Clinical outcomes in patients with melanoma brain metastases at a tertiary cancer center.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13586-e13586
Author(s):  
William J Phillips ◽  
Bryan Lo ◽  
Michael Ong ◽  
Tyler Smith ◽  
Xinni Song
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Clinical Outcomes ◽  
Checkpoint Inhibitors ◽  
Neurological Symptoms ◽  
Cancer Center ◽  
Significant Prognostic Factor ◽  
Stereotactic Radiation ◽  
Asymptomatic Patients ◽  
Melanoma Brain Metastases

e13586 Background: Brain metastases are observed in more than 40% of all patients with stage IV melanoma. In recent years, more extensive use of stereotactic radiation (STRT) and the advent of immune checkpoint inhibitors and BRAF targeted therapies have positively impacted outcomes in patients with metastatic melanoma (MBM) In this study, we examined real-world clinical outcomes of patients presented with melanoma brain metastases (MBM). Methods: This retrospective review evaluated MBM patients treated at the Ottawa Hospital. Clinical, radiologic, and pathologic variables were collected from the electronic medical records from January 2000 to June 2018. Results: A total of 277 patients fulfilled the inclusion criteria. Median overall survival was 4 months. LDH was the only significant prognostic factor in this study. Over 65% of brain metastases were detected due to the presence of neurological symptoms, while surveillance and restaging identified asymptomatic brain metastases in the remaining patients. Detection by neurological symptoms was related to larger (p < 0.001) and haemorrhagic (p = 0.032) intra-cranial lesions as well as decreased overall survival (HR = 1.2, p = 0.018). With regards to locoregional treatment STRT radiation outperformed WBRT alone in patients with single and oligo (2-6 lesions) brain lesions (HR = 0.149, p = 0.001 for oligo; HR = 0.149, p = 0.003 for single) and was associated with approximately a 3-fold increase in median survival. STRT was used 2-fold less frequently in patients with more than one lesion (54.8% in single; 31.7% in oligo). In patients receiving systemic therapy, immunotherapy is the only modality demonstrated overall survival benefit compared to no systemic treatment (HR = 0.511, p = 0.014). Furthermore, patients receiving STRT in combination with immunotherapy outperformed patients receiving STRT with WBRT (HR = 0.389, p = 0.009). Conclusions: Results from this study support the consideration of routine screening of high-risk asymptomatic patients, the increased use of STRT in patients with multiple intra-cranial lesions. The efficacy of immunotherapy in patients with MBM is consistent with current clinical trial data.

scholarly journals Melanoma Brain Metastases in the Era of Targeted Therapy and Checkpoint Inhibitor Therapy

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1489
Author(s):  
John M. Rieth ◽  
Umang Swami ◽  
Sarah L. Mott ◽  
Mario Zanaty ◽  
Michael D. Henry ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Treatment Strategies ◽  
Poor Performance Status ◽  
Poor Overall Survival ◽  
Melanoma Brain Metastases

Brain metastases commonly develop in melanoma and are associated with poor overall survival of about five to nine months. Fortunately, new therapies, including immune checkpoint inhibitors and BRAF/MEK inhibitors, have been developed. The aim of this study was to identify outcomes of different treatment strategies in patients with melanoma brain metastases in the era of checkpoint inhibitors. Patients with brain metastases secondary to melanoma were identified at a single institution. Univariate and multivariable analyses were performed to identify baseline and treatment factors, which correlated with progression-free and overall survival. A total of 209 patients with melanoma brain metastases were identified. The median overall survival of the cohort was 5.3 months. On multivariable analysis, the presence of non-cranial metastatic disease, poor performance status (ECOG 2–4), whole-brain radiation therapy, and older age at diagnosis of brain metastasis were associated with poorer overall survival. Craniotomy (HR 0.66, 95% CI 0.45–0.97) and treatment with a CTLA-4 checkpoint inhibitor (HR 0.55, 95% CI 0.32–0.94) were the only interventions associated with improved overall survival. Further studies with novel agents are needed to extend lifespan in patients with brain metastases in melanoma.

scholarly journals Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy

2016 ◽  
Vol 27 (3) ◽  
pp. 434-441 ◽  
Author(s):  
K.A. Ahmed ◽  
D.G. Stallworth ◽  
Y. Kim ◽  
P.A.S. Johnstone ◽  
L.B. Harrison ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Clinical Outcomes ◽  
Stereotactic Radiation ◽  
Melanoma Brain Metastases

