bluuebunny/crossref_metadata_2025_split huggingface dataset:
Should we routinely screen for frailty prior to gynecologic oncology surgery? Frailty as a potential predictor of adverse postoperative outcomes in elderly patients.
Authors: Mah Sarah , Anpalagan Tharani , Marcucci Maura , Reade Clare , Jimenez Waldo , Eiriksson Lua Ruhiyyih , Carlson Vanessa , Walker Millie , Nguyen Julie My Van 
Published: June 2021

6517 Background: Frailty is increasingly recognized as an adverse prognostic factor of postoperative morbidity and survival in several surgical disciplines. There is no consensus on routine frailty screening in Gynecologic Oncology. Our goal was to evaluate the predictive role of the National Surgical Quality Improvement Program(NSQIP) comorbidity-based modified Frailty Index-5(mFI-5) in Gynecologic Oncology patients over the age of 70. Methods: Elective laparotomies between 01/2016-09/2020 at the Juravinski Hospital in Hamilton, ON were reviewed using prospectively-collected NSQIP data and chart review. Complication severity was assessed by Clavidien-Dindo classification. The primary outcome was rate of 30-day grade III-V complications. Secondary outcomes were: grade II-V complications, myocardial injury, length of stay(LOS), non-home discharge, and non-initiation/non-completion of adjuvant chemotherapy. Logistic regression analysis was performed. Survival analysis and receiver-operator characteristic curves are underway. Results: In this cohort of 259 patients, frail patients(mFI-5≥2) were at significantly greater risk of grade III-V complications (OR23.77, 95%CI 9.69-66.26, p < 0.0001), grade II-V complications (OR3.8, 95%CI 1.96-7.85, p = 0.0002), myocardial injury (OR3.44, 95%CI 1.66-7.05, p = 0.0009), LOS≥5days (OR2.96, 95%CI 1.61-5.52, p = 0.0006), non-home discharge (OR7.37, 95%CI 2.81-20.46, p < 0.0001), and non-initiation/non-completion of chemotherapy (OR7.34, 95%CI 2.43-23.06, p = 0.0006), than non-frail patients on univariate analysis(UVA). On multivariable analysis, frailty remained independently associated with grade II-V complications and grade III-V complications (OR4.64, 95%CI 2.31-9.94, p < 0.0001, controlling for stage, operative duration and intraoperative complication, and OR24.49, 95%CI 9.72-70.67, p < 0.0001, adjusting for BMI, stage and operative duration, respectively). On UVA, age, surgical complexity score, and smoking were not predictive of complications. Frailty also independently predicted non-home discharge (OR7.37, 95%CI 2.81-20.46, p < 0.0001) when adjusting for age. Conclusions: Frailty as assessed with mFI-5, independent of age, strongly predicted morbidity and non-home discharge after Gynecologic Oncology surgery. Strategies for perioperative optimization could help address these disparities. mFI-5 is a concise tool that can be used for routine frailty screening and risk stratification.
Association of parental cancer and school absenteeism, medical financial hardship, healthcare use, and psychological distress among minor children.
Authors: Zheng Zhiyuan , Zhao Jingxuan , Han Xuesong , Nogueira Leticia , Yabroff Robin Robin 
Published: June 2021

6544 Background: A cancer diagnosis can affect the entire family, including minor children. However, little is known about the association of parental cancer on minor children’s school absenteeism, family’s financial ability to afford healthcare for children, as well as healthcare use, psychological distress, and behavioral problems. Methods: The 2015 to 2018 National Health Interview Survey was used to identify minor children (ages 5-17 years) whose parent(s) reported a cancer history (n = 695, representing 1.2 million children) and children whose parent did not report a cancer history (n = 19,122, representing 35.7 million children). Separate multivariable logistic regressions were used to compare school absenteeism, financial hardship, healthcare use, and psychological distress among children with and without parental cancer history. All analyses adjusted for children’s age group (5-11 years, 12-14 years, and 15-17 years), sex, family income as a percentage of the federal poverty line, marital status of their parents, survey year, and region. Results: Children of cancer survivors were more likely to receive annual well-child checkups, experience school absenteeism, take prescription medications for more than 3 months, visit hospital emergency rooms, suffer psychological distress, and have behavioral problems than children of parents without a cancer history (Table). Conclusions: Parental cancer history is associated with disruption in their minor children’s life. The associated psychological distress and physical and emotional health among these children may develop into more severe health issues in adulthood. Special attention to minor children of parents with a cancer history may be required to help prevent development of longer-term physical and mental health problems.[Table: see text]
Prevalence of discordant QTc values among cancer patients by the Bazett, Fridericia, and Framingham formulae: Evidence for a standardized approach.
