NCMP-03. ANATOMIC AND SURGICAL FACTORS PREDICT DEVELOPMENT OF LEPTOMENINGEAL DISEASE IN PATIENTS WITH METASTATIC MELANOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi147-vi147
Author(s):  
Stephen Lowe ◽  
Christopher Wang ◽  
Amanda Brisco ◽  
John Arrington ◽  
Kamran Ahmed ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Primary Melanoma ◽  
Female Gender ◽  
Causative Factor ◽  
Leptomeningeal Disease ◽  
Melanoma Brain Metastases ◽  
Highly Correlated ◽  
Periventricular Lesions ◽  
Dural Metastasis

Abstract Leptomeningeal disease (LMD) is a devastating complication of systemic malignancy, portending a poor prognosis with an estimated median survival of 4-6 weeks if left untreated. Several reports have suggested surgical resection as a potential causative factor. Herein, we explore if surgical and anatomical factors are correlated with development of LMD in patients with melanoma brain metastases. METHODS: Patients treated at our institution between 1999-2019 for primary melanoma with brain metastasis were compiled into a database based on ICD9/10 coding. 1,079 patients with melanoma brain metastases and appropriate imaging were identified, and 834 patients with a minimum of 3 months’ follow up were included. Patients were dichotomized by development of LMD or lack thereof, and categorized into an overall cohort, and surgical and non-surgical cohorts. Anatomic factors and ventricular access during surgery were investigated as possible correlative factors for the development of LMD. RESULTS: In the overall cohort, female gender(p=0.033), presence of dural metastasis(p=0.018), presence of periventricular lesions(p< .001), presence of intraventricular lesions(p< .001), and ventricular access during surgery(p< .001) were significantly associated with LMD. Patients undergoing surgery, or those undergoing surgery without ventricular access, were not at higher risk of LMD. On multivariate analysis, female gender(p=.033), presence of periventricular lesions (p< .001), presence of intraventricular lesions(p< .002), and presence of dural metastasis(p=0.032) were significantly associated with development of LMD. In patients who had surgery, iatrogenic ventricular access(p< .001) was significantly correlated with LMD. In the group of patients without surgery, those with periventricular lesions had significantly higher odds of LMD(p< .001). CONCLUSIONS: In a retrospective cohort of patients with melanoma metastatic to the brain, surgical intervention does not increase odds of LMD; however, iatrogenic access to the CSF space during surgery is highly correlated with LMD development. Anatomic contact with the CSF space predicts LMD regardless of surgical status.

scholarly journals LMD-19. Anatomic and Surgical Factors Predict Development of Leptomeningeal Disease in Patients with Metastatic Melanoma

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii11-iii11
Author(s):  
Stephen Lowe ◽  
Christopher P Wang ◽  
Amanda Brisco ◽  
Kamran Ahmed ◽  
Michael A Vogelbaum ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Univariate Analysis ◽  
Primary Melanoma ◽  
Female Gender ◽  
Causative Factor ◽  
Leptomeningeal Disease ◽  
Melanoma Brain Metastases ◽  
Highly Correlated ◽  
Periventricular Lesions ◽  
Dural Metastasis

