bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of the Optum Clinicogenomics Solid Tumor Database and the SEER Population-Based Cancer Registry.
Authors: Woodward Alexa , Mohanty Pallavi , Yuan Tze-An , Liao Yun , Brenton Ashley 
Published: June 2023

6635 Background: Real-world data (RWD) and real-world evidence (RWE) are increasingly utilized across a range of research and regulatory applications, including biomarker discovery, risk stratification, external control arms, and post-market surveillance. Two-thirds of FDA approvals in 2021 utilized genomic data and the growing interest in targeted therapies will likely continue this trend. While genomics or any one type of RWD alone yields an incomplete view of the patient journey, Optum’s clinicogenomic data links de-identified longitudinal clinical and claims data to next-generation sequencing (NGS) results. Ensuring the value of this data requires identifying and limiting biases and maximizing diversity. Methods: To evaluate the robustness and representativeness of Optum’s Clinicogenomic Solid Tumor Database, we compared demographic and clinical characteristics to the Surveillance, Epidemiology and End Results (SEER) database across 16 solid tumor types. Variables of interest included age at diagnosis, sex, self-identified race, year of diagnosis, and metastatic status. The Optum data was derived from clinical data that includes 156 million lives and claims data that covers 95 million lives. The solid tumor sub-cohort used for this analysis included 157,164 patients diagnosed between January 1, 2011, and December 31, 2021 with linked broad-panel NGS results. SEER Incidence Data included patients diagnosed between January 1, 2011, and December 31, 2018. Using the Optum data, we also report average continuous enrollment and sequential testing frequency across all solid tumor types. Results: The overall distributions of age at diagnosis, sex and race were similar across all cancer types, with a few exceptions. On average, SEER had a larger proportions of patients 80 years and older (15% vs 7.2%, all solid tumors) and of Asian race (7.1% vs 3.2%, all solid tumors). Cancer diagnoses in the Optum data increased year over year corresponding with the increasing availability and uptake of genetic testing in oncology, while the SEER data was equally distributed across all years. The average continuous enrollment for solid tumor patients was 8.1 years in the Optum data, and 13% of patients had sequential testing results from >1 time point. Conclusions: Given the increased reliance on RWD and RWE as part of the drug development and regulatory approval processes, ensuring the representativeness of clinicogenomic databases is paramount. This analysis of general patient characteristics across the Optum Clinicogenomics and SEER solid tumor databases found largely similar distributions of key variables. Observed differences between these two representative databases reflect the genetic testing landscape in oncology and provide the opportunity to investigate disparities related to accessing genetic services, corresponding targeted treatment options, and health outcomes.
Disparity in regional recruitment across global cancer trials: A meta-analysis.
Authors: Asghar Noureen , Naqvi Syed Arsalan Ahmed , Bibi Arifa , Ayaz Ahsan , Khakwani Kaneez Zahra Rubab , Prasad Aishwarya , Raza Umar , Thirumalareddy Joseph , Mirza Mohsin , Florez Narjust , Kamran Sophia C. , Riaz Irbaz Bin 
Published: June 2023

6636 Background: Equitable regional enrollment in clinical trials is critical to addressing global inequities in health care outcomes. Therefore, we quantified disparities in regional recruitment in global cancer trials. Methods: Phase II/III clinical trials in prostate (PC), breast (BC), colorectal (CRC) and lung cancer (LC), and reporting regional recruitment were identified from Medline. Global regions were defined as North-(NA) and South- America (SA), Europe (EU), Africa (AF), Asia (AS), and Australia (AU). For multi-regional trials, enrollment incidence ratios (EIR) which compare region-wise trial enrollment against global estimates of region-wise specific cancer incidence obtained from Global Burden of Disease 2019 database. Trial-level EIRs were pooled using random-effects meta-analysis. A pooled EIR of < 1.0 indicates underrepresentation of a particular region in clinical trial enrollment compared to the actual burden of the specific cancer in that region. Statistical analyses were conducted in R v4.1.2. Results: Of the total 2125 trials identified, 1681 (79.1%) trials with 691,800 participants reported information regarding regional recruitment. Among those, only 1400 (65.9%) trials reported proportions of patients from pre-defined regions. A total of 1231 (57.9%) trials were single-regional recruiting patients from EU (589; 47.8%), NA (329; 26.7%), AS (295; 23.9%), AU (10; 0.8%), AF (4; 0.3%), and SA (4; 0.3%). There was significant underrepresentation of patients from AS (EIR: 0.47; 95% CI: 0.41-0.54) in cancer clinical trials. This was consistent across different cancers: PC (0.49; 0.35-0.71), BC (0.63; 0.43-0.94), CRC (0.63; 0.43-0.94), LC (0.39; 0.30-0.50). Similarly, there is a trend of under-representation of patients from AF (0.67; 0.43-1.04). Consistently, patients from were under-represented in PC (0.43; 0.24-0.77) and LC (0.26; 0.09-0.79) trials. Patients from NA (1.27; 1.08-1.51), EU (1.64; 1.57-1.72), and AU (5.41; 3.90-7.51) were significantly over-represented in multi-regional cancer clinical trials. The results are provided in table. Conclusions: There is suboptimal reporting of region-wise enrollment in cancer clinical trials. Representation of Africa and Asia in cancer clinical trials appears to be less than their expected share based on their burden of cancer incidence. [Table: see text]
Oncologists’ receipt of pharmaceutical industry payments and use of non-recommended and low-value cancer care services.