Authors: Parish P. Christopher , Muluneh Benyam , Hicks Charles , Jensen Brian , Zeidner Joshua F. , Richardson Daniel R. 
Published: June 2021

6575 Background: Many chemotherapies have the potential to prolong the QT interval, requiring monitoring of the corrected QT (QTc) to prevent life-threatening arrhythmias. Most clinical guidelines recommend adjusting/holding chemotherapy with Grade 3 or higher toxicity by CTCAE (QTc≥500). Several formulae are used for QTc monitoring including Bazett, Fridericia, and Framingham. The most commonly used formula, Bazett, is well-documented to result in inappropriately high QTc values although the potential impact of this overcorrection on cancer treatment is unknown. We aimed to describe the prevalence of QTc prolongation among cancer patients and the effects on CTCAE adverse event grading by various QTc formulae to determine the potential impact on clinical management. Methods: We performed a single-center retrospective analysis of QT values from electrocardiograms (ECGs) collected January 2010-April 2020 and evaluated associations between QTc values, medications, and patient characteristics. QTc prolonging agents were determined by FDA package insert and cross-referenced with CredibleMeds.org. Results: 20,017 ECGs were evaluated. 18.6% (3,730) met ACC/ACCF/HRS criteria for prolonged QTc by ≥1 QT correction formula (either Bazett, Fridericia, or Framingham). 7.5% (1,494) were prolonged with all three formulae, and 8.6% (1,635) were prolonged only with Bazett. The CTCAE classification using the Bazett formula differed from both Fridericia and Framingham in 37.9% (7,583) of the ECGs. In contrast, Fridericia and Framingham formulae resulted in the same CTCAE classification in 94.5% (18,912). Of 1,789 ECGs classified as Grade 3 toxicity by Bazett, 72.0% (1,288, 6.4% of all ECGs) were classified as Grade 2 or less by both Fridericia and Framingham. 12.0% (2,340) of all ECGs were taken from patients (n = 421) on 24 different QT-prolonging chemotherapies. In 38.8% (909) of the ECGs, the CTCAE classification using the Bazett formula differed from both Fridericia and Framingham while use of Fridericia and Framingham formulae resulted in the same classification in 93.0% (2,176) of the ECGs. Of 293 ECGs classified as Grade 3 toxicity by Bazett, 65.2% (191) were classified as Grade 2 or less by both Fridericia and Framingham. Conclusions: To our knowledge, this is the largest analysis of discrepancies between different QTc formulae in patients receiving chemotherapy. These findings demonstrate an unacceptably high rate of discordance between formulae. Discordant data can lead to inconsistent clinical management and adverse event grading underscoring the urgent need to standardize QTc monitoring and reporting. These findings support the discontinuation of the routine use of the Bazett correction formula among cancer patients as CTCAE Grade 3 reporting from the Bazett formula is unreliable in over 65% of cases.
Adult Philadelphia-like B-cell acute lymphoblastic leukemia: Characteristics, outcomes, and role of allogeneic hematopoietic cell transplantation in comparison to Philadelphia-positive and Philadelphia-negative acute lymphoblastic leukemia.
