. Mortality data was obtained through linkage with the Victorian Cancer Registry. The primary outcomes were: proportion of patients who had SRS for MBM, and overall survival (OS) following radiotherapy. Multivariate logistic regression was used to evaluate factors associated with SRS use, Kaplan Meier method for estimation of OS, and multivariate Cox regression for evaluation of factors associated with OS. RESULTS 294 patients received 551 courses of radiotherapy for MBM in this study, of which 39% (116/294) patients received SRS. Patients from higher socioeconomic status were more likely to have SRS – 49% in top quintile vs. 22% in lowest quintile (P< 0.009). Patients treated in regional centres were less likely to have SRS compared to metropolitan centres (3% vs. 48%,P< 0.001). In multivariate logistic regression, treatment in regional centres was the only factor independently associated with lower likelihood of receiving SRS (OR=0.04;95%CI=0.01–0.18;P< 0.001). The median follow-up of the cohort was 3.8 months (range: 0.1–42 months). There were 227 death observed, with 12-month OS of 23%. There was significant difference in 12-month OS between patients who received SRS compared to those who did not receive SRS (43% vs. 11%; P< 0.001). In multivariate Cox regression, the use of SRS was the only factor independently associated with OS (HR=0.38;95%CI=0.28–0.51;P< 0.001). CONCLUSION We observed sociodemographic and institutional disparities in SRS use for MBM. The observed impact of SRS use on OS is most likely confounded by patient selections for SRS.

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