bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive Memorial Sloan Kettering Cancer Center real-world data model: Core clinical data elements.
Authors: Shah Neil J. , Bahadur Nadia , Esposito Lauren , Niederhausern Andrew , Nichols Chelsea , Pillai Anjali , Gandhi Fenil , Barton Laura , Chan Kimberly , Estrada Latasha , Goldberg Joshua , Capreol Grace , Bochner Bernard H. , Kollmeier Marisa , Al-Ahmadie Hikmat A. , Brown Samantha , Lee Jasme , Rosenberg Jonathan E. , Philip John , Bakker Theodora 
Published: June 2021

e18755 Background: The 2016 21st Century Cures Act supports the use of Real-World Data (RWD) for regulatory decision/approval. Due to technological advances, a vast amount of health-related data are now available, but most are not standardized nor readily useable for research. Also, currently available standardized RWD models are not applicable across cancer types or oncology specialties (surgery, medical oncology, radiation oncology, pathology, radiology, etc.). To address these deficiencies Memorial Sloan Kettering Cancer Center (MSKCC) built a comprehensive, pan-cancer, pan-specialty RWD model. Methods: The Core Clinical Data Element (CCDE) data model incorporates aspects of existing academic and biopharma data models, including PRISSMM framework, ASCO’s mCODE, and NAACCR tumor registry model. The data model encompasses 11 domains that are critical to the understanding of the patient’s cancer journey, including: demographic, comorbidities, diagnosis, pathology, imaging, genomics, cancer surgeries, radiation oncology treatments, medical oncology treatments, cancer status/progression, and additional health information. To align with current standards, we are using ICD-10, ICDO3, CTACE V5.0, HL7, SNOMED and LOINC code sets. Further, this adaptable model allows for 5-10 disease specific elements to accommodate for disease heterogenicity and capture the differences among cancer types. Results: The CCDE database includes 1,126 of total data elements. MSKCC has 52,704 patients with MSK-IMPACT (Next-Generation sequencing platform with 505 genes panel) testing of which, we have identified 1,132 bladder cancer patients with at-least one year of cancer care follow-up for the initial curation cohort. Patients were identified as having an OncoTree bladder tumor type code that is assigned by a pathologist who attests the diagnosis by reviewing results from clinical tests on tumor specimens. To the date, 641 patients including 46,415 curated forms have been curated (Table). Conclusions: The comprehensive MSKCC’s CCDE data model standardizes the common and critical pan-cancer and pan-specialty elements for RWD. The dataset resulting from this curation efforts will provide robust structured and unified genomic and phenomic data across tumor types for future research enabling greater collaboration across various cancer types as well as oncology specialties.[Table: see text]
Delays in time to antibiotics in inpatient oncologic neutropenic fever do not predict decreased overall survival.
Authors: Villars Jordan , Gardner Christopher Anand , Zhan Tingting , Binder Adam F 
Published: June 2021

e18765 Background: Neutropenic fever (NF) is relatively common oncologic emergency. Present expert consensus is that anti-pseudomonas gram-negative antibiotics should be administered within 60 minutes of detecting NF. To date studies investigating this relationship in neutropenic fever patients have been either limited in size, or have failed to reliably establish a relationship between time to antibiotics (TTA) and clinical outcomes.While some studies have shown an association between TTA and outcomes in NF patients admitted from the Emergency Department, such studies do not control for the time that patients may have been febrile in the community. To address these factors, we conducted a retrospective study on the effect of TTA on mortality in oncologic patients who developed NF as inpatients. Methods: We performed retrospective chart review of all cases of NF at an NCI designated Cancer Center between 7/1/2016 and 3/27/2019. NF was defined as temperature of 101˚ F on one occasion, or 100.4˚ F sustained over 60 minutes, with an absolute neutrophil count (ANC) less than 500. TTA and survival were calculated via chart abstraction; patients lost to follow up within 180 days were censored to the 180-day mortality group. Relationship between TTA and overall survival (OS) was analyzed via multivariable Cox regression. We excluded patients that had non-cancer related NF, were transferred from another institution with NF, were admitted from the ED with NF, or transitioned to hospice. Only the first instance of NF in any admission was analyzed. Results: A total of 187 eligible cases were identified during the study period, mean age was 57.6 +/- 13.6, 100 (53.5%) cases were in males, 114 (61.0%) cases in Caucasians, 53 (28.3%) in Black People. The 3 most common disease subtypes were acute leukemia (42.8%), plasma cell dyscrasias (27.8%), and lymphoma (16.6%). TTA showed no significant correlation with OS at any timeframe studied. Low Charlson Comorbidity Index ( < 3) correlated with increased survival through ̃360 days, however the effect was non-significant at longer timeframes. Immediate antibiotic treatment ( < 40 mins) correlated with poorer patient prognosis and significantly decreased OS (HR 3.08;CI: 1.30-7.28; p 0.010). Conclusions: TTA was not associated with OS in our study. For inpatients with NF, even hours long TTA may not be long enough to result in adverse clinical outcomes. Unlike NF patients presenting to the ED, where true TTA may often be many hours or even days prior to arrival, a few hours-long TTA in the hospital may not be sufficiently long enough to cause significant patient harm. Interestingly, in our cohort, those who received antibiotics quickly had adverse outcomes. It may be that in patients who were clinically unstable, TTA was shorter given the urgency of the situation. Ultimately, this study’s findings question the applicability of the 60-minute guideline when used in the inpatient setting.
