Predictors of survival in metastatic melanoma patients with leptomeningeal disease (LMD)

Ferguson, Sherise D.; Bindal, Shivani; Bassett, Roland L.; Haydu, Lauren E.; McCutcheon, Ian E.; Heimberger, Amy B.; Li, Jing; O’Brien, Barbara; Guha-Thakurta, Nandita; Tetzlaff, Michael T.; Tawbi, Hussein A.; Glitza, Isabella C.

doi:10.1007/s11060-019-03121-2

Cited by 49 publications

(60 citation statements)

References 44 publications

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“…In addition, patients with elevated serum LDH levels at the diagnosis of LMD had worse outcomes than LMD patients with normal LDH levels ( p < .001). Notably, treatment with radiation did not impact survival in either study (Ferguson et al, ; Geukes Foppen et al, ).…”

Section: Survival and Prognostic Factorsmentioning

confidence: 81%

“…Most studies of prognostic factors have included relatively small numbers of patients (i.e., <30–40). The analysis of the largest cohort ( n = 178) did identify several factors independently associated with worse survival, including Eastern Cooperative Oncology Group [ECOG] performance status >0 (HR 2.1, p < .0001), the presence of neurological symptoms (HR 1.6, p < .0001), and lack of concurrent systemic disease (HR 0.4, p < .0001; Ferguson et al, ). Treatment with any therapy directed at LMD was also associated with improved outcomes (HR 0.4, p = .0024), as was treatment with targeted therapy (HR 0.6, p = .0060) and treatment with intrathecal (IT) therapy (HR 0.5, p = .0019).…”

Section: Survival and Prognostic Factorsmentioning

confidence: 99%

“…The risk of significant side effects from entire neuraxis RT generally outweighs the benefits in this relatively radioresistant tumor. It should be noted that a recent review did not find that RT had a positive impact on survival as monotherapy (Ferguson et al, ) while another showed longer survival when RT was used in combination with systemic therapies (Geukes Foppen et al, ).…”

Section: Standard Approach To Lmdmentioning

confidence: 99%

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Leptomeningeal disease in melanoma patients: An update to treatment, challenges, and future directions

Glitza

Smalley

Brastianos

et al. 2020

Pigment Cell Melanoma Res

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In February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System Metastases in Tampa, Florida. The meeting included investigators from multiple academic centers and disciplines. A consensus summary of the progress and challenges in melanoma parenchymal brain metastases was published (Eroglu et al., Pigment Cell & Melanoma Research, 2019, 32, 458). Here, we will describe the current state of basic, translational, clinical research, and therapeutic management, for melanoma patients with leptomeningeal disease. We also outline key challenges and barriers to be overcome to make progress in this deadly disease.

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Section: Survival and Prognostic Factorsmentioning

confidence: 81%

Section: Survival and Prognostic Factorsmentioning

confidence: 99%

Section: Standard Approach To Lmdmentioning

confidence: 99%

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Leptomeningeal disease in melanoma patients: An update to treatment, challenges, and future directions

Glitza

Smalley

Brastianos

et al. 2020

Pigment Cell Melanoma Res

Self Cite

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“…The prognosis for patients with LMD, regardless of malignancy, is poor with a median overall survival (OS) of 4 to 6 weeks without treatment . However, a recent study of 178 patients with LMD from melanoma predicted improved OS for a subset of patients . The Eastern Cooperative Oncology Group performance status was a significant predictor of survival, with a decline in the performance status correlating with a decline in survival.…”

Section: Melanoma‐related Neurologic Complicationsmentioning

confidence: 99%

Neurologic complications of melanoma

Cohen

Wang

Venur

et al. 2019

Cancer

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Neurologic complications are common in patients with melanoma and are often associated with a poor prognosis. In an era with new, effective treatments, patients are living longer, and this has resulted in an increase in complications of both the disease and the therapy. A multidisciplinary approach to neurologic complications in patients with melanoma, with involvement from medical oncology, neurooncology, radiation oncology, and often neurosurgery, is necessary. In this review, neurologic complications of melanoma, including clinical implications and treatment strategies, are described. Cancer 2020;126:477-486.

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“…However, metastatic melanoma patients with evidence of LM were excluded from all these clinical trials [6][7][8][9][10]. There are currently only a handful of reports suggesting that BRAF and MEK inhibitors, or immune checkpoint inhibitors, may induce survival benefit in advanced melanoma patients with LM [11][12][13]. Focal radiotherapy could be used for the treatment of limited macroscopic leptomeningeal disease, whereas the use of WBRT is decreasing owing to poor survival benefit and radiation-induced cognitive toxicity [14].…”

Section: Introductionmentioning

confidence: 99%

Impact of New Systemic Treatment and Radiotherapy in Melanoma Patients with Leptomeningeal Metastases

Tétu

Sirven-Villaros

Cuzzubbo

et al. 2020

Cancers

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Importance: Few data are available on patients with leptomeningeal disease (LM) from melanoma treated with new systemic therapies. Objective: To gain a better understanding of patients, disease characteristics, and therapeutic interventions in melanoma patients with LM in the era of new systemic treatment. Design: Clinical characteristics, treatments, and survival of melanoma patients diagnosed with LM, isolated or associated with brain metastases, were collected. The Cox regression model assessed the influence of patient and melanoma characteristics on survival. Setting: Monocentric, retrospective, real-life cohort of patients with LM from melanoma. Participants: All patients followed up at Saint-Louis University Hospital and diagnosed with LM between December 2013 and February 2020 were included. For each patient identified, a central review by dermato-oncologist and neuro-oncologist experts was performed to confirm the diagnosis of LM. Exposure: Impact of new systemic therapies and radiotherapy. Results: Among the 452 advanced melanoma patients followed at St Louis Hospital between 2013 and 2020, 41 patients with LM from melanoma were identified. Among them, 29 patients with a diagnosis of LM “confirmed” or “probable” after central neuro-oncologists reviewing were included. Nineteen patients had known melanoma brain metastases at LM diagnosis. Among the 27 patients treated with systemic therapy, 17 patients were treated with immunotherapy, 5 patients received targeted therapy, 1 was treated with chemotherapy, and 4 patients were treated with anti-PD-1 in combination with BRAF inhibitor. The median overall survival (OS) from LM diagnosis was 5.1 months. Median OS was 7.1 months for the 9 patients receiving systemic therapy combined with radiotherapy, and 3.2 months for the 20 patients not receiving combined radiotherapy. Elevated serum lactate dehydrogenase (LDH) (HR 1.44, 95% CI 1.09–1.90, p < 0.01) and presence of neurological symptoms at LM diagnosis (HR 2.96, 95% CI 1.25–6.99, p = 0.01) were associated with poor survival. At the time of data analysis, five patients were still alive with a median follow-up of 47.4 months and had persistent complete response. Conclusion: Targeted therapy and immunotherapy are promising new treatment options in LM from melanoma that can increase overall survival, and may induce long lasting remission in some patients.

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Predictors of survival in metastatic melanoma patients with leptomeningeal disease (LMD)

Cited by 49 publications

References 44 publications

Leptomeningeal disease in melanoma patients: An update to treatment, challenges, and future directions

Leptomeningeal disease in melanoma patients: An update to treatment, challenges, and future directions

Neurologic complications of melanoma

Impact of New Systemic Treatment and Radiotherapy in Melanoma Patients with Leptomeningeal Metastases

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