دورية أكاديمية
أعرض في EDS

Detection of Leptomeningeal Disease Using Cell-Free DNA From Cerebrospinal Fluid.

التفاصيل البيبلوغرافية
العنوان: Detection of Leptomeningeal Disease Using Cell-Free DNA From Cerebrospinal Fluid.
المؤلفون: White MD; Division of Neuro-Oncology, Massachusetts General Hospital, Harvard Medical School, Boston.; Cancer Center, Massachusetts General Hospital, Boston.; Division of Comprehensive Neurology, Massachusetts General Hospital, Harvard Medical School, Boston.; Division of Neuro-Oncology, University of Rochester School of Medicine, Rochester, New York., Klein RH; Broad Institute of MIT and Harvard, Boston, Massachusetts.; Division of Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts., Shaw B; Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, Massachusetts., Kim A; Division of Neuro-Oncology, Massachusetts General Hospital, Harvard Medical School, Boston.; Cancer Center, Massachusetts General Hospital, Boston., Subramanian M; Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, Massachusetts.; Alnylam Pharmaceuticals, Cambridge, Massachusetts., Mora JL; Cancer Center, Massachusetts General Hospital, Boston.; Broad Institute of MIT and Harvard, Boston, Massachusetts.; Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, Massachusetts., Giobbie-Hurder A; Division of Biostatistics, Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts., Nagabhushan D; Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, Massachusetts., Jain A; Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, Massachusetts., Singh M; Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, Massachusetts., Kuter BM; Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, Massachusetts.; Boston University, Boston, Massachusetts., Nayyar N; Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, Massachusetts., Bertalan MS; Cancer Center, Massachusetts General Hospital, Boston.; Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, Massachusetts.; Geisel School of Medicine, Dartmouth College, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire., Stocking JH; Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, Massachusetts.; University of Colorado School of Medicine, Aurora., Markson SC; Broad Institute of MIT and Harvard, Boston, Massachusetts.; Division of Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts., Lastrapes M; Broad Institute of MIT and Harvard, Boston, Massachusetts.; Division of Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.; University of Texas Health Science Center at Houston, Houston., Alvarez-Breckenridge C; Broad Institute of MIT and Harvard, Boston, Massachusetts.; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston.; The University of Texas MD Anderson Cancer Center, Houston., Cahill DP; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston., Gydush G; Broad Institute of MIT and Harvard, Boston, Massachusetts., Rhoades J; Broad Institute of MIT and Harvard, Boston, Massachusetts., Rotem D; Broad Institute of MIT and Harvard, Boston, Massachusetts.; Tessera Therapeutics, Cambridge, Massachusetts., Adalsteinsson VA; Broad Institute of MIT and Harvard, Boston, Massachusetts., Mahar M; Division of Neuro-Oncology, Massachusetts General Hospital, Harvard Medical School, Boston.; Cancer Center, Massachusetts General Hospital, Boston., Kaplan A; Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, Massachusetts.; University of Massachusetts, Boston, Massachusetts., Oh K; Cancer Center, Massachusetts General Hospital, Boston., Sullivan RJ; Cancer Center, Massachusetts General Hospital, Boston.; Broad Institute of MIT and Harvard, Boston, Massachusetts.; Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, Massachusetts., Gerstner E; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston.; Department of Radiology, Harvard Medical School, Harvard University, Boston, Massachusetts., Carter SL; Broad Institute of MIT and Harvard, Boston, Massachusetts.; Division of Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Brastianos PK; Cancer Center, Massachusetts General Hospital, Boston.; Broad Institute of MIT and Harvard, Boston, Massachusetts.; Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, Massachusetts.
