Adjuvant systemic chemotherapy with or without bevacizumab in patients with resected pulmonary metastases from colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14533-e14533
Author(s):  
Nedim Turan ◽  
Faysal Dane ◽  
Olcun Umit Unal ◽  
Mustafa Benekli ◽  
Hasan volkan Kara ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pulmonary Metastases ◽  
Univariate Analysis ◽  
Pulmonary Metastasectomy ◽  
Disease Free Interval ◽  
Free Survival ◽  
Lymphatic Involvement ◽  
Significant Difference ◽  
Disease Free

e14533 Background: To determine impact of modern chemotherapy regimens after pulmonary metastasectomy from colorectal cancer (CRC). Methods: A total of 122 consecutive patients who curatively resected for pulmonary metastases of CRC in eleven oncology centers were retrospectively analysed between January 2000 and April 2012. Results: Of 122 patients, 108 who received chemotherapy with fluoropyrimidine-based (n = 12), irinotecan-based (n = 56) and oxaliplatin-based (n = 40) combinations were analyzed. Among these, 52 patients received bevacizumab (BEV) while 56 did not (NoBEV). With a median follow-up of 14 months after metastasectomy, median recurrence-free survival (RFS) was 17 months, overall survival (OS) was not reached. Three and 5-years OS rates were 66% and 53%, respectively. There was no significant difference among cytotoxic regimens in respect to RFS and OS. Similarly, no significant difference was seen between BEV and NoBEV arms in respect to OS and RFS. In univariate analysis prior liver metastasectomy (p = 0.045), positive pulmonary margin (p = 0.028), disease-free interval < 12 months (p = 0.013), and KRAS mutation (0.009) were negative significant prognostic for RFS. Thoracic pathological lymphatic involvement (p = 0.006) and higher prethoracotomy carcinoembryonic antigen (p = 0.038) were negative significant prognostic for OS. In multivariate analysis, positive pulmonary margin was the only negative independent prognostic for RFS, while thoracic lymphatic involvement was the only negative independent prognostic for OS. Conclusions: Chemotherapy type and addition of bevacizumab have no impact on both RFS and OS in the adjuvant setting following complete resection of colorectal pulmonary metastases.

scholarly journals TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Sha Zhou ◽  
Jianhong Peng ◽  
Liuniu Xiao ◽  
Caixia Zhou ◽  
Yujing Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Free Survival ◽  
Epigenetic Regulator ◽  
Crc Management ◽  
Disease Free ◽  
Resistance To Chemotherapy

AbstractResistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.

Radiofrequency Ablation of Hepatic Metastases from Colorectal Cancer: Are Newer Generation Probes Better?

2006 ◽  
Vol 72 (10) ◽  
pp. 875-879 ◽  
Author(s):  
Aziz Ahmad ◽  
Steven L. Chen ◽  
Maihgan A. Kavanagh ◽  
David P. Allegra ◽  
Anton J. Bilchik
Keyword(s):  
Colorectal Cancer ◽  
Radiofrequency Ablation ◽  
First Generation ◽  
Hepatic Metastases ◽  
Disease Free Survival ◽  
Cancer Center ◽  
Free Survival ◽  
Alive With Disease ◽  
Disease Free

Second-generation radiofrequency ablation (RFA) probes and their successors have more power, shorter ablation times, and an increased area of ablation compared with the first-generation probes used before 2000. We examined whether the use of the newer probes has improved the clinical outcome of RFA for hepatic metastases of colorectal cancer at our tertiary cancer center. Of 160 patients who underwent RFA between 1997 and 2003, 52 had metastases confined to the liver: 21 patients underwent 46 ablations with the first-generation probes and 31 patients underwent 58 ablations with the newer probes. The two groups had similar demographic characteristics. At a median follow-up of 26.2 months, patients treated with the newer probes had a longer median disease-free survival (16 months vs 8 months, P < 0.01) and a lower rate of margin recurrence (5.2% vs 17.4%); eight patients had no evidence of disease and one patient was alive with disease. By contrast, of the 46 patients treated with the first-generation probes, 2 patients had no evidence of disease and 1 patient was alive with disease. Newer-generation probes are associated with lower rates of margin recurrence and higher rates of disease-free survival after RFA of hepatic metastases from colorectal cancer.

scholarly journals Combination of CDX2 expression and T stage improves prognostic prediction of colorectal cancer

2019 ◽  
Vol 47 (5) ◽  
pp. 1829-1842 ◽  
Author(s):  
Weimin Xu ◽  
Yilian Zhu ◽  
Wei Shen ◽  
Wenjun Ding ◽  
Tingyu Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Free Survival ◽  
T Stage ◽  
Cdx2 Expression ◽  
Prognostic Prediction ◽  
Disease Free