Clinical Outcomes of Melanoma Brain Metastases Treated With Stereotactic Radiation and Anti-PD-1 Therapy

2015 ◽  
Vol 93 (3) ◽  
pp. S57 ◽  
Author(s):  
K.A. Ahmed ◽  
D.G. Stallworth ◽  
P.A.S. Johnstone ◽  
L.B. Harrison ◽  
A.B. Etame ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Clinical Outcomes ◽  
Stereotactic Radiation ◽  
Melanoma Brain Metastases

scholarly journals A Contemporary Report of Clinical Outcomes in Patients with Melanoma Brain Metastases

2021 ◽  
Vol 28 (1) ◽  
pp. 428-439
Author(s):  
William J. Phillips ◽  
Tabassom Baghai ◽  
Michael Ong ◽  
Bryan Lo ◽  
Andrea M. Ibrahim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Clinical Outcomes ◽  
Real World ◽  
Survival Data ◽  
Immune Checkpoint ◽  
Multivariable Analysis ◽  
Hazard Ratio ◽  
Treatment Type ◽  
Melanoma Brain Metastases

Background: Brain metastases are observed in more than 40% of all patients with stage 4 melanoma. In recent years, more extensive use of stereotactic radiation (STRT) and the advent of immune checkpoint inhibitors have positively impacted outcomes in patients with metastatic melanoma.brain metastases. Here, we examined real world clinical outcomes of patients presenting with melanoma brain metastases (MBMs). Methods: This retrospective review evaluated MBMs patients treated at The Ottawa Hospital from April 2000 to July 2017. Clinical, radiologic, pathologic and treatment information were gathered from the electronic medical records. The primary outcome was overall survival. The proportional Cox regression model was employed for survival data, while the Fisher’s exact and Mann–Whitney U tests analyzed the relationship between categorical and continuous data, respectively. Results: This retrospective study included 276 patients. Brain metastases were detected symptomatically in 191 patients (69.2%); the rates of detection by routine screening were 4.6% in the pre-2012 era and 11.7% in the contemporary era (p = 0.029). Median survival was three months. Predictors of overall survival were age, higher lactate dehydrogenase (LDH) values, multiple brain lesions, more extensive extracranial disease, neurological symptoms, infratentorial lesions and treatment type. Multivariable analysis demonstrated that stereotactic radiotherapy (STRT) was associated with a hazard ratio of 0.401 (p < 0.001) for survival; likewise, immune checkpoint inhibitor therapy was associated with a hazard ratio of 0.375 (p < 0.001). Conclusion: The findings from this study as “real world” data are consistent with results of pivotal clinical trials in MBMs patients and support contemporary locoregional and immunotherapy practices.

scholarly journals Ipilimumab and Stereotactic Radiosurgery with CyberKnife® System in Melanoma Brain Metastases: A Retrospective Monoinstitutional Experience

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1857
Author(s):  
Valentina Borzillo ◽  
Rossella Di Franco ◽  
Diana Giannarelli ◽  
Fabrizio Cammarota ◽  
Esmeralda Scipilliti ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Local Control ◽  
Immune Checkpoint Inhibitors ◽  
Median Overall Survival ◽  
Checkpoint Inhibitors ◽  
Melanoma Brain Metastases ◽  
One Year ◽  
The Impact

The median overall survival (OS) and local control (LC) of patients with melanoma brain metastases (MBMs) are poor even with immune checkpoint inhibitors and/or radiotherapy (RT). The aims of the study were to evaluate the association and timing of stereotactic radiotherapy (SRT)/radiosurgery (SRS) performed with the CyberKnife® System and ipilimumab (IPI). A total of 63 MBMs patients were analyzed: 53 received RT+IPI and 10 RT alone. Therefore, the patients were divided into four groups: RT PRE-PI (>4 weeks before IPI) (18), RT CONC-IPI (4 weeks before/between first and last cycle/within 3 months of last cycle of IPI) (20), RT POST-IPI (>3 months after IPI) (15), and NO-IPI (10). A total of 127 lesions were treated: 75 with SRS (one fraction) and 24 with SRT (three to five fractions). The median follow-up was 10.6 months. The median OS was 10.6 months for all patients, 10.7 months for RT+IPI, and 3.3 months for NO-IPI (p = 0.96). One-year LC was 50% for all patients, 56% for RT+IPI, and 18% for NO-IPI (p = 0.08). The 1-year intracranial control was 45% for all patients, 44% for RT+IPI, and 51% for NO-IPI (p = 0.73). IPI with SRS/SRT in MBMs treatment could improve LC. However, the impact and timing of the two modalities on patients’ outcomes are still unclear.

