Emergency Department Use in Adolescent and Young Adult Cancer Early Survivors from 2006 to 2020.

Purpose: Understanding emergency department (ED) use in adolescent and young adult (AYA) survivors could identify gaps in AYA survivorship. Methods: We conducted a cohort study of 7925 AYA survivors (aged 15-39 years at diagnosis) who were 2-5 years from diagnosis in 2006-2020 at Kaiser Permanente Southern California. We calculated ED utilization rates overall and by indication of the encounter (headache, cardiac issues, and suicide attempts). We estimated rate changes by survivorship year and patient factors associated with ED visit using a Poisson model. Results: Cohort was 65.4% women, 45.8% Hispanic, with mean age at diagnosis at 31.3 years. Overall, 38% of AYA survivors had ≥1 ED visit (95th percentile: 5 ED visits). Unadjusted ED rates declined from 374.2/1000 person-years (PY) in Y2 to 327.2 in Y5 (p change < 0.001). Unadjusted rates declined for headache, cardiac issues, and suicide attempts. Factors associated with increased ED use included: age 20-24 at diagnosis [relative risk (RR) = 1.30, 95% CI 1.09-1.56 vs. 35-39 years]; female (RR = 1.27, 95% CI 1.11-1.47 vs. male); non-Hispanic Black race/ethnicity (RR 1.64, 95% CI 1.38-1.95 vs. non-Hispanic white); comorbidity (RR = 1.34, 95% CI 1.16-1.55 for 1 and RR 1.80, 95% CI 1.40-2.30 for 2+ vs. none); and public insurance (RR = 1.99, 95% CI 1.70-2.32 vs. private). Compared with thyroid cancer, cancers associated with increased ED use were breast (RR = 1.45, 95% CI 1.24-1.70), cervical (RR = 2.18, 95% CI 1.76-2.71), colorectal (RR = 2.34, 95% CI 1.94-2.81), and sarcoma (RR = 1.39, 95% CI 1.03-1.88). Conclusion: ED utilization declined as time from diagnosis elapsed, but higher utilization was associated with social determinants of health and cancer types.

The Adolescent and Young Adult Needs Assessment & Service Bridge (NA-SB): A single-arm feasibility pilot study.

PURPOSE: In this pilot study, we evaluated the feasibility of implementing the Needs Assessment & Service Bridge (NA-SB)- an intervention to address the pervasive unmet needs of adolescents and young adults (AYAs) during cancer treatment. METHODS: We conducted a mixed methods single-arm feasibility pilot study of NA-SB at the North Carolina Basnight Cancer Hospital. Eligible participants were AYAs ages 18-39 in active cancer treatment. After receiving NA-SB, participants completed a postintervention survey assessing their perceptions of NA-SB. We interviewed participating providers to assess their implementation experiences. RESULTS: On average, AYA participants (n = 26) rated NA-SB's feasibility as 4.5/5, its acceptability as 4.5/5, and its appropriateness as 4.4/5. 77% of participants agreed or strongly agreed that their needs were met in the study period. CONCLUSION: This pilot study generated preliminary evidence to establish NA-SB's feasibility as well as proof of concept for the intervention as a viable approach for identifying and addressing AYAs' unmet needs.

Caring for Children in Relation to Financial Hardship, Advance Care Planning, and Genetic Testing Among Adolescent and Young Adults with Cancer.

