@article{a49df17191f44bbbad8e78aec7d49733,
title = "Serial assessment of measurable residual disease in medulloblastoma liquid biopsies",
abstract = "Nearly one-third of children with medulloblastoma, a malignant embryonal tumor of the cerebellum, succumb to their disease. Conventional response monitoring by imaging and cerebrospinal fluid (CSF) cytology remains challenging, and a marker for measurable residual disease (MRD) is lacking. Here, we show the clinical utility of CSF-derived cell-free DNA (cfDNA) as a biomarker of MRD in serial samples collected from children with medulloblastoma (123 patients, 476 samples) enrolled on a prospective trial. Using low-coverage whole-genome sequencing, tumor-associated copy-number variations in CSF-derived cfDNA are investigated as an MRD surrogate. MRD is detected at baseline in 85% and 54% of patients with metastatic and localized disease, respectively. The number of MRD-positive patients declines with therapy, yet those with persistent MRD have significantly higher risk of progression. Importantly, MRD detection precedes radiographic progression in half who relapse. Our findings advocate for the prospective assessment of CSF-derived liquid biopsies in future trials for medulloblastoma.",
keywords = "biomarkers, cell-free DNA, cerebrospinal fluid, childhood cancer, liquid biopsy, measurable residual disease, medulloblastoma, microscopic residual disease, minimal residual disease, relapse disease",
author = "Liu, {Anthony P.Y.} and Smith, {Kyle S.} and Rahul Kumar and Leena Paul and Laure Bihannic and Tong Lin and Maass, {Kendra K.} and Pajtler, {Kristian W.} and Murali Chintagumpala and Su, {Jack M.} and Eric Bouffet and Fisher, {Michael J.} and Sridharan Gururangan and Richard Cohn and Tim Hassall and Hansford, {Jordan R.} and Paul Klimo and Boop, {Frederick A.} and Stewart, {Clinton F.} and Harreld, {Julie H.} and Merchant, {Thomas E.} and Tatevossian, {Ruth G.} and Geoffrey Neale and Matthew Lear and Klco, {Jeffery M.} and Orr, {Brent A.} and Ellison, {David W.} and Gilbertson, {Richard J.} and Arzu Onar-Thomas and Amar Gajjar and Robinson, {Giles W.} and Northcott, {Paul A.}",
note = "Funding Information: The authors acknowledge patients and families, physicians, nursing, research, and administrative staff from all participating institutions. In particular, we thank Aksana Vasilyeva, PhD, and Jana Freeman, CCRP, from the St. Jude Division of Neuro-Oncology for coordination of study material; the St. Jude Biorepository for archiving and providing patient samples; and Scott Olsen and Sanchit Trivedi from the St. Jude Hartwell Center, for their help with next-generation sequencing. We thank Brandon Stelter for assistance with figure preparation and artwork. This study was principally supported by the National Cancer Institute (P.A.N.; R21CA256386). Additional funding was provided by the American Lebanese Syrian Associated Charities, National Cancer Institute Cancer Center Grant (P30CA021765), St. Jude Comprehensive Cancer Center Developmental Funds (P.A.N. and G.W.R.) and Conquer Cancer ? #cureMEdullo powered by Carson Leslie Foundation Young Investigator Award (A.P.Y.L.). A.P.Y.L. is supported by the Li Shu Pui Medical Foundation Training Grant and the Lin Kin Pang-HKU Foundation Scholarship. P.A.N. is a Pew-Stewart Scholar for Cancer Research (Margaret and Alexander Stewart Trust), Sontag Foundation Distinguished Scientist, and recipient of the Robert J. Arceci Innovation Award (St. Baldrick's Foundation). A.P.Y.L. K.S.S. R.K. A.G. G.W.R. and P.A.N. conceptualized the study and developed the methodology. A.P.Y.L. K.S.S. R.K. and L.P. performed the study investigation. A.P.Y.L. K.S.S. R.K. T.L. and A.O.T. performed the formal analysis. K.K.M. K.W.P. M.C. J.M.S. E.B. M.J.F. S.G. R.C. T.H. J.R.H. P.K. F.A.B. C.F.S. J.H.H. T.E.M. R.G.T. J.M.K. B.A.O. D.W.E. and R.J.G. obtained resources. A.P.Y.L. K.S.S. R.K. A.G. G.W.R. and P.A.N. wrote the original draft. All authors reviewed and edited the manuscript. A.G. G.W.R. and P.A.N. obtained funding and supervised the study. The authors declare no competing interests. Funding Information: The authors acknowledge patients and families, physicians, nursing, research, and administrative staff from all participating institutions. In particular, we thank Aksana Vasilyeva, PhD, and Jana Freeman, CCRP, from the St. Jude Division of Neuro-Oncology for coordination of study material; the St. Jude Biorepository for archiving and providing patient samples; and Scott Olsen and Sanchit Trivedi from the St. Jude Hartwell Center, for their help with next-generation sequencing. We thank Brandon Stelter for assistance with figure preparation and artwork. This study was principally supported by the National Cancer Institute (P.A.N.; R21CA256386 ). Additional funding was provided by the American Lebanese Syrian Associated Charities , National Cancer Institute Cancer Center Grant ( P30CA021765 ), St. Jude Comprehensive Cancer Center Developmental Funds (P.A.N. and G.W.R.) and Conquer Cancer – #cureMEdullo powered by Carson Leslie Foundation Young Investigator Award (A.P.Y.L.). A.P.Y.L. is supported by the Li Shu Pui Medical Foundation Training Grant and the Lin Kin Pang-HKU Foundation Scholarship. P.A.N. is a Pew-Stewart Scholar for Cancer Research ( Margaret and Alexander Stewart Trust ), Sontag Foundation Distinguished Scientist, and recipient of the Robert J. Arceci Innovation Award ( St. Baldrick's Foundation ). Publisher Copyright: {\textcopyright} 2021",
year = "2021",
month = nov,
day = "8",
doi = "10.1016/j.ccell.2021.09.012",
language = "English (US)",
volume = "39",
pages = "1519--1530.e4",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "11",
}