bluuebunny/crossref_metadata_2025_split huggingface dataset:
Value of adjuvant radiotherapy in patients with localized Ewing sarcoma at the extremities: Report from the Ewing 2008 trial.
Authors: Heesen Philip , Ranft Andreas , Bhadri Vivek , Brichard Bénédicte , Collaud Stephane , Cyprova Sona , Eich Hans-Theodor , Ek Torben , Gelderblom Hans , Havemann Lianne , Hauser Peter , Juergens Heribert , Kanerva Jukka , Kuehne Thomas , Raciborska Anna , Rascon Jelena , Streitbuerger Arne , Timmermann Beate , Uhlenbruch Yasmine , Dirksen Uta 
Published: June 2022

11531 Background: In patients with Ewing Sarcoma (EWS), adjuvant radiotherapy is often performed after surgery that could not obtain wide margins or after poor histological response to surgery. However, the benefit of adjuvant radiotherapy needs further investigation. Therefore, we compared event-free survival (EFS) between surgery (SX) alone and SX combined with radiation therapy (RT), performed a subgroup analysis and identified independent prognostic factors. Methods: The data from localized EWS patients with tumors at the extremities that were treated in the Ewing 2008 trial from 2009-2018 were included in this analysis. Patients received induction chemotherapy according to the protocol and then underwent local therapy. Patients receiving SX or adjuvant RT (combined SX/RT) were included in this analysis. Hazard ratios (HRs) (95% Confidence Intervals (CIs)) were calculated using Cox regression. Results: 360 out of 863 patients (41.7%) presented with an EWS at the extremities with 81 tumors at the upper extremity, and 279 tumors at the lower extremity. Most patients were treated with surgery only (223, 61.94%), while 125 patients (34.72%) were treated with SX plus RT. Adjuvant radiotherapy was conducted after a median time of 69 days (1st quartile, 3rd quartile; 54, 109). Median EFS at 5-years for all patients was 0.74 (0.69, 0.80), 0.76 (0.70, 0.83) for patients after surgery only, and 0.73 (0.64, 0.83) after combined RT/SX. After adjusting for sex, age, tumor volume, histological response and surgical margins, the HR for combined RT/SX vs SX alone was 0.69 (0.37, 1.26), p = 0.22. In patients with poor histological response to surgery (≥10% vital tumor cells) and with high tumor volume (≥ 200mL), additional radiotherapy did not decrease the hazards of any event, HR 0.72 (0.25, 2.06), p = 0.54. We identified high tumor volume, poor histological response to surgery as well as intralesional resection of the tumor as independent prognostic factors after adjusting for other known prognostic factors with HRs of 1.73 (1.04, 2.90), p = 0.03; 2.79 (1.69, 4.62), p < 0.0001 and 215.9 (13.17, 3538.61), p = 0.0002, respectively. Surgical complication was not a prognostic factor after adjusting for above mentioned variables, HR 0.85 (0.31, 2.34), p = 0.75. Conclusions: In our cohort, adjuvant radiotherapy was not superior compared to surgery alone in all patients with localized EWS at the extremities and neither in a subgroup of patients with high-risk factors. Poor histological response, intralesional tumor resection as well as high tumor volume were identified as independent negative prognostic factors. Clinical trial information: NCT00987636.
Prognostic value of EZH2 expression for immunotherapy-based schemes in advanced soft-tissue sarcoma: A translational research from Spanish Group of Research on Sarcoma (GEIS).
