Risk of arterial and venous thromboembolic events among patients with colorectal carcinoma: a real-world, population-based study

Future Oncology ◽

10.2217/fon-2021-0252 ◽

2021 ◽

Author(s):

Omar Abdel-Rahman ◽

Cynthia Wu ◽

Jacob Easaw

Keyword(s):

Colorectal Cancer ◽

Venous Thromboembolism ◽

Colorectal Carcinoma ◽

Metastatic Disease ◽

Real World ◽

Thromboembolic Event ◽

World Population ◽

Thromboembolic Events ◽

Factors Associated ◽

Male Sex

Objective: To assess real-world patterns of arterial and venous thromboembolism among patients with colorectal carcinoma. Methods: The Alberta provincial cancer registry and other provincial medical records were used to identify patients with colorectal cancer (2004–2018) with no preceding or succeeding cancer diagnosis. The incidence of both arterial and venous thromboembolism in this patient population as well as factors associated with these thromboembolic events were examined through logistic regression analysis. Results: A total of 17,296 patients were found eligible and were included into the current study. We observed that 1564 patients (9%) experienced a thromboembolic event and 15,732 patients (91%) did not. The following factors were associated with any thromboembolic event: male sex (odds ratio [OR]: 1.20; 95% CI: 1.08–1.34), higher comorbidity (OR: 1.36; 95% CI: 1.31–1.41), metastatic disease (OR for nonmetastatic vs metastatic disease: 0.53; 95% CI: 0.47–0.60), living within North zone (OR for Edmonton zone vs North zone: 0.70; 95% CI: 0.59–0.84), treatment with fluoropyrimidines (OR for no fluoropyrimidines vs fluoropyrimidines: 0.53; 95% CI: 0.47–0.60) and treatment with bevacizumab (OR: for no bevacizumab vs bevacizumab: 0.53; 95% CI: 0.47–0.60). Factors associated with venous thromboembolism include, younger age (continuous OR with increasing age: 0.99; 95% CI: 0.98–0.99), higher comorbidity (OR: 1.10; 95% CI: 1.04–1.17), metastatic disease (OR for nonmetastatic disease vs metastatic disease: 0.40; 95% CI: 0.35–0.47), North zone (OR for Edmonton zone vs North zone: 0.70; 95% CI: 0.56–0.86), treatment with fluoropyrimidines (OR for no fluoropyrimidines vs fluoropyrimidines: 0.45; 95% CI: 0.39–0.53) and treatment with bevacizumab (OR for no bevacizumab vs bevacizumab: 0.73; 95% CI: 0.58–0.93). Conclusion: Thromboembolic events are not uncommon among colorectal cancer patients, and the risk is increased with male sex, higher comorbidity, presence of metastatic disease, living within the North zone of the province (where there is limited access to tertiary care centers) and treatment with fluoropyrimidines or bevacizumab.

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NCDB Analysis of Melanoma 2004–2015: Epidemiology and Outcomes by Subtype, Sociodemographic Factors Impacting Clinical Presentation, and Real-World Survival Benefit of Immunotherapy Approval

Cancers ◽

10.3390/cancers13061455 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1455

Author(s):

Sunny R. K. Singh ◽

Sindhu J. Malapati ◽

Rohit Kumar ◽

Christopher Willner ◽

Ding Wang

Keyword(s):

