bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of preparation and execution of strategy to mitigate the platinum shortage within a network of community oncology practices.
Authors: Ginsburg Aimee , Dickens Andrea , Thornby Robert , Dominguez Kaci , Howell Josh , Busby Leslie T. 
Published: May 2024

e13572 Background: The US Oncology Network (USON) is made up of over 600 sites of care and treats 1,400,000 patients annually. Drug shortages have a massive impact on patient outcomes, particularly with limited source oncology medications. Proactive mitigation strategies by the national USON Pharmacy & Therapeutics (P&T) committee are examined to assess impact on cisplatin and carboplatin (cis/carbo) shortages, where a phased approach extended supply for patients. Methods: P&T began implementing gradual reductions in cis/carbo allocations in mid-April 2023. This included stewardship to reserve use in patients with limited alternatives, dose rounding, reducing dose/cycle, and extending cycle interval, when clinically appropriate. As supply depletion became imminent, P&T implemented a novel drug ordering process that restricted cis/carbo use criteria to curative intent without alternative treatment options, requiring case-by-case approval. Comprehensive clinical guidance was developed to provide recommendations for alternative therapies. Alternative regimen templates were built into the centrally managed EHR. To evaluate the impact, drug utilization patterns were tracked during the 6-month shortage (April - September 2023) and compared to historical data. Results: Pronounced impacts were seen during acute supply constraints: cisplatin administrations (admins) and mg decreased to 53% and 48% of baseline, carboplatin admins and mg decreased to 84% and 78%. Compared to the prior 6 months, patients receiving cis/carbo was similar pre-shortage (15,368) vs. during (15,296).Mitigation strategies resulted in preservation of cis/carbo admins for diseases with limited alternatives (NSCLC, head & neck, ovarian/uterine); other cancers with alternatives had a decrease in admins (see table). Dose conservation guidance led to a decrease in average mg administered by 5.1% for cisplatin (72.2 vs. 68.5), and 6.2% for carboplatin (385.5 vs. 361.7). New admins of oxaliplatin increased by 11% (4,230 vs 4,714), primarily in GI malignancies. Conclusions: The rigors of stewardship with a phased approach allowed USON to sustain new patients while conserving cis/carbo for those with limited alternatives. Frequent communication about supply status and conservation guidance was critical for transition to alternative treatment strategies. This experience tested USON organizational readiness for future shortages. [Table: see text]
Perspectives on clinical adoption barriers to blood-based multi-cancer early detection tests across stakeholders.
Authors: Schroll Monica M , Quinn Elissa , Pritchard Daryl , Chang Allina , Garner Amanti Kristen , Perez Omar , Agarwal Arushi , Gustavsen Gary George 
Published: May 2024

e13574 Background: Current United States Preventive Services Task Force (USPSTF) recommendations include routine screening for breast, cervical, colorectal, and lung cancer; however, two out of every three cancer cases occur in other indications leading to diagnosis in advanced stages of the disease and higher likelihood of mortality. Current recommended cancer screening and early detection tests also face several hurdles hindering equitable access in a real-world setting. Blood-based MCED tests can impact cancer screening and early detection by monitoring for multiple different cancer types at once via a blood draw that can detect cancers in multiple indications, including indications where screening is not performed routinely today. Given their nascency, the role of blood-based MCED tests in clinical practice is currently undefined. To help facilitate the appropriate integration of MCED tests into patient care, it is important to understand the perspectives of stakeholders on the anticipated challenges to implementation. Methods: We conducted three separate double-blinded surveys in July 2023 of representative cohorts of U.S. Healthcare providers (HCPs) (n=238) that are or act as primary care providers (general practitioners and obstetrics and gynecologists (OB-GYNs)), payers (n=40), and patients (n=116), to evaluate the current cancer screening and early detection landscape and gather perspectives on barriers to implementation of new cancer screening technologies, including blood-based MCED tests. Results: Of the surveyed HCPs and payers, >90% and 100% respectively reported to be aware of MCED tests. However, <10% of HCPs reported having ordered an MCED test and 80% of payers had not yet evaluated an MCED test for coverage under their plan at the time of the survey. The survey results indicated that there is broad agreement on the value proposition that blood-based MCED tests would improve patient outcomes with earlier intervention. Despite this recognition, the survey highlighted that there is limited use today due to the perceived lack of clinical accuracy and utility data, high out-of-pocket patient costs, and lack of payer coverage. Conclusions: To overcome the hurdles for future widespread adoption of blood-based MCED tests, increased investment in data generation, education, and implementation of logistical support for HCPs will be critical. Initiatives include collaborations between stakeholders to generate near-term clinical utility data, equipping HCPs with the ability to educate patients on test accuracy, and seamlessly integrating the testing process into the patient visit workflow. The findings of this study can help build understanding of the anticipated barriers and inform strategies to alleviate them and build a foundation for clinical adoption of blood-based MCED tests.
