bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of blinded independent central review on subject eligibility in oncology studies.
Authors: Borys Larissa , Marini Matthew , Lu Edwin , Ford Robert 
Published: June 2022

e13603 Background: Oncology clinical trials that use imaging based surrogate endpoints such as Progression Free Survival (PFS) and Overall Response Rate (ORR) generally have eligibility criteria based on imaging. Examples include but are not limited to the presence of a RECIST measurable lesion at baseline for studies where ORR is the primary endpoint, the absence of disease at baseline in recurrence studies, the absence of exclusionary brain metastases, and the presence or absence of a particular stage of disease at baseline, such as the absence of T4b, M1, and >N2 disease in studies of muscle invasive bladder cancer. Our experience suggested the percentage of subjects who did not meet those criteria during Blinded Independent Central Review (BICR) may be higher than expected and could have a significant effect on the statistical power of studies. We reviewed a large cohort of subjects (n = 8746) to determine the fraction of subjects who were considered for enrollment or enrolled in oncology clinical trials by investigators and were deemed ineligible during BICR. Methods: We analyzed 66 trials with a total of 8,746 total subjects. Trials were selected based on initiation between June 2020 and June 2021 and involvement of one (1) or more imaging eligibility criteria. Trials in this cohort fit into 2 categories: those that had prospective real time eligibility review where subjects could not be enrolled until the eligibility review was completed in real time (“eligibility review trials”) and those trials that did not have a prospective eligibility review however the data was available for retrospective analysis (“efficacy only trials”). Our analysis determined the fraction of subjects that were prospectively and retrospectively ineligible under each respective category. Results: In these categories, 56% of the subjects (n = 4934) were involved in efficacy only trials. Following BICR review, 12% (n = 614) of the subjects were found to be ineligible retrospectively. Conversely, 44% of the subjects (n = 3812) were enrolled in trials where Clario performed a prospective eligibility review. We found that only 89 of those subjects were deemed ineligible at the time of the prospective eligibility review (2%). This translates to 2% of the subjects were deemed eligible by the investigators, but ineligible by the Clario review. The 10% difference suggests that the eligibility review prevents inclusion of a significant number of subjects that are subsequently determined to have not met the initial imaging eligibility requirements. Conclusions: Eligibility review appears to improve standardization of subject eligibility. These data suggest that the omission of an eligibility review can cascade into censoring more than 10% of subjects. This could have significant impacts on the statistical power of a study and should be considered during study designs.
Real-world data on the clinical utility of a novel artificial intelligence-based computational method to support treatment decisions in gastrointestinal cancers.
Authors: Petak Istvan , Vodicska Barbara , Kispeter Eniko , Doczi Robert , Tihanyi Dora , Lakatos Dora , Dirner Anna , Vidermann Matyas , Szalkai-Denes Reka , Deri Julia , Kamal Maud , Schwab Richard , Le Tourneau Christophe 
Published: June 2022

e13616 Background: Several molecularly targeted agents (MTA) are registered in the same indication, even in the same line, to treat gastrointestinal (GI) cancers. Comprehensive molecular profiling is readily available for many patients, but only a few biomarkers are used to make clinical decisions between on-label MTAs. Most tumors harbor a combination of driver alterations potentially affecting the sensitivity to MTAs according to hundreds or thousands of evidence items that can explain the heterogeneous clinical response of individual patients to these therapies. We have developed an AI-based computational method, an automated, evidence-based reasoning framework, called digital drug assignment (DDA) to provide decision support based on the complete molecular profile for each patient. DDA has been shown to potentially improve treatment decisions in case of complex molecular profiles acquired in the SHIVA01 trial. In the present study, we analyzed the clinical utility of DDA in on-label treatment decisions in GI cancers. Methods: We analyzed the next-generation sequencing (NGS) data obtained using 50-591-gene panels of 239 patients with GI tract cancers from our everyday practice. Molecular profiles were uploaded to a DDA-based software system to calculate the aggregated evidence level (AEL) values of associated MTAs registered in the same indication of selected GI cancers. Decision support rate (DSR) was calculated as the percentage of patients where DDA could support clinical decisions based on the presence of genetic alterations associated with any of the available MTAs. Results: Targeted treatment options registered in the same indications and the DDA-based decision support rates (DSR) are shown in the table. For example, DDA could support the decision between cetuximab and bevacizumab based on NGS results in 47% of RAS/RAF wild-type colorectal cancer cases. Larger NGS panels yielded higher rates of decision support (44% vs 52% with gene panels under and over 300 genes, respectively). Conclusions: DDA-based computational reasoning can support molecular profile-based treatment decisions among different on-label MTAs in a clinically meaningful fraction of GI cancers.[Table: see text]
Creating diversity, equity, inclusion, and access in cancer clinical research: Drive rank and Drive score.
Authors: Birhiray Maya Nicole , Birhiray Ruemu Ejedafeta 
Published: June 2022

