Risk factors for gastrointestinal perforations in patients with metastatic colorectal cancer receiving bevacizumab plus chemotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3535-3535 ◽  
Author(s):  
M. Sugrue ◽  
M. Kozloff ◽  
J. Hainsworth ◽  
S. Badarinath ◽  
A. Cohn ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Metastatic Colorectal Cancer ◽  
Potential Risk ◽  
Primary Tumor ◽  
Phase Iii ◽  
Community Based ◽  
Large Community ◽  
Significant Difference ◽  
Potential Risk Factors

3535 Background: Bevacizumab (BV) prolongs overall survival and progression-free survival when added to standard chemotherapy in patients (pts) with metastatic colorectal cancer (mCRC). BRiTE is a large, community-based observational registry of pts with mCRC receiving BV plus first-line chemotherapy (CT). Incidence rate, temporal pattern, and potential risk factors associated with gastrointestinal perforation (GIP) were explored. Methods: Baseline patient characteristics (BC), including prospectively identified potential risk factors for GIP, were collected at study entry. Safety data were collected every 3 months (mo). Logistic regression models, adjusted and unadjusted for treatment assignment, were used to identify BC potentially associated with GIP. Results: 1968 pts were enrolled between Feb 2004 and Jun 2005. Median study follow-up was 10 mo as of Nov 4, 2005. GIPs were observed in 34 pts (1.7%). For pts with GIP, median time to first event was 2.1 mo; the majority of events were non-fatal and occurred within the first 3 mo after starting BV. BC including GI medical history (chronic aspirin or NSAID use, peptic ulcer disease, diverticulosis) were similar in pts with or without GIP and with earlier or later GIP onset (≤ or >3 mo from start of BV). Although adjusted models did not show any significant BC, GIP rates were numerically higher in pts with primary tumor intact (2.6%) vs. resected (1.6%). Furthermore, univariate analyses revealed a significant difference between intact (2.3%) and resected (0.8%) primary tumor for earlier GIP (≤3 mo from start of BV). The majority of pts with GIP had at least one of the following: acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, tumor at GIP site, abdominal carcinomatosis, prior abdominal or pelvic radiation therapy. Conclusions: Preliminary analyses indicate the incidence of GIP in this large, community-based observational registry is similar to that previously reported in phase III mCRC trials with BV. No associations between specific BCs and an increased risk of GIP were identified. Patients with primary tumor intact were more likely to incur a GIP within the first 3 mo of starting BV and CT. [Table: see text]

Efficacy of bevacizumab plus chemotherapy as first-line treatment of patients with metastatic colorectal cancer: Updated results from a large observational registry in the US (BRiTE)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3537-3537 ◽  
Author(s):  
M. Kozloff ◽  
J. Hainsworth ◽  
S. Badarinath ◽  
A. Cohn ◽  
P. Flynn ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cox Regression ◽  
Seer Database ◽  
First Line ◽  
Community Based ◽  
Large Community ◽  
Primary Disease ◽  
Significant Difference ◽  
Disease Site

3537 Background: Bevacizumab (BV) prolongs overall survival and progression-free survival (PFS) when added to standard chemotherapy (CT) in patients with metastatic colorectal cancer (mCRC). BRiTE is a large, community-based observational registry of patients with mCRC receiving BV plus first-line CT. Safety and efficacy information in unselected patients with mCRC are collected. Chemotherapy regimen choice is at the physician’s discretion. Methods: 1968 patients receiving BV plus first-line CT were enrolled at 248 sites in 49 states between Feb 2004 and Jun 2005. Patients are followed for up to 3 years, with data reporting every 3 months (mo) including disease status as assessed by investigator using his/her method of choice. Patients were grouped twice by CT. Cox regression models, adjusted and unadjusted for treatment assignment, were used to identify baseline characteristics (BC) and differential chemotherapy effects on PFS. Results: Cohort demographics were consistent with the NCI Surveillance, Epidemiology, and End Results (SEER) database for mCRC. Median study follow-up was 10 months by Nov 4, 2005. CT regimens included FOLFOX (55.8%), FOLFIRI (14.1%), and IFL (9.7%). Based on observed progression events (n=800) or deaths (n=123), projected median PFS is 11.3 mo (95% CI: 10.4–11.7). Median PFS was comparable in patients treated with CT regimen based on irinotecan (11.3 mo), oxaliplatin (11.4 mo), or neither (10.2 mo) (CT Grouping 1); or 5FU infusion (11.5 mo), 5-FU bolus (9.7 mo), or capecitabine (11.6 mo) (CT Grouping 2). Significant BC in adjusted and unadjusted models are ECOG performance status (PS), primary disease site, and albumin, with no significant difference among CT regimens. Conclusions: This large, community-based registry included a patient population with demographics consistent with the SEER database for mCRC. Preliminary median PFS of 11.3 mo compares favorably to that reported in the pivotal trial. Median PFS appears to be comparable for all CTs when combined with BV. Higher baseline albumin, PS of 0, and primary disease site of rectum were associated with improved outcome. [Table: see text]

scholarly journals Correlation between Potential Risk Factors and Pulmonary Embolism in Sarcoidosis Patients Timely Treated

