Erin M. Mobley

PURPOSE: Dexrazoxane has been associated with preservation of left ventricular (LV) systolic function in relatively small studies of long-term childhood cancer survivors. What remains less clear is whether this association is also seen in larger populations over time and what effect dexrazoxane has on cardiomyopathy screening recommendations. METHODS: We analyzed echocardiographic data from participants who received doxorubicin treatment and were enrolled on Children's Oncology Group protocols P9404, P9425, P9426, P9754, and Dana Farber Cancer Institute protocol 95-01. Except for P9754, all protocols featured up-front 1:1 random assignment with dexrazoxane administered uniformly as an intravenous bolus before doxorubicin (10:1 mg/m ² dexrazoxane:doxorubicin dose). Blinded central echocardiogram remeasurements were used when possible; otherwise, data were abstracted from institutional reports. Differences and associations by ± dexrazoxane were estimated using generalized estimating equations and Cox proportional hazard models, adjusting for age, sex, doxorubicin dose, chest radiotherapy, and echocardiogram data type. RESULTS: Among 895 patients (mean follow-up, 5.9 years, 230 with ≥10-year follow-up; median doxorubicin dose, 360 mg/m ² ; 51% dexrazoxane-exposed) with evaluable echocardiograms (n = 2,279; 1,581 centrally remeasured; 698 report only), preserved LV systolic function was observed in patients treated with dexrazoxane (z-score difference 0.4 [95% CI, 0.2 to 0.5]) versus without. Dexrazoxane was also associated with decreased hazards of reduced LV function (fractional shortening P = .001). CONCLUSION: Dexrazoxane exerts a significant doxorubicin cardioprotective effect on LV systolic function long term and may reduce screening needs.

Purpose Adolescents and young adults (AYAs, diagnosed between 15 and 39 years) receive cancer care in diverse settings, posing challenges in delivering survivorship services following treatment. We examined survivorship service availability for AYAs at National Cancer Institute (NCI) Community Oncology Research Program (NCORP) practice groups. Methods We utilized data from the 2022 NCORP Landscape Assessment survey to describe survivorship care among AYA-treating practice groups. Univariable and multivariable analyses describe associations between survivorship clinic availability and ancillary tools or services (health-related screening, information technology, and administrative characteristics). Results Among the 100 AYA-treating practice groups, less than half (48%) had a survivorship clinic. In multivariable analysis, there were greater odds of having a survivorship clinic among practices that routinely screened for financial distress (odds ratio, 7.05; 95% confidence interval, 1.78–27.91). Although significant upon univariable analysis, health literacy screening, electronic health record vendor, Critical Access Hospital designation, and serving pediatric and a high Medicaid patient population were not significant upon multivariable analysis. Conclusions Over half of AYA-treating practices in community settings lacked available survivorship clinics. Understanding how to leverage available resources is needed to facilitate guideline-concordant, high-quality survivorship care for AYAs. Implications for Cancer Survivors Given that about half of the surveyed practice groups do not offer survivorship services, alternative mechanisms for delivery of survivorship care to long-term survivors of AYA cancer are needed, including collaboration with primary care providers. Future pragmatic, real-world approaches could explore less resource-intensive strategies and offer insight into implementation contexts in a community setting.

