Cumulative Intracranial Tumor Volume Augments the Prognostic Value of Diagnosis-Specific Graded Prognostic Assessment Model for Survival in Patients with Melanoma Cerebral Metastases

Hirshman, Brian R.; Wilson, Bayard; Ali, Mir Amaan; Schüpper, Alexander J.; Proudfoot, James; Goetsch, Steven J.; Carter, Bob S.; Sinclair, Georges; Bártek, Jiří; Chiang, Veronica; Fogarty, Gerald B; Hong, Angela; Chen, Clark C.

doi:10.1093/neuros/nyx380

Cited by 23 publications

(17 citation statements)

References 27 publications

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“…VOI total +. 41MAX, the semiautomated segmentation method using 41% of the lesion's SUVmax; A50P, the semi-automated segmentation method using 50% of the lesion's SUVpeak adjusted for background uptake; SUV40, the semiautomated segmentation method using a fixed SUV threshold of 4.0 g/ mL; MV2, consensus "majority-vote" method using agreement between 2 or more of the standard PET-based methods; MV3, consensus "majority-vote" method using agreement between 3 or more of the standard PET-based methods contribution of brain metastasis to the total MATV is generally small [30] and individual brain metastases are often < 1 mL based on MRI [31,32], i.e. below the used threshold of 3 mL lesion volume in the TTB.…”

Section: Discussionmentioning

confidence: 99%

Clinically feasible semi-automatic workflows for measuring metabolically active tumour volume in metastatic melanoma

Sluis

Heer

Boellaard

et al. 2020

Eur J Nucl Med Mol Imaging

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Purpose Metabolically active tumour volume (MATV) is a potential quantitative positron emission tomography (PET) imaging biomarker in melanoma. Accumulating data indicate that low MATV may predict increased chance of response to immunotherapy and overall survival. However, metastatic melanoma can present with numerous (small) tumour lesions, making manual tumour segmentation time-consuming. The aim of this study was to evaluate multiple semi-automatic segmentation workflows to determine reliability and reproducibility of MATV measurements in patients with metastatic melanoma. Methods An existing cohort of 64 adult patients with histologically proven metastatic melanoma was used in this study. 18F-FDG PET/CT diagnostic baseline images were acquired using a European Association of Nuclear Medicine (EANM) Research Limited–accredited Siemens Biograph mCT PET/CT system (Siemens Healthineers, Knoxville, USA). PET data were analysed using manual, gradient-based segmentation and five different semi-automatic methods: three direct PET image–derived delineations (41MAX, A50P and SUV40) and two based on a majority-vote approach (MV2 and MV3), without and with (suffix ‘+’) manual lesion addition. Correlation between the different segmentation methods and their respective associations with overall survival was assessed. Results Correlation between the MATVs derived by the manual segmentation and semi-automated tumour segmentations ranged from R2 = 0.41 for A50P to R2 = 0.85 for SUV40+ and MV2+, respectively. Manual MATV segmentation did not differ significantly from the semi-automatic methods SUV40 (∆MATV mean ± SD 0.08 ± 0.60 mL, P = 0.303), SUV40+ (∆MATV − 0.10 ± 0.51 mL, P = 0.126), MV2+ (∆MATV − 0.09 ± 0.62 mL, P = 0.252) and MV3+ (∆MATV − 0.03 ± 0.55 mL, P = 0.615). Log-rank tests showed statistically significant overall survival differences between above and below median MATV patients for all segmentation methods with areas under the ROC curves of 0.806 for manual segmentation and between 0.756 [41MAX] and 0.807 [MV3+] for semi-automatic segmentations. Conclusions Simple and fast semi-automated FDG PET segmentation workflows yield accurate and reproducible MATV measurements that correlate well with manual segmentation in metastatic melanoma. The most readily applicable and user-friendly SUV40 method allows feasible MATV measurement in prospective multicentre studies required for validation of this potential PET imaging biomarker for clinical use.

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Section: Discussionmentioning

confidence: 99%

Clinically feasible semi-automatic workflows for measuring metabolically active tumour volume in metastatic melanoma

Sluis

Heer

Boellaard

et al. 2020

Eur J Nucl Med Mol Imaging

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“…Detailed descriptions of the SRS technique have previously been provided. 6 , 21 , 23 In brief, patients underwent imaging using 1mm axial and coronal slices, on T1-weighted pre- and post-contrast MRI. All patients were consulted by a multi-disciplinary team of specialists, consisting of a neurosurgeon, radiation oncologist, and medical physicist.…”

