Incidence, patterns of progression, and outcomes of preexisting and newly discovered brain metastases during treatment with anti–PD‐1 in patients with metastatic melanoma

Schvartsman, Gustavo; Ma, Junsheng; Bassett, Roland L.; Haydu, Lauren E.; Amaria, Rodabe N.; Hwu, Patrick; Wong, Michael K.; Hwu, Wen Jen; Diab, Adi; Patel, Sapna; Davies, Michael A.; Hamerschlak, Nelson; Tawbi, Hussein A.

doi:10.1002/cncr.32454

Cited by 12 publications

(7 citation statements)

References 28 publications

(65 reference statements)

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“…However, it did portend a worse prognosis after a diagnosis of MBM, which is not surprising given that this scenario is akin to treatment failure of immunotherapy, which has more limited available salvage options. 43 LMD remained a dismal prognostic factor in our cohort, despite the treatment advances for extracranial and CNS parenchymal control. Previous reports describe an OS of 1.2 to 4.0 months after a diagnosis of LMD, and the current cohort falls within this range, with an OS of 2.3 months after LMD diagnosis.…”

Section: Discussionmentioning

confidence: 78%

“…Furthermore, treatment with immunotherapy before BM diagnosis did not significantly alter the number of BMs present at diagnosis, nor did it significantly alter the timeline of development of LMD once diagnosed with BM. However, it did portend a worse prognosis after a diagnosis of MBM, which is not surprising given that this scenario is akin to treatment failure of immunotherapy, which has more limited available salvage options 43 …”

Section: Discussionmentioning

confidence: 98%

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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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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 98%

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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“…11 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) 5 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) 13 11 *One patient had both treatment (SRT and ICI) on the same day. †Two patients received a combination of ICI and chemotherapy.…”

Section: Patient Characteristicsmentioning

confidence: 99%

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

et al. 2020

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BackgroundThe optimal sequence of stereotactic radiotherapy (SRT) and immune checkpoint inhibition (ICI) and assessment of response in patients with brain metastases from melanoma remain challenging.MethodsWe reviewed clinical and neuroimaging data of 62 patients with melanoma, including 26 patients with BRAF-mutant tumours, with newly diagnosed brain metastases treated with 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 response evaluation criteria in solid tumours (RECIST) V.1.1, response assessment in neuro-oncology (RANO) and immunotherapy RANO (iRANO) criteria. MRI follow-up from 43 patients was available for central review.ResultsPatients treated with ICI alone showed no objective responses and had worse outcome than patients treated with SRT without or with ICI. RECIST, RANO and iRANO criteria were concordant for complete response (CR) and partial response (PR). RANO called progression earlier than RECIST for clinical deterioration without MRI progression in some patients. Progression was called later when using iRANO criteria because of the need for a confirmatory scan. Pseudoprogression was documented in seven patients: three patients in group 2 and four patients in group 3. Radionecrosis was documented in seven patients: two patients in group 2 and five patients in group 3. Regression of non-irradiated lesions was seen neither in two patients treated with SRT alone nor in five patients treated with SRT plus ICI, providing no evidence for rare abscopal effects.ConclusionsPseudoprogression is uncommon with ICI alone, suggesting that growing lesions in such patients should trigger an intervention. Pseudoprogression rates were similar after SRT alone or SRT in combination with ICI. Abscopal effects are rare or do not exist. Response assessment criteria should be considered carefully when designing clinical studies for patients with brain metastases who receive SRT.

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“…Malignant melanoma is the third most common primary in the diagnosis of brain metastases after lung carcinoma, and breast cancer [ 11 ]. Brain metastases occur in up to 50% of patients with metastatic melanoma [ 12 ]. The chances of being cured are good in the early stages of the disease, but the median overall survival (OS) of patients with untreated brain metastases is less than 3 months [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Outcomes after stereotactic radiosurgery of brain metastases in patients with malignant melanoma and validation of the melanoma molGPA

et al. 2021

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Introduction Malignant melanoma is the third most common primary in the diagnosis of brain metastases. Stereotactic radiosurgery (SRS) is a well-established treatment option in limited brain disease. We analyzed outcomes of SRS with a particular focus on the graded prognostic assessment (GPA, melanoma molGPA), prognostic factors, and toxicity. Methods We evaluated 173 brain metastases in 83 patients with malignant melanoma. All were treated with SRS median dose of 20 Gy prescribed to the 80 or 100% isodose line between 2002 and 2019. All patients were followed-up regularly, including contrast‐enhanced brain imaging as well as clinical examination, initially 6 weeks after treatment, then in quarterly follow-up. Results The median age was 61 years (range 27–80); 36 female and 47 male patients were treated. After a median follow-up of 5.7 months, median OS (overall survival) was 9.7 months 95%-KI 4.7–14.7). LC (local control) at 6 months, 12, 24 months was 89%, 86%, and 72%, respectively (median was not reached). Median DBC (distant brain control) was 8.2 months (95%-KI 4.7–11.7). For OS, a KPS ≥ 80%, a positive BRAF mutation status, a small PTV (planning target volume), the absence of extracranial metastases, as well as a GPA and melanoma molGPA > 2 were prognostic factors. In the MVA, a small PTV and a melanoma molGPA > 2 remained significant. Conclusion The present survival outcomes support the use of the disease-specific melanoma molGPA as reliable prognostic score. Favorable outcomes for SRS compared to other studies were observed. In the treatment of brain metastases of malignant melanoma patients, a multidisciplinary approach consisting of surgery, SRS, chemotherapy, and immunotherapy should be considered.

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Incidence, patterns of progression, and outcomes of preexisting and newly discovered brain metastases during treatment with anti–PD‐1 in patients with metastatic melanoma

Cited by 12 publications

References 28 publications

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

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

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

Outcomes after stereotactic radiosurgery of brain metastases in patients with malignant melanoma and validation of the melanoma molGPA

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