PURPOSE: Given the impact of cancer treatment on fertility among adolescents and young adults (AYAs: 15-39 years), it is important to ensure AYAs access to fertility preservation (FP). However, the availability of FP services for AYAs treated in community settings is unknown. We examined FP access at National Cancer Institute Community Oncology Research Program (NCORP) practice groups. METHODS: The 2022 NCORP Landscape Assessment survey captured available resources and cancer care services including FP services at practice groups. We described FP services as accessible (on-site or off-site) versus not accessible by AYA-treating status (as previously defined). Univariable and multivariable analyses were used to evaluate associations between FP services and practice characteristics (NCORP classification [minority/underserved or community] and proportion of Medicaid or uninsured above/below the national average). RESULTS: Among 271 practice groups responding to the survey, 100 were categorized as AYA-treating, of which 32% had neither male nor female FP services available. Sperm banking was available at 59 AYA-treating practices, among which 43 (73%) referred for sperm banking off-site. Although approximately half of AYA-treating practices reported accessible female FP services (embryo = 54%, oocyte = 55%, ovarian tissue = 40%), most of them referred patients off-site (embryo = 72%, oocyte = 80%, ovarian tissue = 83%). The odds of access to male FP were lower at minority/underserved practices (odds ratio, 0.34 [95% CI, 0.13 to 0.88]; P = .026; ref = community); however, this same relationship was not seen for females. CONCLUSION: Despite guidelines surrounding FP discussions before cancer therapy, and strong consensus regarding the importance of FP access, many AYA-treating practices in community settings lack access to FP services. Understanding how to leverage available services and broadly expand access is urgently needed to facilitate guideline-concordant, high-quality cancer care for AYAs.

Introduction: Childhood cancer survivors (CCS) experience many long-term health problems that can be alleviated by receiving guideline-concordant survivorship care. However, many CCS encounter barriers to accessing care and do not receive recommended survivorship care. We reviewed the empirical evidence of barriers to and facilitators of survivorship care for CCS. Methods: As part of a larger project on CCS, this systematic review followed a detailed protocol (CRD42021227965) and searched PubMed, CINAHL, and PsycINFO for studies on survivorship care for CCS without date restriction, and abstracted reported barriers and facilitators. Searches identified 8585 citations and 2 independent reviewers screened 2934 publications at full text. We evaluated the risk of bias for individual studies and quality of evidence (QoE) across barriers and facilitators. Results: A total of 49 studies reported barriers and facilitators (survivors N = 33, clinicians N = 19, family members N = 8, and health system leaders N = 7) addressing knowledge (beliefs, autonomy, culture), prioritization (active avoidance, trust, communication), and infrastructure (health system resources, transitions). We found high QoE of barriers including lack of knowledge and inaccurate beliefs (survivorship care not needed or redundant), active avoidance and lack of trust (high level of emotional trauma and anxiety, lack of confidence in care team, no local providers with experience in survivorship care), and gaps in infrastructure (financial toxicity/hardship, lack of insurance coverage, difficulty scheduling appointments, and lack of stable housing). Conversely, knowledge (providing a survivorship care plan or treatment summary, supporting patient autonomy) and prioritization (close relationships with clinicians, enhanced care coordination, communication) can also facilitate survivorship care engagement, documented with high QoE. Conclusions: We found strong empirical evidence of barriers to and facilitators of survivorship care, including potentially modifiable factors surrounding knowledge, prioritization, and infrastructure survivorship care. Prospective, multilevel approaches are needed to improve the receipt of guideline-concordant survivorship care among CCS.