Purpose: When a cancer diagnosis coincides with caring for children, it may influence the financial impacts of cancer and decisions to pursue advance care planning (ACP) or genetic testing. We examined associations between caring for children and financial hardship, ACP, and genetic testing among female adolescent and young adult (AYA) cancer survivors in North Carolina and California. Methods: Participants were diagnosed at ages 15-39 years with breast, melanoma, gynecologic, lymphoma, or thyroid cancer during 2004-2016. We estimated adjusted prevalence differences (aPDs) and ratios (aPRs) for each outcome by child caring status using marginal structural binomial regression models. Results: Among 1595 women ages 19-54 years at survey (median = 7 years since diagnosis), 819 (51.3%) reported that they were caring for children at diagnosis. Women caring for children had a higher prevalence of material financial hardship (e.g., medical debt; 30% vs. 21.9%; aPD = 9%, 95% confidence interval [CI]: 3 to 14; aPR = 1.39, 95% CI: 1.12 to 1.72) but similar levels of psychological financial hardship compared to noncaregivers. Women caring for children were more likely to complete ACPs (42.2% vs. 30.7%; aPD = 9%, 95% CI: 3 to 16; aPR = 1.30, 95% CI: 1.08 to 1.57). Among the 723 survivors of breast, endometrial, and ovarian cancer, the prevalence of genetic testing was higher among women caring for children (89%) than noncaregivers (81%); this difference was not statistically significant. Conclusion: Women caring for children at diagnosis may be at elevated risk for adverse financial outcomes and may benefit from additional financial navigation support. Childcare responsibilities may further complicate health decision-making for AYAs diagnosed with cancer.

Physical Activity Intervention Characteristics and Effects on Behavioral and Health-Related Outcomes Among Adolescents and Young Adults Living with and Beyond Cancer: A Systematic Review.

Participation in physical activity (PA) during and after cancer treatment is safe and beneficial in the adolescent and young adult (AYA) cancer population. PA can positively impact health-related outcomes; however, participation remains low. This systematic review aims to describe PA intervention characteristics and outcomes in AYA survivors of cancer (AYASCa). This review followed Preferred Reporting Index for Systematic Reviews and Meta Analyses (PRISMA) guidelines and was registered with Prospero (CRD42022365661). PubMed, CINAHL, and Scopus databases were searched for randomized control trials (RCTs) and pre/post-test studies without a control group through December 31, 2022. Data included: participant demographics, PA intervention characteristics, and health-related outcomes. Studies were assessed using the National Institute of Health Critical Appraisal Tools, and findings were synthesized to identify common characteristics of PA interventions and outcomes. Twenty-three studies were included: 15 RCTs and 8 pre/post-test studies. Heterogeneity existed across design, sample demographics, intervention timing, and observed outcomes. The most common characteristics of PA interventions were supervision of PA, wearable device use, tailored/individualized PA prescriptions, and goal setting. PA interventions positively affected health-related outcomes, with 21 studies reporting statistically significant findings. Implementing personalized PA prescriptions, utilizing wearable devices, and incorporating goal setting as characteristics in PA interventions hold potential benefits for AYASCa, leading to improved outcomes. Still, additional research is needed to explore interventions that utilize these PA characteristics and determine which ones are most effective for AYASCa. By further investigating and identifying optimal PA characteristics, interventions can be better tailored to meet this population's specific needs and preferences, ultimately enhancing their overall well-being and recovery.

Vaccination practices of pediatric oncologists from eight states.

BACKGROUND: Vaccinations are a vital part of routine childhood and adolescent preventive care. We sought to identify current oncology provider practices, barriers, and attitudes towards vaccinating childhood and adolescent cancer patients and survivors. METHODS: We conducted a one-time online survey distributed from March-October 2018 to pediatric oncologists at nine institutions across the United States (N = 111, 68.8% participation rate). The survey included 32 items about vaccination practices, barriers to post-treatment vaccination, availability of vaccinations in oncology clinic, familiarity with vaccine guidelines, and attitudes toward vaccination responsibilities. Descriptive statistics were calculated in STATA 14.2. RESULTS: Participants were 54.0% female and 82.9% white, with 12.6% specializing in Bone Marrow Transplants. Influenza was the most commonly resumed vaccine after treatment (7030%). About 50%-60% were familiar with vaccine guidelines for immunocompromised patients. More than half (62.7%) recommended that patients restart most immunizations 6 months to 1 year after chemotherapy. Common barriers to providers recommending vaccinations included not having previous vaccine records for patients (56.8%) or lacking time to ascertain which vaccines are needed (32.4%). Of participants, 66.7% stated that vaccination should be managed by primary care providers, but with guidance from oncologists. CONCLUSIONS: Many pediatric oncologists report being unfamiliar with vaccine guidelines for immunocompromised patients and almost all report barriers in supporting patients regarding vaccines after cancer treatment. Our findings show that further research and interventions are needed to help bridge oncology care and primary care regarding immunizations after treatment.