Metastatic Melanoma ◽

Metastatic Disease ◽

Real World ◽

Care Delivery ◽

Sociodemographic Factors ◽

P Value ◽

Real World Data ◽

Factors Associated ◽

Improvement In Survival ◽

The Impact

Background: The incidence of invasive melanoma is rising, and approval for the first immune checkpoint inhibitor (ICI) to treat metastatic melanoma occurred in 2011. We aim to describe the epidemiology and outcomes in recent years, sociodemographic factors associated with the presence of metastasis at diagnosis, and the real‐world impact of ICI approval on survival based on melanoma subtype and race. Methods: This is a retrospective analysis of the National Cancer Database (NCDB) from the years 2004–2015. The primary outcome was the overall survival of metastatic melanoma by subtype. Secondary outcomes included sociodemographic factors associated with the presence of metastasis at diagnosis and the impact of treatment facility type and ICI approval on the survival of metastatic melanoma. Results: Of the 419,773 invasive melanoma cases, 93.80% were cutaneous, and 4.92% were metastatic at presentation. The odds of presenting with metastatic disease were higher in African Americans (AA) compared to Caucasians (OR 2.37; 95% CI 2.11–2.66, p < 0.001). Treatment of metastatic melanoma at an academic/research facility was associated with lower mortality versus community cancer programs (OR 0.75, 95 % CI 0.69–0.81, p-value<0.001). Improvement in survival of metastatic melanoma was noted for Caucasians after the introduction of ICI (adjusted HR 0.80, 95% CI 0.78–0.83, p < 0.001); however, this was not statistically significant for AA (adjusted HR 0.80, 95% CI 0.62–1.02, p‐value = 0.073) or ocular cases (HR 1.03, 95% CI 0.81–1.31, p‐value 0.797). Conclusion: Real‐world data suggest a 20% improvement in survival of metastatic melanoma since the introduction of ICI. The disproportionately high odds of metastatic disease at presentation in AA patients with melanoma suggest the need for a better understanding of the disease and improvement in care delivery.

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Nasal Cavity Metastasis From Colorectal Cancer Represents End-Stage Disease and Should Be Palliated

Annals of Coloproctology ◽

10.3393/ac.2019.03.04 ◽

2020 ◽

Vol 36 (2) ◽

pp. 119-121

Author(s):

Stephen Hwang ◽

Dedrick Kok Hong Chan ◽

Fredrik Petersson ◽

Ker-Kan Tan

Keyword(s):

Colorectal Cancer ◽

Colorectal Carcinoma ◽

Nasal Cavity ◽

Metastatic Disease ◽

Previous History ◽

Nasal Sinus ◽

Stage Disease ◽

History Of ◽

End Stage ◽

High Index Of Suspicion

Nasal metastases from colorectal cancer is rare. The presentation of nasal metastases is often very similar to primary nasal sinus adenocarcinoma. A high index of suspicion is required, especially in patients who have had a previous history of colorectal carcinoma. Histology is ultimately required for diagnosis. We describe 2 cases of nasal metastases from colorectal carcinoma, and discuss the presentation, diagnosis and management of the case. Such metastatic disease ultimately represents end-stage malignancy, and patients should be palliated.

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Real-world time on treatment and overall survival in patients with metastatic colorectal cancer receiving cetuximab in second line after failing irinotecan or oxaliplatin-based regimens.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e15568 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e15568-e15568

Author(s):

Wambui Gathirua-Mwangi ◽

Tony Yang ◽

Taha Khan ◽

Yixun Wu ◽

Manuel Afable

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Metastatic Colorectal Cancer ◽

