The correlation between mismatch repair status and clinicopathological characteristics in Chinese colorectal cancer patients.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 544-544 ◽  
Author(s):  
Zhi-tao Xiao ◽  
Rong-xin Zhang ◽  
Yang Zhao ◽  
Jian-Hong Peng ◽  
Pei-Rong Ding ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Mismatch Repair ◽  
Mucinous Adenocarcinoma ◽  
Clinicopathological Characteristics ◽  
Left Colon ◽  
Stage Ii ◽  
Chinese Patients ◽  
Right Colon ◽  
Significant Difference

544 Background: Our study aimed to explore the relationship between mismatch repair (MMR) status and clinicopathological characteristics in Chinese patients with colorectal cancer (CRC). Methods: A total of 2684 patients with histologically confirmed adenocarcinoma of CRC were consecutively recruited between May 2011 and May 2015 at Sun Yat-sen University cancer center. The exclusion criteria included multiple primary tumors, synchronous and metachronous CRC, and familial adenomatous polyposis. The CRC was defined as left colon with the tumor located below the splenic flexure or rectum, otherwise grouped as right colon. Correlations of MMR status and patient’s demographics, tumor characteristics and TNM staging (exclude 315 CRC patients receiving neoadjuvant therapy) were investigated. Results: We found that deficient MMR (dMMR) status was more likely detected in younger CRC patients compared to the the elderly (12.7% vs 7.5%, P < 0.001). The dMMR rate in right colon cancer was significantly higher than that in left colon cancer and rectal cancer (22.7% vs 7.2% vs 5.2%, P < 0.001).With respect to tumor differentiation, we found that the mucinous adenocarcinoma had the highest rate of dMMR(24.4%), followed by poorly differentiated adenocarcinoma(18.5%), signet-ring cell carcinoma(17.6%), well differentiated adenocarcinoma(9.5%), moderately differentiated adenocarcinoma(8.9%), and neuroendocrine carcinoma (0%) ( P < 0.001). In addition, the proportions in stage I, stage II, stage III and stage IV CRC were 9.7%, 16.5% , 8.5% and 3.9%, respectively ( P < 0.001). There was no significant difference in gender (P = 0.114). Conclusions: At the first time, our study demonstrated that dMMR status was most likely detected at younger age (less than 59 years) and stage II right colon mucinous adenocarcinoma in large volume Chinese patients, which was similar to the results in western countries.

Development and validation of a robust prognostic and predictive signature for colorectal cancer (CRC) patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4036-4036
Author(s):  
A. M. Glas ◽  
P. Roepman ◽  
R. Salazar ◽  
G. Capella ◽  
V. Moreno ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Gene Signature ◽  
Low Risk ◽  
Stage Ii ◽  
Significant Difference ◽  
Independent Cohort

4036 Background: Between 25 and 35% of stage II CRC patients will experience a recurrence of their disease and may benefit from adjuvant chemotherapy. Official guidelines give suggestions but no clear recommendation for best risk stratification. Here we describe the development a robust signature that predicts disease relapse and can assist in treatment decisions. Methods: Fresh frozen tumor tissues from 180 patients with stage I, II and III colorectal cancer undergoing surgery were analyzed using high density Agilent 44K oligonucleotide arrays. Median FU was 70.2 months; 85% of patients did not receive adjuvant chemotherapy. Unsupervised hierarchical clustering based on full-genome gene expression measurement indicated the existence of 3 main colon molecular subclasses. Survival analysis of the 3 classes showed that subtype C (n= 27) had a poor outcome and subtype A (n= 48) good outcome. Only the intermediate group B (n=104) was used to develop a signature by using a cross validation procedure to score all genes for their association with 5-yr distant metastasis free survival (DMFS) and subsequently applied to all samples (n=180). The obtained gene signature was further validated on an independent cohort of 178 stage II + III colon samples. Results: A set of 38 prognosis related gene probes showed robust DMFS association in over 50% of all iterations in the Training Set of 180 samples. The gene signature was validated on an independent cohort of 178 samples from stage II + III colon cancer patients. The profile classified 61% of the validation samples as low-risk and 39% as high-risk. The low- and high-risk samples showed a significant difference in DMFS with a HR of 3.19 (P= 8.5e-4). Five-year DMFS rates were 89% (95%CI 83–95) for low-risk and 62% (95%CI 50–77) for high-risk samples. Moreover, the profile showed a significant performance within stage II (P=0.0058) and III (P=0.036) only samples. The performance of the profile was significant for both untreated (P=0.0082) and treated patients (P=0.016) suggesting that its power is independent of treatment benefits. Conclusions: ColoPrint is able to predict the prognosis of stage II and III colon cancer patients and facilitates the identification of patients who would benefit from adjuvant chemotherapy. [Table: see text]

Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer

2011 ◽  
Vol 29 (10) ◽  
pp. 1261-1270 ◽  
Author(s):  
Gordon Hutchins ◽  
Katie Southward ◽  
Kelly Handley ◽  
Laura Magill ◽  
Claire Beaumont ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Mutational Analysis ◽  
Left Colon ◽  
Rectal Tumors ◽  
Wild Type ◽  
Right Colon ◽  
Kras Mutations ◽  
Risk Of Recurrence ◽  
Braf Mutant

Purpose It is uncertain whether modest benefits from adjuvant chemotherapy in stage II colorectal cancer justify the toxicity, cost, and inconvenience. We investigated the usefulness of defective mismatch repair (dMMR), BRAF, and KRAS mutations in predicting tumor recurrence and sensitivity to chemotherapy. Patients and Methods Immunohistochemistry for dMMR and pyrosequencing for KRAS/BRAF were performed for 1,913 patients randomly assigned between fluorouracil and folinic acid chemotherapy and no chemotherapy in the Quick and Simple and Reliable (QUASAR) trial. Results Twenty-six percent of 695 right-sided colon, 3% of 685 left-sided colon, and 1% of 407 rectal tumors were dMMR. Similarly, 17% of right colon, 2% of left colon, and 2% of rectal tumors were BRAF mutant. KRAS mutant tumors were more evenly distributed: 40% right colon, 28% left colon, and 36% rectal tumors. Recurrence rate for dMMR tumors was half that for MMR-proficient tumors (11% [25 of 218] v 26% [438 of 1,695] recurred; risk ratio [RR], 0.53; 95% CI, 0.40 to 0.70; P < .001). Risk of recurrence was also significantly higher for KRAS mutant than KRAS wild-type tumors (28% [150 of 542] v 21% [219 of 1,041]; RR, 1.40; 95% CI, 1.12 to 1.74; P = .002) but did not differ significantly between BRAF mutant and wild-type tumors (P = .36). No marker predicted benefit from chemotherapy with efficacy not differing significantly by MMR, KRAS, or BRAF status. The prognostic value of MMR and KRAS was similar in the presence and absence of chemotherapy. Conclusion MMR assays identify patients with a low risk of recurrence. KRAS mutational analysis provides useful additional risk stratification to guide use of chemotherapy.

Oncogenic mutations in colorectal cancer, indications for anatomical sites, and targeted intervention.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22037-e22037
Author(s):  
Giovanni Corso ◽  
Valeria Pascale ◽  
Giuseppe Flauti ◽  
Daniele Marrelli ◽  
Franco Roviello
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Microsatellite Instability ◽  
Cancer Patients ◽  
Left Colon ◽  
Targeted Intervention ◽  
Right Colon ◽  
Right Colon Cancer ◽  
Oncogenic Mutations ◽  
Colorectal Cancer Patients

e22037 Background: Oncogenic mutations, such as KRAS, in colorectal cancer patients are considered standard molecular biomarkers that predict the clinical benefit for the targeted intervention with EGFR inhibitors. In addition, these mutations are associated with specific anatomical area in the colon tumor development, as BRAF mutations with the microsatellite instability. Methods: In this translational study we aim to assess the mutation frequencies of the EGFR [hotspot area and polyadenine deletions (A13_del)], KRAS, BRAFV600E, and PIK3CA oncogenes in a series of 280 colorectal cancer patients. Microsatellite instability phenotype is considered in this series. All patients' clinicopathological data were considered for statistical analysis and associations. Results: In this study, we verified multiple associations between oncogenic mutations and specified clinicopathological tumor features. Respectively, we identified the following significant results: 1) EGFR A13_deletions are associated with right colon carcinoma (22.2% vs. 3.3%; p<0.005), mucinous histotype (16% vs. 7.8%; p=0.042), G3 grading (19% vs. 7.3%; p=0.024) and microsatellite instability status (p<0.005); 2) PIK3CA mutations are related mucinous histotype (12% vs. 4.4%; p=0.021) 3) KRASG12 and KRASG13mutations are correlated respectively with the left (91.4% vs. 59.3%) and right (40.7% vs. 8.6%) colon cancer development (p<0.005), and finally 4) microsatellite instability is associated with right colon tumors (28.4% vs. 5.5%; p<0.005). Conclusions: Mostly, we verified a high frequency rate of the KRASG13 and EGFR A13_del oncogene mutations in right colon cancer; whereas KRASG12 codon mutation occurs more frequently in left colon cancers. In particular, we assessed that right colon cancer is associated with specific molecular characteristics, in comparison to left colon tumors. These evidences, in association with specific clinicopathological data, can delineate novel approaches for the colorectal cancer classification and targeted intervention.

