Visceral fat as a predictive marker of response to bevacizumab-based treatment in metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14665-e14665
Author(s):  
Yuji Miyamoto ◽  
Yasuo Sakamoto ◽  
Masayuki Watanabe ◽  
Hideo Baba
Keyword(s):  
Colorectal Cancer ◽  
Visceral Fat ◽  
Subcutaneous Fat ◽  
Predictive Marker ◽  
Line Treatment ◽  
First Line ◽  
Chemotherapy Group ◽  
Fat Volume ◽  
First Line Treatment

e14665 Background: A large amount of visceral adipose tissue might be correlated with high VEGF levels and with resistance to bevacizumab-based regimens in metastasic colorectal cancer (mCRC). The aim is to evaluate that abdominal obesity can be a predictive marker of response to bevacizumab-based therapy in mCRC. Methods: From January 2005 to December 2010, we performed a retrospective analysis of 74 consecutive patients with mCRC received bevacizumab-based first line treatment. Pretreatment CT was used to measure visceral fat volume (VFV), subcutaneous fat volume (SFV) an waist circumference (WC) in 74 patients with mCRC who received bevacizumab-based first-line treatment (bevacizumab group, n=37) or chemotherapy alone (chemotherapy group, n=37). Associations linkingVFV, SFV and WC to tumor response, progression free survival (PFS) and overall survival (OS) were evaluated. For all analyses, VFV, SFV and WC were dichotomized using the median as the cut-off point. Results: In the bevacizumab group, median follow-up lasted for 25 months (7-47). VFV, SFV and WC values were not associated with response or OS. PFS was shorter in patients with high VFV (12.8 vs 7.7 months; p=0.04). By multivariate analysis, high VFA was independently associated with PFS (HR=4.32, p=0.045). In the chemotherapy group, median follow-up lasted for 26 months (2-68). VFV, SFV and WC were not associated with response, PFS or OS. Conclusions: Visceral fat volume plays a role of predictive marker of PFS to bevacizumab-based therapy for Japanese patients with mCRC.

Soluble CD87 (s-uPAR) predicts bevacizumab-based first line treatment of metastatic colorectal cancer (mCRC): Results from a prospective multi-center study.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 604-604 ◽  
Author(s):  
Matthias Unseld ◽  
Gabriele Kornek ◽  
Andreas Gleiss ◽  
Svitlana Demyantes ◽  
Jost Schwarzwald ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Predictive Marker ◽  
Endothelial Cell Migration ◽  
Migration And Invasion ◽  
Induction Treatment ◽  
Line Treatment ◽  
First Line ◽  
Urokinase Plasminogen Activator Receptor ◽  
First Line Treatment

604 Background: Bevacizumab-combined chemotherapy is well established in the induction treatment of metastatic colorectal cancer (mCRC). Despite tremendous efforts, no valid predictive marker for anti-VEGF treatment has so far been defined. CD87, the urokinase plasminogen activator receptor (uPAR), is centrally regulating VEGF-induced angiogenesis via adapting endothelial cell migration and invasion (Unseld et al.; ThrombHaem,2015, Brunner et al.; Blood 2011, Prager et al; Blood 2009; Prager et al; Blood 2004). Preoperative plasma s-uPAR levels were shown to independently predicted survival of patients resectable colorectal cancer. This study aimed to identify any prognostic or predictive value of s-uPAR in front-line bevacizumab-treated mCRC patients. Methods: In this prospective multi-center trial (NCT02119026), patients were either treated with bevacizumab plus FOLFOX or bevacizumab plus FOLFIRI. Baseline s-uPAR levels were assessed in 80 patients (40 ea. group) using respective CE-certified electro-chemiluminescence immunoassay (ECLIA). Biomarkers were explored using Kaplan-Meier curves and were log transformed for survival analysis by Cox proportional hazards models. All P values reported are two-sided. Results: Data from eighty patients were available for analysis. Progression free survival (PFS) and overall survival (OS) were assessed. Data indicate significance for the angiogenic biomarker uPAR to determine prognostic (HR = 3.06, CI 1.45 - 6.53, p = 0.003) and predictive (HR = 3.41, CI 2.03 - 5.74, p < 0.001) value in the treatment of Bevacizumab. Conclusions: This is the first prospective analysis of baseline s-uPAR. High baseline-s-uPAR levels were an independent predictive marker for worse bevacizumab-based first-line treatment response.