Frailty and comorbidities among young adult cancer survivors enrolled in an mHealth physical activity intervention trial.

PURPOSE: The physical frailty phenotype identifies individuals at risk for adverse health outcomes but has rarely been assessed among young adult cancer survivors (YACS). This study describes frailty status among YACS participating in a physical activity (PA) intervention trial. METHODS: YACS were categorized at baseline using the 5-item FRAIL scale: fatigue; weight loss; illness; ambulation; resistance. Chi-square tests compared frailty and non-cancer comorbidities by characteristics. Prevalence rates (PRs) for the independent associations between characteristics, frailty, and comorbidities were estimated using modified Poisson regression models. RESULTS: Among 280 YACS (82% female; mean (M) age = 33.4 ± 4.8 years, M=3.7 ± 2.4 years post-diagnosis), 11% frail, 17% prefrail; the most frequent criteria were fatigue (41%), resistance (38%), and ambulation (14%). Compared to BMI < 25, higher BMI was associated with increased likelihood of frailty (BMI 25-30, PR: 2.40, 95% CI: 1.38-4.17; BMI > 30, PR: 2.95, 95% CI: 1.71-5.08). Compared to 0, ≥ 30 min/week of moderate-to-vigorous PA was associated with reduced frailty (PR: 0.39, 95% CI: 0.25-0.60). Most YACS (55%) reported ≥ 1 comorbidity, most frequently depression (38%), thyroid condition (19%), and hypertension (10%). Comorbidities were more common for women (59% vs. 37%) and current/former smokers (PR: 1.71, 95% CI: 1.29-2.28). CONCLUSION: Prevalence of frailty and comorbidities in this sample was similar to other YACS cohorts and older adults without cancer and may be an indicator of accelerated aging and increased risk for poor outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Assessment of frailty may help identify YACS at increased risk for adverse health outcomes.

Frailty and Comorbidities Among Young Adult Cancer Survivors Enrolled in an mHealth Physical Activity Intervention Trial.

Purpose: The physical frailty phenotype identifies individuals at risk for adverse health outcomes but has rarely been assessed among young adult cancer survivors (YACS). This study describes frailty status among YACS participating in a PA intervention trial. Methods: YACS were categorized by frailty status at baseline using the 5-item FRAIL index: fatigue; weight loss; illness; ambulation; resistance. Chi-square tests compared frailty and comorbidities by characteristics. Prevalence rates (PRs) for the independent associations between characteristics, frailty, and comorbidities were estimated using modified Poisson regression models. Results: Among 280 YACS (82% female, M=33.4±4.8 years, M=3.7±2.4 years post-diagnosis), 14% had frailty, and 24% prefrailty; the most frequent criteria were fatigue (70%), resistance (38%), and ambulation (14%). Compared to BMI <25, higher BMI (BMI 25-30, PR: 1.65, 95% CI: 1.02-2.65; BMI > 30, PR: 2.36, 95% CI: 1.46-3.81) was associated with increased frailty status. Compared to 0, 1-50 minutes/week of moderate-to-vigorous PA was associated with reduced frailty (PR: 0.62, 95% CI: 0.43-0.90). Most YACS (55%) reported > 1 comorbidity, most frequently depression (38%), thyroid condition (19%), and hypertension (10%). Men were less likely to report comorbidities (PR: 0.63, 95% CI: 0.42-0.93). Current/former smokers (PR: 1.29, 95% CI: 1.01-1.64) were more likely to have comorbidities. Conclusion: Prevalence of frailty and comorbidities in this sample was similar to other YACS cohorts and may be an indicator of accelerated aging and increased risk for poor outcomes. Implications for Cancer Survivors: Assessment of frailty may help identify YACS at risk for adverse health outcomes.

Developing a Comprehensive Adolescent and Young Adult Cancer Program: Lessons Learned from 7 Years of Growth and Progress.

