ERCC1, KRAS mutation, redox status, and oxaliplatin sensitivity in colorectal cancer: “Radical” change in an old model.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14156-e14156
Author(s):  
Armando Orlandi ◽  
Mariantonietta Di Salvatore ◽  
Michele Basso ◽  
Cinzia Bagalà ◽  
Antonia Strippoli ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cell Lines ◽  
Pearson Correlation ◽  
Redox Status ◽  
Mutational Status ◽  
Retrospective Clinical Study ◽  
Significant Difference ◽  
The Impact

e14156 Background: Oxaliplatin (Oxa) is widely used in metastatic colorectal cancer, but currently there are not valid predictors of response to this drug. In our recent retrospective clinical study we have shown a greater efficacy of Oxa in patients with metastatic colorectal cancer with mutated (mt) K-RAS. We hypothesized that the mutational status of K-RAS could influence the expression of ERCC1 and cellular Redox status. Methods: We used four cell lines of colorectal cancer: two K-RAS wild type (wt) (HCT-8, HT-29) and two K-RAS mt (SW620, SW480). We evaluated the sensitivity of these cell lines to Oxa by MTT-test and the ERCC1 levels before and after 24h exposure to Oxa by RT-PCR. We silenced K-RAS in a K-RAS mt cell lines to evaluate the impact on Oxa sensitivity and ERCC1 levels. We also silenced ERCC1 in order to confirm the importance of this protein as a Oxa resistance factor. Cellular oxidative stress was determined by DCFDA. Results: The K-RAS mt cell lines were more sensitive to Oxa (p<0.001). The basal levels of ERCC1 did not show significant differences between K-RAS mt and wt cell line, however, after 24h exposure to Oxa, only the K-RAS wt lines showed the ability to induce ERCC1, with a statistically significant difference (p<0.005). The silencing of K-RAS in K-RAS mt cell lines (SW620s) demonstrated to reduce sensitivity to Oxa associated with the acquisition of the ability to induce ERCC1. The silencing of ERCC1 in K-RAS wt cell lines enhance the sensibility to Oxa. The levels of reactive oxygen species were higher in K-RAS mt cell lines. The Pearson correlation test showed a statistically significant relationship between basal levels of ROS and sensitivity to Oxa ("r" -0,988, p<0.01). The baseline levels of ROS were higher SW620 than the line SW620s. The administration of Oxa in these cell lines resulted in a statistically higher fluorescence index in SW620 versus SW620s (p<0.003). Conclusions: The K-RAS mutated cell lines were more sensitive to Oxa. This feature seems to be secondary to the inability of these cells to induce ERCC1 after exposure to Oxa and to the synergism between K-RAS mutation and Oxa in increasing oxidative stress. K-RAS can thus be a predictor of response to Oxa in colorectal cancer.

ERCC1, KRAS mutation, and oxaliplatin sensitivity in colorectal cancer: Old dogs and new tricks.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 489-489 ◽  
Author(s):  
Armando Orlandi ◽  
Mariantonietta Di Salvatore ◽  
Michele Basso ◽  
Cinzia Bagalà ◽  
Antonia Strippoli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Predictors Of Response ◽  
Mutational Status ◽  
Retrospective Clinical Study ◽  
Significant Difference ◽  
Before And After ◽  
The Impact

489 Background: Oxaliplatin is widely used in metastatic colorectal cancer, but currently there are not valid predictors of response to this drug. In our recent retrospective clinical study we have shown a greater efficacy of Oxaliplatin in patients with metastatic colorectal cancer with mutated (mt) K-RAS. We hypothesized that the mutational status of K-RAS could influence the expression of ERCC1, one of the main mechanisms of Oxaliplatin resistance. Methods: We used four cell lines of colorectal cancer: two K-RAS wild type (wt) (HCT-8 and HT-29) and two K-RAS mt (SW620 and SW480). We evaluated the sensitivity of these cell lines to Oxaliplatin by MTT-test and the ERCC1 levels before and after 24 h exposure to Oxaliplatin by Real-Time PCR. We silenced K-RAS in a K-RAS mt cell line to evaluate the impact on Oxaliplatin sensitivity and ERCC1 levels. We also silenced ERCC1 in order to confirm the importance of this protein as a Oxaliplatin resistance factor. Results: The K-RAS mt cell lines were more sensitive to Oxaliplatin (OR 2.68; IC 95% 1.511-4.757 p<0.001). The basal levels of ERCC1 did not show significant differences between K-RAS mt and wt cell line, however, after 24 h exposure to Oxaliplatin, only the K-RAS wt lines showed the ability to induce ERCC1, with a statistically significant difference (OR 42.9 IC 95% 17.260-106.972 p<0.0005). The silencing of K-RAS in K-RAS mt cell lines demonstrated to reduce sensitivity to Oxaliplatin associated with the acquisition of the ability to induce ERCC1. The silencing of ERCC1 in K-RAS wt cell lines enhance the sensibility to Oxaliplatin. Conclusions: The K-RAS mutated cell lines were more sensitive to Oxaliplatin. This feature seems to be secondary to the inability of these cells to induce ERCC1 after exposure to Oxaliplatin. K-RAS can thus be a predictor of response to Oxaliplatin in colorectal cancer representing a surrogate for ability to induce ERCC1.