Authors: Abdel Rahman Zaid , Heckman Michael , Anagnostou Theodora , White Launia , Kloft-Nelson Sara M. , Knudson Ryan A. , Alkhateeb Hassan , Sproat Lisa Ostrosky , Khera Nandita , Murthy Hemant S. , Ayala Ernesto , Hogan William J. , Roy Vivek , Peterson Jess , Kharfan-Dabaja Mohamed , Ketterling Rhett P. , Litzow Mark Robert , Patnaik Mrinal , Foran James M. , Greipp Patricia T. 
Published: June 2021

7022 Background: Philadelphia-like Acute Lymphoblastic Leukemia (Ph-like ALL) is a high-risk subset of adult ALL. Until recently, there has not been a systematic platform to recognize this entity in clinical practice. Furthermore, data regarding the role of allogeneic hematopoietic cell transplantation (allo-HCT) is lacking. We conducted this study to identify patients with Ph-like ALL and describe their outcomes in comparison to Ph+ and Ph- ALL with emphasis on the role of allo-HCT. Methods: To identify cases of Ph-like ALL, available diagnostic cytogenetic pellets for patients in the Mayo Clinic ALL cohort (N=365) were tested using a targeted fluorescence in situ hybridization (FISH) panel developed by the Mayo Clinic Genomics Laboratory and includes probes to detect Ph-like-specific rearrangements (i.e., ABL1, ABL2, PDGFRB, JAK2 and CRLF2). Results: Thirty-three (9%) patients with Ph-like ALL were identified, the remaining patients were classified as Ph+ (N=132, 36%) or Ph- ALL (N=200, 55%). Patients with Ph-like ALL were younger (Median: 39 vs. 50 vs. 49 years, P=.01), had higher WBC (Median: 27.9 vs. 21.5 vs. 4.5 x109/L, P<.001), were less likely to achieve CR (91% vs. 99% vs. 96%, P=.02), more likely to be MRD+ (64% vs. 34% vs. 36%, P=.03), had a higher relapse rate (5-year: 39% vs. 24% vs. 38%, P=.01) and lower OS (5-year: 41% vs. 64% vs. 49%, P=.02), see Table. Patients who achieved MRD negativity had better OS (MRD+ vs MRD-, P=.01). Importantly, no statistically significant difference in OS, relapse or non-relapse mortality were noted between the 3 groups in patients who underwent allo-HCT in CR1. Conclusions: Ph-like ALL is a high risk subgroup with increased prevalence in younger adults. Allo-HCT appears to offset the poor prognosis associated with this entity. A targeted FISH panel offers timely recognition of this entity in a clinical setting.[Table: see text]
TP53/NPM1-mutated acute myeloid leukemia as a molecularly distinct disease entity.
Authors: Scarpa Frank J , Paul Madhuri , Daringer Rachel , Wolfson Wendy A. , Lopez Diaz Fernando , Agersborg Sally , Funari Vincent Anthony , Weiss Lawrence Martin , Blocker Forrest 
Published: June 2021

7030 Background: TP53-mutated acute myeloid leukemia (AML) is a distinct disease entity associated with a dismal prognosis. This disease group is distinguishable by its low frequency of SNVs, unremarkable transcriptional signatures, and lower leukocyte and myeloblast counts compared to TP53 wildtype disease. Response to gold-standard hypomethylating agents is typically transient. NPM1 mutations in this disease subset are rare despite the fact that NPM1c has been shown to negatively regulate the tumor suppressive functions of p53 .Methods: Bone marrow, peripheral blood, or FFPE tissue samples from 10,118 patients with suspected myeloid disease were sequenced using a dual DNA/RNA 297 gene myeloid panel. Results were validated in a separate independent dataset using a 54 gene TruSight myeloid panel (N = 2463). FISH/cytogenetic data was analyzed across myeloid disease. Patients with confirmed AML (n = 460) were included in the NGS portion of this study. Statistics were performed using Fisher’s exact test for categorical variables and two-tailed T-test for continuous variables. Results: All TP53-mutated myeloid disease (n = 1282 / 10,118) was associated with fewer co-mutations except DNMT3A (13.4%; n = 172), and complex cytogenetics (36.4%; n = 134/381). TP53+/NPM1+ status across all myeloid disease was not associated with a complex karyotype (7.6% vs 38.5%; 1/13 vs. 133/368, p = 0.02). Among AML patients, NPM1+/TP53+ patients (n = 18) were more co-mutated with DNMT3A (33.3% vs. 10.3%, P = 0.01), FLT3 (33.33% vs. 2.5%, P < 0.0001), IDH1 (27.8% vs. 4.4%, P = 0.002), IDH2 (22.2% vs. 6.4%, P = 0.03); and PTPN11 (22.2% vs. 2.5%, P = 0.003) when compared to TP53+/NPM1- patients. NPM1+/TP53+ AML had more mutations in recurrently mutated genes (4.5 vs 2.1; P < 0.0001) than TP53+/NPM1- AML. Conclusions: TP53+/NPM1+ AML harbors molecular signatures which clearly distinguish it from ordinary TP53-mutated AML, and is more reflective of de novo and NPM1+ AML. Further clinical outcome studies are needed to determine the therapeutic and prognostic implications of this subset, and whether other TP53-mutated patients can be better risk stratified.[Table: see text]
Phenotypes and prognostic factors in adults with Langerhans cell histiocytosis.
