bluuebunny/crossref_metadata_2025_split huggingface dataset:
Receipt of financial drug assistance for oral targeted therapy among older adults with advanced non-small cell lung cancer (NSCLC).
Authors: Kumar Anika , Ragavan Meera Vimala , Zeng Sandra , Wong Melisa L. 
Published: June 2023

e18916 Background: Financial drug assistance programs are a critical resource to mitigate financial toxicity for oral targeted therapy but can be challenging to access and navigate. Older adults with cancer frequently face high copayments for oral targeted therapy, yet they may be less able to navigate assistance programs due to functional and cognitive impairments. To identify potential barriers to receipt of assistance among older adults with advanced NSCLC, we evaluated associations between demographic, clinical, and geriatric assessment characteristics and receipt of financial drug assistance. Methods: We conducted a prospective cohort study at a Comprehensive Cancer Center where thoracic oncology nurses and pharmacists are available to help patients navigate financial drug assistance applications. We enrolled adults age > 65 with advanced NSCLC starting a new chemotherapy, immunotherapy, and/or oral targeted therapy regimen with non-curative intent. For this analysis, we included only older adults who received oral targeted therapy. Patients completed a pretreatment geriatric assessment to evaluate function, cognition, social support, comorbidities, mood, and nutrition. Receipt of financial drug assistance was abstracted from the medical record. We used Fisher’s exact tests to evaluate for differences in demographic, clinical, and geriatric assessment characteristics between those who did and did not receive financial drug assistance. Results: Of the 168 older adults with advanced NSCLC in the parent cohort study, 45 received oral targeted therapy and were included in this analysis. Median age was 74 (range 65-94); 56% were White, 40% Asian, 2% Black, and 2% Hispanic. The majority had Medicare (76%) followed by private insurance (18%), Medicare and Medicaid (4%), and Medicaid alone (2%). On the geriatric assessment, 60% were dependent in instrumental activities of daily living, 20% were dependent in basic activities of daily living, 51% had an abnormal Montreal Cognitive Assessment, and 42% had poor tangible social support. Overall, 9 older adults (20%) received financial drug assistance for their oral targeted therapy. Older adults with a lower household income were more likely to receive financial drug assistance (p = 0.007). There were no statistically significant differences in receipt of financial drug assistance according to other demographic, clinical, or geriatric assessment characteristics including function, cognition, and social support. Conclusions: Older adults with advanced NSCLC on oral targeted therapy with lower household incomes were appropriately more likely to receive financial drug assistance. The lack of associations between receipt of financial drug assistance and function, cognition, and social support suggests that thoracic oncology staff are successfully helping older adults navigate financial drug assistance programs.
Cost of breast cancer screening in the USA: Comparison of current practice, advocated guidelines, and a personalized risk-based approach.
Authors: Badal Kimberly , Staib James , Tice Jeffrey , Kim Mi-Ok , Eklund Martin , DaCosta Byfield Stacey , Catlett Kierstin , Wilson Leslie , Maffey Liz , Soonavala Rashna , Stover-Fiscalini Allison , Esserman Laura 
Published: June 2023

e18917 Background: Several clinical trials are comparing the safety and efficacy of risk-based and age-based breast cancer screening. This study aimed to estimate the aggregate yearly cost of screening in the USA for 2019 to 2021 and to project cost of four strategies: annual, biennial, hybrid, and the WISDOM (Women Informed to Screen Depending on Measures of risk) clinical trial’s risk-based strategy. An assessment of screening costs under different strategies can inform policy decisions. Methods: Total cost was estimated for each strategy by summing screening and recall cost for eligible women from a national payer perspective. Data from the FDA Mammography Quality Standards Act and Program was used to estimate the number of screening mammograms in 2019 to 2021. Data from the Optum Labs Data Warehouse (OLDW) was used to estimate utilization of 2D and 3D