All You Need to Know About DPYD Genetic Testing for Patients Treated With Fluorouracil and Capecitabine: A Practitioner-Friendly Guide

Fluoropyrimidines (fluorouracil, capecitabine, and other analogs) are highly used anticancer drugs worldwide. However, patients with cancer treated with these drugs might experience severe, life-threatening toxicity because of germline genetic variation in the DPYD gene. This is a genetic predisposition with an established mechanistic basis that links genetic variation in the DPYD gene to an increase in systemic drug exposure, resulting in an increased risk of toxicity. Pharmacology guidelines provide recommendations on avoiding treatment with fluoropyrimidines or reducing their dose in patients carrying DPYD genetic variants conferring an increased risk of toxicity. However, oncology societies in the United States do not recommend systematic testing. Instead, on April 30, 2020, the European Society for Medical Oncology issued a document recommending genetic testing. In this scenario of contradicting information, practicing oncologists struggle with reaching an informed decision on whether genetic testing should be applied before treatment. This is mostly due to uncertainty about the clinical relevance of genetic testing from the perspective of a practicing oncologist. To reach an informed decision, practicing oncologists need access to concise information on the genetic variants to be tested and a practitioner-friendly interpretation of the test results. We believe this information is currently lacking. To our knowledge, for the first time, we provide a single guide for health care professionals to make an evidence-based decision about DPYD testing for patients with cancer. This article provides the essential knowledge base for oncologists to have an informed discussion with their patients about the genetic testing for DPYD. This document assists practitioners in quickly evaluating whether, when, where, and how to order a DPYD genetic test.

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Elevated Cancer-Specific Mortality Among HIV-Infected Patients in the United States

Journal of Clinical Oncology ◽

10.1200/jco.2014.59.5967 ◽

2015 ◽

Vol 33 (21) ◽

pp. 2376-2383 ◽

Cited By ~ 142

Author(s):

Anna E. Coghill ◽

Meredith S. Shiels ◽

Gita Suneja ◽

Eric A. Engels

Keyword(s):

Cancer Treatment ◽

Cox Regression ◽

B Cell Lymphoma ◽

The United States ◽

Cancer Stage ◽

Infected People ◽

Patients With Cancer ◽

Increased Risk ◽

Specific Mortality ◽

Cancer Specific Mortality

Purpose Despite advances in the treatment of HIV, HIV-infected people remain at increased risk for many cancers, and the number of non–AIDS-defining cancers is increasing with the aging of the HIV-infected population. No prior study has comprehensively evaluated the effect of HIV on cancer-specific mortality. Patients and Methods We identified cases of 14 common cancers occurring from 1996 to 2010 in six US states participating in a linkage of cancer and HIV/AIDS registries. We used Cox regression to examine the association between patient HIV status and death resulting from the presenting cancer (ascertained from death certificates), adjusting for age, sex, race/ethnicity, year of cancer diagnosis, and cancer stage. We included 1,816,461 patients with cancer, 6,459 (0.36%) of whom were HIV infected. Results Cancer-specific mortality was significantly elevated in HIV-infected compared with HIV-uninfected patients for many cancers: colorectum (adjusted hazard ratio [HR], 1.49; 95% CI, 1.21 to 1.84), pancreas (HR, 1.71; 95% CI, 1.35 to 2.18), larynx (HR, 1.62; 95% CI, 1.06 to 2.47), lung (HR, 1.28; 95% CI, 1.17 to 1.39), melanoma (HR, 1.72; 95% CI, 1.09 to 2.70), breast (HR, 2.61; 95% CI, 2.06 to 3.31), and prostate (HR, 1.57; 95% CI, 1.02 to 2.41). HIV was not associated with increased cancer-specific mortality for anal cancer, Hodgkin lymphoma, or diffuse large B-cell lymphoma. After further adjustment for cancer treatment, HIV remained associated with elevated cancer-specific mortality for common non–AIDS-defining cancers: colorectum (HR, 1.40; 95% CI, 1.09 to 1.80), lung (HR, 1.28; 95% CI, 1.14 to 1.44), melanoma (HR, 1.93; 95% CI, 1.14 to 3.27), and breast (HR, 2.64; 95% CI, 1.86 to 3.73). Conclusion HIV-infected patients with cancer experienced higher cancer-specific mortality than HIV-uninfected patients, independent of cancer stage or receipt of cancer treatment. The elevation in cancer-specific mortality among HIV-infected patients may be attributable to unmeasured stage or treatment differences as well as a direct relationship between immunosuppression and tumor progression.

