bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 and hematologic diseases: Risk factors and long-term follow-up of CHRONOS19 Registry.
Authors: Zakurdaeva Kristina , Gavrilina Olga A. , Vasileva Anastasia N. , Dubov Sergei , Dubov Vitaly S. , Butaev Lev S. , Sukhareva Alena M. , Gavrilova Lubov V. , Toropova Inessa Yu. , Popova Marina O. , Siniaev Aleksandr A. , Kaplanov Kamil D. , Petrenko Andrei A. , Ochirova Oksana I. , Chelysheva Ekaterina , Chabaeva Yulia A. , Sveshnikova Yulia V. , Kunst Mikhail A. , Rakhmani Anzhelika F. , Savchenko Valery G. 
Published: June 2021

e18715 Background: Pts with hem diseases are at high risk of COVID-19 severe course and mortality. Emerging data on risk factors and outcomes in this patient population is of great value for developing strategies of medical care. Methods: CHRONOS19 is an ongoing nationwide observational cohort study of adult (≥18 y) pts with hem disease (both malignant and non-malignant) and lab-confirmed or suspected (clinical symptoms and/or CT) COVID-19. Primary objective was to evaluate treatment outcomes. Primary endpoint was 30-day all-cause mortality. Long-term follow-up was performed at 90 and 180 days. Data from 14 centers was collected on a web platform and managed in a deidentified manner. Results: As of data cutoff on January 27, 2021, 575 pts were included in the registry, 486 of them eligible for primary endpoint assessment, n(%): M/F 243(50%)/243(50%), median age 56 [18-90], malignant disease in 452(93%) pts, induction phase/R/R/remission 160(33%)/120(25%)/206(42%). MTA in 93(19%) pts, 158(33%) were transfusion dependent, comorbidities in 278(57%) pts. Complications in 335(69%) pts: pneumonia (67%), CRS (8%), ARDS (7%), sepsis (6%). One-third of pts had severe COVID-19, 25% were admitted to ICU, 20% required mechanical ventilation. All-cause mortality at 30 days – 17%; 80% due to COVID-19 complications. At 90 days, there were 14 new deaths: 6 (43%) due to hem disease progression. Risk factors significantly associated with OS are listed in Tab 1. In multivariate analysis – ICU+mechanical ventilation, HR, 53.3 (29.1-97.8). Acute leukemias were associated with higher risk of death, HR, 2.40 (1.28-4.51), less aggressive diseases (CML, CLL, MM, non-malignant) – with lower risk of death, HR, 0.54 (0.37-0.80). No association between time of COVID-19 diagnosis (Apr-Aug vs. Sep-Jan) and risk of death. COVID-19 affected treatment of hem disease in 65% of pts, 58% experienced treatment delay for a median of 4[1-10] weeks. Relapse rate on Day 30 and 90 – 4%, disease progression on Day 90 detected in 13(7%) pts; 180-day data was not mature at the time of analysis. Several cases of COVID-19 re-infection were described. Conclusions: Thirty-day all-cause mortality in pts with hem disease was higher than in general population with COVID-19. Longer-term follow-up (180 days) for hem disease outcomes and OS will be presented. [Table: see text]
Mental health needs among parents of children with cancer: A commercial claims data analysis.
Authors: Hu Xin , Gilleland Marchak Jordan , Ji Xu 
Published: June 2021

