bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incorporating precision oncology in everyday clinical practice: First two years of comprehensive genomic profiling (CGP) testing experience in Croatia.
Authors: Čerina Dora , Šuto Pavičić Jelena , Njavro Antonela , Librenjak Niksa , Tomaš Ilijan , Šeparović Robert , Plestina Stjepko , Bajić Žarko , Dedic Plavetic Natalija , Vrdoljak Eduard 
Published: June 2024

11151 Background: Despite increased availability of modern technologies and evolution of tailored treatment, which has already significantly changed the outcomes in some cancer types, applicability of precision medicine in everyday clinical practice is still emerging and is one of the hot topics. Croatia is among first ones in the World to have entered into force a country-level based project of precision oncology throughout the CGP analysis in everyday clinical work, fully covered by Croatian health insurance. Hence, here we would like to present our data from everyday clinical practice and analyze the penetration of CGP given the opportunity and challenges we had. Methods: The study was observational and retrospective in nature, conducted on a country level among all patients on whose tumor specimens CGP was performed between January 1, 2020 and December 31, 2021. Eligible patients for the CGP analysis were those with metastatic disease, with at least 6-12 months of life-expectancy, with ECOG performance status ≤ 2, and after the recommendation from the multidisciplinary team. The analysis was performed in accredited laboratory (Foundation Medicine Inc., Cambridge, MA, USA), through FoundationOneCDx for solid tumors, FoundationOne Liquid in case of insufficient tissue or FoundationOneHeme for sarcomas. Results: There was total of 481 patients with CGP results. Median age was 61 years (IQR 49-69) and 58% of patients were women, while 42% were men. Most commonly tested were gastrointestinal (29.1%) and reproductive tumors (28.9%) with colorectal (19.1%) and uterine cancer (11.2%) as the most prevalent. At least one clinically relevant genomic alteration was found in 48.7% of patients. The most frequent mutations were those of KRAS (27.2%), PIK3CA (12.9%), AR (10.6%), NRAS (10.4%) and PTEN (9.1%) genes. Currently clinically not relevant mutations were found in 51.8% of patients with TP53 gene mutation as the most common (42.8%). According to the Croatian cancer registry, there was around 26 000 cancer related deaths during the investigated period defining population of at least more than 10 000 potentially eligible patients for the CGP analysis. Conclusions: Our results have shown that almost 50% of tested patients could have potential treatment benefit based on the detection of clinically relevant genomic alteration. Unfortunately, taking into consideration country level insurance eligibility criteria for CGP testing and number of potentially eligible cancer patients, we could say that only less than 5% of patients with metastatic disease were tested within first two years and that penetration of CGP is rather low, resulting with a significant number of patients underserved.
Medicare reimbursement trends of biological reference agents and their biosimilars.
Authors: Albaugh John , Indurlal Puneeth 
Published: June 2024

11155 Background: Biosimilars have the potential to reduce healthcare costs for payers and provide savings to patients by introducing competition and driving down prices. Centers for Medicare and Medicaid Services’ (CMS) Average Sales Price (ASP) is used as an index price to determine Medicare drug reimbursement (MCR) in the United States and is published on a quarterly basis. We studied the trends of ASP and MCR reimbursement rates for reference and biosimilar agents. Methods: Using publicly available quarterly CMS data, we evaluated and compared the trends of MCR for 7 reference and 25 biosimilar agents for a period of 2 years before and 5 years after launch. We evaluated the MCR for filgrastim, pegfilgrastim, bevacizumab, trastuzumab, rituximab, infliximab, epoetin-alfa, and their respective biosimilars. Results: On average, the published MCR for all reference agents increased by 9.2% (range: 0.6% to 16.8%) over the 2-year period prior to the biosimilar launch. Over the 5-year period following the launch of the first biosimilar, reference agents’ MCR fell 32.7% (range: -8.0% to -78.0%) while biosimilar agents’ MCR fell 50.3% (range: -3.7% to -90.5%) over the same period, with a median follow-up period of 16 quarters. Biosimilar MCR rates fell at an accelerated rate compared to reference agents. 76% (19 of 25) of the biosimilars that entered the market had an initial MCR below, and 20% (5 of 25) above, that of the reference agent. 16 of 18 successive biosimilars for reference agents launched with a MCR above that of the first biosimilar. Despite the fall in MCR, reference agents’ rates in the most recent quarter were 2x higher than their corresponding biosimilar agents, except for pegfilgrastim, which had a precipitous fall in MCR (87%) after biosimilar launch to a price lower than 5 of its 6 biosimilars. Conclusions: Biosimilars, with lower Medicare reimbursement at launch, and an accelerated decline in ASP post-launch, deliver on the goal of driving lower healthcare costs and increased savings. Biosimilar competition breaks the price increase trends with reference agents and contributes to a decrease in reference agent drug reimbursement. The effects of manufacturer rebates, payer policies, 340b programs, and discounts on ASP and Medicare reimbursement are also areas of active investigation.