Authors: Mitchell Aaron Philip , Dusetzina Stacie B , Mishra Meza Akriti , Trivedi Niti U. , Bach Peter Brian , Winn Aaron N 
Published: June 2023

6639 Background: Personal payments from the pharmaceutical industry to US physicians are common and influence physician practice. Prior studies have found that industry payments sway physicians’ selection among effective, medically appropriate treatments. However, whether industry payments may be associated with non-recommended and low-value care has not been assessed. The objective of this study was to estimate the association between oncologists’ receipt of industry payments and use of non-recommended and/or low-value (NR/LV) interventions. Methods: Population-based cohort study using fee-for-service Medicare claims and Open Payments records of industry payments. We identified four NR/LV cancer interventions: 1) denosumab for castrate-sensitive prostate cancer; 2) GCSF for patients at low risk for neutropenic fever; 3) nab-paclitaxel instead of paclitaxel for breast and lung cancer 4) branded drug instead of a generic or biosimilar. Study sample: Medicare beneficiaries with an incident cancer diagnosis (identified by new occurrence of a cancer diagnosis code in proximity to claims for cancer treatment) from 2014-2019. We applied additional requirements as appropriate to identify four sub-cohorts, corresponding to patients at risk for each of the NR/LV treatments, and identified the treating oncologist using claims. The primary exposure was receipt, by a patient’s oncologist, of any industry payments for the corresponding NR/LV treatment of interest, within 365 days before the patient’s index cancer date. The primary outcome was receipt of the corresponding NR/LV treatment. We fit general linear models controlling for patient characteristics and calendar year. To assess robustness, we also accounted for physician-level fixed effects in separate models. Results: Cohort sizes were: denosumab N = 9,799; GCSF N = 271,485; nab-paclitaxel N = 86,394; branded drug N = 13,386. Controlling for patient characteristics and calendar year, industry payment was associated with an increase in the absolute prevalence of denosumab (+17.5% [95%CI:15.3 to 19.7%]), GCSF (+5.8% [95%CI:5.4 to 6.1%]), and nab-paclitaxel (+7.6% [95%CI:7.1 to 8.1%]) use, but lower branded drug use (-4.6 [95%CI:-5.8 to -3.3]). In physician-level fixed effects models, industry payment was associated with increased denosumab (+7.4% [95%CI:2.5 to 12.2%]) and nab-paclitaxel (+1.7% [95%CI:0.9 to 2.5%]) use, but not with GCSF (+0.4% [95%CI:-0.3 to 1.1%]) or branded drugs (+1.2% [95%CI:-5.8 to 8.3%]). Conclusions: Recent receipt of industry payments by physicians was associated with increased use of several forms of NR/LV cancer treatment. These findings raise quality-of-care concerns regarding physician-industry financial relationships. Additional work is needed to further explore the causal relationship between payments and non-recommended treatments, and between payments and patient outcomes.
The role of private insurance characteristics in the out-of-pocket costs of patients with multiple myeloma.
Authors: Gasoyan Hamlet , Rothberg Michael B. 