Abstract Background Leptomeningeal disease (LMD) is a devastating complication of systemic malignancy, portending a poor prognosis with an estimated median survival of 4–6 weeks if left untreated. Several reports have suggested surgical resection, particularly piecemeal resection, as a potential causative factor. Herein, we explore if surgical and anatomical factors are correlated with development of LMD in patients with melanoma brain metastases. Methods Patients treated at our institution between 1999–2019 for primary melanoma with brain metastasis were compiled into a database based on ICD9/10 coding. 1,079 patients with melanoma brain metastases and appropriate imaging were identified, and 834 patients with a minimum of 3 months’ follow up were included. Patients were dichotomized by development of LMD or lack thereof. General demographic information, surgical and anatomic data, and ventricular access during surgery were investigated as possible correlative factors for the development of LMD. Results On univariate analysis, female gender (p=0.033), presence of dural metastasis (p=0.018), presence of periventricular lesions (p<.001), presence of intraventricular lesions (p<.001), and ventricular access during surgery (p<.001) were significantly associated with LMD. Patients undergoing surgery, or those undergoing surgery without ventricular access, were not at higher risk of LMD. Administration of immunotherapy, either as first-line or salvage therapy, did not impact rates of LMD. On multivariate analysis, female gender (p=.033), presence of periventricular lesions (p<.001), presence of intraventricular lesions (p<.002), and presence of dural metastasis (p=0.032) were significantly associated with development of LMD. In patients who had surgery, iatrogenic ventricular access (p<.001) was significantly correlated with LMD. Conclusions In a retrospective cohort of patients with melanoma metastatic to the brain, those patients with pre-existing lesions in contact with the CSF space are more likely to develop LMD than those who do not. In addition, iatrogenic access to the CSF space during surgery is highly correlated with LMD development.

scholarly journals SURG-10. MELANOMA CEREBRAL METASTASES IN IRELAND- GETTING UNDER THE SKIN

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i32-i32
Author(s):  
Philip O’Halloran ◽  
Anna Cleary ◽  
Jane Cryan ◽  
John Caird
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Braf Mutation ◽  
Primary Melanoma ◽  
Cerebral Metastases ◽  
Leptomeningeal Disease ◽  
Anatomical Location ◽  
Age Difference ◽  
Male Predominance ◽  
Melanoma Brain Metastases

Abstract BACKGROUND: Ireland has the highest rate of melanoma related deaths in Europe. Despite the incidence of melanoma reaching record highs there remains a paucity of information in Ireland regarding the factors associated with melanoma brain metastasis (MBM). METHODS: Patients diagnosed with MBM in Ireland were retrospectively identified in Beaumont Hospital between 1999 and 2018. Patient demographics; year of detection of MBM, age at diagnosis of primary melanoma, age at detection of MBM, anatomical location of primary melanoma, BRAF mutation analysis and the number of metastases were investigated. Follow up data was also derived, including overall survival (OS). RESULTS: The incidence of malignant melanoma has increased by 158% over the past 20 years with 1,092 and 422 cases diagnosed in 2018 and 1999, respectively.128 patients with melanoma brain metastases were identified during this period. The median OS after detection of MBM was 5 months (95% CI 0.641–9.359 months). There was a male predominance (n= 77/128; 60%) with a median age of death at 58 years (n=67; range 16–82 years). Although females had a significantly longer time between diagnosis of primary melanoma and detection of MBM compared to males, 4 and 2 years respectively (p=0.02442), there was no significant age difference at death between males and females (p= 0.41294). BRAF mutation was an independent prognostic factor with an improved overall survival compared to those without the mutation, of 8 months and 3.5 months respectively (p=0.0012). Although non significant, the primary location of melanoma, leptomeningeal disease and number of cerebral metastases were all important considerations in this group. CONCLUSIONS: Male predominance and BRAF mutation represent important factors in this population group. The results of this study add to our knowledge concerning outcomes in melanoma brain metastases in Ireland, and may be useful in clinical planning, educational programs and future treatments.

Incidence, timing, and treatment of new brain metastases after Gamma Knife surgery for limited brain disease: the case for reducing the use of whole-brain radiation therapy

2011 ◽  
Vol 115 (1) ◽  
pp. 37-48 ◽  
Author(s):  
Stephen Rush ◽  
Robert E. Elliott ◽  
Amr Morsi ◽  
Nisha Mehta ◽  
Jeri Spriet ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Metastases ◽  
Gamma Knife ◽  
Gamma Knife Surgery ◽  
Whole Brain Radiation Therapy ◽  
Leptomeningeal Disease ◽  
Whole Brain ◽  
Whole Brain Radiation ◽  
Brain Radiation

