scholarly journals Survival Outcomes of Metastatic Colorectal Cancer Patients in Brunei Darussalam and the Impact of KRAS Mutations

2020 ◽  
Author(s):  
Datul Damit ◽  
Ravi Patnaik ◽  
Liling Chaw ◽  
Shir Kiong Lu ◽  
Telisinghe Pemasiri Upali ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Survival Outcome ◽  
Survival Outcomes ◽  
P Value ◽  
Wild Type ◽  
Kras Gene ◽  
Brunei Darussalam ◽  
Significant Difference ◽  
Chi Squared

Colorectal cancer (CRC) is the third most common cancer, with rising incidence due to lifestyle and diet. 40% of CRC cases are found to have KRAS mutations. In this study, we investigate the survival outcome of metastatic Colorectal cancer mCRC) patients in Brunei Darussalam restrospectively. Chi-squared test was used to compare the survival outcomes of mCRC patients, and Mann-Whitney U test was used to compare the median ages of both groups. Kaplan-Meier survival curves were drawn and logrank test was used to compare the survival outcome between two groups. There was a total of 105 patients with stage IV CRC being treated during the study period. 81.6% (n=62) of mCRC patients were found to have the primary tumours on the left side of the colon. 19 of these 26 (73.1%) mutant KRAS mCRC patients died, while 23 of 50 (46.0%) wild-type KRAS mCRC patients died at the end of the study period, contributing to death rates of 45.2% and 54.8%, correspondingly. 30.3% (n=23) of the study population had a single metastatic site detected (either liver, or lung or any other organs), while 69.7% (n=53) of the 76 mCRC patients had two (double) or more metastatic sites. 69.2% (n=18) and 30.8% (n=8) of the mutant KRAS mCRC patients had mutations within codons 12 and 13, respectively. To our knowledge, this is the first study in Brunei Darussalam to analyse both the survival outcomes of metastatic CRC patients and those of mutant KRAS mCRC patients. Chi-squared analysis showed a significant difference between the survival outcomes of wild-type KRAS and mutant KRAS mCRC patients (p-value = 0.024). There was a significant difference in the survival outcome between the mutant KRAS mCRC patients with RCC and mutant KRAS mCRC with LCC patients. There was no significant difference between the survival outcomes of mutant KRAS patients with mutations in either codon 12 or 13 of the KRAS gene (Table 3). However, there is a significant difference in the median survival periods between the mutant KRAS mCRC patients with mutations in codon 12 and those with mutation in codon 13 of the KRAS gene (p-value = 0.003). In conclusion, we found that mutant KRAS mCRC patients had a significantly poorer OS, which was shown to be worse when the primary tumours were found at the left side of the colon. Mutant KRAS mCRC patients with mutations in codon 12 were found to have shorter survival median periods than those with mutations within codon 13.

Abstract 529: A Modern Large-scale Analysis of Heart Transplantation in Elderly Patients

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Manish Suryapalam ◽  
Mohammed Kashem ◽  
Val Rakita ◽  
Yoshiya Toyoda
Keyword(s):  
Heart Transplantation ◽  
Large Scale ◽  
Age Groups ◽  
The Elderly ◽  
Survival Outcome ◽  
Outcome Analysis ◽  
Survival Outcomes ◽  
Ischemic Time ◽  
Significant Difference ◽  
Chi Squared

Introduction: As the prevalence of heart failure increases among older patients, the potential role of heart transplant (HTx) in this demographic demands further investigation. Survival outcome analysis of the elderly has primarily been analyzed in single-center studies, and the few long term studies performed have included a timeframe to the 1980s, introducing substantial variance from much poorer survival outcomes. We investigated the 5 to 10 year survival outcomes of more modern heart transplantation patients by analyzing the UNOS database. Methods: Heart transplantation data for 32,337 patients (2000-2014) was divided into three different age groups- <60, 60-69, and ≥70 years old. Gender, ethnicity, height, weight, BMI, ICU stay, ischemic time, length of stay (LOS), and creatinine level were evaluated for significance using Chi-Squared and H-Tests as appropriate (p<0.05). Survival outcome was assessed using a Kaplan-Meier Curve and log-rank tests. Results: 23,267 were <60, 8,459 were 60-69, and 611 were ≥70, with mean ages of 38±0.1, 64±0.0, and 72±0.1 respectively. The distribution of gender, ethnicity, ischemic time, BMI, height, and weight was significantly different between the cohorts, with p=0.000 for all. Survival analysis indicated complete pairwise significance at 10 years post-HTx, with overall significance of p=0.000. At 5 years post-HTx, only 60-69 vs ≥70 did not have pairwise significance in survival. Conclusion: Contrary to prior studies, results indicate a statistically significant difference in survival the older and younger cohorts. This difference is especially prominent at the 10 th year post-transplant, but can be seen even at the 5 th year.

