DNA repair functionality modulates the clinical outcome of patients with advanced sarcoma treated with trabectedin (ET-743)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9522-9522 ◽  
Author(s):  
P. Schöffski ◽  
P. G. Casali ◽  
M. Taron ◽  
A. T. Van Oosterom ◽  
I. R. Judson ◽  
...  
Keyword(s):  
Median Survival ◽  
Cox Regression ◽  
Excision Repair ◽  
Objective Response ◽  
Progression Free Survival ◽  
High Expression ◽  
Brca1 And Brca2 ◽  
Cox Regression Analysis ◽  
Expression Levels ◽  
Low Expression

9522 Background and Methods: The sensitivity to trabectedin (Yondelis, ET-743) in experimental cancer models correlates with functional transcription-coupled nucleotide excision repair (TC-NER) and with deficient homologous recombination repair (HRR) activity. In order to assess the clinical relevance of this observation we have characterized the mRNA expression levels of ERCC1, XPD, BRCA1 and BRCA2 by RT-PCR in historical tumor samples from 92 sarcoma patients (pts) treated with the agent. Results: The overall objective response (CR+PR) rate to Yondelis in this group was 9%, which confirms the previous clinical experience with the compound in unselected, pre-treated patients with sarcoma. The Kaplan-Meier estimates for progression-free survival at 6 months (PFS6) was 23% and for median survival 8 months (mo). 26% of pts were alive at 24 mo. Correlative Study: Pts with high expression levels (> median) of ERCC1 had better PFS6 (32% vs 15%, p = 0.07) and better median survival (12 vs 7 mo) as compared to pts with low expression ( ≤ to median). Pts with low expression levels of BRCA1 had better PFS6 (33 vs 11%, p = 0.02) and superior median survival (15 vs 5 mo, p = 0.0003) than pts with high expression. Expression levels of XPD and BRCA2 (58 pts) had no significant impact on PFS and survival. The analysis of co-expression of ERCC1-BRCA1 identified a highly sensitive group of pts, characterized by high ERCC1 and low BRCA1 expression levels, with a PFS6 of 50% (p=0.0003) and median survival of 20.4 mo (p = 0.0005). A Cox regression analysis demonstrated that ERCC1 (HR=0.52, p = 0.02) and BRCA1 (HR=2.73, p = 0.0006) are independent variables for PFS, while BRCA1 (HR= 2.57, p = 0.0005) is also an independent variable for survival. Conclusion: This exploratory retrospective study supports the hypothesis that the sensitivity to Yondelis in pts with sarcoma correlates with a functional TC-NER and with deficient HRR. Prospective studies in sarcoma and other potentially sensitive tumor types are required to confirm and validate these findings. [Table: see text]

The predictive value of MAP2K1/2 mutations for efficiency of immunotherapy in melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21587-e21587
Author(s):  
Ting Ye ◽  
Jieying Zhang ◽  
Xinyi Liu ◽  
Mengmei Yang ◽  
Yuhan Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Predictive Value ◽  
Cox Regression ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Driver Mutations ◽  
Cox Regression Analysis ◽  
Melanoma Patients ◽  
The Impact