Authors: Moura David Silva , Zamora Jorge , Hindi Nadia , Lopez-Alvarez Maria , Lacerenza Serena , Grignani Giovanni , Martinez-Trufero Javier , Redondo Andres , Valverde Morales Claudia Maria , Stacchiotti Silvia , Lopez-Pousa Antonio , Gutierrez Antonio , Lopez-Martin Jose A. , Martin Broto Javier 
Published: June 2022

11549 Background: Immunotherapy-based treatments had shown to be active in several solid tumors, including in selected subtypes of sarcomas. IMMUNOSARC (NCT03277924) is a phase Ib/II trial [from Spanish (GEIS) and Italian (ISG) sarcoma groups], that tested the combination of nivolumab (anti-PD-1 inhibitor) plus sunitinib (anti-angiogenic agent) in advanced sarcomas. Among the 65 soft-tissue sarcoma (STS) patients (pts) enrolled, 48% were free of progression at 6 months, meeting the trial’s primary endpoint. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 and it has been described to play an important role in the transcriptional repression of genes involved in T-cell migration and T-cell-mediated anti-tumor activity. The aim of this study was to explore the value of EZH2 gene expression as potential prognostic biomarker of the activity of immunotherapy-based schemes. Methods: The expression of EZH2 was evaluated in 64 paraffin tumor blocks, by direct transcriptomics, using HTG EdgeSeq Oncology Biomarkers Panel (HTG Molecular Diagnostics, Inc.; Tucson, AZ, USA). Data was normalized with DESeq2 and the cut-off of EZH2 expression was calculated with MAXSTAT R package. Gene expression was correlated with progression-free survival (PFS) by RECIST, overall survival (OS) and clinical benefit (patients with response or stable disease vs patients with progressive disease as best response). Results: Among the 64 pts analyzed, 52 (81%) showed overexpression of EZH2, considering a cut-off of 570.15 read counts. Undifferentiated pleomorphic sarcoma (UPS) and epithelioid sarcoma were the subtypes with higher expression of EZH2 with a median of read counts of 1888.04 (n = 10) and 1261.79 (n = 7), respectively. The lowest expressions were observed in extraskeletal myxoid chondrosarcoma (ECM) and alveolar soft-part sarcoma (ASPS) with a median of read counts of 461.42 (n = 4) and 680.84 (n = 7), respectively. Low expression of EZH2 was associated with better PFS (16.8 months vs. 3.9 months; p = 0.001) and better OS (NR vs. 20.0 months; p = 0.006). Moreover, low expression of EZH2 was also significantly associated with a clinical benefit of the patients treated with nivolumab plus sunitinib [relative risk (RR): 13; 95% CI: 3.0-56.9; p = < 0.001). Conclusions: Low expression of EZH2 was associated with better outcome in advanced STS patients treated with immunotherapy-based schemes. These results might support the rationale for the combination of EZH2 inhibitors with immune-modulating agents for future studies.
Bereavement practices of gynecologic oncologists: Physician and care team practices compared to caregiver needs.
Authors: Harrison Lauren , Morosky Christopher M. , Whitcomb Bradford 
Published: June 2022

12021 Background: Gynecologic cancers account for over 34,000 deaths in the United States annually. Family-centered care is beneficial to the family unit and patient throughout the illness course. Research is lacking regarding how physicians should approach family members or other caregivers after a patient dies. We aimed to assess how gynecologic oncologists are currently practicing and compare that to family members’ needs during the bereavement period. Methods: We devised a set of paired surveys that were distributed to the Society for Gynecologic Oncology and to patient families. Families were recruited using social media, publicizing in local organizations, and advertising in University of Connecticut campus-wide emails. Likert-scale style questions with responses ranging from “1” to “10” were used to assess opinions on aspects of bereavement care and reported as means. Differences in means were assessed using ANOVA and T-tests and considered to be statistically significant if the P-value was < 0.05. Results: We received completed surveys from 129 physicians and 17 caregivers from different families. 48% of physicians reported contacting patient families, and, similarly, 47% of family members reported receiving contact from physicians. Physicians had a mean 6.21/10 confidence level (where 10 is maximum confidence) in providing bereavement care, while families reported 5.76/10 confidence in their physician’s ability to provide bereavement support ( P = 0.493). Factors that influenced physicians confidence in providing bereavement support were undergoing formal training in bereavement (6.84/10 vs 5.14/10 for physicians who had not been trained, P < 0.001) and being in practice for more than 11 years (5.65/10 for ≤10 years in practice, 7.05 for ≥11 years, P = 0.001). Physicians who contacted patients personally had a higher confidence level (6.98/10) in providing bereavement support compared with those who did not contact families (5.51/10, P < 0.001). Family members were nearly unanimous in reporting a desire for physicians to contact them personally (16/17), and stated that a phone call (56%) or a sympathy card (38%) were their preferred methods of contact. Conclusions: Our study suggests that although families appreciate contact from physicians after their loss, physicians do not have a high level of confidence in providing this support. Physicians who undergo bereavement training and who reached out after patients had died have higher confidence levels in interacting with family members. Based on these results, formal bereavement training should be incorporated into gynecologic oncology fellowships in order to increase the comfort levels and likelihood of gynecologic oncologists reaching out to families after a patient has died.
