Effects of Adjuvant Chemotherapy on Cognitive Function of Patients With Early-stage Colorectal Cancer

2019 ◽  
Vol 18 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Manuela Vasconcelos Castro Sales ◽  
Claudia K. Suemoto ◽  
Daniel Apolinario ◽  
ValeriaT. Serrao ◽  
Celi S. Andrade ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cognitive Function ◽  
Adjuvant Chemotherapy ◽  
Early Stage

Evaluation of the quality of cancer treatment in a population of patients (pts) with metastatic colorectal cancer (mCRC) in routine clinical practice in different regions of Russia.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18022-e18022
Author(s):  
Mikhail Fedyanin ◽  
Shamai Aliyeva ◽  
Liubov Yu Vladimirova ◽  
Sanal Erdniev ◽  
Alexander Ivanov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Mortality Rate ◽  
Metastatic Disease ◽  
Early Stage ◽  
Care Organization ◽  
Line Treatment ◽  
The Impact ◽  
Regions Of Russia ◽  
Egfr Antibody

e18022 Background: In Russia, there are no federal screening programs for detecting early stage of colon cancer; therefore we can assess the impact of various factors that could potentially affect the mortality of pts with mCRC Methods: We conducted a survey with 13 question according treatment of pts with CRC in 17 regional comprehensive cancer centers in 14 regions of Russia, with a total population of 26.347 billion. Results of the survey were conducted by methods of descriptive statistics. Effects of factors on mortality rate in regions were analyzed by a regression model Results: Only 34% pts with stage II-III received adjuvant chemotherapy. Mutation status of KRAS gene has been evaluated only in 33% pts with mCRC. In 2013, metastasectomy was performed only 13% of pts. Only 80% of pts who needed systemic treatment received chemotherapy (CT): doublets of CT (XELOX/FOLFOX/FLOX or FOLFIRI/XELIRI/IFL) - 49%, monotherapy of fluoropyrimidines - 39% of pts, bevacizumab – in 14% and anti-EGFR antibodies - 5% pts. Only 14% of pts with mCRC was placed central vein devices. Second line CT was performed in 47% pts: doublets – in 54%, monotherapy of fluoropyrimidines - in 24% pts, bevacizumab - 13% and anti-EGFR antibody - 8%. Third-line treatment was performed in 25% of pts: anti-EGFR antibodies - in 7.5%. According to regression analysis adjuvant chemotherapy (р = 0.01), bevacizumab only in the 1st line (р = 0.01), and installation of central venous devises (р = 0.07) and anti-EGFR antibody in the 1st line (р = 0.1) in wtKRAS pts had independent positive effect on the mortality rate in regions. We revealed a significant reverse connection between a high mortality rate in the region and administration of fluoropyrimidine monotherapy as 1st line treatment of metastatic disease (p = 0.01) Conclusions: The mortality with colorectal cancer is depended of complex factors that reflect the health care organization in the region, both at the stage of treatment of pts with early-stage and metastatic disease. We revealed that targeted agents are the most effective only in the 1st line settings.

Racial effect of early stage colorectal cancer outcomes in a comprehensive cancer center.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 710-710
Author(s):  
Benjamin D Fangman ◽  
Muhammad Shaalan Beg ◽  
Aravind Sanjeevaiah ◽  
Farshid Araghizadeh ◽  
Shannon Scielzo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Early Stage ◽  
Stage Ii ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Cancer Outcomes ◽  
Cancer Centers ◽  
Significant Difference ◽  
Oncologic Treatment

