Microsatellite Instability and KRAS Mutation in Stage IV Colorectal Cancer: Prevalence, Geographic Discrepancies, and Outcomes From the National Cancer Database

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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P-320 Genetic testing for microsatellite instability and KRAS mutation in stage IV colorectal cancer: Trends and outcomes from the National Cancer Database

Annals of Oncology ◽

10.1016/j.annonc.2020.04.402 ◽

2020 ◽

Vol 31 ◽

pp. S193-S194

Author(s):

J. Uhlig ◽

S. Stein ◽

M. Cecchini ◽

H. Kim

Keyword(s):

Colorectal Cancer ◽

Genetic Testing ◽

Microsatellite Instability ◽

Kras Mutation ◽

Stage Iv ◽

National Cancer Database ◽

Stage Iv Colorectal Cancer ◽

Cancer Trends

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Vitamin D Status in Patients With Stage IV Colorectal Cancer: Findings From Intergroup Trial N9741

Journal of Clinical Oncology ◽

10.1200/jco.2010.31.7255 ◽

2011 ◽

Vol 29 (12) ◽

pp. 1599-1606 ◽

Cited By ~ 57

Author(s):

Kimmie Ng ◽

Daniel J. Sargent ◽

Richard M. Goldberg ◽

Jeffrey A. Meyerhardt ◽

Erin M. Green ◽

...

Keyword(s):

Colorectal Cancer ◽

Vitamin D ◽

Vitamin D Deficiency ◽

Statistical Power ◽

Proportional Hazards ◽

Stage Iv ◽

Patient Characteristics ◽

Cox Proportional Hazards ◽

Stage Iv Colorectal Cancer ◽

Cox Proportional Hazards Models

Purpose Previous studies have suggested that higher plasma 25-hydroxyvitamin D3 [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival, but the prevalence of vitamin D deficiency in advanced colorectal cancer and its influence on outcomes are unknown. Patients and Methods We prospectively measured plasma 25(OH)D levels in 515 patients with stage IV colorectal cancer participating in a randomized trial of chemotherapy. Vitamin D deficiency was defined as 25(OH)D lower than 20 ng/mL, insufficiency as 20 to 29 ng/mL, and sufficiency as ≥ 30 ng/mL. We examined the association between baseline 25(OH)D level and selected patient characteristics. Cox proportional hazards models were used to calculate hazard ratios (HR) for death, disease progression, and tumor response, adjusted for prognostic factors. Results Among 515 eligible patients, 50% of the study population was vitamin D deficient, and 82% were vitamin D insufficient. Plasma 25(OH)D levels were lower in black patients compared to white patients and patients of other race (median, 10.7 v 21.1 v 19.3 ng/mL, respectively; P < .001), and females compared to males (median, 18.3 v 21.7 ng/mL, respectively; P = .0005). Baseline plasma 25(OH)D levels were not associated with patient outcome, although given the distribution of plasma levels in this cohort, statistical power for survival analyses were limited. Conclusion Vitamin D deficiency is highly prevalent among patients with stage IV colorectal cancer receiving first-line chemotherapy, particularly in black and female patients.

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Metastatic Pattern of Stage IV Colorectal Cancer with High-Frequency Microsatellite Instability as a Prognostic Factor

Anticancer Research ◽

10.21873/anticanres.11313 ◽

2017 ◽

Vol 37 (1) ◽

pp. 239-248 ◽

Cited By ~ 42

Author(s):

KENJI FUJIYOSHI ◽

GOU YAMAMOTO ◽

TAKASHI TAKENOYA ◽

AKEMI TAKAHASHI ◽

YOSHIKO ARAI ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factor ◽

Microsatellite Instability ◽

High Frequency ◽

Stage Iv ◽

Metastatic Pattern ◽

Stage Iv Colorectal Cancer

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Microsatellite instability and KRAS mutation in stage 4 CRC: Prevalence, geographic discrepancies and outcomes from the National Cancer Database.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16052 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16052-e16052

Author(s):

Johannes Uhlig ◽

Michael Cecchini ◽

Stacey Stein ◽

Jill Lacy ◽

Kevin Kim

Keyword(s):