mammograms, MRI and mammogram costs, recall costs and rates. OLDW contains longitudinal de-identified administrative, medical, and pharmacy claims for over 200 million commercial and Medicare Advantage (MA) enrollees and patients. Study subjects were continuously enrolled for approximately three years to capture all encounters. Medicare Advantage claims were used to approximate public payer costs and rates. We assumed 100% adherence to all strategies. The risk-based strategy used a cost of $270 for genetic testing and risk assessment. Probabilistic sensitivity analysis was used to estimate uncertainty in the estimated aggregate cost. One-way deterministic sensitivity analysis was used to determine the impact of each input on the aggregate cost. Results: Median mammogram costs ranged from $139-$360, MRI costs ranged from $545-$2,439, while recall rates ranged from 9.2%-20.9%. The annual cost of screening 50% of eligible women in 2019 was $11.5B ($10.37-13.94B) and cost $77,824 per breast cancer detected. The estimated yearly aggregate cost of screening 100% of eligible women was: $26.71B ($24.61-32.82B) for annual; $18.09B ($16.03-21.16B) for hybrid; $7.57B ($6.97-9.29B) for biennial; and $9.60B ($8.88-11.70B) for risk-based strategies. The estimated average cost per woman screened until 74 years was: $22,315 for annual; $16,552 for hybrid; $4,133 for biennial; and $6,878 for risk-based. The yearly aggregate cost of screening was most sensitive to variations in commercial 3D mammography cost. Conclusions: Biennial and risk-based screening can reduce cost substantially. Risk-based screening reduced cost even with the cost of population genetic testing included while maintaining intensive screening for the highest-risk women. The resources saved can be used to improve screening for women at high-risk of fast-growing disease who are often identified between screens and for improving overall adherence.
Excess testing after diagnosis of incidental pulmonary nodules (IPNs) in the Medicare population.
Authors: Osarogiagbon Raymond U. , Pinsky Paul 
Published: June 2023

e18922 Background: Management of IPNs re-distributes lung cancer to earlier stages at diagnosis, but most people with IPNs will not develop lung cancer. We assessed the rate of diagnostic procedures related to suspected lung cancer in people on Medicare who had IPNs. Methods: We analyzed the 5% SEER-Medicare database for IPNs, diagnostic procedures, and lung cancer status. We analyzed two cohorts: persons with chest CT scan procedure codes accompanied by ICD-9 code 793.11 or ICD-10 code R91.1 during 2014-2017 (IPN cohort) and persons with CT scan procedure codes without the IPN codes during that period (control cohort). We computed rates of lung cancer-related diagnostic procedures (per 100 person-years [PY]) during the 2-year follow-up period, including chest CT, PET/PET-CT, bronchoscopy, needle biopsy, and surgical procedures. We used multivariable Poisson regression to estimate procedure rate ratios (RRs) across cohorts, controlling for demographics and COPD status. Using the regression RRs, we estimated excess procedures in the IPN cohort over the 2-year follow-up period by subtracting the control cohort (background) rate. Based on prior data on the reduced proportion (by 36%) of late-stage disease associated with follow-up of IPNs, we computed a metric of excess procedures per late-stage case avoided by IPN follow-up. Results: Of 19,009 (IPN) and 60,985 (control) persons, 3.6% and 0.8%, respectively, had lung cancer diagnosed during 2-year follow-up. Among IPN cohort without lung cancer, rates per 100 PY were 73.1, 9.4, 4.0, 3.2 and 1.0 for chest CT, PET/PET-CT, bronchoscopy, needle biopsy, and surgical procedures, respectively (Table). Poisson regression showed significantly elevated RRs for the IPN versus control cohort for all procedures, with RRs ranging from 1.27 (bronchoscopy) to 2.03 (Chest CT). Excess procedures in the IPN cohort (per 100 persons) ranged from 63 for chest CT to 0.9 for surgical procedures (Table). Excess procedures per late-stage case avoided ranged from 48 for chest CT to 0.7 for surgical procedures. Conclusions: The burden of diagnostic procedures following reported IPNs is modest relative to the yield of early-stage lung cancer. [Table: see text]
Cost effectiveness of a personalized approach for lung cancer screening with LDCT based on the use of blood-based biomarker test.