The impact of KRAS mutation on radioembolization in the treatment of unresectable liver predominant metastatic colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 664-664
Author(s):  
Michael Schacht ◽  
Douglas M. Coldwell ◽  
Vivek Sharma
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Median Time ◽  
Metastatic Disease ◽  
Disease Burden ◽  
Hepatic Metastases ◽  
Time To Progression ◽  
Kras Status ◽  
Significant Difference ◽  
The Impact

664 Background: Radioembolization with either Yttrium-90 labeled resin or glass microspheres is an FDA approved treatment for hepatic metastases from primary colorectal cancer. Y-90 therapy is used almost exclusively in unresectable liver metastases. However, radioembolization is only an optional part of the treatment process along with first-line, second-line, and salvage chemotherapy. KRAS is a known proto-onco gene that has typically been studied as a negative prognostic factor in the chemotherapeutic treatment of metastatic colorectal cancer (mCRC). KRAS is a known marker for resistance to anti-EGFR antibodies and generally have a poorer prognosis. The aim of this study is to begin to shed light on the impact of KRAS status on the outcome of patients undergoing radioembolization for the treatment of unresectable liver predominant metastatic CRC, regardless of their chemotherapy regimens. Methods: This is a retrospective analysis of 18 subjects treated with radioembolization for liver predominant metastatic CRC. KRAS status and treatment outcomes were followed for each patient up to the study close date of 9/15/13. Statistical analysis was performed using the Mann-Whitney U test. Results: Of the 18 subjects included in the study, 5 were found to have KRAS mutant oncogene. The remaining 13 were found to have the KRAS wildtype. Overall, those subjects with KRAS mutant were found to have a statistically significant difference in median time to progression of intrahepatic metastatic disease burden when compared to KRAS wildtype even when liver-directed therapy was utilized (2.0 vs. 6.4 months). Differences in median time to progression of extrahepatic metastatic disease burden and overall survival were not found to be statistically significant at this time. Conclusions: KRAS mutant patients are exceedingly difficult to treat due to both intrahepatic and extrahepatic disease recurrence/progression.

scholarly journals How to Deal with Second Line Dilemma in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1189 ◽  
Author(s):  
Galvano ◽  
Incorvaia ◽  
Badalamenti ◽  
Rizzo ◽  
Guarini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Phase Iii ◽  
Second Line ◽  
Anti Vegf ◽  
Significant Difference ◽  
Line Setting ◽  
The Impact

Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy with chemotherapy (CT) as second line treatment for metastatic colorectal cancer (mCRC). The right sequence of the treatments in all RAS (KRAS/NRAS) wild type (wt) patients has not precisely defined. We evaluated the impact of aforementioned targeted therapies in second line setting, analyzing efficacy and safety data from phase III clinical trials. We performed both direct and indirect comparisons between anti-EGFR and anti-VEGF. Outcomes included disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and G3-G5 toxicities. Our results showed significantly improved OS (HR 0.83, 95% CI 0.72–0.94) and DCR (HR 1.27, 95% CI 1.04–1.54) favouring anti-VEGF combinations in overall population; no statistically significant differences in all RAS wt patients was observed (HR 0.87, 95% CI 0.70–1.09). Anti-EGFR combinations significantly increased ORR in all patients (RR 0.54, 95% CI 0.31–0.96), showing a trend also in all RAS wt patients (RR 0.63, 95% CI 0.48–0.83). No significant difference in PFS and DCR all RAS was registered. Our results provided for the first time a strong rationale to manage both targeted agents in second line setting.

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.