Overall Survival ◽

Microsatellite Instability ◽

Kras Mutation ◽

Proportional Hazards ◽

A Priori ◽

Stage Iv ◽

Cox Proportional Hazards ◽

Treatment Center ◽

National Cancer Database ◽

Kras Status

e16052 Background: To assess microsatellite instability (MSI) and KRAS mutation prevalence, discrepancies and their impact on outcome in AJCC stage IV colorectal adenocarcinoma (colorectal cancer; CRC). Methods: The 2010-2016 United States National Cancer Database was queried for stage IV CRC patients > 18yo and information on MSI and KRAS mutation. Microsatellite status was stratified as stable microsatellites (MSS, including low instability) and microsatellite instability high (MSI-H). KRAS status was stratified as mutation and wildtype. Prevalence and discrepancies were evaluated according to patient demographics, US geography and CRC factors. Overall survival (OS) was assessed using Cox proportional hazards models adjusting for age, gender, race, comorbidities, metastatic burden, CRC treatment, treatment center type, and year of CRC diagnosis. A priori, a statistical interaction test between microsatellite status, KRAS status and primary CRC site was planned. Results: Microsatellite/KRAS status was available for n = 10,844/n = 25,712 patients, respectively. OS was assessed in n = 5,904 patients with data on both microsatellite and KRAS status, and follow-up. Overall prevalence of MSI-H was 3.1% and KRAS mutation 42.4%. Microsatellite and KRAS status varied according to primary CR site, as presented in Table. Further variation was evident according to US-geography, with MSI-H rates ranging from 1.6% to 4.1%, and KRAS mutation rates ranging from 41.1% to 44%. On multivariable analyses, longer OS was observed in patients with KRAS wildtype versus mutation (HR = 0.91, 95% CI: 0.85-0.97 p = 0.004), MSS versus MSI-H (HR = 0.75, 95% CI: 0.62-0.9, p = 0.003), and left-sided versus right-sided CRC (HR = 0.65, 95% CI: 0.6-0.7, p < 0.001). The effect of KRAS mutation further varied with CRC site and microsatellite status (interaction p = 0.002). Conclusions: Depending on its primary site and US geography, stage IV CRC shows distinct mutational behavior. KRAS mutation, MSI-H, MSI-H and primary CRC sidedness independently affect overall survival and interact with distinct prognostic profiles. Generically classifying adenocarcinomas of different site as “CRC” might deprecate this diversity. [Table: see text]

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

Annals of Oncology ◽

10.1093/annonc/mdy281.075 ◽

2018 ◽

Vol 29 ◽

pp. viii177

Author(s):

J. Uhlig ◽

S. Stein ◽

J. Lacy ◽

C.S. Fuchs ◽

H.S. Kim

Keyword(s):

Colorectal Cancer ◽

Microsatellite Instability ◽

Kras Mutation ◽

Stage Iv ◽

Stage Iv Colorectal Cancer

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Nomogram for predicting overall survival in colorectal cancer with distant metastasis

BMC Gastroenterology ◽

10.1186/s12876-021-01692-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zheng Liu ◽

Yao Xu ◽

Guijun Xu ◽

Vladimir P. Baklaushev ◽

Vladimir P. Chekhonin ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Cancer Patients ◽

Distant Metastasis ◽

Primary Tumour ◽

Stage Iv ◽

Cox Proportional Hazards ◽

Stage Iv Colorectal Cancer ◽

Colorectal Cancer Patients

Abstract Background Colorectal cancer (CRC) is a major cancer burden, and prognosis is determined by many demographic and clinicopathologic factors. The present study aimed to construct a prognostic nomogram for colorectal cancer patients with distant metastasis. Methods Colorectal cancer patients with distant metastasis diagnosed between 2010 and 2016 were selected from the Surveillance, Epidemiology, and End Results database. Cox proportional hazards regression was used to identify independent prognostic factors. A nomogram was constructed to predict survival, and validation was performed. Results A total of 7099 stage IV colorectal cancer patients were enrolled in the construction cohort. The median overall survival was 20.0 (95% CI 19.3–20.7) months. Age at diagnosis, marital status, race, primary tumour site, tumour grade, CEA level, T stage, N stage, presence of bone, brain, liver and lung metastasis, surgery for primary site and performance of chemotherapy were independent prognostic factors. The nomogram was constructed and the calibration curve showed satisfactory agreement. The C-index was 0.742 (95% CI 0.726–0.758). In the validation cohort (7098 patients), the nomogram showed satisfactory discrimination and calibration with a C-index of 0.746 (95% CI 0.730–0.762). Conclusion A series of factors associated with the survival of CRC patients with distant metastasis were found. Based on the identified factors, a nomogram was generated to predict the survival of stage IV colorectal cancer patients. The predictive model showed satisfactory discrimination and calibration, which can provide a reference for survival estimation and individualized treatment decisions.

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