Dana-Farber Cancer Institute, Boston, MA
Lakshmi Nayak , Timothy Smith , Sarah C. Gaffey , Katherine B. Peters , Jennifer Leigh Clarke , Justin T Jordan , John Frederick De Groot , Phioanh Leia Nghiemphu , Thomas Joseph Kaley , Howard Colman , Terri Armstrong , Martin J. Taphoorn , Victoria Caruso , Myriam Bednarek Debruyne , Chinmay Bhavsar , Annette M Molinaro , Mariano Severgnini , Patrick Y. Wen , David A. Reardon
Background: The neurologic assessment in neuro-oncology (NANO) scale was developed as a standardized metric to objectively measure neurologic function in patients (pts) with brain tumors to complement radiographic assessment in defining overall outcome. The scale has been incorporated in various prospective studies to assess pts and to determine its utility. Methods: A multicenter, open label, phase II trial of pembrolizumab with and without bevacizumab in pts with recurrent glioblastoma (GBM) incorporated NANO scale as an exploratory endpoint. Neurologic examination by NANO was documented at baseline and each cycle until pts came off study. Statistical analyses including descriptive data analysis and generalized linear models were performed using R (version 3.4.3). Results: Eighty pts received treatment on study and underwent NANO evaluations. NANO compliance rate was 94%; of a total 388 expected NANO evaluations, 24 were missing. Of 80 pts, 7 missing NANO at baseline visit were excluded from analysis. Fifteen pts did not have end of treatment NANO evaluation. Of 73 pts, 35 (48%) had a normal neurologic examination at baseline by NANO. Two NANO domains (strength and language) accounted for the majority of variability in neurologic function over the course of study treatment. There was a significant correlation between NANO at each cycle and Karnofsky performance status score (p= 0.02). Nineteen pts were on dexamethasone at baseline; 42 required it during study. Corticosteroid requirement (OR = 1.9, p< 0.001) and an increase in corticosteroid dose (OR = 2.6, p< 0.001) were associated with higher risk of NANO progression (PD). Eighteen pts (25%) met NANO criteria for PD, including 2 without PD on MRI. Three pts (4%) had a neurologic response per NANO criteria associated with stability on MRI. Conclusions: Evaluation of neurologic function by NANO was feasible in a multicenter prospective study in GBM pts with a high compliance rate. NANO was able to objectively track neurologic function throughout the trial including preservation of baseline status in non-progressors. Clinical trial information: NCT02337491
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