Academic Journal
Treatment outcome according to genetic tumour alterations and clinical characteristics in digestive high-grade neuroendocrine neoplasms.
| Τίτλος: | Treatment outcome according to genetic tumour alterations and clinical characteristics in digestive high-grade neuroendocrine neoplasms. |
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| Συγγραφείς: | Elvebakken H; Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway. Hege.Elvebakken@helse-mr.no.; Department of Oncology, Ålesund Hospital, Møre and Romsdal Hospital Trust, Ålesund, Norway. Hege.Elvebakken@helse-mr.no., Venizelos A; K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway., Perren A; Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland., Couvelard A; Department of Pathology, Université Paris Cité and AP-HP, Bichat Hospital, Paris, France., Lothe IMB; Department of Pathology, Oslo University Hospital, Oslo, Norway., Hjortland GO; Department of Oncology, Oslo University Hospital, Oslo, Norway., Myklebust TÅ; Department of Research and Innovation, Møre and Romsdal Hospital Trust, Ålesund, Norway.; Department of Registration, Cancer Registry Norway, Oslo, Norway., Svensson J; Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden., Garresori H; Department of Oncology, Stavanger University Hospital, Stavanger, Norway., Kersten C; Department of Research, Hospital of Southern Norway, Kristiansand, Norway., Hofsli E; Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.; Department of Oncology, St.Olavs Hospital, Trondheim, Norway., Detlefsen S; Department of Pathology, Odense University Hospital, Odense, Denmark.; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark., Vestermark LW; Danish Medicines Agency, Copenhagen, Denmark., Knappskog S; K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Oncology, Haukeland University Hospital, Bergen, Norway., Sorbye H; Department of Oncology, Haukeland University Hospital, Bergen, Norway.; Department of Clinical Science, University of Bergen, Bergen, Norway. |
| Πηγή: | British journal of cancer [Br J Cancer] 2024 Sep; Vol. 131 (4), pp. 676-684. Date of Electronic Publication: 2024 Jun 22. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-1827 (Electronic) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK Original Publication: London, Lewis. |
| Ιατρικοί όροι (MeSH): | Neuroendocrine Tumors*/genetics , Neuroendocrine Tumors*/pathology , Neuroendocrine Tumors*/drug therapy , Mutation*, Etoposide/administration & dosage ; Carcinoma, Neuroendocrine/genetics ; Carcinoma, Neuroendocrine/pathology ; Carcinoma, Neuroendocrine/drug therapy ; Carboplatin/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Tumor Suppressor Protein p53/genetics ; Humans ; Male ; Female ; Middle Aged ; Aged ; Adult ; Treatment Outcome ; Prognosis ; Aged, 80 and over ; DNA Copy Number Variations ; Prospective Studies ; Neoplasm Grading ; Young Adult |
| Περίληψη: | Background: Chemotherapy has limited efficacy in advanced digestive high-grade neuroendocrine neoplasms (HG-NEN) and prognosis is dismal. Predictive markers for palliative chemotherapy are lacking, and prognostic markers are limited. Methods: Digestive HG-NEN patients (n = 229) were prospectively included 2013-2017. Pathological re-assessment revealed 188 neuroendocrine carcinomas (NEC) and 41 neuroendocrine tumours (NET G3). Tumour-DNA was sequenced across 360 cancer-related genes, assessing mutations (mut) and copy number alterations. We linked sequencing results to clinical information and explored potential markers for first-line chemotherapy efficacy and survival. Results: In NEC given cis/carboplatin and etoposide (PE), TP53mut predicted inferior response rate in multivariate analyses (p = 0.009) and no BRAFmut NEC showed response. In overall assessment of PE-treated NEC, no genetic alterations were prognostic for OS. For small-cell NEC, TP53mut were associated with longer OS (p = 0.011) and RB1 deletions predicted lack of immediate-progression (p = 0.003). In non-small cell NEC, APC mut were associated with immediate-progression and shorter PFS (p = 0.008/p = 0.004). For NET G3, ATRXmut, ARID1A- and ERS1 deletions were associated with shorter PFS. Conclusion: Correlations between genetic alterations and response/immediate-progression to PE were frequent in NEC but affected PFS or OS only when subdividing for cell-type. The classification of digestive NEC into large- and small-cell seems therefore molecularly and clinically relevant. (© 2024. The Author(s).) |
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| Substance Nomenclature: | 6PLQ3CP4P3 (Etoposide) BG3F62OND5 (Carboplatin) 0 (Tumor Suppressor Protein p53) |
| Entry Date(s): | Date Created: 20240622 Date Completed: 20240819 Latest Revision: 20240822 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11333587 |
| DOI: | 10.1038/s41416-024-02773-w |
| PMID: | 38909137 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1532-1827 |
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| DOI: | 10.1038/s41416-024-02773-w |