e21587 Background: Immunotherapies targeting immune checkpoint receptors have become the cornerstone of systemic treatment options for malignant melanoma. The response to these immunotherapies may correlate with driver mutations. MAP2K1/2 genes are mutated in approximately 10% of melanomas, however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. Methods: Six metastatic melanoma clinical cohorts treated with ICIs were included to investigate the association between clinical efficacy of immunotherapy and MAP2K1/2 mutations. Survival analyses were conducted in cohorts receiving two kinds of ICB agents, namely anti-CTLA-4 or anti-PD-1. RNA expression profiling from these cohorts and from the TCGA melanoma cohort were used to explore the potential mechanism related to immune activation. Results: In an independent anti-CTLA-4-treated cohort (n = 110), we found that MAP2K1/2 mutations are predictive of high objective response rate (17.6% vs 1.3%, p = 0.0185) and long progression-free survival [median OS, 49.2 months vs 8.3 months; hazard ratio (HR) = 0.37; 95% CI, 0.15–0.91; p = 0.0307] and overall survival (median PFS, 19.4 months vs 2.8 months; HR = 0.2; 95% CI, 0.05–0.83; p = 0.0262). This predictive value was further validated in a pooled anti-CTLA-4-treated cohort (n = 235) in terms of overall survival (median OS, 49.3 months vs 22.0 months; HR = 0.44; 95% CI, 0.22–0.91; p = 0.0255). However, no correlation between MAP2K1/2 mutations and overall survival was observed in the anti-PD-1-treated cohort (n = 285). Subgroup Cox regression analysis indicated that MAP2K-mutated patients receive less benefit from the anti-PD-1 monotherapy than from the anti-CTLA-4 treatment (median OS, 27.0 months vs 49.3 months; HR = 3.26; 95% CI, 1.18–9.02; p = 0.0225), which was contrary to the result obtained for the total population. Furthermore, transcriptome profiling analysis revealed that MAP2K-mutated tumors are enriched in CD8+ T cells, B cells, and neutrophil cells and also express high levels of CD33 and IL10, which might be the underlying mechanism for melanoma patients with MAP2K1/2-mutated benefit more from anti-CTLA-4 treatment. Conclusions: We identified mutations in MAP2K1/2 genes as the independent predictive factors for anti-CTLA-4 therapy in melanoma patients and found that anti-CTLA-4 treatment in patient harbouring MAP2K1/2 mutations might be more effective than the anti-PD-1 therapy.

scholarly journals Exploration of Various Roles of Hypoxia Genes in Osteosarcoma

2021 ◽  
Author(s):  
Jimin Ma ◽  
Yakun Zhu ◽  
Ziming Guo ◽  
Xuefei Yang ◽  
Haitao Fan
Keyword(s):  
High Risk ◽  
Immune Cells ◽  
Prognostic Model ◽  
Cox Regression ◽  
High Expression ◽  
Cox Regression Analysis ◽  
Model Based ◽  
Survival Difference ◽  
High Expression Group ◽  
Low Expression

Abstract Background: Osteosarcoma is a primary malignant tumor that often metastasizes in orthopedic diseases. Although multi-drug chemotherapy and surgical treatment have significantly improved the survival and prognosis of patients with osteosarcoma, the survival rate is still very low due to frequent metastases in patients with osteosarcoma. In-depth exploration of the relationship between various influencing factors of osteosarcoma is very important for screening promising therapeutic targets. Methods: This study used multivariate COX regression analysis to select the hypoxia genes SLC2A1 and FBP1 in patients with osteosarcoma, and used the expression of these two genes to divide the patients with osteosarcoma into high-risk and low-risk groups. Then, we first constructed a prognostic model based on the patient's risk value, and compared the survival difference between the high expression group and the low expression group. Second, in the high expression group and the low expression group, compare the differences in tumor invasion and inflammatory gene expression between the two groups of immune cells. Finally, the ferroptosis-related genes with differences between the high expression group and the low expression group were screened, and the correlation between these genes was analyzed. Results: In the high-risk group, immune cells with higher tumor invasiveness, macrophages M0 and immune cells with lower invasiveness included: mast cell resting, regulatory T cells (Tregs) and monocytes. Finally, among genes related to ferroptosis, we found AKR1C2, AKR1C1 and ALOX15 that may be related to hypoxia. These ferroptosis-related genes were discovered for the first time in osteosarcoma. Among them, the hypoxia gene FBP1 is positively correlated with the ferroptosis genes AKR1C1 and ALOX15, and the hypoxia gene SLC2A1 is negatively correlated with the ferroptosis genes AKR1C2, AKR1C1 and ALOX15. Conclusion: This study constructed a prognostic model based on hypoxia-related genes SLC2A1 and FBP1 in patients with osteosarcoma, and explored their correlation with immune cells, inflammatory markers and ferroptosis-related genes. This indicates that SLC2A1 and FBP1 are promising targets for osteosarcoma research.

scholarly journals Excision Repair Cross-Complementation Group 6 Gene Polymorphism Is Associated with the Response to FOLFIRINOX Chemotherapy in Asian Patients with Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1196
Author(s):  
Young Hoon Choi ◽  
Younggyun Lim ◽  
Ji Kon Ryu ◽  
Woo Hyun Paik ◽  
Sang Hyub Lee ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Excision Repair ◽  
Cox Model ◽  
Progression Free Survival ◽  
Complementation Group ◽  
Cox Regression Analysis ◽  
Asian Patients ◽  
Damage Repair

