bluuebunny/crossref_metadata_2025_split huggingface dataset:
Practice efficiency of treatment with epcoritamab versus glofitamab in relapsed/refractory diffuse large B-cell lymphoma.
Authors: Meyer Kellie , Huang Danmeng , O'Day Ken , Lahue Betsy J. , Wang Anthony , Mutebi Alex , Brodkin Samantha , Jun Monika P. 
Published: June 2023

e18919 Background: Bispecific antibodies are an emerging class of immunotherapies with demonstrated efficacy in the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Since epcoritamab is administered subcutaneously, it provides an opportunity for reduced healthcare provider (HCP) and patient burden compared to intravenous (IV) glofitamab. This study assessed HCP and chair time saved treating R/R DLBCL patients with epcoritamab versus glofitamab. Methods: An efficiency model was developed to comprehensively capture time and resources utilized in the administration of epcoritamab and glofitamab from the perspective of institutional decision makers in the United States. The model was informed by the administration process and dosing schedules outlined in the pivotal publications as well as published literature examining HCP’s tasks and the time required to complete these tasks. A 6-month time horizon as was adopted as the base case due to its relevance in the Enhancing Oncology Model, and scenario analyses were performed examining various time horizons. Results: Treating patients with SC epcoritamab compared to IV glofitamab was estimated to reduce HCP time by 29% (45.4 hours for 19 doses of epcoritamab vs. 63.9 hours for 10 doses of glofitamab) and chair time by 38% (55.8 vs. 90.6 hours) per patient over a 6-month time horizon. Time saved for epcoritamab was mainly driven by glofitamab’s infusion time and required pre-treatment with obinutuzumab. For 100 hypothetical patients treated with SC epcoritamab vs. IV glofitamab, a savings of 3,478 chair hours was generated, which could free up capacity to treat 62 additional patients. In the scenario analyses examining different time horizons, the capacity savings advantage of epcoritamab over glofitamab remained. Conclusions: In this model, the use of SC epcoritamab improved practice efficiency compared to IV glofitamab. For institutional decision makers, reduced chair time may increase the total number of treated patients and lead to reduced waiting lists.
Impact of economic inequality on Kaposi sarcoma of the lung: A retrospective cohort.
Authors: Guevara Nehemias , Francis-Morel Garry , Perez Esmirna , Bustamante Alvarez Jean Gabriel 
Published: June 2023

e18920 Background: Kaposi Sarcoma of the lung is a rare entity; it is unclear if a below-average household income has an impact on outcomes. Methods: This is a retrospective cohort study of patients with Kaposi Sarcoma of the lung that were admitted to acute care from 2016 to 2020. Data is derived from the National Inpatient Sample (NIS). We compared outcomes in 2 cohorts: those with household income < $50,000 versus those with > $50,000. The primary endpoint was differences in all-cause in-patient mortality. Secondary endpoints included differences in length of stay (LoS) and admission cost. Results: A total of 460 patients met inclusion criteria; 40% had income < $50K, and 60% > $50K (p < 0.001). There was a trend to male predominance (100% of < $50K, 95% > $50K; p 0.147) with a mean age of 39 (35 for < 50K, 41 for > 50K; p 0.015). Black patients were the most afflicted group (46%; 71% of < $50K, 29% > $50K; p < 0.001), followed by White patients (33%, 20% of < $50K, 43% of > $50K; p < 0.001). Additionally, patients with household income < $50K (40%; p < 0.001) and hospitals located in the South (43%, 48% of < $50K, 40% of > %50K; p < 0.001) and West (32%, 11% of < $50K, 46% of > 50K; p < 0.001) represented the largest group. Majority of patients were under Medicaid insurance coverage, however there was no relationship between Medicaid coverage and mortality (p = 0.709, CI 0.16-3.42). There was no difference in distribution based on primary payer, hospital bed size, hospital teaching status, and hospital ownership (p > 0.05). No differences in mortality were noted among groups (p 0.845). No differences in LoS were seen (p 0.560), but younger patients were more likely to have shorter LoS (p 0.033). Ultimately, no differences in hospitalization costs were noted (p 0.426). Furthermore, from the 460 patients with Kaposi lung sarcoma, 5 were post-transplant patients, and 130 were patients with HIV; in this sub-group of analysis, were no differences between ages. The mean age in patients with lung transplants was 39.5, and the HIV group was 40 years. The black population was the most affected, with an income below $50 000. Conclusions: Income did not impact mortality in patients admitted for Kaposi sarcoma of the lung. Black patients and patients with income < $50,000 represented the largest group. Nevertheless, more research is needed for better stratification and to elucidate many factors that play a role in the mortality of patients with Kaposi sarcoma of the lung.