Use of a deep learning model on H&E slides to predict nucleic acid yield for NGS testing.
Authors: Och Josh , Muller Yoni , Nagpal Kunal , Osinski Boleslaw , Hong Sun Hae , Stumpe Martin C. , Beaubier Nike , Jones Ryan D 
Published: May 2024

e13589 Background: Samples sent for NGS may fail testing, leading to treatment delays or missed opportunities to offer patients targeted therapies. A common reason for assay failure is insufficient total nucleic acid (TNA). We developed and validated a model based on a digitized H&E slide and readily available clinical data that predicts whether samples will yield sufficient TNA for NGS testing. This model could lead to faster turnaround times and lower failure rates by helping choose patient blocks most likely to complete sequencing, or routing likely-to-fail samples to specialized extraction methods or smaller panel assays with lower input TNA requirements. We also evaluated the model’s ability to identify samples that yield abundant TNA, which could help pathologists spare tissue for other testing. Methods: We developed our model on samples received for NGS testing from January 1 - June 30, 2023, and tested on a large, real-world cohort of 9,707 samples received from July 1 - September 30, 2023. Cell count, assessed by a previously developed deep learning model on digitized H&E slides, along with the number of slides scraped, sample age, procedure type, and tissue site were used as model inputs. We measured the model’s ability to predict whether a sample yielded less than 100 ng of TNA (the target mass for the NGS assay used) and whether it failed sequencing. We also evaluated the model’s ability to predict whether a sample would have abundant TNA (defined here as yielding more than 1000 ng of TNA, 10x the target mass for the assay). Results: On the validation set, the model predicted samples that yielded TNA < 100 ng with a specificity of 98%, sensitivity of 26% and PPV of 82% (prevalence = 24%). It predicted samples that failed DNA sequencing with a specificity of 96%, sensitivity of 30% and PPV of 58% (prevalence = 15%); and samples that failed either DNA or RNA sequencing with a specificity of 98%, sensitivity of 23%, and PPV of 80% (prevalence = 27%). On the validation set, 742 samples were flagged, 430 of which failed DNA sequencing, and 590 of which failed either DNA or RNA sequencing. When predicting abundant TNA, the model predicted samples yielding TNA > 1000 ng at a specificity of 97%, sensitivity of 54% and PPV of 88% (prevalence = 26%). On the validation set, the model predicted 1544 samples as abundant, only 185 of which yielded TNA < 1000 ng and only 16 with TNA < 100 ng. Conclusions: The developed model holds promise as a tool for use at the beginning of NGS assays. It can be utilized to optimize testing decisions including selection of which samples to sequence, routing likely-to-fail samples to alternate testing methods, and sparing tissue for future assays from samples with abundant tissue.
Utility of liquid biopsy for predicting cancer type and informing treatment of carcinoma with unknown primary.