710 Background: Oncologic treatment at National Cancer Institute (NCI) designated comprehensive cancer centers improves outcomes in a variety of malignancies. Racial disparity plays an important role in cancer outcomes and prognosis. Racial outcomes were compared in early stage colorectal cancer patients that presented to a comprehensive cancer center. Methods: This is a retrospective analysis on patients diagnosed with AJCC stage II or stage III colorectal cancer and underwent surgery or adjuvant chemotherapy within the University of Texas Southwestern and Simmons Comprehensive Cancer Center. Pertinent data points were abstracted from EMR including demographic data and dates of initial diagnosis, surgery, adjuvant chemotherapy, progression, and death. Results: Between 4/2011 and 11/2015, 203 patients were identified and 167 patients had complete follow up data available. Median age of cohort was 62 (range 21-90) and most of the patients were men (52.7%). Stage II comprised 44.3% of patients while 55.7% were diagnosed at stage III. One hundred and twenty patients (71.9%) were white, while 34 patients (20.4%) identified as black and the rest belonged to other races. Hispanic ethnicity was identified in 10.4% of patients. There was no significant difference between white and black cohorts between variables age (median 62 vs. 64.5 years; p = 0.44), gender (p = 0.43), and stage (p = 0.99) of colorectal cancer. Similarly there was no significant difference between white and black race in regards to days to surgery (median 17 vs 32 days; p = 0.53), first medical oncology appointment (30 vs. 34 days; p = 0.23) and days to adjuvant chemotherapy (42 vs 52 days; p = 0.24). The rate of recurrence (10.9% vs. 26%; p = 0.09), rate of death (14.1% vs 14.7%; p = 1.0), median relapse free survival (41.7 vs. 36.2 months; p = 0.173) and median overall survival (42 vs. 38.5 months; p = 0.491) from colorectal cancer were also not significantly different between white and black races. Conclusions: Oncologic treatment at NCI designated comprehensive cancer centers may lead to racial parity in colorectal cancer outcomes. Further research should be completed to compare these results to those seen at safety net hospitals.

scholarly journals ctDNA to Guide Adjuvant Therapy in Localized Colorectal Cancer (CRC)

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2869
Author(s):  
Laura Masfarré ◽  
Joana Vidal ◽  
Concepción Fernández-Rodríguez ◽  
Clara Montagut
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Adjuvant Chemotherapy ◽  
Residual Disease ◽  
Early Stage ◽  
Recurrence Risk ◽  
Circulating Tumor Dna ◽  
Key Points ◽  
The Impact ◽  
Critical Overview

Currently, the standard treatment for patients with localized colorectal cancer (CRC) includes surgical resection followed by adjuvant chemotherapy based on clinicopathological features. Recurrence risk stratification in those patients is of utmost importance to guide clinicians to avoid both under- and overtreatment. Recently, the concept of minimal residual disease (MRD) has emerged as the detection of circulating tumor DNA (ctDNA) carrying tumor-specific genomic or epigenomic alterations in the bloodstream of patients after surgery. Emerging studies described how the detection of MRD is a powerful prognostic biomarker to identify patients at higher risk of recurrence and who will potentially benefit the most from a systemic adjuvant treatment. Based on that unprecedented finding, several clinical trials involving stage II and III CRC patients are ongoing evaluating the impact of ctDNA guided treatment by escalating or deescalating adjuvant chemotherapy based on ctDNA MRD detection. This review provides a critical overview of current perspectives of liquid biopsy in early-stage CRC including technical, biological, and clinical key points, as well as ongoing ctDNA-based clinical trials that ultimately aim to improve clinical outcomes of patients with CRC.

Exploring fingerprint ctDNA as a stratifying factor in colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16101-e16101
Author(s):  
Wending Sun ◽  
Jianwei Zhang ◽  
Jinwang Wei ◽  
Chun Dai ◽  
Jun Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Early Stage ◽  
Disease Free Survival ◽  
Predictive Biomarker ◽  
Clinical Decision ◽  
Circulating Tumor Dna ◽  
Good Prognosis ◽  
Gene Copy ◽  
Significant Difference