Breaking down cancer costs: Hospital charges for patients with melanoma.
Authors: Hundal Henna , Taneja Kamil , Patel Karan , Zhang Alex , Diaz Michael , Chandragiri Sahas , Cohen Jules A. 
Published: June 2023

e18921 Background: 78,000 new melanoma cases are diagnosed every year in the US and many present to the emergency department (ED). Furthermore, the increasing cost of healthcare has been well established. However, there is little data on the annual trends of hospital charges and risk factors for a high charge for these patients. Methods: We utilized the 2006-2012 Nationwide Emergency Department Sample to analyze the charges of melanoma patients. Multivariate linear regressions were used to identify factors associated with higher ED and inpatient (IP) costs. The 20 most common primary diagnoses of these patients were included in the analysis to consider the reason to visit the ED. Charges were corrected for inflation by normalizing to the 2012 US Dollar. Results: Between 2006 and 2012, 239,956 melanoma patients presented to the ED. In this time period, melanoma patients were charged a total of $567,834,100 (95% Confidence Interval (CI): $519,399,100 - $616,269,100) in the ED. The average per-patient ED charge was $3,284 (95% CI: $3,152-$3,416). The per-patient ED charge increased from $2,309 (95% CI:$2,144-$2,476) in 2006 to $3,844 (95% CI:$3,638-$4,049) in 2012 (p < 0.001), even after correcting for inflation. In the IP setting (57.6% of melanoma patients were admitted), melanoma patients were charged a total of $5,151,730,000 (95% CI:$4,768,685,000-$5,534,776,000). The average per-patient IP charge during this time period was $38,304 (95% CI: $36,952-$39,656). Over time, the per-patient IP charge increased from $34,591 (95% CI: $32,606-$36,576) in 2006 to $41,245 (95% CI:$39,151-$43,448) in 2012 (p < 0.001), even after correcting for inflation. Table 1 shows the top 5 factors associated with higher ED and IP charges. Conclusions: The ED and IP charges associated with melanoma patients has steadily increased during this period, even after correcting for inflation. ED per-patient charges have increased by a factor of 1.7 and IP per-patient charges have increased by a factor of 1.2. Furthermore, patients that present to hospitals in the West or to a Trauma Level I center have significantly higher charges. [Table: see text]
Cost-effectiveness of novel systemic therapies for advanced breast cancer: Global representativeness and influence of funding.
