bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical utility of a novel non-invasive technology for monitoring severe neutropenia in anticancer therapy.
Authors: Alva Bianchi Manuel , Iwase Toshiaki , Tolosa Ortega Pablo , Justo Jiménez Pablo , Rodriguez Izquierdo Antonia , Baumann Tycho , Jiménez Ubieto Ana , Sanchez-Bayona Rodrigo , Pottier Elizabeth , Shelton Anthony , Pérez-García José Manuel , Garcia-Mosquera Juan Jose , Martinez-Bueno Alejandro , Hochberg Ephraim P. , Martinez Andrea , Nunez Cesar , McCall David , Ueno Naoto T. , Ciruelos Eva M , Cuglievan Branko 
Published: June 2023

e13632 Background: Every year more than 140,000 patients receiving anticancer therapy for malignancies in the US experience febrile neutropenia. Early detection of severe neutropenia could enable preventive strategies to reduce the incidence of febrile episodes. PointCheck is a novel portable optical device that can noninvasively monitor for severe neutropenia at home using microscopy and artificial intelligence. Preliminary clinical results of this device including usability (Lamaj et al., 2022), and sensitivity, and specificity (Pablo-Trinidad et al., 2019) for detection of severe neutropenia have already been reported. Here, we describe an exploratory clinical utility subanalysis. Methods: We conducted an international multicenter study with a primary endpoint of usability including mainly patients with hematological or breast cancer receiving therapy with intermediate/high risk for severe neutropenia, tested at two time points (baseline and nadir tests). Data included demographic information, cancer type, and a differential cell count within 120 minutes of the optical testing. The treating physician also completed an exploratory survey with 11 questions about the device´s potential clinical utility. A mixed-methods approach (descriptive statistics & “Likert” analyses with R 4.2.2) was used to evaluate the results. Results: 79 patients were included in this exploratory subanalysis. The median age was 49.5 (IQR 10.5-78.5) years, and 64 (81%) patients were female. The most common diagnoses were breast cancer (63%) and lymphoma (20%). Preliminary utility results were favorable with attending physicians agreeing that PointCheck could have helped evaluate 85% of the patients. In 82% of the patients, physicians felt that the device could avoid preparation of chemotherapy infusions in the setting of neutropenia. In 73% of the patients, physicians would consider administration of G-CSF or prophylactic antibiotics when sustained grade IV neutropenia was detected. Conclusions: This novel technology is able to non-invasively monitor for severe neutropenia and can add clinical utility as assessed by treating oncologists. Further studies are needed to validate these results.
An ultra-sensitive amplicon-based NGS assay for MRD detection.
Authors: Li Liangjian , Chen Meihong , Xiao Shanshan , Jia Lei , Wu Yalin , Wang Tao 
Published: June 2023

e13634 Background: Detection of the minimal residual disease (MRD) has proven a promising noninvasive approach for monitoring the tumor remissions and relapses after surgical resection or other therapies. However, circulating tumor DNA (ctDNA) after surgery in the early-stage cancers can be at very low levels, which makes the MRD detection quite challengeable if the plasma sample only contains a few ctDNA copies. In the clinical practice, an ultra-sensitive and tumor-informed multiplexing variant detection system is required for postsurgical cancer surveillance. Methods: In this study we developed an ultra-sensitive amplicon-based NGS approach, namely UMIamp, to provide a personalized and tumor-informed strategy for MRD detection using plasma sample. Firstly, up to 16 clonal somatic variants can be obtained by whole exome sequencing (WES) of the tumor tissue samples. Then optimized primers were designed to uniformly cover the target DNA regions and those target regions were efficiently enriched by linear amplification. With randomly unique molecular identifiers (UMI) attached to DNA templates and ultra-deep NGS sequencing, the somatic target mutations with very low frequency can be identified using a customized bioinformatic pipeline. To validate the performance of the limit of detection (LOD), the reference standard samples were diluted to the allele frequencies of 0.02%, 0.01%, 0.005% and 0.002%, respectively. Each sample contained 14 single nucleotide variants (SNVs). The sensitivity and specificity were calculated based the mutations called. Results: Single site level sensitivity and specificity were 75% and 100% with the allele frequency of 0.02%, while they were 70.73% and 95.08% with the allele frequency of 0.01%. The results showed UMIamp was very sensitive and was able to detect 2 copies from 60ng cfDNA sample at 0.01% mutation level. Even at the 0.005% and 0.002% allele frequency levels there were less than two copies in 60ng cfDNA, UMIamp still achieved single site sensitivities of 24.18% and 23.07%, respectively. In the MRD clinical practice, sample level sensitivity was important to evaluate the detection capability based on more gene mutations. When combined the 14 variants as a unified indicator to detect the sample level MRD status, the positive rates at the VAFs of 0.02%, 0.01%, 0.005% and 0.002% were all 100%, which demonstrated the LOD of UMIamp approach can reach to as low as 0.002%. Such sensitivity will be adequate for post-surgical early-stage cancer surveillance. Conclusions: We developed an ultra-sensitive amplicon-based NGS approach which can effectively detect MRD status at the allele frequency of 0.002%. The developed approach can be applied in a personalized, tumor-informed MRD detection settings in post-surgical early-stage cancers.
The CLARIFY digital decision support platform: An artificial intelligence tool for exploring multidimensional cancer data.
Authors: Torrente Maria , Menasalvas Ernestina , Sousa Pedro Da Costa , Provencio Mariano 
Published: June 2023

