bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frailty and neurocognitive decline in young adult survivors of childhood cancer: A longitudinal analysis from the St. Jude lifetime cohort.
Authors: Williams AnnaLynn , Krull Kevin R. , Howell Carrie R , Banerjee Pia , Brinkman Tara M. , Kaste Sue C. , Partin, MS Robyn , Srivastava Deokumar , Armstrong Gregory T. , Robison Leslie L. , Hudson Melissa M. , Ness Kirsten K. 
Published: May 2020

10555 Background: Among young adult childhood cancer survivors, 8% meet the criteria for frailty, an aging phenotype associated with poor health. Frailty is associated with neurocognitive decline in the elderly general population, but this association has not been examined in young adult survivors of childhood cancer. Methods: Childhood cancer survivors (N = 845, mean [SD] age 30 [7] years, 22 [7] years post diagnosis, 52% male) were clinically evaluated for prefrailty/frailty (defined as ≥2/≥3 of muscle wasting, muscle weakness, low energy expenditure, slow walking speed, exhaustion) and completed neuropsychological assessments at baseline and five years later. Linear regression models estimated mean differences in neurocognitive decline in prefrail/frail survivors vs. non-frail survivors adjusting for age, sex, race, CNS therapy (cranial radiation, intrathecal chemotherapy, neurosurgery), and baseline neurocognitive performance. P-values were adjusted for multiple comparisons using false discovery rate (FDR). Results: 18% and 6% of survivors were prefrail and frail at baseline. Baseline frailty was associated with declines in visual-motor processing speed, short-term memory, and sustained attention (Table). Prefrailty and frailty were associated with declines in focused attention and executive function (Table). No significant associations were observed between prefrailty or frailty and decline in global cognition, academics, motor processing speed, long-term memory, verbal learning, or verbal fluency despite significant baseline cross-sectional associations. Conclusions: Young adult prefrail and frail survivors had greater declines in attention and executive function compared to non-frail survivors, domains commonly associated with aging. These findings suggest that interventions designed to mitigate components of frailty may also mitigate or prevent neurocognitive decline. [Table: see text]
Prevalence and predictors of high-intensity end-of-life care among adolescents and young adults with cancer in Ontario: a population-based study using the IMPACT cohort.
Authors: Coltin Hallie , Rapoport Adam , Nagamuthu Chenthila , Baxter Nancy N. , Nathan Paul C. , Pole Jason D. , Momoli Franco , Gupta Sumit 
Published: May 2020

10559 Background: End-of-life (EOL) care in adolescents and young adults (AYA) with cancer is poorly characterized, though this group may be at risk of elevated rates of high-intensity (HI) care and consequently, increased EOL suffering. Few population-based studies exist, and are limited by incomplete clinical information. AYA care patterns can vary by locus of care (LOC – pediatric v. adult), but LOC disparities in AYA EOL care are unstudied. Methods: We conducted a retrospective decedent population-based cohort study of all Ontario AYA diagnosed between 15-21 years of age with 6 prevalent primary cancers between 1992-2012, who died ≤5 years from diagnosis. Chart-abstracted clinical data were linked to health services data. The primary composite outcome (HI-EOL care) included any of: intravenous chemotherapy ≤14 days from death; > 1 emergency department visit ≤30 days from death; or > 1 hospitalization or intensive care unit (ICU) admission ≤30 days from death. Secondary outcomes included measures of the most invasive (MI) EOL care: mechanical ventilation ≤14 days from death, and death in the ICU. Factors associated with HI-EOL were examined. Results: Of 483 patients, 292 (60.5%) experienced HI-EOL care, 98 (20.3%) were mechanically ventilated ≤14 days from death, and 110 (22.8%) died in the ICU. Patients with hematological malignancies (v. solid tumors) were at greatest risk of HI-EOL care (OR, 2.3; 95CI, 1.5-3.5, p < 0.01), mechanical ventilation (OR, 5.4; 95CI, 3.0-9.7, p < 0.01), and death in an ICU (OR, 4.9; 95CI, 2.8-8.5, p < 0.01). AYA who died in a pediatric center were substantially more likely to experience MI-EOL measures compared to those dying in adult centers (mechanical ventilation, OR 3.2, 95CI 1.3-7.6, p = 0.01). Assessment of interactions showed LOC-based disparities widening over the study period (ICU death in pediatric v. adult centres: early period OR 0.9, 95CI 0.3-2.9, p = 0.91; late period OR 3.3, 95CI 1.2-9.2, p = 0.02; interaction term p = 0.04). AYA living in rural areas were also at higher risk of experiencing mechanical ventilation (OR, 2.0; 95CI, 1.0-3.8, p = 0.04) and death in ICU (OR, 2.1; 95CI, 1.1-4.0, p = 0.02). Conclusions: AYA with cancer experience high rates of HI-EOL care, with patients in pediatric centers and those living in rural areas at highest risk of MI-EOL care. Our study is the first to identify LOC-based disparities in AYA EOL care. Future studies should explore mechanisms underlying these disparities, including potential differences in palliative care services.
Serum biomarkers of inflammation (ferritin, IL-8, TNFR1) and outcomes in BOLERO-2, a phase III trial of HR+/HER2- metastatic breast cancer treated with everolimus (mTOR inhibitor).
Authors: Ali Suhail M. , Reising Albert , Leitzel Kim , Drabick Joseph J. , Truica Cristina I. , Vasekar Monali K. , Menon Harry , Nagabhairu Vinod , Polimera Hyma Vani , Pancholy Neha , Moku Prashanth Reddy , Maddukuri Ashok , Schmid Herbert , He Wei , Millholland John , Lavin Meredith , Hofsess Scott J. , Sweetman Robert William , Hortobagyi Gabriel N. , Lipton Allan 
Published: May 2020