e16101 Background: Colorectal cancer (CRC) ranks near the top in tumor-related deaths. Its standard-of-care is surgical resection plus adjuvant chemotherapy, which can extend patient’s live and disease-free survival for up to several years. However, choosing an appropriate chemotherapy agent is difficult because CRC is a heterogenous disease. It is believed that molecular stratification can help to improve treatment accuracy and this has been proven by the consensus molecular subtypes (CMS) classification. However, the CMS classification relies on expensive and complex gene-expression profiling, and more cumbersomely, is limited to early stage patients without prior chemotherapy, radiation and metastasis. This situation denies many CRC patients from the benefit of CMS classification. Circulating tumor DNA (ctDNA) is a minimally invasive way to monitor disease progression and treatment response in solid tumors but its clinical utility in CRC remains to be validated. We explore the potential of using patient’s fingerprint ctDNA (defined below) as a stratifying factor in CRC patients to assist clinical decision. Methods: WES is performed on tumor and matched blood samples from 149 CRC patients. Based on the WES result, 20-30 tumor specific genes are selected for each patient and form their ctDNA fingerprints. The patients are grouped according to their level of fingerprint ctDNA (high- vs. low-ctDNA). Results: The two groups of patients show significant difference in treatment responses and mutational profiles. The low-ctDNA group in general respond to treatment well and have good prognosis. The high-ctDNA group, in contrast, often experience relapse or recurrence. Interestingly, the low-ctDNA group is dominated by point and small indel mutations in the top mutated genes while the high-ctDNA group is dominated by gene copy variations (CNV). SMAD4 deficit and DCC amplification are well known CNV in CRC, but they only appear in the high-ctDNA group. Similarly, CNV of AGO2, ACTG1, MYC, and BRD3 are only associated with the high-ctDNA group but not the low-ctDNA group. Conclusions: Our result indicates a strong correlation of fingerprint ctDNA level to both tumor mutational profile and prognosis. This suggests fingerprint ctDNA level may be used as an effective stratifying factor in CRC. At the same time, possibly a common molecular cause is driving persistent ctDNA production in CRC patients, including a large portion of them who have received surgical and adjuvant chemotherapy. Further perspective study, however, is needed to test whether fingerprint ctDNA can be a predictive biomarker.

Is mucinous histology a prognostic marker in early and advanced colorectal cancer?

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 253-253
Author(s):  
Rosemary Habib ◽  
Val Gebski ◽  
Kenneth Micklethwaite ◽  
Duncan McLeod ◽  
James Toh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Proportional Hazards ◽  
Advanced Colorectal Cancer ◽  
Early Stage ◽  
Stage Iv ◽  
Clinical Information ◽  
Poor Response ◽  
Female Gender ◽  
Stage Ii

253 Background: In early and advanced colorectal cancer (CRC), there is limited data comparing the influence of mucinous (MAC) with non-mucinous adenocarcinoma (NMAC) histology on clinical outcomes. We investigated the association between histological type and outcomes in CRC. Methods: Medical records of patients with stage II, III and IV CRC referred to a tertiary centre in Western Sydney between 2009-2016 were examined and demographic and clinical information extracted. Key prognostic factors were modeled using log rank tests and proportional hazards (PH) regression methods in multivariate analyses. Results: Data on 686 patients was extracted. Median age was 70 years (19 – 94). Median follow up was 38.4 months. 98 patients (12%) had MAC and no differences in stage were observed at presentation between MAC and NMAC (p = 0.16). MAC was associated with increased prevalence of microsatellite instability (36% v 11% p < 0.01), high grade tumours (51% v 18% p < 0.01), female gender (61% v 45% p < 0.01) and right sided primary (65% v 40% p < 0.01). In stage II/III, MAC had comparable relapse free survival (RFS) versus NMAC (median 79 vs 97 months; P = 0.21). However, in the adjuvant chemotherapy group, a poorer RFS was seen for MAC (52 Vs 82 months, HR = 0.52, P = 0.03). In all patients with relapsed disease, MAC was more likely to be associated with peritoneal carcinomatosis (51% vs 26%; P < 0.01), and less likely to be associated with liver metastases (45% Vs 70%, P < 0.01) than NMAC. PH analysis of the MAC cohort revealed poorer RFS for LVI (HR 2.85; p = 0.03), T4 stage (HR 3.15, p = 0.01) and adjuvant chemotherapy (HR 5.49, p < 0.01). On multivariate analysis, T4 remained significant for poorer RFS. No differences were seen in OS in early stage CRC between MAC and NMAC. However, right sided and female gender with stage IV MAC had poorer OS (Right colon: HR 6.6; P = 0.03) (Female: HR 4.90, P = 0.03). Conclusions: MAC is associated with poorer RFS in early stage CRC irrespective of sidedness, and with poorer OS in right sided CRC. Given their poor response to adjuvant chemotherapy, novel adjuvant treatments should be considered for early MAC CRC. In the palliative setting, novel therapies and clinical trials are required for patients with MAC, particularly with right sided primaries.