Authors: Irajizad Ehsan , Fahrmann Johannes , Vykoukal Jody , Do Kim-Anh , Dennison Jennifer , Ostrin Edwin J. , Hanash Samir M 
Published: June 2023

e18927 Background: We previously reported that a circulating panel of protein biomarkers together with a risk model based on subject characteristics improves lung cancer risk assessment for lung cancer screening compared to current screening eligibility criteria (JCO 2022 PMID 34995129). The goal of this study is to assess cost-effectiveness of a personalized approach to lung cancer screening with LDCT. Methods: We conducted retrospective analyses using data from the US Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial and protein biomarker data measured on prospectively collected pre-clinical sera from the PLCO biorepository. For determination of cost-effectiveness of using the biomarker test for risk based referral for LDCT, we assumed screening of 27.0 million US ever smokers. The reference scenario assumed eligibility using the risk-based smoking approach with no cost. We predicted that the proportion of upcoming lung cancer cases categorized as screening eligible will increase as a result of biomarker-informed eligibility. We used direct NLST costs using 2009 Medicare prices for screening (per person screened), workup (per positive screen), and treatment (per lung cancer case) and evaluated the effectiveness at different biomarker costs. We used life year gained for cases and non-cases, with and without screening. Results: With 80.4% sensitivity at 66.9% specificity; performance of our previously established lung panel, assuming a willingness-to-pay threshold of $70 000 per life-year gained, the biomarker test for referral to screening is cost-effective up to 300$. At a willingness-to-pay threshold of $100,000 per life-year, the biomarker test is cost-effective up to $500. Conclusions: A cost effective blood-based biomarker test has been developed for referral for lung cancer screening with LDCT.
Cost-utility analyses of later-line treatments for metastatic colorectal cancer (mCRC) by network meta-analysis (NMA) approach: Conventional constant hazard ratio vs novel survival curves methodologies.
Authors: Obeng-Kusi Mavis , Erstad Brian L , Roe Denise , Abraham Ivo 
Published: June 2023

e18928 Background: Cost-utility analyses of later-line treatments for metastatic colorectal cancer (mCRC) differ based on network meta-analysis (NMA) approach: conventional constant hazard ratio vs novel survival curves methodologies. Methods: We conducted a CUA estimating the incremental cost utility ratio (ICUR) over a 5-year time horizon from the US payer perspective. The 3-state partitioned survival models included efficacy inputs from a novel one-step multivariate NMA of progression-free and overall survival curves and from a conventional constant hazard ratio NMA. Utilities, as well as drug acquisition, administration, adverse event, monitoring and end of life costs were sourced from literature. We compared results and examined statistical factors in either approach that may explain the observed results. Results: The multivariate NMA produced lower estimates of survival benefits over placebo compared to the NMA based on constant hazard ratios, at the same incremental costs (Table). This reduction in incremental benefits led to higher estimates of cost-effectiveness and cost-utility when using the multivariate NMA. Probabilistic sensitivity analyses showed greater uncertainty in the model based on the constant hazard NMA. Conclusions: The multivariate NMA produced lower estimates of survival benefits over placebo compared to the NMA based on constant hazard ratios, at the same incremental costs (Table). This reduction in incremental benefits led to higher estimates of cost-effectiveness and cost-utility when using the multivariate NMA. Probabilistic sensitivity analyses showed greater uncertainty in the model based on the constant hazard NMA. [Table: see text]
Novel RNA epigenetics-driven technologies for rapid prediction of cancer drug resistance.