Authors: Lazar Neto Felippe , Melo Marina , Hidalgo Filho Cassio Murilo Trovo , Mathias Maria Cecilia , Testa Laura , Campolina Alessandro 
Published: June 2023

e18924 Background: Approval of expensive novel treatments increases costs of cancer care and undermines access, particularly in low and middle-income countries. As the most incident neoplasm, breast cancer (BC) therapies have an enormous budget impact if incorporated. Therefore, cost-effectiveness (CE) studies are essential to guide such decisions. Methods: A systematic literature search of Medline, Scopus, and Web of Science from January 1st 2012 to July 8th 2022 was conducted to identify CE studies of tumor-targeted systemic therapies for advanced BC. Articles without CE (or utility) ratio calculations were excluded. Information on the country and drug studied, authors’ conflicts of interests (COI) and funding, and authors' conclusions were manually reviewed by two independent investigators. Results: Of 1103 screened records, 74 studies comprising 212 CE comparisons were included. Most studied scenarios were from high-income countries (70%, 141/212), with only 10% from Latin America and none from Africa. The most studied drug classes were iCDK4/6 (23%), anti-HER2 directed therapy (21%), anti-PD1/PDL1 (12%) and endocrine therapy (11%). In 46% of the comparisons, a new drug combined with standard of care was compared to placebo and/or standard of care, and in 37% the compared treatment were alternative same class therapies. Nearly 46% (97/212) had pharmaceutical industry funding or author’s COI associated with industry. Overall, 56% of authors’ conclusions were unfavorable. Pharmaceutical industry related-studies were associated with high-income countries (75% vs. 64%, p = 0.006), same-class drug comparators (52% vs. 33%, p = 0.047), and favorable conclusions (60% vs. 15%, p < 0.001). A combination of drugs (addition to standard of care) was associated with unfavorable conclusions (56% vs 28%, p < 0.001). Conclusions: Industry-related studies target high-income countries' scenarios and are more likely to have favorable conclusions. As expected, the addition of drugs to standard treatments (combinations) is less likely to be cost-effective. Government funding in low and middle-income countries is needed to decrease the current literature gap and provide stakeholders with proper information to make incorporation decisions.
Multi-cancer early detection screening tools: A dream come true or a nightmare in the offing.
Authors: Fleck Leonard M , Dave Aakash 
Published: June 2023

e18926 Background: US cancer deaths were at 610,000 in 2022 with 1.9 million new diagnoses of cancer, 86% of which were patients over age fifty. Roughly 150,000 advanced cancers were diagnosed with five current screening techniques. That leaves 1.75 million cancers to be diagnosed symptomatically, largely in advanced stages. The dream is to screen in a minimally invasive fashion for multiple types of cancer at earlier, treatable, life-saving stages. The Galleri test claims to fulfill that dream by identifying more than fifty different cancers, and their location, using a blood test that captures ctDNA linked to aberrant methylation. As their dream approaches reality, with a dozen US hospital systems already offering Galleri, a fiscal and ethical nightmare is likely to ensue. We will demonstrate to providers that Galleri’s analytical validity and clinical utility is marginal at best – largely due to uncertainty surrounding the nature of those fifty malignancies. Methods: Systematic review of literature was performed across multiple databases using the key terms "Cancer Early Detection" AND OR "MCED" AND OR "GALLERI." Grail’s optimistic portrayal of the test’s current efficacy is largely derived from Hubbell and colleagues’ recent work modelling a Galleri-like test that claimed an achievable 24% reduction in cancer mortality (~150,000 lives). Critics contend that their assumptions are too optimistic. The natural histories of most of those fifty cancers are poorly understood, such as tumor latency periods, which means the cancer shift detection to an earlier stage is unknowable. Moreover, we cannot know whether these cancers would have been caught earlier, symptomatically, and successfully treated - which is true of 68% of diagnosed cancers. Etzioni and colleagues concluded that 6% of cancer deaths might be reduced by Galleri, despite that number is still uncertain and optimistic. Galleri cannot take credit for those saved lives. Results: GRAIL proposes population-based screening for 110 million Americans over age fifty annually at a cost of $950 per test. That would add over $100 billion per year to the health costs to discover no cancer in 99% of the persons tested. Roughly $50 billion would be added to Medicare program costs, now at $1 trillion. To save 18,000 Medicare lives would cost $2.8 million per life saved, a significant misallocation of Medicare resources, given many less costly opportunities to save more lives. Finally, individuals with marginal or no health insurance would be informed by Galleri they had an early-stage cancer unaffordable to treat. They represent statistically salvageable lives not actually salvaged, which is a presumptive injustice. This argument holds, despite the company’s pledge to reduce cost by over 40% over four years. Conclusions: In sum, Galleri, as a population-based cancer screening test, is not economically affordable, not ethically equitable, and only marginally medically beneficial.