e18722 Background: Caring for a child diagnosed with cancer may adversely affect mental health (MH) of parents. However, little is known about MH care needs among parents of pediatric cancer patients. This study examined the patterns of MH care for parents of children diagnosed with cancer, as compared to parents of children without cancer. Methods: We used MarketScan® Commercial Database to identify continuously-insured parents of children receiving therapy for leukemia, lymphoma, central nervous system, bone, or gonadal cancers (aged ≤21 years at diagnosis) in 2009-2017. We also identified parents who matched eligibility criteria but had no child with cancer (with a randomly-assigned, fictitious date of cancer diagnosis) as controls. Outcomes included parents’ visits related to a MH disorder (anxiety, depression, substance use disorder [SUD], post-traumatic stress disorder [PTSD]) during six months before to 12 months after their child’s cancer diagnosis. Multivariable regressions were estimated to compare MH visits between 9,870 parents of pediatric cancer patients and 3,396,097 parents in the control group, adjusting for sociodemographic factors (parents’ age and sex, rurality, region, number of children in household) and presence of MH history. Among parents of pediatric cancer patients, we explored sociodemographic factors, MH history, and clinical factors (children’s cancer types, age at diagnosis, therapeutic modalities) associated with MH-related visits in multivariable regression analyses. Results: While the likelihood of MH history was similar between the two groups, a higher proportion of parents caring for cancer patients than controls had any visits related to anxiety (13.1%% vs. 9.5%), depression (9.6% vs. 7.5%), PTSD (0.5% vs. 0.4%), or any MH disorders (22.0% vs. 17.6%). These differences persisted in adjusted analyses. For example, parents of cancer patients were 24%, 37%, and 27% ( p-values < 0.001) more likely than controls to have any MH visits, anxiety-related visits, and depression-related visits, respectively. No difference was observed in SUD-related visits. Among MH care utilizers, no significant difference was observed in the number of MH visits. Among parents of cancer patients, those with MH history, mothers (vs. fathers), and parents of children with bone cancer (vs. leukemia) were more likely to have any MH visits ( p-values < 0.05). Parents whose children received surgery only and those with ≥3 children in household were less likely to have any MH visits ( p-values < 0.05). Conclusions: Parents of pediatric cancer patients have significantly higher needs for MH care as compared to the general parent population. Our finding underlines the importance of future interventions toward targeted MH counseling and supportive strategies for vulnerable parent groups, such as mothers and those caring for children undergoing more complex treatment plans.
ctDNA analysis in patients with cancer of unknown primary and its value in guiding targeted treatment when combined with predicted cancer types by 90-gene reverse-transcription polymerase chain reaction assay.
Authors: Liu Xin , Jiang Shiyu , Zhang Xiaowei , Zhou Xiaoyan , Luo Zhiguo , Hu Xichun 
Published: June 2021

e18730 Background: No targeted agents except for drugs against NTRK fusion, dMMR/MSI-H or TMB-H are recommended for the treatment of cancer of unknown primary (CUP), despite of the occurrence of multiple actionable mutations identified by NGS. We aimed to explore the characteristics of circulating tumor DNA (ctDNA) and its value in guiding targeted treatment in combination with predicted cancer types by 90-gene reverse-transcription polymerase chain reaction assay for tissue origin. Methods: 172 treatment-naïve CUP patients with ctDNA testing were retrospectively included between April 2017 and Oct 2020. Of them, 98 patients had primary site predicted. Genetic alterations were reclassified based on their predicted primary site and the oncoKB scale. 153 patients treated with the first-line therapy and available survival data were used to explore prognostic value of detected genetic alterations in ctDNA. Results: We identified 82.6% (142/172) of patients had alterations detected, with the most commonly seen mutations of TP53 (51%), ARID1A (11%), KRAS (10%), RB1 (9%), APC (8%), PI3KCA (8%) and NFE2L2 (7%). The most commonly observed actionable mutations were PIK3CA (n=14, 9.8%), ERBB2 (n=7, 4.9%), BRAF (n=6, 4.2%), MET (n=6, 4.2%) and EGFR (n=5, 3.5%). After introducing predicted primary site in the 98 patients, 6.1% (n=6) of patients upgraded to a Level 1 alteration, 1.0% (n=1) to a Level 2 alteration (Table). In these 7 patients, only one patient with predicted lung cancer and EGFR 19 del received gefitinib with partial response for 5+ months. In multivariate analysis, NFE2L2 (hazard ratio [HR] = 2.96, 95%CI=1.32-6.61, P = .008) and CDKN2A mutation (HR = 2.50, 95%CI=1.26-4.96, P = .009) were independently associated with shorter PFS. Furthermore, NFE2L2 (HR = 4.96, 95%CI=1.98-12.43, P ＜ .001) and CDKN2A mutation (HR = 4.84, 95%CI=1.63-14.40, P = .005) were correlated with worse OS. Conclusions: This is the first attempt to integrate ctDNA sequencing and gene expression profiling for tissue of origin in OncoKB classification schema, resulting in 7.1% (7/98) of the genetic alterations reclassified to level 1 or 2, which might identify patients benefiting from corresponding targeted treatment. NFE2L2 and CDKN2A mutations in ctDNA were associated poor prognosis.[Table: see text]
Barriers to next-generation sequencing despite increased utilization: U.S. physician survey results.
Authors: Kaminski Allysen , Szamreta Elizabeth A. , Shah Ruchit , Ning Ning , Aggarwal Jyoti , Hussain Arif , Adeboyeje Gboyega 
Published: June 2021