Object In this paper, the authors' goal was to analyze the incidence, timing, and treatment of new metastases following initial treatment with 20-Gy Gamma Knife surgery (GKS) alone in patients with limited brain metastases without whole-brain radiation therapy (WBRT). Methods A retrospective analysis of 114 consecutive adults (75 women and 34 men; median age 61 years) with KPS scores of 60 or higher who received GKS for 1–3 brain metastases ≤ 2 cm was performed (median lesion volume 0.35 cm3). Five patients lacking follow-up data were excluded from analysis. After treatment, patients underwent MR imaging at 6 weeks and every 3 months thereafter. New metastases were preferentially treated with additional GKS. Indications for WBRT included development of numerous metastases, leptomeningeal disease, or diffuse surgical-site recurrence. Results The median overall survival from GKS was 13.8 months. Excluding the 3 patients who died before follow-up imaging, 12 patients (11.3%) experienced local failure at a median of 7.4 months. Fifty-three patients (50%) developed new metastases at a median of 5 months. Six (7%) of 86 instances of new lesions were symptomatic. Most patients (67%) with distant failures were successfully treated using salvage GKS alone. Whole-brain radiotherapy was indicated in 20 patients (18.3%). Thirteen patients (11.9%) died of neurological disease. Conclusions For patients with limited brain metastases and functional independence, 20-Gy GKS provides excellent disease control and high-functioning survival with minimal morbidity. New metastases developed in almost 50% of patients, but additional GKS was extremely effective in controlling disease. Using our algorithm, fewer than 20% of patients required WBRT, and only 12% died of progressive intracranial disease.

Five-year overall survival from the anti-PD1 brain collaboration (ABC Study): Randomized phase 2 study of nivolumab (nivo) or nivo+ipilimumab (ipi) in patients (pts) with melanoma brain metastases (mets).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9508-9508
Author(s):  
Georgina V. Long ◽  
Victoria Atkinson ◽  
Serigne Lo ◽  
Alexander David Guminski ◽  
Shahneen Kaur Sandhu ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Braf Inhibitor ◽  
Local Therapy ◽  
Leptomeningeal Disease ◽  
Open Label ◽  
Phase 2 Study ◽  
Melanoma Brain Metastases ◽  
Secondary Endpoints ◽  
Local Brain ◽  
Clinical Trial Information

9508 Background: Preliminary data from the ABC (76 pts) and CheckMate 204 (94 pts) trials showed that nivo and nivo+ipi have activity in active melanoma brain metastases, with durable responses in a subset of pts. Here, we report updated 5-yr data from all pts enrolled on the ABC trial (NCT02374242). Methods: This open-label ph2 trial enrolled 3 cohorts of pts with active melanoma brain mets naïve to anti-PD1/PDL1/PDL2/CTLA4 from Nov 2014-Apr 2017. Pts with asymptomatic brain mets with no prior local brain therapy were randomised to cohort A (nivo 1mg/kg + ipi 3mg/kg, Q3Wx4, then nivo 3mg/kg Q2W) or cohort B (nivo 3mg/kg Q2W). Cohort C (nivo 3mg/kg Q2W) had brain mets i) that failed local therapy, ii) with neuro symptoms and/or iii) with leptomeningeal disease. Prior BRAF inhibitor (BRAFi) was allowed. The primary endpoint was best intracranial response (ICR) ≥wk12. Key secondary endpoints were IC PFS, overall PFS, OS, & safety. Results: A total of 76 pts (med f/u 54 mo) were enrolled; median age 59y, 78% male. For cohorts A, B and C: elevated LDH 51%, 58% and 19%; V600BRAF 54%, 56% and 81%; prior BRAFi 23%, 24%, 75%. Efficacy and toxicity are shown in the table. There were no treatment-related deaths. 1/17 deaths in cohort A & 4/16 in cohort B were due to IC progression only. Conclusions: Nivo monotherapy and ipi+nivo are active in melanoma brain mets, with durable responses in the majority of patients who received ipi+nivo upfront. A study of upfront ipi+nivo+/-SRS is underway (NCT03340129). Clinical trial information: NCT02374242. [Table: see text]

scholarly journals Predictors of leptomeningeal disease following hypofractionated stereotactic radiotherapy for intact and resected brain metastases