Authors: Goyal Gaurav , Acosta-Medina Aldo A. , Hu Marie , Abeykoon Jithma P. , Ravindran Aishwarya , Bennani N. Nora , Davidge-Pitts Caroline , Shah Mithun Vinod , Tobin W. Oliver , Young Jason R. , Ryu Jay H. , Vassallo Robert , Rech Karen , Go Ronald S. ,   Mayo Clinic-University of Alabama at Birmingham Histiocytosis Working Group
Published: June 2021

7049 Background: Langerhans cell histiocytosis (LCH) can manifest as single system (SS) disease, multisystem (MS) disease, or pulmonary LCH (smoking-related). There is a paucity of data on prognostic factors including risk organ (RO) involvement (liver, spleen, and bone marrow) in adult LCH, which we sought to address in this study. Methods: Single-center retrospective study of patients ≥18y diagnosed with LCH from 1998 to 2020. Univariate and multivariate analyses for progression free survival (PFS) and overall survival (OS) were conducted using age, sex, organ involvement, LCH subtype, year of diagnosis, BRAF V600E status, and treatments. Results: We included 219 patients with LCH; median age 43y (range 19-88), females 51%, SS unifocal (23%), SS multifocal (6%), pulmonary (31%) and MS (40%). Commonly involved organs included lung (53%), bone (42%), skin (24%), pituitary (16%), and CNS (12%). BRAF V600E was positive in 40/88 (46%). Median follow-up duration was 6.1y (95% CI, 5.1- 7.1). On univariate analysis, factors associated with worse PFS were bone LCH, RO involvement, multifocal/MS LCH, and radiation therapy alone; those with worse OS included RO involvement, MS disease, BRAF V600E+, and age ≥45y at diagnosis. In multivariate analysis, BRAF V600E and age ≥45y at diagnosis were associated with worse mortality (Table). Median PFS was not reached (NR-NR) for SS unifocal LCH, 5mo (0-12.7) for SS multifocal LCH, 110mo (84.7-135.3) for pulmonary LCH, and 27mo (17.2-36.8) for MS LCH. 5-year OS was 97.4% for SS unifocal LCH, 100% for SS multifocal LCH, 96.1% for pulmonary LCH, and 79.9% for MS LCH. 41 (18.7%) developed a second primary malignancy (SPM), of which 11 were hematologic neoplasms. There was a trend towards a higher prevalence of SPMs in patients with BRAF V600E (28% vs. 17%; p = 0.22). Conclusions: In our large single-center study, PFS for multifocal and MS LCH was worse than SS unifocal or pulmonary LCH. RO involvement was not associated with outcomes in multivariate analysis. Overall prognosis was excellent for all subtypes except MS LCH. BRAF V600E and older age were associated with worse OS. The prevalence of SPMs was very high and needs to be explored further.[Table: see text]
BRAFV600E frequency and impact on outcomes in adults with langerhans cell histiocytosis.