Authors: Wood Shaun , Willbanks Amber , Tang Derrick , Arber Daniel A , Oakes Scott , Shammo Jamile M. , Odenike Olatoyosi , Stock Wendy , Larson Richard , Cheng Jason X 
Published: June 2023

e19001 Background: The human genome comprises ~99% non-coding DNA sequences (ncDNAs), most of which are actively transcribed into various forms of non-coding RNAs (ncRNAs) that undergo extensive chemical modifications to regulate various functions of the subcellular organelles in human cells ( Statello, et al. Nat Rev Mol Cell Biol 2020). However, the clinical potential of RNA modifications and RNA modifying proteins, i.e., RNA epigenetics, is largely unexplored. In a recent study ( Cheng et al. Nat Commun 2018), we first demonstrated that specific RNA cytosine methyltransferases (RCMTs), namely NSUN1 and NSUN2, directly interact with elongating RNA polymerase II (eRNAPII) and the bromodomain-containing protein 4 (BRD4) to form distinct active chromatin structures (ACS) that regulate drug resistance in leukemia cells. This proof-of-concept study enabled us to develop the first-generation of RNA epigenetics-driven drug-predictive system. The primary goal of this study is to validate and optimize this novel drug-predictive system with clinical myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Methods: We developed new technologies, including 5-ethynyl uridine click chemistry (EC) and proximity ligation rolling cycle amplification (PL-RCA)-coupled confocal microscopy (CM), flow cytometry (FCM) and RNA sequencing (RNA-seq). Immunohistochemistry (IHC), western blot (WB), co-immunoprecipitation (co-IP), and dot blot were also used in this study. Results: Our data demonstrated significantly increased expression of the NSUN1, NSUN2 and other key components of the drug-resistant ACS in MDS/AML, which is correlated with disease progression and drug resistance in MDS and AML. We have developed novel technologies, i.e., EC- and PL-RCA-coupled CM and FCM (EC-/PL-RCA/CM & FCM) to visualize and quantify RCMTs-mediated ACS and nascent RNA synthesis in MDS/AML. We discovered nascent RNA synthesis as a highly sensitive and super-fast drug-predictive marker that is independent of cell death and apoptosis. Our data demonstrated that PL-RCA/FCM and EC-/CM have a very high sensitivity to detect the NSUN1/2-mediated ACS in leukemia cell lines and clinical MDS/AML specimens. Our preliminary data demonstrated that increased levels of NSUN1/2-mediated ACS detected by PL-RCA/FCM in pre-treatment MDS/AML can rapidly predict the responses to venetoclax and/or azacitidine. We are actively pursuing RNA-seq targeting NSUN1/2-associated nascent RNAs and ACS, which provides a novel strategy to dissect the functional genomics and RNA epigenetics underlying cancer drug resistance. Conclusions: We have developed a novel RCMTs/NSUN1/2-targeting system for rapid prediction and in-depth analysis of drug resistance in MDS/AML. A large sized clinical study is needed to further validate its usefulness in clinical settings.
Defining risk of central nervous system relapse in acute myeloid leukemia following allogeneic stem cell transplantation.
Authors: Nicchi Vincent , Roloff Gregory , Gomez Kayeromi , Campo Loredana , Badami Ami , Tsai Stephanie , Stiff Patrick J. , Hagen Patrick 
Published: June 2023

e19009 Background: Relapse following allogeneic stem cell transplant (AlloSCT) for acute myeloid leukemia (AML) remains the commonest cause of death post-transplant. Central nervous system (CNS) relapse is a devastating complication. With an estimated incidence of 2-8%, defining those patients at high risk and the management following CNS relapse remains controversial. We sought to identify demographic, clinical, molecular, and laboratory risk factors that would predispose AML patients to CNS relapse. Methods: This was a single institution retrospective study at Loyola University Medical Center. Inclusion criteria were adult patients with AML undergoing first AlloSCT from January 2012 to June 2021. Diagnosis of CNS relapse following AlloSCT was defined as leukemic blasts detected in spinal fluid analysis in accordance with established criteria. Chi-square tests were used to test the association between the experiencing of relapse and the categorical variables recorded. Wilcoxon Rank Sum test were used to assess the