Purpose: Every year, nearly 100,000 adolescents and young adults (15-39 years, AYAs) are diagnosed with cancer in the United States and many have unmet physical, psychosocial, and practical needs during and after cancer treatment. In response to demands for improved cancer care delivery for this population, specialized AYA cancer programs have emerged across the country. However, cancer centers face multilevel barriers to developing and implementing AYA cancer programs and would benefit from more robust guidance on how to approach AYA program development. Methods: To contribute to this guidance, we describe the development of an AYA cancer program at the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center. Results: We summarize the evolution of UNC's AYA Cancer Program since it was established in 2015, offering pragmatic strategies for developing, implementing, and sustaining AYA cancer programs. Conclusion: The development of the UNC AYA Cancer Program since 2015 has generated many lessons learned that we hope may be informative to other cancer centers seeking to build specialized services for AYAs.

Accelerated epigenetic aging and myopenia in young adult cancer survivors.

BACKGROUND: Young adult cancer survivors experience early aging-related morbidities and mortality. Biological aging biomarkers may identify at-risk survivors and increase our understanding of mechanisms underlying this accelerated aging. METHODS: Using an observational study design, we cross-sectionally measured DNA methylation-based epigenetic age in young adult cancer survivors at a tertiary, academic state cancer hospital. Participants were a convenience sample of consecutively enrolled survivors of childhood, adolescent, and young adult cancers treated with either an anthracycline or alkylating agent, and who were at least 3 months post-treatment. Similarly aged healthy comparators were consecutively enrolled. Cancer treatment and treatment intensity were compared to DNA methylation-based epigenetic age and pace of aging. RESULTS: Sixty survivors (58 completing assessments, mean age 20.5 years, range 18-29) and 27 comparators (mean age 20 years, range 17-29) underwent DNA methylation measurement. Survivors were predominantly female (62%) and white (60%) and averaged nearly 6 years post-treatment (range 0.2-25 years). Both epigenetic age (AgeAccelGrim: 1.5 vs. -2.4, p < 0.0001; AgeAccelPheno 2.3 vs. -3.8, p = 0.0013) and pace of aging (DunedinPACE 0.99 vs. 0.83, p < 0.0001) were greater in survivors versus comparators. In case-case adjusted analysis, compared to survivors with normal muscle mass, myopenic survivors had higher AgeAccelGrim (2.2 years, 95% CI 0.02-4.33, p = 0.02), AgeAccelPheno (6.2 years, 2.36-10.09, p < 0.001), and DunedinPACE (0.11, 0.05-0.17, p < 0.001). CONCLUSIONS: Epigenetic age is older and pace of aging is faster in young adult cancer survivors compared to noncancer peers, which is evident in the early post-therapy period. Survivors with physiological impairment demonstrate greater epigenetic age advancement. Measures of epigenetic age may identify young adult survivors at higher risk for poor functional and health outcomes.

Active Treatment to Survivorship Care: A Mixed-Methods Study Exploring Resource Needs and Preferences of Young Adult Cancer Survivors in Transition.

Purpose: The purpose of this study was to identify resource needs and preferences of young adult cancer survivors (YAs) during the transition from active treatment to survivorship care to inform tailored care tools to support YAs during this period. Methods: A mixed methods study following a sequential explanatory approach was conducted among YAs between the ages of 15 and 39. Online surveys were distributed to assess participant information and resource needs, and responses were further explored during virtual focus group and interview discussions. Frequencies and proportions were calculated to identify quantitative resource needs, and a descriptive qualitative approach was used to gather and analyze qualitative data. Results: Thirty-one participants completed the online surveys, and 27 participated in qualitative data collection. The top resource needs identified in the surveys and discussed in focus groups and interviews were (1) fear of recurrence, (2) sleep and fatigue, (3) anxiety, (4) nutrition, (5) physical activity, and (6) finances. Emergent themes identified during transcript analyses included the need for (1) tailored, customizable resources, (2) connection with other survivors, (3) tools to guide conversations about cancer, (4) clarity in what to expect during treatment and survivorship, and (5) consistent and equitable care in YA oncology. Conclusions: Participants identified six important information needs in addition to an overarching need for tailored support and equitable distribution of resources while transitioning into early survivorship. Thus, tailored interventions are needed to enhance the distribution of YA-centered resources, improve equity in YA cancer care, and connect YAs with peer survivors.

