Raymond Y Huang1, Robert J Young2, Benjamin M Ellingson3, Harini Veeraraghavan4, Wei Wang5, Florent Tixier4, Hyemin Um4, Rasheed Nawaz1, Tracy Luks6, John Kim7, Elizabeth R Gerstner8, David Schiff9, Katherine B Peters10, Ingo K Mellinghoff11, Susan M Chang12, Timothy F Cloughesy13, Patrick Y Wen14. 1. Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts. 2. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. 3. UCLA Brain Tumor Imaging Laboratory, Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. 4. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York. 5. Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts. 6. Department of Radiology, University of California San Francisco, San Francisco, California. 7. Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan. 8. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts. 9. Departments of Neurology, Neurological Surgery, and Medicine, University of Virginia, Charlottesville, Virginia. 10. Department of Neurology and Neurosurgery, Preston Robert Tisch Brain Tumor Center, Duke University, Durham, North Carolina. 11. Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York. 12. Department of Neurological Surgery, University of California San Francisco, San Francisco, California. 13. Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. 14. Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Abstract
BACKGROUND: Lower-grade gliomas (LGGs) with isocitrate dehydrogenase 1 and/or 2 (IDH1/2) mutations have long survival times, making evaluation of treatment efficacy difficult. We investigated the volumetric growth rate of IDH mutant gliomas before and after treatment with established glioma therapies to determine whether a significant change in growth rate could be documented and perhaps be used in the future to evaluate treatment response to investigational agents in LGG trials. METHODS: In this multicenter retrospective study, 230 adult patients with IDH1/2 mutated LGGs (World Health Organization grade II or III) undergoing surgery, radiation, or chemotherapy for progressive non-enhancing tumor were identified. Subjects were required to have 3 MRI scans containing T2/fluid attenuated inversion recovery imaging spanning a minimum of 6 months prior to treatment. A mixed-effect model was used to estimate tumor growth prior to treatment. A subset of 95 patients who received chemotherapy, radiotherapy, or chemoradiotherapy and had 2 posttreatment imaging time points available were evaluated for change in pre- and posttreatment volumetric growth rates using a piecewise mixed model. RESULTS: The pretreatment volumetric growth rate across all 230 patients was 27.37%/180 days (95% CI: [23.36%, 31.51%]). In the 95 patients with both pre- and posttreatment scans available, there was a significant difference in volumetric growth rates before (26.63%/180 days, 95% CI: [19.31%, 34.40%]) and after treatment (-15.24% /180 days, 95% CI: [-21.37%, -8.62%]) (P < 0.0001). The growth rates for patient subgroup with 1p/19q codeletion (N = 118) was significantly slower than the rate of the 1p/19q non-codeleted group (N = 68) (22.84% vs 35.49%, P = 0.0108). CONCLUSION: In this study, we evaluated the growth rates of IDH mutant gliomas before and after standard therapy. Further study is needed to establish whether a change in growth rate is associated with patient survival and its use as a surrogate endpoint in clinical trials for IDH mutant LGGs.
BACKGROUND: Lower-grade gliomas (LGGs) with isocitrate dehydrogenase 1 and/or 2 (IDH1/2) mutations have long survival times, making evaluation of treatment efficacy difficult. We investigated the volumetric growth rate of IDH mutant gliomas before and after treatment with established glioma therapies to determine whether a significant change in growth rate could be documented and perhaps be used in the future to evaluate treatment response to investigational agents in LGG trials. METHODS: In this multicenter retrospective study, 230 adult patients with IDH1/2 mutated LGGs (World Health Organization grade II or III) undergoing surgery, radiation, or chemotherapy for progressive non-enhancing tumor were identified. Subjects were required to have 3 MRI scans containing T2/fluid attenuated inversion recovery imaging spanning a minimum of 6 months prior to treatment. A mixed-effect model was used to estimate tumor growth prior to treatment. A subset of 95 patients who received chemotherapy, radiotherapy, or chemoradiotherapy and had 2 posttreatment imaging time points available were evaluated for change in pre- and posttreatment volumetric growth rates using a piecewise mixed model. RESULTS: The pretreatment volumetric growth rate across all 230 patients was 27.37%/180 days (95% CI: [23.36%, 31.51%]). In the 95 patients with both pre- and posttreatment scans available, there was a significant difference in volumetric growth rates before (26.63%/180 days, 95% CI: [19.31%, 34.40%]) and after treatment (-15.24% /180 days, 95% CI: [-21.37%, -8.62%]) (P < 0.0001). The growth rates for patient subgroup with 1p/19q codeletion (N = 118) was significantly slower than the rate of the 1p/19q non-codeleted group (N = 68) (22.84% vs 35.49%, P = 0.0108). CONCLUSION: In this study, we evaluated the growth rates of IDH mutant gliomas before and after standard therapy. Further study is needed to establish whether a change in growth rate is associated with patient survival and its use as a surrogate endpoint in clinical trials for IDH mutant LGGs.
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