Real World ◽

Index Date ◽

Growth Factor Receptor ◽

Community Setting ◽

Second Line ◽

Cox Models ◽

Factors Associated

e15568 Background: Anti-epidermal growth factor receptor agents are increasingly used in later lines of therapy for the treatment of metastatic colorectal cancer (mCRC). However, the real-world time on treatment (TOT) and overall survival (OS) of patients with mCRC receiving cetuximab in second-line (2L) setting have not been described. Therefore, we sought to evaluate TOT, OS and identify factors associated with longer TOT and OS based on retrospective observational data. Methods: A total of 1,011 patients were selected from the nationwide Flatiron electronic health record database (January 2013-August 2020) who were: 1) diagnosed with mCRC, 2) received 2L treatment with cetuximab containing regimens, and 3) had failed oxaliplatin/irinotecan-based regimens in first-line (1L). TOT was defined as the time from initiation of cetuximab in 2L (index date), to the last date showing evidence of cetuximab administration. End of therapy was defined if patients progressed to third-line of therapy, or having a death record. OS was calculated from the index date to the date of death or censored to last visit date available. The Kaplan-Meier estimates, and stepwise Cox models were adapted to calculate hazard ratios (HR) and 95% confidence intervals (CI) for associated factors. Results: Majority of patients receiving 2L treatment with cetuximab containing regimens were: less than 65 years old (58%), male (60%), had a median body mass index (BMI) of 26.6 kg/m², received FOLFOX regimens in 1L (61%) and were treated in the community setting (96%). The most common 2L regimens were cetuximab+FOLFIRI (46%) and cetuximab+Irinotecan (29%). Overall, the median TOT (mTOT) for patients receiving 2L cetuximab was 3.94 months (median Interquartile range (mIQR) 3.51-4.40), and median OS (mOS) was 14.36 months (mIQR 13.01-15.70). Of all cetuximab containing regimens, receiving cetuximab+FOLFIRI in 2L (mTOT = 4.43 months, mIQR 3.71-5.36), KRAS wild-type (vs. KRAS+), and receiving 2L cetuximab after prior therapy with 1L CapeOX (vs. FOLFOX) were associated with a longer mTOT. Living in the South region (vs. Midwest) was associated with a shorter mTOT. Having a higher BMI (obese vs. underweight HR = 0.46, 95% CI 0.32-0.66) was associated with a longer mOS, while receiving cetuximab+FOLFOX in 2L (mOS = 10.97 months, mIQR 5.55-14.06) or being older (≥65 vs. < 65 years; HR = 1.24, 95% CI 1.05-1.46) were associated with a shorter mOS. Conclusions: In this real-world retrospective analysis we show TOT and OS overall in mCRC patients who received cetuximab containing regimens in 2L. These patients were mostly male, < 65 years, and majority received FOLFOX regimens in 1L therapy. Key factors associated with TOT and OS were treatment regimens received in 1L and 2L. In addition, KRAS status and region were associated with TOT, while BMI and age were associated with OS only.

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Oral Anticoagulation Treatment and Persistence After Venous Thromboembolism In a Real World Population: The Q-VTE Study Cohort

Blood ◽

10.1182/blood.v122.21.2386.2386 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2386-2386

Author(s):

Vicky Tagalakis ◽

Valerie Patenaude ◽

Susan R. Kahn ◽

Samy Suissa

Keyword(s):

Venous Thromboembolism ◽

Real World ◽

Oral Anticoagulation ◽

Clinical Guidelines ◽

Conflicts Of Interest ◽

Vitamin K Antagonists ◽

Study Cohort ◽

World Population ◽

Treatment Persistence ◽

Number Of Patients

Abstract Background For patients who are diagnosed with venous thromboembolism (VTE) provoked by transient risk factors, clinical guidelines typically recommend 3 months of oral anticoagulation, with longer treatment considered for unprovoked VTE. Describing treatment patterns of VTE in a real world population may identify remedial gaps in patient care. Aim We aimed to characterize oral anticoagulant treatment with vitamin K antagonists (VKA) following incident VTE and assess persistence of VKA therapy in patients with provoked vs. unprovoked VTE in a real world setting. Methods We used the linked administrative healthcare databases of the province of Québec, Canada, including the hospitalization, universal healthcare services, and out-patient prescription databases. We identified all beneficiaries with an incident DVT or PE between 2000 and 2009, which we classified as definite or probable VTE using a priori determined diagnostic algorithms based on ICD-9-CM or ICD-10-CA diagnosis codes. We formed two patient cohorts, one with definite and the other including definite or probable first-time VTE, that were followed until death or end of study (December 31, 2009). Anticoagulant out-patient prescription patterns were analyzed for both patient cohorts. Results From 245,452 Québec residents between 2000 and 2009 with at least 1 VTE diagnosis in RAMQ or MED-ÉCHO, we formed the definite VTE cohort including 40,776 definite cases and the any VTE cohort consisting of 54,803 definite or probable cases. From the 40,776 patients with a first definite VTE, there were 24,860 patients with DVT alone (61%) and 15,916 with PE with or without DVT (39%). Furthermore, there were 78% of patients over the age of 60 and 58.3% of patients were women. In all, 8,998 (22.1%) patients had an unprovoked VTE event while 19,010 (46.6%) patients had a provoked non-cancer event. Similar findings were found in the any VTE cohort. Among definite VTE cohort patients with a provoked non-cancer VTE, 68.6% of patients received anticoagulation after the VTE event. Most were dispensed VKA (64.9%) and 23.9% received a prescription for low molecular weight heparin (LMWH). Among patients with an unprovoked VTE, 86.3% of patients were prescribed anticoagulation (84.5% used VKA and 39.9% used LMWH). Overall, a greater number of patients received anticoagulation following PE (85.2%) than DVT alone (66.2%). Results were similar in the any VTE cohort. Persistence with VKA therapy among patients with provoked VTE was 86.9% at 90 days, 59.5% at 180 days and 19.9% at 365 days. Treatment persistence for patients with unprovoked non-cancer VTE was 88.8%, 66.8% and 22.9% for 90, 180 and 365 days, respectively. Similar findings were found in the any VTE cohort. Conclusions Our study provides useful information on VTE management in a real world population. Treatment persistence was similar for patients with provoked and unprovoked VTE. VKA therapy duration after provoked VTE was longer than the recommended 3 months, whereas treatment was shorter than suggested in patients with unprovoked VTE. Further investigation is needed to determine reasons for non-adherence to clinical guidelines. Disclosures: No relevant conflicts of interest to declare.