Low Risk of Lymphoma in Pediatric Patients Treated for Inflammatory Bowel Disease.

INTRODUCTION: Despite the effectiveness of immune-suppressing therapies in treating pediatric inflammatory bowel diseases (IBDs), concerns of lymphoma may limit their use. We used a large administrative claims database to evaluate the risk of lymphoma in pediatric IBD and conducted a case series analysis of medication exposure in children diagnosed with lymphoma. METHODS: We analyzed administrative claims from the 2007 to 2018 IQVIA database and identified pediatric (≤18 years) patients with Crohn's disease or ulcerative colitis using International Classification of Diseases, 9th or 10th Revision codes and pharmacy claims. Lymphoma cases were identified by diagnosis codes and confirmed by independent claim-by-claim review by a pediatric oncologist and gastroenterologist. We calculated incidence rates for lymphoma among patients with and without pharmacy claims for treatment followed by treatment description among those who developed lymphoma during follow-up. RESULTS: A total of 10,777 pediatric patients with IBD received ≥1 IBD therapy (median age 15 years [12-17], 45% female and 61% diagnosed with Crohn's disease) during 28,292 patient-years of follow-up. Among treated patients, 5 lymphoma cases were identified (incidence rate 17.7/100,000 patient-years; 95% confidence interval 6.5-39.2). Of these, 4 were treated with a thiopurine before lymphoma diagnosis, and none received anti-tumor necrosis factor-α (anti-TNF) monotherapy. DISCUSSION: The overall lymphoma incidence was low among our cohort of treated pediatric patients with IBD. We observed no cases of lymphoma among patients prescribed anti-TNF monotherapy. These findings reinforce the relative safety of anti-TNF monotherapy for the treatment of pediatric IBD.

Time to cancer treatment and reproductive outcomes after fertility preservation among adolescent and young adult women with cancer.

BACKGROUND: Fertility preservation (FP) may be underused after cancer diagnosis because of uncertainty around delays to cancer treatment and subsequent reproductive success. METHODS: Women aged 15 to 39 years diagnosed with cancer between 2004 and 2015 were identified from the North Carolina Central Cancer Registry. Use of assisted reproductive technology (ART) after cancer diagnosis between 2004 and 2018 (including FP) was assessed through linkage to the Society for Assisted Reproductive Technology. Linear regression was used to examine time to cancer treatment among women who did (n = 95) or did not (n = 469) use FP. Modified Poisson regression was used to estimate risk ratios (RRs) and 95% CIs for pregnancy and birth based on timing of ART initiation relative to cancer treatment (n = 18 initiated before treatment for FP vs n = 26 initiated after treatment without FP). RESULTS: The median time to cancer treatment was 9 to 33 days longer among women who used FP compared with women who did not, matched on clinical factors. Women who initiated ART before cancer treatment may be more likely to have a live birth given pregnancy compared with women who initiated ART after cancer treatment (age-adjusted RR, 1.47; 95% CI, 0.98-2.23), though this may be affected by the more frequent use of gestational carriers in the former group (47% vs 20% of transfer cycles, respectively). CONCLUSIONS: FP delayed gonadotoxic cancer treatment by up to 4.5 weeks, a delay that would not be expected to alter prognosis for many women. Further study of the use of gestational carriers in cancer populations is warranted to better understand its effect on reproductive outcomes.

Disparities in fertility preservation use among adolescent and young adult women with cancer.