2021 ◽  
Vol 10 (11) ◽  
pp. 2462
Author(s):  
Barbara Ruaro ◽  
Paola Confalonieri ◽  
Mario Santagiuliana ◽  
Barbara Wade ◽  
Elisa Baratella ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Embolism ◽  
Potential Risk ◽  
Smoking Habit ◽  
Age At Diagnosis ◽  
Antiphospholipid Antibody ◽  
Increased Risk ◽  
Significant Difference ◽  
Antibody Positivity ◽  
Potential Risk Factors

Background. Some studies with inconclusive results have reported a link between sarcoidosis and an increased risk of pulmonary embolism (PE). This study aimed at assessing a possible correlation between potential risk factors and PE in sarcoidosis patients. Methods. A total of 256 sarcoidosis patients (84 males and 172 females; mean age at diagnosis 49 ± 13) were enrolled after giving written informed consent. Clinical evaluations, laboratory and radiology tests were performed to evaluate the presence of pulmonary embolism. Results. Fifteen sarcoidosis patients with PE (4 males and 11 females; mean age at diagnosis 50 ± 11), diagnosed by lung scintigraphy and 241 sarcoidosis patients without PE (80 males and 161 females; mean age at diagnosis 47 ± 13), were observed. There was a statistically significant increase of the presence of antiphospholipid antibodies in the sarcoidosis group with pulmonary embolism. There was no statistically significant difference between the two groups as to smoking habit, obesity or hereditary thrombophilia frequency (p > 0.05, respectively). Conclusions. This study demonstrates a significant correlation between the presence of antiphospholipid antibody positivity and the pulmonary embolism events in our sarcoidosis patients. Furthermore, we propose screening for these antibodies and monitoring, aimed at timely treatment.

scholarly journals Seroprevalence of infectious bursal disease and its potential risk factors in backyard chicken production of Waliso district, South Western Shoa Zone, Ethiopia

2021 ◽  
Vol 20 (1) ◽  
pp. 95-105
Author(s):  
Chala Bedasa ◽  
◽  
Ararsa Duguma ◽  
Asamenew Tesfaye ◽  
Tadele Tolosa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Potential Risk ◽  
Animal Health ◽  
Infectious Bursal Disease ◽  
Flock Size ◽  
Serum Samples ◽  
Significant Difference ◽  
Bursal Disease ◽  
Potential Risk Factors ◽  
Backyard Chicken

A cross sectional study on infectious bursal disease was conducted in apparently healthy backyard chicken at Waliso district of Southwestern Shoa, central oromia, Ethiopia from from November, 2018 to October, 2019. A total of 282 chickens were randomly selected to estimate seroprevalence of IBD infection and to identify the likely potential risk factors for the disease. Serum samples collected and serological test conducted in laboratory at National Animal Health Diagnosis and Investigation Center Sebeta, Ethopia. Out of 282 serum samples tested 224 were positive for indirect ELISA technique and the overall seroprevalence of IBDV in the study area was found to be 79.43% at individual level. Educational level of owners, kebeles and flock size significantly affect seroprevalence of IBD in the study area. The effect of difference in managements like source of replacement, frequency of house cleaning, use of disinfectant and isolation practice has a significant effect on IBDV sero-prevalence. A lower seroprevalence of IBDV was reported in good hygienic level of house (26.7%) than poor level of chicken house hygiene (96.4%) with statistically significant difference (P < 0.05). The seroprevalence of IBDV in the present study associated with chicken management, flock size, owner education level and other animal related risk factors for occurrence of the disease. Therefore, awareness on chicken health management, and importance of immunization would help to minimize the prevalence of the disease and play crucial role in the control of the disease. Furthermore, characterizing virus strains circulating in the area in future study is recommended.

scholarly journals Systemic therapy for colorectal cancer

2003 ◽  
Vol 11 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Borut Stabuc
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Metastatic Colorectal Cancer ◽  
Adjuvant Treatment ◽  
Randomized Clinical Trials ◽  
Response Rate ◽  
Phase Iii ◽  
Oral Fluoropyrimidines ◽  
Significant Difference

