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  • Open Access Icon
  • Research Article
  • Cite Count Icon 2
  • 10.1093/jncimonographs/lgad015
Adapting a model of cervical carcinogenesis to self-identified Black women to evaluate racial disparities in the United States.
  • Nov 8, 2023
  • JNCI Monographs
  • Jennifer C Spencer + 5 more

Self-identified Black women in the United States have higher cervical cancer incidence and mortality than the general population, but these differences have not been clearly attributed across described cancer care inequities. A previously established microsimulation model of cervical cancer was adapted to reflect demographic, screening, and survival data for Black US women and compared with a model reflecting data for all US women. Each model input with stratified data (all-cause mortality, hysterectomy rates, screening frequency, screening modality, follow-up, and cancer survival) was sequentially replaced with Black-race specific data to arrive at a fully specified model reflecting Black women. At each step, we estimated the relative contribution of inputs to observed disparities. Estimated (hysterectomy-adjusted) cervical cancer incidence was 8.6 per 100 000 in the all-race model vs 10.8 per 100 000 in the Black-race model (relative risk [RR] = 1.24, range = 1.23-1.27). Estimated all-race cervical cancer mortality was 2.9 per 100 000 vs 5.5 per 100 000 in the Black-race model (RR = 1.92, range = 1.85-2.00). We found the largest contributors of incidence disparities were follow-up from positive screening results (47.3% of the total disparity) and screening frequency (32.7%). For mortality disparities, the largest contributor was cancer survival differences (70.1%) followed by screening follow-up (12.7%). To reduce disparities in cervical cancer incidence and mortality, it is important to understand and address differences in care access and quality across the continuum of care. Focusing on the practices and policies that drive differences in treatment and follow-up from cervical abnormalities may have the highest impact.

  • Open Access Icon
  • Research Article
  • Cite Count Icon 4
  • 10.1093/jncimonographs/lgad004
Linking social and built environmental factors to leisure-time physical activity in rural cancer survivors.
  • May 4, 2023
  • JNCI Monographs
  • Courtney J Stevens + 8 more

This study explored associations between social and built environmental factors and leisure-time physical activity (LTPA) in rural cancer survivors (RCS) and whether these associations differed by exercise stage of change (SOC). RCS (n = 219) completed questionnaires assessing LTPA, SOC, and social (social status, connectedness, support) and environmental (home environment, neighborhood environment) factors. Linear regression models examined associations between social and built environmental factors and LTPA and tested for moderation by SOC. Half (50.7%) of RCS were physically active, and 49.3% were not active. Social factors positively associated with LTPA included subjective social status in the community (B = 89.0, P = .014) and in the United States (B = 181.3, P < .001), social connectedness (B = 122.3, P = .024), and social support for physical activity from family (B = 41.9, P < .001) and friends (B = 44.3, P < .001). Environmental factors positively associated with LTPA included the home environment (B = 111.2, P < .001), perceived environmental support for PA (B = 355.4, P = .004), and neighborhood attributes, including bicycling infrastructure (B = 191.3, P = .003), proximity to recreation facilities (B = 140.1, P = .021), traffic safety (B = 184.5, P = .025), and aesthetics (B = 342.6, P < .001). SOC statistically significantly moderated the association between social status in the United States and LTPA (B = 160.3, P = .031). Social and built environmental factors were consistently linked with LTPA and provide context for multilevel interventions promoting LTPA in RCS.

  • Open Access Icon
  • Research Article
  • Cite Count Icon 8
  • 10.1093/jncimonographs/lgad012
Body composition and endometrial cancer outcomes.
  • May 4, 2023
  • JNCI Monographs
  • Diana P Arteaga + 8 more

Obesity is a known risk factor for developing endometrial cancer. However, the association of obesity with endometrial cancer (EC) outcomes has not been clearly established. This study examined how outcomes in women with early stage EC vary with body composition measured via computed tomography (CT). In this retrospective study, patients diagnosed with EC international Federation of Gynecology and Obstetrics stages I-III and available CT scans were included. Automatica software was used to assess the areas of visceral adipose tissue, subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) and skeletal muscle area. Of 293 patient charts assessed, 199 met eligibility criteria. Median body mass index (BMI) was 32.8 kg/m2 (interquartile range [IQ] = 26.8-38.9); 61.8% had histologic subtype endometrioid carcinoma. Adjusted for age, international Federation of Gynecology and Obstetrics stage, and histologic subtype, a BMI of at least 30 vs less than 30 kg/m2 was associated with lower endometrial cancer-specific survival (ECSS) (hazard ratio [HR] = 2.32, 95% confidence interval [CI] = 1.27 to 4.25) and overall survival (OS) (HR = 2.7, 95% CI = 1.35 to 5.39). Higher IMAT 75th vs 25th percentile and SAT of at least 225.6 vs less than 225.6 cm2 were associated with lower ECSS (HR = 1.53, 95% CI = 1.1 to 2.13, and HR = 2.57, 95% CI = 1.13 to 5.88) and OS (HR = 1.50, 95% CI = 1.11 to 2.02, and HR = 2.46, 95% CI = 1.2 to 5.01), respectively. The association of visceral adipose tissue (75th vs 25th percentile) with ECSS and OS was not statistically significant (HR = 1.42, 95% CI = 0.91 to 2.22, and HR = 1.24, 95% CI = 0.81 to 1.89). Higher BMI, IMAT, and SAT were associated with higher mortality from EC and lower OS. A better understanding of the mechanisms underlying these relationships could inform strategies to improve patient outcomes.