1067 Background: Everolimus (EVE) plus exemestane (EXE) doubled PFS while maintaining quality of life versus EXE alone in postmenopausal hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (MBC) (BOLERO-2 phase 3; NCT00863655). Here we investigated several serum biomarkers of inflammation: ferritin, interleukin-8 (IL-8), and tumor necrosis factor receptor 1 (TNFR1). Both higher IL-8 (ASCO 2018, #3025) and TNF (Nature 569:428-32, 2019) have been reported to be associated with worsened outcome to immune checkpoint inhibitors (ICI), and IL-8- and TNF-targeted therapies combined with ICIs are in phase I trials. We evaluated the prognostic/predictive ability of serum ferritin, IL-8, and TNFR1 to everolimus in BOLERO-2. Methods: Serum biomarkers were determined on pretreatment serum samples using the ELLA immunoassay platform (ProteinSimple, San Jose, CA). Cox-proportional hazards model was used to assess the efficacy of EVE, and the prognostic and predictive effect on PFS and OS. Results: Pretreatment serum biomarker levels were determined in 510 patients (70 %) of 725 BOLERO-2 patients randomized 2:1 to EVE+EXE or EXE). Serum levels (25%, 50%, 75%) were: ferritin (68.9, 125.5, 253.1 ng/ml); IL-8 (14.5, 19.4, 27.7 pg/ml); and TNFR1 (1205, 1470, 1868 pg/ml). Ferritin correlated significantly with TNFR1 (r=0.45, p<0.0001), while IL-8 correlated weakly with TNFR1 (r=0.10, p=0.023). Higher levels of all 3 biomarkers were prognostic for significantly shorter PFS and OS (table). But no biomarkers were predictive: everolimus was efficacious regardless of the 3 biomarker levels (p>0.05). Conclusions: High levels of serum ferritin, IL-8, and TNFR1 were significantly associated with shorter PFS and OS in HR+/HER2- MBC patients. Everolimus had superior outcomes compared to placebo, regardless of serum biomarker level. These 3 significant prognostic biomarkers are all associated with increased inflammatory processes through different pathways. Anti-inflammatory therapy targeted against these biomarkers should be evaluated based on serum level as potential combination therapy with everolimus or CDK 4/6 inhibitors in HR+ MBC. [Table: see text]
Disparities in the receipt of National Comprehensive Cancer Network (NCCN) guideline adherent care in triple-negative breast cancer (TNBC) by race/ethnicity, socioeconomic status, and insurance type.
Authors: Ubbaonu Chimezie , Chang Jenny , Ziogas Argyrios , Clair Kiran , Tanjasiri Sora Park , Bristow Robert E. , Patel Neha , Mehta Rita S. , Kansal Kari Joanne , Zell Jason A. 
Published: May 2020