Authors: Acosta-Medina Aldo A. , Abeykoon Jithma P. , Bennani N. Nora , Davidge-Pitts Caroline , Koster Matthew J. , Ravindran Aishwarya , Rech Karen , Ryu Jay H. , Schram Susan M. , Shah Mithun Vinod , Tobin W. Oliver , Vassallo Robert , Young Jason R. , Go Ronald S. , Goyal Gaurav ,   Mayo Clinic - University of Alabama at Birmingham Histiocytosis Working Group
Published: June 2021

7050 Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm manifesting as unifocal, multifocal, multisystem (MS) or pulmonary LCH (smoking-related). In pediatric LCH, somatic BRAFV600E prevalence is reported at 55-70%, and associated with increased risk of multisystem disease and early treatment failure. Our aim was to describe the prevalence of BRAFV600E mutation and evaluate its association with clinical manifestations and outcomes in adults with LCH. Methods: A retrospective review of adult patients diagnosed with LCH consecutively seen at Mayo Clinic from 2011 to 2020 was performed.Evaluation of association of BRAFV600E mutational status and clinical factors was conducted by the Chi-square test for independence. Progression-free survival (PFS) and overall survival (OS) were analyzed via the Kaplan Meier method and compared with the log-rank test to assess the effect of BRAFV600E. Results: Of the total LCH cohort ( n= 128), 88 patients with available BRAFV600E results were included in the study. Median age at diagnosis was 41y (range 19 - 88); 52.3% were male. 40 (45.5%) patients had a BRAFV600E mutation. Increasing age was associated with BRAFV600E (10-year increase OR 1.42, 95%CI 1.07-1.89; p= 0.017). No correlation was observed between BRAFV600E status and site of disease, risk organ (RO: liver, spleen, marrow) involvement, or MS disease. Patients with BRAFV600E were 4 times more likely to receive targeted therapy ( BRAF inhibitor) than non- BRAFV600E patients ( p= 0.018). After a median follow up of 46 mo (95% CI 30.8-61.2), PFS was similar between BRAFV600E and non- BRAFV600E patients ( p= 0.167). However, patients with BRAFV600E had a worse 3-year OS compared with non- BRAFV600E patients (84% vs. 97.1%, p= 0.027). Patients who died had a significantly higher age at LCH diagnosis (median 62 vs. 38 years; p= 0.0002). Conclusions: In our cohort of adults with LCH, BRAFV600E was less frequent than reported in pediatric literature and was associated with worse OS. The frequency of BRAFV600E was positively correlated with increasing age. Contrary to reports in pediatric LCH, there were no significant associations between BRAFV600E and high-risk or multisystem disease.[Table: see text]
Preliminary safety and efficacy of PBCAR0191, an allogeneic, off-the-shelf CD19-targeting CAR-T product, in relapsed/refractory (r/r) CD19+ NHL.
