Stereotactic radiosurgery and immunotherapy in melanoma brain metastases: Patterns of care and treatment outcomes

Gabani, Prashant; Fischer‐Valuck, Benjamin W.; Johanns, Tanner M.; Hernandez‐Aya, Leonel F.; Keller, Jesse; Rich, Keith M.; Kim, Albert H.; Dunn, Gavin P.; Robinson, Clifford G.; Chicoine, Michael R.; Huang, Jiayi; Abraham, Christopher

doi:10.1016/j.radonc.2018.06.017

Cited by 51 publications

(35 citation statements)

References 30 publications

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“…Additionally, in clinical practice, the choice of an RT regimen is often dictated by other disease characteristics and symptoms, such as the number of brain metastases; this may further complicate the interpretation of outcomes from individual studies ( 69 ). For example, a lower milestone 1-year OS in patients treated with WBRT and ICI vs. patients treated with SRT regimens and ICI was found, in retrospective studies by Silk et al ( 48 ), Gerber et al ( 70 ), and Gabani et al ( 37 ). However, the authors emphasized that this observation can be driven by confounding factors.…”

Section: Discussionmentioning

confidence: 95%

Quantification of Scheduling Impact on Safety and Efficacy Outcomes of Brain Metastasis Radio- and Immuno-Therapies: A Systematic Review and Meta-Analysis

Voronova¹,

Sekacheva

Helmlinger³

et al. 2020

Front. Oncol.

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Objectives: The goal of this quantitative research was to evaluate the impact of various factors (e.g., scheduling or radiotherapy (RT) type) on outcomes for RT vs. RT in combination with immune checkpoint inhibitors (ICI), in the treatment of brain metastases, via a meta-analysis. Methods: Clinical studies with at least one ICI+RT treatment combination arm with brain metastasis patients were identified via a systematic literature search. Data on 1-year overall survival (OS), 1-year local control (LC) and radionecrosis rate (RNR) were extracted; for combination studies which included an RT monotherapy arm, odds ratios (OR) for the aforementioned endpoints were additionally calculated and analyzed. Mixed-effects meta-analysis models were tested to evaluate impact on outcome, for different factors such as combination treatment scheduling and the type of ICI or RT used. Results: 40 studies representing a total of 4,359 patients were identified. Higher 1-year OS was observed in ICI and RT combination vs. RT alone, with corresponding incidence rates of 59% [95% CI: 54-63%] vs. 32% [95% CI: 25-39%] ( P < 0.001). Concurrent ICI and RT treatment was associated with significantly higher 1-year OS vs. sequential combinations: 68% [95% CI: 60-75%] vs. 54% [95% CI: 47-61%]. No statistically significant differences were observed in 1-year LC and RNR, when comparing combinations vs. RT monotherapies, with 1-year LC rates of 68% [95% CI: 40-90%] vs. 72% [95% CI: 63-80%] ( P = 0.73) and RNR rates of 6% [95% CI: 2-13%] vs. 9% [95% CI: 5-14%] ( P = 0.37). Conclusions: A comprehensive, study-level meta-analysis of brain metastasis disease treatments suggest that combinations of RT and ICI result in higher OS, yet comparable neurotoxicity profiles vs. RT alone, with a superiority of concurrent vs. sequential combination regimens. A similar meta-analysis using patient-level data from past trials, as well as future prospective randomized trials would help confirming these findings.

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Section: Discussionmentioning

confidence: 95%

Quantification of Scheduling Impact on Safety and Efficacy Outcomes of Brain Metastasis Radio- and Immuno-Therapies: A Systematic Review and Meta-Analysis

Voronova¹,

Sekacheva

Helmlinger³

et al. 2020

Front. Oncol.