PURPOSE: Women face multiple barriers to fertility preservation after cancer diagnosis, but few studies have examined disparities in use of these services. METHODS: Women aged 15-39 years diagnosed with cancer during 2004-2015 were identified from the North Carolina Central Cancer Registry and linked to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. Women who cryopreserved oocytes or embryos for fertility preservation (n = 96) were compared to women who received gonadotoxic treatment but did not use fertility preservation (n = 7964). Conditional logistic and log-binomial regression were used to estimate odds ratios (ORs) or prevalence ratios (PRs) and 95% confidence intervals (CIs). RESULTS: Few adolescent and young adult women with cancer in our study (1.2%) used fertility preservation. In multivariable regression, women less likely to use fertility preservation were older at diagnosis (ages 25-29 vs. 35-39: OR = 6.27, 95% CI: 3.35, 11.73); non-Hispanic Black (vs. non-Hispanic White: PR = 0.44, 95% CI: 0.24, 0.79); and parous at diagnosis (vs. nulliparous: PR = 0.24, 95% CI: 0.13, 0.45); or lived in census tracts that were non-urban (vs. urban: PR = 0.12, 95% CI: 0.04, 0.37) or of lower socioeconomic status (quintiles 1-3 vs. quintiles 4 and 5: PR = 0.39, 95% CI: 0.25, 0.61). CONCLUSIONS: Women with cancer who were older, non-Hispanic Black, parous, or living in areas that were non-urban or of lower socioeconomic position were less likely to use fertility preservation. IMPLICATIONS FOR CANCER SURVIVORS: Clinical and policy interventions are needed to ensure equitable access to fertility services among women facing cancer treatment-related infertility.

Frail young adult cancer survivors experience poor health-related quality of life.

BACKGROUND: Young adult cancer survivors experience frailty and decreased muscle mass at rates equivalent to much older noncancer populations, which indicate accelerated aging. Although frailty and low muscle mass can be identified in survivors, their implications for health-related quality of life are not well understood. METHODS: Through a cross-sectional analysis of young adult cancer survivors, frailty was assessed with the Fried frailty phenotype and skeletal muscle mass in relation to functional and quality of life outcomes measured by the Medical Outcomes Survey Short-Form 36 (SF-36). z tests compared survivors with US population means, and multivariable linear regression models estimated mean SF-36 scores by frailty and muscle mass with adjustments made for comorbidities, sex, and time from treatment. RESULTS: Sixty survivors (median age, 21 years; range, 18-29) participated in the study. Twenty-five (42%) had low muscle mass, and 25 were either frail or prefrail. Compared with US population means, survivors reported worse health and functional impairments across SF-36 domains that were more common among survivors with (pre)frailty or low muscle mass. In multivariable linear modeling, (pre)frail survivors (vs nonfrail) exhibited lower mean scores for general health (-9.1; P = .05), physical function (-14.9; P < .01), and overall physical health (-5.6; P = .02) independent of comorbid conditions. CONCLUSIONS: Measures of frailty and skeletal muscle mass identify subgroups of young adult cancer survivors with significantly impaired health, functional status, and quality of life independent of medical comorbidities. Identifying survivors with frailty or low muscle mass may provide opportunities for interventions to prevent functional and health declines or to reverse this process. LAY SUMMARY: Young adult cancer survivors age more quickly than peers without cancer, which is evidenced by a syndrome of decreased resilience known as frailty. The relationship between frailty (and one of its common components, decreased muscle mass) and quality of life among young adult cancer survivors was examined. Measuring decreased muscle mass and frailty identifies young survivors with poor quality of life, including worse general health, fatigue, physical function, and overall physical health, compared with nonfrail survivors. Interventions to address components of frailty (low muscle mass and weakness) may improve function and quality of life among young adult cancer survivors.

Ethnography and user-centered design to inform context-driven implementation.

Despite pervasive findings pointing to its inextricable role in intervention implementation, context remains poorly understood in implementation science. Existing approaches for describing context (e.g., surveys, interviews) may be narrow in scope or superficial in their elicitation of contextual data. Thus, in-depth and multilevel approaches are needed to meaningfully describe the contexts into which interventions will be implemented. Moreover, many studies assess context without subsequently using contextual information to enhance implementation. To be useful for improving implementation, though, methods are needed to apply contextual information during implementation. In the case example presented in this paper, we embedded an ethnographic assessment of context within a user-centered design approach to describe implementation context and apply that information to promote implementation. We developed a patient-reported outcome measure-based clinical intervention to assess and address the pervasive unmet needs of young adults with cancer: the Needs Assessment & Service Bridge (NA-SB). In this paper, we describe the user-centered design process that we used to anticipate context modifications needed to deliver NA-SB and implementation strategies needed to facilitate its implementation. Our ethnographic contextual inquiry yielded a rich understanding of local implementation context and contextual variation across potential scale-up contexts. Other methods from user-centered design (i.e., translation tables and a design team prototyping workshop) allowed us to translate that information into specifications for NA-SB delivery and a plan for implementation. Embedding ethnographic methods within a user-centered design approach can help us to tailor interventions and implementation strategies to their contexts of use to promote implementation.