Microsatellite instability in colorectal cancer: An analysis of the National Cancer Database.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 134-134
Author(s):  
Kamelah Abushalha ◽  
Sawsan Abulaimoun ◽  
Sarah J Aurit ◽  
Erin Jenkins ◽  
Peter T. Silberstein
Keyword(s):  
Colorectal Cancer ◽  
Regression Model ◽  
Microsatellite Instability ◽  
Mucinous Adenocarcinoma ◽  
Medullary Carcinoma ◽  
Left Colon ◽  
Right Colon ◽  
White Race ◽  
Factors Associated ◽  
Colon And Rectum

134 Background: High-frequency microsatellite instability (MSI-H) accounts for roughly 15% of all cases of colorectal cancer (CRC). Studies suggest a significant non-adherence to routine MSI testing in patients diagnosed with CRC despite universal guidelines. Methods: We used the NCDB to identify adults with MSI-H status CRC from 2010-2015 with the following histologic subtypes: mucinous and not otherwise specified adenocarcinoma, and medullary carcinoma. The primary site was localized to the right colon, left colon, and rectum; demographic factors, clinicopathologic features, and treatments were identified. Patients were stratified by site and discrete and continuous variable comparisons were made using the chi-square and Mann-Whitney test, respectively. Survival was examined with the Kaplan-Meier method and a Cox proportional hazards regression model. A logistic regression model was used to examine MSI status. All analyses were conducted with SAS version 9.4. Results: A total of 5364 patients were identified and stratified by site into 3 groups: right colon (n = 4004, 74.6%), left colon (n = 890, 16.59%) and rectum (n = 470, 8.76%). Compared to the left colon and rectum, right colon patients were more likely to be older females with larger tumors and less likely to receive chemoradiation. After adjusting for all else, we found statistical evidence that female vs. male gender (OR = 1.47; 95% CI: 1.24 to 1.73), Black vs. White race (OR = 0.61; 0.45 to 0.83), left vs. right colon (OR = 0.33, 0.27 to 0.41), rectum vs. right colon (OR = 0.08, 0.05 to 0.13), mucinous adenocarcinoma vs. adenocarcinoma (OR = 2.37, 1.92 to 2.93), medullary carcinoma vs. adenocarcinoma (OR = 8.86, 4.56 to 17.22), positive vs. negative k-RAS mutation (OR = 0.49, 0.41 to 0.59), and positive vs. negative CEA status (OR = 0.79, 0.66 to 0.94) were factors associated with MSI-H status. Improved survival was associated were Hispanic white race, stage 1, and free surgical margins within a multivariable context. Factors associated with poor survival: increased Charlson/Deyo score, advanced stage, lymphovascular invasion, and positive CEA status. Conclusions: In settings where resources are scarce and universal testing is not possible, there is a benefit from MSI testing in female patients, those with right-sided colon cancer, mucinous adenocarcinoma, and medullary carcinoma.

scholarly journals Smoking-Related Risks of Colorectal Cancer by Anatomical Subsite and Sex

2020 ◽  
Vol 189 (6) ◽  
pp. 543-553 ◽  
Author(s):  
Inger T Gram ◽  
Song-Yi Park ◽  
Lynne R Wilkens ◽  
Christopher A Haiman ◽  
Loïc Le Marchand
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Cox Regression ◽  
Left Colon ◽  
Right Colon ◽  
Right Colon Cancer ◽  
Increased Risk ◽  
The Right ◽  
Incident Cases