Authors: Bao Hua , Tang Haimeng , Chen Xiaoxi , Wu Xuxiaochen , Zhu Dongqin , Chang Shuang , Wu Xue , Shao Yang 
Published: May 2024

e13606 Background: The advent of next-generation sequencing has greatly facilitated physicians in recommending tailored treatments for cancer patients. Despite these advancements, the dependence on the primary tumor site remains crucial for accurate diagnoses, posing a substantial obstacle in cases of carcinomas of unknown primary (CUPs) and hindering optimal patient care. To address this challenge, we propose the implementation of a machine learning model capable of identifying the tissue of origin (TOO) across 16 cancer types. Current standards gravitate to the use of tumor tissue for identifying primary tumor site. Leveraging the advantages of cell-free DNA (cfDNA), our approach provides a non-invasive and highly sensitive alternative to traditional biopsy or radiography methods. Methods: Cell-free DNA was extracted from patients diagnosed with carcinoma of known origin. The model underwent training using a dataset comprising 2,793 cfDNA samples, while the validation set consisted of 1,863 samples. The training and validation cohorts exhibited comparable demographics in terms of sex, age, and cancer types. Employing low-coverage whole genome sequencing (WGS), samples were analyzed to capture cfDNA features, including DNA fragment size distribution, copy number variation, nucleosome coverage pattern, mutational signature, and hotspot regions associated with cancer-related mutations. The final prediction model's accuracy was evaluated based on top 1 and top 2 predictions in accordance with the true tumor site of origin. Results: Overall accuracy of TOO predictions in the training cohort is 80.20% (2240/2793) for top 1 site and 90.26% (2521/2793) for top 2 sites. Overall accuracy of TOO predictions in the validation cohort is 81.80% (1524/1863) for top 1 site and 90.07% (1678/1863) for top 2 sites. Accuracy of tumor site prediction in the validation cohort is highest for lung cancer (Top 1 = 95.9%; Top 2 = 98.0%) tumor sites and lowest for biliary system and kidney tumor types (Top 1 = 54.3% & 57.4%; Top 2 = 71.6% & 63.2%). In the clinical setting, TOO estimation of 12/16 patients with CUP were identified to be in concordance with majority pathological consensus. Of note, two patients with CUP were diagnosed as lung cancer patients through TOO estimation. Molecular biomarkers of lung adenocarcinoma were also identified through targeted sequencing which corroborated the diagnosis, and chemoradiotherapy was recommended to the patient. Conclusions: We developed an accurate predictor of TOO by leveraging machine learning algorithm and incorporating cfDNA mutational, fragmentomic, and epigenetic features. Our results demonstrate high concordance between model-predicted and actual tumor sites across all examined cancer types. This model shows promise in offering valuable insights for the identification of cancers with an unknown primary origin using non-invasive cell free DNA samples.
Quantifying clinical actionability of updated tumor profiling reports through electronic health record (EHR)-enabled, on-demand ordering and resulting.
Authors: Huelsman Karen M. , Maher James F. , Parchman Andrew J. , Jones Ryan D , Posteraro Leo , Chen James Lin 
Published: May 2024

e13621 Background: Next-generation sequencing reports provide matched therapies and clinical trials based on genomic alterations to drive therapeutic decisions in clinical practice. Biomarker-matched oncology drug approvals and trials have grown tremendously over the past decade. From January 2000 to October 2022 alone, a total of 573 agents were approved for various oncology indications, with nearly half being targeted therapies. While matched therapies and clinical trials are current at time of issue, updated variant classification, changes in FDA approvals, and trials available are not reflected in static reports. It is not always practical nor feasible to provide a new biopsy specimen. To address this gap in clinical care, we piloted Tempus Refresh, an on-demand informatics service that provides clinicians with refreshed therapy and trial matches from prior molecular reports directly through the EHR. Here we quantify the clinical actionability of Refresh reports. Methods: TriHealth piloted the Tempus Refresh orderable through the Epic EHR at the treating physician’s discretion. The clinical team specified prior DNA molecular reports (tissue or blood) to update. Orders were transmitted to Tempus through an HL7 interface. All alterations provided on the prior report were updated for therapeutic and trial matches through existing workflows. An updated structured report was then delivered to the TriHealth Epic EHR linked in the lab tab. Results: From 2/2023 to 11/2023, 10 TriHealth providers participated. A total of 35 unique Refresh orders were placed via custom HL7 Epic order, of which 3 were canceled due to orders outside of pilot parameters. Of the 32 Refresh reports, 34% (11/32) contained new FDA-approved therapies (OncoKB Level 1 or 2), and 78% (25/32) were annotated with new clinical trials. The average elapsed time from original date of report issuance to Refresh order delivery was 14.5 months (range 1 month to 45 months). The mean turnaround time for issuance of a Refresh report was 29 hours (range 5 hours to 53 hours). Conclusions: These results demonstrate that on-demand report updates increase the availability of tumor biomarker-matched therapies and trials. Furthermore, the study exhibits the feasibility of integrating updates directly into the standard EHR clinical workflow. This service provides visibility across teams and can support specialty pharmacists in therapy authorization. Considering the success of this pilot, future studies will assess the expansion of Tempus Refresh to additional sites.