Objective Prognostic prediction of colorectal cancer (CRC) remains challenging because of its heterogeneity. Aberrant expression of caudal-type homeobox transcription factor 2 (CDX2) is strongly correlated with the prognosis of CRC. Methods Tissue samples of patients with CRC who underwent surgery in Xinhua Hospital (Shanghai, China) from January 2010 to January 2013 were collected. CDX2 expression was semiquantitatively evaluated via immunohistochemistry. Results In total, 138 patients were enrolled in this study from a prospectively maintained institutional cancer database. The median follow-up duration was 57.5 months (interquartile range, 17.0–71.0 months). In the Cox proportional hazards model, low CDX2 expression combined with stage T4 CRC was significantly the worst prognostic factor for disease-free survival (hazard ratio = 7.020, 95% confidence interval = 3.922–12.564) and overall survival (hazard ratio = 5.176, 95% CI = 3.237–10.091). In the Kaplan–Meier survival analysis, patients with low CDX2 expression and stage T4 CRC showed significantly worse disease-free survival and overall survival than those with low CDX2 expression alone. Conclusion CDX2 expression combined with the T stage was more accurate for predicting the prognosis of CRC. Determining the prognosis of CRC using more than one variable is valuable in developing appropriate treatment and follow-up strategies.

DNA copy number alterations, gene expression changes and disease-free survival in patients with colorectal cancer: a 10 year follow-up

2016 ◽  
Vol 39 (6) ◽  
pp. 545-558 ◽  
Author(s):  
Elisabetta Bigagli ◽  
Carlotta De Filippo ◽  
Cinzia Castagnini ◽  
Simona Toti ◽  
Francesco Acquadro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Copy Number ◽  
Disease Free Survival ◽  
Copy Number Alterations ◽  
Dna Copy Number ◽  
Free Survival ◽  
Dna Copy Number Alterations ◽  
Disease Free

Percutaneous radiofrequency ablation of inoperable pulmonary metastases from colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3502-3502
Author(s):  
T. D. Yan ◽  
J. King ◽  
D. Glenn ◽  
K. Steinke ◽  
D. L. Morris
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Radiofrequency Ablation ◽  
Lung Metastasis ◽  
Pulmonary Metastases ◽  
Lung Metastases ◽  
Univariate Analysis ◽  
Prognostic Parameters ◽  
Percutaneous Radiofrequency Ablation

3502 Background: This current study was an open, prospective and nonrandomized phase II study, which critically evaluated the prognostic parameters for local disease-free survival (DFS) and overall survival (OS) in patients who underwent percutaneous radiofrequency ablation (RFA) for inoperable colorectal pulmonary metastases (CRPM). Methods: The inclusion criteria were patients who had inoperable CRPM, due to number, distribution, poor performance status or patients’ refusal to accept surgery. The exclusion criteria were lesions > 6 per hemithorax; diameter of metastases > 5 cm; bleeding diathesis; and/or significantly compromised lung function. All patients underwent percutaneous RFA with a radiological clear margin of at least 2 cm. The end-points of this study were local DFS and OS, determined from the time of RFA intervention. Ten clinical and six treatment-related prognostic parameters were assessed in univariate and multivariate analyses. All patients were reviewed at one week, one month and every three months thereafter with chest CT. Fifty-five patients entered into the study. The follow-up was complete and the median follow-up was 24 months (6 to 40). Results: The median local DFS was not reached and 2-year local DFS was 57%. Univariate analysis demonstrated that largest size of lung metastasis, location of lung metastases, post-RFA CEA at 1 month and 3 months were significant for local DFS. In multivariate analysis, largest size of lung metastasis of ≤ 3 cm and post-RFA CEA of ≤ 5 ng/ml at 1 month were independently associated with an improved local DFS. The median OS was 33 months (4 to 40), with 1-, 2-, and 3-year survival of 85%, 64% and 46%, respectively. Univariate analysis demonstrated that interval between the diagnoses of colorectal cancer and pulmonary metastasis; largest size of lung metastasis and location of lung metastases were significant for OS. In multivariate analysis, only size of lung metastasis of ≤ 3 cm was independently associated with an improved OS. Conclusions: Percutaneous RFA of inoperable CRPM may have a useful role in patients with a lesion of ≤ 3 cm. No significant financial relationships to disclose.