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Clinical Characteristics and Outcomes of COVID-19–Infected Cancer Patients: A Systematic Review and Meta-Analysis

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djaa168 ◽

2020 ◽

Cited By ~ 3

Author(s):

Hua Zhang ◽

Han Han ◽

Tianhui He ◽

Kristen E Labbe ◽

Adrian V Hernandez ◽

...

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Case Fatality Rate ◽

Meta Analysis ◽

Univariate Analysis ◽

Case Fatality ◽

The United States ◽

Fatality Rate ◽

Patients With Cancer ◽

Increased Risk

Abstract Background Previous studies have indicated coronavirus disease 2019 (COVID-19) patients with cancer have a high fatality rate. Methods We conducted a systematic review of studies that reported fatalities in COVID-19 patients with cancer. A comprehensive meta-analysis that assessed the overall case fatality rate and associated risk factors was performed. Using individual patient data, univariate and multivariable logistic regression analyses were used to estimate odds ratios (OR) for each variable with outcomes. Results We included 15 studies with 3019 patients, of which 1628 were men; 41.0% were from the United Kingdom and Europe, followed by the United States and Canada (35.7%), and Asia (China, 23.3%). The overall case fatality rate of COVID-19 patients with cancer measured 22.4% (95% confidence interval [CI] = 17.3% to 28.0%). Univariate analysis revealed age (OR = 3.57, 95% CI = 1.80 to 7.06), male sex (OR = 2.10, 95% CI = 1.07 to 4.13), and comorbidity (OR = 2.00, 95% CI = 1.04 to 3.85) were associated with increased risk of severe events (defined as the individuals being admitted to the intensive care unit, or requiring invasive ventilation, or death). In multivariable analysis, only age greater than 65 years (OR = 3.16, 95% CI = 1.45 to 6.88) and being male (OR = 2.29, 95% CI = 1.07 to 4.87) were associated with increased risk of severe events. Conclusions Our analysis demonstrated that COVID-19 patients with cancer have a higher fatality rate compared with that of COVID-19 patients without cancer. Age and sex appear to be risk factors associated with a poorer prognosis.

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9p21 and the Genetic Revolution for Coronary Artery Disease

Clinical Chemistry ◽

10.1373/clinchem.2011.172759 ◽

2012 ◽

Vol 58 (1) ◽

pp. 104-112 ◽

Cited By ~ 34

Author(s):

Robert Roberts ◽

Alexandre F R Stewart

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Risk Factor ◽

Genetic Testing ◽

Coronary Artery ◽

Genetic Variants ◽

Genetic Factors ◽

Genomic Study ◽

Increased Risk ◽

Artery Disease

Abstract BACKGROUND It has long been recognized that 50% of the susceptibility for coronary artery disease (CAD) is due to predisposing genetic factors. Comprehensive prevention is likely to require knowledge of these genetic factors. CONTENT Using a genomewide association study (GWAS), the Ottawa Heart Genomic Study and the deCODE group simultaneously identified the first genetic risk variant, at chromosome 9p21. The 9p21 variant became the first risk factor to be identified since 1964. 9p21 occurs in 75% of the population except for African Americans and is associated with a 25% increased risk for CAD with 1 copy and a 50% increased risk with 2 copies. Perhaps the most remarkable finding is that 9p21 is independent of all known risk factors, indicating there are factors contributing to the pathogenesis of CAD that are yet unknown. 9p21 in individuals with premature CAD is associated with a 2-fold increase in risk, similar to that of smoking and cholesterol. Routine genetic testing will probably remain controversial until a specific treatment is developed. Over a period of 5 years, however, GWASs have identified 30 genetic variants for CAD risk, of which only 6 act through the known risk factors. SUMMARY The 9p21 variant has now been established as an independent risk factor for CAD and, along with the additional 29 risk genetic variants recently identified, is likely to provide the thrust for genetic testing and personalized medicine in the near future.