Effect of change in ECOG performance status at diagnosis and relapse in patients with acute myeloid leukemia.
Authors: Zhang Michelle , Shaw Carole , Russell Katie , Halpern Anna B. , Appelbaum Jacob , Hendrie Paul , Ghiuzeli Cristina Maria , Walter Roland B. , Percival Mary-Elizabeth M. 
Published: June 2023

e19007 Background: ECOG performance status (PS) is often utilized in treatment decision-making for patients with acute myeloid leukemia (AML). Patients with relapsed or refractory (R/R) disease have a particularly poor prognosis and require complex treatment decisions that weight patient preference, disease risk and PS. Currently, limited data exist on changes in performance status from initial diagnosis to the time when R/R AML is found. It would be interesting to characterize whether patients with R/R AML have worse performance status due to progression of disease or stable or improved performance status after initial therapy. Given there are additional factors such as induction chemotherapy that impact performance status at R/R disease, we were also interested in characterizing the association of PS in R/R AML with short and long term survival. Methods: We utilized an institutional database from University of Washington/Fred Hutchinson Cancer Center to retrospectively identify patients with AML or other high-grade myeloid neoplasms (≥10% blasts) who received both induction and salvage chemotherapy between January 1, 2008 through December 1, 2021. Patients with missing performance status at R/R were excluded. Salvage treatment was divided into high (cytarabine greater than 1g/m2/dose), intermediate (7+3 or similar), or reduced intensity (i.e., hypomethylating agents). The McNemar test was used for matched-pair analysis of PS at two timepoints. The Kaplan-Meier method was used for overall survival (OS). Univariate and multivariable linear regression models were used to evaluate associations with 4 week survival. All statistical analyses were performed using R 4.2.1 (2022). Results: Of the patients identified (n = 614), only patients with PS documented at R/R (n = 51) were included in the analysis (baseline characteristics in Table 1). No significant change was identified in PS at diagnosis versus R/R (PS≤1 66.7% vs 70.6%, p = 0.80). Better performance status (PS≤1) at R/R was correlated with improved OS (11.4 months vs 2.33 months, p = 0.003). The 4-week unadjusted mortality rate was 8.5% for patients with PS≤1, and 33.3% for patients with PS > 1 (p = 0.04). Poor performance status (PS > 1) at R/R was associated with significantly increased 4 week mortality (OR 5.5, 95% CI 1.2-30.9), even after adjustment for age and ELN2017 risk (OR 6.2, 95% CI 1.1-41.3). When OS was further stratified by chemotherapy intensity, patients with PS≤1 (n = 36) treated with high intensity chemotherapy (n = 22) had improved OS (14.1 vs 4.3 months, p = 0.007). Conclusions: PS tends to be stable at R/R disease, and poor PS is associated with very poor survival. Further work is needed to characterize the patients with R/R AML who benefit from intensive re-induction chemotherapy.
Early death (ED) in elderly acute promyelocytic leukemia (APL) patients treated with lower induction doses of all-trans retinoic acid (ATRA).
