Metastatic melanoma: prognostic factors and survival in patients with brain metastases

Frinton, E.; Tong, Daniel; Tan, Jie; Read, G.; Kumar, V.; Kennedy, S.; Lim, C.C.; Board, Ruth

doi:10.1016/s0959-8049(17)30486-0

Cited by 4 publications

(5 citation statements)

References 21 publications

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“…[14][15][16] The use of BRAF inhibitor targeted therapies such as Vemurafenib and Dabrafenib have resulted in anti-neoplastic effects and improved survival in patients with metastatic melanoma. [14][15][16][17] Also similar to previous studies, a slightly better prognosis was seen in this study in patients with only a single MBM (median OS -6 months), compared to those with multiple metastases (median OS -4.5 months), although not significant. 1,4 Furthermore, the presence of LMD had a significant impact on the median OS 0.5 months, (p ¼ 0.0002), however, this could be due to the small sample size(n ¼ 3).…”

Section: Discussionsupporting

confidence: 88%

Melanoma brain metastases in Ireland: surgical and systemic considerations

O'Halloran

Cleary

Cryan

et al. 2021

British Journal of Neurosurgery

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Background: Cerebral metastases is a common complication in patients with melanoma. There is a paucity of information in the Republic of Ireland regarding the factors associated with melanoma brain metastases (MBM). Methods: Patients diagnosed with melanoma brain metastases in Ireland were retrospectively identified in Beaumont Hospital between 1999 and 2018. Patient demographics; age at diagnosis of primary melanoma, age at detection of MBM, year of detection of MBM, anatomical location of primary melanoma, BRAF mutation analysis and the number of metastases were investigated. Follow-up data were also derived, including overall survival.Results: There has being a 158% increase in the incidence of primary melanoma from 1999 compared to 2016. Over the same time period 128 patients with melanoma brain metastases were diagnosed. There was a significant male predominance (n ¼ 77/128; 60%; p < 0.0001). BRAF mutation and leptomeningeal disease were independent prognostic factors in our cohort with a median survival 8 months and 0.5 months, respectively. Conclusions: Male predominance, leptomeningeal disease and BRAF mutation represent important considerations in this population group. The results of this study add to our knowledge concerning outcomes in melanoma brain metastases and may be useful in clinical planning and future treatments.

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Section: Discussionsupporting

confidence: 88%

Melanoma brain metastases in Ireland: surgical and systemic considerations

O'Halloran

Cleary

Cryan

et al. 2021

British Journal of Neurosurgery

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“…Brain metastases are more commonly associated with poor prognosis in melanoma [ 10 , 11 , 12 , 13 ]. A notable observation from this analysis was that brain metastases were somewhat similar across all groups (short-term, 22.1%; long-term, 17.3%), while liver metastases were the highest in the short-term duration of benefit group (short-term, 28.3%; long-term, 11.1%).…”

Section: Discussionmentioning

confidence: 99%

A Retrospective Analysis of Dabrafenib and/or Dabrafenib Plus Trametinib Combination in Patients with Metastatic Melanoma to Characterize Patients with Long-Term Benefit in the Individual Patient Program (DESCRIBE III)

Atkinson

Quaglino

Vecchio

et al. 2021

Cancers

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The dabrafenib plus trametinib (dab + tram) combination has demonstrated durable long-term efficacy in patients with BRAF V600–mutant metastatic melanoma. However, real-world data characterizing patients with long-term benefit are limited. DESCRIBE III was a global, observational, retrospective, chart review study in patients with unresectable or metastatic melanoma treated with dab monotherapy and/or dab + tram combination therapy as part of the Named Patient Program or Individual Patient Program. Overall, 509 patients were enrolled. Patients were categorized into three groups based on their observed treatment duration: long-term (on therapy ≥12 months), intermediate (on therapy ≥6 months and <12 months), and short-term (on therapy <6 months) duration of benefit. More patients in the short-term duration of benefit group had baseline characteristics associated with poor prognosis compared with the other two groups. Median lactate dehydrogenase (LDH) levels (368 U/L) at baseline were also higher in the short-term duration of benefit group. No new safety signals were identified. DESCRIBE III identified baseline characteristics associated with long-term benefit of dab + tram. Lower LDH level and <3 metastatic sites at baseline were associated with a longer duration of benefit, confirming that the findings from COMBI-d and COMBI-v are relevant to patients treated in a real-world setting.