scholarly journals Comparison of Survival Rates of Stainless-Steel Crowns Placed with and without Pulpotomy: A Two-Year Retrospective Study

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Fatmah N. AlMotawah ◽  
Sharat Chandra Pani ◽  
Tala AlKharashi ◽  
Saleh AlKhalaf ◽  
Mohammed AlKhathlan ◽  
...  
Keyword(s):  
Stainless Steel ◽  
General Anesthesia ◽  
Survival Rates ◽  
Survival Outcome ◽  
Survival Outcomes ◽  
Proximal Caries ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Chi Squared

Aim. This study aimed to retrospectively compare the survival outcomes over two years between teeth with proximal dental caries that were restored with stainless-steel crowns to those that were pulpotomized and then restored with a stainless-steel crown in patients who were rehabilitated under general anesthesia. Participants and Methods. The records of 131 patients aged between two to six years who had stainless-steel crowns placed under general anesthesia and had two-year follow-up were screened. 340 teeth with moderate proximal caries on the radiograph (D2) were included in the study. Of these, 164 teeth were treated with a pulpotomy and stainless-steel crown, while 176 teeth were crowned without a pulpotomy. The type of each tooth was compared using the Chi-squared test and Kaplan–Meier survival analysis, and curves were plotted based on the two-year outcomes. Results. Treatment: the sample comprised 59 males (mean age 4.73 years, SD ± 1.4 years) and 72 females (mean age 5.2 years, SD ± 2.0 years). The Kaplan–Meier regression model showed no significant difference in survival outcomes between teeth that had been pulpotomized and those that had not ( p  = 0.283). Conclusion. Within the limitations of the current study, we can conclude that performing a pulpotomy does not influence the survival outcome of mild/moderate proximal caries restored with stainless-steel crowns under general anesthesia.

scholarly journals Correlation between UGT1A1 gene polymorphism and irinotecan chemotherapy in metastatic colorectal cancer：a study from Guangxi Zhuang

2020 ◽  
Author(s):  
Shaojun Chen ◽  
Li Hua ◽  
Chenjun Feng ◽  
Qia Mo ◽  
Mengzhuan Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Polymorphism ◽  
Metastatic Colorectal Cancer ◽  
Heterozygous Mutation ◽  
Wild Type ◽  
Ugt1a1 Gene ◽  
Geographical Regions ◽  
Significant Difference ◽  
Homozygous Mutant ◽  
Grade 3

Abstract Background: UGTlA1 gene polymorphism has different distribution in different ethnicities, geographical regions and ethnic groups, which may lead to different toxicity and efficacy of irinotecan. The study aimed to explore the correlation of UGT1A1 gene polymorphism of Guangxi Zhuang metastatic colorectal cancer (mCRC) with irinotecan -based chemotherapy, in order to develop an individualized irinotecan regimen for mCRC patients of Guangxi Zhuang. Methods: From June 2013 and June 2015, a total of 406 patients of Guangxi who were histologically diagnosed as metastatic colorectal cancer with 102 patients of this cohort with three generations of Zhuang, and 86 patients that conformed to inclusion and exclusion criteria were competitively enrolled . The distribution of UGT1A1 gene polymorphism was analyzed-retrospectively in all patients. Pyrosequencing method was used to detect the UGT1A1 * 28 and * 6 gene polymorphism in the 86 Guangxi Zhuang mCRC patients. After first-line chemotherapy with FOLFIRI regimen, the relationship between gene polymorphism of UGT1A1 and adverse reactions, and efficacy of Irinotecan were analyzed with χ2 test and Kaplan-Meier method.Results: UGT1A1 * 28 wild-type (TA6 / 6), heterozygous mutant (TA6 /7) and homozygous mutant (TA7 / 7) accounted for 69.8%, 30.2% and 0%, respectively. UGT1A1 * 6 wild type (G / G), heterozygous mutation type (G / A) and homozygous mutant (A / A) accounted for 76.7%，20.9% and 2.3%，respectively.UGT1A1 * 28 TA6 / 7 type could increase the risk of grade 3-4 diarrhea (P=0.027), which did not increase the risk of grade 3-4 neutropenia (P=0.092). UGT1A1 * 6 G / A and A / A type could increase the risk of grade 3-4 diarrhea and neutropenia (P=0.001; P=0.017). After chemotherapy with FOLFIRI, there was no significant difference in response rate (RR) (P=0.729; P=0.745) or in median progression-free survival (mPFS) between the wild-type, mutant treatment of UGT1A1 * 28 and UGT1A1 * 6 (7.0 m vs 7.4 m, P=0.427; 6.9 m vs 7.0m P=0.408).Conclusions: The distribution of UGT1A1*28 and UGT1A1* 6 gene polymorphism in Guangxi Zhuang patients were differed from the existing reported of European people and Chinese Han population. The UGT1A1 gene polymorphism with irinotecan chemotherapy-associated diarrhea and neutropenia were closely related. There was no significant association between UGT1A1 gene polymorphism and therapeutic efficacy of irinotecan.