e13638 Background: Artificial intelligence has emerged as a mean of improving cancer care with the use of computer science. A digital framework that includes heterogeneous pipelines of real-world data can take advantage of AI, genomics and natural language processing to uncover insights that support decision-making in daily clinical practice. The goal of this study is to present an AI-based solution tool for cancer patients’ and identify clinical factors associated with relapse and survival, and to develop a prognostic model that identifies features associated with poor prognosis and stratifies patients by risk. Methods: This is a hospital-based retrospective registry included in CLARIFY (Cancer Long Survivor Artificial Intelligence Follow-up), a European project supported by the EU Horizon 2020 (grant agreement nº 875160), including 2275 patients diagnosed since 2008 at Medical Oncology Department at Hospital Universitario Puerta de Hierro-Majadahonda with non-small cell lung cancer (NSCLC) and 3000 breast cancer patients. The study was approved by the Ethics Committee at HUPHM (No. PI 148/15) and was carried out in accordance with the Helsinki Declaration. CLARIFY Decision Support Platform (DSP) is an AI-based solution tool which centralizes and analyzes real time anonymized clinical data from heterogeneous sources of data. It shows the clinical user information about individual patients or about the whole population and produces real-time descriptive statistics along with survival analysis (Kaplan Meier estimates and Cox regression model). Integrated data include clinical data from electronic health records from more than 5000 NSCLC patients and breast cancer patients, including more than 1,000,000 clinical notes, more than 900.000 clinical reports, data from wearable devices that produced around 1,000,000 variable values per patient, genomic data and data from quality of life questionnaires. Results: Using the DSP we obtained patients’ profiles, survival probabilities, we stratified over 2000 patients in low and high-risk profile and developed a machine-aided tumour-recurrence prediction model. This computational infrastructure was able to extract knowledge from different data sources allowing clinicians to analyse multiple factors that help stratifying patients by risk, in order to implement a personalized follow up care programme, aiming to make a significant impact in the patients’ quality of life. Conclusions: The reconstruction of the population’s risk profile was achieved and proved useful in clinical practice using AI. This DSP has potential application in clinical settings to improve risk stratification, early detection, and personalized surveillance management of cancer patients and may assist clinicians in their daily clinical practice.
Reveal irAE by analysis of 197,921 claim-based prescriptions.
Authors: Scholl Jeremiah Gordon , Long An Jim , Li Yu-Chuan (Jack) 
Published: June 2023

e13639 Background: immune-related adverse effects (irAE) are widely known for immune checkpoint inhibitors (ICI), but medications used to relieve irAE based on patient profile and condition are not offered in guidelines. Publications are available to reveal irAE from hospitals, but the number of cases are normally only a few hundred and insufficient to stratify by more variables. Claim-based data points were also used in a few publications, based on analysis of diagnosis code such as ICD-9 and ICD-10. However, missing or wrong coding of adverse effects are well-known and over-exaggerated for severe adverse events, and are also affected by reimbursement policy. This research used medications from a large national health system to understand irAE and treatments related to them. Methods: 2017-2019 National Health Insurance database (NHIDB) in Taiwan was used. The case group was identified as (2,474) patients who used PD-1 inhibitors (more specifically Nivolumab, Pembrolizumab, and Atezolizumab because only those three were available in the duration). A control group was identified as (6,207) patients given platinum-based chemotherapy (cases using other cancer drugs at the same time were excluded). Odds ratios were calculated to see frequency of irAE and medications in both groups. Results: Top 10 medications are listed. Diphenhydramine and pain killers were the most common AE-relief medications for cancer patients in NHIDB and only anilides (mostly propacetamol) are overlapped. The rest of the drugs with OR > 3, especially steroids (thyroid and corticosteroids), were used mainly for irAE. Conclusions: The research reveals a novel approach to understand how physicians prescribe to treat irAE. The larger number of cases reported compared to previous studies suggests that such a database can be used for future research, including to reveal demographic patterns, and to aid the development of guidelines, teaching aids, and decision support.[Table: see text]
Trends in Medicare utilization and reimbursement for hematology/oncology procedures.
Authors: Conic Julijana Zoran , Reske Thomas 
Published: June 2023

