Clinical characteristics and molecular aspects of low-grade serous ovarian and peritoneal cancer: a multicenter, observational, retrospective analysis of MITO Group (MITO 22).
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
09
02
2022
accepted:
13
06
2022
revised:
07
06
2022
pubmed:
23
7
2022
medline:
14
10
2022
entrez:
22
7
2022
Statut:
ppublish
Résumé
Low-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published. A retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed. Additionally, the tumor molecular profile of 56 patients was evaluated using the Next Generation Sequencing (NGS) FoundationOne CDX (Foundation Medicine®). A total of 128 patients with complete clinical data and pathologically confirmed diagnosis of LGSC were identified. ORR to first and subsequent therapies were 23.7% and 33.7%, respectively. PFS was 43.9 months (95% CI:32.4-53.1) and OS was 105.4 months (95% CI: 82.7-not reached). The most common gene alterations were: KRAS (n = 12, 21%), CDKN2A/B (n = 11, 20%), NRAS (n = 8, 14%), FANCA (n = 8, 14%), NF1 (n = 7, 13%) and BRAF (n = 6, 11%). Unexpectedly, pathogenetic BRCA1 (n = 2, 4%), BRCA2 (n = 1, 2%) and PALB2 (n = 1, 2%) mutations were found. MITO 22 suggests that LGSC is an heterogenous disease for both its clinical behavior in response to standard therapies and its molecular alterations. Future prospective studies should test treatments according to biological and molecular tumor's characteristics. This study is registered under NCT02408536 on ClinicalTrials.gov .
Sections du résumé
BACKGROUND
Low-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published.
METHODS
A retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed. Additionally, the tumor molecular profile of 56 patients was evaluated using the Next Generation Sequencing (NGS) FoundationOne CDX (Foundation Medicine®).
RESULTS
A total of 128 patients with complete clinical data and pathologically confirmed diagnosis of LGSC were identified. ORR to first and subsequent therapies were 23.7% and 33.7%, respectively. PFS was 43.9 months (95% CI:32.4-53.1) and OS was 105.4 months (95% CI: 82.7-not reached). The most common gene alterations were: KRAS (n = 12, 21%), CDKN2A/B (n = 11, 20%), NRAS (n = 8, 14%), FANCA (n = 8, 14%), NF1 (n = 7, 13%) and BRAF (n = 6, 11%). Unexpectedly, pathogenetic BRCA1 (n = 2, 4%), BRCA2 (n = 1, 2%) and PALB2 (n = 1, 2%) mutations were found.
CONCLUSIONS
MITO 22 suggests that LGSC is an heterogenous disease for both its clinical behavior in response to standard therapies and its molecular alterations. Future prospective studies should test treatments according to biological and molecular tumor's characteristics.
CLINICAL TRIAL REGISTRATION
This study is registered under NCT02408536 on ClinicalTrials.gov .
Identifiants
pubmed: 35869143
doi: 10.1038/s41416-022-01897-1
pii: 10.1038/s41416-022-01897-1
pmc: PMC9553882
doi:
Substances chimiques
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Banques de données
ClinicalTrials.gov
['NCT02408536']
Types de publication
Journal Article
Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1479-1486Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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