The field of implementation science studies how to better integrate research evidence into practice. To accomplish this integration, it is important to understand the contexts into which interventions are being implemented. For example, implementation may be influenced by contextual factors such as patient/provider beliefs about an intervention, budget constraints, leadership buy-in, an organization's readiness to change, and many others. Understanding these factors upfront can allow us to adapt interventions to better suit context (e.g., tailoring intervention content to patients' needs), change context to make it more ready for implementation (e.g., changing provider workflow to accommodate an intervention), and anticipate strategies that may be needed to implement an intervention (e.g., delivering training on the intervention to providers). To do this, the field of implementation science is in need of methods for assessing context and using that information to improve implementation. In this paper, we present several methods, including ethnography and methods from user-centered design, for using context to inform implementation efforts.

Health Insurance Payer Type and Ethnicity Are Associated with Cancer Clinical Trial Enrollment Among Adolescents and Young Adults.

Purpose: Adolescents and young adults (AYAs) have experienced inferior improvements in cancer survival outcomes. One potential explanation is the low rate of enrollment in cancer clinical trials. While the reasons behind this are multifactual, sociodemographic factors are probably contributory. We examined the impact of factors such as insurance type and race/ethnicity on clinical trial enrollment among AYAs treated for cancer at an academic medical center. Methods: We identified AYAs (ages 15-39 years) treated for cancer at the University of North Carolina between April 2014 and April 2019. Cancer registry data were linked to electronic health record data to associate treatment and sociodemographic factors with clinical trial enrollment. A multivariable log-binomial model was used to estimate adjusted risk ratios. Results: In a 5-year period, 1574 AYA patients were identified, 59% female, 21% non-Hispanic Black and 9% Hispanic. Overall, 37% of AYAs participated in any clinical trial and 14% enrolled on a therapeutic trial. When compared to publicly insured AYAs, those with private insurance [adjusted RR: 1.52, 95% CI: 1.05-2.22] or with no insurance [adjusted RR: 2.12, 95% CI: 1.34-3.33] were more likely to enroll in a therapeutic clinical trial. Hispanic AYAs were less likely to enroll [adjusted RR: 0.50, 95% CI: 0.27-0.93] when compared to non-Hispanic White patients. Conclusions: Rates of clinical trial enrollment among AYAs vary based on health insurance type and race/ethnicity, suggesting possible disparities in access. Attention to resource, cultural, and language barriers may improve trial enrollment and cancer outcomes among vulnerable AYA subpopulations.

Autoimmune Cytopenia as an Early and Initial Presenting Manifestation in Activated PI3 Kinase Delta Syndrome: Case Report and Review.

Activated PI3 kinase delta syndrome (APDS) is a combined immunodeficiency characterized by recurrent sinopulmonary infections, increased risk of herpesvirus infections, lymphoproliferation, autoimmunity, and increased risk of lymphoid malignancies. Gain-of-function mutations in PIK3CD and PIK3R1 result in increased phosphoinositide-3-kinase-delta activity which causes hyperactivation of lymphocytes and abnormal development and activation of T and B cells. Cytopenias are the most common autoimmune process occurring in patients with APDS and typically occur as a later manifestation of the disease. Here we present a female patient with an early autoimmune hemolytic anemia, hepatosplenomegaly, and frequent infections presenting in infancy, followed by development of significant lymphadenopathy before her diagnosis with APDS type 1. She had significant improvement in her infectious history with immunoglobulin replacement, and control of autoimmune hemolytic anemia with initiation of sirolimus after her diagnosis with APDS type 1. We utilize this case to review the literature on APDS and present the novel finding of early-onset autoimmune disease in the setting of APDS. Autoimmune cytopenias are seen in many primary immunodeficiencies, and workup of autoimmune cytopenias in young patients should include evaluation for underlying immune disorder.

