KRAS mutation and microsatellite instability in colorectal cancer: Screening pattern and mutational landscape across the US.

e15138 Background: To assess screening patterns for KRAS mutation and microsatellite instability (MSI), associated mutational prevalence in colorectal cancer (CRC), and whether mutational screening affects survival. Methods: Patients with adenocarcinoma of the colon, sigmoid, and rectum were included from the 2010-2015 National Cancer Database. Socioeconomic, geographic and cancer factors were correlated with screening patterns. Propensity score matching was used to account for confounding. Overall survival was assessed in the matched cohort via Cox proportional hazards models. Results: 371,669 patients were included, of which 113,197 (30.4%) were screened: n=63,967 for MSI, n=33,319 for KRAS, and n=15,911 for MSI + KRAS. Younger patients with private insurance, high income locally advanced and metastatic sigmoid CRC treated at academic centers in Middle Atlantic and New England states were more likely to be screened. MSI was more prevalent among older female Caucasians from East South Central and Middle Atlantic States. KRAS mutation showed no significant discrepancies according to patient age or US geography, but was more prevalent among female African Americans. KRAS mutation was associated with locally advanced and metastatic CRC. MSI was more common in localized, non-metastatic CRC. Distinct mutational patterns were evident among primary CRC sites, with highest mutation rates in cecum/appendix and ascending colon (table). In the propensity score matched cohort with balanced distribution of confounders (n=157,678), mutational screening was not associated with overall survival (HR=1.012, 95% CI: 0.99-1.03, p=0.15). MSI versus MSS did not significantly influence patients´ overall survival (matched cohort n=26,014, HR=1.00, 95% CI: 0.96-1.05, p=0.88). Kras mutation versus wildtype showed decreased overall survival after accounting for confounders (matched cohort n=28,084, HR=1.11, 95% CI: 1.07-1.15, p<0.001). Conclusions: Testing for MSI and Kras mutation in CRC shows distinct patterns across the US, but does not influence outcomes. Decreased overall survival is observed in those patients with Kras mutation versus wildtype. [Table: see text]

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Decreased mean platelet volume is associated with microsatellite instability in colorectal cancer: A propensity score-matched analysis

Cancer Biomarkers ◽

10.3233/cbm-203250 ◽

2021 ◽

pp. 1-9

Author(s):

Wen Wang ◽

Guangyu Wang ◽

Shuang Fu ◽

Beibei Zhang ◽

Zengyao Liu ◽

...

Keyword(s):

Colorectal Cancer ◽

Propensity Score ◽

Microsatellite Instability ◽

Propensity Score Matching ◽

Mean Platelet Volume ◽

Innate Immune ◽

Platelet Volume ◽

Activated Platelets ◽

Medical University ◽

Potential Parameters

BACKGROUND: Patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC) generally have a better prognosis and a more effective immune response than patients with microsatellite stable (MSS) CRC. Moreover, activated platelets play a crucial role in modulating innate immune cells. Mean platelet volume (MPV) is an indicator of platelet activation. This study is to examine the association between MPV and MSI status in CRC. METHODS: We collected the clinical and pathological variables of 424 CRC patients diagnosed at the Harbin Medical University Cancer Hospital from January 2018 to December 2018. Associations between MPV levels and MSI status were examined. Propensity score matching (PSM) was performed to reduce the possibility of selection bias. RESULTS: 424 CRC patients were divided into low-MPV group and high-MPV group according to the optimal cut-off value of MPV. 131 high-MPV patients were matched to low-MPV counterparts in a 1:1 ratio by propensity score matching. As MPV levels increased, the percentage of patients with MSI-H reduced. Furthermore, compared with MSS group, the MSI-H group had a significantly lower MPV levels (p= 0.003 after matching). In addition, logistic regression analysis identified reduced MPV as an independent risk factor for MSI-H in CRC patients after controlling for other potential parameters. CONCLUSION: Lower MPV is associated with MSI-H subtype of CRC. Further study on MPV in MSI-H CRC is warranted.