Published: June 2023

6641 Background: Over the past two decades, the major advances in the treatment of multiple myeloma have improved overall survival considerably. High costs of novel medications and patient out-of-pocket costs were suggested to have a role in treatment disparities but available data on total- and patient-out-of-pocket costs are dated. We examined the costs in privately insured patients with newly diagnosed multiple myeloma in the first year after the diagnosis, based on insurance plan characteristics. Methods: This retrospective study used the IBM MarketScan Commercial Database for the years 2011–2019, which consists of medical and prescription medications data from 120+ large employers and 40+ health plans in the US. The primary outcome variables were total- and patient out-of-pocket costs during 1 year after the index diagnosis. Results: 5,487 privately insured adults with an index multiple myeloma diagnosis during 2012-2018 were identified. Approximately 41% (n=2,240) of the study population received bortezomib, 38.6% (n=2,117) received lenalidomide, and 5.7% (n=314) received carfilzomib during 1 year after the index diagnosis. The median total cost of care in the first year after multiple myeloma diagnosis increased from $133,938 (interquartile range, $19,770 – $292,501, expressed in 2018 USD) in patients diagnoses in 2012 to $252,559 ($33,089 – $380,662) in patients diagnoses in 2018. The median patient out-of-pocket costs were $3,147 (interquartile range $1,562 - $5,441, 2018 USD) in patients diagnosed in 2012 and $3,711 ($1,756 – $6,466) in patients diagnosed in 2018. Among patients diagnosed in 2018, the median patient out-of-pocket cost was $1,706 ($902 – $2,873) for patients with low out-of-pocket cost plans, $3,428 ($1,794 – $6,371) for those with average out-of-pocket cost plans, and $5,623 ($3,517 - $7,810) for patients with high out-of-pocket cost plans. Conclusions: While the total cost of care in the first year after multiple myeloma almost doubled during the study period, the patient out-of-pocket costs remained relatively stable. The protections imposed by the Affordable Care Act are likely key in preventing surges in patient out-of-pocket costs. Additional legislative action could help curb the price increases for multiple myeloma medications. [Table: see text]
Assessment of price variation in colorectal cancer screening procedures at US hospitals.
Authors: Paranjpe Ishan , Sharma Pranav , Wei Chen , Puram Vikram , Kamat Samir , Khaki Ali Raza 
Published: June 2023

6652 Background: Following the 2021 Hospital Price Transparency Final Rule, US hospitals were mandated to publish their insurer-negotiated prices. We identified factors contributing to price variability of colorectal cancer (CRC) screening procedures across the US. Methods: We compared prices of colonoscopy, flexible sigmoidoscopy, CT colonography, fecal occult blood test, fecal immunochemical test, and Cologuard across U.S. hospitals using the Turquoise dataset (N = 6,378). Psychiatric, rehabilitation, and pediatric hospitals were excluded. Prices in the top and bottom 1% were also excluded to minimize the effect of outliers. Prices were adjusted by the Medicare Geographic Price Index to account for regional variability. We then compared prices across several subgroups, including National Cancer Institute (NCI) designated hospitals, teaching hospitals, and investor owned hospitals. Significance was assessed using the Kruskal-Wallis test. To quantify price variability across insurance plans within a hospital, we defined the within-center-ratio as the 90th percentile rate at a hospital divided by the 10th percentile rate. To quantify variability across hospitals, the across-center-ratio was defined as the 90th percentile median rate across all hospitals divided by the 10th percentile median rate. Results: 1,460 hospitals reported commercial prices for colonoscopy with a median commercial price of $1,867 (IQR: $1,208 - $2,689). For colonoscopy, the within center ratio was 2.5 (IQR: 1.5 – 3.8) and the across-center ratio was 6.2. Prices for other procedures are provided in the table. Compared to non-investor owned hospitals, prices of colonoscopy ($2,082 vs $1,787, P <0.001) and flexible sigmoidoscopy ($2,022 vs $1,289, P <0.001) were significantly higher at investor owned hospitals. Furthermore, across investor classes, hospitals with >5% ownership from private equity firms had the highest median price for both colonoscopy ($2,898), and flexible sigmoidoscopy ($2,697). We did not find significant differences in price by NCI designation, academic teaching center affiliation, overall hospital mortality, overall hospital readmission rate, or urban/rural location. Conclusions: CRC screening procedure prices vary significantly both within and across hospitals. Private equity and other investor owned hospitals had significantly higher prices compared to non-investor owned hospitals. [Table: see text]
Specialty cancer care and survival in AYA ALL: A U.S. multi-state analysis.
