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.

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

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 Immune checkpoint inhibitors in combination with radiotherapy as salvage treatment for relapsed/refractory classical Hodgkin lymphoma: A retrospective analysis in 12 patients

2021 ◽  
Vol 13 (2) ◽  
Author(s):  
Elisa Lucchini ◽  
Chiara Rusconi ◽  
Mario Levis ◽  
Francesca Ricci ◽  
Armando Santoro ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Median Number ◽  
Brentuximab Vedotin ◽  
Salvage Treatment ◽  
Classical Hodgkin Lymphoma ◽  
Highly Active

The rate of complete remission (CR) with the anti-PD1 immune checkpoint inhibitors (ICI) nivolumab (N) and pembrolizumab (P) in patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) is low (20-30%), and the majority of patients eventually relapse. One strategy to improve their outcome is to combine ICI with radiotherapy (ICI-RT), taking advantage of a supposed synergistic effect. We retrospectively collected data of 12 adult patients with R/R cHL treated with ICI-RT delivered during or within 8 weeks from the start or after the end of ICI. Median age at ICI-RT was 37 years, 50% had previously received an autologous stem cell transplantation (SCT) and 92% brentuximab vedotin. RT was given concurrently, before or after ICI in 4, 1 and 7 patients. Median RT dose was 30Gy, for a median duration of 22 days. Median number of ICI administrations was 15. Overall response and CR rate were 100% and 58%. Nine patients received subsequent SCT consolidation (7 allogeneic and 2 autologous). After a median follow-up of 18 months, 92% of patients were in CR. No major concerns about safety were reported. ICI-RT combination appears to be a feasible and highly active bridge treatment to transplant consolidation.

scholarly journals Stereotactic radiosurgery combined with immune checkpoint inhibition for the treatment of melanoma brain metastases is associated with high levels of extracranial disease control and survivorship - an abscopal effect?

2021 ◽  
Vol 23 (Supplement_4) ◽  
pp. iv16-iv16
Author(s):  
Philip Webb ◽  
Mark Zorman ◽  
Rhona Watson ◽  
Gemma Austin ◽  
Carol Thurgood ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Immune Checkpoint ◽  
Progression Free Survival ◽  
Median Number ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Free Survival ◽  
Start Date ◽  
Melanoma Brain Metastases ◽  
Extracranial Disease

Abstract Aims Melanoma brain metastases (MBM) are a common presentation to the neuro-oncology MDT. Stereotactic radiosurgery (SRS) is a highly effective treatment for cerebral metastases, with at least 70% control rates of individual metastases,[1] whilst immune checkpoint blockade has revolutionised the management of metastatic melanoma in recent years.[2] Recent studies have demonstrated that immune checkpoint inhibition alone also has activity in the brain, with MBM response rates of 50% or more.[3, 4] When MBM are treated with combination immunotherapy and SRS together, 12-month intracranial progression free survival (PFS) rates of 85% have been achieved.[4, 5] The aim of the current study was to evaluate the local control of MBM treated at our tertiary referral centre, which benefits from specialist neuro-radiology peer review of SRS contour volumes, and further to investigate whether overall survival is also improved, and what the mechanism of this may be. Method A retrospective analysis of all patients treated with SRS for brain metastases at our teriary SRS centre between June 2017 – January 2020 was performed. Inclusion criteria included patients treated for MBM, who received at least 2 doses of any combination of immune checkpoint inhibition concurrently with (defined as at the time of or commenced within 3 months of) SRS. The primary endpoints were the intracranial and extracranial response rates and survival rate at 12 months. Response was defined as complete response, partial response or stable disease. Secondary endpoints included the rate of imaging-defined radionecrosis, median lesional progression free survival (mPFSlesion), non-lesional intracranial PFS (mPFSintracranial), extracranial PFS (mPFSextracranial) and overall survival (mOS), measured from the start date of SRS to the date of event or censored at the start date of data collection. Kaplan-Meier curves and survival statistics were generated using SPSS v26. Results 33 MBM from 18 patients were identified. The median follow up was 25.8 months (minimum 12 months). Of the 18 patients: the median age was 60 (IQR 48 – 72); 17 (94%) patients were ECOG performance status 0-1; the median number of extracranial disease sites was 2 (pre-immunotherapy) and 1 (pre-SRS); the median duration of immunotherapy treatment was 17.6 (12.9 – 28.5) months, and the median number of metastases treated per patient was 2. Of the 33 metastases: 31 (94%) were supratentorial; 6 (18%) underwent prior neurosurgical resection; the median GTV volume (cc) of unresected metastases was 0.5cc (0.1 – 2.7), and 21 (64%) were treated with single fraction SRS. The median OS and PFS for all subtypes were not reached. The rates of OS, PFSlesion, PFSintracranial and PFSextracranial at 12 months were 93.9%, 87.9%, 81.8% & 75.8% respectively. Conclusion Our cohort of MBM patients appear to perform favourably when compared with the current literature. When compared to a recent extensive systematic review of modern management of MBM, our lesional control rate is as good as the weighted average of concurrent SRS + immunotherapy studies (87.9% vs 85.4% 12-month PFS), however we demonstrate a significantly improved 12-month OS rate (93.9% vs 52.8%) compared to the same (mOS of 15.8 – 17.4 months in other studies).[6,7] Our extra-lesional PFS is high and, compared to extracranial PFS rates from 51% at 6-months to 70.4% at 9-months in the literature,[3,4] our 75.8% control at 12 months suggests that extracranial control could drive the OS benefit. This suggests a benefit of SRS beyond the local control of MBM and questions whether patients without brain metastases may benefit from body SABR to extracranial metastases, to elicit a similar, potentially abscopal type effect.

