bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between psychosocial and lifestyle factors and biological age acceleration among long-term survivors of childhood cancer: A prospective study from the St. Jude Lifetime Cohort.
Authors: Streck Brennan , Hyun Geehong , Armstrong Gregory T. , Belsky Daniel W , Ehrhardt Matthew J. , Hudson Melissa , Green Paige , Robison Leslie L. , Tonorezos Emily S. , Yasui Yutaka , Wang Zhaoming , Wilson Carmen L , Brinkman Tara M. , Ness Kirsten K. , Guida Jennifer Lyn 
Published: June 2023

10049 Background: Survivors of childhood cancers may be at risk for premature, or accelerated, biological age aging, which is associated with cancer treatment exposures. However, life course theory and a growing body of evidence suggest that psychosocial and lifestyle factors may also contribute. The objective of this study was to explore associations between psychosocial and lifestyle factors and biological age acceleration in the St. Jude Lifetime Cohort. Methods: In this cross-sectional study, we applied physiology-based methods (Klemera-Doubal method and Phenotypic Age) and DNA methylation-based epigenetic clocks (Horvath’s, Hannum’s, Levine’s PhenoAge, GrimAge, and DunedinPACE clocks) to compare biological age acceleration, estimated as the residual from regressing biological age on chronological age, among survivors (n = 4,117) and age- and sex-frequency-matched non-cancer community controls (n = 606). We compared psychosocial and lifestyle factors between survivors and controls using t-tests/Wilcoxan rank sums, and chi-square. Multivariable linear regression was used to assess associations of self-reported smoking, alcohol use, physical activity, overweight/obesity, and depressive symptoms with biological age acceleration in survivors, adjusted for age, race/ethnicity, sex, education, and cancer treatment. Results: Childhood cancer survivors at a mean chronological age of 35.1 years (SD 10.2) were biologically older than controls according to KDM-BA, Phenotypic Age, Hannum’s clock, Levine’s PhenoAge clock, and DunedinPACE, with biological age acceleration ranging from 1.7-4.7 years (p < 0.05.) A greater proportion of survivors reported elevated depressive symptoms (10.3% v. 8.7%), current smoking (17.8% v. 12.3%), < 150 minutes of physical activity (47.3% v. 38.2%), and were overweight/obese (66.0% v. 59.9%) compared to controls (p’s < 0.001). In survivors, < 150 minutes of physical activity (B’s (difference in biological age acceleration [years]) = 1.10-2.68), current (B’s = 1.18-5.96) and former smoking (B’s = 2.53-4.29) were consistently associated with higher biological age acceleration across measures (p’s < 0.05). Risky drinking and higher depressive symptoms were associated with higher biological age acceleration, but only for KDM (B = 1.26, p < 0.021) and DunedinPACE measures (B = 0.15, p < 0.001), respectively. Conclusions: Biological aging in childhood cancer survivors is associated with psychosocial and lifestyle factors. Interventions designed to optimize healthy behaviors and mitigate poor emotional health may have potential to prevent or remediate this phenotype in childhood cancer survivors.
Demographic predictors of successful transition to adult survivorship care for survivors of pediatric cancer.
Authors: Gilbert Renee , Bates Carolyn , Alsman Kyla , Fulbright Joy M. , Lowry Becky N. , Nelson Eve-Lynn 
Published: June 2023

10050 Background: There is a growing number of childhood cancer survivors in the U.S. (Chow et al., 2020) who are at risk for experiencing negative long-term health outcomes (Oeffinger et al., 2006). Current guidelines state the importance of receiving risk-based follow-up at adult survivorship clinics, yet available estimates suggest that less than 50% of survivors receive yearly survivorship care (Landier et al., 2004; Daly et al., 2018). The transition from pediatric to adult care is a difficult process, with various factors acting as barriers (Devine et al., 2017). The present study sought to evaluate demographic predictors of successful transition to adult survivorship care in a Midwestern clinic serving a large urban and rural catchment area. Methods: The study includes adult survivors of childhood cancer (n = 203) who received pediatric or adult survivorship care in a Midwestern metropolitan area from 2015 to 2022. For this study, successful transition to adult care was defined as attending at least one appointment in the adult survivorship clinic. Dates of clinic attendance, cancer diagnosis, insurance data, and zip code were abstracted from the medical record. 86.2% of survivors had commercial insurance, 13.8% had government -sponsored insurance, self-pay or other insurance. Participant zip codes were 66.7% urban, 19.5% metropolitan (low and high commuting), 9.2% micropolitan, and 4.6% rural. Survivor ages ranged from 20 to 68 years (M = 29.48, SD = 7.74) and 53.2% were female. Participant-reported race/ethnicity was 90.1% White, 5.4% Hispanic, 3.4% Black and 1% Other. Results: 66% of the sample attended at least 1 appointment in the adult survivorship clinic. Chi-square analyses revealed a significant relationship between insurance type and attendance at the clinic, [Χ2(1) = 16.60, p < .001], such that a greater proportion of survivors with commercial insurance transitioned to adult survivorship care (71%), compared to government-assisted (Medicare), self-pay or other insurance (32%). Analyses revealed a significant relationship between rurality and transition, [Χ2(3) = 14.11, p < .01], such that a greater proportion of survivors from urban areas transitioned (74%) compared to rural areas (22%). Race/ethnicity, gender and cancer type were not significantly associated with transition. Conclusions: Results suggest that a lack of commercial insurance and rurality served as risk factors for not successfully transitioning to an adult survivorship clinic, highlighting opportunities for improvement in clinic reach.
