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.

scholarly journals Neutrophil to lymphocyte ratio influences impact of steroids on efficacy of immune checkpoint inhibitors in lung cancer brain metastases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adam Lauko ◽  
Bicky Thapa ◽  
Mayur Sharma ◽  
Baha’eddin Muhsen ◽  
Addison Barnett ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Neutrophil To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Significant Difference ◽  
The Impact

AbstractSteroids are often utilized to manage patients with non-small cell lung cancer brain metastases (NSCLCBM). Steroids and elevated neutrophil-to-lymphocyte ratio (NLR) have been associated with decreased overall survival (OS) in patients treated with immune checkpoint inhibitors (ICI). We retrospectively investigated patients treated with ICI after the diagnosis of NSCLCBM at a single tertiary care institution examing the impact of steroids and NLR. Overall survival (OS) and intracranial progression-free survival (PFS) were analyzed. 171 patients treated with ICI for NSCLCBM were included. Thirty-six received steroids within 30 days of the start of ICI, and 53 patients had an NLR ≥ 5 before the start of ICI. Upfront steroids was associated with decreased OS on multivariable analysis (median OS 10.5 vs. 17.9 months, p = .03) and intracranial PFS (5.0 vs. 8.7 months, p = .045). NLR ≥ 5 was indicative of worse OS (10.5 vs. 18.4 months, p = .04) but not intracranial PFS (7.2 vs. 7.7 months, p = .61). When NLR and upfront steroids are modeled together, there is a strong interaction (p = .0008) indicating that the impact of steroids depended on the patient’s NLR. In a subgroup analysis, only in patients with NLR < 4 was there a significant difference in OS with upfront steroids (26.1 vs. 15.6 months, p = .032). The impact of steroids on the efficacy of ICI in patients with NSCLCBM is dependent on the patient's NLR underscoring its importance in these patients. Patients with a low NLR, steroid use decreases the efficacy of ICI. These results can inform clinicians about the impact of steroids in patients treated with ICI.

scholarly journals Treatment of Angiosarcoma with Pazopanib and Paclitaxel: Results of the EVA (Evaluation of Votrient® in Angiosarcoma) Phase II Trial of the German Interdisciplinary Sarcoma Group (GISG-06)

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1223
Author(s):  
Daniel Pink ◽  
Dimosthenis Andreou ◽  
Sebastian Bauer ◽  
Thomas Brodowicz ◽  
Bernd Kasper ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Median Overall Survival ◽  
Phase Ii Trial ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Future Studies ◽  
Entire Cohort

We aimed to evaluate the efficacy and toxicity of paclitaxel combined with pazopanib in advanced angiosarcoma (AS). The primary end point was progression-free survival (PFS) rate at six months (PFSR6). Planned accrual was 44 patients in order to detect a PFSR6 of >55%, with an interim futility analysis of the first 14 patients. The study did not meet its predetermined interim target of 6/14 patients progression-free at 6 months. At the time of this finding, 26 patients had been enrolled between July 2014 and April 2016, resulting in an overrunning of 12 patients. After a median follow-up of 9.5 (IQR 7.7–15.4) months, PFSR6 amounted to 46%. Two patients had a complete and seven patients a partial response. Patients with superficial AS had a significantly higher PFSR6 (61% vs. 13%, p = 0.0247) and PFS (11.3 vs. 2.7 months, p < 0.0001) compared to patients with visceral AS. The median overall survival in the entire cohort was 21.6 months. A total of 10 drug-related serious adverse effects were reported in 5 patients, including a fatal hepatic failure. Although our study did not meet its primary endpoint, the median PFS of 11.6 months in patients with superficial AS appears to be promising. Taking recent reports into consideration, future studies should evaluate the safety and efficacy of VEGFR and immune checkpoint inhibitors with or without paclitaxel in a randomized, multiarm setting.

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 Association of Brain Metastases With Immune Checkpoint Inhibitors Efficacy in Advanced Lung Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yanning Wang ◽  
Qianning Zhang ◽  
Chuansheng Chen ◽  
Yuxuan Hu ◽  
Liyun Miao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Advanced Lung Cancer ◽  
Lung Cancer Patients ◽  
Hazard Ratios

BackgroundIn pivotal immunotherapy trials, the efficacy of immune checkpoint inhibitors as treatments for lung cancer patients with brain metastases remains controversial. The aim of this study was to assess the relative efficacy of immunotherapy versus standard systemic therapy in advanced lung cancer patients with and without brain metastases.MethodsSystematic searches of PubMed, Embase, Cochrane database, and conference proceedings up to Aug 6, 2020 without year and language restrictions. The main outcomes were the overall survival in patients with and without brain metastases measured by hazard ratios, and the difference in efficacy between patients with and without brain metastases was measured by ratio of hazard ratios.ResultsNine eligible randomized controlled trials involving 6241 patients (682 [11%] with brain metastases and 5559 [89%] without brain metastases) were included in the analysis. A survival benefit of immunotherapy was observed for both patients with brain metastases (HR, 0.75; 95%CI, 0.53-0.97; P = .026) and patients without brain metastases (HR, 0.75; 95%CI, 0.67-0.83; P &lt;.001). However, patients without brain metastases benefit more from immunotherapy than patients with brain metastases (HR, 1.37; 95%CI, 1.15-1.63; P = .001). Additionally, subgroup analyses indicated that tumor type affect the efficacy of immunotherapy in patients with brain metastases (HR, 1.04 vs 1.54; interaction, P = .041).ConclusionsImmunotherapy can significantly improve overall survival for advanced lung cancer patients with asymptomatic brain metastases, especially in patients with non-small-cell lung cancer, but the magnitude of benefit is brain metastases dependent.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020206597.