Impact of circuit, interval-based exercise on insulin resistance and adiponectin among minority cancer survivors.
Authors: Christopher Cameron , Kang Dong-Woo , Normann Amber , Norris Mary , Dieli-Conwright Christina Marie 
Published: June 2022

12059 Background: Hispanic and Black adults have a heightened risk of metabolic syndrome compared to non-Hispanic white adults, increasing the risk of cardiovascular disease, diabetes, and co-morbid outcomes. Further, Hispanic and Black adults are more likely to be sedentary and obese than non-Hispanic white adults, leading to an increased risk of insulin resistance and poor metabolic health. Exercise improves cardiometabolic health, including insulin sensitivity and adiponectin, however few studies have focused on minority cancer survivors. The aim of our (NCT03284346) was to determine whether a 4-month circuit-based aerobic and resistance exercise intervention can improve insulin resistance and adiponectin levels in breast, prostate, and colorectal Hispanic and Black cancer survivors. Methods: Overweight or obese (BMI > 25.0 kg/m2), sedentary breast, prostate or colorectal cancer survivors who self-identified as Hispanic or Black were randomized to exercise (n = 30) or usual care (n = 10). Survivors in the 4-month supervised exercise intervention participated in a thrice weekly, circuit, interval-based moderate-vigorous aerobic (65-85% of VO2max) and resistance (65-85% of 1-repetition maximum). Insulin resistance, assessed by Homeostasis Model of Assessment (HOMA-IR), and adiponectin levels were collected at baseline and post-intervention from fasting blood sample collection. Repeated-measures analysis of variance and t-tests were performed to assess within- and between-group differences. Results: The study sample was 66 ± 10.4 years old, Hispanic (55%), Black (45%), overweight (78%), and female (60%). Adherence to the intervention was 90% and post-intervention outcome measures were available on 100% of participants. Post-intervention, insulin resistance (within group mean difference: -3.2, p < 0.01; between group mean difference: -4.5, p < 0.01) and adiponectin levels (6.1 ug/mg, p < 0.01; 8.6 ug/mg, p < 0.01) significantly improved in the exercise group when compared to baseline and to usual care, respectively. Conclusions: A circuit, interval-based aerobic and resistance exercise intervention improved insulin resistance and adiponectin levels in breast, prostate, and colorectal minority cancer survivors. Accessible exercise interventions for minority cancer survivors may be effective to mitigate metabolic dysregulation and co-morbid conditions in survivorship and support cardiometabolic health. Clinical trial information: NCT03284346.
Trajectory of aging following diagnosis of cancer.
Authors: Simons Morgan , Lyu Chen , Osman Iman , Zhong Hua 
Published: June 2022

12087 Background: Aging is a nebulous concept with several definitions, but they all generally include physical and cognitive decline in function as a key component. We hypothesized that following cancer diagnosis, patients decline in physical and cognitive function would correspond with accelerated and/or accentuated aging trajectories. The magnitude of the functional changes could inform strategies to minimize impact of cancer diagnosis on trajectory of aging. Methods: We analyzed 32,935 participants >50 years enrolled between 1995-2018 in the Health and Retirement Study (HRS), a population-based, biennial longitudinal health interview survey of older adults in the United States. We assessed the changes in physical and cognitive function among cancer patients controlling for their pre-cancer trajectories and comparing it with aged population with no cancer diagnosis as control. The primary outcomes were change in physical function (Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL): range 0–11) and global cognitive function (Telephone Interview for Cognitive Status (TICS): range 0–27). The secondary outcome was change in self-rated health (SRH: range 1-5). We estimated the effect of acute change based on the immediate post-cancer outcome measurements compared to the trajectories before cancer; and the long-term effect as the per-year change in outcome decline post cancer compared to aging of cancer-free respondents adjusting covariates by linear mixed models. Results: 5,101 developed incident cancer: 1,514 in the 50-64 age group, 1,901 in the 65-74 age group, and 1,686 in the 75+ age group. 27,834 participants were cancer-free throughout. Cancer was associated with acute declines in physical function (0.06 [0.01– 0.10] and 0.25 [0.14– 0.36] points), cognitive function (0.22 [0.04–0.39] and 0.24 [0.01– 0.46] points), and SRH (0.19 [0.14–0.23] and 0.22 [0.12–0.33] points) for age of onset groups 50- and 75+ respectively. Moreover, participants with cancer demonstrated accelerated decline in physical function (0.02 [0.01–0.03], and 0.06 [0.05–0.07] points per year faster for 50-74 and 75+ age-of-onset groups respectively) compared to cancer-free participants, but not in cognitive and SRH. Lung, colorectal & breast cancer were associated with the highest acute and accelerated decline in functions, while prostate cancer was associated with moderate and insignificant decline. Conclusions: Using 24 years of nationally representative longitudinal data, this study provides, for the first time, evidence for the heterogeneous aging trajectories of cancer patients across varying age-of-onset and cancer types. Our results supported an accelerated aging trajectory of physical function with increased acceleration with increasing age-of-onset compared to the non-cancer population. It also provides evidence for accentuated aging trajectories of cognitive function and self-rated health.