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Comparison of dose-dense vs. 3-weekly paclitaxel and carboplatin in the first-line treatment of ovarian cancer in a propensity score-matched cohort

BMC Cancer ◽

10.1186/s12885-021-08270-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Rafaela Pirolli ◽

Viviane Teixeira Loiola de Alencar ◽

Felipe Leonardo Estati ◽

Adriana Regina Gonçalves Ribeiro ◽

Daniella Yumi Tsuji Honda ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Propensity Score ◽

Ovarian Carcinoma ◽

Matched Cohort ◽

Line Treatment ◽

First Line ◽

Western Population ◽

Dose Dense ◽

First Line Treatment

Abstract Background Benefit of carboplatin and dose-dense weekly paclitaxel (ddCT) in first line treatment of ovarian cancer patients has been different in Western and Asian studies. In the present study we compare progression-free survival (PFS) of ddCT to three-weekly carboplatin and paclitaxel (CT) in first-line treatment of ovarian carcinoma in a single institution in a Western population. Materials and methods We conducted a retrospective review of medical records from patients with ovarian carcinoma treated in a tertiary cancer center from 2007 to 2018. All patients treated with ddCT or CT in the first-line setting were included. Patients who received first-line bevacizumab were not included. PFS and overall survival (OS) were compared in a propensity score-matched cohort to address selection bias. Patients were matched according to age, ECOG performance status, CA 125, FIGO stage, residual disease, and histological subtype, in a 1:2 ratio. Results Five hundred eighty-eight patients were eligible for propensity score matching, the final cohort consisted of 69 patients treated with ddCT and 138 CT group. Baseline characteristics were well-balanced. After a median follow-up of 65.1 months, median PFS was 29.3 vs 20.0 months, favouring ddCT treatment (p = 0.035). In the multivariate cox regression ddCT showed a 18% lower risk of progression (HR 0.82, 95% CI 0.68–0.99, p = 0.04). Overall survival data is immature, but suggested better outcomes for ddCT (not reached versus 78.8 months; p = 0.07). Conclusion Our retrospective study has shown superior PFS of ddCT over CT regimen in first-line treatment of ovarian carcinoma in a Western population not treated with bevacizumab.

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Association of KRAS mutation with tumor deposit status and overall survival of colorectal cancer

Cancer Causes & Control ◽

10.1007/s10552-020-01313-0 ◽

2020 ◽

Vol 31 (7) ◽

pp. 683-689 ◽

Cited By ~ 1

Author(s):

Meifang Zhang ◽

Wenwei Hu ◽

Kun Hu ◽

Yong Lin ◽

Zhaohui Feng ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Kras Mutation ◽

Tumor Deposit

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IMPACT OF KRAS MUTATIONS IN CLINICAL FEATURES IN COLORECTAL CANCER

ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) ◽

10.1590/0102-672020200003e1524 ◽

2020 ◽

Vol 33 (3) ◽

Author(s):

Renato Morato ZANATTO ◽

Gianni SANTOS ◽

Júnea Caris OLIVEIRA ◽

Eduardo Marcucci PRACUCHO ◽

Adauto José Ferreira NUNES ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Kras Mutation ◽

Direct Sequencing ◽

Colorectal Carcinogenesis ◽

Kras Mutations ◽

Primary Tumor Site ◽

Exon 2 ◽

Metastatic Site ◽

Colorectal Cancer Patients

ABSTRACT Background: KRAS mutations are important events in colorectal carcinogenesis, as well as negative predictors of response to EGFR inhibitors treatment. Aim: To investigate the association of clinical-pathological features with KRAS mutations in colorectal cancer patients treated. Methods: Data from 69 patients with colorectal cancer either metastatic at diagnosis or later, were retrospectively analyzed. The direct sequencing and pyrosequencing techniques were related to KRAS exon 2. The mutation diagnosis and its type were determined. Results: KRAS mutation was identified in 43.4% of patients. The most common was c.35G>T (p.G12V), c.35G>A (p.G12D) and c.38G>A (p.G13D). No correlation was found between KRAS mutation and age (p=0.646) or gender (p=0.815). However, mutated group had higher CEA levels at admission (p=0.048) and codon 13 mutation was associated with involvement of more than one metastatic site in disease progression (p=0.029). Although there was no association between primary tumor site and mutation diagnosis (p=0.568), primary colon was associated with worse overall survival (p=0.009). Conclusion: The KRAS mutation was identified in almost half of patients. Mutated KRAS group had higher levels of CEA at admission and the mutation at codon 13 was associated with involvement of more than one metastatic site in the course of the disease. Colon disease was associated with the worst overall survival.