Authors: Muffly Lori S. , Miller Kate , Maguire Frances Belda , Li Qian , Parsons Helen M. , Keegan Theresa 
Published: June 2023

7008 Background: Unlike children with acute lymphoblastic leukemia (ALL) who receive cancer care almost exclusively from pediatric oncologists at specialized cancer centers (SCC; defined here as National Cancer Institute and/or Children’s Oncology Group designated cancer centers), adolescents and young adults (AYAs; 15-39 years) in the United States receive care in a variety of settings. Using state-wide population-based data, we sought to describe the health care delivery settings in which AYAs with ALL receive treatment and determine associations between front-line treatment at an SCC and leukemia-specific and overall survival (LSS/OS). Methods: We used data from the 2004-2018 California (CA), New York (NY), and Texas (TX) state cancer registries to identify front-line treatment setting of AYAs newly diagnosed with ALL. Multivariable logistic regression models evaluated characteristics associated with receiving treatment at an SCC. Cox proportional hazards regression models evaluated the associations with LSS/OS. All models were adjusted for gender, age, sex, race/ethnicity, socioeconomic status, insurance, and diagnosis year. Results: The cohort was comprised of 2283 (CA), 795 (NY), and 955 (TX) AYAs with ALL. Across all states, approximately 70% were ³18 years and 65% were male. Race/ethnicity varied by state: a majority in CA (63%) and TX (64%) were Hispanic, while most in NY were non-Hispanic White (NHW) (50%). Health insurance coverage also varied: most in CA were publicly insured (48%), while most in NY were privately insured (54%); TX had the highest rate of uninsured (18%). Treatment at an SCC occurred in 48.2% (CA), 44.4% (NY), and 19.5% (TX) of AYAs, increasing in CA and NY over time, but remaining unchanged in TX. Among all states, older age and uninsured status were significantly associated with lower odds of treatment at an SCC. In both CA (OR 0.58, 95% CI 0.45-0.74) and TX (OR 0.55, 95% CI 0.35-0.86), Hispanic patients had significantly lower odds of treatment at an SCC than NHW. In NY (OR 0.45, 95% CI 0.31-0.67) and TX (OR 0.49, 95% CI 0.3-0.8), publicly insured AYAs had significantly lower odds of receiving treatment at an SCC than those with private insurance. Front-line treatment at an SCC was significantly associated with both superior LSS (HR 0.73, 95% CI 0.63-0.85) and OS (HR 0.73, 95% CI 0.63-0.85) in CA and superior LSS (HR 0.70, 95% CI 0.51-0.94) and OS (HR 0.61, 95% CI 0.45-0.83) in TX; a non-significant association was seen in NY (LSS: HR 0.86, 95% CI 0.65-1.12; OS: HR 0.83, 95% CI .64-1.08). Conclusions: Only 20-50% of newly diagnosed AYA ALL patients receive front-line treatment at SCCs, with age, race/ethnicity, and insurance type independently influencing AYA ALL care setting. We show that the treatment of ALL at an SCC is associated with superior survival, highlighting the importance of statewide and national policy efforts to improve access and reduce inequities in AYA ALL.
Outcomes of 10-day decitabine with venetoclax for AML.
Authors: Coltoff Alexander , Baratam Praneeth , Green Kimberly Michelle , Davis James A. , Smith Deidra , Gaffney Kelly , Dougherty Elizabeth , Milligan Laura 
Published: June 2023

7022 Background: Venetoclax (VEN) + a hypomethylating agent (HMA) has improved outcomes for patients with acute myeloid leukemia (AML). VIALE-A showed improved overall response rate (ORR) and overall survival (OS) with VEN + HMA in newly diagnosed AML (ND AML); the complete remission (CR) rate was 36.7% and the median OS was 14.7 months. Later, DiNardo et al. reported a trial of 10-day decitabine (DEC10) + VEN with a CR rate of 65.7% and a median OS of 18 months in a ND AML cohort. We report real world outcomes of VEN + DEC10 for AML induction. Methods: We reviewed 82 adult patients treated with VEN + DEC10 at our institution. Patients received 1 or 2 cycles of VEN + DEC10 followed by additional cycles of VEN + 5-day decitabine (DEC5) per physician discretion. Results: Twenty-four patients had ND AML, 28 had secondary AML (sAML) and 30 had relapsed/refractory (R/R AML) with a median age (years) of 72, 70, and 59 in each group, respectively. Cytogenetics were poor-risk in 13 ND patients (54.2%), 14 sAML patients (50%), and 17 R/R patients (56.7%). Twenty-two patients (26.8%) had TP53 mutations. Six patients (7.3%) received rasburicase. Neutropenic fever was seen in 46 patients (56.1%), and 34 (41.5%) had documented infections. Thirty-eight patients (46.3%) were re-hospitalized during cycle 1 (C1), at a median of 22 days after starting. The median time from the start of C1 to C2 was 41 days. Thirty-day mortality was 7.3%. In ND AML, ORR was 91.7% and composite CR rate (CRc; CR + CR with incomplete hematologic recovery[CRi]) was 75%. Nine of 15 patients (60%) in CR were negative for measurable residual disease (MRD-). In sAML, ORR was 53.6% and CRc rate was 50% (35.7% MRD- CR). CRc was achieved by eight of 16 (50%) untreated sAML patients vs six of 12 (50%) who were previously treated. In R/R AML, ORR was 56.7% and CRc rate was 43.3% (53.8% MRD- CR). TP53-mutated AML had an ORR of 59% and a CRc of 50%. Median OS was 5.5 months in TP53-mutant AML, 7.4 months in R/R AML, and was not reached in ND AML or sAML. Fifteen patients (18.3%) received an allogeneic transplant (3 ND, 3 sAML and 9 R/R) in MRD- CR (n = 11), MRD+ CR (n = 2) and CRi (n = 2). At a median of 263 days post-transplant, there were 3 relapses and the median OS was not reached. Conclusions: VEN + DEC10 compared favorably with published data, yielding high ORR, CR, and MRD- CR rates in ND AML. CR rate for R/R AML with VEN + DAC10 was similar to that for ND AML in the VIALE-A trial. These results warrant a prospective, randomized trial of VEN + DEC10 vs VEN + DEC5 in AML. [Table: see text]
BOS-371, a monoclonal antibody against IL1RAP: Characterization in preclinical models of AML.
Authors: West Kip A , Kumar Sanjay , Scott Martin , Emery John G , Steidl Ulrich G , Narayanagari Swathi-Rao , Mitchell Kelly , Ren Fang , Ying Hua , Fei Qi , Yang Teddy , Svensson Eric , Rosen Galit 
Published: June 2023

7030 Background: IL1 receptor accessory protein (IL1RAP) is a cell surface protein overexpressed on leukemia stem cells (LSC) and progenitors in AML, CML and high-risk MDS. It is an indispensable co-receptor for the IL1 superfamily, but its role reaches beyond anti-apoptotic pathways. IL1RAP directly interacts with and potentiates signaling of FLT3 and c-KIT which have significant roles in AML pathogenesis. High IL1RAP is correlated with poor prognosis and IL1 blockade attenuates expansion of LSCs. Thus, targeting IL1RAP has emerged as a promising immunotherapeutic approach for myeloid malignancies. BOS-371 is a humanized monoclonal antibody targeting IL1RAP that has been Fc-engineered to enhance its capacity to induce antibody directed cell cytotoxicity (ADCC) and deplete IL1RAP-expressing AML cells. Methods: The preclinical activity of BOS-371 was characterized using multiple assays. In vitro analysis included: binding affinity in IL1RAP-expressing cell lines; inhibition of IL1-dependent signaling as measured by IL1a -stimulated secretion of IL6 from MRC5 lung cancer cells; measurement of ADCC in co-cultures of human NK cells with either IL1RAP-expressing cell lines or primary AML cells; and cell growth by monitoring metabolic activity of primary AML cells. In vivo efficacy of BOS-371 was determined in AML models: MV4-11 and ML2 cells (CDX) implanted in NOG and NOD-SCID mice, respectively, and patient-derived (PDX) leukemia cells implanted in NOG mice. Results: BOS-371 binds with high affinity to IL1RAP-expressing cells (average EC50 337pM) leading to potent inhibition of IL1 signaling (IC50 600pM). Co-culture assays in the presence of BOS-371 showed potent induction of ADCC with an EC50 of 60-70pM (cell lines) or 4-11pM (primary cells) and 80-100% cell lysis (both cell lines and primary cells). The ability of BOS-371 to impact AML cell growth exclusively through inhibition of IL1 signaling was measured in a panel of 15 primary AML samples. Incubation with BOS-371 led to IC50s ranging from 20-700nM in responsive samples. Evaluation of BOS-371 activity in vivo showed that administration of BOS-371 resulted in significant anti-leukemic activity. In CDX studies, BOS-371 treatment led to > 50% decrease in systemic disease and engraftment in bones and organs. The results observed in CDX AML models were reproduced in PDX mouse models of AML, where decreases in both peripheral ( > 70%) and bone marrow ( > 50%) disease burden in response to BOS-371 were observed. Conclusions: These findings demonstrate that BOS-371 binds with high affinity to IL1RAP, potently inhibits IL1 signaling and induces ADCC, leading to anti-leukemic activity in vitro and in vivo. The preclinical results support the clinical investigation of BOS-371 for the treatment of myeloid malignancies. A Phase 1 trial is currently in development.