On improving clinical trial diversity: Viewpoints from underrepresented breast cancer survivors.
Authors: Lee Kimberley T , Blackwell Rebecca M. , Maconi Melinda Leigh , Geiss Carley , Vadaparampil Susan Thomas , Gonzalez Brian D. , Jim Heather S.L. , Gwede Clement K , Soliman Hatem Hussein 
Published: May 2024

e13674 Background: Racial and ethnic diversity in cancer clinical trials remains low. In this formative work, we sought to better characterize patient attitudes towards clinical trial participation. The goal is to build a framework that can be leveraged to develop an intervention to increase enrollment of participants from racial and ethnic minority groups in clinical trials. Methods: Semi-structured interviews were conducted with 10 Black and 10 Hispanic breast cancer survivors receiving care at a comprehensive cancer center in the South. Interviews were recorded, transcribed verbatim, and coded using thematic analysis. Results: Patient attitudes to clinical trials were generally positive. Many felt that trials were beneficial and a necessary part of advancing medical science. However, many expressed hesitations with regards to trial participation due to safety and efficacy concerns and distrust regarding motivation of healthcare system. Facilitators of positive attitudes towards clinical trials included positive social circles including family and community, as well as altruism regarding supporting racial and ethnic diversity in clinical trials. Conclusions: Collectively, these findings underscore the importance of implementing strategies to foster diversity in the biomedical research community, community outreach, and lay education, to improve trust in the system and therefore attitudes towards clinical trial participation in minority populations. [Table: see text]
UK Cancer and Transition Service (UCATS): Providing tailored cancer care to the gender-diverse community.
Authors: Berner Alison May , O'Callaghan Stewart , Lander Frances , Bower Mark 
Published: May 2024

e13676 Background: Gender-diverse individuals identify their gender as different to the sex they were assigned at birth. This population experiences health inequity throughout the cancer care pathway partly stemming from limited access to specialist knowledge of gender-affirming care and its intersections with cancer. Notable issues include safety of gender affirming hormones, mutual implications of gender affirming surgeries with cancer surgeries and radiotherapy, and psychological support when dysphoria is exacerbated by a cancer diagnosis. Methods: In response, we established the UK Cancer and Transition Service (UCATS), a national virtual monthly multidisciplinary meeting (MDM) and clinic. Patients are eligible for referral if they identify as gender-diverse and have active or historical malignancy. The service was coproduced with patient and public involvement, including input from a specialist cancer charity for gender and sexual minority people. The service launched in June 2022 and began advertising and requesting patient feedback from January 2023. Results: Between June 2023 and January 2024 UCATS received 20 referrals (10 from gender services, 5 from oncology, and 5 self-referrals). Patients were aged 18 - 68 years. The most common tumour types were breast (n = 6), prostate (n = 5), and gastrointestinal (n = 3). Others were haematological, testicular, gynaecological, and central nervous system. One patient had a familial cancer syndrome, not active cancer. Patients were offered a virtual clinic appointment and MDM discussion. Reasons for referral included safety of gender affirming hormones and surgeries, and expedited gender consultations in view of prognosis, or need for cancer treatments that may affect gender-affirming care. Two patients did not attend, with one sending a nominated family member. Six patients had at least one external clinician dial in for the appointment. Seven patients received follow-up appointments. There were nine completed feedback forms, 4 after first appointment and 5 after follow-up. All patients rated both the communication at the appointment and the information given as 5/5. All patients rated their likelihood to recommend the service as 4 or 5/5. Other points of positive feedback were the detailed outcome letter, speed of appointment, and a sense of advocacy. Next steps include routine follow-up appointments (in response to feedback), wider advertising, increased frequency, and recruitment of nursing support. Conclusions: UCATS successfully caters to an unmet need, coordinating cancer and gender affirming care for gender diverse patients, and providing specialist knowledge and support for patients and care teams.