Patterns and costs of hospital-based cancer care in the last year of life: A national data linkage study in England.
Authors: Luta Xhyljeta , Diernberger Katharina , Bowden Joanna , Droney Joanne , Hall Peter S , Marti Joachim 
Published: June 2021

e18769 Background: Delivery of high quality cancer care is associated with rising costs, both in earlier stages of the illness trajectory and at the end of life. A significant portion of the costs and health care utilisation occurs in the last year of life. Most publications to date have focused on costs in hospital. Little is known about the costs of care for cancer patients across the entire health service. The aim was to examine primary, secondary and acute health care utilisation and cost in the last 12 months of life and how these differ by cancer diagnosis and other patient characteristics among decedent patients aged 60 and over. Methods: We conducted a retrospective cohort study of people aged 60 years and over (N=26,077) who died in England between 2010 and 2017. We used routinely collected and linked data from primary care (Clinical Practice Research Datalink (CPRD) secondary and acute care, (Hospital Episode Statistics (HES), and death data (Office for National Statistics (ONS)). This provided a nationally representative sample of the English population. We analysed of healthcare utilisation and resource use amongst decedents by gender, primary cause of death, age, geography, socio-economic status and comorbidities. Results: Overall, 90.2 % of the cancer decedents were admitted in the hospital at least once in the last 12 months of life. About 50% of patients we admitted to hospital in the last month of life with 37.6 being admitted to the hospital more than once in the last month of life. The health care utilisation and costs increased sharply in the last month of life. life. The mean number of hospital admissions in the last year of life was 3.7 (SD, 5.8). Those dying of haematological cancers (N=2093) had highest number of hospital admissions (mean:7.2, SD:10.8) and longer average hospital stay (mean:36.7, SD:33.0) (mean:12.0, SD:14.4). Use of outpatient services was highest in the group dying of haematological cancers (mean:12.0, SD:14.4) whereas those dying of prostate cancer (N= 2197) had higher number of emergency (mean:2.0, SD: 1.9) and GP visits (mean:30.8, SD: 20.7). Healthcare costs were highest among haematological cancers and lowest among those dying of breast cancer. Proximity to death and comorbidities were the main contributors of end-of-life care health care utilisation and costs. Conclusions: This study uses large linked datasets (linked to the whole spectrum of hospital episode statistics) providing a comprehensive picture of healthcare services accessed by cancer patients at end of life in England. There is significant variation in use and cost of care for cancer patients in the last year and month of life. Further analysis of variation according to hospice, palliative, and social care service provision may identify strategies to address this variation.
Real-world clinical practice: Toxicities of maintenance PARP inhibitors in recurrent ovarian cancer—The Royal Marsden experience.
Authors: Ali Zohra , Appadu Laura , Kitetere Ellen , Wampfler Julian , Yang Dorothy , Jupp Philippa , George Angela , Banerjee Susana N. 