FOLFIRINOX is currently one of the standard chemotherapy regimens for pancreatic cancer patients, but little is known about the factors that can predict a response to it. We performed a study to discover novel DNA damage repair (DDR) gene variants associated with the response to FOLFIRINOX chemotherapy in patients with pancreatic cancer. We queried a cohort of pancreatic cancer patients who received FOLFIRINOX chemotherapy as the first treatment and who had tissue obtained through an endoscopic ultrasound-guided biopsy that was suitable for DNA sequencing. We explored variants of 148 DDR genes based on whole exome sequencing and performed multivariate Cox regression to find genetic variants associated with progression-free survival (PFS). Overall, 103 patients were included. Among 2384 variants of 141 DDR genes, 612 non-synonymous variants of 123 genes were selected for Cox regression analysis. The multivariate Cox model showed that rs2228528 in ERCC6 was significantly associated with improved PFS (hazard ratio 0.54, p = 0.001). The median PFS was significantly longer in patients with rs2228528 genotype AA vs. genotype GA and GG (23.5 vs. 16.2 and 8.6 months; log-rank p < 0.001). This study suggests that rs2228528 in ERCC6 could be a potential predictor of response to FOLFIRINOX chemotherapy in patients with pancreatic cancer.

scholarly journals The Clinical Implications and Molecular Mechanism of CX3CL1 Expression in Urothelial Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Guangliang Jiang ◽  
Hui Wang ◽  
Da Huang ◽  
Yishuo Wu ◽  
Weihong Ding ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Mapk Signaling ◽  
High Expression ◽  
Pathway Enrichment Analysis ◽  
Cancer Specific Survival ◽  
Cox Regression Analysis

BackgroundCX3CL1 is a chemokine that may play important roles in cancer immune regulation. Its mechanism in bladder cancer (BCa) is poorly understood. The objective of the current study was to evaluate the association between CX3CL1 and BCa and the related biological mechanisms.MethodsA total of 277 patients with BCa were enrolled in the present study. The association between CX3CL1 expression and disease outcome was evaluated. In vitro and in vivo experiments were performed using the TCCSUP cell line to investigate the function of CX3CL1 in BCa.ResultsCompared with low expression, high expression of CX3CL1 was significantly associated with poorer progression-free survival (hazard ratio [HR]=2.03, 95% confidence interval [95% CI]: 1.26-3.27, P=0.006), cancer-specific survival (HR=2.16, 95% CI: 1.59-2.93, P&lt;0.001), and overall survival (HR=1.55, 95% CI: 1.08-2.24, P=0.039). Multivariable Cox regression analysis suggested that CX3CL1 was an independent prognostic factor for BCa outcomes. In vitro and in vivo experiments indicated that high expression of CX3CL1 was significantly associated with cell proliferation (P&lt;0.001) and invasion (P&lt;0.001). Gene expression profiling results showed that after CX3CL1 knockdown, CDH1 was significantly upregulated, while ETS1, RAF1, and EIF4E were significantly downregulated. Pathway enrichment analysis suggested that the ERK/MAPK signaling pathway was significantly inhibited (P&lt;0.001).ConclusionsCX3CL1 is an independent predictor of a poor prognosis in BCa and can promote the proliferation and invasion of BCa cells.

scholarly journals SCUBE3 Serves as an Independent Poor Prognostic Factor in Breast Cancer

2020 ◽  
Author(s):  
Qin Huo ◽  
Xi He ◽  
Zhenwei Li ◽  
Fan Yang ◽  
Shengnan He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Prognostic Factor ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Cox Regression ◽  
Functional Enrichment ◽  
High Expression ◽  
Cox Regression Analysis ◽  
Expression Levels