scholarly journals Acute neurologic toxicity of palliative radiotherapy for brain metastases in patients receiving immune checkpoint blockade

2018 ◽  
Vol 6 (4) ◽  
pp. 297-304 ◽  
Author(s):  
W Tristram Arscott ◽  
Simeng Zhu ◽  
John P Plastaras ◽  
Amit Maity ◽  
Michelle Alonso-Basanta ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Immune Checkpoint ◽  
Performance Status ◽  
Single Agent ◽  
Whole Brain Radiotherapy ◽  
Nonsmall Cell Lung Cancer ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Acute Neurotoxicity

Abstract Background The interaction between immune checkpoint blockade (ICB) and radiation (RT) for brain metastases has not been well understood. Given that acute neurotoxicity from this combination is not well characterized, we reviewed patients receiving ICB and RT for brain metastases. Methods Patients treated with ICB and cranial RT from 2010 through 2017 were reviewed. ICB and RT must have been administered within 30 days of each other. Treatment parameters, performance status, symptoms prior to treatment, and toxicity were extracted from the electronic medical record. Survival was calculated from the end of RT to last follow-up or death. Results Seventy-eight patients were included. Median follow-up was 177 days (range, 12-1603). Median age was 64 years old (range, 29-98) and 47 (63%) were male. The main tumor types were melanoma (n = 47) and nonsmall-cell lung cancer (n = 19). Fifty-seven patients were treated with stereotactic radiosurgery (SRS) and 21 with whole-brain radiotherapy (WBRT). Most patients received single-agent ICB, though 4 patients received nivolumab and ipilimumab. Forty-one (53%) patients reported no neurologic toxicity. Grade 2 or greater neurologic toxicities were reported in 12 (21%) and 8 (38%) patients in the SRS and WBRT groups, respectively. WBRT was associated with a greater risk of any neurotoxicity, though there was no correlation between ICB agent and toxicity. Sequencing of ICB and RT (ie, <30 days vs <7) did not influence rates of toxicity. Conclusions ICB during SRS or WBRT does not appear to worsen acute neurotoxicity compared to historical controls of RT alone.

scholarly journals Response assessment and outcome of combining immunotherapy and radiosurgery for brain metastasis from malignant melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2532-2532
Author(s):  
Emilie Le Rhun ◽  
Fabian Wolpert ◽  
Maud Fialek ◽  
Patrick Devos ◽  
Nicolaus Andratschke ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Response Assessment ◽  
Steroid Use ◽  
Best Response ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

2532 Background: The evaluation of response in the context of treatment with stereotactic radiotherapy (SRT) or immune checkpoint inhibitors (ICI) or both, which represent major therapeutic options for patients with melanoma brain metastases, remains challenging due to potential tumor hemorrhage, pseudoprogression, and radionecrosis. Methods: We reviewed clinical and neuroimaging data of 62 melanoma patients, including 26 patients with BRAF-mutant tumors, with newly diagnosed brain metastases treated with immune checkpoint inhibitors (ICI) alone (n = 10, group 1), SRT alone or in combination with other systemic therapies (n = 20, group 2) or ICI plus SRT (n = 32, group 3). Response was assessed retrospectively using RECIST 1.1, RANO or iRANO criteria. Results: The MRI scans of 52 patients were available for central review. Patients received steroids at BM diagnosis in 10% in group 1, 60% in group 2 and 50% in group 3. Pseudoprogression was documented in 7 patients: 3 patients in group 2 (19%) and 4 patients (12%) in group 3. Radionecrosis was documented in 7 patients: 2 patients in group 2 (12%) and 5 patients (16%) in group 3. Patients treated with ICI alone had the worst outcome. Using RANO criteria by central review instead of local investigator assessment increased the rate of progressive disease (PD) as best response for the evaluation of SRT targets but not for the evaluation of the overall brain. Using complete RANO (including clinical assessment and steroid use) instead of RECIST criteria increased the rate of PD as best response, due to clinical deterioration noted in patients with MRI findings that did not qualify for PD. This pattern was seen in patients from all three groups. In contrast, the complete response (CR) rate was unaffected by the criteria used. More PD were also observed when comparing MRI only iRANO criteria versus complete iRANO criteria including clinical status and steroid use. Conclusions: Pseudoprogression is uncommon with ICI alone, suggesting that growing lesions in such patients should trigger an intervention. Pseudoprogression rates were similar after SRT alone or in combination with ICI. Response assessment criteria should be considered carefully when designing clinical studies for patients with brain metastases who receive SRT.

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