1080 Background: Breast cancer is the most commonly diagnosed cancer in women in the United States and the second leading cause of cancer mortality in women.TNBC is more likely to present at an earlier age with more advanced and aggressive disease. The overarching goal of treatment recommendations listed in the National Comprehensive Cancer Network (NCCN) guidelines are to improve patient outcomes. Here we examine factors which may contribute to NCCN guideline adherence. Methods: This was a retrospective cohort study of women with triple negative breast cancer using data from the California Cancer Registry (CCR) between 2004-2016 (with follow-up through 11/2018). Indicators for concordance with NCCN guidelines for TNBC was used as the dependent variable in the analysis. A multivariable logistic regression was used to determine the effects of independent variables on adherence to NCCN guidelines. Odds ratios and 95% Confidence Intervals (CI) were calculated. Non-Hispanic Whites, having medical insurance and highest socioeconomic status (SES) were set as references values in the regression models. Disease specific survival was calculated using the Cox regression analysis. Results: A total of 16,858 women were included in this study, 32.5% (n = 5,472) received NCCN adherent care (p < 0.0001). Non-Hispanic Blacks (NHB) and Hispanic patients were less likely to receive guideline adherent care (respectively, OR 0.87, 95%CI 0.79-0.95 and OR 0.87, 95%CI 0.79-0.95). Patients of lowest and lower-middle socioeconomic status (SES) were less likely to receive NCCN guideline adherent care (respectively, OR 0.77, 95%CI 0.68-0.87 and OR 0.88, 95%CI 0.79-0.98). Overall, non-adherent care was associated with an increased disease-specific mortality (HR 1.21, 95%CI 1.11-1.31, p < 0.0001). Hazard ratios were calculated after adjusting for adherent care and NHB patients had an increased disease-specific mortality (HR 1.28, 95%CI 1.16-1.42, p < 0.0001) in addition to patients with Medicare or Medicaid payer status (respectively, HR 1.20, 95%CI 1.08-1.34, p < 0.001 and HR 1.29, 95%CI 1.15-1.43, p < 0.0001). Conclusions: A significant portion of TNBC patients in California continue to receive non-guideline adherent care. Non-Hispanic black patients and lower SES quintile groups were less likely to receive guideline adherent care. Patients with non-adherent care had worse disease specific survival compared to recipients of NCCN-adherent care.
Diagnostic yield and clinical utility of germline genetic testing following somatic testing in breast cancer patients.
Authors: Lincoln Stephen E , Das Kingshuk , Ngo Nhu , Nielsen Sarah M. , Michalski Scott T. , Yang Shan , Pineda Alvarez Daniel Esteban , Nussbaum Robert Luke , Esplin Edward D. 
Published: May 2020

1092 Background: Germline genetic testing is recommended for breast cancer patients with specific presentations or family histories. Separately, tumor DNA sequencing is increasingly used to inform therapy, most often in patients with advanced disease. Recent NCCN and ESMO guidelines recommend germline testing following somatic testing, under specific circumstances and for specific genes. We examined the utility of germline findings in patients referred for both test modalities. Methods: We reviewed somatic and germline mutations in a consecutive series of patients who: (a) had a current or previous breast cancer diagnosis, (b) were referred for germline testing, and (c) previously received tumor sequencing. Diverse reasons for germline testing included: a tumor finding of potential germline origin, treatment or surgical planning, personal or family history, and patient concern. Results: 227 patients met study criteria of whom 88 (39%) harbored a pathogenic germline variant (PGV) in a high or moderate risk cancer predisposition gene. Mutations in certain genes were most likely to be of germline origin, and most PGVs were potentially actionable (Table). 13% of PGVs were not reported by tumor tests as either germline or somatic findings, usually a result of tumor test limitations. Of note, 27 of the patients with PGVs (31%) had these variants uncovered only after presenting with a second, possibly preventable, malignancy. Conclusions: Germline testing following tumor sequencing often yielded findings that may impact care. Indeed, the 39% PGV rate we observed suggests that such testing may be underutilized. We observed actionable PGVs missed by somatic tests, PGVs uncovered in patients’ second malignancies, and PGVs not within germline reflex testing criteria. These results reinforce the utility of germline testing separate from somatic testing in appropriate patients. [Table: see text]
Veliparib (V) monotherapy after progression on placebo (PL) + carboplatin/paclitaxel (CP) in patients with advanced HER2-negative gBRCA-associated breast cancer: Crossover outcomes and exploratory biomarker analyses in BROCADE3.
Authors: Puhalla Shannon L , Dieras Veronique , Arun Banu , Kaufman Bella , Wildiers Hans , Han Hyo S. , Ayoub Jean-Pierre M. , Stearns Vered , Yuan Yuan , Helsten Teresa L. , Riley-Gillis Bridget , Murphy Erin , Kundu Madan Gopal , Wu Meijing , Maag David , Ratajczak Christine , Ramathal Cyril , Friedlander Michael 
Published: May 2020