Authors: Shah Bijal D. , Jacobson Caron A. , Solomon Scott , Jain Nitin , Vainorius Monika , Heery Christopher Ryan , He Fiona C. , Reshef Ran , Herrera Alex Francisco , Akard Luke Paul , Sauter Craig Steven 
Published: June 2021

7516 Background: Although autologous CD19-directed CAR T products have demonstrated unprecedented efficacy in chemorefractory patients, manufacturing failure or delays remain important barriers to care, limiting utility for those with more rapidly growing disease and/or impaired T cell fitness. Here, we present an update to preliminary safety, efficacy, and correlative data for the subjects dosed with at least 3 x 106 CAR-T+ cells/kg, or equivalent, of PBCAR0191, an off-the-shelf allogeneic CAR T product. Methods: Subjects were required to have evaluable CD19+ r/r NHL, adequate organ function, 2+ prior treatment regimens, and no active GvHD, CNS disease, infections or active medical issues. Prior stem cell transplant and/or CAR-T therapy were allowed. All subjects were lymphodepleted prior to administration of PBCAR0191with either standard (sLD; 30/500mg/m2/day x 3 days fludarbine/cyclophosphamide) or enhanced (eLD; 30 x 4 days and 1000mg/m2/day x 3 days flu/cy) lymphodepletion. Correlative laboratory samples were taken at baseline and while patients remained on study for CAR T cell expansion, persistence, response to treatment and safety assessments. Results: As of February 2021, 13 subjects were evaluable meeting these criteria. Demographics, baseline disease characteristics, and prior therapy data are presented in the table. Median time from eligibility confirmation to PBCAR0191 infusion was 6.5 days (1 day to start LD). To date, most adverse events (AE) reported were mild, with no cases of GvHD or Grade ≥3 CRS/ ICANS. PBCAR0191 related serious AEs were reported for 31% (4/13) of the subjects and 1 subject (9%) died of Febrile neutropenia on day 42 after treatment. Infections and cytokine release related AEs occurred at higher frequency in the eLD group. Efficacy of PBCAR0191 in 13 NHL subjects with available 28 day follow up is presented in the table. Peak PBCAR0191 expansion was increased 56-fold and was associated with CR rate of 71% in eLD group versus 33% in sLD group. Duration of response assessment is ongoing. Conclusions: PBCAR0191 has demonstrated dose and LD-dependent cell expansion kinetics with encouraging anti-tumor activity. Host-versus-graft rejection may have a role in depth and durability of response. CR rates with PBCAR0191 are preliminarily comparable to those observed with autologous CAR T in this population. Updated response durability assessment will be presented at the time of the meeting. Clinical trial information: NCT03666000. [Table: see text]
Survival trends in chronic lymphocytic leukemia in the era of oral targeted therapies in the United States: SEER database analyses (1985 to 2017).
Authors: Alrawashdh Neda , McBride Ali , Persky Daniel O. , Sweasy Joann , Erstad Brian , Abraham Ivo 
Published: June 2021

7524 Background: The survival of chronic lymphocytic leukemia (CLL) patients has progressively improved after the approval of new targeted therapy for first-line treatment and relapsed disease. We performed a corresponding analysis from the U.S. population-based SEER database (1973–2017) to explore the trend of survival and the effect of advanced CLL treatment on overall survival in CLL patients. Methods: Data were extracted from SEER*Stat for all patients 15 years or older with a primary diagnosis of CLL with or without subsequent cancers. A period analysis was performed to estimate the 5- and 10-year relative survival rates for patients diagnosed (dx) during different calendar periods from 1985 to 2017, based on gender and age at time of diagnosis (15–44, 45–54, 55–64, 65–74, 75–84, 85 years or older). A mixture cure model was used to examine the proportion of long-term survivors per gender and age category among CLL patients diagnosed between 1985 and 2015. Cox proportional hazard modeling was used to calculate the hazard ratios (HRs) of death adjusted for gender and age at diagnosis for two cohorts: (a) diagnosed in 2000–2003 and followed to 2012; (b) 2004–2007 and followed to 2015. Results: For males, the 5-year age-adjusted relative survival rate improved progressively from 72.0% (dx 1985-1989) to 88.2% (dx 2010-2014); for females, from 76.8% (dx 1985-1989) to 90.8% (dx 2010-2014). The corresponding 10-year age-adjusted relative survival rates were 47.3% (dx 1985-1989) and 72.5% (dx 2005-2009) for males; and 58.2% (dx 1985-1989) and 78.7% (dx 2005-2009) for females. The table below shows the proportions of long-term survivors for the 1985–2017 cohort as estimated in the mixed cure model. The HRs (95%CI) of death for cohort (b) in comparison to cohort (a) were 0.58 (0.43–0.78), 0.58 (0.48–0.70), 0.57 (0.49–0.67), 0.68 (0.54–0.85); and 0.83 (0.68–1.02) for age categories of 45–54, 55–64, 65–74, 75–84, and 85 years or old. Conclusions: Survival is significantly improved by calendar period among patients diagnosed after 2004 and treated in the era of advanced therapies. Females and younger patients had a higher probability of long term survival. Future studies should consider such covariates as treatment type, disease stage and genetics.[Table: see text]