relationship between relapse experience and each of the demographic variables. Due to the low count of patients with CNS relapse and in order to avoid a poor estimation of confidence limits of any effect size, we limited our analyses to descriptive statistics and univariable analyses. Results: 198 patients met inclusion criteria with 8 cases (4.0% total) identified with CNS relapse following AlloSCT. Our analysis initially characterized 44 variables including age, race, HCT-CI risk, and day 100 chimerism. Univariate analysis is shown in the table below. Of note, it revealed that 62.50% of patients with CNS relapse had a chimerism value ≤98% at day 100 post-transplant as compared to 22.58% of patients without CNS relapse (p-value 0.02). Additionally, 87.50% of the CNS relapse group versus 51.38% of the group without relapse had favorable to intermediate AML risk scores (p-value 0.07). Conclusions: We observed a 4.0% rate of CNS relapse, which is consistent with what has been repored in the literature. Our results suggest that day 100 chimerism and disease risk index may be predictive of CNS relapse. Since there is a 10.6% incidence (5/47) of eventual CNS relapse amongst those with ≤98% chimerism at day 100, these patients could be considered for a lumbar puncture and bone marrow biopsy to prevent full relapse. Further research in this topic would be valuable to provide additional AML guidance in managing this uncommon complication, such as which patients may benefit from prophylactic strategies. [Table: see text]
Responses in patients with AML and treated with entospletinib monotherapy.
Authors: Lin Tara L. , Cutler Richard E. , Olek Elizabeth , Carvajal Luis A. , DiMartino Jorge F. , Walker Alison R. 
Published: June 2023

e19010 Background: AML is a disease defined by the acquisition of genetic lesions in normal hematopoietic stem cells and progenitors resulting in poorly differentiated and highly proliferative leukemic blasts. Spleen tyrosine kinase (SYK) is a nonreceptor tyrosine kinase that maintains de-differentiation and leukemogenesis. MLL rearrangements (MLL-r) occur in up to 10% of adult AML and are associated with upregulated expression of the transcription factors HOXA9 and MEIS1 and worse clinical outcomes. Entospletinib (ENTO), an oral, selective inhibitor of SYK, has been studied in clinical trials for unselected AML patients as well as MLL-r patients. ENTO plus standard induction chemotherapy in front line had a 76% (13/17) composite complete response (CR) in AML patients with high HOXA9 and MEIS1. We have 3 patients that achieved CRs with ENTO monotherapy; one patient achieved CR to 14 days of ENTO monotherapy prior to initiation of chemotherapy; 2 patients with relapsed/refractory AML with MLL-r treated with ENTO monotherapy achieved CRs. Methods: This was part of an international multicenter phase Ib/II study (NCT02343939) which evaluated the efficacy, safety, and tolerability of ENTO in subjects with AML. During dose escalation, ENTO was administered in combination with induction chemotherapy (Group A) or with a hypomethylating agent (Group B). ENTO was administered as monotherapy for R/R AML in Group C. This report includes one patient from group A (newly diagnosed AML, MLL-r, 14-day monotherapy lead-in with ENTO) and two patients from group C monotherapy (relapsed/refractory AML, MLL-r). Results: Three patients receiving ENTO monotherapy had CRs. 18-year-old male from group A, that was MLL-r, NPM1-mutant (-). Patient treated at 400 mg PO, BID, achieved a cytogenetic CR with incomplete count recovery after cycle 0 (before chemotherapy); the patient continued study with induction chemotherapy and ultimately received ASCT in CR. Two additional patients in group C (with multiple therapies), both at 400 mg bid: (i) 37-year-old male, MLL-r, NPM1(-), was on study for 28 days, achieved CR; (ii) 28-year-old female, MLL-r, NPM1(-) on study for 60 days, achieved CR, both proceeded to SCT. Conclusions: Based on the results from these three patients, the clinical activity of SYK inhibition should be explored further in AML. We are testing Lanraplenib, a next-generation SYK inhibitor with enhanced selectivity, and more favorable pharmacologic properties in combination in genetically defined subsets of AML (NCT05028751). Clinical trial information: NCT02343939 .