Meat consumption and BRAF mutation status in colorectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15135-e15135
Author(s):  
Rosa L. Frias ◽  
Michael Lam ◽  
Michael J. Overman ◽  
Van K. Morris ◽  
David R. Fogelman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Logistic Regression ◽  
Meat Consumption ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
P Value ◽  
Mutation Status ◽  
Molecular Features ◽  
Total Meat

e15135 Background: Consumption of red and processed meat has been associated with increased risk of developing colorectal cancers, but less is known about the association of meat consumption with tumor molecular features. In this study, we tested the association of total meat consumption with molecular features of colorectal cancer and overall survival in a local cohort of patients. Methods: Data on meat consumption were collected using self-directed environmental surveys from patients with stage IV/locally advanced, treatment refractory colorectal cancer who were enrolled on the Assessment of Targeted Therapies Against Colorectal Cancer clinical protocol. Data on tumor molecular features were collected through medical record review. Patients were categorized into low, medium or high meat consumption groups based on servings per day tertile. Associations between tumor molecular features and meat intake were evaluated by Chi-square and logistic regression. Potential effects of meat consumption on overall survival were assessed using Cox Proportional Hazards models. Analyses were conducted with IBM SPSS v25. Results: Patients consumed an average of 0.74, 1.57 and 3.32 servings of meat per day in the low, medium and high categories, respectively. Out of 593 patients with evaluable data, 27 were found to have a BRAF V600E mutation. Total meat consumption differed significantly by BRAF V600E mutation status (p value 0.02) and by sex (p value < .01), but did not differ by tumor location, microsatellite instability, or RAS mutation status. Using logistic regression, we found that compared to patients with the highest level of meat consumption, those in the medium consumption group may be less likely to have a BRAF V600E mutation (OR 0.24; p value 0.08). Although meat consumption may be associated with BRAF mutation status, it was not predictive of overall survival in our analyses. Conclusions: Among patients in our study, meat consumption may be associated with tumor BRAF V600E mutation status but is not directly associated with survival. Additional work is needed to test this association in cohorts including more BRAF mutant cases. If confirmed, this finding may add further insight into the etiology and biology of these tumors.

Clinicopathologic features and impact of metastasectomy in patients with BRAF-mutant metastatic colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15547-e15547
Author(s):  
Jianwei Zhang ◽  
Cailu Shen ◽  
Jianxia Li ◽  
Zehua Wu ◽  
Huabin Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Systemic Treatment ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Clinicopathologic Features ◽  
Significant Difference ◽  
The Impact ◽  
Braf Mutant

e15547 Background: BRAF V600E mutation is associated with poor prognosis in patients with metastatic colorectal cancer (mCRC), while the non-V600E mutation mCRC patients showed better prognosis than that of V600E mutation. The clinicopathologic features between V600E and non-V600E mutation has not yet been fully evaluated. And the impact of metastasectomy for patients with BRAF-mutant mCRC was not well-known. Methods: A retrospective study was conducted to evaluate the clinical and pathological characteristics of patients with BRAF-mutant mCRC. Next generation sequencing (22-gene panel) was performed in some of the patients. Survival was also analyzed in the cohort of BRAF V600E and non-V600E mutation with or without metastasectomy. Results: Between December 2014 and August 2020, 116 patients with BRAF-mutant mCRC were enrolled, including 94 patients with BRAF V600E mutation and 22 patients with non-V600E mutation. Significant difference was observed in the prevalence of peritoneal metastasis (69.1% vs. 27.3%, P = 0.001) and lung metastasis (11.7% vs. 36.4%, P = 0.009) between BRAF V600E mutation and non-V600E mutations. In genomic profile, SMAD4 mutation (30.7% vs. 13.7%) showed higher prevalence in patients with BRAF V600E mutation than that of non-V600E mutations, while RAS mutation (18.2% vs. 6.4%) and FBXW7 mutation (13.7% vs 3.1%) had higher incidence in BRAF non-V600E mutations than that of V600E mutation. Patients with BRAF V600E mutation showed a poorer overall survival than those with non-V600E mutations (13.9 vs. 26.8 months, P = 0.038). Totally, 46 patients received metastasectomy after systemic treatment. The median survival for BRAF V600E patients with or without metastasectomy was not reach (42.3+ months) vs. 8.3 months, respectively ( P < 0.001), and for non-V600E patients with or without metastasectomy was not reach (64.2+ months) vs. 23.3 months, respectively (P < 0.001). In multivariate analysis, ECOG performance status (0-1 vs. 2) ( P = 0.001), Staging (IVa-b vs. IVc) ( P = 0.01) and metastasectomy ( P = 0.001) were independent prognostic factors of overall survival. Conclusions: BRAF V600E mutation defines a subgroup of mCRC with worse prognosis. Metastasectomy might improve the survival benefit in carefully selected BRAF-mutant mCRC patients after systemic treatment.