Abstract The purpose of this study was to examine whether the increased risk of colorectal cancer due to cigarette smoking differed by anatomical subsite or sex. We analyzed data from 188,052 participants aged 45–75 years (45% men) who were enrolled in the Multiethnic Cohort Study in 1993–1996. During a mean follow-up period of 16.7 years, we identified 4,879 incident cases of invasive colorectal adenocarcinoma. In multivariate Cox regression models, as compared with never smokers of the same sex, male ever smokers had a 39% higher risk (hazard ratio (HR) = 1.39, 95% confidence interval (CI): 1.16, 1.67) of cancer of the left (distal or descending) colon but not of the right (proximal or ascending) colon (HR = 1.03, 95% CI: 0.89, 1.18), while female ever smokers had a 20% higher risk (HR = 1.20, 95% CI: 1.06, 1.36) of cancer of the right colon but not of the left colon (HR = 0.96, 95% CI: 0.80, 1.15). Compared with male smokers, female smokers had a greater increase in risk of rectal cancer with number of pack-years of smoking (P for heterogeneity = 0.03). Our results suggest that male smokers are at increased risk of left colon cancer and female smokers are at increased risk of right colon cancer. Our study also suggests that females who smoke may have a higher risk of rectal cancer due to smoking than their male counterparts.

scholarly journals Association between local immune cell infiltration, mismatch repair status and systemic inflammatory response in colorectal cancer

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Ulf Gunnarsson ◽  
Karin Strigård ◽  
Sofia Edin ◽  
Ioannis Gkekas ◽  
Harri Mustonen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Mismatch Repair ◽  
Immune Cell ◽  
Immune Cell Infiltration ◽  
Right Colon ◽  
Cancer Specific Survival ◽  
Significant Difference ◽  
Mismatch Repair Status ◽  
The Right

Abstract Background Systemic inflammatory response in colorectal cancer (CRC) has been established as a prognostic factor for impaired cancer-specific survival, predominantly in patients with right-sided tumors. On the other hand, defective mismatch repair (dMMR) tumors, primarily located in the right colon, are known to have favorable survival and dense local immune infiltration. The aim of this study was to see if there is any form of relationship between these seemingly diverse entities. Methods Complete clinical and long-term survival data were retrieved for 316 CRC patients operated at Helsinki University Hospital between the years 1998 and 2003. Tissue microarrays were prepared from surgical specimens and further processed and analyzed for local immune cell infiltration using multispectral imaging with a Vectra quantitative pathology imaging system and Inform software. Multiplex immunohistochemistry was applied using antibodies against CD66b, CD8, CD20, FoxP3, CD68 and pan-Cytokeratin. After exclusions, data on immune infiltration were available for 275 patients. Mismatch repair status was determined by immunohistochemistry. Results CRP was seen to be an independent predictor of cancer-specific survival but not overall survival in uni- and multivariable (HR 1.01 (1.00–1.02); p = 0.028) analyses of non-irradiated patients. There was no significant difference in CRP according to mismatch repair status, but all cases (n = 10) with CRP ≥ 75 mg/l had proficient mismatch repair (pMMR). There was a significant negative correlation between intratumor stromal infiltration by T-regulatory FOXP3+ cells and CRP (p = 0.006). There was significantly lower intratumor stromal infiltration by FOXP3+ cells (p = 0.043) in the right colon compared to the rectum, but no significant difference in CRP (p = 0.44). CRP was not a predictor of overall survival (HR 0.99, 95% CI 0.98–1.01) nor cancer-specific survival in irradiated patients (HR 0.94, 95% CI 0.94–1.02). Conclusions There was a significant negative relationship between SIR, defined as an elevated CRP, and intratumor stromal infiltration by T-regulatory FOXP3+ cells. This and the fact that all cases with a CRP > 75 mg/l had pMMR suggests that SIR and dMMR are independent entities in CRC. Indeed, the general lack of difference in CRP between cases with dMMR and pMMR may be evidence of overlap in cases with a less pronounced SIR.

Association of antibiotic exposure with the mortality in bevacizumab-treated metastatic colorectal cancer: A secondary analysis from Dryad database.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15609-e15609
Author(s):  
Chenyu Sun ◽  
Xianwei Guo ◽  
Kelly Kozma ◽  
Chandur Bhan ◽  
Na Hyun Kim
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Chemotherapy Regimen ◽  
Radical Surgery ◽  
Secondary Analysis ◽  
Palliative Surgery ◽  
Left Colon ◽  
Antibiotic Exposure ◽  
Right Colon ◽  
Surgical Treatments