e13641 Background: Medicare Part B pays for physician services such as office visits and procedures based on the Medicare Physician Fee Schedule which is re-evaluated annually to maintain budget neutrality. Moreover, national cancer-attributed medical care costs in 2015 were $183 billion and projected to increase 34% to $246 billion by 2030 (Green et al: J Clin Oncol, PMID: 31804856). The aim of this study is to evaluate trends in Medicare reimbursement for procedures in hematology/oncology between 2012-2022. Methods: The data analyzed were extracted from the Physician Fee Schedule Look-Up Tool. CPT Codes were obtained from the Medicare Coverage Database. The following CPT codes were extracted: antineoplastic chemotherapy administration (96405, 96406, 96401, 96409, 96411, 96413, 96415, 96416, 96417, 96420, 96422, 96423, 96425, 96440, 96446, 96450, 96542), antineoplastic hormone therapy administration (96402), non-chemotherapy infusion (96360, 96361, 96365, 96366, 96367, 96368, 96369, 96370, 96371, 96372, 96373, 96374, 96375, 96376 ), bone marrow sampling (38220, 38221, 38222), bone marrow harvest (38230, 38232) and bone marrow transplant (38240, 38241, 38242). Consumer Price Index (CPI) obtained from the U.S. Department of Labor's Bureau of Labor Statistics was used to adjust reimbursement rates for cumulative inflation to 2022 U.S. dollars. The T-test was used to compare the mean prices for each procedure. This research contains publicly available data and as such is exempt from the IRB according to the Institutional Review Board at LSU Health Sciences Center in New Orleans, Louisiana. Results: The procedure with the highest reimbursement rate in 2012 was bone marrow harvest and the procedure with the lowest reimbursement rate in the same year was antineoplastic hormone therapy administration. The procedure with the highest reimbursement rate in 2022 was bone marrow harvest. The procedure with the lowest reimbursement rate in 2022 was antineoplastic hormone therapy. All procedure reimbursement fell significantly (p value of <0.001) over the timer period studied. Conclusions: Between 2012 and 2022 the reimbursement rates for common hematology oncology services fell significantly when adjusted for inflation due to reforms in Medicare part B. [Table: see text]
Temporal trends of atypical drug access at an academic oncology unit: The Verona University Hospital experience.
Authors: Atsina Francesca Mansa , Rossi Alice , Bolcato Ilaria , Fraccaroli Roberta , Alberti Chiara , Scardoni Laura , Patruno Isabella , Zacchi Francesca , Moscarda Viola , Messineo Luisa , Lucin Eleonora , Scaglione Ilaria Mariangela , Dodi Alessandra , Pavarana Michele , Melisi Davide , Leone Roberto , Scroccaro Giovanna , Marini Paola , Milella Michele 
Published: June 2023

e13651 Background: In Italy, patient (pt) access to oncological drugs is almost exclusively provided by the NHS, following authorization by the European Medicines Agency (EMA) and negotiation with the Italian Medicines Agency (AIFA) for specific indications. However, regulatory delays (with respect to the availability of scientific evidence) and the need for rapid access to innovative drugs, particularly in the context of orphan and rare diseases, have prompted the utilization of atypical drug access pathways. In addition to enrollment in clinical trials, atypical drug access pathways are expected to be increasingly used in the context of a Precision Oncology practice. Methods: We explored trends in atypical drug access at the Oncology Section of the Verona University and Hospital Trust, by interrogating Oncology and Pharmacy databases and regional registries of rare diseases and reviewing AIFA registries records. Data on atypical drug access were also correlated with the use of NGS-based molecular profiling. Results: Between January 2016 and December 2022, a total of 355 atypical drug access requests for the treatment of cancer pts were recorded, with a peak in 2017 and no discernible temporal trend. Over this period, the two most common atypical access schemes were compassionate (including named patient and early access programs, 61%) and off-label (21%) use. The latter steadily increased over time (from 8% in 2017 to 39% in 2021). Overall, the type of drugs requested through atypical access were almost equally distributed between classical cytotoxic agents (CHT, 36%), immuno-oncology drugs (IO, 29%) and molecularly targeted agents (TT, 35%). Temporal trends in the usage of different classes of drugs are shown. Interestingly, TT requests decreased between 2016 and 2018 and stabilized at approximately 50% of total requests since 2019. Between 2019 and 2021, atypical drug access requests triggered by NGS-based extended molecular profiling significantly increased from 2.8% to 23.1% (p=0.0007). Conclusions: Although atypical drug access did not increase overall during the observation period, a trend towards increased off-label use of TT was identified, especially from 2019 onwards; figures for 2022 are being analyzed and will be presented at the Meeting. Since 2019, NGS-informed requests have significantly increased to constitute almost 1/4 of all atypical drug access requests, clearly identifying a trend towards implementation of Precision Oncology in routine clinical practice and evolving towards the implementation of Molecular Tumor Board case discussions. [Table: see text]
Overall survival information and population correspondence for FDA cancer accelerated approval indications between 2006 and 2021.
Authors: Benedict Agnes , Szabó Gabor , Doherty Bridget , Martin Silas , Marczell Kinga 
Published: June 2023