scholarly journals Significance of BRAF V600E Mutation and Cytomorphological Features for the Optimization of Papillary Thyroid Cancer Diagnostics in Cytologically Indeterminate Thyroid Nodules

2018 ◽  
Vol 127 (04) ◽  
pp. 247-254 ◽  
Author(s):  
Augustas Beiša ◽  
Mindaugas Kvietkauskas ◽  
Virgilijus Beiša ◽  
Mindaugas Stoškus ◽  
Elvyra Ostanevičiūtė ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Thyroid Cancer ◽  
Logistic Regression Model ◽  
Thyroid Nodules ◽  
Needle Aspiration ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Mutation Status ◽  
Fine Needle

Abstract Background Ultrasound guided fine needle aspiration biopsy with cytologic analysis is an initial step in diagnostic of thyroid nodules. Unfortunately, up to 30% of biopsies are indeterminate and diagnostic surgery is required. The aim of this study was to estimate the diagnostic value of BRAF V600E mutation status combined with cytomorphological features for diagnosis of papillary thyroid cancer (PTC) in cytologically indeterminate thyroid nodules. Methods A prospective study analyzed patients who had ultrasound suspicious thyroid nodules, underwent fine needle aspiration and cytological examination, and were classified according to the Bethesda system. Patients from indeterminate diagnostic categories were examined for BRAF V600E mutation and 22 cytomorphological features, and underwent thyroid surgery. A binary logistic regression model was used to evaluate the diagnostic utility. Results A total of 219 patients met study criteria. After histological examination, 77 (35.2%) patients were diagnosed with PTC and 142 (64.8%) with benign nodular thyroid disease. According to logistic regression model, significant features for PTC diagnosis were: liquid colloid consistency, papillary structures, eosinophilic colloid bodies, and BRAF V600E mutation. Risk groups classified by this model have sensitivity of 80.5% (95% CI: 69.9 to 88.7), specificity of 99.3% (95% CI: 96.1 to 100), positive predictive value of 98.4% (95% CI: 89.8 to 99.8), negative predictive value of 90.4% (95% CI: 85.7 to 93.7), and accuracy of 92.7% (95% CI: 88.4 to 95.8) for PTC diagnosis. Conclusions Evaluation of BRAF V600E mutation status combined with cytomorphological features for diagnosis of PTC in cytologically indeterminate thyroid nodules can significantly improve diagnostic accuracy and reduce the number of diagnostic operations (calculator available at www.ptc-calc.we2host.lt).

scholarly journals Frequency detection of BRAF V600E mutation in a cohort of pediatric langerhans cell histiocytosis patients by next-generation sequencing

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shunqiao Feng ◽  
Lin Han ◽  
Mei Yue ◽  
Dixiao Zhong ◽  
Jing Cao ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Langerhans Cell Histiocytosis ◽  
Mutation Screening ◽  
Langerhans Cell ◽  
Braf V600e ◽  
P Value ◽  
Type I ◽  
Next Generation ◽  
Mutation Status ◽  
Generation Sequencing

Abstract Background Langerhans cell histiocytosis (LCH) is a rare neoplastic disease that occurs in both children and adults, and BRAF V600E is detected in up to 64% of the patients. Several studies have discussed the associations between BRAF V600E mutation and clinicopathological manifestations, but no clear conclusions have been drawn regarding the clinical significance of the mutation in pediatric patients. Results We retrieved the clinical information for 148 pediatric LCH patients and investigated the BRAF V600E mutation using next-generation sequencing alone or with droplet digital PCR. The overall positive rate of BRAF V600E was 60/148 (41%). The type of sample (peripheral blood and formalin-fixed paraffin-embedded tissue) used for testing was significantly associated with the BRAF V600E mutation status (p-value = 0.000 and 0.000). The risk of recurrence declined in patients who received targeted therapy (p-value = 0.006; hazard ratio 0.164, 95%CI: 0.046 to 0.583). However, no correlation was found between the BRAF V600E status and gender, age, stage, specific organ affected, TP53 mutation status, masses close to the lesion or recurrence. Conclusions This is the largest pediatric LCH study conducted with a Chinese population to date. BRAF V600E in LCH may occur less in East Asian populations than in other ethnic groups, regardless of age. Biopsy tissue is a more sensitive sample for BRAF mutation screening because not all of circulating DNA is tumoral. Approaches with low limit of detection or high sensitivity are recommended for mutation screening to avoid type I and II errors.