2019 ◽  
Vol 22 (1) ◽  
pp. 84-93 ◽  
Author(s):  
Timothy K Nguyen ◽  
Arjun Sahgal ◽  
Jay Detsky ◽  
Eshetu G Atenafu ◽  
Sten Myrehaug ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiotherapy ◽  
Median Overall Survival ◽  
Multivariable Analysis ◽  
Leptomeningeal Disease ◽  
Hypofractionated Stereotactic Radiotherapy ◽  
Increased Risk ◽  
Intact Brain ◽  
Intracranial Lesions

Abstract Background The objective was to evaluate the risk and predictors of developing leptomeningeal disease (LMD) in patients with brain metastases treated with 5-fraction hypofractionated stereotactic radiotherapy (HSRT). Methods Patients treated with HSRT for intact brain metastases and/or surgical cavities were reviewed from a prospectively maintained database. Radiographic patterns of LMD were classified as focal classical, diffuse classical, focal nodular, and diffuse nodular. Results HSRT was delivered, most commonly 30 Gy in 5 fractions, to 320 intracranial lesions (57% intact and 43% surgical cavities) in 235 patients. The median follow-up was 13.4 months (range, 0.8 to 60 mo). LMD developed in 19% of patients with a 1-year LMD rate of 12%. From the diagnosis of LMD, the median overall survival (OS) was 3.8 months (range, 2–20.8 mo). The most common LMD pattern was diffuse nodular (44%). No difference in OS was observed between LMD patterns (P = 0.203). Multivariable analysis identified surgical cavities at significantly higher risk of LMD compared with intact lesions (odds ratio [OR] = 2.30, 95% CI: 1.24, 4.29, P = 0.008). For cavities, radiosensitive tumors (OR = 2.35, 95% CI: 1.04, 5.35, P = 0.041) predicted for LMD, while, for intact metastases, patients receiving treatment with targeted agents or immunotherapy (TA/I) were at lower risk (OR = 0.178, 95% CI: 0.04, 0.79, P = 0.023). Conclusions Patients who had a brain metastasis resected were at an increased risk of LMD. OS was poor despite treatment of LMD, and no differences in OS based on the pattern of LMD was observed. Treatment with TA/I was observed to be protective against LMD and requires further study.

RADT-06. RADIOTHERAPY FOR BRAIN METASTASES FROM THYROID CANCER: A RETROSPECTIVE COHORT STUDY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi42-vi42
Author(s):  
Erik Blomain ◽  
Scott Berta ◽  
Nicholas Hug ◽  
Duc Giao ◽  
Antonio Meola ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Brain Metastases ◽  
Radiation Necrosis ◽  
Local Failure ◽  
Competing Risk ◽  
Treatment Modalities ◽  
Leptomeningeal Disease ◽  
Risk Of Death ◽  
Anaplastic Histology