e18754 Background: The value of using next-generation sequencing (NGS) to inform oncology care decisions is increasingly apparent, yet many challenges persist that may inhibit routine adoption of NGS into clinical care. The purpose of this study was to identify existing barriers to NGS access and possible solutions from the physician perspective. Methods: A cross-sectional online survey, including both closed- and open-ended questions, was sent to a nationally representative sample of oncologists/hematologists, surgeons, and pathologists (N=201). The survey gathered information on physician demographics, practice characteristics, perceived barriers to testing, and strategies for increasing adoption. Results: Over 99% of physicians, 20.5% of whom worked in an academic setting, reported using NGS in the past 12 months, and 73.0% used NGS always or most of the time. Despite this high utilization, 80.1% of physicians experienced at least one barrier to testing. Reimbursement challenges were among the top reported barriers (87.5%), followed by a lack of knowledge of NGS testing methodologies (81.0%), and lacking evidence of clinical utility (80.1%). These barriers were more likely to be reported by pathologists and surgeons compared to oncologists/hematologists. Potential strategies for addressing these differed by specialty: While most oncologists/hematologists (84.0%) reported increased NGS coverage as a top priority, most surgeons (88.0%) prioritized improved multidisciplinary communications, and most pathologists (84.4%) prioritized increased access to educational content on cancer genomics and resources for physicians. Conclusions: Despite the high utilization of NGS among the surveyed stakeholders, several barriers, including limited reimbursement, knowledge gaps, and lack of clinical utility evidence were reported that may impact clinical optimization. Interestingly, the perceived barriers to NGS use varied by specialty, which may be driven by the differing roles these specialists play in patient management. Oncologists/hematologists, who are more likely involved in long-term patient care, were most concerned with identifying strategies to improve coverage of technology, whereas surgeons and pathologists were most concerned with strategies that would improve understanding and education. This research highlights the need for multi-faceted strategies to address barriers to NGS adoption. [Table: see text]
Survey study of barriers to evidence-based decision-making in oncology care using next-generation sequencing.
Authors: Szamreta Elizabeth A. , Kaminski Allysen , Shah Ruchit , Ning Ning , Aggarwal Jyoti , Hussain Arif , Adeboyeje Gboyega 
Published: June 2021

e18757 Background: Next-generation sequencing (NGS) has the potential to accelerate precision medicine in oncology by informing efficient and improved clinical treatment decision-making. However, discussions on the utility of NGS in clinical practice are ongoing. This survey study examined clinical utility barriers to adoption of NGS into oncologic care. Methods: A cross-sectional online survey was sent to a nationally representative sample of oncologists/hematologists, surgeons, and pathologists (N=201). The survey gathered information on physician demographics, practice characteristics, perceived barriers to NGS testing, and potential strategies for increasing adoption. Results: Almost all physicians in the sample (99.5%) reported using NGS. Physicians reported the following aspects of NGS as the most valuable: ability to guide decision-making (73.1%), more accurate identification of corresponding treatment (56.7%), comprehensive genomic coverage (54.2%), efficient technology with faster turnaround time (49.8%), and more accurate diagnosis or prognosis (41.3%). Physicians reported that NGS results guided treatment decisions for 63% of patients (Range: 2% - 100%). Over 85% of physicians reported that confidence in interpreting results and availability of clinical guidelines were important in undertaking NGS. Correspondingly, limited evidence of clinical utility was a top barrier to testing (80.1%), with pathologists and surgeons more likely than oncologists/hematologists to consider this. Overall, 76% of physicians shared that strategies to alleviate these clinical utility barriers included increased evidence, standardized guidelines, and interpretation support. Conclusions: Given the high uptake of NGS testing in this physician sample, but the lower rates of application of test results to guide treatment, the clinical impact of NGS may not be fully optimized. This discrepancy highlights the ongoing need for real-world evidence to better understand and further optimize the evolving role of NGS in the context of the overall management of the cancer patient. [Table: see text]
Real-world risk of anosmia with cancer directed systemic therapy: A pharmacovigilance assessment using FDA Adverse Events Reporting System (FAERS) database.
Authors: Kaur Anahat , Wang Shuai , Yu Arlene , Elrafei Tarek N. , Steinberg Lewis , Kumar Abhishek 
Published: June 2021