KRAS mutational status in metastatic colorectal cancer and thrombotic risk.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15140-e15140 ◽  
Author(s):  
Laurel Anne Menapace ◽  
James Bena ◽  
Shannon Morrison ◽  
Alok A. Khorana
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Thrombotic Event ◽  
Cleveland Clinic ◽  
Kras Mutations ◽  
Thrombotic Risk ◽  
Vein Thrombosis ◽  
Mutational Status ◽  
Significant Difference ◽  
Tissue Specimens

e15140 Background: There is limited clinical evidence suggesting a possible association between KRAS mutational status and thrombotic risk in metastatic colorectal cancer (mCRC). We attempted to confirm previously published findings in a single institution study of mCRC patients initiating treatment at Cleveland Clinic. Methods: We evaluated the association of observed venous thromboembolic (VTE) events in relation to KRAS mutational status in a retrospective cohort of mCRC patients receiving treatment at Taussig Cancer Institute between 2009 and 2013.KRAS mutational status obtained from pathologic tissue specimens,specifically wild-type (WT) or mutant status, was recorded for each patient. Both inpatient and outpatient radiologic reports were reviewed for presence of pulmonary embolism (PE), deep venous thrombosis (DVT), and visceral vein thrombosis (VVT). All observed VTE events were analyzed, including asymptomatic or incidentally discovered VTE. Results: A total of 184 patients with newly diagnosed metastatic colorectal cancer were included in the analysis. There were a total of 47 combined VTE events observed in 42 patients. 5 subjects had more than one thrombotic event during the investigative period. 55.4% (n = 102) of mCRC patients were identified as WT whereas the remainder harbored a KRAS mutation (44.6%, n = 82). Both groups had similar rates of bevacizumab exposure. There were slightly more VTE events in the KRAS mutant cohort, with a total of 26 observed VTE events in 24 patients (29.3%) versus a total of 21 thrombotic events in 18 mCRC WT patients (17.6%). There were 16 DVTs, 6 PEs and 4 VVTs in the KRAS mutant group as compared to 10 DVTs, 9 PEs, and 2 VVTs in the WT cohort. There was no statistically significant difference in combined VTE (Odds Ratio 1.90 [0.96 - 3.91], p = 0.062), DVT (OR 0.82 [0.28 - 2.39], p = 0.06), PE (OR 2.23 [0.95 - 5.22], p = 0.71) and VVT (OR 2.60 [0.46 -14.4], p = 0.41) between groups. There was no difference in survival measured in days between KRAS mutant and WT mCRC patients. Conclusions: Based on these results, there is limited evidence that mCRC patients harboring KRAS mutations may be at greater risk for VTE. Further study of KRAS mutational status as a biomarker of thrombotic risk in cancer is indicated.

A retrospective cohort study evaluating the safety and efficacy of TAS-102 in patients with metastatic colorectal cancer (HGCSG1503): Analysis of tumor location.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 802-802
Author(s):  
Kohei Ogawa ◽  
Satoshi Yuki ◽  
Yasuyuki Kawamoto ◽  
Masataka Yagisawa ◽  
Kazuaki Harada ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Patient Characteristics ◽  
Tumor Location ◽  
Recent Analysis ◽  
Safety And Efficacy ◽  
Primary Tumor Location ◽  
Significant Difference ◽  
The Impact