Clinical Outcomes of Breast Brain Metastases by Subtype following LINAC Based Stereotactic Radiation

2020 ◽  
Vol 108 (2) ◽  
pp. E18-E19
Author(s):  
Matthew Mills ◽  
Chetna Thawani ◽  
Nicholas Figura ◽  
Siriporn Sarangkasiri ◽  
Iman Washington ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Clinical Outcomes ◽  
Stereotactic Radiation

637 Immune-related adverse events (irAEs) may indicate a favorable prognosis in metastatic renal cell carcinoma (mRCC) patients treated with immune checkpoint inhibitors (ICI)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A672-A673
Author(s):  
Dylan Martini ◽  
Sean Evans ◽  
Subir Goyal ◽  
Yuan Liu ◽  
T Anders Olsen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Adverse Events ◽  
Clinical Outcomes ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
Emory University

BackgroundImmune checkpoint inhibitors (ICI) have become an increasingly utilized treatment in metastatic renal cell carcinoma (mRCC). Although they have a favorable toxicity profile, immune-related adverse events (irAEs) can have a significant impact on patients‘ quality of life. It is not well understood whether irAEs are associated with improved clinical outcomes. We investigated the relationship between irAEs and clinical outcomes in mRCC patients treated with ICI.MethodsWe performed a retrospective study of 200 patients with mRCC who received ICI at Winship Cancer Institute of Emory University from 2015–2020. Clinical outcomes were measured by overall survival (OS), progression-free survival (PFS), and clinical benefit (CB). OS and PFS were calculated from ICI-initiation to date of death and radiographic or clinical progression, respectively. CB was defined as a best radiographic response of complete response (CR), partial response (PR), or stable disease (SD) for >6 months per response evaluation criteria in solid tumors (RECIST) version 1.1. Toxicity data was collected from clinic notes and laboratory values. The association with OS and PFS was modeled by Cox proportional hazards model. Kaplan-Meier curves were created for survival estimates.ResultsMost patients were males (71%), and 78% had clear-cell RCC (ccRCC). Most patients (58%) received anti-PD-1 monotherapy. The majority were international mRCC database consortium (IMDC) intermediate (57%) or poor-risk (26%). Anti-PD-1 monotherapy was the most common (58%) treatment regimen and most patients received ICI as first (38%) or second-line (42%) treatment. One-third of patients (33%) experienced an irAE, with the most common being endocrine (13%), gastrointestinal (11%), and dermatologic (10%). Patients who experienced irAEs had significantly longer OS (HR: 0.52, 95% CI: 0.32–0.87, p=0.013), higher chance of CB (OR: 2.10, 95% CI: 1.11–4.00, p=0.023) and showed a trend towards longer PFS (HR: 0.71, 95% CI: 0.49–1.02, p=0.065) in MVA (table 1). Patients who had thyroid irAEs had significantly longer OS, PFS, and higher chance of CB in MVA (table 1). The objective response rate was higher for patients who experienced irAEs (34% vs. 18%). Patients who experienced irAEs had significantly longer median OS (44.5 vs. 18.2 months, p=0.005) and PFS (7.5 vs 3.6 months, p=0.0028) compared to patients who did not (figure 1).Abstract 637 Table 1MVA* of association between irAEs and clinical outcomesAbstract 637 Figure 1Kaplan-Meier curves of association between immune-related adverse events (irAEs) and overall survival (OS, top panel) and progression-free survival (PFS, bottom panel)ConclusionsWe showed that mRCC patients who experienced irAEs, particularly thyroid irAEs, had improved clinical outcomes. This suggests that irAEs may be prognostic of favorable outcomes in mRCC patients treated with ICI. Larger, prospective studies are needed to validate these findings.AcknowledgementsResearch reported in this publication was supported in part by the Breen Foundation and the Biostatistics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Trial RegistrationNot applicableEthics ApprovalThis retrospective study was approved by the Emory University Institutional Review Board.ConsentNot applicableReferencesNot applicable

scholarly journals 236 Predictors of ICI renal toxicity: a pathological approach

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A252-A252
Author(s):  
Ala Abudayyeh ◽  
Liye Suo ◽  
Heather Lin ◽  
Omar Mamlouk ◽  
Cassian Yee ◽  
...  
Keyword(s):  
Overall Survival ◽  
Renal Toxicity ◽  
Checkpoint Inhibitors ◽  
Interstitial Fibrosis ◽  
Transplant Rejection ◽  
Categorical Variables ◽  
Rank Test ◽  
Cancer Center ◽  
Renal Response ◽  
Md Anderson