e13653 Background: The US Food and Drug Administration (FDA) Accelerated Approval Program (AAP) was instituted to allow patients earlier access to medications that address large unmet need and are approved based on surrogate endpoints. Recently, approvals have been criticized for not providing overall survival data, and for confirmatory trials conducted in alternative populations. We investigated the availability of overall survival (OS) data for cancer accelerated approval (AA) indications and the correspondence between the population providing OS information and that of the original indication to assess the merit of these critiques. Methods: Approval letters and labels of cancer therapy products approved between January 1, 2006 and June 31, 2021 based on their verification status as of June 10, 2022 were identified from Drugs@FDA. Information was extracted irrespective of the final decision. Information about the exact indications and the trials that were used for AA and were cited for RA (confirmatory trial). OS data was searched for both AA and RA trials irrespective of approval dates, linked by NCT numbers identified in labels and letters. When OS was available only from the trial indicated for the RA, level of correspondence between the source of the OS data and the AA indication were described and then categorized in terms of the population characteristics, treatment lines, disease stage and changes in treatment regimen, to indicate level of correspondence. Results: OS data is available for 83% of closed AAs: 50 among the 57 converted and 12 among 18 withdrawn AAs. Further OS data was identified for seven AAs among the 55 ongoing reviews, creating a set of OS data for 69 out of the 130 total number of AAs identified. Exact or very good population overlap is evident in 50% of cases, defined as the availability of the trial reporting results for a population exact or very close to the original AA population; line change down was defined if the RA trial was conducted in an earlier line (without overlap with the original AA trial); and some additional categories were identified. Conclusions: Overall, OS information was available, and in half of the cases it was reported for a population very close to the original AA indication. Likely for ethical and practical reasons, RA trials are conducted in an indication that differs from the original AA indication and changes in the population was with the consent of the FDA. Policy discussions about AAP are incomplete without assessing its impact on survival and real-world considerations for conducting confirmatory trials. [Table: see text]
Increasing the study of novel anticancer therapies in adolescents: Facilitating adolescent inclusion in adult research.
Authors: Bucci-Rechtweg Christina , Zacharoulis Stergios , Mengou Evgenia , Corriol-Rohou Solange , Gaspar Nathalie , Copland Christopher 
Published: June 2023

e13654 Background: Adolescent cancer patients are disproportionately excluded from clinical trials due to trial designs with lower age limits set to the legal age of majority. This has led to a persistent time lag between adult and pediatric approval of new medicines. Publication of new US regulatory guidance encourages inclusion of adolescents in disease- and/or target-appropriate adult trials to facilitate earlier adolescent access to effective therapies. To understand impacts of this and other initiatives fostering adolescent inclusion, a review of recent cancer drug approvals was performed by the ACCELERATE Fostering Age Inclusive Research (FAIR) group. FAIR is an international research collaborative whose aim is to reduce adolescent inequities in access to novel anticancer therapies. Methods: A comprehensive analysis of new oncology drug approvals in Europe (EMA) and the US (FDA) will be conducted. EMA and FDA databases will be interrogated to identify all novel anticancer drug approvals and new use approvals (innovator and generic or biosimilar) between 2018 and 2022. Specific sections of drug labels (Indications and Usage, Dosing and Administration, Use in Specific Populations, Clinical Pharmacology, Clinical studies) will be evaluated. The study team will assess: inclusiveness of the Indication for Use statement; applicability of the approved indication to an adolescent cohort. This analysis will be conducted in sequence: phase 1 analyzes the EMA approvals, phase 2 analyzes the FDA approvals, followed by a comparative analysis across the regions. Phase 1 data are presented using descriptive statistics. Results:. Conclusions: This research evaluating new European drug approvals shows a limited number of anticancer therapies have been adequately studied or approved for adolescent use, even when the approved indication is relevant to adolescents. Recent regulatory guidance to promote the inclusion of adolescents in adult oncology drug trials has not yet led to an increase in adolescent labelling. Increasing awareness of medical oncologists and study sponsors may facilitate cultural mindset change, leading to expansion of eligibility criterion to adolescents and shortening the time lag of adolescent access to novel anticancer therapies. [Table: see text]