1097 Background: In BROCADE3 (NCT02163694), addition of the PARP inhibitor (PARPi) V to CP improved PFS in patients (pts) with g BRCA-associated advanced breast cancer (hazard ratio 0.71 [95% CI 0.57–0.88], p = 0.002). Reversion mutations may account for resistance to platinum-based CT and PARPi. Efficacy, safety, and exploratory biomarker analyses for pts randomized to PL + CP who received crossover (Cx) V monotherapy after progression are reported. Methods: 513 total pts were randomized 2:1 to V + CP or PL + CP. V/PL, C, and P could be discontinued independently prior to progression, leading to varying platinum-free intervals at the time of progression. After progression, pts in the PL + CP arm could receive open-label Cx V monotherapy (300–400 mg BID continuous), beginning within 60 d of progression and continuing to second progression. Adverse events (AEs) and activity during Cx V were assessed. Exploratory analysis of BRCA reversion mutations restoring BRCA1/2 protein function that emerged during PL + CP treatment was performed on plasma circulating tumor DNA using targeted-amplicon next generation sequencing. Results: At data cutoff, 75 pts initially randomized to PL + CP had ≥1 dose of Cx V. Mean (range) duration of Cx V was 154 d (2–966). Activity during Cx V is in the Table. Mean (range) platinum-free interval at time of first dose of Cx V was 3.1 mos (0.4–10.9) vs 8.1 mos (1.0–34.9) in pts who had progressed vs had not progressed by 24 wks after first dose of Cx V. BRCA reversion analysis was completed for 18 Cx pts. Reversion mutations were identified in 1/18 pts (5.6%). This patient had Cx V duration of 19 d and had progressed by 24 wks. BRCA reversion analysis on additional Cx pts will be presented. Most common AEs during Cx V were nausea (61%), vomiting (29%), fatigue (24%), and diarrhea (21%). Any grade anemia, neutropenia, and thrombocytopenia occurred in 7%, 15%, and 7% of pts. Three pts (4%) experienced a convulsion event. Conclusions: Platinum-free interval may influence efficacy of subsequent PARPi. Impact of BRCA reversion mutations warrants further evaluation. Cross-resistance may limit PARPi efficacy after platinum failure. Clinical trial information: NCT02163694 . [Table: see text]
A comprehensive analysis of the demographics and citation-based productivity of radiation oncologists practicing at comprehensive cancer centers.
Authors: McClelland Shearwood , Huang Christina C , Holliday Emma Brey , Jagsi Reshma , Zellars Richard C. 
Published: May 2020

11001 Background: Academic radiation oncology represents a constantly changing landscape. We sought to determine the demographic makeup of the current academic radiation oncology workforce. Methods: Internet searches of the 51 National Cancer Institute-designated Comprehensive Cancer Centers were conducted in September 2019. The Scopus database was subsequently searched in December 2019 to ascertain the h-index for each radiation oncologist. H-indices were analyzed by faculty rank (junior faculty versus associate professor versus full professor) and gender. Variables were coalesced for statistical analysis using Fisher’s exact test and two-tailed t-tests. Results: Analysis of 993 radiation oncologists revealed that 53.6% are junior faculty, 24.8% are associate professors, and 21.7% are full professors. The average radiation oncologist has been an MD for 19.6 years; 32.5% (232/993) are women, and less than 5% (47/993) are underrepresented minorities (URM). Of the 51 department chairs, 11.8% are women and 5.6% are underrepresented minorities. Women are significantly underrepresented among full professors (odds ratio = 1.78; p = 0.010) and departmental chairs (odds ratio = 3.80; p = 0.0007); there was no significant difference for assistant professorship (p = 0.067) nor associate professorship (p = 0.348). The overall mean h-index for all faculty was 17.64. Mean h-index was 8.21 for junior faculty, 18.46 for associate professors, and 40.05 for full professors; these differences were statistically significant (p < 0.0001). The overall mean h-index was 19.35 for men (n = 668) and 14.11 for women (n = 323); this difference was statistically significant (p < 0.0001). Conclusions: The majority of academic radiation oncologists are assistant professors; fewer than 5% are underrepresented minorities. Men comprise more than two-thirds of the workforce, and are significantly overrepresented at the full professor (by 78%) and departmental chair (by 280%) levels in academic radiation oncology. The average radiation oncologist at a comprehensive cancer center has published more than 17 manuscripts cited at least 17 times. Contrary to previous findings comparing male and female residents, the difference in academic productivity by gender among faculty was statistically significant. These findings provide objective data to assess the radiation oncology academic workforce and provide a useful benchmark to measure change going forward.
Student loan debt and visa status influence on career choices for hematology and medical oncology fellows in the United States.
Authors: Al-Issa Karam , Rangaraju Sravanti , Al-Hader Ahmad Abdelfattah 
Published: May 2020