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Efficacy and safety of FOLFIRI/aflibercept in second‐line treatment of metastatic colorectal cancer in a real‐world population: Prognostic and predictive markers

Cancer Medicine ◽

10.1002/cam4.1903 ◽

2019 ◽

Vol 8 (3) ◽

pp. 882-889 ◽

Cited By ~ 7

Author(s):

Ana Fernández Montes ◽

Nieves Martínez Lago ◽

Marta Covela Rúa ◽

Juan de la Cámara Gómez ◽

Paula González Villaroel ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Real World ◽

Predictive Markers ◽

World Population ◽

Line Treatment ◽

Second Line ◽

Efficacy And Safety ◽

Prognostic And Predictive Markers

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Mutations and Allelic Loss of p53 in Primary Tumor DNA From Potentially Cured Patients With Colorectal Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.11.2829 ◽

2001 ◽

Vol 19 (11) ◽

pp. 2829-2836 ◽

Cited By ~ 12

Author(s):

Ann Forslund ◽

Christina Lönnroth ◽

Marianne Andersson ◽

Hans Brevinge ◽

Kent Lundholm

Keyword(s):

Colorectal Cancer ◽

Colorectal Carcinoma ◽

Metastatic Disease ◽

Denaturing Gradient Gel Electrophoresis ◽

P53 Gene ◽

Allelic Loss ◽

P53 Mutations ◽

Conserved Regions ◽

Primary Surgery ◽

Significant Difference

PURPOSE: To compare p53 alterations in survivors and nonsurvivors after surgery for colorectal cancer. PATIENTS AND METHODS: Twenty-nine potentially cured patients with colorectal carcinoma, without recurrent disease for more than 6 years after their primary surgery, were selected to match a group of 41 colorectal cancer patients with early metastatic spread to the liver. All patients were screened for mutations in the p53 gene, exons 5 to 9, by denaturing gradient gel electrophoresis and subsequent sequencing. RESULTS: The frequency of p53 mutations was significantly different in cured patients (60%) compared with patients with early relapse (41%, P < .05). A significant difference was found in the distribution of mutations, indicating that potentially cured patients had a different proportion of mutations in conserved regions of p53 (P = .02). This difference was explained by a significantly different frequency of mutations in exon 8 (40% v 15%, P = .03), which is part of the conserved region V. All mutations in region V were codon 273 mutations in cured patients, whereas three of four mutations were located in codon 273 in patients with metastatic disease. Allelic loss of p53 (loss of heterozygosity [LOH]) was demonstrated in 26% of the cured patients and in 39% of patients with metastatic disease (P = .36). The combination of mutation and LOH of p53 was the same (17%) in both groups. CONCLUSION: A large number of p53 mutations in colorectal cancer do not promote disease progression. Some mutations, particularly within conserved regions, may even counteract negative functional effects of other p53 structural alterations. A complete loss of p53 function was not related to survival or progression after curative operation of colorectal carcinoma.

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