Comparing available criteria for measuring brain metastasis response to immunotherapy

• Published in: Journal of neuro-oncology Vol. 132; no. 3; pp. 479 - 485
• Main Authors: Qian, Jack M., Mahajan, Amit, Yu, James B., Tsiouris, A. John, Goldberg, Sarah B., Kluger, Harriet M., Chiang, Veronica L. S.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.05.2017; Springer Nature B.V
• Subjects: Brain cancer; Brain tumors; Clinical Study; Clinical trials; Glioma; Immunotherapy; Magnetic resonance imaging; Medicine; Medicine & Public Health; Metastases; Metastasis; Monoclonal antibodies; Neurology; Oncology; Targeted cancer therapy; RANO-BM; Brain metastases; RECIST; anti-PD-1; Immunotherapy; Response criteria
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-017-2398-8

The response assessment in neuro-oncology (RANO) working group recently proposed standardized response criteria for brain metastases (RANO-BM). We sought to compare RANO-BM to other criteria in an ongoing brain metastasis trial. The first 36 patients enrolled on NCT02085070, an ongoing trial of pembrolizumab for patients with untreated brain metastases, were included in this analysis. As RANO-BM had not been proposed when the protocol was written, response on trial was assessed using an institutional modification of RECIST 1.1 (mRECIST), wherein minimum target brain lesion size was 5 mm in longest diameter and up to five target brain lesions were followed. We here additionally assessed response using standard RECIST 1.1, RANO high-grade glioma (RANO-HGG), and RANO-BM. Comparison between the four criteria sets using cases eligible across the board revealed excellent concordance (kappa statistic > 0.8), with only one discordant case. However, compared to RECIST 1.1 or RANO-BM, using a 5 mm threshold for target brain lesions in mRECIST allowed enrollment of 13 additional patients, five of whom had durable responses. Compared to RANO-HGG, 19 additional patients were enrolled using mRECIST, eight of whom had durable responses. Consequently, this resulted in response rates ranging from 12% with RANO-HGG to 28% with mRECIST. This study supports using a 5 mm threshold for target brain lesions when using high resolution MRI with ≤2 mm slices to facilitate accrual to similar clinical trials and provide earlier access to novel therapies for brain metastasis patients. Concordance among the four criteria studied was otherwise very high.