Associations between DNA methylation age and chronic health conditions in survivors of childhood leukemia and CNS tumor.
Authors: Gramatges Maria Monica , LeJeune Wanda , Hernandez Evelyn , Lupo Philip , Richard Melissa A. 
Published: June 2022

12088 Background: Survivors of childhood cancer are at risk for treatment related morbidities, including an early onset of chronic health conditions (CHC). Survivors are at risk for epigenetic age acceleration (EAA), i.e. when DNA methylation (DNAm)-predicted age exceeds chronologic age. EAA has been associated with treatment exposures and incidence of cardiometabolic, pulmonary, and neurologic CHC. We characterized the burden of CHCs in survivors of acute lymphoblastic leukemia (ALL) and central nervous system (CNS) tumors, two of the most common childhood cancers, and determined the association between EAA, cancer diagnosis, and burden of CHC. Methods: We included survivors of CNS tumor or ALL diagnosed at Texas Children’s Hospital (TCH) between 1992-2013, who were seen at least once in the TCH Long-Term Survivor Clinic. Demographics, diagnosis, treatment data and date of onset and type of CHC were abstracted from the electronic health record. All CHCs required subspecialty care, were present for at least 1 year, and were classified by system into one of 8 categories. Germline samples were obtained at an average of 10.5 years after diagnosis, and at an average age of 15.9 years of age. Samples were analyzed by Illumina MethylationEPIC BeadChip array on an iScan System in the Baylor College of Medicine (BCM) Laboratory for Translational Genomics. Methylation data were processed using minfi, normalized with noob, and EAA estimated using the Horvath calculator. The relationship between EAA, diagnosis, and CHCs was determined by multivariable linear regression. Results: Endocrine (65%), neuropsychiatric (78%), and sensory/motor (73%) CHCs were common in the CNS tumor group (n = 77). Metabolic (22%) and neuropsychiatric (59%) CHCs were common in the ALL group (n = 268). Survivors of CNS tumor had an earlier time of CHC onset, were more likely to have endocrine and sensory motor outcomes, and less likely to have metabolic outcomes vs. ALL survivors. On average, both survivor groups had EAA: 3.3 years (range: -12.2-15.5 years) for 138 ALL survivors and 4.4 years (range: -0.9-10.9 years) for 38 CNS tumor survivors, but EAA did not differ between diagnoses after adjustment for RT (p = 0.75). For CNS tumor survivors, EAA was 0.8 years greater for each system affected by CHC (beta = 0.8, p = 0.043) after adjustment for RT. For ALL survivors, EAA was not associated with CHCs (p = 0.33), but was associated with RT (p = 0.007). Conclusions: CHCs are prevalent in survivors of childhood ALL and CNS tumors, with patterns that differ by cancer diagnosis. In this cohort of relatively young 5 year + survivors of ALL and CNS tumor, all survivors had similar EAA but demonstrated cancer diagnosis-specific differences in associations between EAA, RT and burden of CHC.
Patient- and provider-level factors associated with telehealth utilization across a multisite, multiregional cancer practice.
Authors: Pritchett Joshua , Borah Bijan J. , Dholakia Ruchita , Moriarty James P. , Ahn Hannah , Huang Ming , Khera Nandita , Kharfan-Dabaja Mohamed , Ticku Jonathan , Leppin Aaron L. , Tilburt Jon Charles , Paludo Jonas , Haddad Tufia C. 
