Impact of KRAS and BRAF mutations on treatment efficacy and survival in high-grade gastroenteropancreatic neuroendocrine neoplasms.

Autor: Elvebakken H; Department of Oncology, Ålesund Hospital, Møre og Romsdal Hospital Trust, Ålesund, Norway.; Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway., Hjortland GO; Department of Oncology, Oslo University Hospital, Oslo, Norway., Garresori H; Department of Haematology and Oncology, Stavanger University Hospital, Stavanger, Norway., Andresen PA; Department of Pathology, Oslo University Hospital, Oslo, Norway., Janssen EAM; Department of Pathology, Stavanger University Hospital, Stavanger, Norway.; Department of Chemistry, Bioscience and Environmental Engineering, Stavanger University, Stavanger, Norway., Vintermyr OK; Department of Pathology, Haukeland University Hospital, Bergen, Norway., Lothe IMB; Department of Pathology, Oslo University Hospital, Oslo, Norway., Sorbye H; Department of Oncology, Haukeland University Hospital, Bergen, Norway.; Department of Clinical Science, University of Bergen, Bergen, Norway.
Jazyk: angličtina
Zdroj: Journal of neuroendocrinology [J Neuroendocrinol] 2023 Apr; Vol. 35 (4), pp. e13256. Date of Electronic Publication: 2023 Apr 05.
DOI: 10.1111/jne.13256
Abstrakt: High-grade gastroenteropancreatic neuroendocrine neoplasms (HG GEP-NEN) typically disseminate early. Treatment of metastatic disease has limited benefit and prognosis is generally discouraging. Data on the clinical impact of mutations in HG GEP-NEN are scarce. There is an unmet need for reliable biomarkers to predict treatment outcome and prognosis in metastatic HG GEP-NEN. Patients with metastatic HG GEP-NEN diagnosed at three centres were selected for KRAS-, BRAF mutation and microsatellite instability (MSI) analyses. Results were linked to treatment outcome and overall survival. After pathological re-evaluation, 83 patients met inclusion criteria: 77 (93%) GEP neuroendocrine carcinomas (NEC) and six (7%) GEP neuroendocrine tumours (NET) G3. NEC harboured higher frequency of mutations than NET G3. Colon NEC harboured a particular high frequency of BRAF mutations (63%). Immediate disease progression on first-line chemotherapy was significantly higher for NEC with BRAF mutation (73%) versus wild-type (27%) (p = .016) and for colonic primary (65%) versus other NEC (28%) (p = .011). Colon NEC had a significant shorter PFS compared to other primary sites, a finding independent of BRAF status. Immediate disease progression was particularly frequent for BRAF mutated colon NEC (OR 10.2, p = .007). Surprisingly, BRAF mutation did not influence overall survival. KRAS mutation was associated with inferior overall survival for the whole NEC population (HR 2.02, p = .015), but not for those given first-line chemotherapy. All long-term survivors (>24 m) were double wild-type. Three NEC cases (4.8%) were MSI. Colon NEC with BRAF mutation predicted immediate disease progression on first-line chemotherapy, but did not affect PFS or OS. Benefit of first-line platinum/etoposide treatment seems limited for colon NEC, especially for BRAF mutated cases. KRAS mutations did not influence treatment efficacy nor survival for patients receiving first-line chemotherapy. Both frequency and clinical impact of KRAS/BRAF mutations in digestive NEC differ from prior results on digestive adenocarcinoma.
(© 2023 British Society for Neuroendocrinology.)
Databáze: MEDLINE
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