e15609 Background: Colorectal cancer (CRC) is one of the most diagnosed cancers and the second leading cause of cancer-related death worldwide. Globally, more than 1.8 million people are diagnosed of colorectal cancer (CRC) in 2018. In advanced CRC patients, bevacizumab plus 5-fluorouracil-based or platinum-based therapy has become one of the standard first-line chemotherapy regimen. A recent study also found that antibiotic exposure could be inversely associated with the mortality in metastatic colorectal cancer (mCRC) patients treated with bevacizumab. However, subgroup analysis of this study was no sufficient. Therefore, we conducted a secondary analysis based on the data of this study from Dryad database. Methods: In this retrospective cohort study, 147 mCRC patients treated with bevacizumab were included. All data was obtained from Dryad database (https://doi.org/10.5061/dryad.ft5sk66). Patients were divided into follow subgroups: (1) left colon vs right colon; (2) BMI < 18.5 vs BMI 18.5-24 vs BMI≥24;(3) Age < 45 vs Age≥45, (4) no surgery vs palliative surgery vs radical surgery, (5) bevacizumab plus FOLFIRI vs bevacizumab plus capeOX/FOLFOX vs bevacizumab plus other chemotherapy regimen. Specific survival of each subgroup was analyzed through the Kaplan-Meier curve, and the survival curves of the variables were compared using the log-rank test. Results: Survival analysis found no statistically significant differences of the cumulative survival rates between left colon cancer and right colon cancer, (58.9% vs 62.5%, respectively; χ2 = 0.043, P = 0.836), groups of different BMI (57.9% of BMI < 18.5 vs 55.2% of 18.5≤BMI < 24 vs 70.7% of BMI ≥24，χ2 = 3.026, P = 0.220), Age < 45 group and Age≥45 group (54.8% vs 61.2%, respectively; χ2 = 0.001, P = 0.976), surgical treatments (No surgery 59.0% vs Palliative surgery 57.6% vs Radical Surgery 61.3%; χ2 = 1.885, P = 0.390), as well as groups of different chemotherapy regimens (66.7% of FLOFIRI vs 52.0% of CapeOX/FOLFOX vs 59.9% of others; χ2 = 1.572, P = 0.456). Conclusions: Based on the data from this study, we found that different sites of colon cancer, age, BMI, different surgical treatments, and different chemotherapy regimens did not affect the survival outcome of patients with mCRC treated with bevacizumab after antibiotic exposure. Subsequent studies with larger sample size are still needed to further elaborate the effects of different antibiotics on survival outcomes.

scholarly journals Olaparib-mediated enhancement of 5-fluorouracil cytotoxicity in mismatch repair deficient colorectal cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Helena de Castro e Gloria ◽  
Laura Jesuíno Nogueira ◽  
Patrícia Bencke Grudzinski ◽  
Paola Victória da Costa Ghignatti ◽  
Temenouga Nikolova Guecheva ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Mismatch Repair ◽  
Cell Cycle Progression ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Human Colon ◽  
Human Colon Cancer

Abstract Background The advances in colorectal cancer (CRC) treatment include the identification of deficiencies in Mismatch Repair (MMR) pathway to predict the benefit of adjuvant 5-fluorouracil (5-FU) and oxaliplatin for stage II CRC and immunotherapy. Defective MMR contributes to chemoresistance in CRC. A growing body of evidence supports the role of Poly-(ADP-ribose) polymerase (PARP) inhibitors, such as Olaparib, in the treatment of different subsets of cancer beyond the tumors with homologous recombination deficiencies. In this work we evaluated the effect of Olaparib on 5-FU cytotoxicity in MMR-deficient and proficient CRC cells and the mechanisms involved. Methods Human colon cancer cell lines, proficient (HT29) and deficient (HCT116) in MMR, were treated with 5-FU and Olaparib. Cytotoxicity was assessed by MTT and clonogenic assays, apoptosis induction and cell cycle progression by flow cytometry, DNA damage by comet assay. Adhesion and transwell migration assays were also performed. Results Our results showed enhancement of the 5-FU citotoxicity by Olaparib in MMR-deficient HCT116 colon cancer cells. Moreover, the combined treatment with Olaparib and 5-FU induced G2/M arrest, apoptosis and polyploidy in these cells. In MMR proficient HT29 cells, the Olaparib alone reduced clonogenic survival, induced DNA damage accumulation and decreased the adhesion and migration capacities. Conclusion Our results suggest benefits of Olaparib inclusion in CRC treatment, as combination with 5-FU for MMR deficient CRC and as monotherapy for MMR proficient CRC. Thus, combined therapy with Olaparib could be a strategy to overcome 5-FU chemotherapeutic resistance in MMR-deficient CRC.

