APC and PIK3CA Mutational Cooperativity Predicts Pathologic Response and Survival in Patients Undergoing Resection for Colorectal Liver Metastases.
Adenomatous Polyposis Coli Protein
/ genetics
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
/ therapeutic use
Class I Phosphatidylinositol 3-Kinases
/ genetics
Colorectal Neoplasms
/ genetics
Combined Modality Therapy
Female
Hepatectomy
Humans
Liver Neoplasms
/ genetics
Male
Middle Aged
Mutation
Prognosis
Retrospective Studies
Survival Rate
Young Adult
Journal
Annals of surgery
ISSN: 1528-1140
Titre abrégé: Ann Surg
Pays: United States
ID NLM: 0372354
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
pubmed:
6
4
2017
medline:
15
12
2020
entrez:
6
4
2017
Statut:
ppublish
Résumé
The aim of the study was to determine the prognostic impact of co-existence of APC and PIK3CA mutations in patients undergoing preoperative chemotherapy and resection for colorectal liver metastases (CLM). Co-occurring genetic events have been shown to drive carcinogenesis in multiple malignancies. We identified 396 patients with primary colorectal cancer and known somatic mutation status by next-generation sequencing who underwent hepatectomy for CLM (2005-2015). Survival after hepatectomy in patients with double mutation of APC and PIK3CA and others was analyzed. Predictors of pathologic response and survival were determined. The prognostic value of double mutation was evaluated with a separate cohort of 157 patients with CLM undergoing chemotherapy alone. Forty-five patients had double mutation of APC and PIK3CA; 351 did not. Recurrence-free survival (RFS) and overall survival (OS) after hepatectomy were worse in patients with double mutation (3-year RFS, 3.1% vs 20% [P < 0.001]; 3-year OS, 44% vs 84% [P < 0.001]). Independent predictors of major pathologic response were bevacizumab use (odds ratio [OR] 2.22; P = 0.001), tumor size <3 cm (OR 1.97; P = 0.004), wild-type RAS (OR 2.00; P = 0.003), and absence of double mutation (OR 2.91; P = 0.002). Independent predictors of worse OS were primary advanced T category (hazard ratio [HR] 2.12; P = 0.021), RAS mutation (HR 1.74; P = 0.015), and double mutation (HR 3.09; P < 0.001). In the different medical cohort, patients with double mutation had worse 3-year OS of 18%, compared with 35% without double mutation (P = 0.023). Double mutation of APC and PIK3CA predicts inferior response to preoperative chemotherapy and poor survival in patients with CLM.
Sections du résumé
OBJECTIVE
The aim of the study was to determine the prognostic impact of co-existence of APC and PIK3CA mutations in patients undergoing preoperative chemotherapy and resection for colorectal liver metastases (CLM).
BACKGROUND
Co-occurring genetic events have been shown to drive carcinogenesis in multiple malignancies.
METHODS
We identified 396 patients with primary colorectal cancer and known somatic mutation status by next-generation sequencing who underwent hepatectomy for CLM (2005-2015). Survival after hepatectomy in patients with double mutation of APC and PIK3CA and others was analyzed. Predictors of pathologic response and survival were determined. The prognostic value of double mutation was evaluated with a separate cohort of 157 patients with CLM undergoing chemotherapy alone.
RESULTS
Forty-five patients had double mutation of APC and PIK3CA; 351 did not. Recurrence-free survival (RFS) and overall survival (OS) after hepatectomy were worse in patients with double mutation (3-year RFS, 3.1% vs 20% [P < 0.001]; 3-year OS, 44% vs 84% [P < 0.001]). Independent predictors of major pathologic response were bevacizumab use (odds ratio [OR] 2.22; P = 0.001), tumor size <3 cm (OR 1.97; P = 0.004), wild-type RAS (OR 2.00; P = 0.003), and absence of double mutation (OR 2.91; P = 0.002). Independent predictors of worse OS were primary advanced T category (hazard ratio [HR] 2.12; P = 0.021), RAS mutation (HR 1.74; P = 0.015), and double mutation (HR 3.09; P < 0.001). In the different medical cohort, patients with double mutation had worse 3-year OS of 18%, compared with 35% without double mutation (P = 0.023).
CONCLUSIONS
Double mutation of APC and PIK3CA predicts inferior response to preoperative chemotherapy and poor survival in patients with CLM.
Identifiants
pubmed: 28379870
doi: 10.1097/SLA.0000000000002245
pii: 00000658-202012000-00032
doi:
Substances chimiques
APC protein, human
0
Adenomatous Polyposis Coli Protein
0
Antineoplastic Agents
0
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1080-1085Références
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