Mortality and the burden of subsequent malignant neoplasms in survivors of childhood cancer beyond age 50: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Bhandari Rusha , Chen Yan , Chow Eric Jessen , Howell Rebecca M. , Kenney Lisa Brazzamano , Krull Kevin R. , Leisenring Wendy M. , Nathan Paul C. , Neglia Joseph Philip , Ness Kirsten K. , Oeffinger Kevin C. , Snyder Claire Frances , Turcotte Lucie Marie , Wong Florence Lennie , Yasui Yutaka , Armstrong Gregory T. , Armenian Saro 
Published: June 2023

10052 Background: The first generation of survivors of childhood cancer is now older than 50 years (y) of age. There is a paucity of information on the risk for late mortality and the evolving burden of subsequent malignant neoplasms (SMNs) in these aging survivors. Methods: We assessed cause-specific mortality (National Death Index) and self-reported SMNs (excluding nonmelanoma skin cancers) among CCSS participants diagnosed between 1970-1999, conditional on having survived to 50y by 12/31/2017. There were 4,772 survivors alive at 50y eligible for mortality analyses. Of the 3,355 who completed a baseline CCSS questionnaire, 2,273 also completed a follow-up questionnaire at ≥50y and were included in the SMN analyses. Cumulative mortality, standardized mortality ratios (SMRs), and, for SMNs, cumulative burden, standardized incidence ratios (SIRs), and relative rate (RR) with 95% confidence intervals (CIs) were calculated, compared with the general US population and by survivor subgroups. Piecewise-exponential multivariable regression was used to identify risk factors associated with the development of SMNs after 50y. Results: Mean age at diagnosis was 14y (standard deviation 4.2y). Mortality: Among survivors who attained 50y of age, the subsequent 5y, 10y, and 15y incidences of all-cause mortality were 9%, 19%, and 35%, respectively, (overall SMR 3.7 [95% CI 3.4-4.1]). SMRs were highest for SMN (SMR 5.1 [95% CI 4.4-5.9]), pulmonary (SMR 4.7 [95% CI 3.3-6.5]) and cardiovascular (SMR 3.9 [95% CI 3.2-4.8]) causes of death. The highest SMR (SMR 9.2 [95% CI 7.7-10.8]) was seen in female survivors of Hodgkin lymphoma. SMN: By age 50y, 14% of CCSS participants reported >1 SMN. History of SMN <50y was independently associated with the rate of developing another SMN at >50y (RR 1.6 [95% CI 1.1-2.3]). The most frequent SMNs ≥50y were breast (41%) in females and prostate (21%) in males, followed by gastrointestinal cancers in both (14% [females], 19% [males]). The cumulative burden of SMNs in survivors treated with radiation therapy (RT) increased sharply with age and exceeded 50 per 100 survivors by 65y (SIR 3.3 95%CI 2.0-5.2]). Survivors who did not receive RT had a SMN rate comparable to the general population (Table). Conclusions: This sentinel population of survivors of childhood cancer is at high risk for poor outcomes as they enter older adulthood. RT exposure and history of SMN <50y are associated with increased risk for developing SMNs after 50y. The evolving burden of late morbidity attributed to SMNs may be lower for contemporary survivors projected to have less RT exposure. [Table: see text]
Longitudinal associations between peripheral neuropathy and neurocognitive decline in long-term survivors of pediatric cancer treated without central nervous system (CNS) directed therapy.