Genetic polymorphisms of CCL5 and CCR5 to predict efficacy of cetuximab-based treatment in metastatic colorectal cancer patients depending on primary tumor location.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3594-3594 ◽  
Author(s):  
Mitsukuni Suenaga ◽  
Shu Cao ◽  
Sebastian Stintzing ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Genetic Polymorphisms ◽  
Multivariable Analysis ◽  
Tumor Location ◽  
Line Treatment ◽  
Control Cohort ◽  
First Line ◽  
First Line Treatment

3594 Background: EGFR signaling blockade increases CCL5 expression, which attracts with tumor-infiltrating leukocytes regulating either the host-derived anti-tumor immunity or tumor progression. We tested whether genetic polymorphisms in the CCL5/CCR5 axis could predict efficacy of cetuximab (CET)-based first-line treatment in metastatic colorectal cancer (mCRC) patients (pts). Methods: Genomic DNA was extracted from 491 samples of two different cohorts with KRAS wild-type mCRC in the FIRE-3 study: an evaluation cohort of 244 pts receiving CET plus FOLFIRI (median age 64 yrs; median follow-up 34.1 mos); and a control cohort of 247 pts receiving bevacizumab plus FOLFIRI (median age 65 yrs; median follow-up 39.4 mos); Single nucleotide polymorphisms (SNPs) of CCL5 and CCR5 genes were analyzed by PCR-based direct sequencing. Results: Pts in the evaluation cohort with any CCL5 rs2280789 G allele had shorter OS compared to those with the A/A variant (19.9 vs. 33.4 mos, HR 1.56, 95%CI: 1.05–2.30, P= 0.024), which was confirmed in multivariable analysis (HR 1.64, P= 0.015). Pts carrying any CCR5 rs1799988 T allele had a trend lower response rate than those with the C/C variant (68 vs. 81%, P= 0.078). Statistically significant differences in efficacy were shown between the groups consisting SNPs and tumor location (Table). The findings were not confirmed in the control cohort. Conclusions: Genetic variants of CCL5 and CCR5 SNPs may predict outcomes in mCRC pts receiving CET-based first-line treatment depending on tumor location. [Table: see text]

FOLFOXIRI plus bevacizumab as first-line treatment of BRAF-mutant metastatic colorectal cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3585-3585 ◽  
Author(s):  
Lisa Salvatore ◽  
Fotios Loupakis ◽  
Chiara Cremolini ◽  
Marta Schirripa ◽  
Gianluca Masi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Line Treatment ◽  
First Line ◽  
Validation Set ◽  
Colorectal Cancer Patients ◽  
Braf Mutant ◽  
First Line Treatment

3585 Background: BRAF V600E mutation plays a negative prognostic role in metastatic colorectal cancer (mCRC) patients, leading to a median PFS of 4-6 months with first-line conventional treatments. Recently, results from a retrospective exploratory analysis suggested that an up-front intensive treatment with FOLFOXIRI plus bevacizumab could improve the outcome of BRAF mutant mCRC. Methods: Fifteen consecutive BRAF mutant mCRC patients treated with first-line FOLFOXIRI plus bevacizumab were included in a validation set. The primary endpoint was 6-months progression free rate (6m-PFR). Secondary endpoints were: overall survival, response rate and the pooled analysis of all main outcome parameters in both the exploratory and validation set. Results: In the validation set, 11 out 15 patients included were progression-free at 6 months, for a 6m-PFR of 73.3%. Primary endpoint was met. At a median follow-up of 21.6 months, median progression-free survival was 9.2 months while median OS has not yet been reached. In the pooled data analysis of the validation set and the initial retrospective cohort 24 out 25 total patients were evaluable for response: partial or complete response was obtained in 17 (68%) and in 1 (4%) patient, respectively, for an overall response rate of 72%. At a median follow-up of 34.1 months, the pooled set of patients showed a median PFS of 11.8 months and a median OS of 23.8 months. Conclusions: These data suggest that FOLFOXIRI plus bevacizumab could be a reasonable option for the first-line treatment of BRAF mutant metastatic colorectal cancer patients.

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