Racial Disparity in Consultation, Treatment, and the Impact on Survival in Metastatic Colorectal Cancer

470 Background: Black patients with colorectal cancer have worse outcomes compared to white patients, however the underlying source of this racial disparity remains unclear. This population-based study evaluates the impact of race on referral patterns and subsequent treatment with chemotherapy or radiotherapy in metastatic colorectal cancer. Methods: This study used the Surveillance, Epidemiology, and End Results–Medicare linked database to identify 11,125 patients with stage IV colorectal cancer diagnosed between 2000-2007. Patient demographic data were abstracted from the SEER database, and referral and treatment information were derived from Medicare claims data. Multivariate logistic regression models determined the impact of race on 1) consultation patterns with medical oncology and radiation oncology, and 2) subsequent treatment with chemotherapy and radiation therapy. Results are presented as adjusted odds ratios (OR) that control for potential confounding factors including age, comorbidity, socioeconomic status, geography, gender, marital status, and year of diagnosis. Results: Of the entire patient cohort, 2,025 (18%) were seen in consultation by a radiation oncologist, and among these patients, 1,221 (60%) ultimately received radiotherapy. Black patients had significantly lower rates of consultation with a radiation oncologist compared to white patients (OR=0.79, 95% CI=0.65-0.96; p=0.016). Among patients with a radiation oncology consultation, fewer black patients were subsequently treated with radiotherapy (OR=0.67, 95% CI=0.46-0.99; p=0.046). There was no difference between black and white patients in time from diagnosis to radiation treatment, and no difference in radiation treatment duration. We found no race-related difference in medical oncology consultation rates (p=0.24), nor in subsequent treatment with chemotherapy (p=0.95). Conclusions: This study shows racial disparity in radiation oncology consultation rates, and in radiation therapy treatment. Further research evaluating these barriers to care will help us achieve equality in treatment of metastatic colorectal cancer.

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Lonsurf (trifluridine/tipiracil): Assessing the impact of dose related toxicities and progression free survival in (refractory) metastatic colorectal cancer

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211017973 ◽

2021 ◽

pp. 107815522110179

Author(s):

Olivia R Court

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Dose Reduction ◽

Progression Free Survival ◽

Electronic Patient Records ◽

Free Survival ◽

Length Of Treatment ◽

Common Grade ◽

Grade 3 ◽

The Impact

In the RECOURSE trial which lead to its accreditation, Lonsurf (trifluridine/tipiracil) was shown to extend progression free survival (PFS) by 1.8 months in metastatic colorectal cancer. This Trust audit aims to assess the average quantity of cycles of Lonsurf received by participants and the length of time it extends PFS. Similarly, to identify how many participants required a dose-reduction or experienced toxicities which necessitated supportive therapies. Quantitative data was collected retrospectively from all participants who had received ≥1 cycle of Lonsurf from The Clatterbridge Cancer Centre (CCC) from 2016 until June 2020. Participant electronic patient records were accessed to identify toxicity grading, length of treatment received, the date progression was identified, if dose reductions were applied and if supportive therapies were administered. Lonsurf extends PFS in patients with metastatic colorectal cancer at CCC by 3.0 months (95% CI: 2.73–3.27) and average treatment length was 2.4 months. However, 78 participants (41.5%) received a dose reduction due to toxicities. A total of 955 toxicities were recorded by participants; the most commonly reported toxicities irrespective of grade were fatigue (33.8%), diarrhoea (13.8%) and nausea (12.3%). The most common grade ≥3 toxicities were constipation and infection. The most frequently utilised supportive therapies were loperamide (49.6%) and domperidone (49.1%). Granulocyte colony stimulating factor (GCSF) was required by patients on 5 occasions (0.3%) in total. Lonsurf extends median PFS in patients with metastatic colorectal cancer by 3.0 months. The most common grade ≥3 toxicities which necessitated supportive therapies or a dose reduction were gastrointestinal and infection.

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Treatment with Antiangiogenic Drugs in Multiple Lines in Patients with Metastatic Colorectal Cancer: Meta-Analysis of Randomized Trials

Gastroenterology Research and Practice ◽

10.1155/2016/9189483 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

R.-D. Hofheinz ◽

U. Ronellenfitsch ◽

S. Kubicka ◽

A. Falcone ◽

I. Burkholder ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Kinase Inhibitors ◽

Meta Analysis ◽

Progression Free Survival ◽

Optimal Sequence ◽

Primary Endpoints ◽

Disease Stabilization ◽

Antiangiogenic Drugs ◽

The Impact

Background. In metastatic colorectal cancer (mCRC), continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis.Patients and Methods. We conducted a meta-analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the impact of continuing antiangiogenic drugs (i) in subgroups, (ii) in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors), and (iii) on remission rates and prevention of progression.Results. Eight studies (3,668 patients) were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55–0.75) and OS (HR 0.83; 95%-CI, 0.76–0.89). PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95%-CI, 1.41–3.58).Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs.