Background: Colorectal cancer is now the leading cause of cancer-related deaths among young Americans. Accurate early prediction and a thorough understanding of the risk factors for early-onset colorectal cancer (EOCRC) are vital for effective prevention and treatment, particularly for patients below the recommended screening age. Objective: Our study aims to predict EOCRC using machine learning (ML) and structured electronic health record data for individuals under the screening age of 45 years, with the aim of exploring potential risk and protective factors that could support early diagnosis. Methods: We identified a cohort of patients under the age of 45 years from the OneFlorida+ Clinical Research Consortium. Given the distinct pathology of colon cancer (CC) and rectal cancer (RC), we created separate prediction models for each cancer type with various ML algorithms. We assessed multiple prediction time windows (ie, 0, 1, 3, and 5 y) and ensured robustness through propensity score matching to account for confounding variables including sex, race, ethnicity, and birth year. We conducted a comprehensive performance evaluation using metrics including area under the curve (AUC), sensitivity, specificity, positive predictive value, negative predictive value, and F₁-score. Both linear (ie, logistic regression, support vector machine) and nonlinear (ie, Extreme Gradient Boosting and random forest) models were assessed to enable rigorous comparison across different classification strategies. In addition, we used the Shapley Additive Explanations to interpret the models and identify key risk and protective factors associated with EOCRC. Results: The final cohort included 1358 CC cases with 6790 matched controls, and 560 RC cases with 2800 matched controls. The RC group had a more balanced sex distribution (2:3 male-to-female) compared to the CC group (2:5 male-to-female), and both groups showed diverse racial and ethnic representation. Our predictive models demonstrated reasonable results, with AUC scores for CC prediction of 0.811, 0.748, 0.689, and 0.686 at 0, 1, 3, and 5 years before diagnosis, respectively. For RC prediction, AUC scores were 0.829, 0.771, 0.727, and 0.721 across the same time windows. Key predictive features across both cancer types included immune and digestive system disorders, secondary malignancies, and underweight status. In addition, blood diseases emerged as prominent indicators specifically for CC. Conclusions: Our findings demonstrate the potential of ML models leveraging electronic health record data to facilitate the early prediction of EOCRC in individuals under 45 years. By uncovering important risk factors and achieving promising predictive performance, this study provides preliminary insights that could inform future efforts toward earlier detection and prevention in younger populations.

Introduction: We evaluated whether Medicaid expansion (ME) was associated with improved 2‐year survival and time to treatment initiation (TTI) among patients with gastrointestinal (GI) cancer.Methods: GI cancer patients diagnosed 40–64 years were queried from the National Cancer Database. Those diagnosed from 2010 to 2012 were considered pre‐expansion; those diagnosed from 2014 to 2016 were considered post‐expansion. Cox models estimated hazard ratios and 95% confidence intervals (CIs) for 2‐year overall survival. Generalized estimating equations (GEE) estimated odds ratios (OR) and 95% CI of TTI within 30‐ and 90 days. Multivariable Difference‐in‐Difference models were used to compare expansion/nonexpansion cohorts pre‐/post‐expansion, adjusting for patient, clinical, and hospital factors.Results: 377,063 patients were included. No significant difference in 2‐year survival was demonstrated across ME and non‐ME states overall or in site‐based subgroup analysis. In stage‐based subgroup analysis, 2‐year survival significantly improved among stage II cancer, with an 8% decreased hazard of death at 2 years (0.92; 0.87–0.97). Those with stage IV had a 4% increased hazard of death at 2 years (1.04; 1.01–1.07). Multivariable GEE models showed increased TTI within 30 days (1.12; 1.09–1.16) and 90 days (1.22; 1.17–1.27). Site‐based subgroup analyses indicated increased likelihood of TTI within 30 and 90 days among colon, liver, pancreas, rectum, and stomach cancers, by 30 days for small intestinal cancer, and by 90 days for esophageal cancer. In subgroup analyses, all stages experienced improved odds of TTI within 30 and 90 days.Conclusion: ME was not associated with significant improvement in 2‐year survival for those with GI cancer. Although TTI increased after ME for both cohorts, the 30‐ and 90‐day odds of TTI was higher for those from ME compared with non‐ME states. Our findings add to growing evidence of associations with ME for those diagnosed with GI cancer.