Authors: Dalgetty Mark , Kota Vamsi , Jillella Anand P. , Bryan Locke Johnson , Shah Anvay , Dontu Sruthi , Nain Priyanshu , Pavkov Isabela 
Published: June 2023

e19012 Background: With the introduction of the differentiating agent ATRA, APL has progressed from being one of the most life-threatening diseases to becoming the most curable subtype of adult AML. However, despite this advancement, death within the first 30 days of treatment amongst elderly patients remains a critical issue with ED rates reportedly as high as 20-50%. There is limited data looking at the elderly population due to often being excluded from clinical trials given age associated with being prominent negative risk factor. Pharmacokinetic studies comparing 25 mg/m2/day and 45 mg/m2/day doses in adult patients have shown similar peak concentrations and mean area under the curve. Notably, low dose ATRA has been offered in pediatric patients in order to reduce incidence of differentiation syndrome. Differentiation syndrome is a key contributor to ED in elderly APL patients causing treatment failure. We propose that lower doses of ATRA in the elderly reduces the impact differentiation syndrome has on induction mortality amongst elderly APL patients and leads to a lower rate of ED. Methods: Fifteen APL patients > 60 years of age were treated. Thirteen received low doses of ATRA (equal to or less than 25mg/m2/day) and two received standard doses of ATRA (45mg/m2/day). Arsenic trioxide was also used in addition to cytoreductive agents, such as cytarabine, hydroxyurea, and idarubicin as needed during induction. Dose reductions and regimens were based on age, comorbidities, and overall clinical judgement. During the course of treatment, further dose reductions and pauses in therapy were made based on clinical course. Results: A total of 15 elderly APL patients were treated between May 2017 and November 2020 at cancer centers within Georgia and South Carolina. The age range was 65-88 years old with a median age of 71 years old. 9/15 (60%) were female and 2/15 (13%) were classified as high risk. 13/15 were Caucasian and the remaining 2 were African American. Amongst the 13 APL patients who received lower doses of ATRA, one ED was noted. This occurred in 81-year-old Caucasian male with low risk APL who had multiple significant comorbidities and elected to halt treatment and pursue hospice. Amongst the 2 low risk APL patients who received standard doses of ATRA, one ED was noted due to differentiation syndrome. This patient also had many significant comorbidities. Conclusions: The ED rate in elderly APL patients treated with low doses of ATRA during induction was noted to be 1/13 (7.7%) which is significantly lower than what has been reported in literature. [Table: see text]
Pevonedistat plus belinostat in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome: A phase I multicenter study.
Authors: Maher Keri Renee , Schafer Danielle , Schaar Dale , Sabo Roy , Bandyopadhyay Dipankar , Grant Steven 
Published: June 2023

e19015 Background: Acute Myeloid Leukemia (AML) is an aggressive hematologic malignancy, with particularly dismal prognosis in the relapsed or refractory (R/R) setting, with a median overall survival of approximately 6 months. There has been increasing interest in novel therapeutic approaches to intelligently harness cellular pathways to improve outcomes in this difficult to treat population. Pevonedistat, a first-in-class NEDD8 inhibitor, and Belinostat a HDAC inhibitor work synergistically in AML cells and human xenograft AML models supporting the clinical rationale for this Phase I study. Methods: A Phase I dose-escalation study with a 3+3 design was performed to assess safety and tolerability of pevonedistat plus belinostat. Beliniostat (D1-5) and Pevonedistat(D1,3,5) were administered in a 21 day cycle until disease progression or unacceptable toxicity. Primary endpoint was identification of MTD/RP2D, secondary endpoints included toxicity, efficacy, pharmacokinetic interactions, and pharmacodynamic studies. Results: 18 patients (67% female; median age 67.5 (41-74)), 16 of whom had AML, were treated at 5 dose levels (belinostat 800-1000mg/m2, pevonedistat 20-50mg/m2), no dose limiting toxicities were noted. Average number of prior lines of therapy was 3. Most Grade 3 or 4 toxicities were hematologic (Table). Maximum number of cycles reached was 8. Best response was stable disease in four patients, and CR in one patient. The remainder had progressive disease or were not evaluable. Most common reason for discontinuation was disease progression (67%), 11% treatment ended per protocol criteria, 6% pursued alternative therapy, 6% due to side effects. The patient achieving CR was a 54 year old female with BRAF and TET2 mutation, primarily refractory to 7+3 and also unresponsive to second line azacitidine and venetoclax. After CR, she received an allogeneic stem cell transplant and remains in remission with 2 years of follow up. Conclusions: The combination of pevonedistat plus belinostat is safe in adult R/R AML with a manageable, primarily hematologic profile, and modest but notable activity in this heavily treated population. This regimen may be effective as a bridge to transplant in some patients. MTD was not reached in this study. Clinical trial information: NCT03772925 . [Table: see text]