An actionable needs assessment for adolescents and young adults with cancer: the AYA Needs Assessment & Service Bridge (NA-SB).

PURPOSE: In the USA, many of the nearly 90,000 adolescents and young adults (AYAs) diagnosed with cancer each year do not receive services to address the full scope of needs they experience during and after cancer treatment. To facilitate a systematic and patient-centered approach to delivering services to address the unmet needs of AYAs with cancer, we developed the AYA Needs Assessment & Service Bridge (NA-SB). METHODS: To develop NA-SB, we leveraged user-centered design, an iterative process for intervention development based on prospective user (i.e., provider and AYA) engagement. Specifically, we conducted usability testing and concept mapping to refine an existing tool-the Cancer Needs Questionnaire-Young People-to promote its usability and usefulness in routine cancer practice. RESULTS: Our user-centered design process yielded a need assessment which assesses AYAs' physical, psychosocial, and practical needs. Importantly, needs in the assessment are grouped by services expected to address them, creating an intuitive and actionable link between needs and services. CONCLUSION: NA-SB has the potential to improve care coordination at the individual level by allowing cancer care programs to tailor service delivery and resource provision to the individual needs of AYAs they serve.

Accelerated aging among childhood, adolescent, and young adult cancer survivors is evidenced by increased expression of p16INK4a and frailty.

BACKGROUND: Cellular senescence, measured by expression of the cell cycle kinase inhibitor p16INK4a , may contribute to accelerated aging in survivors of childhood, adolescent, and young adult cancer. The authors measured peripheral blood T-lymphocyte p16INK4a expression among pediatric and young adult cancer survivors, hypothesizing that p16INK4a expression is higher after chemotherapy and among frail survivors. METHODS: A cross-sectional cohort of young adult survivors and age-matched, cancer-free controls were assessed for p16INK4a expression and frailty. Newly diagnosed pediatric patients underwent prospective measurements of p16INK4a expression before and after cancer therapy. Frailty was measured with a modified Fried frailty phenotype evaluating sarcopenia, weakness, slowness, energy expenditure, and exhaustion. RESULTS: The cross-sectional cohort enrolled 60 survivors and 29 age-matched controls with a median age of 21 years (range, 17-29 years). The prospective cohort enrolled 9 newly diagnosed patients (age range, 1-18 years). Expression of p16INK4a was higher among survivors compared with controls (9.6 vs 8.9 log2 p16 units; 2-sided P = .005, representing a 25-year age acceleration in survivors) and increased among newly diagnosed patients from matched pretreatment to posttreatment samples (7.3-8.9 log2 p16 units; 2-sided P = .002). Nine survivors (16%) were frail and had higher p16INK4a expression compared with robust survivors (10.5 [frail] vs 9.5 [robust] log2 p16 units; 2-sided P = .055), representing a 35-year age acceleration among frail survivors. CONCLUSIONS: Chemotherapy is associated with increased cellular senescence and molecular age in pediatric and young adult cancer survivors. Frail survivors, compared with robust survivors, exhibit higher levels of p16INK4a , suggesting that cellular senescence may be associated with early aging in survivors.

p16 a biomarker of aging and tolerance for cancer therapy.

There is great variability in life-expectancy, physical, cognitive, and functional domains in cancer patients of similar chronologic age. Nowhere is this more apparent than among middle-aged and older patients. However, even in younger patients of similar age, extensive exposure to environmental stressors can cause great variability in health status. A biomarker that would reflect biologic age and any and all health deficits in a cancer patient at a distinct point in time might help predict long term outcomes related to treatment, especially toxicity and overall survival. p16INK4a (hereafter referred to as p16) expression represents an ideal biomarker that reflects both cellular senescence and biologic aging. In murine models, p16 expression reflects biologic aging in almost all organs. Preliminary findings in patients with cancer support p16 measurement as a marker of physiologic aging and predictor of toxicity in patients treated with chemotherapy. This review describes the role of p16 in cell senescence, the methodology of p16 measurement in humans, preliminary studies of p16 in humans, and the potential clinical utility of p16 in guiding treatment for cancer patients.