  • Open Access Icon
  • Research Article
  • Cite Count Icon 6
  • 10.1093/jncimonographs/lgad014
The 'omics of obesity in B-cell acute lymphoblastic leukemia.
  • May 4, 2023
  • JNCI Monographs
  • Delaney K Geitgey + 25 more

The obesity pandemic currently affects more than 70 million Americans and more than 650 million individuals worldwide. In addition to increasing susceptibility to pathogenic infections (eg, SARS-CoV-2), obesity promotes the development of many cancer subtypes and increases mortality rates in most cases. We and others have demonstrated that, in the context of B-cell acute lymphoblastic leukemia (B-ALL), adipocytes promote multidrug chemoresistance. Furthermore, others have demonstrated that B-ALL cells exposed to the adipocyte secretome alter their metabolic states to circumvent chemotherapy-mediated cytotoxicity. To better understand how adipocytes impact the function of human B-ALL cells, we used a multi-omic RNA-sequencing (single-cell and bulk transcriptomic) and mass spectroscopy (metabolomic and proteomic) approaches to define adipocyte-induced changes in normal and malignant B cells. These analyses revealed that the adipocyte secretome directly modulates programs in human B-ALL cells associated with metabolism, protection from oxidative stress, increased survival, B-cell development, and drivers of chemoresistance. Single-cell RNA sequencing analysis of mice on low- and high-fat diets revealed that obesity suppresses an immunologically active B-cell subpopulation and that the loss of this transcriptomic signature in patients with B-ALL is associated with poor survival outcomes. Analyses of sera and plasma samples from healthy donors and those with B-ALL revealed that obesity is associated with higher circulating levels of immunoglobulin-associated proteins, which support observations in obese mice of altered immunological homeostasis. In all, our multi-omics approach increases our understanding of pathways that may promote chemoresistance in human B-ALL and highlight a novel B-cell-specific signature in patients associated with survival outcomes.

  • Open Access Icon
  • Research Article
  • Cite Count Icon 8
  • 10.1093/jncimonographs/lgad006
Skeletal muscle omics signatures in cancer cachexia: perspectives and opportunities.
  • May 4, 2023
  • JNCI Monographs
  • L Anne Gilmore + 3 more

Cachexia is a life-threatening complication of cancer that occurs in up to 80% of patients with advanced cancer. Cachexia reflects the systemic consequences of cancer and prominently features unintended weight loss and skeletal muscle wasting. Cachexia impairs cancer treatment tolerance, lowers quality of life, and contributes to cancer-related mortality. Effective treatments for cancer cachexia are lacking despite decades of research. High-throughput omics technologies are increasingly implemented in many fields including cancer cachexia to stimulate discovery of disease biology and inform therapy choice. In this paper, we present selected applications of omics technologies as tools to study skeletal muscle alterations in cancer cachexia. We discuss how comprehensive, omics-derived molecular profiles were used to discern muscle loss in cancer cachexia compared with other muscle-wasting conditions, to distinguish cancer cachexia from treatment-related muscle alterations, and to reveal severity-specific mechanisms during the progression of cancer cachexia from early toward severe disease.

  • Open Access Icon
  • Research Article
  • Cite Count Icon 11
  • 10.1093/jncimonographs/lgac028
Embedding lifestyle interventions into cancer care: has telehealth narrowed the equity gap?
  • May 4, 2023
  • JNCI Monographs
  • Amy M Dennett + 8 more

Lifestyle interventions targeting energy balance (ie, diet, exercise) are critical for optimizing the health and well-being of cancer survivors. Despite their benefits, access to these interventions is limited, especially in underserved populations, including older people, minority populations and those living in rural and remote areas. Telehealth has the potential to improve equity and increase access. This article outlines the advantages and challenges of using telehealth to support the integration of lifestyle interventions into cancer care. We describe 2 recent studies, GO-EXCAP and weSurvive, as examples of telehealth lifestyle intervention in underserved populations (older people and rural cancer survivors) and offer practical recommendations for future implementation. Innovative approaches to the use of telehealth-delivered lifestyle intervention during cancer survivorship offer great potential to reduce cancer burden.