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The bevacizumab plus oxaliplatin-based chemotherapy regimen is more suitable for metastatic colorectal cancer patients with a history of schistosomiasis

10.21203/rs.2.18346/v1 ◽

2019 ◽

Author(s):

Li-Na Zhou ◽

Li-Qiang Weng ◽

Chun-Xia Feng ◽

Yan Zhang ◽

Ping Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Platelet Count ◽

Liver Fibrosis ◽

Metastatic Colorectal Cancer ◽

Medical Records ◽

Chemotherapy Regimen ◽

Splenic Enlargement ◽

History Of ◽

Colorectal Cancer Patients ◽

The Impact

Abstract Background: People suffer from schistosomiasis, leading to liver fibrosis, splenomegaly and thrombocytopenia. The effects of bevacizumab plus oxaliplatin or irinotecan-based chemotherapy regimens on platelets are different, but have not been determined. We conducted a retrospective analysis in metastatic colorectal cancer (mCRC) patients evaluating the impact of bevacizumab on platelet, in order to find a more suitable plan for mCRC patients with a history of schistosomiasis.Methods: The medical records of all mCRC patients with a history of schistosomiasis who received FOLFOX or FOLFIRI with or without bevacizumab from September 1, 2017 to June 30, 2019 in Kunshan Hospital were reviewed. Platelet counts and spleen sizes were compared from the first cycle until completion of chemotherapy.Results: Evaluable splenic enlargement and thrombocytopenia results were obtained from 73 Bevacizumab-treated patients and 80 non-bevacizumab treated patients. In patients treated with oxaliplatin, the rates of splenic enlargement (19.5% vs. 66.7%, P=0.01) and thrombocytopenia (31.7% vs. 77.2%, P=0.02) were lower in the bevacizumab-treated cohort than that in the nonbevacizumab cohort. When stratified for irinotecan, there were no statistical differences of frequency of splenic enlargement between the two groups, however, the rates of thrombocytopenia were higher in the bevacizumab-treated cohort than that in the nonbevacizumab cohort (59.4% vs. 8.7%, P=0.01 ).Conclusion: The bevacizumab plus oxaliplatin-based chemotherapy regimen is more suitable for mCRC patients with a history of schistosomiasis, especially for lower platelet count patients.

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The impact of panitumumab treatment on survival and quality of life in patients with RAS wild-type metastatic colorectal cancer

Cancer Management and Research ◽

10.2147/cmar.s186042 ◽

2019 ◽

Vol Volume 11 ◽

pp. 5911-5924 ◽

Cited By ~ 3

Author(s):

Francesca Battaglin ◽

Alberto Puccini ◽

Selma Ahcene Djaballah ◽

Heinz-Josef Lenz

Keyword(s):

Quality Of Life ◽

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Wild Type ◽

The Impact

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The impact of data errors on the outcome of randomized clinical trials

Clinical Trials ◽

10.1177/1740774517716158 ◽

2017 ◽

Vol 14 (5) ◽

pp. 499-506 ◽

Cited By ~ 9

Author(s):

Marc Buyse ◽

Pierre Squifflet ◽

Elisabeth Coart ◽

Emmanuel Quinaux ◽

Cornelis JA Punt ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Trials ◽

Metastatic Colorectal Cancer ◽

Randomized Clinical Trials ◽

Systematic Errors ◽

Age Related Macular Degeneration ◽

Random Errors ◽

Significant Treatment ◽

Age Related ◽

The Impact

Background/aims Considerable human and financial resources are typically spent to ensure that data collected for clinical trials are free from errors. We investigated the impact of random and systematic errors on the outcome of randomized clinical trials. Methods We used individual patient data relating to response endpoints of interest in two published randomized clinical trials, one in ophthalmology and one in oncology. These randomized clinical trials enrolled 1186 patients with age-related macular degeneration and 736 patients with metastatic colorectal cancer. The ophthalmology trial tested the benefit of pegaptanib for the treatment of age-related macular degeneration and identified a statistically significant treatment benefit, whereas the oncology trial assessed the benefit of adding cetuximab to a regimen of capecitabine, oxaliplatin, and bevacizumab for the treatment of metastatic colorectal cancer and failed to identify a statistically significant treatment difference. We simulated trial results by adding errors that were independent of the treatment group (random errors) and errors that favored one of the treatment groups (systematic errors). We added such errors to the data for the response endpoint of interest for increasing proportions of randomly selected patients. Results Random errors added to up to 50% of the cases produced only slightly inflated variance in the estimated treatment effect of both trials, with no qualitative change in the p-value. In contrast, systematic errors produced bias even for very small proportions of patients with added errors. Conclusion A substantial amount of random errors is required before appreciable effects on the outcome of randomized clinical trials are noted. In contrast, even a small amount of systematic errors can severely bias the estimated treatment effects. Therefore, resources devoted to randomized clinical trials should be spent primarily on minimizing sources of systematic errors which can bias the analyses, rather than on random errors which result only in a small loss in power.

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450P The impact of late-line treatment on overall survival (OS) from the initiation of first-line chemotherapy (CT) for patients (pts) with metastatic colorectal cancer (mCRC): Updated analysis

Annals of Oncology ◽

10.1016/j.annonc.2020.08.561 ◽

2020 ◽

Vol 31 ◽

pp. S433

Author(s):

T. Kawakami ◽

K. Yamazaki ◽

H. Go ◽

T. Masuishi ◽

Y. Kawamoto ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Metastatic Colorectal Cancer ◽

Line Treatment ◽

First Line ◽

The Impact ◽

Line Chemotherapy

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

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e14156 ◽

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.

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