Abstract Background: Accumulating evidences indicate that the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) plays a key role in the development and progression of many human cancers. However, the underlying mechanism and prognosis value of SCUBE3 in breast cancer are still unclear. Methods: The clinical data of 137 patients with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. We first conducted a comprehensive study on the expression pattern of SCUBE3 using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. In addition, the expression of SCUBE3 in breast tumor tissues was confirmed by immunohistochemistry. The protein-protein interaction analysis and functional enrichment analysis of SCUBE3 were analyzed using the STRING and Enrichr databases. Moreover, tissue microarray (TMA) was used to analyze the relationship between SCUBE3 expression levels and clinical-pathological parameters, such as histological type, grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). We further supplemented and identified the above results using the UALCAN and bc-GenExMiner v4.4 databases from TCGA data. The correlation between the expression of SCUBE3 and survival was calculated by univariate Cox regression analysis to investigate whether SCUBE3 expression may be an independent prognostic factor of breast cancer. Results: We found that the expression level of SCUBE3 was significantly upregulated in breast cancer tissue compared with adjacent normal tissues. SCUBE3 expression was significantly correlated with ER (p = 0.018), PR (p = 0.015), HER2 (p = 0.039), and triple-negative status (p = 0.049) of patients with breast cancer. We further verified that the expression levels of SCUBE3 mRNA was significantly correlated with ER (p = 0.0007), PR (p = 0.0295), and triple-negative (p = 0.0024), respectively. There was no significant expression difference in the expression of SCUBE3 mRNA in age, HER2 receptor status, and nodal status (p > 0.05). In addition, the high expression of SCUBE3 was associated with relatively poor prognosis of ER- (p = 0.012), PR- (p = 0.029), HER2+ (p = 0.007). The univariate Cox regression analysis showed that the hazard ratio (HR) was 2.80 (95% CI: 1.20-6.51, p = 0.0168) in individuals with high SCUBE3 expression, and HR was increased by 1.86 (95% CI: 1.06-3.25, p = 0.0300) for per 1-point increase of SCUBE3 expression.Conclusions: These findings demonstrate that the high expression of SCUBE3 indicates poor prognosis in breast cancer. SCUBE3 expression may serve as a potential diagnostic indicator of breast cancer.

scholarly journals Association between Renal Podocalyxin Expression and Renal Dysfunction in Patients with Diabetic Nephropathy: A Single-Center, Retrospective Case-Control Study

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Rongzhen Wang ◽  
Can Yao ◽  
Feng Liu
Keyword(s):  
Diabetic Nephropathy ◽  
Retrospective Study ◽  
Cox Regression ◽  
High Expression ◽  
Renal Outcome ◽  
Control Group ◽  
Creatinine Ratio ◽  
Cox Regression Analysis ◽  
High Expression Group ◽  
Low Expression

This retrospective study investigated whether podocalyxin expression in renal biopsies and urine of patients with diabetic nephropathy (DN) is associated with renal function. This retrospective study included 32 patients with nephropathy, secondary to type 2 diabetes treated at the First Hospital of Lanzhou University (January 2010 to January 2015). Compared with the control group, the DN group had a significantly lower renal expression of podocalyxin and higher urinary podocalyxin/creatinine ratio. Patients with DN were divided into the high and low expression groups according to podocalyxin expression in renal tissues. Patients in the low expression group had longer diabetes duration, lower plasma albumin and eGFR, higher glycated hemoglobin (HbA1c), 24 h urinary protein, serum creatinine, and urinary podocalyxin/creatinine ratio, and more severe glomerular, tubulointerstitial, and renal interstitial inflammation than patients in the high expression group (all P<0.01). The renal survival rate was significantly lower in the low expression group than in the high expression group (P<0.01). Single-factor Cox regression analysis showed that reduced podocalyxin expression and increased urinary podocalyxin excretion were associated with poor renal outcome. Measuring podocalyxin levels in renal tissues and urine could help evaluate the progression of DN.

scholarly journals Real-world data on camrelizumab in digestive system cancers: a retrospective observational study

2021 ◽  
Vol 6 (9) ◽  
Keyword(s):  
Gastric Cancer ◽  
Real World ◽  
Digestive System ◽  
Response Rate ◽  
Cox Regression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Real World Data ◽  
Cox Regression Analysis ◽  
Best Response

