Proof-of-Concept Pilot Study on Comprehensive Spatiotemporal Intra-Patient Heterogeneity for Colorectal Cancer With Liver Metastasis
IntroductionThe mechanisms underlying high drug resistance and relapse rates after multi-modal treatment in patients with colorectal cancer (CRC) and liver metastasis (LM) remain poorly understood.ObjectiveWe evaluate the potential translational implications of intra-patient heterogeneity (IPH) comp...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.855463/full |
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| author | Ioannis D. Kyrochristos Ioannis D. Kyrochristos Georgios K. Glantzounis Anna Goussia Alexia Eliades Achilleas Achilleos Kyriakos Tsangaras Irene Hadjidemetriou Marilena Elpidorou Marios Ioannides George Koumbaris Michail Mitsis Michail Mitsis Philippos C. Patsalis Philippos C. Patsalis Dimitrios Roukos Dimitrios Roukos Dimitrios Roukos |
| author_facet | Ioannis D. Kyrochristos Ioannis D. Kyrochristos Georgios K. Glantzounis Anna Goussia Alexia Eliades Achilleas Achilleos Kyriakos Tsangaras Irene Hadjidemetriou Marilena Elpidorou Marios Ioannides George Koumbaris Michail Mitsis Michail Mitsis Philippos C. Patsalis Philippos C. Patsalis Dimitrios Roukos Dimitrios Roukos Dimitrios Roukos |
| author_sort | Ioannis D. Kyrochristos |
| collection | DOAJ |
| description | IntroductionThe mechanisms underlying high drug resistance and relapse rates after multi-modal treatment in patients with colorectal cancer (CRC) and liver metastasis (LM) remain poorly understood.ObjectiveWe evaluate the potential translational implications of intra-patient heterogeneity (IPH) comprising primary and matched metastatic intratumor heterogeneity (ITH) coupled with circulating tumor DNA (ctDNA) variability.MethodsA total of 122 multi-regional tumor and perioperative liquid biopsies from 18 patients were analyzed via targeted next-generation sequencing (NGS).ResultsThe proportion of patients with ITH were 53% and 56% in primary CRC and LM respectively, while 35% of patients harbored de novo mutations in LM indicating spatiotemporal tumor evolution and the necessity of multiregional analysis. Among the 56% of patients with alterations in liquid biopsies, de novo mutations in cfDNA were identified in 25% of patients, which were undetectable in both CRC and LM. All 17 patients with driver alterations harbored mutations targetable by molecularly targeted drugs, either approved or currently under evaluation.ConclusionOur proof-of-concept prospective study provides initial evidence on potential clinical superiority of IPH and warrants the conduction of precision oncology trials to evaluate the clinical utility of I PH-driven matched therapy. |
| first_indexed | 2024-04-13T10:23:57Z |
| format | Article |
| id | doaj.art-6c2e9e360b214662b6d27ac42404d714 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T10:23:57Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-6c2e9e360b214662b6d27ac42404d7142022-12-22T02:50:22ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-03-011210.3389/fonc.2022.855463855463Proof-of-Concept Pilot Study on Comprehensive Spatiotemporal Intra-Patient Heterogeneity for Colorectal Cancer With Liver MetastasisIoannis D. Kyrochristos0Ioannis D. Kyrochristos1Georgios K. Glantzounis2Anna Goussia3Alexia Eliades4Achilleas Achilleos5Kyriakos Tsangaras6Irene Hadjidemetriou7Marilena Elpidorou8Marios Ioannides9George Koumbaris10Michail Mitsis11Michail Mitsis12Philippos C. Patsalis13Philippos C. Patsalis14Dimitrios Roukos15Dimitrios Roukos16Dimitrios Roukos17Centre for Biosystems and Genome Network Medicine, Ioannina University, Ioannina, GreeceDepartment of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, GermanyDepartment of Surgery, Ioannina University Hospital, Ioannina, GreeceDepartment of Pathology, Ioannina University Hospital, Ioannina, GreeceNIPD Genetics, Nicosia, CyprusNIPD Genetics, Nicosia, CyprusNIPD Genetics, Nicosia, CyprusNIPD Genetics, Nicosia, CyprusNIPD Genetics, Nicosia, CyprusNIPD Genetics, Nicosia, CyprusNIPD