Regorafenib plus PD-1 inhibitors in Chinese patients with microsatellite stable/mismatch repair proficient metastatic colorectal cancer: A real-world study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15585-e15585
Author(s):  
Kaili Yang ◽  
Lu Han ◽  
Yun-Bo Zhao ◽  
Yang Ge ◽  
Qin LI ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Mismatch Repair ◽  
Real World ◽  
Objective Response ◽  
Disease Control Rate ◽  
Chinese Patients ◽  
Hand Foot Syndrome

e15585 Background: A previous phase 1b trial has shown encouraging efficacy of regorafenib plus nivolumab in patients with microsatellite stable/mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (mCRC). We aimed to evaluate the efficacy and safety of this regimen in Chinese patients in the real world. Methods: We retrospectively identified patients with MSS/pMMR mCRC who received at least one dose of programmed cell death-1 (PD-1) inhibitors plus regorafenib from 5/2019 to 2/2021 in 10 Chinese medical centers. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and the safety. Results: Fifty-two patients were identified. Liver metastases were presented in 35 patients (67%). A total of 48 patients (92%) received regorafenib plus a PD-1 inhibitor as the third or later line treatment. At the data cut-off, 11 patients (21%) were still on treatment. Other patients terminated treatment because of progressive disease (45%), treatment-related adverse events (TRAEs) (14%) or treatment-unrelated deaths (6%). The median treatment cycle was 3 (range, 1-18). At a median follow-up of 4.9 months, the median OS was 17.3 months (95% CI, 10.2-NR) and the median PFS was 3.1 months (95%CI, 2.5-6.0). Baseline liver metastases were associated with inferior PFS (2.7 versus 6.3 months, p <0.05), but not OS (17.3 months versus NR, p =0.6). Among 38 patients evaluable for response, two patients (5%) achieved partial response, and 17 patients (45%) experienced stable disease as the best response. The DCR was 50% (95%CI, 5.0-NR) and was similar among different PD-1 inhibitors (Table). TRAEs were observed in 30 patients (58%). Fatigue (21%), hand-foot syndrome (19%) and rash (13%) were the most common TRAEs. Eight patients (15%) experienced grade 3-4 TRAEs, including rash (n=3), hand-foot syndrome (n=2), hypertension (n=1), myocardial enzyme elevation (n=1) and visual field loss (n=1). No treatment-related death occurred. Conclusions: The combination of regorafenib plus PD-1 inhibitors was generally tolerated and exhibited potential benefit in terms of OS and DCR. The presence of baseline liver metastases was predictive for shorter PFS but requires further investigation. Disease control rate of different PD-1 inhibitors.[Table: see text]

scholarly journals HER2 and BRAF mutation in colorectal cancer patients: a retrospective study in Eastern China

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8602 ◽  
Author(s):  
Xiangyan Zhang ◽  
Jie Wu ◽  
Lili Wang ◽  
Han Zhao ◽  
Hong Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Eastern China ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Molecular Classification ◽  
Clinicopathological Characteristics ◽  
Stage I ◽  
Chinese Patients ◽  
Poor Differentiation ◽  
Colorectal Cancer Patients

Objective To investigate the frequency and prognostic role of the human epidermal growth factor receptor 2 gene (HER2) and BRAF V600E gene mutation in Chinese patients with colorectal cancer (CRC). Methods Clinicopathological and survival information from 480 patients with stage I–III CRC were reviewed and recorded. HER2 amplification was analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), BRAF V600E mutation was tested by IHC and Sanger sequencing. The relationship between HER2 and BRAF V600E mutation status and clinicopathological characteristics and outcomes were determined. Results The amplification of HER2 and BRAF V600E mutation were identified in 27 of 480 (5.63%) and 19 of 480 (3.96%) CRC patients, respectively. HER2 amplification significantly correlated with greater bowel wall invasion (P = 0.041) and more advanced TNM stage (I vs. II vs. III; 0 vs 5.78% vs. 7.41%, P = 0.013). Patients suffering from tumors with poor differentiation had a higher incidence rate of BRAF V600E mutation than those with moderate/well differentiation (7.77% vs 2.92%, P = 0.04). HER2 amplification was an independent prognostic factor for worse disease-free survival (DFS) (HR = 2.53, 95% CI: 1.21–5.30, P = 0.014). Conclusion The prevalence of HER2 amplification and BRAF V600E mutation in stage I–III CRC patients in Chinese was 6% and 4%, respectively, and HER2 amplification appeared to be associated with a worse DFS. More comprehensive molecular classification and survival analysis are needed to validate our findings.

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