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. |
|---|---|
| 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).) |
| References: | Eur J Cancer. 2017 Jul;79:158-165. (PMID: 28501762) Mol Oncol. 2022 Nov;16(21):3828-3854. (PMID: 36214609) Cancers (Basel). 2021 Feb 05;13(4):. (PMID: 33562726) Pancreas. 2010 Aug;39(6):799-800. (PMID: 20664477) Sci Rep. 2022 Jan 25;12(1):1317. (PMID: 35079034) Clin Cancer Res. 2017 Aug 15;23(16):4625-4632. (PMID: 28455360) Endocr Relat Cancer. 2015 Aug;22(4):657-64. (PMID: 26113608) Hum Pathol. 2015 Dec;46(12):1890-900. (PMID: 26434631) PLoS One. 2017 Nov 7;12(11):e0187667. (PMID: 29112960) Mod Pathol. 2017 Apr;30(4):587-598. (PMID: 28059098) Eur J Cancer. 2021 Jul;152:100-115. (PMID: 34090142) Nucleic Acids Res. 2019 Jan 8;47(D1):D941-D947. (PMID: 30371878) J Neuroendocrinol. 2023 Apr;35(4):e13256. (PMID: 37017614) JAMA Oncol. 2022 Oct 1;8(10):1447-1455. (PMID: 35980649) Endocrinol Metab Clin North Am. 2018 Sep;47(3):683-698. (PMID: 30098724) Mol Cancer Ther. 2016 Aug;15(8):1781-91. (PMID: 27413114) Ann Oncol. 2013 Jan;24(1):152-60. (PMID: 22967994) Ann Oncol. 2016 Apr;27(4):642-7. (PMID: 26802149) Genome Med. 2020 Jan 14;12(1):8. (PMID: 31937368) Medicine (Baltimore). 2021 Feb 5;100(5):e24194. (PMID: 33592864) Cancer Discov. 2021 Jan;11(1):80-91. (PMID: 32988960) Cancers (Basel). 2021 Aug 23;13(16):. (PMID: 34439386) Neuroendocrinology. 2021;111(9):883-894. (PMID: 33002892) Nat Commun. 2021 Jul 29;12(1):4612. (PMID: 34326338) Neuroendocrinology. 2020;110(7-8):616-629. (PMID: 31557757) Sci Rep. 2019 Feb 27;9(1):2858. (PMID: 30814645) Endocr Relat Cancer. 2021 Nov 11;29(1):1-14. (PMID: 34647903) Int J Cancer. 2019 Mar 15;144(6):1379-1390. (PMID: 30144031) Front Oncol. 2018 Feb 05;8:16. (PMID: 29459887) J Neuroendocrinol. 2021 May;33(5):e12971. (PMID: 33870570) Front Oncol. 2021 Oct 11;11:662055. (PMID: 34707985) J Natl Compr Canc Netw. 2021 Jul 28;19(7):839-868. (PMID: 34340212) Endocr Relat Cancer. 2023 Jul 11;30(8):. (PMID: 37184955) Clin Cancer Res. 2001 Oct;7(10):2984-97. (PMID: 11595686) Nat Med. 2015 Jul;21(7):751-9. (PMID: 26099045) Endocr Relat Cancer. 2022 Aug 17;29(10):569-580. (PMID: 35920609) Ther Adv Med Oncol. 2023 Mar 1;15:17588359231156870. (PMID: 36872945) Clin Cancer Res. 2020 Feb 15;26(4):902-909. (PMID: 31672771) J Natl Cancer Inst. 2017 Jan 27;109(5):. (PMID: 28130474) Am J Surg Pathol. 2012 Feb;36(2):173-84. (PMID: 22251937) Endocr Relat Cancer. 2021 Jun 23;28(8):549-561. (PMID: 34061764) Clin Cancer Res. 2022 May 13;28(10):1999-2019. (PMID: 35091446) Cancer Commun (Lond). 2022 Dec;42(12):1367-1386. (PMID: 36264285) J Neuroendocrinol. 2023 Mar;35(3):e13249. (PMID: 36924180) Nat Rev Cancer. 2001 Dec;1(3):233-40. (PMID: 11902578) Cancer Discov. 2016 Jun;6(6):594-600. (PMID: 27048246) |
| 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 |
καταχωρήστε σχόλιο πρώτοι!