S Vajapeyam1, D Brown2, A Ziaei3, S Wu4, G Vezina5, J S Stern6, A Panigrahy7, Z Patay8, B Tamrazi9, J Y Jones10, S S Haque11, D S Enterline12, S Cha13, B V Jones14, K W Yeom15, A Onar-Thomas4, I J Dunkel11, M Fouladi10, J R Fangusaro16, T Y Poussaint17. 1. From the Department of Radiology (S.V., T.Y.P.), Boston Children's Hospital,Harvard Medical School, Boston, Massachusetts sridhar.vajapeyam@childrens.harvard.edu. 2. Department of Radiology (D.B.), Massachusetts General Hospital, Boston, Massachusetts. 3. Department of Radiology (A.Z.), Boston Children's Hospital, Boston, Massachusetts. 4. Department of Biostatistics (S.W., A.O.-T.), St Jude Children's Research Hospital, Memphis, Tennessee. 5. Department of Radiology (G.V.), Children's National Medical Center, Washington, DC. 6. Department of Radiology (J.S.S.), Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois. 7. Department of Radiology (A.P.), Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania. 8. Department of Diagnostic Imaging (Z.P.), St Jude Children's Research Hospital, Memphis, Tennessee. 9. Department of Radiology (B.T.), Children's Hospital Los Angeles, Los Angeles, California. 10. Department of Radiology (J.Y.J., M.F.), Nationwide Children's Hospital, Columbus, Ohio. 11. Department of Radiology (S.S.H., I.J.D.), Memorial Sloan Kettering Cancer Center, New York, New York. 12. Department of Radiology (D.S.E.), Duke University School of Medicine, Durham, North Carolina. 13. Department of Radiology (S.C.), University of California San Francisco, San Francisco, California. 14. Department of Radiology (B.V.J.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 15. Department of Radiology (K.W.Y.), Stanford University School of Medicine, Stanford, California. 16. Department of Hematology, Oncology, and Stem Cell Transplantation (J.R.F.), Children's Healthcare of Atlanta and Emory University, Atlanta, Georgia. 17. From the Department of Radiology (S.V., T.Y.P.), Boston Children's Hospital,Harvard Medical School, Boston, Massachusetts.
Abstract
BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: Children with recurrent, refractory, or progressive pediatric low-grade gliomas who had World Health Organization grade I pilocytic astrocytoma with KIAA1549-BRAF fusion or the BRAF 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. RESULTS: 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. CONCLUSIONS: ADC histogram metrics are associated with progression-free survival and response to treatment with selumetinib in pediatric low-grade gliomas.
BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: Children with recurrent, refractory, or progressive pediatric low-grade gliomas who had World Health Organization grade I pilocytic astrocytoma with KIAA1549-BRAF fusion or the BRAF 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. RESULTS: 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. CONCLUSIONS: ADC histogram metrics are associated with progression-free survival and response to treatment with selumetinib in pediatric low-grade gliomas.
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