Peri-SRS Administration of Immune Checkpoint Therapy for Melanoma Metastatic to the Brain: Investigating Efficacy and the Effects of Relative Treatment Timing on Lesion Response

Yusuf, Mehran; Burton, Eric; Chesney, Jason; Woo, Shiao Y.

doi:10.1016/j.wneu.2017.01.101

Cited by 46 publications

(26 citation statements)

References 35 publications

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“…TT/IT concurrent with SRS revealed a statistically significant better LC than non-concurrent TT/IT /SRS alone (one-year LC 100% versus 83%; p = 0.023). This finding is in accordance with preceding studies, which showed a statistically significant difference in LC favoring concurrent therapy [17][18][19]. Our analysis also confirmed that Melanoma-molGPA, which incorporated BRAF mutation status into its calculation, is a prognostic factor for LC.…”

Section: Discussionsupporting

confidence: 93%

Stereotactic radiosurgery combined with targeted/ immunotherapy in patients with melanoma brain metastasis

et al. 2020

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Background: There is limited data on the use of targeted or immunotherapy (TT/IT) in combination with single fraction stereotactic radiosurgery (SRS) in patients with melanoma brain metastasis (MBM). Therefore, we analyzed the outcome and toxicity of SRS alone compared to SRS in combination with TT/IT. Methods: Patients with MBM treated with single session SRS at our department between 2014 and 2017 with a minimum follow-up of 3 months after first SRS were included. The primary endpoint of this study was local control (LC). Secondary endpoints were distant intracranial control, radiation necrosis-free survival (RNFS), and overall survival (OS). The local/ distant intracranial control rates, RNFS and OS were analyzed using the Kaplan-Meier method. The log-rank test was used to test differences between groups. Cox proportional hazard model was performed for univariate continuous variables and multivariate analyses. Results: Twenty-eight patients (17 male and 11 female) with 52 SRS-lesions were included. The median follow-up was 19 months (range 14-24 months) after first SRS. Thirty-six lesions (69.2%) were treated with TT/IT simultaneously (4 weeks before and 4 weeks after SRS), while 16 lesions (30.8%) were treated with SRS alone or with sequential TT/ IT. The 1-year local control rate was 100 and 83.3% for SRS with TT/IT and SRS alone (p = 0.023), respectively. The estimated 1-year RNFS was 90.0 and 82.1% for SRS in combination with TT/IT and SRS alone (p = 0.935). The distant intracranial control rate after 1 year was 47.7 and 50% for SRS in combination with TT/IT and SRS alone (p = 0.933). On univariate analysis, the diagnosis-specific Graded Prognostic Assessment including the BRAF status (Melanoma-molGPA) was associated with a significantly improved LC. Neither gender nor SRS-PTV margin had a prognostic impact on LC. V10 and V12 were significantly associated with RNFS (p < 0.001 and p = 0.004). Conclusion: SRS with simultaneous TT/IT significantly improved LC with no significant difference in radiation necrosis rate. The therapy combination appears to be effective and safe. However, prospective studies on SRS with simultaneous TT/IT are necessary and ongoing. Trial registration: The institutional review board approved this analysis on 10th of February 2015 and all patients signed informed consent (UE nr. 128-14).

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Section: Discussionsupporting

confidence: 93%

Stereotactic radiosurgery combined with targeted/ immunotherapy in patients with melanoma brain metastasis

et al. 2020

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“…Our findings indicate that these immune checkpoint inhibitors are effective for controlling not only the primary melanoma but also distant metastases to the brain. Several previous reports have shown a regional immunomodulatory effect and penetration of novel systemic agents into the brain [8,11,12,15,18,20,21,23]. The present results might indicate passage of these agents thorough the bloodbrain barrier in melanoma patients, thereby leading to suppression of new metastases to the brain.…”

Section: Discussionsupporting

confidence: 67%

Gamma Knife Radiosurgery for Metastatic Brain Tumors from Malignant Melanomas: A Japanese Multi-Institutional Cooperative and Retrospective Cohort Study (JLGK1501)