Authors: Williams AnnaLynn , Phillips Nicholas Steve , Goodenough Chelsea Goodliffe , Brinkman Tara M. , Papini Chiara , Jacola Lisa M , Delaney Angela , Armstrong Gregory T. , Jefferies John L. , Khan Raja B. , Robison Leslie L. , Hudson Melissa M. , Ness Kirsten K. , Krull Kevin R. 
Published: June 2023

10054 Background: Survivors of pediatric cancer treated without CNS-directed therapy are at risk of neurocognitive impairment and peripheral neuropathies. Using the St. Jude Lifetime Cohort, we investigated longitudinal associations with neuropathy to inform contributors to long-term cancer-related neurocognitive decline. Methods: Survivors of pediatric cancer (N=899 mean age 32 [SD 12], 24[10] years from diagnosis) treated without CNS-directed therapy completed neurocognitive testing and medical assessments at two timepoints (T1, T2 4.4[2.3] years apart). Peripheral sensory and motor neuropathy subscales combined with functional tasks were severity graded using a modified CTCAE (no neuropathy = none or grade 1 at T1 and T2; new onset = new grade 2 or 3 at T2; persistent = grade 2 or 3 at T1 & T2). Linear regression models estimated change in neurocognitive Z-score associated with neuropathy groups, adjusted for diagnosis age, time between visits, sex, race/ethnicity, high-dose intravenous methotrexate & baseline neurocognitive Z-score. Results: New onset sensory (n=33, 3.6%) and motor (n=35, 3.9%) neuropathy was associated with a 0.33 standard deviation (SD) decline in visual-motor processing speed (Table). New onset motor neuropathy was associated with a 0.50 SD decline in sustained attention as well as significant declines in verbal recall, working memory, and cognitive flexibility (p’s<0.05). Persistent sensory neuropathy (n=25, 2.8%) was associated with large declines in focused attention and cognitive flexibility (p’s<0.05). Persistent motor neuropathy (n=18, 2.0%) was associated with a 0.50 SD decline in sustained attention, verbal recall, and working memory (p’s<0.05). Conclusions: Peripheral neuropathies are associated with future neurocognitive decline in adult survivors of pediatric cancer. Research is needed to understand shared mechanisms (e.g. pain, inflammation) to inform targeted interventions to improve neuropathic symptoms and neurocognitive function. [Table: see text]
Subsequent meningiomas in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Cooney Tab , Chen Yan , Yuan Yan , Galvin Robert Thomas , Leisenring Wendy M. , Smith Susan A. , Howell Rebecca M. , Arnold Michael A. , Conces Miriam , Bowers Daniel C. , Yasui Yutaka , Diller Lisa , Armstrong Gregory T. , Neglia Joseph Philip , Turcotte Lucie Marie 
Published: June 2023

10058 Background: Meningiomas are the most common subsequent central nervous system tumor among aging survivors of childhood cancer, yet incidence across the lifespan, occurrence of multiple meningiomas, and risk for mortality are not established. Methods: Meningiomas were identified by self-report and validated with pathology/medical records. Twenty-year cumulative incidence of meningioma (95% confidence interval) was estimated and multivariable models assessed demographic- and treatment-related meningioma risk factors. Results: Among 24,902 5-year survivors of childhood cancer diagnosed 1970-1999, we identified 472 survivors with 710 meningiomas, 145 (20.4%) of which were WHO grade 2/3. Among survivors with meningioma, 137 (28%) had ≥2 meningiomas, and 80 (16%) met criteria for meningiomatosis. The median latency from childhood cancer to first meningioma diagnosis was 26.2 years (range 5.6-48.2), and the median time from first to second meningioma (among those without meningiomatosis) was 1.4 years (range 0-30.2 years). The twenty-year cumulative incidence did not significantly decrease between survivors diagnosed in the 1970s (0.58, 95% CI 0.41-0.79) and the 1990s (0.42, 95% CI 0.32-0.55). In multivariable analysis, female sex (HR 1.52, 95% CI 1.21-1.91) and all cranial radiotherapy dose levels ( > 0-30Gy, HR 57.0, 95% CI 7.93-419.60; 30.1-50 Gy, HR 228.90, 95% CI 30.89-1695.99; > 50 Gy, HR 113.29, 95% CI 15.09-850.34) were associated with increased meningioma risk, while older age at diagnosis (10-14 years, HR 0.60, 95% CI 0.44-0.82; 15-20 years, HR 0.35, 95% CI 0.22-0.55) was associated with reduced meningioma risk. Among 71 deaths in survivors with meningioma, the most prevalent cause of death was meningioma (N = 25, 35.2%). The 5-year all-cause mortality from first meningioma diagnosis was 4.20% (95% CI: 2.44-5.96%). Conclusions: In conclusion, cranial radiation, younger diagnostic age and female sex were identified as independent meningioma risk factors in, to our knowledge, the largest study to date. The risk for meningioma-associated mortality argues for assertive meningioma surveillance and treatment in this population.