Published: June 2021

e18770 Background: Maintenance therapy with PARP inhibitors (PARPi) in recurrent high grade ovarian cancer is standard of care for patients who have responded to second or subsequent lines of platinum-based chemotherapy. The increased access to PARP inhibitors (Olaparib, Niraparib and Rucaparib) has provided the opportunity to explore the real-world toxicities in routine clinical practice, toxicity management and the consequent impact on maintenance therapy outcomes. Methods: Patients with relapsed ovarian cancer that received maintenance PARP inhibitor therapy in routine clinical practice between April 2015 and April 2020 were identified. Electronic patient records were reviewed retrospectively to retrieve details of any reported toxicities (occurring at any time during therapy) and their management. Data was entered into and analysed in a Microsoft Excel spreadsheet. Results: 99 patients who received second or subsequent line maintenance PARPi therapy were included (median age 63.6 years). 36% had a germline BRCA1/2 mutation, 6% had a somatic BRCA1/2 mutation and 58% were BRCA wild-type. 69% received 2nd line maintenance therapy; 22% and 9% received a maintenance PARP inhibitor following 3rd or 4+ line therapy respectively. 56% had not received previous maintenance therapy; 43% had received Bevacizumab. 48% patients commenced maintenance therapy at full dose. 13% of patients experienced no toxicities. 60% of patients experienced G1-2 toxicities, with 42% experiencing >2 episodes; most common toxicities were fatigue, nausea/vomiting and thrombocytopenia. 26% of patients experienced >G3 toxicity, with 9% experiencing >2 episodes, 4% of which were recurring toxicities; most common toxicities were hypertension, neutropenia and anaemia. 64% of patients developed toxicity within the first cycle of treatment; 39% had a dose interruption, 56% of which were < 2 weeks duration. 59% patients required a dose reduction from their starting dose due to toxicities. There was no significant difference in median PFS between patients who had been dose reduced compared to those who received full starting dose (p > 0.05). Conclusions: In keeping with phase III clinical trials, our real-world experience is that most PARPi toxicities are low grade and occur early in treatment. Toxicities can be effectively managed with brief dose interruptions and dose reductions, without adverse impact on survival outcomes.
Association of azole antifungals with survival in patients with non-small cell lung cancer receiving immunotherapy.
Authors: Sebastian Nikhil , Stokes William A. , Behera Madhusmita , Jiang Renjian , Gutman David , Giuste Felipe , Burns Abigail , Ramalingam Selvi , Sukhatme Vidula , Lowe Michael C. , Ramalingam Suresh S. , Sukhatme Vikas , Moghanaki Drew 
Published: June 2021

e18777 Background: Preclinical data suggest certain azole derivatives may have antitumor efficacy and modulate responses to immune checkpoint inhibitors (ICIs). Clinical evidence of synergy can support ongoing research that is investigating the role of repurposing current FDA-approved azole medications to improve outcomes in people with non-small cell lung cancer (NSCLC). We evaluated the association of concomitant azole drugs in a population of NSCLC patients treated with ICI within the Veterans Health Administration. Methods: We conducted a retrospective cohort study of veterans diagnosed with NSCLC between 2010-2018 who were treated with ICI. Receipt of azole drugs was defined as taking a systemic azole within 90 days of ICI therapy. Overall survival (OS) was measured from the start of ICI therapy using Cox-Proportional Hazard (PH) multivariable regression. Patients whose earliest azole administration occurred more than 30 days after initiation of ICI were excluded. Results: We identified 3,413 Veterans treated with ICI; of these, 324 (9.5%) were treated with an azole, most commonly clotrimazole (3.0%) and fluconazole (2.5%). Patients had predominantly stage IV disease (40.8%) at initial diagnosis, followed by stage III (27.1%), stage I-II (19.9%), and unknown stage (12.1%). There was no significant difference in OS multivariable analysis (HR = 0.93 [0.81-1.06]; p = 0.28). Propensity score-matched analysis with 324 patients in each cohort also did not measure a significant difference in OS (HR = 0.89 [0.75-1.06]; p = 0.18) between patients who received any azole versus those who did not. When evaluating specific azole agents on multivariable analysis, there was an association of higher OS with receipt of clotrimazole (HR = 0.72 [0.56 – 0.92]; p = 0.009) and more than one azole (HR = 0.71 [0.53-0.96]; p = 0.026) when compared with no azole. There was an association of shorter OS with miconazole (HR = 1.92 [1.30-2.832]; p = 0.001) and no association with itraconazole (p = 0.08), fluconazole (p = 0.20), or ketoconazole (p = 0.87). In the matched analysis of 102 clotrimazole patients versus no azole, OS was longer in patients who received clotrimazole (HR = 0.76; 95% CI 0.55 – 1.04; p = 0.087), although this effect was not statistically significant. Conclusions: This analysis demonstrated a trend towards longer survival with concomitant clotrimazole and ICI for advanced NSCLC. This association was not seen for other azole mediations.