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“…Melanoma is one of the primary causes of malignant metastases to the central nervous system (CNS), accounting for 6% to 12% of all metastatic brain tumors 1‐3 . Survival after a diagnosis of melanoma brain metastasis (MBM) has historically been dismal, with an overall survival (OS) of 4 to 6 months 4‐8 . However, over the recent decade, numerous advances have been made in targeted therapy for melanoma, such as BRAF and MEK inhibition, and in immunotherapy with approval of the checkpoint inhibitors ipilimumab, nivolumab, and pembrolizumab 9 .…”

Section: Introductionmentioning

confidence: 99%

Melanoma brain metastasis presentation, treatment, and outcomes in the age of targeted and immunotherapies

Bander

Yuan

Carnevale

et al. 2021

Cancer

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BACKGROUND: Historically, the prognosis for patients who have melanoma brain metastasis (MBM) has been dismal. However, breakthroughs in targeted and immunotherapies have improved long-term survival in those with advanced melanoma. Therefore, MBM presentation, prognosis, and the use of multimodality central nervous system (CNS)-directed treatment were reassessed. METHODS: In this retrospective study, the authors evaluated patients with MBM who received treatment at Memorial Sloan Kettering Cancer Center between 2010 and 2019. Kaplan-Meier methodology was used to describe overall survival (OS). Recursive partitioning analysis and timedependent multivariable Cox modeling were used to assess prognostic variables and to associate CNS-directed treatments with OS. RESULTS: Four hundred twenty-five patients with 2488 brain metastases were included. The median OS after an MBM diagnosis was 8.9 months (95% CI, 7.9-11.3 months). Patients who were diagnosed with MBM between 2015 and 2019 experienced longer OS compared to those who were diagnosed between 2010 and 2014 (OS, 13.0 months [95% CI, 10.47-17.06 months] vs 7.0 months [95% CI, 6.1-8.3 months]; P = .0003). Prognostic multivariable modeling significantly associated shortened OS independently with leptomeningeal dissemination (P < .0001), increasing numbers of brain metastases at diagnosis (P < .0001), earlier MBM diagnosis year (P = .0008), higher serum levels of lactate dehydrogenase (P < .0001), receipt of immunotherapy before MBM diagnosis (P = .003), and the presence of extracranial disease (P = .02). The use of different CNS-directed treatment modalities was associated with presenting symptoms, diagnosis year, number and size of brain metastases, and the presence of extracranial disease. Multivariable analysis demonstrated improved survival for patients who underwent craniotomy (P = .01). CONCLUSIONS: The prognosis for patients with MBM has improved within the last 5 years, coinciding with the approval of PD-1 immune checkpoint blockade and combined BRAF/MEK targeting. Improving survival reflects and may influence the willingness to use aggressive multimodality treatment for MBM.

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Metastatic melanoma: prognostic factors and survival in patients with brain metastases

Cited by 4 publications

References 21 publications

Melanoma brain metastases in Ireland: surgical and systemic considerations

Melanoma brain metastases in Ireland: surgical and systemic considerations

A Retrospective Analysis of Dabrafenib and/or Dabrafenib Plus Trametinib Combination in Patients with Metastatic Melanoma to Characterize Patients with Long-Term Benefit in the Individual Patient Program (DESCRIBE III)

Melanoma brain metastasis presentation, treatment, and outcomes in the age of targeted and immunotherapies

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