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A Global Review on the Utility of Genetic Testing for Familial Hypercholesterolemia

Journal of Personalized Medicine ◽

10.3390/jpm10020023 ◽

2020 ◽

Vol 10 (2) ◽

pp. 23 ◽

Cited By ~ 2

Author(s):

Rachele M. Hendricks-Sturrup ◽

Jodi Clark-LoCascio ◽

Christine Y. Lu

Keyword(s):

United States ◽

Genetic Testing ◽

Familial Hypercholesterolemia ◽

Clinical Outcomes ◽

Ldl Cholesterol ◽

The United States ◽

Global Perspective ◽

Ongoing Research ◽

Increased Risk ◽

Patient Reported

Familial hypercholesterolemia (FH) is a genetic disorder of cholesterol metabolism that affects an estimated 1/250 persons in the United States and abroad. FH is hallmarked by high low-density lipoprotein (LDL) cholesterol and an increased risk of premature atherosclerotic cardiovascular disease. This review summarizes recent global evidence showing the utility of FH genetic testing across diverse populations. Clinical and other qualitative outcomes following FH genetic testing were improved FH diagnosis, treatment initiation or continued treatment, treatment modification, improved total or LDL cholesterol levels, education on lifestyle management, and genetic counseling. This summary of evidence should be considered by those seeking overall evidence and knowledge gaps on the utility of FH genetic testing from a global perspective and for certain ethnic and age populations. These findings can be used to inform insurance policies and coverage decisions for FH genetic testing, policy recommendations to reduce the clinical and public health burden of FH, clinical practice and guidelines to improve the management of FH populations, and ongoing research involving FH genetic testing. We conclude that further investigations are needed to examine: (1) non-clinical outcomes following FH genetic testing; (2) patient-reported outcomes following FH genetic testing to convey patient experiences, values, and goals; and (3) clinical outcomes following FH genetic testing in non-Caucasian and pediatric populations in the United States and abroad.

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Safety and efficacy of COVID-19 vaccination in patients receiving systemic anticancer therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.39.28_suppl.245 ◽

2021 ◽

Vol 39 (28_suppl) ◽

pp. 245-245

Author(s):

Mahir Khan ◽

Ryan Huu-Tuan Nguyen ◽

James Love ◽

Alexander Krule ◽

Michael Weinfeld ◽

...

Keyword(s):

Cancer Treatment ◽

Vaccine Dose ◽

Female Gender ◽

Anticancer Therapy ◽

The United States ◽

Hospitalization Rate ◽

Asian Ethnicity ◽

Treatment Regimens ◽

Patients With Cancer ◽

Increased Risk

245 Background: Patients with cancer who have been treated with systemic anticancer therapy are at increased risk of morbidity and mortality from COVID-19 and have been considered a high-priority group for COVID-19 vaccination in the United States. There is limited guidance and data on the appropriate timing of COVID-19 vaccination relative to receipt of systemic anticancer therapy. Methods: We queried the electronic medical record at the University of Illinois Hospital for patients with gastrointestinal, breast, lung, genitourinary, and head and neck tumors who had received intravenous systemic anticancer therapy between January 1, 2021 and May 25, 2021. Baseline variables were obtained as well as details of cancer treatment, vaccination timing relative to cancer treatment, and clinical outcomes. Results: A total of 274 patients received intravenous systemic anticancer therapy during the study period, of which 161 (58.8%) received at least one vaccine dose, and 138 (42.7%) were fully vaccinated. Of the 122 patients who received cancer treatment within 30 days of any vaccine dose, the median age was 64, and 72 (59%) were female gender. Race distribution was 50% Black, 15.6% White, 3.3% Asian; ethnicity was 24.6% Hispanic and 73% not-Hispanic. Treatment regimens consisted of 37.7% chemotherapy, 25.4% immunotherapy, 27.9% combination therapy, and 9.0% targeted therapy. For those who received anticancer therapy within 30 days of a vaccine, median time between any vaccination and treatment was 10 days (range 0-29 days). For those who had at least 60 days of follow-up after first vaccination, all-cause hospitalization rate was 22.4% (23/106). There was no statistical difference in all-cause 60-day hospitalization rate between those who received vaccination within 5 days of anticancer therapy versus those who received it between 6 and 30 days from anticancer therapy (14.3% vs 28.1%, p = 0.1). One patient (0.8%) developed a COVID-19 illness after any vaccine and did not require hospitalization. Conclusions: We observed safe and efficacious COVID-19 vaccination of patients with cancer receiving systemic IV anticancer therapy. COVID-19 infection after vaccination was rare, with no cases requiring hospitalization for COVID-19 illness post-vaccination in this cohort. All-cause hospitalization rates were similar among patients who received a vaccine within or after 5 days of receiving systemic anticancer therapy, suggesting vaccination side effect tolerability. Further quality improvement studies are needed on interventions to increase vaccination rates in this vulnerable population.

