دورية أكاديمية
Serial H3K27M cell-free tumor DNA (cf-tDNA) tracking predicts ONC201 treatment response and progression in diffuse midline glioma
| العنوان: | Serial H3K27M cell-free tumor DNA (cf-tDNA) tracking predicts ONC201 treatment response and progression in diffuse midline glioma |
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| المؤلفون: | Cantor, Evan, Wierzbicki, Kyle, Tarapore, Rohinton S, Ravi, Karthik, Thomas, Chase, Cartaxo, Rodrigo, Nand Yadav, Viveka, Ravindran, Ramya, Bruzek, Amy K, Wadden, Jack, John, Vishal, May Babila, Clarissa, Cummings, Jessica R, Rahman Kawakibi, Abed, Ji, Sunjong, Ramos, Johanna, Paul, Alyssa, Walling, Dustin, Leonard, Marcia, Robertson, Patricia, Franson, Andrea, Mody, Rajen, Garton, Hugh J L, Venneti, Sriram, Odia, Yazmin, Kline, Cassie, Vitanza, Nicholas A, Khatua, Soumen, Mueller, Sabine, Allen, Joshua E, Gardner, Sharon L, Koschmann, Carl |
| المساهمون: | NIH, NINDS, Department of Defense |
| المصدر: | Neuro-Oncology ; volume 24, issue 8, page 1366-1374 ; ISSN 1522-8517 1523-5866 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2022 |
| الوصف: | Background Diffuse Midline Glioma (DMG) with the H3K27M mutation is a lethal childhood brain cancer, with patients rarely surviving 2 years from diagnosis. Methods We conducted a multi-site Phase 1 trial of the imipridone ONC201 for children with H3K27M-mutant glioma (NCT03416530). Patients enrolled on Arm D of the trial (n = 24) underwent serial lumbar puncture for cell-free tumor DNA (cf-tDNA) analysis and patients on all arms at the University of Michigan underwent serial plasma collection. We performed digital droplet polymerase chain reaction (ddPCR) analysis of cf-tDNA samples and compared variant allele fraction (VAF) to radiographic change (maximal 2D tumor area on MRI). Results Change in H3.3K27M VAF over time (“VAF delta”) correlated with prolonged PFS in both CSF and plasma samples. Nonrecurrent patients that had a decrease in CSF VAF displayed a longer progression free survival (P = .0042). Decrease in plasma VAF displayed a similar trend (P = .085). VAF “spikes” (increase of at least 25%) preceded tumor progression in 8/16 cases (50%) in plasma and 5/11 cases (45.4%) in CSF. In individual cases, early reduction in H3K27M VAF predicted long-term clinical response (>1 year) to ONC201, and did not increase in cases of later-defined pseudo-progression. Conclusion Our work demonstrates the feasibility and potential utility of serial cf-tDNA in both plasma and CSF of DMG patients to supplement radiographic monitoring. Patterns of change in H3K27M VAF over time demonstrate clinical utility in terms of predicting progression and sustained response and possible differentiation of pseudo-progression and pseudo-response. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/neuonc/noac030 |
| DOI: | 10.1093/neuonc/noac030/42711324/noac030.pdf |
| الإتاحة: | https://doi.org/10.1093/neuonc/noac030Test https://academic.oup.com/neuro-oncology/article-pdf/24/8/1366/45187365/noac030.pdfTest |
| حقوق: | https://creativecommons.org/licenses/by-nc/4.0Test/ |
| رقم الانضمام: | edsbas.BCFB9CBD |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/neuonc/noac030 |
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