Racial disparities in breast cancer care among reproductive-aged women continued after COVID-19 pandemic.
Authors: Periyanayagam Usha , Yung Ethan , Kim Christine , Popadic Lyuba , Devine Francesca 
Published: May 2024

e13757 Background: Despite the aggressive nature of breast cancer (BC) among women under 45 years old, racial disparities in BC care still exist. The COVID-19 pandemic highlighted racial disparities in care management. This study described staging, treatment use, and healthcare resource use (BC-HCRU) among reproductive-aged White, Asian, and Black women before and after COVID-19 to identify possible care changes. Methods: This retrospective claims study assessed White, Asian, and Black women aged 18 to 44 years old with newly diagnosed BC in the Komodo Research Dataset from August 2018-May 2023. Women were stratified based on their first observable BC diagnosis (index) into two cohorts, pre-COVID-19 (pre) (February-July 2019) and post-COVID-19 (post) (July-November 2022). Patients were required to have >6 months of medical and pharmacy continuous enrollment before (baseline) and after index (follow-up), and a second BC diagnosis during follow-up. BC-HCRU was defined as a claim with a BC diagnosis. Results: Pre-COVID-19 included 875 White, 116 Asian, and 267 Black women (mean age 39.0 years, 38.5 years and 37.8 years respectively) and post-COVID-19 included 879 White, 127 Asian, 386 Black women (mean age 38.8 years, 38.9 years and 37.9 years respectively). While the proportions with commercial insurance decreased (pre: White, Asian, Black: 72.5%, 71.6%, 42.7%; post: 51.9%, 61.4%, 23.6%) and with Medicaid increased (pre: White, Asian, Black: 24.3%, 27.6%, 53.6%; post: 45.2%, 38.6%, 75.1%) for all, most White and Asian women had commercial insurance and most Black women had Medicaid pre- and post-COVID-19. The proportion with metastatic BC increased for all in the post period, but lower incidences remained among White (pre: 20.7%; post: 25.1%) and Asian (pre: 17.2%; post: 22.8%) than Black women (pre: 25.5%; post: 28.0%). While both the proportions of White and Asian women with BC-related ER visits increased, suggesting greater acute care needs, the proportion of Asian women doubled and became higher than White women; the highest incidence also remained among Black women (pre: White, Asian, Black: 13.1%, 7.8%, 22.8%; post: 15.4%, 18.1%, 21.0%). The proportion with any treatment (medication, surgery, radiation) remained highest for Asian women (pre: 87.9%; post: 90.6%) and decreasingly lowest for Black women (pre: 84.3%; post: 80.3%), and the mean time to treatment remained shortest for White women (pre: 40.3 days; post: 44.3) and longest for Black women (pre: 47.4; post: 49.8). Conclusions: While COVID-19 affected BC care among all reproductive-aged women, racial disparities in BC care remained or increased in this vulnerable population. Comparative analyses assessing the factors driving these disparities should be explored to understand these health inequities further, and real-world clinical practice should consider these differences when implementing necessary BC management.