Abstract PURPOSE/OBJECTIVE(S) Brain metastases from thyroid carcinoma are rare. Although stereotactic radiosurgery (SRS) is a standard of care for patients with brain metastases across many histologies, the current NCCN guidelines do not support a universal role for this modality in thyroid cancer. MATERIALS AND METHODS Thyroid cancer patients with brain metastases treated with radiotherapy at our institution from 2002-2020 were studied. Cumulative risk of local failure, distant intracranial failure and radiation necrosis were calculated using a competing risk of death analysis and censored at the last imaging follow-up. Overall survival was analyzed using Kaplan-Meier method. Stratified cox regression was used to study per-lesion outcomes. RESULTS We identified 34 patients with 203 treated brain metastases. 179 (88.2%) lesions were of differentiated histology; the remainder were anaplastic histology. Four patients received whole brain radiotherapy (WBRT) while 30 patients received SRS (SFED 22, interquartile (IQ) range 20-22). Of the patients receiving WBRT, one (25%) had anaplastic histology, and the median number of lesions was 15 (as compared to 2 for SRS). Median follow up among survivors was 32.3 months and median survival was 10.8 months. There were no observed failures (local or distant intracranial) observed at 1 year in the 24 metastases with anaplastic histology, although competing risk of death was high (91.7%). The 1 year cumulative incidences of local failure and distant intracranial failures were 9.8% (95CI 5.7%-13.9%) and 35.0% (95CI 29.0%-41.0%), respectively, in differentiated tumors. 6 (10.2%) of the distant intracranial failures were new cases of leptomeningeal disease. The 1 year risk of radiation necrosis was 15.5%. Of these cases, most were Grade 2 (57.1%); 3 (42.9%) were Grade 4 (there were no Grade 1 or 3 events). CONCLUSION In the largest known cohort of thyroid cancer brain metastasis patients, radiotherapy and SRS appear to be safe and effective treatment modalities.

scholarly journals Prognostic factors for melanoma brain metastases treated with stereotactic radiosurgery

2016 ◽  
Vol 125 (Supplement_1) ◽  
pp. 31-39 ◽  
Author(s):  
Shelly X. Bian ◽  
David Routman ◽  
Jonathan Liu ◽  
Dongyun Yang ◽  
Susan Groshen ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Tumor Volume ◽  
Cox Regression ◽  
Intracranial Tumor ◽  
Entire Cohort ◽  
Hazard Ratios ◽  
Melanoma Brain Metastases ◽  
Lesion Number ◽  
Male Sex

OBJECTIVEStereotactic radiosurgery (SRS) is routinely used to treat brain metastases from melanoma due to their radioresistant nature. The median survival for these patients is 4–6 months, according to earlier studies. The aim of this study was to evaluate prognostic factors that influence survival in patients with metastatic melanoma to the brain treated with SRS.METHODSThis retrospective analysis included all patients with melanoma brain metastases treated with SRS at the University of Southern California between 1994 and 2015. For the entire cohort, the authors performed a multivariable Cox regression analysis with an end point of survival. Covariates included number of lesions, total intracranial tumor volume, age, sex, and treatment date prior to 2005 or 2005 onward.In the subset of patients with > 1 lesion, additional multivariable Cox regression was performed, with covariates of Karnofsky Performance Scale, Graded Prognostic Assessment, Recursive Partitioning Analysis, timing of metastases (synchronous/metachronous), change in lesion number, and previous whole-brain radiation therapy or resection in addition to the previously mentioned covariates. Overall survival (OS) was calculated from the day SRS was performed to the date of last follow-up or date of death.RESULTSA total of 401 patients were available for analysis. The median follow-up was 35.1 months for patients alive at the time of analysis, and the median OS was 7.7 months for the entire cohort (95% CI 6.7–8.3 months). In the entire cohort, greater number of brain lesions, higher total intracranial tumor volume, age > 50 years, treatment prior to 2005, and male sex were found to be statistically significant factors associated with worse survival. The strongest risk factors for decreased OS were tumor volume > 10 cm3 and ≥ 5 lesions, with hazard ratios for risk of death of 1.7 and 2.2, respectively. In the subset of patients with > 1 lesion, tumor volume > 10 cm3 and no resection were the only factors significantly associated with decreased OS, with hazard ratios of 1.9 and 2.0 (hazard ratio of 0.49 for resection), respectively.CONCLUSIONSThis study suggests that greater lesion number, higher intracranial tumor volume, older age, treatment prior to 2005, and male sex have prognostic significance for decreased OS in patients with melanoma brain metastases treated with SRS. Additionally, in the subset of patients with > 1 lesion, only higher total tumor volume and no resection were associated with worse survival.