Real-world outcomes in patients with biomarker-selected early-stage non-small cell lung cancer.
Authors: Abu Rous Fawzi , Sussell Jesse , Ngiam Celina , Zhang Qing , Majda Thomas , Sheinson Daniel , Ogale Sarika , Bara Ilze , Schulze Katja , Gadgeel Shirish M. 
Published: June 2024

11156 Background: Extensive literature has assessed the prognostic value of Lung driver mutations (LDMs) in advanced non-small cell lung cancer (aNSCLC). However, their role in predicting outcomes in early-stage cases (eNSCLC) is less defined due to limited data on biomarker-selected eNSCLC. Study variations have led to diverse findings on the prognostic value of individual LDMs in eNSCLC. Methods: We retrospectively analyzed patients with resected stage I-IIIa NSCLC diagnosed between 2011-2023 using the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine lung clinico-genomic database, which consolidates data from approximately 280 US cancer clinics (~800 sites of care). We allocated patients to five cohorts classified by early-stage LDM status: ALK+, EGFR+, KRAS G12C+, KRAS non-G12C+ and wild-type (WT - negative for the listed biomarkers). The clinical attributes and treatment patterns for this cohort were described by our group in a previous abstract; here we analyze recurrence-free and overall survival (RFS and OS) by cohort, using the Kaplan-Meier method. We used Cox regression for multivariate analysis, controlling for demographic and clinical characteristics including age, race, insurance status, stage, histology, and smoking status. Results: The sample contained 1,595 stage I-IIIa patients with known LDM status. Of these, 2.8%, 20.4%, 10.7%, 19.3%, and 46.8% were ALK+, EGFR+, KRAS G12C+, KRAS non-G12C+, and WT. Median OS and RFS were shorter in the WT group compared to any LDM group; results can be found in the table. These differences in OS and RFS persisted in multivariate analysis; hazard ratios (HR) were all statistically significant (p<0.05) and can be found in the table below. Conclusions: In this real-world analysis, patients with eNSCLC LDM-positive tumors had improved OS and RFS relative to WT patients. Differences in OS between WT and LDM+ patients are likely due to frequent receipt of targeted therapy (TT) following progression to advanced disease. However, the small fraction of patients that received adjuvant TT within 6 months of surgery (described in our previous abstract) is not likely to explain observed differences in RFS; thus the differences may be due to innate characteristics of these LDMs. [Table: see text]
Biomarker testing and targeted therapy use among patients with non-small cell lung cancer in the United States: An analysis using a physician notes real-world database.