e18790 Background: Anosmia is a rare and under-reported adverse event associated with the use of several oncologic drugs. Instances of olfactory disturbances following administration of chemotherapeutic agents have been sporadically documented in case reports and case series. We aimed to conduct a more comprehensive study to generate signal for anosmia as adverse effect of drugs used for oncologic indications. Methods: The United States Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database, a pharmacovigilance database, was used to extract data. All reported cases of anosmia in the database were filtered for an indication of cancer. Descriptive analysis was conducted using SPSS 26. Results: Total 10250 cases of anosmia were extracted from FAERS database. Out of these, cancer as an indication for medication use was noted in 139 cases. Some of the most common suspect medications exclusively associated with more than one case of anosmia were palbociclib (n=16), enzalutamide (13), pazopanib (8), cabozantinib (8), letrozole (6), leuprolide (5), niraparib (5), rucaparib (4), tamoxifen (4), capecitabine (3), everolimus (3), anastrazole (2), exemestane (2), zoledronic acid (2), vandetanib (2) and vismodegib (2). Detailed description of medications with highest number of reported cases is listed in Table. Median age at diagnosis was 66 years (interquartile range 58-71). Anosmia was reported more commonly in females (64% ) as compared to males (33.8%). Reactions were reported to the FDA more commonly by consumers (56.8%) as compared to healthcare professionals (40.3% cases). Out of 139 patients with anosmia, 93 (66.9%) had concomitant ageusia, 8 (5.7 %) had dysgeusia and 6 (4.3%) patients had neuropathy. Conclusions: This study demonstrates a signal for anosmia as side effect in patients receiving select oncologic medications based on the FAERS database. It is worth noting that none of the suspect medications identified in this study have anosmia listed as known adverse reaction on accompanying package insert. Further studies need to be conducted to confirm if causal relationship exists between use of these drugs and olfactory function compromise. [Table: see text]
Cost-effectiveness of atezolizumab and bevacizumab in advanced hepatocellular carcinoma.
Authors: Patel Kishan , Stein Stacey , Luther Janki , Huntington Scott F. 
Published: June 2021

e18829 Background: The IMbrave150 trial found that atezolizumab and bevacizumab significantly prolonged progression-free survival (PFS) and overall survival (OS) in patients with locally advanced metastatic or unresectable hepatocellular carcinoma (HCC), compared to sorafenib. However, atezolizumab and bevacizumab are costly treatments and are administered indefinitely until disease progression. Therefore, it is unclear whether atezolizumab-bevacizumab is cost-effective in this clinical setting. Methods: We constructed a partitioned survival model to compare the costs and effectiveness of atezolizumab-bevacizumab to sorafenib in advanced HCC. PFS and OS curves for each treatment strategy were derived from the IMbrave150 trial using parametric survival modeling. The utility of each health state and the costs of treatment, adverse events, and terminal care were derived from literature and Medicare fee schedules. We calculated the incremental cost-effectiveness ratio (ICER) of atezolizumab-bevacizumab from a US healthcare perspective, using a lifetime horizon, an annual discount rate of 3%, and a willingness-to-pay threshold of $150,000/quality-adjusted life year (QALY). One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of model conclusions. Results: Atezolizumab-bevacizumab was associated with an incremental cost of $102,648 and an incremental effectiveness of 0.42 QALYs compared to sorafenib, leading to an ICER of $244,213/QALY (Table). The price of atezolizumab would need to be reduced by 40% (from ̃$9,400 to ̃$5,700 per dose) or the price of bevacizumab would need to be reduced by 47% (from ̃$8,400 to ̃$4,400 per dose) for atezolizumab-bevacizumab to be cost-effective compared to sorafenib. Alternatively, the price of both atezolizumab and bevacizumab would need to be simultaneously decreased by ̃21% for the combination therapy to be cost-effective. Our model was most sensitive to the hazard ratios (HR) of OS and PFS; varying the HRs across the 95% confidence interval reported in IMbrave150 (0.42-0.79) corresponded to ICERs of $137,435/QALY and $621,365/QALY, respectively. During probabilistic sensitivity analyses, >99%, 99%, and 90% of iterations produced ICERs greater than willingness-to-pay thresholds of $50,000/QALY, $100,000/QALY, and $150,000/QALY, respectively. Conclusions: Use of atezolizumab-bevacizumab for advanced HCC is unlikely to be cost-effective under current pricing. Significant price reduction of atezolizumab and/or bevacizumab would be required to reduce the ICER to a more widely acceptable value.[Table: see text]
Cost-efficiency analysis of conversion from reference pegfilgrastim to its biosimilar (pegfilgrastim-jmdb) and expanded access to food and transportation support for Medicare/Medicaid patients within the CMS Oncology Care Model.
Authors: MacDonald Karen , AlRawashdh Neda , McBride Ali , Abraham Ivo 
Published: June 2021