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Incidence of Suicide in Persons With Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.13.8941 ◽

2008 ◽

Vol 26 (29) ◽

pp. 4731-4738 ◽

Cited By ~ 303

Author(s):

Stephanie Misono ◽

Noel S. Weiss ◽

Jesse R. Fann ◽

Mary Redman ◽

Bevan Yueh

Keyword(s):

United States ◽

General Population ◽

The United States ◽

Mortality Data ◽

Standardized Mortality Ratio ◽

Patients With Cancer ◽

Suicide Rates ◽

Increased Risk ◽

Mortality Ratio ◽

Adjusted Rate

Purpose The purpose of this study was to characterize suicide rates among patients with cancer in the United States and identify patient and disease characteristics associated with higher suicide rates. Prior studies, mostly in Europe, have suggested that patients with cancer may be at increased risk for suicide, but large cohort studies comparing patients with cancer with the general population have not been performed in the United States. Methods Patients in the study were residents of geographic areas served by the Surveillance, Epidemiology, and End Results (SEER) program who were diagnosed with cancer from 1973 to 2002. Comparisons with the general US population were based on mortality data collected by the National Center for Health Statistics. This was a retrospective cohort study of suicide in persons with cancer. Results Among 3,594,750 SEER registry patients observed for 18,604,308 person-years, 5,838 suicides were identified, for an age-, sex-, and race-adjusted rate of 31.4/100,000 person-years. In contrast, the suicide rate in the general US population was 16.7/100,000 person-years. Higher suicide rates were associated with male sex, white race, and older age at diagnosis. The highest suicide risks were observed in patients with cancers of the lung and bronchus (standardized mortality ratio [SMR] = 5.74; 95% CI, 5.30 to 6.22), stomach (SMR = 4.68; 95% CI, 3.81 to 5.70), oral cavity and pharynx (SMR = 3.66; 95% CI, 3.16 to 4.22), and larynx (SMR = 2.83; 95% CI, 2.31 to 3.44). SMRs were highest in the first 5 years after diagnosis with cancer. Conclusion Patients with cancer in the United States have nearly twice the incidence of suicide of the general population, and suicide rates vary among patients with cancers of different anatomic sites. Further examination of the psychological experience of patients with cancer, particularly that of patients with certain types of cancer, is warranted.

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Biomarkers and functional foods for obesity and diabetes

British Journal Of Nutrition ◽

10.1079/bjn2002685 ◽

2002 ◽

Vol 88 (S2) ◽

pp. S213-S218 ◽

Cited By ~ 30

Author(s):

James O. Hill ◽

John C. Peters

Keyword(s):

Type 2 Diabetes ◽

Insulin Sensitivity ◽

Health Care Professionals ◽

Functional Foods ◽

Energy Content ◽

Adult Population ◽

The United States ◽

Obesity And Diabetes ◽

Increased Risk

Obesity has reached epidemic proportions in many countries around the world. Because of the close relationship between obesity and type 2 diabetes, an epidemic of diabetes is close behind the obesity epidemic. Preventing and treating obesity is becoming an increasing priority. In the United States, over 60% of the adult population is overweight or obese and thus at increased risk of developing diabetes and cardiovascular disease. While the aetiology of obesity and diabetes is complex, diet clearly plays an important role both in the development and management of these diseases. There is interest in functional foods that could help in prevention and/or management of obesity and type 2 diabetes. This could involve food products that help management of ‘hunger’ or that increase ‘satiety’. It could also involve foods that contribute to more inefficient use of ingested energy (i.e. foods that stimulate energy expenditure more than would be expected from their energy content). As the concept of insulin sensitivity becomes generally more accepted by health care professionals and the public, foods may be targeted towards maximizing insulin sensitivity and towards ‘prevention’ of diabetes. In addition to foods that impact upon body weight, these may include foods that affect the glucose and/or insulin levels that are seen either following the ingestion of food or later in the day. The present paper reviews the complex aetiology of obesity and diabetes and considers a potential role for functional foods in prevention and treatment of obesity and diabetes.

