Elvebakken, Hege; Venizelos, Andreas; Perren, Aurel; Couvelard, Anne; Lothe, Inger Marie B; Hjortland, Geir O; Myklebust, Tor Å; Svensson, Johanna; Garresori, Herish; Kersten, Christian; Hofsli, Eva; Detlefsen, Sönke; Vestermark, Lene W; Knappskog, Stian; Sorbye, Halfdan (2024). Treatment outcome according to genetic tumour alterations and clinical characteristics in digestive high-grade neuroendocrine neoplasms. British journal of cancer, 131(4), pp. 676-684. Springer Nature 10.1038/s41416-024-02773-w
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology 04 Faculty of Medicine > Service Sector > Institute of Pathology |
UniBE Contributor: |
Perren, Aurel |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
1532-1827 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
25 Jun 2024 11:18 |
Last Modified: |
21 Aug 2024 00:14 |
Publisher DOI: |
10.1038/s41416-024-02773-w |
PubMed ID: |
38909137 |
BORIS DOI: |
10.48350/198045 |
URI: |
https://boris.unibe.ch/id/eprint/198045 |
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