scholarly journals IL15RA and SMAD3 Genetic Variants Predict Overall Survival in Metastatic Colorectal Cancer Patients Treated with FOLFIRI Therapy: A New Paradigm

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1705
Author(s):  
Elena De Mattia ◽  
Jerry Polesel ◽  
Rossana Roncato ◽  
Adrien Labriet ◽  
Alessia Bignucolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Prognostic Score ◽  
Chemotherapeutic Agents ◽  
Rank Test ◽  
P Value ◽  
Genetic Determinants ◽  
New Paradigm

A new paradigm in cancer chemotherapy derives from the interaction between chemotherapeutics, including irinotecan and 5-fluorouracil (5-FU), and the immune system. The patient’s immune response can modulate chemotherapy effectiveness, and, on the other hand, chemotherapeutic agents can foster tumor cell immunogenicity. On these grounds, the analysis of the cancer patients’ immunogenetic characteristics and their effect on survival after chemotherapy represent a new frontier. This study aims to identify genetic determinants in the immuno-related pathways predictive of overall survival (OS) after FOLFIRI (irinotecan, 5-FU, leucovorin) therapy. Two independent cohorts comprising a total of 335 patients with metastatic colorectal cancer (mCRC) homogeneously treated with first-line FOLFIRI were included in the study. The prognostic effect of 192 tagging genetic polymorphisms in 34 immune-related genes was evaluated using the bead array technology. The IL15RA rs7910212-C allele was associated with worse OS in both discovery (HR: 1.57, p = 0.0327, Bootstrap p-value = 0.0280) and replication (HR:1.71, p = 0.0411) cohorts. Conversely, SMAD3 rs7179840-C allele was associated with better OS in both discovery (HR:0.65, p = 0.0202, Bootstrap p-value = 0.0203) and replication (HR:0.61, p = 0.0216) cohorts. A genetic prognostic score was generated integrating IL15RA-rs7910212 and SMAD3-rs7179840 markers with inflammation-related prognostic polymorphisms we previously identified in the same study population (i.e., PXR [NR1I2]-rs1054190, VDR-rs7299460). The calculated genetic score successfully discriminated patients with different survival probabilities (p < 0.0001 log-rank test). These findings provide new insight on the prognostic value of genetic determinants, such as IL15RA and SMAD3 markers, and could offer a new decision tool to improve the clinical management of patients with mCRC receiving FOLFIRI.

Efficacy and prognostic significance of triflurodine/tipiracil beyond oxaliplatin and irinotecan based chemotherapy in patients with refractory metastatic colorectal cancer: An observational multicenter study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15586-e15586
Author(s):  
Mohamed Alghamdi ◽  
Shouki Bazarbashi ◽  
Elsamany Shereef ◽  
Mervat Mahrous ◽  
Omar Al shaer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Saudi Arabia ◽  
Neutrophil Count ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
P Value ◽  
Second Line ◽  
First Line ◽  
Free Survival