Section: Methodsmentioning

confidence: 99%

“…For CITV, a cutoff of 4 cubic centimeters (cc) was used, corresponding to point values of 0 (< 4cc) and 2 (>= 4cc) as previously published. 21 For BRAF mutation status, 0 points were assigned for absence of the mutation, and 2 points for presence of the mutation. We constructed 3 different ds-GPA models (original ds-GPA, CITV-modified ds-GPA, and CITV-BRAF-modified ds-GPA) and compared them using the Akaike Information Criterion (AIC).…”

Section: Methodsmentioning

confidence: 99%

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An integrated disease-specific graded prognostic assessment scale for melanoma: contributions of KPS, CITV, number of metastases, and BRAF mutation status

Ahluwalia

Ali

Joshi

et al. 2020

Neuro-Oncology Advances

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Background Stereotactic radiosurgery (SRS) remains a mainstay therapy in the treatment of melanoma brain metastases (BM). While prognostic scales have been developed for melanoma patients who underwent SRS treatment for BM, the pertinence of these scales in the context of molecularly targeted therapies remains unclear. Methods Through a multi-institutional collaboration, we collated the survival patterns of 331 melanoma BM patients with known BRAF mutation status treated with SRS. We established a prognostic scale that was validated in an independent cohort of 174 patients. All patients with BRAF mutations in this series were treated with BRAF inhibitors. Prognostic utility was assessed using net reclassification index (NRI > 0) and integrated discrimination improvement (IDI) metrics. Results In a multivariate Cox proportional hazards model, BRAF mutation status, Karnofsky Performance Score (KPS), number of metastases, and cumulative intracranial tumor volume (CITV) independently contributed to survival prognostication for melanoma patients with SRS-treated BM (p < 0.05 for all variables). These variables were incorporated into a prognostic scale using the disease-specific graded prognostic assessment (ds-GPA) framework. This integrated melanoma ds-GPA scale was validated in two independent cohorts collated through a multi-institutional collaboration. In terms of order of prognostic importance, BRAF mutation status exerted the greatest influence on survival, while KPS, the number of metastases, and CITV exhibited comparable, lesser impacts. Conclusions Optimal survival prognostication for SRS-treated patients with melanoma BM requires an integrated assessment of patient characteristics (KPS), tumor characteristics (CITV and number of metastases), and the mutational profile of the melanoma (BRAF mutation status).

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“…Several studies indicate a median survival of ~4 months once patients are diagnosed with melanoma brain metastasis (2, 3). Poor non-CNS disease control, poor performance status, leptomeningeal disease (LMD) defined as the infiltration of cancer cells in pia mater and arachnoid membrane, more than three CNS brain metastatic melanoma lesions, and a higher cumulative intracranial tumor volume have been associated with poor survival (2, 4, 5). Surgery for melanoma brain metastasis with or without adjuvant whole brain radiation therapy has been shown to improve the median survival to ~9 months regardless whether patients have single or multiple brain metastases (3).…”

Section: Introductionmentioning

confidence: 99%

Targeted Therapy After Brain Radiotherapy for BRAF-Mutated Melanoma With Extensive Ependymal Disease With Prolonged Survival: Case Report and Review of the Literature

et al. 2019

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Melanoma brain metastasis with ependymal spread/metastases is uncommon. These cases are frequently classified together with leptomeningeal disease. However, the commonalities and differences in the underlying pathophysiology and clinical outcomes between these two types of spread are not clear. Very few reports on long term outcome and durable central nervous system (CNS) disease control have been reported in the literature. Here, we report a case of a 45 year-old Caucasian lady with BRAF-V600E mutant metastatic melanoma to the brain who had whole brain radiotherapy followed by two Gamma knife radiosurgery treatments for localized disease progression. She then developed extensive ependymal disease progression with no evidence of leptomeningeal spread. She was treated with a repeat course of whole brain radiotherapy and maintained on BRAF and MEK inhibitors with durable CNS disease control for more than a year. This study reviews the management of BRAF-V600E mutant melanoma with ependymal involvement. Management using radiation therapy with maintenance targeted therapy seems to be a reasonable approach to this challenging disease.

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Cumulative Intracranial Tumor Volume Augments the Prognostic Value of Diagnosis-Specific Graded Prognostic Assessment Model for Survival in Patients with Melanoma Cerebral Metastases

Abstract: The prognostic value of the ds-GPA scale for melanoma BM is enhanced by the incorporation of CITV.

Cited by 23 publications

References 27 publications

Clinically feasible semi-automatic workflows for measuring metabolically active tumour volume in metastatic melanoma

Clinically feasible semi-automatic workflows for measuring metabolically active tumour volume in metastatic melanoma

An integrated disease-specific graded prognostic assessment scale for melanoma: contributions of KPS, CITV, number of metastases, and BRAF mutation status

Targeted Therapy After Brain Radiotherapy for BRAF-Mutated Melanoma With Extensive Ependymal Disease With Prolonged Survival: Case Report and Review of the Literature

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