scholarly journals SURG-11. Surgery for control of brain metastases after prior checkpoint inhibitor immunotherapy: a single-center series

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii25-iii26
Author(s):  
Ramin Morshed ◽  
Jason Chung ◽  
Vivek Sudhakar ◽  
Daniel Cummins ◽  
Jacob Young ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Brain Metastases ◽  
Surgical Resection ◽  
Checkpoint Inhibitor ◽  
Leptomeningeal Disease ◽  
Single Center ◽  
Factors Associated ◽  
Local Progression ◽  
Inhibitor Treatment

Abstract Background Despite the promising results for treating metastatic cancer with checkpoint inhibitor immunotherapies, there are limited data on surgical outcomes for brain metastases (BMs) that have progressed after prior checkpoint inhibitor treatment. The objective of this study was to identify factors associated with local progression, leptomeningeal disease, and survival for patients undergoing surgical resection of a BM in patients previously treated with checkpoint inhibitor immunotherapy. Methods A retrospective, single-center cohort study was conducted with inclusion of adult patients undergoing surgical resection of a BM in the setting of progression after prior checkpoint inhibitor treatment. Univariate and multivariate analyses were performed to identify factors associated with outcomes of interest. Results Over an 8-year period, 26 patients who underwent resection of 30 BMs met inclusion criteria. Median patient age at surgery was 63.9 years, and median clinical follow-up was 6.9 months (range 0.1 – 52.9). Extracranial disease was present at the time of surgery in 73.3% of cases. There were 6 postoperative complication events (20% of cases) by 30-days. By last follow-up, 65.4% of the cohort had died with a median censored survival of 7.6 months from surgery. Eight patients (30.8%) died within 3 months of surgery. On multivariate analysis, postoperative complications were associated with worse survival (HR 5.33, 95%CI 1.15–24.77, p=0.03). Four BMs had local progression (13.3%), and 60% of procedures were associated with distant progression within a median time of 3.6 months. Leptomeningeal disease developed in 32% of cases. On multivariate analysis, increased time from BM diagnosis to surgery was associated with a greater risk of leptomeningeal disease (OR 1.2, 95%CI 1.00–1.43, p=0.021). Conclusion Patients who require BM resection after prior checkpoint inhibitor treatment have an overall poor prognosis. Although local control rates are acceptable, these patients are at high risk for developing leptomeningeal disease postoperatively.

scholarly journals RADI-37. CLINICAL RISK FACTORS FOR INTRACRANIAL HEMORRHAGE OF SOLID MELANOMA BRAIN METASTASES AFTER RADIOSURGERY

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i29-i29
Author(s):  
Catherine Okoukoni ◽  
Michael LeCompte ◽  
Ryan Hughes ◽  
Emory McTyre ◽  
Christina Cramer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Brain Metastases ◽  
Intracranial Hemorrhage ◽  
Imaging Data ◽  
Free Survival ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Melanoma Brain Metastases ◽  
Impact Risk

