Survival of stage IV colorectal cancer: Interaction of cancer location, microsatellite instability and KRAS mutation

Background: This study sought to assess microsatellite and KRAS status, prevalence, and impact on outcome in stage IV colorectal cancer (CRC). Materials and Methods: The 2010 to 2016 US National Cancer Database was queried for adult patients with stage IV CRC. Prevalence of microsatellite status (microsatellite instability–high [MSI-H] or microsatellite stable [MSS]) and KRAS status (KRAS mutation or wild-type) of the primary CRC was assessed. Overall survival (OS) was evaluated using multivariable Cox proportional hazards models in patients with complete data on both microsatellite and KRAS status and information on follow-up. Results: Information on microsatellite and KRAS status was available for 10,844 and 25,712 patients, respectively, and OS data were available for 5,904 patients. The overall prevalence of MSI-H status and KRAS mutation was 3.1% and 42.4%, respectively. Prevalence of MSI-H ranged between 1.6% (rectosigmoid junction) and 5.2% (transverse colon), and between 34.7% (sigmoid colon) and 58.2% (cecum) for KRAS mutation. MSI-H rates were highest in East North Central US states (4.1%), and KRAS mutation rates were highest in West South Central US states (44.1%). Multivariable analyses revealed longer OS for patients with KRAS wild-type versus mutation status (hazard ratio [HR], 0.91; 95% CI, 0.85–0.97; P=.004), those with MSS versus MSI-H status (HR, 0.75; 95% CI, 0.62–0.9; P=.003), and those with left-sided versus right-sided CRC (multivariable HR, 0.65; 95% CI, 0.6–0.7; P<.001). The effect of KRAS mutation further varied with CRC site and microsatellite status (P=.002 for interaction). Conclusions: Depending on the primary site and US geography, stage IV CRC shows distinct mutational behavior. KRAS mutation, MSI-H, and primary CRC sidedness independently affect OS and interact with distinct prognostic profiles. Generically classifying adenocarcinomas at different sites as CRC might deprecate this diversity.

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Prognostic factors of survival in stage IV colorectal cancer with synchronous liver metastasis: Negative effect of the KRAS mutation

Molecular and Clinical Oncology ◽

10.3892/mco.2021.2255 ◽

2021 ◽

Vol 14 (5) ◽

Author(s):

Manuel Díez‑alonso ◽

Fernando Mendoza‑Moreno ◽

Laura Jiménez‑Alvarez ◽

Oscar Nuñez ◽

Alma Blazquez‑Martín ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factors ◽

Liver Metastasis ◽

Kras Mutation ◽

Stage Iv ◽

Synchronous Liver Metastasis ◽

Stage Iv Colorectal Cancer ◽

Negative Effect

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Correlation between KRAS mutation and 18F-FDG uptake in stage IV colorectal cancer

Abdominal Radiology ◽

10.1007/s00261-017-1054-2 ◽

2017 ◽

Vol 42 (6) ◽

pp. 1621-1626 ◽

Cited By ~ 9

Author(s):

Arthur Cho ◽

Kwanhyeong Jo ◽

Sang Hyun Hwang ◽

Narae Lee ◽

Minkyu Jung ◽

...

Keyword(s):

Colorectal Cancer ◽

Kras Mutation ◽

Stage Iv ◽

Fdg Uptake ◽

Stage Iv Colorectal Cancer ◽

18F Fdg

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Study of Folfiri/Cetuximab in FcGammaRIIIa V/V Stage IV Colorectal Cancer Patients

Case Medical Research ◽

10.31525/ct1-nct03874026 ◽

2019 ◽

Author(s):

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Stage Iv ◽

Stage Iv Colorectal Cancer ◽

Colorectal Cancer Patients

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INVESTIGATION KRAS MUTATION IN CIRCULATION TUMOR DNA IN DIFFERENT STAGES OF COLORECTAL CANCER

Problems in oncology ◽

10.37469/0507-3758-2019-65-5-701-707 ◽

2019 ◽

Vol 65 (5) ◽

pp. 701-707

Author(s):

Vitaliy Shubin ◽

Yuriy Shelygin ◽

Sergey Achkasov ◽

Yevgeniy Rybakov ◽

Aleksey Ponomarenko ◽

...

Keyword(s):

Colorectal Cancer ◽

Plasma Volume ◽

Kras Mutation ◽

Stage Iv ◽

Circulating Tumor Dna ◽

Stage Ii ◽

Kras Gene ◽

Kras Mutations ◽

Droplet Pcr ◽

Tumor Dna

To determine mutations in the plasma KRAS gene in patients with colorectal cancer was the aim of this study. The material was obtained from 44 patients with colorectal cancer of different stages (T1-4N0-2bM0-1c). Plasma for the presence of KRAS gene mutation in circulating tumor DNA was investigated using digital droplet polymerase chain reaction (PCR). KRAS mutations in circulating tumor DNA isolated from 1 ml of plasma were detected in 13 (30%) patients with cancer of different stages. Of these, with stage II, there were 3 patients, with III - 5 and with IV - 5. Patients who did not have mutations in 1 ml of plasma were analyzed for mutations of KRAS in circulating tumor DNA isolated from 3 ml of plasma. Five more patients with KRAS mutations were found with II and III stages. The highest concentrations of circulating tumor DNA with KRAS mutation were found in patients with stage IV. The increase in plasma volume to 3 ml did not lead to the identification of mutations in I stage. This study showed that digital droplet PCR allows identification of circulating tumor DNA with the KRAS mutations in patients with stage II-IV of colon cancer. The results can be used to determine the degree of aggressiveness of the tumor at different stages of the disease, but not the 1st, and it is recommended to use a plasma volume of at least 3 ml.

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