  • Open Access Icon
  • Research Article
  • Cite Count Icon 12
  • 10.1093/jncimonographs/lgad010
Pharmacokinetics of cancer therapeutics and energy balance: the role of diet intake, energy expenditure, and body composition.
  • May 4, 2023
  • JNCI Monographs
  • Sarah A Purcell + 7 more

Energy balance accounts for an individual's energy intake, expenditure, and storage. Each aspect of energy balance has implications for the pharmacokinetics of cancer treatments and may impact an individual's drug exposure and subsequently its tolerance and efficacy. However, the integrated effects of diet, physical activity, and body composition on drug absorption, metabolism, distribution, and excretion are not yet fully understood. This review examines the existing literature on energy balance, specifically the role of dietary intake and nutritional status, physical activity and energy expenditure, and body composition on the pharmacokinetics of cancer therapeutics. As energy balance and pharmacokinetic factors can be influenced by age-related states of metabolism and comorbidities, this review also explores the age-related impact of body composition and physiologic changes on pharmacokinetics among pediatric and older adult populations with cancer.

  • Research Article
  • Cite Count Icon 19
  • 10.1093/jncimonographs/lgac023
Trial Design Considerations to Increase Older Adult Accrual to National Cancer Institute Clinical Trials.
  • Dec 15, 2022
  • JNCI Monographs
  • Jennifer Le-Rademacher + 15 more

Although adults aged 65 years or older make up a strong majority of cancer patients, their underrepresentation in cancer clinical trials leads to the lack of representative data to guide evidence-based therapeutic decisions in this patient population. The Trial Design Working Group, convened as part of the workshop titled, Engaging Older Adults in the National Cancer Institute Clinical Trials Network: Challenges and Opportunities, recommended study designs and design elements that could improve accrual of older adults in National Cancer Institute-funded clinical trials. These include trials that are specifically designed to enroll older adults, trials that include a cohort of older patients (parallel cohort, stratified cohort, or embedded cohort), and trials with pragmatic design elements to facilitate enrollment of older adults. This manuscript provides brief descriptions of the recommended designs, examples of successful trials, and considerations for implementation of these designs. As with any clinical trial, the scientific questions and trial objectives should drive the study design, the selection of endpoints and intervention, and eligibility criteria. When designing trials that include older adults, the heterogeneity of fitness levels is an important consideration as fitness can influence accrual rates and outcomes. Appropriately incorporating geriatric assessments can help identify the optimal subset of older patients for inclusion and minimize selection bias. Incorporating pragmatic design elements to reduce the burden on trial participants as well as on accruing sites and retaining essential elements to ensure that the main goal of the trial can be accomplished can enhance enrollment without compromising the integrity of trials.

  • Research Article
  • Cite Count Icon 12
  • 10.1093/jncimonographs/lgac017
Update on Enrollment of Older Adults Onto National Cancer Institute National Clinical Trials Network Trials
  • Dec 15, 2022
  • JNCI Monographs
  • Grace E Mishkin + 3 more

Older adults are a large and growing proportion of cancer cases in the United States, but concerns persist about whether older adults are adequately represented in the cancer clinical trials that test new options for treatment and cancer care. This paper describes adult patient enrollments by age group to the National Cancer Institute's National Clinical Trials Network (NCTN) from 2016 to 2021, compares patient enrollment by age with the estimated incident cancer population across cancer types, and explores possible associations between patient age and patient race, ethnicity, and sex. This analysis found that patients aged 18 to 69 years were overrepresented in NCTN trials, whereas patients aged 70 years and older were underrepresented compared with the estimated incident cancer population. Underrepresentation of older patients was seen across cancer types. Older patients who enrolled to NCTN trials were more likely to be non-Hispanic White than the estimated incident cancer population. Compared with earlier analyses, NCTN trials are enrolling greater proportions of older adults, primarily driven by higher enrollment among patients aged 65 to 74 years. There is still significant room for improvement, however, especially among patients aged 75 years and older. Additionally, patient demographics should not be viewed in isolation: older Hispanic patients, for instance, were particularly underrepresented among patients enrolled to NCTN trials. The intersection between trial enrollment and age, race, and ethnicity warrants further study so that more targeted enrollment enhancement efforts can be developed that enhance trial diversity across demographic groups.

  • Front Matter
  • Cite Count Icon 4
  • 10.1093/jncimonographs/lgac020
Preface: Engaging Older Adults in Cancer Clinical Trials Conducted in the National Cancer Institute Clinical Trials Network: Opportunities to Enhance Accrual
  • Dec 15, 2022
  • JNCI Monographs
  • Diane St Germain + 1 more