Objective: To explore the clinical efficacy and safety of camrelizumab in the treatment of digestive system malignancies in the real world. Methods: A retrospective study was designed. A total of 34 patients with advanced gastrointestinal cancer who received camrelizumab treatment in the xx hospital from July 2019 to May 2020 were included. The follow-up endpoint was set for October 30, 2020. The primary endpoint was objective response rate (ORR) and safety. Secondary endpoint measures included progression-free survival (PFS), and overall survival (OS). Cox regression was used for the analysis of factors associated with PFS. Results: As the best response, only 5 patients achieved a partial response and 10 patients had disease progression, with an ORR of 14.31%. Compared with gastric cancer, the ORR of esophageal cancer (3.0% vs 0.0%) (P<0.05). The PFS was 4.5 months (2-10 months). OS ranged from 4 to 11 months, and median OS has not been reached. Multivariate Cox regression analysis showed that gastric cancer (HR=1.695, 95% CI:11.216–2.435, P<0.05) was associated with still shorter PFS, and camrelizumab combined with other drugs (HR=0.512, 95% CI: 0.095–0.737, P<0.01) was associated with PFS in patients. The most common AEs were anemia (41.2%, 14/34) in all grades 1 to 2. Grade 3 AEs occurred in 3 patients (2.9%), including 1 case of immune pneumonitis, 1 case of hemangioma, and 1 case of transaminase increased. Other adverse events included diarrhea, nausea, neutropenia, thrombocytopenia, reactive cutaneous capillary proliferation (RCCEP), fatigue, and hypothyroidism, all of which did not exceed 12%. Conclusion: Camrelizumab is effective and safe in the treatment of patients with digestive system malignancies, but the overall response rate is limited.

Randomized multicenter phase II trial evaluating the sequencing of PD-1 inhibition with pembrolizumab (P) and standard platinum-based chemotherapy (C) in patients (pts) with metastatic non-small cell lung cancer (NSCLC) (AFT-09).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9088-9088
Author(s):  
Thomas A. Hensing ◽  
Xiaofei F. Wang ◽  
Junheng Gao ◽  
Tom Stinchcombe ◽  
Michael V. Knopp ◽  
...  
Keyword(s):  
Phase Ii ◽  
Cox Regression ◽  
Single Agent ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Cox Regression Analysis ◽  
Recist 1.1 ◽  
Platinum Based Chemotherapy ◽  
Significant Difference

9088 Background: KEYNOTE-024 established single-agent P as a 1st-line option for pts with metastatic NSCLC without targetable alterations and PD-L1 tumor proportion score (TPS) ≥ 50%. KEYNOTE-189 and 407 established concurrent C + P as a treatment option irrespective of PD-L1 expression. In this randomized phase II selection trial, we explored sequencing of C and P in this pt. population. Methods: Eligible pts were randomized 1:1 to (arm A) C (carboplatin (AUC 6) + pemetrexed 500 mg/m2 (non-squamous) or paclitaxel 200 mg/m2 (squamous)) x 4 cycles followed by P 200 mg x 4 cycles, or the reverse sequence (arm B) of P x 4 cycles followed by C x 4 cycles. After 8 cycles, pts on both arms were eligible to receive maintenance P for up to 24 months. Primary endpoint was objective response rate (ORR) per RECIST 1.1 by independent review. Secondary endpoints included progression free survival (PFS) per RECIST 1.1 and overall survival (OS). Efficacy endpoints were also evaluated by PD-L1 expression. Results: 89 pts (47 arm B & 42 arm A) were enrolled and are included in the analysis (PD-L1 TPS 0/1-49%/≥50% = 24 pts (34%)/25 pts (36%)/21 pts (30%)). There was no significant difference in ORR (36% vs 38%, p = 0.829), median PFS (2.7 vs 5.5 months (mo), HR 1.25, 95% CI 0.77-2.02, p = 0.363) or OS (13.1 vs 19.8 mo, HR 1.25, 95% CI 0.69-2.25, p = 0.4573), arm B (Px4→C) vs arm A (Cx4→P). Multivariable Cox regression analysis demonstrated significant interaction between treatment and PD-L1 TPS ( < 50% vs ≥ 50%) for PFS (HR 6.76, 95% CI 2.14-21.35, p = 0.0011) and a trend for OS (HR 5.02, 95% CI 0.92-27.55, p = 0.0632), arm B vs arm A. Incidence of grade ≥3 adverse events was 71% for arm A and 65% for arm B. No new safety signals were observed. Conclusions: In pts with stage IV NSCLC and PD-L1 TPS ≥ 50% there was an observed improvement in PFS and OS in favor of C followed by P vs P x 4 followed by C. Given small # of pts and trial design, this observation should be considered hypothesis-generating, but supports further exploration of sequential C + P in this setting. Support:Merck Sharp & Dohme Corp.; https://acknowledgments.alliancefound.org Clinical trial information: NCT02591615.

