ADC Histogram Analysis of Pediatric Low-Grade Glioma Treated with Selumetinib: A Report from the Pediatric Brain Tumor Consortium

• Published in: American journal of neuroradiology : AJNR Vol. 43; no. 3; pp. 455 - 461
• Main Authors: Vajapeyam, S, Brown, D, Ziaei, A, Wu, S, Vezina, G, Stern, J S, Panigrahy, A, Patay, Z, Tamrazi, B, Jones, J Y, Haque, S S, Enterline, D S, Cha, S, Jones, B V, Yeom, K W, Onar-Thomas, A, Dunkel, I J, Fouladi, M, Fangusaro, J R, Poussaint, T Y
• Format: Journal Article
• Language: English
• Published: United States American Society of Neuroradiology 01.03.2022
• Subjects: Benzimidazoles; Brain Neoplasms - diagnostic imaging; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Child; Diffusion Magnetic Resonance Imaging; Editor's Choice; Functional; Glioma - diagnostic imaging; Glioma - drug therapy; Glioma - genetics; Humans; Neurofibromatosis 1 - diagnostic imaging; Neurofibromatosis 1 - drug therapy; Pediatrics; Proto-Oncogene Proteins B-raf
• ISSN: 0195-6108; 1936-959X
• DOI: 10.3174/ajnr.A7433

Selumetinib is a promising MAP (mitogen-activated protein) kinase (MEK) 1/2 inhibitor treatment for pediatric low-grade gliomas. We hypothesized that MR imaging-derived ADC histogram metrics would be associated with survival and response to treatment with selumetinib. Children with recurrent, refractory, or progressive pediatric low-grade gliomas who had World Health Organization grade I pilocytic astrocytoma with fusion or the V600E mutation (stratum 1), neurofibromatosis type 1-associated pediatric low-grade gliomas (stratum 3), or sporadic non-neurofibromatosis type 1 optic pathway and hypothalamic glioma (OPHG) (stratum 4) were treated with selumetinib for up to 2 years. Quantitative ADC histogram metrics were analyzed for total and enhancing tumor volumes at baseline and during treatment. Each stratum comprised 25 patients. Stratum 1 responders showed lower values of SD of baseline ADC_total as well as a larger decrease with time on treatment in ADC_total mean, mode, and median compared with nonresponders. Stratum 3 responders showed a greater longitudinal decrease in ADC_total. In stratum 4, higher baseline ADC_total skewness and kurtosis were associated with shorter progression-free survival. When all 3 strata were combined, responders showed a greater decrease with time in ADC_total mode and median. Compared with sporadic OPHG, neurofibromatosis type 1-associated OPHG had lower values of ADC_total mean, mode, and median as well as ADC_enhancement mean and median and higher values of ADC_total skewness and kurtosis at baseline. The longitudinal decrease in ADC_total median during treatment was significantly greater in sporadic OPHG compared with neurofibromatosis type 1-associated OPHG. ADC histogram metrics are associated with progression-free survival and response to treatment with selumetinib in pediatric low-grade gliomas.