Background: Childhood cancer survivors (CCS) experience many long‐term health problems that can be mitigated with recommended survivorship care. However, many CCS do not have access to survivorship care nor receive recommended survivorship care. We reviewed the empirical evidence of disparities in survivorship care for CCS.Methods: This systematic review searched PubMed, CINAHL, and PsycINFO for studies on survivorship care for CCS (PROSPERO: CRD42021227965) and abstracted the reported presence or absence of disparities in care. We screened 7945 citations, and of those, we reviewed 2760 publications at full text.Results: A total of 22 studies reported in 61 publications met inclusion criteria. Potential disparities by cancer treatment (N = 14), diagnosis (N = 13), sex (N = 13), and current age (N = 13) were frequently studied. There was high quality of evidence (QOE) of survivorship care disparities associated with non‐White race, Hispanic ethnicity, and being uninsured. Moderate QOE demonstrated disparities among CCS who were unemployed and older. Lower QOE was found for disparities based on cancer diagnosis, cancer treatment, age at diagnosis, time since diagnosis, sex, insurance type, income, educational attainment, and geographic area.Conclusions: We found strong empirical evidence of disparities in survivorship care for CCS associated with race, ethnicity, and insurance status. Multiple other disparate groups, such as those by employment, income, insurance type, education, cancer diagnosis, age at diagnosis, time since diagnosis, cancer treatment, geographic area, sex, and self‐identified gender warrant further investigation. Prospective, multilevel research is needed to examine the role of other patient characteristics as potential disparities hindering adequate survivorship care in CCS.

Purpose: Although participation of adolescents and young adults (AYAs) in cancer clinical trials (CCTs, i.e., cancer-directed treatment studies) is low, their decision-making perspectives are not well understood, especially following recent diagnosis. Methods: Semistructured interviews with younger AYAs (15–21 years old) eligible for a CCT were to be held within 60 days of beginning treatment at Children's Hospital Los Angeles, an academic pediatric hospital. Using grounded theory methods, key themes regarding CCT participation, barriers, and facilitators were identified from interview transcripts. Thematic saturation was confirmed. Results: Of nine participants, three were <18 years old, four Hispanic, six male, six diagnosed with leukemia, eight enrolled in a CCT, and eight also enrolled in ancillary studies. Four overarching themes emerged: (1) Initial Consent encompassed the first discussion of CCT with patients reflecting positive and negative effects of timing, decisional role, and the emotional impact following cancer diagnosis; (2) Informing Participation involved decision-making processes, specific knowledge, comprehension, and external influences; (3) Participant Relationships emphasized the importance of communication and relationships with providers and parents; and (4) Patient Determinants centered on motives from different perspectives, pre-conceived attitudes, and understanding of CCTs. Conclusion: Recommendations for improving CCT participation among younger AYAs include separating the diagnosis/treatment and CCT discussions, assigning AYAs a meaningful decisional role, having ongoing provider conversations, designing trials to minimize burden, and developing age-appropriate decision aids.

Introduction We evaluated whether Medicaid expansion is associated with earlier stage at diagnosis for pancreatic cancer taking into account key demographic, clinical, and geographic factors. Methods We obtained Surveillance, Epidemiology, and End-Results (SEER-18) data on individuals diagnosed with pancreatic cancer from 2007 to 2016 (< 65 years of age). We defined non-metastatic as either local or regional disease (vs. metastatic disease). To estimate the association of Medicaid expansion with pancreatic cancer stage at diagnosis, we used a difference-in-differences model, at the individual level, comparing those from early-adopting states in 2014 to non-early-adopting states. We utilized cluster-robust standard errors and explored the role of demographic factors (race, sex, insurance at diagnosis), clinical indicator (disease in the head of the pancreas), and county characteristics (Urban Influence Code, Social Deprivation Index). Results In the univariable setting, the probability of non-metastatic disease at diagnosis increased by 3.9 percentage points (ppt) for those from Medicaid expansion states post-expansion (n = 36,609). After adjustment for covariates, the ppt was attenuated to 2.7. Of particular note, we observed evidence of interactions with sex and race. The beneficial effect was less pronounced for men (increase in the probability of non-metastatic stage at diagnosis by 2.1ppt) than women (3.6ppt) and non-existent for blacks (− 3.1ppt) compared to whites (4.9ppt) and other races (4.8ppt). Conclusion Medicaid expansion is associated with increased probability of non-metastatic stage at diagnosis for pancreatic cancer; however, this beneficial effect is not uniform across sex and race. This underscores the need to investigate the impact of policy and implementation strategies on pancreatic cancer survival disparities.