Abstract PURPOSE: Melanoma brain metastases (MBM) are among the most common solid tumors associated with intracranial hemorrhage (ICH). Our objective is to investigate risk factors for post-radiosurgery intracranial hemorrhage (PRH). METHODS: We collected demographic, clinical, treatment, toxicity, survival, and imaging data for patients with solid MBM who underwent SRS between 2000 and 2016 at our institution. Bleed free survival (BFS) and overall survival (OS) analyses were performed using Kaplan–Meier methods. Logistic regression was used to identify PRH risk factors. RESULTS: From 2000 to 2016, 107 patients with a total of 548 solid MBM received SRS. Median patient age at time of SRS was 63.2 years. Median MBM volume was 2.8 cm3 (range 0.01–21.3 cm3). MBM were in the cortex (n = 431), cerebellum (n= 85), basal ganglia (n= 23), and brain stem (n= 9). MBM were treated to a median dose of 20 Gy (range 14–20 Gy). Seventeen patients received immunotherapy (IT) within 1 year of SRS, 7 patients received concurrent immunotherapy (XR-IT). Median follow-up and OS was 13.5 months and 10.8 months, respectively. Median BFS was 8.3 months. PRH occurred in 123 MBM (22%). MBM volume (p= 0.0001), total MBM volume (p= 0.0006), IT (p= 0.04), and XR-IT (p= 0.03) were associated with increased PRH. PRH cumulative incidence within 24 mo of SRS was increased in MBM > 2.8 cm3 compared with patients with smaller MBM: 27.5% verse 5.3%, respectively. Age, sex, hypertension, MBM location, total MBM number, and marginal dose (p > 0.05) did not significantly impact risk of PRH. No significant difference in 6, 12, or 24 mo actuarial OS rates were observed in patients with PRH (p > 0.05). CONCLUSIONS: Patients with larger MBM volume and IT within 1 year of SRS have the greatest risk of PRH. PRH did not significantly impact OS in this study.

Outcomes of melanoma brain metastases treated with stereotactic radiosurgery with and without concurrent immune checkpoint therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21026-e21026
Author(s):  
Jessica Yang ◽  
Laurent Dercle ◽  
Andrew M. Yaeh ◽  
Randy Yeh ◽  
Daniel K. Manson ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Gamma Knife Radiosurgery ◽  
Median Number ◽  
Immune Checkpoint Blockade ◽  
Tumor Growth Rate ◽  
Best Response ◽  
Melanoma Brain Metastases

e21026 Background: Evidence supports a synergistic effect between immunotherapy and radiotherapy. In this single-institution study, we compared outcomes of patients (pts) with melanoma brain metastases (BMs) who received Gamma Knife Radiosurgery (GKRS) with and without concurrent immune checkpoint blockade (ICB). Methods: Using an IRB-approved protocol, we identified pts with melanoma BMs who received GKRS from 5/2000 to 8/2016. Treatment was deemed concurrent if patients had GKRS within 4 weeks of ICB. Irradiated lesion control, tumor growth rate (TGR; percent change in product diameters per month), distant brain control, overall response rate (ORR) by modified WHO criteria, best response, and overall survival (OS) were compared. Results: 28 pts were identified: 17 (34 BMs total) received GKRS alone; 11 (23 BMs total) received concurrent GKRS/ICB. ICB included: ipilimumab (n = 3), anti-programmed death-1 (anti-PD-1) therapy (n = 4), and combined ipilimumab + nivolumab (n = 4). In comparing baseline characteristics between the GKRS alone and GKRS/ICB groups: median age was 65 v. 59 years, proportion of males was 53% v. 73%, 41% v. 45% had prior neurosurgery, and median number of prior systemic therapies was 1 v. 0. There was no difference in irradiated lesion control (6-month control rate 86% v. 96%; n = 57; p = 0.65), median TGR (-14% [range -100% to +61%] v. -20% [range -71% to 0%]; n = 42 lesions, p = 0.38), or distant brain control (6-month control rate 68% v. 60%; p = 0.51; median follow-up 8.6 months v. 8.0 months) with GKRS/ICB v. GKRS alone. The ORR with GKRS alone v. GKRS/ICB was 61% v. 47% (p = 0.33), and the median maximum reduction in BM bidimensional measurement was -69% v. -45% (p = 0.43). Median OS from the date of GKRS was not reached for the GKRS/ICB group and was 16.6 months for the GKRS alone group (p = 0.03). Conclusions: There was no difference in local lesion control, TGR, or distant brain control with concurrent GKRS/ICB compared to GKRS alone, but the study was limited by small patient numbers and biased by closer follow-up in the GKRS/ICB group. OS was longer with concurrent ICB, likely reflecting the survival improvement with immune checkpoint inhibitors.

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