Clinical utility of tumor genomic profiling in patients with high plasma circulating tumor DNA burden or metabolically active tumors
Abstract Background This retrospective study was undertaken to determine if the plasma circulating tumor DNA (ctDNA) level and tumor biological features in patients with advanced solid tumors affected the detection of genomic alterations (GAs) by a plasma ctDNA assay. Method Cell-free DNA (cfDNA) ex...
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| Format: | Article |
| Language: | English |
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BMC
2018-11-01
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| Series: | Journal of Hematology & Oncology |
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| Online Access: | http://link.springer.com/article/10.1186/s13045-018-0671-8 |
| _version_ | 1828895855009071104 |
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| author | Cathy Zhou Zilong Yuan Weijie Ma Lihong Qi Angelique Mahavongtrakul Ying Li Hong Li Jay Gong Reggie R. Fan Jin Li Michael Molmen Travis A. Clark Dean Pavlick Garrett M. Frampton Brady Forcier Elizabeth H. Moore David K. Shelton Matthew Cooke Siraj M. Ali Vincent A. Miller Jeffrey P. Gregg Philip J. Stephens Tianhong Li |
| author_facet | Cathy Zhou Zilong Yuan Weijie Ma Lihong Qi Angelique Mahavongtrakul Ying Li Hong Li Jay Gong Reggie R. Fan Jin Li Michael Molmen Travis A. Clark Dean Pavlick Garrett M. Frampton Brady Forcier Elizabeth H. Moore David K. Shelton Matthew Cooke Siraj M. Ali Vincent A. Miller Jeffrey P. Gregg Philip J. Stephens Tianhong Li |
| author_sort | Cathy Zhou |
| collection | DOAJ |
| description | Abstract Background This retrospective study was undertaken to determine if the plasma circulating tumor DNA (ctDNA) level and tumor biological features in patients with advanced solid tumors affected the detection of genomic alterations (GAs) by a plasma ctDNA assay. Method Cell-free DNA (cfDNA) extracted from frozen plasma (N = 35) or fresh whole blood (N = 90) samples were subjected to a 62-gene hybrid capture-based next-generation sequencing assay FoundationACT. Concordance was analyzed for 51 matched FoundationACT and FoundationOne (tissue) cases. The maximum somatic allele frequency (MSAF) was used to estimate the amount of tumor fraction of cfDNA in each sample. The detection of GAs was correlated with the amount of cfDNA, MSAF, total tumor anatomic burden (dimensional sum), and total tumor metabolic burden (SUVmax sum) of the largest ten tumor lesions on PET/CT scans. Results FoundationACT detected GAs in 69 of 81 (85%) cases with MSAF > 0. Forty-two of 51 (82%) cases had ≥ 1 concordance GAs matched with FoundationOne, and 22 (52%) matched to the National Comprehensive Cancer Network (NCCN)-recommended molecular targets. FoundationACT also detected 8 unique molecular targets, which changed the therapy in 7 (88%) patients who did not have tumor rebiopsy or sufficient tumor DNA for genomic profiling assay. In all samples (N = 81), GAs were detected in plasma cfDNA from cancer patients with high MSAF quantity (P = 0.0006) or high tumor metabolic burden (P = 0.0006) regardless of cfDNA quantity (P = 0.2362). Conclusion This study supports the utility of using plasma-based genomic assays in cancer patients with high plasma MSAF level or high tumor metabolic burden. |
| first_indexed | 2024-12-13T14:33:29Z |
| format | Article |
| id | doaj.art-f7a6b3e50e784343a7af265214bc7dc3 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-12-13T14:33:29Z |
| publishDate | 2018-11-01 |
| publisher | BMC |
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| series | Journal of Hematology & Oncology |
| spelling | doaj.art-f7a6b3e50e784343a7af265214bc7dc32022-12-21T23:41:47ZengBMCJournal of Hematology & Oncology1756-87222018-11-0111111310.1186/s13045-018-0671-8Clinical utility of tumor genomic profiling in patients with high plasma circulating tumor DNA burden or metabolically active tumorsCathy Zhou0Zilong Yuan1Weijie Ma2Lihong Qi3Angelique Mahavongtrakul4Ying Li5Hong Li6Jay Gong7Reggie R. Fan8Jin Li9Michael Molmen10Travis A. Clark11Dean Pavlick12Garrett M. Frampton13Brady Forcier14Elizabeth H. Moore15David K. Shelton16Matthew Cooke17Siraj M. Ali18Vincent A. Miller19Jeffrey P. Gregg20Philip J. Stephens21Tianhong Li22Department of Radiology, University of California Davis School of MedicineUniversity of California Davis Comprehensive Cancer CenterDivision of Hematology and Oncology, Department of Internal Medicine University of California Davis School of MedicineUniversity of California Davis Comprehensive Cancer CenterDivision of Hematology and Oncology, Department of Internal Medicine University of California Davis School of MedicineDivision of Hematology