Racial disparities in treatment and outcomes of pediatric hepatoblastoma.
Authors: Billion Taylor , Holland Eva , Silberstein Peter T. , Braaten Marco 
Published: June 2023

10062 Background: Hepatoblastoma is the most common malignant liver tumor which affects pediatric patients. However, the incidence is rare with 100 cases reported per year.1 Current management consists of surgery and adjuvant cisplatin chemotherapy and radiation depending on tumor histology, resectability, and metastasis.2 However, due to its rarity, optimal treatment protocol remains unclear. The 5-year overall survival rate in the US is approximately 57-69%1. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with hepatoblastoma from 2004 to 2020 using the histology codes 8970 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, Chi-Square, and ANOVA tests were performed. Data was analyzed using SPSS version 27 and statistical significance was set at α = 0.05. Results: This study identified 1215 patients with hepatoblastoma. Black patients had a significantly lower median survival rate compared to White and other race patients (126.2 months vs 165.4 months vs 166.1 months; all p<0.05). Black patients were more likely to be from low-income households than White patients (29.6% vs 17.3%; p<0.05). The mean age of diagnosis was higher for Black patients compared to White patients (2.42 vs 1.99; p<0.05). Black patients were less likely to receive surgery (63.5% vs. 75.4%; p<0.05). Black patients on average had shorter distances to travel from their residence to the hospital (30.61 vs. 59.52 miles; p<0.05). Black patients had longer mean stay times compared to white patients (16.7 days vs 11.2 days; p<0.05). There was no significant difference in survival across incomes. When comparing Black and White patients there was no significant difference in insurance type, surgical margins, grade, stage, size of tumor, regional lymph nodes and time of diagnosis to treatment. No significant difference was shown between adjuvant therapies including chemotherapy and radiation. Conclusions: This study showed Black patients experienced inferior overall survival when diagnosed and treated for hepatoblastoma compared to White patients. This population was less likely to receive surgery, older when diagnosed, and had longer hospital stays. Poorer outcomes suggest a disparity in hepatoblastoma treatment. References: 1. Rangaswami, Arun A. “Pediatric Hepatoblastoma Treatment & Management: Medical Care, Surgical Care, Consultations.” Pediatric Hepatoblastoma Treatment & Management: Medical Care, Surgical Care, Consultations, Medscape, 9 Dec. 2021, https://emedicine.medscape.com/article/986802-treatment . 2. Pritchard J, Brown J, Shafford E, et al.: Cisplatin, doxorubicin, and delayed surgery for childhood hepatoblastoma: a successful approach--results of the first prospective study of the International Society of Pediatric Oncology. J Clin Oncol 18 (22): 3819-28, 2000.
Randomized trial of fixed dose capecitabine compared to standard dose capecitabine in metastatic breast cancer: The X-7/7 trial.
Authors: Khan Qamar J. , Bohnenkamp Colleen , Monson Taylor , Smith Holly E , Phadnis Milind A. , Raja Vinay , Elia Manana , O'Dea Anne , Crane Gregory James , Fesen Mark Robert , Nye Lauren Elizabeth , Sheehan Maureen , Pluenneke Robert E. , Al-Rajabi Raed Moh'd Taiseer , Baranda Joaquina Celebre , Kasi Anup , McKittrick Richard J. , Mitchell Laura , LaFaver Stephanie , Sharma Priyanka 
Published: June 2023

1007 Background: In metastatic breast cancer (MBC), oral capecitabine prescribed at the FDA approved dose of 1250 mg/m2 twice daily, 14 days on followed by 7 days off, is associated with poor tolerance and high discontinuation rates. Mathematical models suggest a fixed dose, dose dense (7 days on, 7 days off) schedule may be optimal for capecitabine efficacy. We conducted a randomized trial to compare the efficacy and tolerability of fixed-dose capecitabine, 1500 mg twice daily, 7 days on, 7 days off (FD) to the FDA approved dose and schedule (SD). Methods: Females with MBC and any prior lines of endocrine therapy or chemotherapy were included. HER-2 positive patients were allowed with concurrent trastuzumab. Patients were stratified by line of chemotherapy (first or subsequent), measurable disease, and ER status, and randomized 1:1 to either FD or SD. The primary endpoint was 3-month progression free survival (PFS). Additional endpoints included PFS and overall survival (OS). Capecitabine related toxicities were solicited and graded at each visit. Results: Between October 2015 and April 2021, 153 patients were enrolled (N=80 FD, N=73 SD) . 