Matsunaga¹,

Shuto

Yamamoto

et al. 2018

Stereotact Funct Neurosurg

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Background: The incidences of metastatic brain tumors from malignant melanomas have increased and survival has been prolonged by novel molecular targeted agents and immunotherapy. However, malignant melanomas are uncommon in Asian populations. Objectives: We retrospectively analyzed treatment efficacy and identified prognostic factors impacting tumor control and survival in Japanese melanoma patients with brain metastases treated with gamma knife radiosurgery (GKRS). Methods: We retrospectively reviewed the medical records of 177 patients with 1,500 tumors who underwent GKRS for brain metastases from malignant melanomas. This study was conducted by the Japanese Leksell Gamma Knife Society (JLGK1501). Results: Six and 12 months after GKRS, the cumulative incidences of local tumor recurrence were 9.2 and 13.8%. Intratumoral hemorrhage (p < 0.0001) and larger tumor volume (p = 0.001) in GKRS were associated with significantly poorer local control outcomes. The use of immune checkpoint inhibitors before GKRS was significantly associated with symptomatic adverse events (p = 0.037). The median overall survival time after the initial GKRS was 7.3 months. Lower Karnofsky performance status scores (p = 0.016), uncontrolled primary cancer (p < 0.0001), and multiple brain metastases (p = 0.014) significantly influenced unfavorable overall survival outcomes. The cumulative incidences of neurological death 6 and 12 months after GKRS were 9.7 and 17.4%, those of neurological deterioration were 14.2 and 19.6%, and those of new tumor appearance were 34.5 and 40.5%. Conclusions: The results of the present multicenter study suggest that GKRS is a relatively effective and safe modality for control of tumor progression in Japanese patients with brain metastases from malignant melanomas.

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“…very inhomogeneous dose distribution inside the central metastases). Although there exist some recent data about toxicity and efficacy of similar regimens, all of these series are retrospective, mostly included smaller patient numbers, or investigated solely and separately the combination of SRS with BRAF/MEKi [10,[27][28][29] or with ICI [30][31][32][33]. Furthermore, only a limited number of metastases were treated with each SRS session in those studies.…”

Section: Discussionmentioning

confidence: 99%

“…Mounting evidence suggests an enhanced effect of concomitant application of SRS together with BRAF/MEKi [35] and ICI [31][32][33]. Yet, it remains to be elucidated how narrow the timeframe of the combination should be and if drug application shortly before or after SRS could provide comparable results.…”

Section: Discussionmentioning

confidence: 99%

Stereotactic radiosurgery combined with immune checkpoint inhibitors or kinase inhibitors for patients with multiple brain metastases of malignant melanoma

et al. 2019

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The aim was to evaluate toxicity and oncological outcome of combined stereotactic radiosurgery (SRS) and immunotherapy or targeted therapy in patients with multiple brain metastases originating from malignant melanoma. Despite the fact that both SRS and kinase inhibitors or immune checkpoint inhibitors are considered standard treatment options for this indication, the optimal combination and sequence of these modalities remains largely unknown, especially for patients with a high number of brain metastases. For this retrospective analysis, conducted in two large SRS dedicated centers, we identified patients with brain metastases from malignant melanoma and simultaneous application of immunotherapy or targeted therapy within 30 days of SRS. Forty-eight patients with a total of 250 lesions (median: 3) were treated in 65 single fraction SRS sessions from 2012 to 2018. After a median follow-up of 8.3 months (range: 1.2-43.6 months), the 6-month and 1-year overall survival rates were 75.3 and 50.8%, respectively. The local control rate at one year was 89.5%. Immunotherapy and the application of systemic treatment directly before or concomitant to SRS were both associated with improved overall survival (P = 0.037 and 0.045, respectively). We observed four grade III toxicities, of which only two can be clearly attributed to the combined treatment. Various combinations of SRS and kinase inhibitors or immune checkpoint inhibitors appear feasible and provide promising oncological results and safety profiles for treating few (n = 1-4) and also multiple (n ≥ 5) melanoma brain metastases.

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Peri-SRS Administration of Immune Checkpoint Therapy for Melanoma Metastatic to the Brain: Investigating Efficacy and the Effects of Relative Treatment Timing on Lesion Response

Cited by 46 publications

References 35 publications

Stereotactic radiosurgery combined with targeted/ immunotherapy in patients with melanoma brain metastasis

Stereotactic radiosurgery combined with targeted/ immunotherapy in patients with melanoma brain metastasis

Gamma Knife Radiosurgery for Metastatic Brain Tumors from Malignant Melanomas: A Japanese Multi-Institutional Cooperative and Retrospective Cohort Study (JLGK1501)

Stereotactic radiosurgery combined with immune checkpoint inhibitors or kinase inhibitors for patients with multiple brain metastases of malignant melanoma

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