Colorectal cancer alone accounts for around 200,000 deaths in Europe and represents a significant health problem. Although about fifty percent of patients are cured by surgery alone, the other half will eventually die due to metastatic disease, which includes approximately 25% of patients who have evidence of metastases at the time of diagnosis. Surgical resection of the primary tumor and regional lymph nodes is the only curative therapy for colorectal cancer. However, adjuvant chemotherapy in stage III for colon cancer following curative resection has been shown to reduce the risk of recurrence by 19-40% and of death by 16-33%. Today, 5-fluoroUracil and Leucovorin given for six months may represent the best adjuvant treatment available The contribution of levamisole to adjuvant treatment seems to be marginal, if any. The benefit of adjuvant chemotherapy for the patients with Dukes B colon cancer is less clear. A meta-analysis of 1,381 patients with advanced colorectal cancer showed a significant increase in response rate with the bolus 5-fluoroUracil and Leucovorin versus 5-fluoroUracil alone but no significant difference in median survival. Continuous infusion allows higher doses of 5-FU than rapid bolus infusion and improves response rate survival and time to progression. Oral fluoropyrimidines (capecitabine and Uracil/Tegafur [UFT]) are as active as intravenous fluoropyrimidines. Compared to intravenous 5FU, oral fluoropyrimidines have safety advantages clinical benefits, and are more convenient for patients. Phase III randomized clinical trials in patients with metastatic colorectal cancer demonstrate the significant superiority of combining irinotecan with 5-fluoroUracil and Leucovorin or oxaliplatin with 5-fluoroUracil and Leucovorin over the same 5-fluoroUracil and Leucovorin alone. Several phase II studies have shown that the combination of the oral fluoropyrimidines plus irinotecan or oxaliplatin is very active in metastatic colorectal cancer. Trials with agents acting on novel targets in colorectal cancer are progressing rapidly, including doxifluridine, new inhibitors of thymidylate synthase (ZD9331), oral camptothecins (Rubitecan), multitarget antifolate antimetabolite (Premetrexet), inhibitors of epidermal growth factor receptor (Cetuximab), COX-2 inhibitors (celecoxib) and farnesyltransferaze inhibitors (Zarnestra). However, a few randomized trials failed to show a survival advantage compared with placebo in patients with advanced refractory colorectal cancer.

scholarly journals Mutational Analysis of Patients With Colorectal Cancer in CALGB/SWOG 80405 Identifies New Roles of Microsatellite Instability and Tumor Mutational Burden for Patient Outcome

2019 ◽  
Vol 37 (14) ◽  
pp. 1217-1227 ◽  
Author(s):  
Federico Innocenti ◽  
Fang-Shu Ou ◽  
Xueping Qu ◽  
Tyler J. Zemla ◽  
Donna Niedzwiecki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Metastatic Colorectal Cancer ◽  
Mutational Analysis ◽  
Gene Mutations ◽  
Phase Iii ◽  
First Line ◽  
Mutational Burden ◽  
Significant Difference ◽  
Tumor Mutational Burden

PURPOSE CALGB/SWOG 80405 was a randomized phase III trial that found no statistically significant difference in overall survival (OS) in patients with first-line metastatic colorectal cancer treated with chemotherapy plus either bevacizumab or cetuximab. Primary tumor DNA from 843 patients has been used to discover genetic markers of OS. PATIENTS AND METHODS Gene mutations were determined by polymerase chain reaction. Microsatellite status was determined by genotyping of microsatellites. Tumor mutational burden (TMB) was determined by next-generation sequencing. Cox proportional hazard models were used, with adjusting factors. Interaction of molecular alterations with either the bevacizumab or the cetuximab arms was tested. RESULTS Patients with high TMB in their tumors had longer OS than did patients with low TMB (hazard ratio [HR], 0.73 [95% CI, 0.57 to 0.95]; P = .02). In patients with microsatellite instability–high (MSI-H) tumors, longer OS was observed in the bevacizumab arm than in the cetuximab arm (HR, 0.13 [95% CI, 0.06 to 0.30]; interaction P < .001 for interaction between microsatellite status and the two arms). Patients with BRAF mutant tumors had shorter OS than did patients with wild-type (WT) tumors (HR, 2.01 [95% CI, 1.49 to 2.71]; P < .001). Patients with extended RAS mutant tumors had shorter OS than did patients with WT tumors (HR, 1.52 [95% CI, 1.26 to 1.84]; P < .001). Patients with triple-negative tumors (WT for NRAS/ KRAS/ BRAF) had a median OS of 35.9 months (95% CI, 33.0 to 38.8 months) versus 22.2 months (95% CI, 19.6 to 24.4 months ) in patients with at least one mutated gene in their tumors ( P < .001). CONCLUSION In patients with metastatic colorectal cancer treated in first line, low TMB, and BRAF and RAS mutations are negative prognostic factors. Patients with MSI-H tumors benefited more from bevacizumab than from cetuximab, and studies to confirm this effect of MSI-H are warranted.

