In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 3563-3563
Abstract:
3563 Background: Prognosis of patients (pts) with metastatic colorectal cancer (mCRC) harboring microsatellite instability (MSI) is poorly characterized. We aimed to assess the clinical relevance of distinguishing sporadic (SP) from Lynch syndrome (LS)-related mismatch repair deficiency (dMMR). Methods: Pts with diagnostic of dMMR and/or MSI mCRC between 1998 and 2016 were retrospectively identified in 6 French hospitals. Tumor samples were systematically collected and screened for RAS/RAF mutations and MLH1 promotor methylation. dMMR and MSI statuses were confirmed using immunohistochemistry and Pentaplex© PCR assay. Sporadic cases were molecularly defined as those displaying MLH1 loss of expression with BRAFV600E mutation and/or MLH1 hypermethylation. Clinical data (demographic data, metastatic sites, therapeutic strategies) were recorded. Results: 129 pts, of which 48 SP and 81 LS, were included. Compared with LS, SP were associated with female (P 〈 .001), older age at diagnostic (P 〈 .001), proximal colon (P = 0.002), and less liver metastasis (25% vs 47%, P = .02). For initially localized CRC, median disease free survivals (DFS) were 9.1 months (m) for SP (n = 22) and 12.3 m for LS (n = 47) (hazard ratio (HR) = 0.5, 95%CI 0.28-0.90, P = .02). Median overall survivals (OS) from stage IV diagnosis were 43.9 m in the overall population, 23 m for SP and not reached for LS (HR = 0.23, 95%CI 0.10-0.52, P 〈 .001). BRAF mutation was harbored by 29 SP tumors (60%) and did not impact OS among SP pts (P = .52). Metastatic disease was less frequently resectable for SP than LS (21% vs 56%, P 〈 .001). Median DFS for pts with resected metastatic disease (n = 55) were respectively 6.7 and 10.5 m (HR = 0.28, 95%CI 0.10-0.73, P = .01). At the data cut-off date, 16 pts (15 LS and 1 SP) were still in complete remission. Median progression free survivals with first-line chemotherapy for pts with unresectable metastasis (n = 61) were 3.9 m for SP and 5.0 m for LS (P = .71). Conclusions: This retrospective study suggests a worse prognosis of pts with SP MSI mCRC compared to these with LS-related mCRC.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.15_suppl.3563
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