802 Background: Recent analysis from some clinical trials showed that primary tumor location in patients with metastatic colorectal cancer (mCRC) correlates with different outcome. The J003 trial and RECOURSE trial revealed the safety and efficacy of TAS-102 for patients with metastatic colorectal cancer (mCRC). In March 2014, TAS-102 was approved in Japan. However, the impact of primary tumor location in mCRC treated TAS-102 is unclear. Methods: We retrospectively analyzed the clinical data of 411 patients who received TAS-102 in the multi-institutional retrospective study (HGCSG1503). This study was analyzed by CTCAE v4.0 for adverse events (AEs), RECIST v1.1 for response rate (RR)/disease control rate (DCR). To compare with right-sided tumor (RT : Cecum to Transverse colon) and left-sided tumor (LT : Descending colon to Rectum), Fisher’s exact test was used in terms of patient characteristics, AE, RR/DCR, and Log-rank test was used in terms of TTF, PFS and OS. Results: Patients with RT and LT were 137 and 274, respectively. The patient’ characteristics between RT and LT were generally balanced except for Gender (Male ; 45.3% in RT, 56.9% in LT ; p = 0.028), Age (Median ; 68.0y in RT, 66.0y in LT ; p = 0.007), Liver metastasis (70.8% in RT, 57.7% in LT ; p = 0.010), Peritoneal metastasis (47.4% in RT, 24.5% in LT ; p < 0.001), and KRAS exon2 status (wild ; 40.5% in RT, 59.0% in LT ; p = 0.001). The AEs between RT and LT were also generally balanced except for Platelet count decreased (≥Grade 3 ; 8.8% in RT, 2.9% in LT ; p = 0.014). RR/DCR were 0/30.9% in the RT and 0.8/40.3% in the LT (p = 1.000/0.088). Median TTF was 2.2 months in the RT and 2.1 months in the LT (HR 0.962, p = 0.712). Median PFS was 2.2 months in the RT and 2.2 months in the LT (HR 1.024, p = 0.826). Median OS was 7.3 months in the RT and 7.3 months in the LT (HR 1.114, p = 0.327). Conclusions: As a result of this analysis, efficacy was no significant difference between RT and LT for patients who were administered TAS-102 in the real-world clinical practice. This analysis suggested TAS-102 benefits mCRC patients regardless of primary tumor location. Clinical trial information: 000020551.

scholarly journals Clinical Pathways: Management of Quality and Cost in Oncology Networks in the Metastatic Colorectal Cancer Setting

2017 ◽  
Vol 13 (5) ◽  
pp. e522-e529 ◽  
Author(s):  
Peter G. Ellis ◽  
Bert H. O’Neil ◽  
Martin F. Earle ◽  
Stephanie McCutcheon ◽  
Hans Benson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Clinical Pathways ◽  
Cost Savings ◽  
Cost Information ◽  
Health Networks ◽  
Specific Patient ◽  
Significant Difference ◽  
Clinical Trial Results ◽  
The Impact

Purpose: Via Pathways (clinical pathways for cancer) provide evidence-based guidance for specific patient presentations based on the merit of efficacy, then toxicity, and finally cost (if efficacy and toxicity are comparable). We evaluated the impact of a change to the guidance in the metastatic colorectal cancer (mCRC) setting across two large, integrated health networks. Methods: Cetuximab and panitumumab were determined to have equal efficacy in the treatment of mCRC with no significant difference in toxicity based on recent data from key clinical studies. A cost analysis using Centers for Medicare and Medicaid Services average sales data determined a cost advantage for panitumumab. A substitution of panitumumab for cetuximab in the clinical pathway for all mCRC lines of therapy was initiated as of August 2014. Results: In the preimplementation period, 86 (93.5%) and six (6.5%) treatment selections were for cetuximab and panitumumab, respectively. After the pathway change was implemented, 13 (18.1%) and 59 (81.9%) treatment selections were for cetuximab and panitumumab, respectively. The change in prescribing habits was rapidly altered by the pathway change. The estimated annualized cost savings for the two health networks resulting from the response to the pathway change was $711,021. Conclusion: This study demonstrates that clinical pathways can act as a tool to assist oncology practices in decreasing costs and quickly responding to changing treatment paradigms by providing clinicians with consensus-driven treatment recommendations that incorporate the most up-to-date clinical trial results, toxicity considerations, and regimen cost information.

scholarly journals How to deal with second line dilemma in metastatic colorectal cancer? A systematic review and meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15006-e15006
Author(s):  
Antonio Galvano ◽  
Aurelia Guarini ◽  
Stefania Cusenza ◽  
Nadia Barraco ◽  
Marta Castiglia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Phase Iii ◽  
Second Line ◽  
Targeted Agents ◽  
Anti Vegf ◽  
Significant Difference ◽  
The Impact ◽  
Indirect Comparisons