e15586 Background: In Saudi Arabia, the incidence of colorectal cancer has been increased over the past few years. The optimal treatment beyond the second line is not fully understood. To the best of our knowledge, the efficacy and disease outcomes of triflurodine/tipiracil in Saudi patients with refractory metastatic colorectal cancer(mCRC) has not been studied yet. Our study is a real-life practice evaluation of the efficacy of triflurodine/tipiracil in patients with refractory mCRC. Moreover, the prognosis and the prognostic significance of the different clinical variables have been analyzed. Methods: A retrospective, multi-centers ( 5 centers representative of Saudi Arabia )observational study in patients with mCRC who have received triflurodine/tipiracil beyond oxaliplatin & Irinotecan-based chemotherapy between December 2018-December 2020.We aimed to assess the response to triflurodine/tipiracil, to evaluate the progression-free survival (PFS ), the overall survival (OS), and the associated factors of prognostic significance. Results:The data of 100 patients with refractory mCRC who has received triflurodine/tipiracil have been analyzed. The mean age was 55.2 +11.8 years. Forty-two patients were (42%) females and 58 (58%) were male patients. Sigmoid was the most common primary site of cancer in 35 (35%) patients, followed by rectum 29 (29%). Peritoneal metastasis was present in 17 (23.3%) patients ,liver in 51(56.6%) and lung in 39 (50.7%). Metastatic sites were ≥ 2 in 45 (45%) patients. Metastatic lesions were ≥ 5 in 65 (65%) patients. Xelox chemotherapy regimen was the most commonly used first-line chemotherapy which represents 43%, while Folfiri or Xeliri combination was the most used second line in 57 (60%). For the third line, Folfox or Xelox was used in 81 (83.5%) patients. The fourth line was given to 49 (67.1%). For first-line biological agents, Cetuximab was used most frequently 31 (46.3%).Evaluation of the response to treatment with triflurodine/tipiracil revealed one patient (1%) with a complete response,3 patients (3%) with partial response, 28 (28%) patients with stable disease, and 66 (66%) showed progressive disease. The estimated median progression-free survival was 5 months ( 3.839 - 6.161) and the median overall survival was 12 months (9.732-14.268). The log-rank analysis showed that the baseline neutrophils ≤ 75 % ( P-value= 0.0092) and low hemoglobin level (P-value= 0.0245) were strongly associated with a higher survival. By multivariate Cox regression analysis, the neutrophil count ≤ 75 % was the only independent predictor for survival. Conclusions: Trifluridine/tipiracil is effective in patients with refractory mCRC. The low neutrophil count might predict a better overall survival.

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

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]

scholarly journals BRAF V600E mutation in metastatic colorectal cancer: Methods of detection and correlation with clinical and pathologic features

2016 ◽  
Vol 17 (8) ◽  
pp. 840-848 ◽  
Author(s):  
Cristin Roma ◽  
Anna Maria Rachiglio ◽  
Raffaella Pasquale ◽  
Francesca Fenizia ◽  
Alessia Iannaccone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Pathologic Features

Impact of clinical and molecular features on risk of recurrence following curative intent resection of metastases in metastatic colorectal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 785-785
Author(s):  
Matthew E. Burge ◽  
Belinda Lee ◽  
Margaret Lee ◽  
Rachel Wong ◽  
Phillip Parente ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Primary Tumour ◽  
Clinical Predictors ◽  
Curative Intent ◽  
Mutation Status ◽  
Molecular Features ◽  
Kaplan Meier ◽  
Resection Of Metastases ◽  
Primary 76

785 Background: Resection of metastases with curative intent is an integral component of mCRC management. However, relapse rates are high and identifying patients most likely to benefit from this approach is of considerable importance. Among patients with mCRC, mutations (mt) in RAS and BRAF genes portent a worse prognosis. Our hypothesis, therefore, is that patients harbouring these mutations may have a higher relapse rate after resection of metastases. We also wished to analyse clinical predictors of relapse, including site of metastases. Methods: We interrogated the TRACC database of patients undergoing resection with curative intent who had mutation status available. The frequency of RAS and BRAF mt was established and their association with clinical parameters determined. Relapse free (RFS) and overall survival (OS), from the date of resection, was estimated for the mt and wild type (wt) groups using the Kaplan Meier method. Multivariate analysis is planned to investigate factors associated with RFS, including stage of the primary tumour, synchronous metastases, site and number of metastases, CEA, peri-operative chemotherapy use, site of the primary (left v right) and RAS and BRAF mutation status. Results: 188 patients were identified. 89 were KRAS/BRAF wt, 92 KRAS mt and 7 BRAF mt. 40% had presented with metastatic disease and 27% had a right sided primary. 76%, 22% and 2% underwent resection of liver, lung or both metastases. Microscopic resection margin was involved in 6%. Resection was performed prior to any chemotherapy in 48%. No difference was seen in relapse free or overall survival between the mt and wt groups. Conclusions: We found no difference in relapse free or overall survival by mutation subgroup suggesting this should not influence suitability for curative intent resection, but analyses is planned on a much larger cohort once data is available. A multivariate analysis, adjusting for important prognostic variables, is planned.

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