Authors: Videna Vernon , Iwanyckyj Dave , Otalora Fernando , Jardim Melanie 
Published: June 2024

11175 Background: Biomarker testing informs treatment decisions by identifying patients who would clinically benefit from targeted regimens, leading to improved patient outcomes. However, the use of guideline-recommended biomarker testing in patients with advanced non-small cell lung cancer (NSCLC) is inconsistent. This study investigates the rates of biomarker testing in patients with NSCLC using a qualitative, real-world database. Methods: Natural language processing (NLP) was used to search and analyze the Amplity Insights database, consisting of transcribed, de-identified, records of physician-patient interactions obtained from patient medical records across the United States. This was a retrospective analysis of patients with a diagnosis of NSCLC (October 2003 - November 2023). Patient characteristics, biomarker testing, and treatment use were summarized and described. Results: 61,018 patients with NSCLC (mean [standard deviation] age of 69.8 [10.5] years) were identified. Among these, 50.6% were female and 87.9% identified as white. Among records with staging information, 26.6% had early-stage disease (stage 0-II) and 73.4% had late stage (stage III-IV) disease. In total, 13.4% (n=8,151) of all patients received biomarker testing. 13.3% (n=879) and 22.4% (n=2,402) of patients with stage III and IV, respectively, had biomarker testing performed; rates were higher in patients who were receiving care from an oncologist (16.8%, 31.0%, respectively). Among patients who had a confirmed actionable mutation (n=6,387), 35.9% received an appropriately matched targeted therapy and 10.1% received a nonindicated targeted therapy without harboring the indicated mutation. Of these, 40.7%, 22.7%, and 37.7% of patients harbored EGFR or ALK mutations, or were PD-L1 positive, respectively, and 35.8%, 17.8%, and 40.2% received the appropriate indicated treatment, respectively, based on testing. ALK-, EGFR-, and PD-L1-targeted therapies were taken by 12.1%, 9.4%, and 1.9% of patients, respectively, without evidence of the indicated biomarkers. Conclusions: These findings suggest that biomarker testing may be underutilized and that many patients may not be benefitting from treatment with precision therapies, highlighting the need for additional educational strategies to optimize precision oncology and elevate patient outcomes.
Impact on biomarker documentation in community oncology by optimizing clinical decision support.
Authors: Rubin Daniel , Handy Victoria , Gilmore Steven , Ginsburg Aimee , Dickens Andrea , Howell Josh , Hough Shannon 
Published: June 2024

11182 Background: Timing of biomarker results is critical to informing the selection of appropriate precision medicine-based treatment options for patients. Prior studies have demonstrated that low rates of biomarker testing may be driven by poor documentation. Our clinical decision support (CDS) tool aims to provide community oncology clinicians with a clear picture of the ever-growing available treatments. Evaluation of CDS data revealed an excess of biomarker results documented as “unknown” thought to be related to results availability. Methods: During treatment selection in the CDS tool, providers answer various prompts related to the patient’s disease, staging, treatment intent, and biomarker results. Prompts are aligned with NCCN guidelines for the respective cancer type. Changes were implemented to ease providers’ documentation of biomarker results. For adjuvant (adjNSCLC) and metastatic NSCLC (mNSCLC), prompts were relocated to align with when biomarker results were likely to be available. For metastatic castrate resistant prostate cancer (mCRPC), some biomarkers are only needed after a patient has received prior docetaxel and hormone therapy, thus prompts were moved to that scenario. Re-prompting of biomarker status for subsequent therapy was also implemented if the initial response was “unknown.” We report changes in percentage of known biomarkers specifically in adjNSCLC, mNSCLC, and mCRPC. Descriptive statistics were used to describe the rates of known biomarkers, and a chi-square test was used to analyze differences from pre and post changes. Results: In this evaluation, 85,493 biomarkers were documented. In adjNSCLC and mNSCLC, biomarker prompt changes increased documentation of known biomarkers from 69% to 78% and 59% to 79% pre- to post-implementation. In adjNSCLC, ALK and PD-L1 recording increased by ≥10% (P<0.00001). For mNSCLC, documentation increased for all known biomarkers (P<0.00001), including ≥15% increases for 8 of 10 biomarkers. In mCRPC, known biomarker documentation improved from 34% pre-implementation to 61% post-implementation. BRCA1/2, MSI, MMR, TMB, and PSMA biomarker recording increased by ≥20% (P<0.00001) after prompt changes. Selected biomarkers are shown in the table. Conclusions: Adjusting prompts in a CDS tool to align with the availability of biomarkers in clinical practice increased the documentation of known biomarker results for adjNSCLC, mNSCLC, and mCRPC. Based on these findings, similar changes are being implemented for other cancer types in the CDS tool. [Table: see text]
Disparities in frontline treatment and overall survival in the era of targeted tyrosine kinase inhibitor therapy for chronic myeloid leukemia: 2004-2021.