e18837 Background: The CMS Oncology Care Model (OCM) aims to improve quality of care and health outcomes in cancer centers at the same or lower cost. We performed cost-efficiency analyses of converting selected cancer patients (pts) from reference pegfilgrastim (PFG) to its biosimilar (PFG-jmdb); and simulated re-allocating savings to provide nutrition and transportation support to CMS beneficiaries within OCM. Methods: Incidence rates for breast, ovarian, lung, colorectal cancers and non-Hodgkin lymphoma were extracted from SEER, further stratified by age <65 (commercial insurance) or >65 (Medicare) adjusted for Medicare/Medicaid mix. Chemotherapy (CTX) rates were matched to tumor type; of these 19.4% were assumed to require PFG prophylaxis (PPX). Two models compared respectively prefilled syringe (PFS) and on-body injector (OBI) reference PFG to PFS PFG-jmdb. Cost inputs included Average Sales Price (ASP) 3Q20 for Medicare and National Average Drug Acquisition Cost (NADAC, estimated by wholesale acquisition cost (WAC)-3.9%) for Medicaid pts plus medication administration. Cost savings across various biosimilar conversion rates for CTX cycles 1-6 were translated into $100 units of healthy food or medical transportation. Results: In 2020, biosimilar conversion for the estimated 31,210 Medicare and 1,722 Medicaid pts in the 5 tumor types needing PFG PPX yielded savings of up to ̃$19M (Medicare) and ̃$20M (Medicaid). These savings could have provided a monthly $100 food or transportation check to at least 24,716 Medicare or 33,630 Medicaid pts for 6 months. Conclusions: Savings from biosimilar conversion can be re-allocated on a budget neutral basis to food and transportation support to pts with such needs. This achieves the dual OCM aim of reducing drug budgets while enhancing patient-centric support services.[Table: see text]
Cost-effectiveness of atezolizumab monotherapy versus pembrolizumab monotherapy for first-line (1L) treatment of metastatic non-small cell lung cancer (mNSCLC).
Authors: Lin Chia-Wei , Rosettie Katherine , Bilir Pinar , Celik Hazal , Abogunrin Seye , Ogale Sarika 
Published: June 2021

e18847 Background: Atezolizumab monotherapy is indicated as 1L treatment for mNSCLC patients with high programmed death ligand-1 (PD-L1) expression (≥ 50%) and without epidermal growth factor receptor or anaplastic lymphoma kinase mutations. This analysis assessed the cost-effectiveness of 1L atezolizumab monotherapy vs. pembrolizumab monotherapy for mNSCLC patients with high PD-L1 expression from a US third-party payer perspective. Methods: A Markov model with progression-free, progressive disease (PD), and death states was developed in Microsoft Excel to compare clinical and cost outcomes of atezolizumab monotherapy vs. pembrolizumab monotherapy. Efficacy, safety, and utility data were derived from systematic reviews and indirect comparisons of the IMpower110, Keynote-024, and Keynote-042 trials. Product prescribing information and clinical trials informed dosing and administration. Wholesale acquisition cost (WAC, accessed in January 2021) for drugs were used while other cost inputs were derived from publicly available fee schedules and peer-reviewed literature. The key outcome of interest was the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained. Deterministic sensitivity analysis with 20% variation and probabilistic sensitivity analyses (PSA) were performed to address uncertainties around input parameters. Results: In the base case, 1L atezolizumab monotherapy was projected to increase life expectancy for patients by 0.60 life-years (4.35 vs. 3.75) and 0.47 QALYs (3.46 vs. 2.98) over pembrolizumab monotherapy at an incremental cost of $27,947 (mean total cost: $396,811 vs. $368,864), resulting in an ICER of $58,841/QALY gained. Results of the deterministic sensitivity analysis were most sensitive to changes in discount rates for costs and care costs in the PD state. The PSA showed that the probability of atezolizumab being cost-effective at willingness-to-pay thresholds of $100,000 and $150,000 was 41% and 49%, respectively. Conclusions: First-line atezolizumab monotherapy had 0.6 life-years and 0.47 QALYs gained compared with pembrolizumab monotherapy and was estimated to be cost-effective (ICER $58,841/QALY). As the ICER falls below the US cost-effectiveness thresholds ( < $100,000-$150,000/QALY), clinicians and payers should consider atezolizumab monotherapy as a cost-effective 1L option for mNSCLC patients with high PD-L1 expression.