Use of the intensity of membranous EGFR staining by immunohistochemistry to predict the efficacy of chemotherapy containing cetuximab in KRAS wild-type patients with metastatic colorectal cancer: A retrospective analysis.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 516-516
Author(s):  
Naoki Takahashi ◽  
Yasuhide Yamada ◽  
Hirokazu Taniguchi ◽  
Kohei Akiyoshi ◽  
Yoshitaka Honma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Kras Mutation ◽  
Objective Response ◽  
Endoscopic Biopsy ◽  
Rank Test ◽  
Wild Type ◽  
Mutation Status ◽  
Significant Difference ◽  
Kras Mutation Status

516 Background: KRAS mutation status is a strong predictive factor for anti-EGFR monoclonal antibody therapy efficacy in metastatic colorectal cancer (mCRC). In the BOND trial, objective response rates to cetuximab in irinotecan-refractory mCRC were not significantly different based on the intensity of EGFR staining by immunohistrochemistry (IHC). However, this result was not evaluated by KRAS mutation status, so we retrospectively evaluated the relationship between the efficacy of chemotherapy containing cetuximab and the intensity of membranous EGFR staining in KRAS wild type (KRAS-WT) patients. Methods: Between August 2008 and July 2011, specimens of 391 CRC patients were collected by endoscopic biopsy or surgical resection. EGFR staining by IHC and genetic screening for KRAS status were performed and intensity of EGFR staining was scored by the Guidelines for Interpreting EGFR pharmDx, DAKO. We analyzed 94 KRAS-WT patients who received combination chemotherapy with an irinotecan-regimen plus cetuximab or cetuximab monotherapy and met the following criteria: histologically proven mCRC adenocarcinoma , at least 1 previous regimen of standard fluoropyrimidine - containing chemotherapy , ECOG PS score 0-2, and adequate hepatic and renal function. Patients were classified into 2 groups by intensity of EGFR staining: (A) absence of staining and weakly to moderately positive (IHC 1+ and IHC 2+), (B) strongly positive (IHC 3+). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and compared in Groups A and B by the log-rank test. Results: There was no significant difference in patient characteristics between the 2 groups except for primary site. The median PFS of Groups A (n=76) and B (n=18) were 5.4 months and 9.1 months (p= 0.029), the median OS was 8.1 months and 13.2 months (p=0.054) and response rate was 20.1% and 33.3%, respectively. Conclusions: In KRAS-WT patients with fluoropyrimidine-containing chemotherapy-refractory mCRC, strong intensity of EGFR staining by IHC might be predictive for efficacy of chemotherapy containing cetuximab.

Safety and efficacy of the addition of simvastatin to panitumumab in KRAS mutant metastatic colorectal cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14558-e14558
Author(s):  
Henk-jan Guchelaar ◽  
Jara M Baas ◽  
Lisanne Krens ◽  
Monique M.E.M. Bos ◽  
Johanna Elisabeth A. Portielje ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Colorectal Tumors ◽  
Wild Type ◽  
Kras Gene ◽  
Once Daily ◽  
Colorectal Cancer Patients