Authors: Vardell Victoria , Tantravahi Srinivas Kiran 
Published: June 2024

11187 Background: The treatment of chronic myeloid leukemia (CML) was revolutionized in 2001 with the introduction of the BCR::ABL tyrosine kinase inhibitor (TKI), imatinib. In 2006, dasatinib was approved, followed by nilotinib in 2007. Two other TKIs, bosutinib & ponatinib were approved in 2012, followed by the allosteric ABL myristoyl inhibitor asciminib in 2021, providing multiple options for patients (pts) who have refractory disease. In this study we examine how survival has improved in CML pts with the availability of multiple TKI’s and identify disadvantaged socioeconomic & demographic groups which continue to have disparate survival. Methods: The National Cancer Database was used to identify CML pts diagnosed (dx) from 2004-2021. Demographic, treatment, & overall survival (OS) were compared by era of TKI availability, with pts dx from 2004-2005 considered to be treated in the imatinib era, 2006-2011 for dasatinib & nilotinib, 2012-2020 with access to bosutinib & ponatinib, and 2021 for asciminib. Results: Of 44,993 CML pts identified, 55.8% were male & 82.5% were White, with median age of 58 years. The portion of pts who were untreated (due to contraindication or early death) decreased by each time period, from 17.8% in the imatinib era to only 7.8% in 2021. The rate of upfront transplant decreased from 2.5% from 2004-2005, to 0.8% in 2021. For dx 2004-2005 median OS was 11.5 yrs (95% CI 10.6-12.5). This increased to 13.6 yrs (CI 13.1-14.1), with age-adjusted hazard ratio (HR) of 0.86 (CI 0.81-0.91) for pts dx 2006-2011, with median OS unreached for 2012-2020, HR 0.67 (CI 0.63-0.71, p<0.001); referenced to 2004-2006. Survival at 1-, 5- & 10-yrs was improved for each subsequent time period of dx, with 5-yr OS of 65%, 71%, & 76%, respectively, p<0.001. On multivariate cox regression adjusted for yr of dx, features associated with reduced OS included age (HR 1.06 [95% CI 1.05-1.06], p<0.001 for each yr), Black race (HR 1.11 [95% CI 1.05-1.18], p<0.001), increased comorbidity index (HR 1.94 [95% CI 1.84-2.04], p<0.001 for index ≥2), uninsured (HR 2.20 [95% CI 2.01-2.41], p<0.001), or insured through Medicaid (HR 2.40 [95% CI 2.23-2.58], p<0.001). Conclusions: Survival for CML pts has significantly improved during the last 20 yrs with the availability of each additional TKI, likely related to increased treatment options for pts with resistance or intolerance. Additional TKI options, particularly approval of ponatinib for patients with T315I mutation, have a secondary benefit of decreasing the utilization of allogenic transplant. Though survival has improved for all pts, pts from traditionally underserved populations, including pts who are underinsured or from racial minority groups, have reduced OS. Continued advances in treatment & efforts to improve access to care for underserved populations is vital to achieve equitable survival outcomes in CML.
Informal caregiving for older adults on systemic treatment for hepatocellular carcinoma.
Authors: Wu Meng , Watman Deborah , Perez Sasha , Chen Yingtong , Woodrell Christopher D. 