BackgroundInflammatory response in unintended tissues and organs associated with the use of immune checkpoint inhibitors also known as immune related adverse events (irAEs) is a management challenge, and renal irAEs are associated with increased patient morbidity and mortality. The most common renal toxicity is acute interstitial nephritis (AIN), characterized by infiltration of renal tissue with immune cells, and may be analogous to kidney transplant rejection. Using both clinical variables and tissue findings we evaluated a large cohort of ICI cases to determine predictors of renal response and overall survival.MethodsWe retrospectively reviewed all patients treated with ICI (August 2007 to August 2020) at MD Anderson Cancer Center. A total of 38 patients with biopsy confirmed AIN and available tissue were identified. All slides were reviewed by two board certified renal pathologists and the severity of inflammation and chronicity was graded using transplant rejection BANFF criteria. Patients were categorized as renal responders if creatinine improved or returned to baseline after treatment and non-responders if it did not. Fisher’s exact tests for categorical variables and t-test/ANOVA or the counterparts of the non-parametric approaches (Wilcoxon rank-sum or Kruskal-Wallis) for continuous variables were used to compare patient‘s characteristics between groups. The distribution of overall survival (OS) was estimated by the Kaplan-Meier method. Log-rank test was performed to test the difference in survival between groups.ResultsBased on the detailed pathological findings, patients with increased interstitial fibrosis were less likely to have renal response with treatment compared to patients with less fibrosis, (p < 0.05). Inflammation, tubulitis, number of eosinophils and neutrophils had no impact on renal response. Patients with response within 3 months of AKI treatment had a superior OS in comparison to patients who responded late (12-month OS rate: 77% vs 27%, p < 0.05). Notably, patients who received concurrent ICI and achieved renal response within 3 months had the best OS while those who did not receive concurrent ICI nor achieved renal response had worst OS (12-month OS rate: 100% (renal response and concurrent ICI) vs 72% ( renal response with no concurrent ICI), vs 27% ( no renal response and nonconcurrent ICI) (p < 0.05).ConclusionsThis is the first analysis of ICI induced nephritis where a detailed pathological and clinical evaluation was performed to predict renal response. Our findings highlight the importance of early diagnosis and treatment of ICI-AIN while continuing concurrent ICI therapy.Ethics ApprovalThis retrospective study was approved by the institutional review board at The University of Texas MD Anderson Cancer Center, and the procedures followed were in accordance with the principles of the Declaration of Helsinki.

scholarly journals The Impact of Prolonged Mechanical Ventilation on Overall Survival in Patients With Surgically Treated Brain Metastases

2021 ◽  
Vol 11 ◽  
Author(s):  
Patrick Schuss ◽  
Niklas Schäfer ◽  
Christian Bode ◽  
Valeri Borger ◽  
Lars Eichhorn ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Overall Survival ◽  
Surgical Treatment ◽  
Brain Metastases ◽  
Prolonged Mechanical Ventilation ◽  
Postoperative Phase ◽  
Significant Prognostic Factor ◽  
Cancer Disease ◽  
Definition Of ◽  
The Impact

ObjectiveSurgical resection represents a common treatment modality in patients with brain metastasis (BM). Postoperative prolonged mechanical ventilation (PMV) might have an enormous impact on the overall survival (OS) of these patients suffering from advanced cancer disease. We therefore have analyzed our institutional database with regard to a potential impact of PMV on OS of patients who had undergone surgery for brain metastases.Methods360 patients with surgically treated brain metastases were included. The definition of PMV consisted of postoperative mechanical ventilation lasting for more than 48 hours. Analysis of survival incorporating established prognostic factors such as age, location of BM, and preoperative physical status was performed.Results14 of 360 patients with BM (4%) suffered from postoperative PMV after surgical treatment of BM. Patients with PMV presented in a significantly more impaired neurological condition preoperatively than patients without (p&lt;0.0001). Multivariate analysis determined PMV to be a significant prognostic factor for OS after surgical treatment in patients with BM, independent of other predictive factors (p&lt;0.0001).ConclusionsThe present study demonstrates postoperative PMV as significantly related to poor OS in patients with surgically treated BM. Postoperative PMV is a so far underestimated prognostic predictor, but might be utilized for optimized patient management early in the postoperative phase. For this purpose, the results of the present study should encourage the initiation of further scientific efforts.

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