<i>BRAF</i>‐V600 mutational status affects recurrence patterns of melanoma brain metastasis

Maxwell, Russell; Garzón-Muvdi, Tomás; Lipson, Evan J.; Sharfman, William H.; Bettegowda, Chetan; Redmond, Kristin J.; Kleinberg, Lawrence; Ye, Xiaobu; Lim, Michael

doi:10.1002/ijc.30241

Cited by 26 publications

(28 citation statements)

References 50 publications

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“…Jakob et al [27] reported a higher prevalence observed in BRAF-mutant (24%) and NRAS-mutant (23%) patients than in “wild-type” patients (12%), and Maxwell et al [28] similarly found that BRAF mutations were associated with an increased risk of BM. On the other hand, Schoenewolf et al [25] found that BRAF mutant versus wild-type tumors showed no significant differences in propensity for BM.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis

Gardner¹,

Ward

Andtbacka

et al. 2017

Melanoma Research

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Objective Melanoma metastasis to the brain is associated with poor prognosis. We sought to determine patient demographics and primary tumor factors associated with development of brain metastasis (BM) and survival. We also investigated whether the BM detection setting (routine screening vs. symptomatic presentation) affected clinical outcomes. Methods A database of melanoma patients seen from 1999-2015 at our institution was reviewed to identify patients that developed BM. Patients with BM were matched by initial stage with patients who did not develop BM as a control group. Patient demographics, primary tumor characteristics, and clinical outcomes were analyzed. Results 123 patients with BM were matched by initial presenting stage to 237 patients without BM. Characteristics of the primary melanoma tumor associated with BM development included location on the scalp (P=0.030), nodular histologic type (P=0.020) and Breslow depth >4mm (P=0.048), while location on the leg was associated with decreased BM risk (P=0.006). In patients with BM, time to first recurrence for melanomas of the scalp was significantly shorter (10.8 vs. 24.8 months, p=0.007) than non-scalp head and neck tumors. Patient stage, tumor depth, nodular type, and ulceration were also associated with worse clinical outcomes. There were no differences in clinical outcomes between patients whose BM were detected upon routine screening vs. upon symptomatic presentation. Conclusions Factors predictive of developing BM included primary scalp location, nodular type, and depth. In BM patients, scalp location, stage, tumor depth, nodular type and ulceration, but not detection setting, were associated with worse clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis

Gardner¹,

Ward

Andtbacka

et al. 2017

Melanoma Research

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“…Spagnolo et al calculated a median OS of 7.9 months for patients treated with BRAF inhibitors, relative to the historical survival of 6.2 months for patients with metastatic melanoma overall and 2.2–4.7 months for patients with intracranial metastases [ 137 ]. In addition, evidence for the importance of treating patients with effective BRAF V600 inhibitors has come from several reports that have determined that inhibiting BRAF V600 significantly prolonged the time between the initial metastatic melanoma diagnosis and the subsequent brain metastasis diagnosis [ 159 ] and also lowered the incidence of brain metastasis formation [ 160 ].…”

Section: Melanoma Brain Metastasis Therapiesmentioning

confidence: 99%

Melanoma Brain Metastasis: Mechanisms, Models, and Medicine

Kircher

Silvis

Cho

et al. 2016

IJMS

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The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases.

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“…No correlation was found between traditional radiological features and BRAF status, further emphasizing the need for novel radiological biomarkers for this mutation 33 . Since the use of BRAF inhibitors have dramatically improved the prognosis of advanced-stage melanoma and allow for long-term control in some cases, it is critical to assess the mutation status of the tumor 12,[34][35][36] . This especially holds true for patients with non-resectable BMM who are candidates for stereotactic radiosurgery.…”

Section: Discussionmentioning

confidence: 99%

Virtual biopsy using MRI radiomics for prediction of BRAF status in melanoma brain metastasis

Shofty

Artzi

Shtrozberg

et al. 2020

Sci Rep

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Brain metastases are common in patients with advanced melanoma and constitute a major cause of morbidity and mortality. Between 40% and 60% of melanomas harbor BRAF mutations. Selective BRAf inhibitor therapy has yielded improvement in clinical outcome; however, genetic discordance between the primary lesion and the metastatic tumor has been shown to occur. currently, the only way to characterize the genetic landscape of a brain metastasis is by tissue sampling, which carries risks and potential complications. the aim of this study was to investigate the use of radiomics analysis for non-invasive identification of BRAF mutation in patients with melanoma brain metastases, based on conventional magnetic resonance imaging (MRi) data. We applied a machine-learning method, based on MRi radiomics features for noninvasive characterization of the BRAf status of brain metastases from melanoma (BMM) and applied it to BMM patients from two tertiary neuro-oncological centers. All patients underwent surgical resection for BMM, and their BRAf mutation status was determined as part of their oncological work-up. their routine preoperative MRi study was used for radiomicsbased analysis in which 195 features were extracted and classified according to their BRAF status via a support vector machine. The BRAF status of 53 study patients, with 54 brain metastases (25 positive, 29 negative for BRAF mutation) was predicted with mean accuracy = 0.79 ± 0.13, mean precision = 0.77 ± 0.14, mean sensitivity = 0.72 ± 0.20, mean specificity = 0.83 ± 0.11 and with a 0.78 area under the receiver operating characteristic curve for positive BRAf mutation prediction. Radiomics-based noninvasive genetic characterization is feasible and should be further verified using large prospective cohorts. Melanoma is the third most common cutaneous tumor after basal cell carcinoma and squamous cell carcinoma. Melanomas account for up to 1.6% of newly diagnosed malignancies in the developed world 1. The worldwide incidence of malignant melanoma is rising, with approximately 290,000 new cases diagnosed per year, resulting in up to 60,000 mortalities 2. Systemic melanoma carries a high risk of central nervous system (CNS) spread 3. Up to 75% of stage IV patients with systemic melanoma eventually develop CNS metastases, which account for up to 50% of melanoma-related mortalities 4,5. The risk of brain metastases from melanoma (BMM) rises with disease duration. While 20-30% of patients will develop BMM in one year, 30-40% will develop BMM in 3 years 6. Identification of BRAF activating mutation as a key oncogene in approximately half of all melanomas has dramatically changed the current treatment strategy for metastatic melanoma 7-10. BRAF mutation has been assumed to be an early evolutionary event in tumor maturation, and play a central role in melanoma pathogenesis 11. At the cellular level, BRAF mutations drive oncogenic behavior of melanoma cells, leading to unrestricted cell growth, increased cell survival, and local invasion through activation of the mitogen-...

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BRAF‐V600 mutational status affects recurrence patterns of melanoma brain metastasis

Cited by 26 publications

References 50 publications

Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis

Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis

Melanoma Brain Metastasis: Mechanisms, Models, and Medicine

Virtual biopsy using MRI radiomics for prediction of BRAF status in melanoma brain metastasis

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