scholarly journals Colorectal Cancer Care Among Young Adult Patients After the Dependent Coverage Expansion Under the Affordable Care Act

2019 ◽  
Vol 112 (10) ◽  
pp. 1063-1066 ◽  
Author(s):  
Leticia Nogueira ◽  
Neetu Chawla ◽  
Xuesong Han ◽  
Ahmedin Jemal ◽  
K Robin Yabroff
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Confidence Interval ◽  
Affordable Care Act ◽  
Cancer Care ◽  
Early Stage ◽  
Hazard Ratio ◽  
Coverage Expansion ◽  
The Affordable Care Act ◽  
Dependent Coverage

Abstract The effect of the Dependent Coverage Expansion (DCE) under the Affordable Care Act (ACA) on receipt of colorectal cancer treatment has yet to be determined. We identified newly diagnosed DCE–eligible (aged 19–25 years, n = 1924) and DCE–ineligible (aged 27–34 years, n = 8313) colorectal cancer patients from the National Cancer Database from 2007 to 2013. All statistical tests were two-sided. Post-ACA, there was a statistically significant increase in early-stage diagnosis among DCE–eligible (15 percentage point increase, confidence interval = 9.8, 20.2; P &lt; .001), but not DCE–ineligible (P = .09), patients. DCE–eligible patients resected for IIB–IIIC colorectal cancer were more likely to receive timely adjuvant chemotherapy (hazard ratio = 1.34, 95% confidence interval = 1.05 to 1.71; 7.0 days’ decrease in restricted mean time from surgery to chemotherapy, P = .01), with no differences in DCE–ineligible patients (hazard ratio = 1.10, 95% confidence interval = 0.98 to 1.24; 2.1 days’ decrease, P = .41) post-ACA. Our findings highlight the role of the ACA in improving access to potentially lifesaving cancer care, including a shift to early-stage diagnosis and more timely receipt of adjuvant chemotherapy.

scholarly journals Association of DNA repair gene variants with colorectal cancer: risk, toxicity, and survival

2020 ◽  
Author(s):  
Hamideh Salimzadeh ◽  
Elinor Bexe Lindskog ◽  
Bengt Gustavsson ◽  
Yvonne Wettergren ◽  
David Ljungman
Keyword(s):  
Colorectal Cancer ◽  
Dna Repair ◽  
Adjuvant Chemotherapy ◽  
Early Stage ◽  
Rank Test ◽  
First Line ◽  
Clinical Value ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Increased Risk

Abstract Background : Single nucleotide polymorphisms (SNPs) in DNA repair genes have a potential clinical value in predicting treatment outcomes. In the current study, we examined the association of SNPs in the genes XRCC1-rs25487, ERCC1-rs11615, ERCC2-rs238406, and ERCC2-rs13181 with colorectal cancer (CRC) risk, relapse-free survival (RFS), overall survival (OS), and toxicity during chemotherapy. Methods: SNPs were analysed in 590 CRC cases and 300 controls using TaqMan technology. The association of SNPs with CRC risk and toxicity during chemotherapy was analysed using Chi2 test. The Kaplan–Meier method and Log-rank test was used to measure the effects of the SNPs on RFS and OS. Results: The ERCC2-rs238406 A allele and the ERCC2-rs13181 C allele were associated with a significantly increased risk of CRC. The ERCC1-rs11615 genotype T/T was associated with stomatitis in adjuvant chemotherapy ( p = 0.03). Also, more patients with the ERCC2rs13181 C allele needed dose reduction compared to patients with the A/A genotype ( p = 0.02). In first line chemotherapy, more patients with the ERCC1-rs11615 C allele suffered from nausea compared with those with the T/T genotype ( p = 0.04) and eye reactions and thrombocytopenia were more common in patients with the ERCC2-rs13181 C allele compared to the A/A genotype ( p = 0.006 and p = 0.004, respectively). Also, ERCC2- rs238406 C/C was associated with a higher frequency of thrombocytopenia ( p =0.03). A shorter 5-year OS was detected in stage I & II CRC patients with the ERCC2- rs238406 C allele ( p = 0.02). However, there was no significant association between the SNPs and 5-year RFS. Conclusions: Both SNPs in ERCC2 were associated with risk of CRC as well as toxicity during first line treatment. In addition, ERCC2- rs238406 was linked to OS in early stage CRC. The ERCC1-rs11615 variant was associated with toxicity during adjuvant chemotherapy. The results add support to previous findings that SNPs in ERCC1 and ERCC2 have a prognostic and predictive value in clinical management of CRC.