Understanding the Prognostic Value of Primary Tumor Location and KRAS in Metastatic Colorectal Cancer: A Post Hoc Analysis of the OPTIMOX3 DREAM Phase III Study

2020 ◽  
Vol 19 (3) ◽  
pp. 200-208.e1 ◽  
Author(s):  
Benoist Chibaudel ◽  
Thierry André ◽  
Christophe Tournigand ◽  
Christophe Louvet ◽  
Magdalena Benetkiewicz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Prognostic Value ◽  
Tumor Location ◽  
Phase Iii ◽  
Primary Tumor Location ◽  
Post Hoc Analysis ◽  
Phase Iii Study ◽  
Post Hoc

Impact of primary tumor sidedness on erlotinib efficacy in patients with metastatic colorectal cancer treated with bevacizumab maintenance: Results from the DREAM phase III trial.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 737-737 ◽  
Author(s):  
Benoist Chibaudel ◽  
Thierry Andre ◽  
Benoit Samson ◽  
Marie-Line Garcia-Larnicol ◽  
Jérôme Dauba ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibodies ◽  
Maintenance Therapy ◽  
Metastatic Colorectal Cancer ◽  
Clinical Outcomes ◽  
Primary Tumor ◽  
Phase Iii ◽  
Primary Tumors ◽  
Phase Iii Trial ◽  
Mutational Status

737 Background: Primary tumor sidedness (PTS) could be a predictive maker for treatment efficacy of EGFR inhibitors monoclonal antibodies in patients with wild-type (WT) RAS metastatic colorectal cancer (MCRC), cetuximab having limited efficacy in patients with WT-RAS right-sided tumors. DREAM study demonstrated that adding erlotinib, an oral EGFR tyrosine kinase inhibitor (TKI) to bevacizumab during maintenance therapy improved clinical outcomes (RR, PFS, OS) in patients with MCRC, whatever KRAS status. The aim of this post-hoc analysis is to evaluate the clinical outcomes according to KRAS mutational status and PTS when adding erlotinib to bevacizumab maintenance therapy. Methods: PTS was retrospectively collected in patients from the DREAM phase III trial treated with bevacizumab with or without erlotinib as maintenance therapy for MCRC who have been controlled by induction therapy. The limit for the definition of PTS was splenic flexure, and rectal tumors were considered as left-sided tumors. The primary endpoint was overall survival (OS). Results: Among 452 patients who received maintenance therapy, PTS ascertainment was 84.7% (n = 383) with 265 (71.0%) patients having left-sided primary tumor and 108 (28.9%) having right-sided primary tumors (3 patients had both and tumor location was unknown in 7 patients). Median OS and treatment effect are presented in table 1. Conclusions: The greatest OS benefit of adding erlotinib to bevacizumab maintenance therapy was observed in patients with WT-KRAS and right-sided MCRC, suggesting a clinical impact of the different mechanism of action between EGFR TKI and monoclonal antibodies. Clinical trial information: NCT00265824. [Table: see text]

scholarly journals Prevalence of and risk factors for feline hyperthyroidism in Hong Kong

2009 ◽  
Vol 11 (4) ◽  
pp. 315-321 ◽  
Author(s):  
Cornelia S. De Wet ◽  
Carmel T. Mooney ◽  
Peter N. Thompson ◽  
Johan P. Schoeman
Keyword(s):  
Risk Factors ◽  
Hong Kong ◽  
Potential Risk ◽  
The Other ◽  
Food Type ◽  
Significant Difference ◽  
The World ◽  
Total Thyroxine ◽  
Potential Risk Factors ◽  
Specific Association

A study was conducted to determine the prevalence of and potential risk factors for feline hyperthyroidism in Hong Kong. Serum total thyroxine (T4) was measured in 305 cats aged 10 years and older that presented at various veterinary clinics in Hong Kong. The prevalence of hyperthyroidism (T4>50 nmol/l) within this population was 3.93% and there was no significant difference in prevalence between healthy (3.16%) and sick (4.37%) cats. Older cats (>15 years) were more likely to be affected and domestic shorthair cats were less likely to be diagnosed with hyperthyroidism than the other breeds combined. No specific association between the development of feline hyperthyroidism and food type was observed. The prevalence of feline hyperthyroidism in Hong Kong was less than that reported for most other parts of the world, despite the presence of previously identified risk factors.

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