Published: June 2024

12059 Background: Hepatocellular carcinoma (HCC) disproportionately affects older adults who are often supported by informal or unpaid family caregivers (CGs). Despite rising incidence of advanced HCC worldwide, little is known about the experiences and unmet supportive needs of patients (pts) and their informal CGs, particularly in the context of contemporary first-line immunotherapy-based treatment. Methods: As part of two cross-sectional descriptive studies conducted in parallel at a single academic center, we interviewed non-dyadic older pts on systemic HCC treatment and family CGs and examined themes of informal caregiving. Eligible CGs were ≥18 years old and identified by pts; eligible pts were ≥60 years old and on systemic treatment for BCLC stage B or C HCC. CGs completed the Zarit Burden Interview (ZBI). Participants completed semi-structured interviews focused on pt and CG experiences and needs, which were transcribed and analyzed using an inductive approach by at least two investigators. Results: Transcripts (n=16) from 11/2021-11/2023 of interviews with CGs (n=8) and pts (n=8) were analyzed. CGs were 87.5% female. Their median ZBI score was 20/88, indicating little or no burden, although scores ranged from 2-64; higher scores indicate greater burden. Four themes emerged: CG tasks, sources of burden, sources of support, and views of palliative care. CG tasks included coordinating medical appointments and transport, attending appointments, advocating for pt interests, and helping with household chores. Two sources of burden most commonly identified were logistics of medical visits and supporting pts through physical and emotional symptoms. CGs recognized multiple sources of support, including spouses, family, friends, church groups, and therapists. Pts were 87.5% male, median aged 70, 25% Black, 50% non-Hispanic white, and 25% Hispanic. Their responses about caregiving, in contrast to the CGs interviewed, showed strong themes of independence. Representative quotes include, “I don’t need any help,” “I am independent..so far,” and “I live alone, I’ve got my own place, I do the best I can for myself.” Some shared that the support of CGs is more spiritual or emotional, “I feel stronger because you’re there,” which was needed mostly with new diagnoses or disease progression. Conclusions: Levels of burden varied among CG participants; pt participants felt independent for the most part while receiving their treatments, consistent with improved functional status and quality of life experienced by those receiving combination therapy. The task of juggling logistics for numerous medical visits between multiple subspecialties emerged as a major challenge. Strategies to optimize care coordination, including increased use of navigation for those with advanced HCC, may help pts and their CGs live better as they live longer on improved treatments.
Effect of palliative care on economic burden in lung cancer admissions: Insights from the NIS database.
Authors: Turk Ekrem , Olafimihan Ayobami Gbenga , James George Lina , Aryal Badri , Oh Youjin , Deenadayalan Vaishali , Batra Kunnal 
Published: June 2024

12081 Background: Lung cancer (LC) remains the leading cause of cancer mortality globally, presenting substantial challenges in symptom management and quality of life (QoL) for affected patients. Despite the crucial role of palliative care (PC) in alleviating suffering and enhancing QoL, its integration into LC treatment is inconsistent, attributed to healthcare provider perceptions and systemic barriers. This study examines the utilization of PC consultations in LC admissions using the National Inpatient Sample (NIS) database, seeking to identify patterns of use and opportunities for improved care integration. Methods: The study queried the NIS database from 2016 to 2020 for adult hospitalized patients with a primary diagnosis of LC using ICD-10 codes. The primary outcome examined was the impact of PC consultations on length of stay (LOS), total hospital charges (THC), and healthcare utilization, with inpatient mortality as a secondary outcome. Baseline characteristics were assessed using t-tests and chi-square tests, while multivariable logistic regression analysis adjusted for age, gender, race, Charlson index, insurance type, and household income was employed to evaluate the outcomes. Results: Among 584,055 LC patients, 50.4% was female and 14.6% had a PC consult. These patients were typically older (68.4 vs. 70.6 years, p <0.001), more likely to be male (51.1% vs. 49.3%, p < 0.001) and African American (13.3% vs. 11.9% p < 0.001), and had Medicaid coverage (11.1% vs. 9.7%, p < 0.001) compared to their counterparts . PC was more frequently consulted in non-teaching hospitals (16.3% vs 14.1%, p < 0.001). Patients with PC consults also had a higher Charlson Comorbidity index 6.4 vs. 4.9 (p < 0.001). The overall inpatient mortality rate was 7.4%, with a significantly higher rate in patients with PC (32%) versus without (3.2%) (p < 0.001). While PC was associated with a longer LOS (7.6 vs. 5.9 days, p < 0.001), it resulted in lower THC ($74,399 vs. $84,233, adjusted difference: $6,874 p < 0.0001) and increased discharges with home health care and to nursing homes. Conclusions: PC consultations in LC patients are associated with reduced THC despite a slight increase in LOS. This finding emphasizes the economic and therapeutic value of PC in the treatment of LC, advocating for its earlier and broader integration. By addressing both symptom management and healthcare costs, palliative care can play a significant role in enhancing the comprehensive care of lung cancer patients, highlighting the need for overcoming existing barriers to its adoption. [Table: see text]