scholarly journals Association of DNA repair gene variants with colorectal cancer: risk, toxicity, and survival

2020 ◽  
Author(s):  
Hamideh Salimzadeh ◽  
Elinor Bexe Lindskog ◽  
Bengt Gustavsson ◽  
Yvonne Wettergren ◽  
David Ljungman
Keyword(s):  
Colorectal Cancer ◽  
Dna Repair ◽  
Adjuvant Chemotherapy ◽  
Early Stage ◽  
Rank Test ◽  
First Line ◽  
Clinical Value ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Increased Risk

Abstract Background: Single nucleotide polymorphisms (SNPs) in DNA repair genes have a potential clinical value in predicting treatment outcomes. In the current study, we examined the association of SNPs in the genes XRCC1-rs25487, ERCC1-rs11615, ERCC2-rs238406, and ERCC2-rs13181 with colorectal cancer (CRC) risk, relapse-free survival (RFS), overall survival (OS), and toxicity during chemotherapy.Methods: SNPs were analysed in 590 CRC cases and 300 controls using TaqMan technology. The association of SNPs with CRC risk and toxicity during chemotherapy was analysed using Chi2 test. The Kaplan–Meier method and log-rank test was used to measure the effects of the SNPs on RFS and OS.Results: The CC genotype of ERCC2-rs238406 and the ERCC2-rs13181 C allele were associated with a significantly increased risk of CRC. The ERCC1-rs11615 genotype T/T was associated with stomatitis in adjuvant chemotherapy (p= 0.03). Also, more patients with the ERCC2-rs13181 C allele needed dose reduction compared to patients with the A/A genotype (p= 0.02). In first line chemotherapy, more patients with the ERCC1-rs11615 C allele suffered from nausea compared to those with the T/T genotype (p= 0.04) and eye reactions and thrombocytopenia were more common in patients with the ERCC2-rs13181 C allele compared to the A/A genotype (p= 0.006 and p= 0.004, respectively). ERCC2- rs238406 C/C was also associated with a higher frequency of thrombocytopenia (p= 0.03). A shorter 5-year OS was detected in stage I & II CRC patients with the ERCC2- rs238406 C allele (p= 0.02). However, there was no significant association between the SNPs and 5-year RFS.Conclusions: Both SNPs in ERCC2 were associated with risk of CRC as well as toxicity during first line treatment. In addition, ERCC2- rs238406 was linked to OS in early stage CRC. The ERCC1-rs11615 variant was associated with toxicity during adjuvant chemotherapy. The results add support to previous findings that SNPs in ERCC1 and ERCC2 have a prognostic and predictive value in clinical management of CRC.

A Tale of Two Colons and Two Cancers

Swiss Surgery ◽  
2003 ◽  
Vol 9 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Gervaz ◽  
Bühler ◽  
Scheiwiller ◽  
Morel
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Splenic Flexure ◽  
Chromosomal Instability ◽  
Proximal Colon ◽  
Colorectal Carcinogenesis ◽  
Physiological Data ◽  
Central Hypothesis ◽  
Group Stratification

The central hypothesis explored in this paper is that colorectal cancer (CRC) is a heterogeneous disease. The initial clue to this heterogeneity was provided by genetic findings; however, embryological and physiological data had previously been gathered, showing that proximal (in relation to the splenic flexure) and distal parts of the colon represent distinct entities. Molecular biologists have identified two distinct pathways, microsatellite instability (MSI) and chromosomal instability (CIN), which are involved in CRC progression. In summary, there may be not one, but two colons and two types of colorectal carcinogenesis, with distinct clinical outcome. The implications for the clinicians are two-folds; 1) tumors originating from the proximal colon have a better prognosis due to a high percentage of MSI-positive lesions; and 2) location of the neoplasm in reference to the splenic flexure should be documented before group stratification in future trials of adjuvant chemotherapy in patients with stage II and III colon cancer.

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