11024 Background: There are multiple factors influencing future career plans for US hematology/oncology fellows. The objective of this study is to evaluate the effects of student loan debt and visa status as potential factors affecting their career choices. Methods: A total of 159 US hematology/oncology fellowship programs were contacted, program directors forwarded the survey to current hematology/oncology fellows and recent graduates (classes of 2019, 2018 and 2017). The survey consisted of 13 questions regarding their student loan debt and visa status, research experience, initial career plan, current career for graduates, the influence of student loan debt and visa status on their career decisions (academic, private practice, industry), and whether or not their training programs had resources or mentorship to help them deal with those factors. We used a scale of 1-5 to determine how much each factor affected career choice (1 = extremely unaffected, 5 = extremely affected). Results: A total of 220 physicians have participated, 177 (80.5%) fellows and 43 (19.5%) graduates. For graduates, 35% had student loans during fellowship, 40% of them thought that their loans affected their career choice with a score of 4-5. 93% of graduates with student loans answered that they weren't aware of resources/mentorship to address their loans effect on their career. 44% of graduates were on J1/H1 visa during training, 74% of them thought that their visa status affected their career choice with score of 4-5. 63% of graduates who were on visa answered that they weren't aware of resources/mentorship to address visa status as a factor influencing their career options. For current fellows, 51% have student loans, one third of them thought that their loans affected their career choice with score 4-5. 77% of fellows with student loans answered that they weren't aware of resources/mentorship to address their loans effect on their career. 16% of current fellows are on J1/H1 visa, 66% of them thought that their visa status is affecting their career choice with score 4-5. 62% of fellows who are on visa answered that they weren't aware of resources/mentorship to address visa status as a factor influencing their career options. Conclusions: Hematology/oncology fellows report that student loan debt and visa status are important factors affecting their career decisions. The majority of hematology/oncology fellows in this survey weren’t aware of resources or mentorship to help deal with these factors. Mentors need to be aware of these factors to help fellows achieve their career goals.
Delivery of cancer survivorship education to community health care professionals.
Authors: Pariser Ashley , Brita Javin , Harrigan Maura , Capozza Scott , Khairallah Angela , Sanft Tara B. 
Published: May 2020

11032 Background: Cancer survivorship care is an integral part of oncology care. Although oncologists overwhelmingly demonstrate a desire to be a part of their cancer survivors’ care and management, only 60% of oncologists feel comfortable promoting healthy lifestyle behaviors, screening and prevention care. There is currently no standard of care for survivorship care education and data evaluating current educational models is limited. Methods: Project ECHO (Extension for Community Healthcare Outcomes) utilizes telehealth to promote long-distance learning and sharing of best practices. We utilized the Project ECHO model to deliver a survivorship curriculum in 6 hourly, biweekly sessions from October 2019 to December 2019. The curriculum was aligned with the 4 central tenets of survivorship care and was developed based on a needs assessment. Recruited participants included registered nurses (RN), registered dietitians (RD), advanced practice providers (APP), radiation oncologists and medical oncologists. Participants were enrolled in either a local ECHO curriculum or a national ECHO curriculum. Local Connecticut participants were invited to participate in semi-structured interviews to evaluate their experience. Results: Eight participants including 3 MDs, 1 APP, 1 SW and 3 RNs from 3 community oncology clinics in suburban Connecticut enrolled in the local ECHO curriculum. Twenty-eight participants including 17 RDs, 2 MDs, and 3 APPs from 13 hospital and community practices enrolled in the national ECHO curriculum. Four participants (50%) agreed to participate in semi-structured interviews. Motivations to participate included ease of participation and interest in survivorship. Participants described a positive experience, citing a well-structured curriculum and sense of community as highlights. Two participants described the sessions as empowering, leading to more discussions and engagement with survivors. All participants described an increased awareness of resources available for cancer survivors. Areas for improvement included greater assistance with technology and session time management. Concomitant patient care was the most cited barrier to participation. Conclusions: This pilot study is the first to demonstrate the feasibility of the Project ECHO model for delivering cancer survivorship education to community oncology providers. Further research evaluating the correlation between improved provider knowledge and survivorship care outcomes is needed.