and Oncology, Department of Internal Medicine University of California Davis School of MedicineDivision of Hematology and Oncology, Department of Internal Medicine University of California Davis School of MedicineDivision of Hematology and Oncology, Department of Internal Medicine University of California Davis School of MedicineDivision of Hematology and Oncology, Department of Internal Medicine University of California Davis School of MedicineDepartment of Public Health Sciences, University of CaliforniaFoundation Medicine, Inc.Foundation Medicine, Inc.Foundation Medicine, Inc.Foundation Medicine, Inc.Foundation Medicine, Inc.Department of Radiology, University of California Davis School of MedicineDepartment of Radiology, University of California Davis School of MedicineFoundation Medicine, Inc.Foundation Medicine, Inc.Foundation Medicine, Inc.University of California Davis Comprehensive Cancer CenterFoundation Medicine, Inc.University of California Davis Comprehensive Cancer CenterAbstract Background This retrospective study was undertaken to determine if the plasma circulating tumor DNA (ctDNA) level and tumor biological features in patients with advanced solid tumors affected the detection of genomic alterations (GAs) by a plasma ctDNA assay. Method Cell-free DNA (cfDNA) extracted from frozen plasma (N = 35) or fresh whole blood (N = 90) samples were subjected to a 62-gene hybrid capture-based next-generation sequencing assay FoundationACT. Concordance was analyzed for 51 matched FoundationACT and FoundationOne (tissue) cases. The maximum somatic allele frequency (MSAF) was used to estimate the amount of tumor fraction of cfDNA in each sample. The detection of GAs was correlated with the amount of cfDNA, MSAF, total tumor anatomic burden (dimensional sum), and total tumor metabolic burden (SUVmax sum) of the largest ten tumor lesions on PET/CT scans. Results FoundationACT detected GAs in 69 of 81 (85%) cases with MSAF > 0. Forty-two of 51 (82%) cases had ≥ 1 concordance GAs matched with FoundationOne, and 22 (52%) matched to the National Comprehensive Cancer Network (NCCN)-recommended molecular targets. FoundationACT also detected 8 unique molecular targets, which changed the therapy in 7 (88%) patients who did not have tumor rebiopsy or sufficient tumor DNA for genomic profiling assay. In all samples (N = 81), GAs were detected in plasma cfDNA from cancer patients with high MSAF quantity (P = 0.0006) or high tumor metabolic burden (P = 0.0006) regardless of cfDNA quantity (P = 0.2362). Conclusion This study supports the utility of using plasma-based genomic assays in cancer patients with high plasma MSAF level or high tumor metabolic burden.http://link.springer.com/article/10.1186/s13045-018-0671-8Next-generation sequencing (NGS)PlasmaCell-free DNA (cfDNA)Circulating tumor DNA (ctDNA)Genomic alterations (GAs)Maximum somatic allele frequency (MSAF) |
| spellingShingle | Cathy Zhou Zilong Yuan Weijie Ma Lihong Qi Angelique Mahavongtrakul Ying Li Hong Li Jay Gong Reggie R. Fan Jin Li Michael Molmen Travis A. Clark Dean Pavlick Garrett M. Frampton Brady Forcier Elizabeth H. Moore David K. Shelton Matthew Cooke Siraj M. Ali Vincent A. Miller Jeffrey P. Gregg Philip J. Stephens Tianhong Li Clinical utility of tumor genomic profiling in patients with high plasma circulating tumor DNA burden or metabolically active tumors Journal of Hematology & Oncology Next-generation sequencing (NGS) Plasma Cell-free DNA (cfDNA) Circulating tumor DNA (ctDNA) Genomic alterations (GAs) Maximum somatic allele frequency (MSAF) |
| title | Clinical utility of tumor genomic profiling in patients with high plasma circulating tumor DNA burden or metabolically active tumors |
| title_full | Clinical utility of tumor genomic profiling in patients with high plasma circulating tumor DNA burden or metabolically active tumors |
| title_fullStr | Clinical utility of tumor genomic profiling in patients with high plasma circulating tumor DNA burden or metabolically active tumors |
| title_full_unstemmed | Clinical utility of tumor genomic profiling in patients with high plasma circulating tumor DNA burden or metabolically active tumors |
| title_short | Clinical utility of tumor genomic profiling in patients with high plasma circulating tumor DNA burden or metabolically active tumors |
| title_sort | clinical utility of tumor genomic profiling in patients with high plasma circulating tumor dna burden or metabolically active tumors |
| topic | Next-generation sequencing (NGS) Plasma Cell-free DNA (cfDNA) Circulating tumor DNA (ctDNA) Genomic alterations (GAs) Maximum somatic allele frequency (MSAF) |
| url | http://link.springer.com/article/10.1186/s13045-018-0671-8 |
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