Real-world BRAF testing patterns for patients with metastatic colorectal cancer (mCRC), metastatic melanoma, and non-small cell lung cancer (NSCLC).
Authors: Edwards Michelle L. , Levin Rebecca , Abraham Anup , Amari Diana T. , Kelton John M. , Vieira Maria Cecilia 
Published: June 2021

e18778 Background: BRAF mutations are estimated to occur in up to 10% of people with colorectal cancer, 45% with melanoma, and 2-4% with NSCLC and generally represent a poor prognosis for these patients. The National Comprehensive Cancer Network (NCCN) recommends BRAF testing for patients with mCRC, melanoma and NSCLC, however adherence to guidelines and real-world testing rates are not well known. This study describes real-world BRAF testing rates among mCRC, m-melanoma and NSCLC patients. Methods: We performed a retrospective study of adult patients diagnosed with mCRC or m-melanoma from 1/2013 to 11/2020 in the nationwide Flatiron Health EHR-derived de-identified database and with NSCLC from 1/2013 to 11/2020 in the ConcertAI Definitive Oncology Dataset. We measured the proportion of patients receiving a BRAF test and timing of testing in relation to diagnosis and treatment line, concentrating the latter on a limited time frame when there was a stable period of testing (2018-2019 for mCRC and m-melanoma; 2018 for NSCLC). Results: We included 21,758 patients with mCRC, 4,276 patients with m-melanoma, and 12,236 patients with NSCLC of whom 52.7%, 92.0% and 17.2%, respectively, received a BRAF test. Testing rates for mCRC and NSCLC increased over time (mCRC: 27.3% in 2013, 49.9% in 2016, 71.4% in 2020; NSCLC: 6.4% in 2013, 13.5% in 2016 and 29.5% in 2018) and were relatively stable for m-melanoma (94.5% in 2013, 90.6% in 2016, 89.5% in 2020). Among BRAF-tested mCRC patients in 2018-2019 (70.3%, n=5,874), 7.8% were tested before metastatic (m-) diagnosis, with median time from test to m-diagnosis of 8.5 months; 32.1% on or after m-diagnosis and before 1L and 55.8% on or after 1L, with median time from m-diagnosis to test of 1.4 months. Among BRAF-tested m-melanoma patients in 2018-2019 (91.7%, n=1,174), 31.0% were tested before m-diagnosis, with median time from test to m-diagnosis of 9.5 months; 62.2% on or after m-diagnosis and before 1L and 2.5% on or after 1L, with median time from m-diagnosis to test of 0.0 months. Among BRAF-tested NSCLC patients in 2018 (29.5%, n=2,010), 3.0% were tested before earliest diagnosis, with median time from test to diagnosis of 0.3 months; 24.6% on or after earliest diagnosis and before 1L and 15.4% on or after 1L, with median time from diagnosis to test of 1.1 months. (For about 60% of the BRAF-tested patients, it was not possible to identify at which stage of treatment the test was conducted). Conclusions: BRAF testing rates were highest among m-melanoma patients, followed by mCRC and NSCLC. Testing rates for mCRC and NSCLC increased from 2013 to 2020, which may have been in response to guideline changes and availability of targeted treatments. The majority of BRAF testing occurred before 1L in melanoma and NSCLC, and on or after 1L in mCRC.
Clinical trials participation is directly influenced by the information received by cancer patients (pts) and caregivers: Real-world evidence with the use of a specialized digital health platform.
