scholarly journals Cetuximab could be more effective without prior bevacizumab treatment in metastatic colorectal cancer patients

2015 ◽  
pp. 3329 ◽  
Author(s):  
Yasuyoshi Sato ◽  
Satoshi Matsusaka ◽  
Mitsukuni Suenaga ◽  
Eiji Shinozaki ◽  
Nobuyuki Mizunuma
2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21024-e21024
Author(s):  
Sinead Noonan ◽  
Petra Martin ◽  
Aoife Maguire ◽  
Monika Biniecka ◽  
Miriam Tosetto ◽  
...  

e21024 Background: Angiogenesis drives cancer growth, tumour progression and metastases. Hypoxic tumours initiate recruitment of their own blood supply and enhance expression of vascular endothelial growth factor (VEGF). Bevacizumab is a recombinant humanised monoclonal anti-VEGF antibody which prevents VEGF binding to its receptors and improves overall survival in metastatic colorectal cancer patients when combined with cytotoxic chemotherapy. Currently, Bevacizumab is indicated as a first line treatment in all metastatic colorectal cancer patients, however only 38-44% of these patients will have a response to treatment. There is no good marker to predict treatment response. The role of inflammation and oxidative damage in driving angiogenesis and clinical response to bevacizumab is poorly understood. The aim of this study was to investigate the levels of oxidative damage and inflammation in the tissue and in the circulation of patients receiving Bevacizumab. Methods: Tissue from 80 patients was constructed into tissue microarrays (TMAs) and screened by immunohistochemistry for the levels of a DNA adduct marker 8oxodG and a lipid peroxidation marker 4HNE in addition to Ki67 status. Serum was screened for 8oxodG, 4HNE and the inflammatory cytokines; IL1β, IL6, IL8, TNFα and pro-angiogenic factors; Ang 2, TGFβ, VEGF using ELISA. Data was correlated with patient survival following Bevacizumab treatment. Results: 8oxodG stromal nuclear positivity significantly correlated with survival following bevacizumab (p=0.035) and this was independent of cell proliferation status. Following multivariate analysis, circulating IL6 levels also significantly correlated with survival following bevacizumab treatment (p=0.01). Using linear regression, circulating levels of 8oxodG correlated with IL6 levels (p=0.016). Circulating Ang 2 levels correlated with IL6 (p=0.006). Conclusions: We have shown for the first time that levels of a DNA adduct marker 8oxodG and circulating levels of IL6 correlate with survival in metastatic patients receiving Bevacizumab.


Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2410
Author(s):  
Chungyeop Lee ◽  
In-Ja Park ◽  
Kyung-Won Kim ◽  
Yongbin Shin ◽  
Seok-Byung Lim ◽  
...  

The effect of perioperative sarcopenic changes on prognosis remains unclear. We conducted a retrospective cohort study with 2333 non-metastatic colorectal cancer patients treated between January 2009 and December 2012 at the Asan Medical Center. The body composition at diagnosis was measured via abdominopelvic computed tomography (CT) using Asan-J software. Patients underwent CT scans preoperatively, as well as at 6 months–1 year and 2–3 years postoperatively. The primary outcome was the association between perioperative sarcopenic changes and survival. According to sarcopenic criteria, 1155 (49.5%), 890 (38.2%), and 893 (38.3%) patients had sarcopenia preoperatively, 6 months–1 year, and 2–3 years postoperatively, respectively. The 5-year overall survival (OS) (95.8% vs. 92.1%, hazard ratio (HR) = 2.234, p < 0.001) and 5-year recurrence-free survival (RFS) (93.2% vs. 86.2%, HR = 2.251, p < 0.001) rates were significantly lower in patients with preoperative sarcopenia. Both OS and RFS were lower in patients with persistent sarcopenia 2–3 years postoperatively than in those who recovered (OS: 96.2% vs. 90.2%, p = 0.001; RFS: 91.1% vs. 83.9%, p = 0.002). In multivariate analysis, postoperative sarcopenia was confirmed as an independent factor associated with decreased OS and RFS. Pre- and postoperative sarcopenia and changes in the condition during surveillance were associated with oncological outcomes.


2021 ◽  
Vol 14 (2) ◽  
pp. 128
Author(s):  
Silvia Galbiati ◽  
Francesco Damin ◽  
Dario Brambilla ◽  
Lucia Ferraro ◽  
Nadia Soriani ◽  
...  

It is widely accepted that assessing circular tumor DNA (ctDNA) in the plasma of cancer patients is a promising practice to evaluate somatic mutations from solid tumors noninvasively. Recently, it was reported that isolation of extracellular vesicles improves the detection of mutant DNA from plasma in metastatic patients; however, no consensus on the presence of dsDNA in exosomes has been reached yet. We analyzed small extracellular vesicle (sEV)-associated DNA of eleven metastatic colorectal cancer (mCRC) patients and compared the results obtained by microarray and droplet digital PCR (ddPCR) to those reported on the ctDNA fraction. We detected the same mutations found in tissue biopsies and ctDNA in all samples but, unexpectedly, in one sample, we found a KRAS mutation that was not identified either in ctDNA or tissue biopsy. Furthermore, to assess the exact location of sEV-associated DNA (outside or inside the vesicle), we treated with DNase I sEVs isolated with three different methodologies. We found that the DNA inside the vesicles is only a small fraction of that surrounding the vesicles. Its amount seems to correlate with the total amount of circulating tumor DNA. The results obtained in our experimental setting suggest that integrating ctDNA and sEV-associated DNA in mCRC patient management could provide a complete real-time assessment of the cancer mutation status.


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