Cure rate in early colorectal cancer estimated from disease-free survival curves from phase III comparative clinical trials: Necessity of long follow-up

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15006-e15006
Author(s):  
E. Barrajon ◽  
A. Lopez ◽  
G. Esquerdo ◽  
J. M. Cervera
Keyword(s):  
Colorectal Cancer ◽  
Event Rate ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Early Colorectal Cancer ◽  
Cure Rate ◽  
Survival Curves ◽  
Free Survival ◽  
Disease Free

e15006 Background: The traditional end point for adjuvant clinical trials is overall survival (OS). Short-term disease-free survival (DFS) has been accepted as a surrogate of 5-year OS in colorectal cancer trials. Nevertheless, recent adjuvant trials have not shown a consistent improvement in OS despite a significant improvement in DFS. Two reasons may explain this effect: 1) a delay in relapse produced by treatment, not affecting the cure rate, or 2) more effective treatments in relapsing patients which delay death, hiding a real difference in cure rates. The aim of this project is to study the relationship between DFS and OS in trials of early colorectal cancer. Methods: Phase III comparative trials in colorectal cancer were searched in databases and cancer meetings. Trials were split to build and validate the model. United States 2000 population life table data were obtained from Berkeley Mortality Database. Survival curves were modelled according to a cured fraction following a Weibull distribution and a relapsing fraction following a binomial distribution. DFS was modelled as time to a single event and OS was modelled as time to two events. Cured fraction was estimated and odds ratio (OR) with 95% confidence interval was calculated for experimental arms. Time to achieve a plateau in DFS was estimated as the curve point with a risk of relapse below 1%. Regression analysis between DFS and OS was performed for different intervals of follow up. Results: Thirty six study arms reporting DFS were analyzed to build the model. The model is consistent with an annual event rate of 0.33. DFS curves with this event rate predict a mean cure rate of 0.58 (range: 0.11–0.73). Estimated time to achieve a plateau in DFS is 9.3 years (range: 8.3–11.2 years). Significance of OR is coherent with hazard ratio reported in the studies. Trials finished after 1999 show more OS related to DFS. Regression analysis between DFS and OS show changing parameters at different intervals of follow up and some non-linearities. Trial validation, and analysis with trials reporting relapse free survival will be presented. Conclusions: Follow up of up to 10 years in colon adjuvant trials appears to be appropriate to reliably detect benefit in OS instead of a delay effect on relapse. No significant financial relationships to disclose.

Polymorphism of the chemokine CXCR4 to predict treatment benefit of first-line bevacizumab-based chemotherapy in patients with metastatic colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 635-635
Author(s):  
Satoshi Matsusaka ◽  
Fotios Loupakis ◽  
Wu Zhang ◽  
Shu Cao ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Metastatic Colorectal Cancer ◽  
Tumor Cells ◽  
Direct Sequencing ◽  
Univariate Analysis ◽  
Candidate Snps ◽  
First Line ◽  
Significant Difference

635 Background: The chemokine receptor CXCR4 and its ligand CXCL12 promote angiogenesis and the migration of tumor cells into the metastatic sites in many cancers. CXCR4 expression on tumor cells is upregulated by hypoxia and angiogenic factors, such as vascular endothelial growth factor. Therefore, we analyzed the association between CXCR4/CXCL12 polymorphisms and prognosis in metastatic colorectal cancer (mCRC) patients underwent bevacizumab-based chemotherapy. Methods: This study included 144 Japanese patients (pts) for evaluation set and 424 patients from two clinical trials (204 of TRIBE arm A and 220 of PROVETTA) for validation set, with mCRC treated with bevacizumab-based chemotherapy as first line. A total of 144 Japanese pts with (male/female; 81/63, median age 61 years, median follow-up 4.2 years) and 424 pts (male/female; 252/172, median age 62 years; median follow-up time; 2.8 years) were enrolled in a pharmacogenomics translational study. Genomic DNA was extracted from the pts’ blood or tissue. One CXCR4 single nucleotide polymorphisms (SNP) (rs2228014) and two CXCL12 SNPs (rs1801157, rs3740085) were analyzed by PCR-based direct sequencing. All candidate SNPs were analyzed for association with the clinical outcome. Results: In univariate analysis, CXCR4 rs2228014 showed a significant difference in PFS [(G/G 15.3 months, any A allele 13.7 months, HR (95% CI) 1.64 (1.01-2.68), p=0.036)]. After multivariate analysis, CXCR4 rs2228014 remained to be a significant for PFS [HR (95% CI) 1.67 (1.01-2.78), p =0.046]. However, this polymorphism was not associated with tumor response and survival. In the validation cohort, pts with GG genotype had significantly longer PFS compared to those with any A allele (10.5 vs 9.6 months, HR (95% CI) 1.40 (1.02-1.93), p =0.035). CXCL12 polymorphisms were not associated with the clinical outcome. Conclusions: This study shows for the first time that CXCR4 rs2228014 may serve as a predictive marker in patients with mCRC treated with bevacizumab-based chemotherapy.