e14558 Background: Epithelial growth factor receptor (EGFR) inhibitors are not effective in KRAS mutant colorectal tumors. In these tumors the k-ras protein is activated by post-translational modification by binding farnesyl (C15) and geranylgeranyl (C17) moieties. Both are products of the mevalonate pathway, as is cholesterol. Statins (HMG-CoA-reductase inhibitors) not only inhibit synthesis of cholesterol, but also of C15 and C17 and thus may relevantly inhibit post-translational activation of ras proteins. Therefore, statins may inhibit the expression of the mutant KRAS phenotype and normalize the phenotype into KRAS wild type. In a phase II study we investigated whether simvastatin treatment renders KRAS mutant colorectal tumors sensitive to panitumumab. Methods: Major eligibility criteria were advanced or metastatic colorectal cancer failing prior 5FU, oxaliplatin and irinotecan containing regimens, with a mutation in codon 12, 13 or 61 of KRAS gene on tumor sample. Patients were treated with simvastatin 80mg once daily and panitumumab 6mg/kg every 2 weeks. Primary objective was to investigate the percentage of patients free from progression and alive 11 weeks after the first administration of panitumumab. This phase II study was performed in a Simon two stage design, performing an interim analysis after the enrolment of 15 patients. When at least 6 of these patients (i.e. 40%) were to be alive and free from progression free at 11 weeks after the first administration of panitumumab (similar to the results of the KRAS wild type population of the phase III study), another 31 patients would be included during stage 2. Results: Fifteen evaluable patients were enrolled by 4 study sites. Only one patient was free from progression 11 weeks after start of panitumumab treatment (6.7%). Mean progression free survival was 9.1 weeks (range 5-17 weeks). Most frequent reported side effect was skin toxicity (40%), one patient experienced myositis grade 3. Conclusions: Simvastatin 80mg once daily was not able to inhibit the KRAS mutant phenotype sufficiently to reach sensitivity to panitumumab in colorectal cancer patients with a mutation in the KRAS gene. Clinical trial information: NCT01110785.

Survival outcomes in patients (pts) with KRAS/NRAS (RAS) wild-type (WT) metastatic colorectal cancer (mCRC) and non-liver-limited disease (non-LLD): Data from the PRIME study.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 3550-3550 ◽  
Author(s):  
Jean-Yves Douillard ◽  
Josep Tabernero ◽  
Salvatore Siena ◽  
Marc Peeters ◽  
Reija Koukakis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Survival Outcomes ◽  
Wild Type ◽  
Limited Disease

Drug cost and outcome in metastatic colorectal cancer with emphasis on monoclonal antibodies.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 567-567
Author(s):  
Helmy M. Guirgis
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibodies ◽  
Metastatic Colorectal Cancer ◽  
Drug Cost ◽  
Outcome Evaluation ◽  
Wild Type ◽  
First Line ◽  
Significant Difference ◽  
Number Of Cycles ◽  
The Cost

567 Background: Patients with wild type KRAS metastatic colorectal cancer (mCRC), treated with first-line cetuximab (Cet) or bevacizumab (Bev) and chemotherapy demonstrated similar overall survival (OS). In the Western world, costs of anticancer drugs ranged from $59,000 to $100,000 per life-year gain (LYG). Hazard ratios (HR) have rarely been integrated in cost/outcome evaluation. Objective: Weigh drug cost against survival and hazard ratio (HR) in mCRC with emphasis on monoclonal antibodies (MABs). Methods: Estimated costs in United States dollars (US$) were calculated for 70 kg or 1.7/m2 patients. Costs were divided by the reported median OS gain over control in days (OSg) and by probability of survival (PoS) calculated as (1.0 – HR). Relative values (RV) were computed as 100,000/cost/outcome. Results: There was no significant difference in cost/outcome of Pan and Cet in first-line wild KRAS mCRC. At 12 week (w), the cost/LYG of panitumumab (Pan), Cet, and Bev were $64,947, $82,224, and $36,919 with RVs of 1.54, 1.22 and 2.71 respectively. Using HRs, the corresponding PoS were $140,082, $137,040, and $42,524 with RVs of 0.71, 0.73, and 2.35. Wild RAS testing improved the cost/outcome of Pan by 25%. Increasing number of cycles increased the cost/outcome and decreased the RVs of all MOAs. Conclusions: In first-line wild KRAS mCRC at 12 w, the cost/outcome of Bev was approximately 30% to 57% that of Pan and Cet. Cost/outcome of Pan significantly improved in RAS wild type. The cost/outcome of MABs was determined by the number of cycles.

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