Genetics, Nicosia, CyprusDepartment of Surgery, Ioannina University Hospital, Ioannina, GreeceCancer Biobank Centre, Ioannina University, Ioannina, GreeceNIPD Genetics, Nicosia, CyprusDepartment of Human Genetics, School of Medicine, University of Nicosia Medical School, Nicosia, CyprusCentre for Biosystems and Genome Network Medicine, Ioannina University, Ioannina, GreeceDepartment of Surgery, Ioannina University Hospital, Ioannina, GreeceDepartment of Systems Biology, Biomedical Research Foundation of the Academy of Athens, Athens, GreeceIntroductionThe mechanisms underlying high drug resistance and relapse rates after multi-modal treatment in patients with colorectal cancer (CRC) and liver metastasis (LM) remain poorly understood.ObjectiveWe evaluate the potential translational implications of intra-patient heterogeneity (IPH) comprising primary and matched metastatic intratumor heterogeneity (ITH) coupled with circulating tumor DNA (ctDNA) variability.MethodsA total of 122 multi-regional tumor and perioperative liquid biopsies from 18 patients were analyzed via targeted next-generation sequencing (NGS).ResultsThe proportion of patients with ITH were 53% and 56% in primary CRC and LM respectively, while 35% of patients harbored de novo mutations in LM indicating spatiotemporal tumor evolution and the necessity of multiregional analysis. Among the 56% of patients with alterations in liquid biopsies, de novo mutations in cfDNA were identified in 25% of patients, which were undetectable in both CRC and LM. All 17 patients with driver alterations harbored mutations targetable by molecularly targeted drugs, either approved or currently under evaluation.ConclusionOur proof-of-concept prospective study provides initial evidence on potential clinical superiority of IPH and warrants the conduction of precision oncology trials to evaluate the clinical utility of I PH-driven matched therapy.https://www.frontiersin.org/articles/10.3389/fonc.2022.855463/fullactionable mutationscirculating variabilitycomprehensive intra-patient heterogeneityintratumor heterogeneitynext-generation sequencingprecision cancer medicine |
| spellingShingle | Ioannis D. Kyrochristos Ioannis D. Kyrochristos Georgios K. Glantzounis Anna Goussia Alexia Eliades Achilleas Achilleos Kyriakos Tsangaras Irene Hadjidemetriou Marilena Elpidorou Marios Ioannides George Koumbaris Michail Mitsis Michail Mitsis Philippos C. Patsalis Philippos C. Patsalis Dimitrios Roukos Dimitrios Roukos Dimitrios Roukos Proof-of-Concept Pilot Study on Comprehensive Spatiotemporal Intra-Patient Heterogeneity for Colorectal Cancer With Liver Metastasis Frontiers in Oncology actionable mutations circulating variability comprehensive intra-patient heterogeneity intratumor heterogeneity next-generation sequencing precision cancer medicine |
| title | Proof-of-Concept Pilot Study on Comprehensive Spatiotemporal Intra-Patient Heterogeneity for Colorectal Cancer With Liver Metastasis |
| title_full | Proof-of-Concept Pilot Study on Comprehensive Spatiotemporal Intra-Patient Heterogeneity for Colorectal Cancer With Liver Metastasis |
| title_fullStr | Proof-of-Concept Pilot Study on Comprehensive Spatiotemporal Intra-Patient Heterogeneity for Colorectal Cancer With Liver Metastasis |
| title_full_unstemmed | Proof-of-Concept Pilot Study on Comprehensive Spatiotemporal Intra-Patient Heterogeneity for Colorectal Cancer With Liver Metastasis |
| title_short | Proof-of-Concept Pilot Study on Comprehensive Spatiotemporal Intra-Patient Heterogeneity for Colorectal Cancer With Liver Metastasis |
| title_sort | proof of concept pilot study on comprehensive spatiotemporal intra patient heterogeneity for colorectal cancer with liver metastasis |
| topic | actionable mutations circulating variability comprehensive intra-patient heterogeneity intratumor heterogeneity next-generation sequencing precision cancer medicine |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.855463/full |
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