scholarly journals Adult Granulosa Cell Tumors of the Ovary: A Retrospective Study of 36 FIGO Stage I Cases with Emphasis on Prognostic Pathohistological Features

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Emina Babarović ◽  
Ivan Franin ◽  
Marko Klarić ◽  
Ani Mihaljević Ferrari ◽  
Ružica Karnjuš-Begonja ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Univariate Analysis ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Figo Stage ◽  
Free Survival ◽  
Granulosa Cell Tumors ◽  
Diffuse Growth ◽  
Disease Free

Objective. Adult granulosa cell tumors (AGCTs) represent 2%–5% of all ovarian malignancies. The aim of this study was to analyze clinical and pathohistological parameters and their impact on recurrence, overall, and disease-free survival in FIGO stage I AGCT patients. Methods. The tumor specimens analyzed in this retrospective study were obtained from a total of 36 patients with diagnosis of ovarian AGCT surgically treated at the Department of Gynecology, Rijeka University Hospital Centre, between 1994 and 2012. Clinical, pathological, and follow-up data were collected. Results. The mean age at diagnosis was 54.5 years with a range of 24–84. The majority of the patients, 30 (83%), were in FIGO stage IA, 3 (8%) in stage IC1, 1 (3%) in stage IC2, and 2 (6%) in stage IC3. During follow-up period (median 117.5 months, range 26–276), recurrence occurred in 4 patients (12%) with 2 deaths of the disease recorded. In univariate analysis, the 5-year survival rates were significantly shorter in patients with FIGO substage IC (p=0.019), with positive LVSI (p=0.022), with presence of necrosis (p=0.040), and with hemorrhage (p=0.017). In univariate analysis, the 5-year disease-free survival rates were significantly shorter in patients treated with fertility surgery (p=0.004), with diffuse growth pattern (p=0.012), with moderate and severe nuclear atypia (p=0.032), and with presence of hemorrhage (p=0.022). FIGO substage IC proved to be independent predictor for recurrence (OR = 16.87, p=0.015, and OR = 23.49, p=0.023, resp.) and disease-free survival (p=0.0002; HR 20.84, p=0.02) at the uni- and multivariate analyses. Conclusions. FIGO substage IC is predictive of recurrence and disease-free survival in patients with early-stage AGCTs. LVSI, presence of necrosis and hemorrhage, diffuse growth pattern, and nuclear atypia in AGCTs seem to be associated with overall and disease-free survival, so these pathological features should be taken into consideration when managing patients with AGCT.

scholarly journals 15-year Follow-up of Comparing Mastoscopic and Conventional Axillary Dissection in Breast Cancer: A Multicentres, Randomized Controlled Trial

2020 ◽  
Author(s):  
Chengyu Luo ◽  
Guang Cao ◽  
wenbin Guo ◽  
Jie Yang ◽  
Qiuru Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Axillary Lymph ◽  
Term Survival ◽  
Free Survival ◽  
Significant Difference ◽  
Disease Free

Abstract Backgroud: Longer follow-up was necessary to testify the exact value of mastoscopic axillary lymph node dissection (MALND).Methods：From January 1, 2003 to December 31, 2005,1027 patients with operable breast cancer were randomly assigned to two groups: MALND and CALND. 996 eligible patients were enrolled. The end points are disease free survival and overall survival.Results：The final cohort of 996 patients was followed for an average of 184 months. The distribution of all events was fairly similar between two groups of patients. The incidence of local in-breast events did not differ in a significant manner between two cohorts. Similarly, the rate of distant metastases was not significantly different with 30.0% in MLND and 32.6% in CALND. And no significant difference was observed in other primary tumor between two groups (p=0.46). Patients who remain alive with no event comprise a total of 37.2% in MALND and 35.4% in CALND. Other primary cancers and deaths from other causes were distributed equally between two groups. The 15-year disease-free survival rates were41.1 percent for the MALND group and 39.6 percent for the CALND group (p=0.79). MALND was found to be not inferior for overall survival (P =0.54). The 15-year overall survival rates were 49.5 percentafter MALND and 51.2 percentafter CALND (p=0.86). Probability of overall survival was not significantly different between two groups.Conclusions：MALND does not increase unfavorable events, and also does not affect the long-term survival of patients. Therefore, MALND should be one of the preferred approaches for breast cancer surgery.

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