78% were hormone receptor positive/HER-2 negative, 11% each were HER-2 positive and triple negative. The 3-month PFS was 76% in the FD arm and 76% in the SD arm (HR=1.01; 95% CI, 0.52 to 1.94; p=0.99). Landmark analysis of PFS at 12, 24 and 36 months is reported. Non-proportional hazards were detected, so restricted mean survival time (RMST) was used to report estimates of effect. PFS (restricted mean) at 36 months was 13.9 months in the FD arm versus 14.6 months in the SD arm (hazard ratio for progression or death, 1.31; 95% CI, 0.56 to 1.15; p=0.24). OS (restricted mean) at 36 months was 21.2 months in the FD arm versus 19.6 months in the SD arm (hazard ratio for death, 0.80; 95% CI, 0.55 to 1.81; p=0.27). Toxicity related treatment discontinuation occurred in 21 patients (28.8%) in the SD arm compared to 6 patients (7.5%) in the FD arm (p<0.0006). Grade 2-4 toxicities (Table) occurred more frequently in patients receiving SD capecitabine (49.3%) as compared to FD capecitabine (25.0%) (p=0.0018). Conclusions: Fixed dose capecitabine (1500 mg twice daily) on a 7/7 schedule has less toxicity and similar survival when compared to standard BSA-based dosing on a 14/7 schedule in MBC. Clinical trial information: NCT02595320 . [Table: see text]
RNA expression levels from peripheral immune cells, a minimally invasive liquid biopsy source to predict response to therapy, survival and immune-related adverse events in patients with triple negative breast cancer enrolled in the GeparNuevo trial.
Authors: Huebner Hanna , Rübner Matthias , Schneeweiss Andreas , Denkert Carsten , Sinn Hans Peter , Braun Michael , Karn Thomas , Sinn Bruno Valentin , Zahm Dirk Michael , Thomalla Jörg , Huober Jens Bodo , Hanusch Claus , Untch Michael , Solbach Christine , Link Theresa , Filmann Natalie , Rey Julia , Loibl Sibylle , Fasching Peter A. 
Published: June 2023

1011 Background: The impact of immune checkpoint therapy on the tumor microenvironment including tumor-infiltrating immune cells is well described. However, little is known about the circulating immune repertoire and its association with treatment outcome. Hence, we set out to investigate the RNA phenotype of peripheral immune cells before and during treatment of patients enrolled in the GeparNuevo trial (Loibl S et al. Annals Oncol 2022). Methods: The GeparNuevo trial investigated the outcome after neoadjuvant nabP-EC-chemotherapy in combination with the anti-PD-L1 immune checkpoint inhibitor durvalumab versus placebo in patients with non-metastatic triple negative breast cancer. Blood was collected before therapy (baseline), after window, before epirubicin/cyclophosphamide and at end of treatment. RNA from circulating leucocytes of 117 patients was extracted and analyzed using a custom NanoString nCounter CodeSet. Expression of 290 immune-related genes was quantified. The association of RNA expression and signatures with outcome parameters like pathologic complete response (pCR), distant disease-free survival (DDFS), invasive disease-free survival (iDFS), overall survival (OS), and immune-related adverse events (irAEs) were investigated. Results: Immune cell type scores representing macrophages and neutrophils significantly increased during treatment, while B cell, T and Th1 cell scores decreased (p < 0.0001, respectively) regardless of treatment arm. Multivariate logistic respectively multivariate Cox regression analysis revealed a significant association of each baseline DPP4 and MYC gene expression with pCR, DDFS, iDFS, and OS in patients. CDK2, F5 and HLA-DR mRNA expressions were associated with the presence of irAEs. The signature score for TNFR2 non-canonical NF-kB pathway, which is known for its protective capacity, was inversely associated with irAEs in the durvalumab arm (OR = 0.454, 95% CI 0.231-0.892, p = 0.0220). Multiple immune-related signatures at baseline were associated with tumor mutational burden. Conclusions: Our study indicates the importance of the peripheral immune phenotype for treatment response and survival. This association between RNA expression levels of circulating immune cells and outcome seems to be not only relevant for patients receiving immune checkpoint therapy, but also for those under standard chemotherapy alone. Clinical trial information: NCT02685059 .