Authors: Greenfeld-Barsky Keren , Hasid Lior , Vorobiof Daniel A. , Malki Eliran 
Published: June 2021

e18779 Background: Clinical trials (CT) participation is both crucial for medical advancement and an important treatment option, at times the only one, for oncological pts. However, only an estimate of ̃3% of cancer pts worldwide enrolls into such trials. Different factors have been implicated in underlying this low participation rate, with little current data on patients’ own perspective. In this study, pts & caregivers’ perception, knowledge and experience with CT were assessed via a unique digital health platform. Methods: 290 American and Israeli members of Belong.life cancer application (app) anonymously & voluntarily replied to a 10 questions survey detailing their demographics, diagnosis, and experience with CT as a treatment option. Results: 234 participants were pts (81%) and 56 (19%) caregivers. 73% of participants were US based. 35 participants (12%) were < 50 years of age (yoa), 94 (32%) were 50-59 yoa, 117 (40%) were 60-69 and 44 (15%) were > 70 yoa. There were 79 males and 211 females.The most common diagnosis was breast cancer in 74 (26%), hematologic in 36 (12%), lung in 35 (12%), colorectal in 26 (9%) and ovarian in 26 (9%). Stages were 4 in 117 (40%) and 3 in 52 (18%), early (1&2) in 73 (25%). 134 (46%) have not heard about CT participation as a treatment option. Among 125 participants of the 134 who were not familiar with CT as a treatment option, 115 (92%) stated they would like to learn more about it. Among the 156 participants who were acquainted with this option, 52 (33%) heard about it from medical staff, 41(26%) from multiple online resources, and 39 (25%) only through the Belong.life app. Only 23 participants (8%) previously participated in a CT. The most common reason for not participating was not being offered this treatment option (55, 49%) followed by lack of suitable trials for their condition (26, 23%). The most common reason for considering it was to receive an innovative treatment (60, 44%). Conclusions: Almost half of the pts and caregivers were not aware of CT participation as a valid treatment option. Among them, nearly all have expressed an interest to be better informed. This significant dissonance was also evident among those aware but who were not offered to participate, while expressing a favorable perception regarding participation. While the medical staff is a key source for CT awareness, and whilst patients are exposed to multiple online sources of information, this survey confirmed that 25% of Belong.life members received information about CT availability and participation singly from the app and 8% of them actively participated in a clinical trial. In sum, emphasis should be placed on providing personally tailored CT information to all cancer patients and caregivers. Digital health platforms are an important source for patients CT awareness.
Thrombotic complications with SARS-CoV-2 infection in patients with cancer on high-risk therapies: Data from the COVID-19 and Cancer Consortium (CCC19).
Authors: Gulati Shuchi , Shah Surbhi , Kulkarni Amit , Desai Aakash , Fu Julie , Zon Rebecca , Kumar Vaibhav , Hsu Chih-Yuan , Hwang Clara , Doroshow Deborah Blythe , Akpan Imo , Girard Jennifer , Yu Peter Paul , McKay Rana R. , Bakouny Ziad , Connors Jean , Shah Dimpy P. , Warner Jeremy Lyle , Rosovsky Rachel Pam Greenerger , Grivas Petros 
Published: June 2021

e18788 Background: Patients (pts) with cancer have a high risk of venous thromboembolic (VTE) complications, further enhanced by anti-cancer treatments, specifically hormonal therapies, targeted therapies (VEGF inhibitors, other TKIs) and immune checkpoint inhibitors (ICIs). We hypothesized that high-risk therapies would predispose pts with cancer and COVID-19 to higher risk of VTE complications. Methods: CCC19 is the largest international registry (NCT04354701) recording outcomes of pts with cancer and COVID-19. The registry was queried for hospitalized pts who developed VTE and received systemic cancer treatment in the year prior to COVID-19. Incidence of VTE was analyzed as the primary endpoint; 30-day any cause mortality & need for ICU admission at baseline were secondary endpoints in pts with and without VTE respectively. Pts were stratified by treatment type and time from last treatment dose: <2 wk, 2-4 wk, 1-3 months (mos), 3-12 mos. Results: As of February 9th 2021, 4217 hospitalized pts with complications data were present in the registry. 1867 (44%) pts had received systemic anti-cancer therapy within the year prior to COVID-19 and were analyzed. There were a total of 186 (10%) VTE events. Of these, VTE incidence was 141 (10.5%) in pts with solid tumors and 57 (9%) in pts with hematologic malignancies. Overall 30-day mortality was 20% and 22% in pts with and without VTE respectively, while direct admission to ICU at presentation was seen in 17% and 10% of pts with and without VTE, respectively. Treatment timing and drug exposures are below (Table). Receipt of systemic anti-cancer treatment within 3 mos vs 3-12 mos was associated with increased rate of VTE, OR 2.44, 95% CI 1.18-5.84, p=0.011 (univariate Fisher test). Conclusions: We describe the incidence of VTE events in pts with cancer and COVID-19 with recent systemic cancer therapy. ICI and VEGFi were associated with numerically higher rates of VTE; other examined drugs and drug classes were not. Timing of therapy appears to modify risk of VTE. Although retrospective, with possible selection and confounding biases, our analysis suggests that factors other than anti-cancer drug exposures may drive VTE events in this population.[Table: see text]