e15006 Background: Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy in combination with chemotherapy as second line for metastatic colorectal cancer (mCRC). However, there is still a paucity of evidence or guidelines suggesting the right sequential treatment in all RAS (KRAS/NRAS) wild type(wt)mCRC. Therefore, we aimed to evaluate the impact of these targeted therapies by reviewing literature data. Methods: We used Cochrane, EMBASE and Medline databases to select phase III clinical trials containing efficacy and safety data about chemotherapy (CT) or CT + targeted agents combination (Anti-VEGF and Anti-EGFR) in second line mCRC setting. We performed direct comparisons to obtain pooled data for anti-VEGF + CT versus CT and anti-EGFR +CT versus CT comparisons. Then we performed indirect comparisons between anti-EGFR and Anti-VEGF. Outcomes were disease control rate (DCR), response rate (RR), progression-free survival (PFS), overall survival (OS) and most common G3-G5 toxicities. Results: Eight eligible RCTs (6793 pts) were included: 5 studies compared anti-VEGF + CT and 3 anti-EGFR + CT combinations to CT. After direct comparisons, pooled indirect results showed significantly improved OS (HR 0.83, 95% CI 0.72–0.94) and DCR (HR 1.27, 95% CI 1.04–1.54) favouring anti-VEGF combinations in overall population; however, no statistically significant differences in all RAS wt patients was observed (HR 0.87, 95% CI 0.70–1.09). Additionally, anti-EGFR combinations significantly increased ORR in all patients (RR 0.54, 95% CI 0.31–0.96), showing a trend in all RAS wt patients (RR 0.63, 95% CI 0.48–0.83) too. Furthermore, no significant difference in PFS and DCR all RAS was registered. Anti-VEGF combination significantly increased Only a significant asthenia difference (RR 1.34, 95% CI 1.03–1.75) was registered. Conclusions: At our knowledge, our indirect comparisons between anti-VEGF and anti-EGFR combinations showed for the first time better OS and DCR for anti-VEGF combinations, whereas better RR is observed for anti-EGFR combinatory regimens, defining a role of both targeted agents in second line mCRC setting.

RAS mutational status and CEA production at initial presentation in metastatic colorectal cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 542-542
Author(s):  
May Thet Cho ◽  
Leanne Goldstein ◽  
Chie Akiba ◽  
S. Cecilia Lau ◽  
Milhan Telatar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Metastatic Colorectal Cancer ◽  
Metastatic Disease ◽  
Hepatic Metastases ◽  
Small Sample ◽  
Eligibility Criteria ◽  
Mutational Status ◽  
Ras Status ◽  
The Impact

542 Background: Serial CEA testing is recommended in the surveillance of patients with resected stage II-IV colorectal cancer. However, the sensitivity of CEA in identifying metastatic disease has not been evaluated in the settings of RAS mutant (MT) and RAS/BRAF wild-type tumors (WT). In order to evaluate the impact of RAS mutational status on CEA production, we retrospectively evaluated a single-institute metastatic colorectal cancer (mCRC) population. Methods: We retrospectively reviewed, in a single center, all cases with mCRC with known RAS mutational status based on next generation sequencing (ONCO44 and ONCO48). These assays identify clinically relevant mutations in BRAF, KRAS, and NRAS. Additional eligibility criteria included the availability of CEA levels and imaging studies at first diagnosis of mCRC. Patient demographics, primary tumor location and sites of metastatic disease at 1st diagnosis were captured. CEA levels were stratified as normal or elevated based on a cut point of 5ng/ml. Results: 139 mCRC patients satisfied the eligibility criteria (75 RAS-MT, 59 RAS/BRAF-WT, and 5 BRAF-MT). BRAF-MT patients were excluded from the analysis due to their small sample size. Patients with RAS/BRAF-WT tumors were more likely to present with metastatic disease to the liver, but this did not reach statistical significance (p = 0.056). There was no difference in the incidence of normal CEA at presentation in RAS-MT (30%) and RAS/BRAF-WT (28%) cohorts. CEA production was dependent on the pattern of metastatic disease. Elevated CEA was associated with the presence of liver metastases versus no metastases among RAS-MT (92% vs 47% p <.0001) and RAS/BRAF-WT patients (82% vs 50% p = 0.0101). RAS status did not impact the likelihood of CEA production within the hepatic metastases and non-hepatic metastases groups. Conclusions: RAS status does not appear to influence CEA production in patients with mCRC. CEA elevations are highly associated with liver metastases and are less prevalent in patients without hepatic involvement. These findings confirm the limited predictive value of CEA for non-hepatic recurrence, irrespective of RAS status.

Efficacy and Toxicity of Addition of Bevacizumab to Chemotherapy in Patients with Metastatic Colorectal Cancer

2019 ◽  
Vol 21 (10) ◽  
pp. 718-724 ◽  
Author(s):  
Wen-Cong Ruan ◽  
Yue-Ping Che ◽  
Li Ding ◽  
Hai-Feng Li
Keyword(s):  
Colorectal Cancer ◽  
Adverse Event ◽  
Metastatic Colorectal Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Clinical Prognosis ◽  
Line Therapy ◽  
Significant Difference

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

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