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Extending Oncology Clinical Services to Rural Areas of Texas Via Teleoncology

Journal of Oncology Practice ◽

10.1200/jop.2011.000436 ◽

2012 ◽

Vol 8 (2) ◽

pp. 68-68 ◽

Cited By ~ 8

Author(s):

Jivesh J. Sharma ◽

Gary Gross ◽

Poonam Sharma

Keyword(s):

Health Care Professionals ◽

Cancer Care ◽

Urban Areas ◽

Underserved Populations ◽

High Reliability ◽

The United States ◽

Physician Satisfaction ◽

Patients With Cancer ◽

Telemedicine Application

Abstracts Purpose: For patients in rural Texas, accessing cancer specialists is quite challenging. Texas has many remote areas without community-based cancer care, requiring patients to travel long distances for specialized cancer professional consultations and services. An anticipated shortage of medical oncology expertise will exacerbate this situation. The advent of telemedicine tools has created an opportunity to easily extend specialized cancer services to underserved populations of patients with cancer in Texas. However, more research is needed to explore how well telemedicine tools will be accepted and used by both patients and oncologists alike. Data suggesting that teleoncology services are well accepted and liked by patients and health care professionals would provide a basis for expanding this method of delivering care. If effective, telemedicine tools could help patients with cancer in rural Texas, and throughout the United States, access the same quality of cancer care as their counterparts living in urban areas. Methods: This pilot study will compare the effectiveness and reliability of remote oncologic clinical evaluations conducted via a telemedicine application with the traditional method of onsite evaluations in a private practice setting in rural East Texas. Patient and physician satisfaction with the clinical consultations and their perceptions of the telemedicine application will be assessed using a questionnaire administered at the conclusion of the clinical meetings. Results: Initial results indicate high patient and physician satisfaction scores as well as high reliability and adequacy of the equipment and technology being used. Conclusion: Both patients and physicians are highly satisfied with the quality of teleoncology examinations and express openness to this method of delivering care.

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Association of the APOE, MTHFR and ACE genes polymorphisms and stroke in Zambian patients

Neurology International ◽

10.4081/ni.2013.e20 ◽

2013 ◽

Vol 5 (4) ◽

pp. 20 ◽

Cited By ~ 13

Author(s):

Masharip Atadzhanov ◽

Mwila H. Mwaba ◽

Patrice N. Mukomena ◽

Shabir Lakhi ◽

Sruti Rayaprolu ◽

...

Keyword(s):

Genetic Variation ◽

Ischemic Stroke ◽

Genetic Variants ◽

Hemorrhagic Stroke ◽

The Other ◽

Stroke Patients ◽

Stroke Subtype ◽

Increased Risk ◽

Apoe Locus ◽

The Difference

The aim of the present study was to investigate the association of APOE, MTHFR and ACE polymorphisms with stroke in the Zambian population. We analyzed 41 stroke patients and 116 control subjects all of Zambian origin for associations between the genotype of the APOE, MTHFR and ACE polymorphisms and stroke. The APOE ε2ε4 genotype showed increased risk for hemorrhagic stroke (P<0.05) and also a high risk for ischemic stroke (P=0.05). There was complete absence of the APOE ε2ε2 and the MTHFR TT genotypes in the Zambian population. The difference between cases and controls was not significant for the other genetic variants when analyzed for relationship between stroke, stroke subtype and genotype. We show that genetic variation at the APOE locus affects susceptibility to stroke. No detectable association were observed for the MTHFR and ACE genotypes and stroke in the Zambian population.

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Barriers and Facilitators to Telemedicine: Can You Hear Me Now?

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_320827 ◽

2021 ◽

pp. 25-36

Author(s):

Ana Maria Lopez ◽

Kenneth Lam ◽

Ramya Thota

Keyword(s):

Health Care ◽

Rural Communities ◽

Health Care Professionals ◽

Scaling Up ◽

The United States ◽

Barriers And Facilitators ◽

Patients With Cancer ◽

Barriers To Access ◽

Direct Interpretation ◽

History Of

In its most direct interpretation, telemedicine is medical care provided at a distance. Although telemedicine’s use had been steadily increasing, the COVID-19 pandemic prompted an unprecedented interest and urgency among patients, health care professionals, and policymakers to facilitate health care devoid of the need for in-person contact. The growth in personal access to telecommunications technology meant an unprecedented number of people in the United States and around the world had access to the equipment and technology that would make virtual care possible from the home. As the mass implementation of telemedicine unfolded, it became quickly apparent that scaling up the use of telemedicine presented considerable new challenges, some of which worsened disparities. This article describes those challenges by examining the history of telemedicine, its role in both supporting access and creating new barriers to access in trying to get everyone connected, frameworks for thinking about those barriers, and facilitators that may help overcome them, with a particular focus on older adults and patients with cancer in rural communities.

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