Published: June 2022

1512 Background: In response to the COVID-19 pandemic, many cancer practices adopted telehealth, including telephone and video appointments. Following a period of initial expansion that began in March 2020, sustained telehealth integration has emerged across the Mayo Clinic Cancer Practice (MCCP) in 2021. The primary objective of this study was to identify factors associated with utilization of telehealth appointments. Methods: A cross-sectional, multi-site, retrospective analysis was conducted across MCCP – a multisite, multiregional cancer practice with tertiary referral campuses in Minnesota, Florida, and Arizona, as well as rural, community-based hospitals and clinics throughout the Upper Midwest. Multivariable models were used to examine the association of patient- and provider-level variables with telehealth utilization. Results: Outpatient appointments conducted in July – August 2019 (n = 32,932) were compared with those from 2020 (n = 33,662) and 2021 (n = 35,486). The rate of telehealth appointment utilization increased from <0.01% in 2019 to 11.0% in 2020 and 14.0% in 2021. The strongest provider-level predictor of telehealth utilization was female physician provider type (OR 1.06, 95% CI 1.01 to 1.11; P = 0.0297), a trend consistently observed across career stages, practice locations and settings in 2020 and 2021. Additionally, while the rate of telehealth utilization was not significantly different at referral and community-based campuses in 2020, providers at referral campuses were significantly more likely to utilize telehealth than community-based campuses in 2021 (OR 1.1, 95% CI 1.01 to 1.12; P = 0.0289). Regarding patient-level factors, rural residence (defined by Rural-Urban Commuting Area codes), which accounted for 44.2% of the patient population, was significantly associated with lower telehealth utilization as compared to patients with urban residences, particularly for video appointments (OR 1.04, 95% CI 1.02 to 1.07; P < 0.0001). Notably, the disparity in telehealth utilization between rural and urban populations was found to be less pronounced in 2021 as compared to 2020. Conclusions: Multivariable analysis across a multi-site, multi-regional cancer practice identified several factors associated with increased telehealth utilization. These included female physician provider type, referral-based campuses, and patients residing in urban settings. A detailed understanding of the factors that influence telehealth utilization – a method of care delivery which represents a “new normal” across many cancer practices – will be essential to enable continued equitable access to high-quality, high-impact, patient-centered cancer care.
Electronic research consents for complex early-phase I-II clinical trials integrated with telemedicine visits compared with in-person encounters.
Authors: Buckley Michael T. , O'Shea Molly , Lipitz-Snyderman Allison , Kuperman Gilad , Shah Suken , Redelman-Sidi Yael , Lengfellner Joseph M. , Terzulli Stephanie Lucia , Houston Collette , Sabbatini Paul 
Published: June 2022

1514 Background: Based on our previous research with patient satisfaction for electronic consenting (95% of 940 respondents would recommend it another patient), we hypothesized that telemedicine (telemed) would be received as well as or better than in-person clinical research (CR) consent encounters for complex early-phase clinical trial (Phase I-II) and clinical genetic consent discussions by patients. Oncologist experiences to date have shown that telemed works well for uncomplicated clinical scenarios, but its performance alongside increased care complexity is less clear from the patient perspective. Methods: We conducted a one-time survey of adult patients having a telemed consent visit between 8/31/21 and 2/13/22 and an in-person clinic visit. Nine CR specific questions covered visit preference and empowerment across 6 high value consent agency domains. Results: 513 patients completed the survey and consented across 96 Clinical trials (CT), including genetic, therapeutic, diagnostic, and quality of life. Consent discussions were performed by 75 clinicians and 41 non-clinicians, with the majority (64%) for clinical genetic and Phase I-II CTs. Most patients (52%) preferred telemed over in-person clinic visits (19%) when all visit related factors (time, cost, convenience, quality of care, healthcare team interaction) were considered ( P<.05) (Table). Comparing their last in-person visit with telemed, patients reported feeling either less stressed/overwhelmed (16%) for their consent discussion or about the same (39%) using telemed, and 6% were more stressed ( P<.05). Patients expressed equal comfort taking agency-supported action across 6 domains regardless of consent setting. Conclusions: Electronic consenting via telemed is the preferred method for consent in complex early-phase clinical trials when all visit factors are considered and performs as well across 6 key agency domains when compared with in-person visits. Telemed does not contribute additional stress to consent appointments for most patients and performs well across complex clinical genetic and Phase I-II clinical trial discussions. Our findings suggest telemed and electronic consent should be offered as an option for patients throughout their treatment continuum. Beyond MSK, our data support a broader call for organizations to offer telemed platforms for CT discussions to increase overall patient satisfaction and potentially increase participation. [Table: see text]