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Palliative resection of the primary tumor is associated with improved overall survival in incurable stage IV colorectal cancer: A nationwide population-based propensity-score adjusted study in the Netherlands

International Journal of Cancer ◽

10.1002/ijc.30240 ◽

2016 ◽

Vol 139 (9) ◽

pp. 2082-2094 ◽

Cited By ~ 22

Author(s):

Jorine 't Lam-Boer ◽

Lydia G. Van der Geest ◽

Cees Verhoef ◽

Marloes E. Elferink ◽

Miriam Koopman ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Propensity Score ◽

The Netherlands ◽

Primary Tumor ◽

Stage Iv ◽

Population Based ◽

Palliative Resection ◽

Stage Iv Colorectal Cancer

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Overall survival based on MSI and BRAF mutation status for stage II/III colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.132 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 132-132

Author(s):

Sophiya Karki ◽

Rashna Madan ◽

Sarah Schmitt ◽

Ziyan Y. Pessetto ◽

Andrew K. Godwin ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Microsatellite Instability ◽

Median Survival ◽

Braf Mutation ◽

Prognostic Value ◽

Stage Ii ◽

Age At Diagnosis ◽

Mutation Status ◽

Braf Mutant

132 Background: Colorectal cancer (CRC) is the second leading cause of cancer-associated deaths in the United States. Some of the poor prognostic factors for metastatic CRC (mCRC) include BRAF V600E mutation and microsatellite instability (MSI) that result from mutation or loss of mismatch-repair genes. While the prognostic value of MSI-high CRC for early-stage patients treated with resection and adjuvant chemotherapy is favorable, the prognostic value of BRAF mutation is still unclear. Furthermore, the impact of BRAF mutation with concurrent microsatellite instability on overall survival has not been well investigated. Methods: Here, we collected BRAF mutation status and MSI status of stage II/III CRC patients (n=106) treated at the University of Kansas Cancer Center between September 2009 and July 2020 and compared overall survival between 4 subtypes:MSI-H/BRAF mutant (n=16), MSS/BRAF mutant (n=4), MSI-H/BRAF WT (n=17) and MSS/BRAF WT (n=69), further stratifying patients by age at diagnosis and tumor location. Molecular data were obtained from molecular oncology laboratory as PCR or IHC-based or acquired from outside records. Subgroup analyses were done for stage II and stage III cancers. Results: Table shows the patient characteristics. From our preliminary analysis, MSI-H CRC was found to be primarily a right-sided tumor (MSI-H/BRAF mutant: 94% and MSI-H/BRAF WT 76%). On the contrary, MSS CRC had a more heterogenous localization, spanning left colon, right colon and rectum. In our patient cohort, median survival was not reached for stage II patients whereas for stage III patients, BRAF mutation was associated with poor median survival irrespective of MSI status (MSS/BRAF mutant: 27 months and MSI-H/BRAF mutant 29 months). Median overall survival was found to be 87 months, not reached, 27 months and 29 months for MSS/BRAF WT, MSI-H/BRAF WT, MSS/BRAF mutant and MSI-H/BRAF mutant, respectively. Although associated with poor survival, MSI-H/BRAF mutant displayed later age at diagnosis (mean age 73) compared to MSS/BRAF mutant (mean age 60, p-value<0.029). Conclusions: Our finding suggests that BRAF mutation has poor prognosis even at earlier stages of the disease and that MSS/BRAF mutation, in particular, has the worst prognostic features. These findings highlight the need for BRAF-targeted therapy for CRC at any stage. Due to small sample size, however, our results warrant validation in a larger cohort. [Table: see text]

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