Bevacizumab associated calcifications might be a prognostic marker in patients with metastatic colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16108-e16108
Author(s):  
Yuwen Zhou ◽  
Qiu Meng
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Prognostic Marker ◽  
Cox Regression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
First Line ◽  
Cox Regression Analysis ◽  
First Line Therapy

e16108 Background: Cetuximab associated calcifications is a positive predictive factor in metastatic colorectal cancer (mCRC). In patients with glioblastoma, bevacizumab-induced calcifications are also related to a better prognosis. However, tumor calcifications are rarely recognized in mCRC patients treated with bevacizumab. This study was to investigate the correlation between clinical outcome and calcification in mCRC who received bevacizumab and chemotherapy as the first-line treatment. Methods: A single retrospective cohort study was conducted with all diagnosed mCRC cases who received bevacizumab and chemotherapy as the first-line therapy in our hospital from January 2016 to January 2019. Clinical variables were retrieved from medical records and tumor calcification were evaluated independently by radiologists on the basis of computed tomography scans. A univariate and multivariate COX regression analysis was performed to evaluate the association between calcification and outcome. Results: 159 patients with an average age of 59.0 years were included. Median follow-up was 29.6 months. Among all enrolled patients, 31 had tumor calcification [31/159 (19.5%)]. The median overall survival (OS) and progression-free survival (PFS) was significantly better in patients with calcification than those without calcification (28.0 vs. 24.9 months, p= 0.024; 12.0 vs. 10.0 months, p= 0.026). A higher objective response rate (61.3% vs. 50.0%) was also observed in calcification group. On multivariate analysis, tumor calcification was independently associated with OS (hazard ratio 1.799, 95% CI 1.002–3.230) and PFS (hazard ratio 1.609, 95% CI 1.013–2.557). Conclusions: Tumor calcification was independently associated with improved prognosis in colorectal cancer. It might be a potential prognostic marker.

The prognostic importance of VEGF-A, PDGF-BB and c-MET in patients with metastatic colorectal cancer

2020 ◽  
Vol 26 (8) ◽  
pp. 1878-1885
Author(s):  
Mevlude Inanc ◽  
Hatice Aslan Sirakaya ◽  
Hatice Karaman ◽  
Oktay Bozkurt
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
High Expression ◽  
Free Survival ◽  
Expression Levels ◽  
Prognostic Importance ◽  
Low Expression

Introduction We aimed to assess the effect of VEGF-A, PDGF-BB, and c-Met expression levels on survival in patients with metastatic colorectal cancer receiving bevacizumab therapies. Patients and methods A total of 105 patients diagnosed with metastatic colorectal cancer between the years 2006 and 2016 were included in the research retrospectively. Results The progression-free survival (PFS) durations of patients with high expression levels of VEGF-A and with low expression levels of VEGF-A were 11 months and 10 months (p = 0.44), respectively. The PFS durations of patients with high PDGF-BB expression and low PDGF-BB expression were 12 months and 10 months (p = 0.16), respectively, while the PFS durations of patients with high and low c-Met expression were 8 months and 13 months (p = 0.005), respectively. Metastatic overall survival was 27 months and 18 months (p = 0.05) in patients with high and low VEGF-A expression levels, respectively, 31 months and 21 months (p = 0.16) in patients with high and low PDGF-BB expression levels, respectively, and 21 months and 26 months (p = 0.11) in patients with high and low c-Met expression levels, respectively. Conclusion The results of this research revealed a high c-Met expression relationship with worse PFS and low VEGF-A expression associated with poor metastatic overall survival in patients with metastatic colorectal cancer receiving bevacizumab therapies.

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