scholarly journals Immune checkpoint inhibitors and radiosurgery for newly diagnosed melanoma brain metastases

2018 ◽  
Vol 140 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Tyler P. Robin ◽  
Robert E. Breeze ◽  
Derek E. Smith ◽  
Chad G. Rusthoven ◽  
Karl D. Lewis ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Newly Diagnosed ◽  
Melanoma Brain Metastases

Incidence and characterization of venous thromboembolic events (VTE) in patients with pancreatic cancer: Effect of timing of VTE on survival.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4037-4037
Author(s):  
Maithili A Shethia ◽  
Aparna Hegde ◽  
Xiao Zhou ◽  
Michael J. Overman ◽  
Saroj Vadhan-Raj
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Survival Analysis ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Venous Thromboembolic Events ◽  
Venous Thromboembolic ◽  
One Year ◽  
The Impact

4037 Background: Patients (pts) with pancreatic cancer are at high risk for VTE, and the occurrence of VTE can affect pts’ prognosis. The purpose of this study was to evaluate the incidence of VTE and the impact of timing of VTE (early vs. late) on survival. Methods: Medical record of 260 pts with pancreatic cancer, newly referred to UT MDACC during one year period from 1/1/2006 to 12/31/2006, were reviewed for the incidence of VTE during a 2-year follow-up period from the date of diagnosis. All VTE episodes were confirmed by radiologic studies. Survival analysis was conducted using Kaplan-Meier analysis and Cox proportional hazard models. Results: Of the 260 pts, 47 pts (18%) had 51 episodes of VTE during the 2-year follow-up. The median age of the pts with VTE was 61 years (range: 28-86) and 53% were males. Of the 47 pts with VTE, 27 (57%) had PE, 19 (40%) had DVT and 1 had concurrent PE/DVT. Three pts had recurrent VTE during the study period. Median follow-up time for OS was 192 days (range: 1-1652 days). Kaplan-Meier Survival analysis showed that those who developed VTE earlier (within 30 or 90 days) had shorter median overall survival (OS) compared with those who had VTE beyond these time points. The hazard ratios, 95% CI, and median OS at 1 year are summarized in the table below. Conclusions: The incidence of VTE is high in pts with pancreatic cancer. The timing of VTE had a significant impact on OS; pts who had an early development of VTE had a shorter overall survival. [Table: see text]

Immune checkpoint inhibitors and stereotactic radiosurgery (SRS) in melanoma brain metastases.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e21523-e21523
Author(s):  
Charlotte Fenioux ◽  
Idriss Troussier ◽  
Jean-Jacques Mazeron ◽  
Charles Henry Canova ◽  
Philippe Saiag ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Melanoma Brain Metastases

scholarly journals P.109 Increased survival when combining BRAF inhibitors and stereotactic radiosurgery in patients with melanoma brain metastases

2016 ◽  
Vol 43 (S2) ◽  
pp. S45-S46
Author(s):  
A Wolf ◽  
A Pavlick ◽  
M Wilson ◽  
J Silverman ◽  
D Kondziolka
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Systemic Disease ◽  
Braf Inhibitor ◽  
Braf Inhibitors ◽  
Actuarial Survival ◽  
Early Management ◽  
Melanoma Brain Metastases ◽  
The Impact

Background: The purpose of the study was to evaluate the impact of BRAF inhibitors on survival outcomes in patients receiving stereotactic radiosurgery (SRS) for melanoma brain metastases. Methods: We prospectively collected treatment outcomes for 80 patients with melanoma brain metastases who underwent SRS. Thirty-five patients harbored the BRAF mutation (BRAF-M) and 45 patients did not (BRAF-WT). Results: The median overall survival from first SRS procedure was 11.2 months if treated with a BRAF inhibitor and 4.5 months for BRAF-WT. Actuarial survival rates for BRAF-M patients on an inhibitor were 54% and 41% at 6 and 12 months after radiosurgery, in contrast to 28% and 19% for BRAF-WT. Overall survival was extended for patients on a BRAF inhibitor if initiated at or after the first SRS. The local control rate did not differ based on BRAF status and was over 90%. Patients with higher KPS, fewer treated metastases, controlled systemic disease, RPA class 1 and BRAF-M patients had extended overall survival. Conclusions: Patients with BRAF-M treated with both SRS and BRAF inhibitors, at or after SRS, have increased overall survival. As patients live longer due to more effective systemic and local therapies, close surveillance and early management of intracranial disease with SRS will become increasingly important.

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