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“…Other investigations evaluating the role of immunotherapy using NCDB data have used similar date-based cutoffs to infer specific therapeutics used as standard-of-care for given diseases, or have assumed that immunotherapy consisted of checkpoint inhibitors. 42,[44][45][46] The only other NCDB study evaluating immunotherapy in SNM examined patients diagnosed from 2004 to 2015, without stratification based on time period or regard for changes in the definition of "immunotherapy." 42 Such an approach is unlikely to elucidate the role of checkpoint inhibition in this disease, as prior to 2011 the vast majority of immunotherapy likely consisted of other targeted agents.…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy in sinonasal melanoma: treatment patterns and outcomes compared to cutaneous melanoma

Klebaner

Saddawi‐Konefka

Finegersh

et al. 2020

Int Forum Allergy Rhinol

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Background Although treatment with checkpoint blockade is now accepted as standard of care for cutaneous melanoma, few studies have investigated its role in sinonasal melanoma (SNM). We aimed to evaluate whether immunotherapy was associated with improved survival in SNM and to compare the effect of immunotherapy in metastatic sinonasal and cutaneous melanoma. Methods This was a cohort study of patients included in the United States National Cancer Database who had been diagnosed with sinonasal or cutaneous melanoma between 2012 and 2015 and had complete information regarding immunotherapy status. The primary outcome was overall survival. The influence of immunotherapy on overall survival was compared by Kaplan‐Meier and Cox proportional hazards models. Propensity score matched analyses between SNM patients who received immunotherapy and those who did not were based on clinicopathological covariates associated with survival in univariate Cox models. Results The analytic cohort consisted of 704 patients with SNM, 94 of whom were treated with immunotherapy and 152,896 patients with cutaneous melanoma, 8055 of whom were treated with immunotherapy. Immunotherapy was not associated with survival in the propensity‐score matched cohort (n = 195; hazard ratio [HR] = 1.0; 95% confidence interval [CI], 0.7 to 1.5; p = 0.88) or in adjusted Cox proportional hazards model (n = 549; HR = 1.0; 95% CI, 0.74 to 1.4; p = 0.88). Regimens including immunotherapy were associated with improved overall survival in metastatic cutaneous melanoma (HR = 0.57; 95% CI, 0.49 to 0.66; p < 0.0001), but not metastatic SNM (HR = 1.1; 95% CI, 0.67 to 1.7; p = 0.75). Conclusion Compared to current standard of care therapy, inclusion of immunotherapy as first‐line therapy was not associated with improved survival in SNM.

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“…Despite the fact that both SRS and targeted/immunetherapies are considered standard treatment options for brain metastases of malignant melanoma, the optimal combination strategy and sequence of these modalities remains largely unknown [3,4,7,16,17]. The implementation of BRAF/MEKi and the advent of immunotherapy revolutionized treatment of metastatic melanoma compared with the unsatisfactory control rates provided with classical chemotherapy [18].…”

Section: Discussionmentioning

confidence: 99%

“…targeted therapies and ICI) have proven their efficacy, there is a lack of prospective, randomized data regarding their combination, especially in terms of sequence and toxicity [6]. Moreover, several retrospective analyses indicated a possible improvement in tumor control using these treatments, and also raised concerns regarding toxicity of the combined application [7][8][9][10]. This bi-centric study, conducted in two large radiosurgery dedicated centers with strict treatment quality control, retrospectively evaluates the oncological results and adverse effects of several combinations of kinase inhibitors or ICI with SRS in a relatively large number of patients (n = 48) with one or multiple newly diagnosed and/or recurrent brain metastases (total, n = 250).…”

Section: Introductionmentioning

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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Stereotactic radiosurgery and immunotherapy in melanoma brain metastases: Patterns of care and treatment outcomes

Cited by 51 publications

References 30 publications

Quantification of Scheduling Impact on Safety and Efficacy Outcomes of Brain Metastasis Radio- and Immuno-Therapies: A Systematic Review and Meta-Analysis

Quantification of Scheduling Impact on Safety and Efficacy Outcomes of Brain Metastasis Radio- and Immuno-Therapies: A Systematic Review and Meta-Analysis

Immunotherapy in sinonasal melanoma: treatment patterns and outcomes compared to cutaneous melanoma

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

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