Melanoma brain metastases: correlation of imaging features with genomic markers and patient survival

Bordia, Ritu; Zhong, Judy; Lee, Joon; Weiss, Sarah A.; Han, Sung Won; Osman, Iman; Jain, Rajan

doi:10.1007/s11060-016-2305-8

Cited by 16 publications

(7 citation statements)

References 23 publications

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“…After lung and breast cancer, melanoma is the most common cancer that metastasizes to the brain [2]. Approximately 10% of patients with a history of invasive melanoma will ultimately develop brain metastasis (BM) [2], which contributes significantly to melanoma-related morbidity and mortality [3,4]. Treatment of BM is difficult, and historically such patients have had an overall survival in the range of 3-6 months [4-7].…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…Aside from the number of metastases, they reported that BRAF mutation status and concomitant BRAF inhibitor treatment was the most significant prognostic factor. 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] .…”

Section: Discussionmentioning

confidence: 91%

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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“…Of note, Bordia et al . [21] did not find any significant correlations between signal characteristics of IMM and patient survival, other than for a larger number of lesions being associated with worse survival.…”

Section: Discussionmentioning

confidence: 92%

“…Previously, Bordia et al . [21] did not find any significant correlations between BRAF status and T1 signal. Our study has some notable advantages, however, and we feel these account for our ability to identify such a difference.…”

Section: Discussionmentioning

confidence: 96%

“…To our knowledge, the only previous study correlating T1 signal on MRI with BRAF status has been by Bordia et al . [21], and this failed to find any significant differences. With the likelihood of haemorrhage increasing with lesion size [16], we aimed to examine the differences in signal characteristics between BRAF mut and BRAF wt IMM with a focus on small (<10 mm) lesions.…”

Section: Introductionmentioning

confidence: 91%

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Correlation of MRI signal characteristics of intracranial melanoma metastases with BRAF mutation status

Lasocki

McArthur

2022

Melanoma Research

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BRAF V600 mutations (BRAFmut) are associated with more pigmentation in primary melanomas, but data on melanin content of metastases are limited. This study compares signal characteristics of BRAFmut and BRAF-wildtype (BRAFwt) intracranial melanoma metastases (IMM). MRI brain examinations at first diagnosis of IMM were identified, all performed at 3-Tesla including 1 mm volumetric pre- and postcontrast T1-weighted imaging and susceptibility-weighted imaging (SWI). Individual metastases were assessed by a neuroradiologist, stratified by size (≥10 mm, ‘larger’, vs. 2–9 mm, ‘small’; up to 10 per group); presence of intrinsic T1-hyperintensity (T1H) and, if present, whether confidently attributable to melanin as opposed to haemorrhage; evidence of haemorrhage; presence of central necrosis. A total of 267 IMM in 73 patients were assessed (87 larger IMM, 180 small). The proportion of larger IMM was similar in both groups (31% BRAFmut and 36% BRAFwt). In small IMM, MRI evidence of melanin was more common in BRAFmut patients (42% vs. 26%; P = 0.038). Haemorrhage was more common in larger IMM (51%, vs. 20% of small IMM; P < 0.0001), but did not differ based on BRAF status. Central necrosis was more common in larger IMM (44% vs. 7%; P < 0.0001) and in BRAFmut IMM (23% vs. 11%; P = 0.011). In the BRAFmut cohort, central necrosis was more common in patients without previous anti-BRAF therapy (33% vs. 7%; P = 0.0001). T1H attributable to melanin is only slightly more common in BRAFmut IMM than BRAFwt. Higher rates of central necrosis in BRAFmut patients without previous anti-BRAF therapy suggest that anti-BRAF therapy may affect the patterns of IMM growth.

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Melanoma brain metastases: correlation of imaging features with genomic markers and patient survival

Cited by 16 publications

References 23 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

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

Correlation of MRI signal characteristics of intracranial melanoma metastases with BRAF mutation status

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