المصدر: JAMA network open [JAMA Netw Open] 2021 Aug 02; Vol. 4 (8), pp. e2120040. Date of Electronic Publication: 2021 Aug 02.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Medical Association Country of Publication: United States NLM ID: 101729235 Publication Model: Electronic Cited Medium: Internet ISSN: 2574-3805 (Electronic) Linking ISSN: 25743805 NLM ISO Abbreviation: JAMA Netw Open Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Chicago, IL : American Medical Association, [2018]-
مواضيع طبية MeSH: Diagnostic Tests, Routine*, Circulating Tumor DNA/*cerebrospinal fluid , Meningeal Neoplasms/*cerebrospinal fluid , Meningeal Neoplasms/*diagnosis , Meningeal Neoplasms/*genetics , Neoplasms/*complications , Neoplasms/*genetics, Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Neoplasms, Second Primary/cerebrospinal fluid ; Neoplasms, Second Primary/diagnosis ; Neoplasms, Second Primary/genetics ; Predictive Value of Tests
مستخلص: Importance: Leptomeningeal disease (LMD) is a devastating complication of cancer that is frequently underdiagnosed owing to the low sensitivity of cerebrospinal fluid (CSF) cytologic assessment, the current benchmark diagnostic method. Improving diagnostic sensitivity may lead to improved treatment decisions.
Objective: To assess whether cell-free DNA (cfDNA) analysis of CSF may be used to diagnose LMD more accurately than cytologic analysis.
Design, Setting, and Participants: This diagnostic study conducted in a neuro-oncology clinic at 2 large, tertiary medical centers assessed the use of genomic sequencing of CSF samples obtained from 30 patients with suspected or confirmed LMD from 2015 through 2018 to identify tumor-derived cfDNA. From the same CSF samples, cytologic analyses were conducted, and the results of the 2 tests were compared. This study consisted of 2 patient populations: 22 patients with cytologically confirmed LMD without parenchymal tumors abutting their CSF and 8 patients with parenchymal brain metastases with no evidence of LMD. Patients were considered positive for the presence of LMD if previous CSF cytologic analysis was positive for malignant cells. The analysis was conducted from 2015 to 2018.
Main Outcomes and Measures: The primary outcome was the diagnostic accuracy of cfDNA analysis, defined as the number of tests that resulted in correct diagnoses out of the total number of tests assayed. Hypotheses were formed before data collection.
Results: In total, 30 patients (23 women [77%]; median age, 51 years [range, 28-81 years]), primarily presenting with metastatic solid malignant neoplasms, participated in this study. For 48 follow-up samples from patients previously diagnosed via cytologic analysis as having LMD with no parenchymal tumor abutting CSF, cfDNA findings were accurate in the assessment of LMD in 45 samples (94%; 95% CI, 83%-99%), whereas cytologic analysis was accurate in 36 samples (75%; 95% CI, 60%-86%), a significant difference (P = .02). Of 43 LMD-positive samples, CSF cfDNA analysis was sensitive to LMD in 40 samples (93%; 95% CI, 81%-99%), and cytologic analysis was sensitive to LMD in 31 samples (72%; 95% CI, 56%-85%), a significant difference (P = .02). For 3 patients with parenchymal brain metastases abutting the CSF and no suspicion of LMD, cytologic findings were negative for LMD in all 3 patients, whereas cfDNA findings were positive in all 3 patients.
Conclusions and Relevance: This diagnostic study found improved sensitivity and accuracy of cfDNA CSF testing vs cytologic assessment for diagnosing LMD with the exception of parenchymal tumors abutting CSF, suggesting improved ability to diagnosis LMD. Consideration of incorporating CSF cfDNA analysis into clinical care is warranted.
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المشرفين على المادة: 0 (Circulating Tumor DNA)
تواريخ الأحداث: Date Created: 20210809 Date Completed: 20220110 Latest Revision: 20240403
رمز التحديث: 20240403
مُعرف محوري في PubMed: PMC8353541
DOI: 10.1001/jamanetworkopen.2021.20040
PMID: 34369989
قاعدة البيانات: MEDLINE
الوصف
تدمد:2574-3805
DOI:10.1001/jamanetworkopen.2021.20040