e13636 Background: The inequalities in improving cancer mortality rates in the United States can be ascribed to treatment disparities that are largely due to unequal access to clinical trials in cancer care, resulting in adverse clinical and economic effects. D.R.I.V.E is a five-step strategy for promoting and improving DEIA in clinical trials for minority patients based on the following steps. Methods: Appointing a clinical trial Diversity Officer, creating a RANK SCORE based on minority enrollment, Individual diversity plan, Verification of study diversity, and Elevate and Enhanced training of minority investigators and research team members. Results: Global Performance Indicators (GPIs), which rate and rank states relative to one another, shape decisions. Rankings should be reported by authors and required for publication in peer-reviewed journals and should be included in journal impact factor assessment. Conclusions: DRIVE aims to use these strategies to correct inequalities and promote the overall health of mankind, using proven principles and techniques to create meaningful improvements in cancer care and outcomes. DRIVE RANK), based on the achievement of minority participant representation relative to the epidemiology of disease, is an informational tool to evaluate DEIA efforts and provide a readily accessible measurement of the applicability of clinical data to all patient subgroups with the potential to force positive changes to promote DEIA and the health of mankind. We propose a ranking of 0-5 for diversity (Table). Establish a corporate ranking system (DRIVE SCORE) based on the diversity of clinical data from the totality of studies of the company to inform the choice of ethical investors. Studies will be ranked at the next lower rank if all criteria for next higher rank are not reached.[Table: see text]
Single institution assessment of compliance with guideline directed aspirin therapy in the prevention of colorectal cancer in Lynch syndrome.
Authors: Wu Kathie , Williams Heinric , Ramdin Nadia N. 
Published: June 2022

e13637 Background: Patients with Lynch syndrome have up to 80% lifetime risk of developing colorectal cancer. Research shows chemoprevention with aspirin 600 mg for 25 months can reduce this risk for Lynch syndrome patients by 59%. In our study, we evaluated the compliance with aspirin therapy among Lynch patients at our institution. Methods: Our clinic identifies and follows all patients with a history of Lynch syndrome. Of our 125 patients, 62% were discovered after a family member was found to have a high-risk cancer, 29% were identified through MyCode, a DNA sequencing program which looks for gene mutations specific to Lynch. All patients in the clinic undergo discussion about starting aspirin therapy. Medication agreements and dosing are documented in the chart. Data was retrospectively reviewed to assess our patient compliance with recommendations. All data was based on subjective reports of compliance and reported doses. Results: 125 patients were included in the data analysis. Various risk factors were assessed including age, gender, history of cancer, and other comorbidities. Ages ranged from 20 to 78; 74% were female, 26% male. 90% of patients had a family cancer and of those, 47% had a personal history of cancer. Overall, 57% of patients agreed to take aspirin with doses ranging between 81 mg to 600 mg. 60.8% of patients took 81 mg of aspirin daily and 30.6% took 325 mg daily, citing concerns for bleeding and ulcer at higher doses. Only 8% of all patients agreeable to aspirin therapy took the recommended 600 mg dose. Of those who refused aspirin therapy, 5% reported allergy or prior intolerance, 13% had history of gastric ulcer or prior bleeding, 2% were taking medications which taken concomitantly with aspirin would increase risk of bleeding, and 80% provided no reason. Chi square test of independence was performed to examine the relationship between aspirin use and gender (χ² = 0.76, p = 0.38), age (χ² = 1.99, p = 0.37), and personal or family history of cancer (χ² = 9.89, p = .002). Results showed a patient with personal, or family history of cancer was more likely to take aspirin therapy, but there was no significant relationship among gender or age. Conclusions: Aspirin serves as an effective and affordable therapy for the prevention of colorectal cancer in patients with Lynch syndrome. Barriers to compliance should be identified and chemoprophylaxis should be initiated in all qualified patients. Future studies should be performed to establish more concrete recommendations about dosing and duration of aspirin therapy especially given the ease of access and cost effectiveness.[Table: see text]
Real-world practice patterns in the diagnosis of recurrent metastatic breast cancer in Washington state.
Authors: Manohar Poorni , Fedorenko Catherine R. , Sun Qin , Voutsinas Jenna M. , Wu Vicky , Roth Josh , Linden Hannah M. , Shankaran Veena 
Published: June 2022

e13640 Background: Evidence-based, national guidelines for the diagnosis of recurrent metastatic breast cancer (MBC) recommend confirmation of recurrence with biopsy and reassessment of biomarker status. Real world practice patterns may demonstrate disparities in adherence to guidelines with implications for patients and health systems. Methods: We utilized the Hutchinson Institute for Cancer Outcomes Research (HICOR) data repository that links Washington State cancer registry data to enrollment and claims from the major insurance payers in the state. We identified women > 18 years old diagnosed with recurrent MBC between 2008 and 2017 with evidence of enrollment in a commercial plan (Premera or Regence), Medicare, or Medicaid. Recurrence in Stage I-III patients was detected through identification of ICD 9/10 codes for metastatic disease or resumption of breast cancer systemic therapy (after minimum of 4 months from completion of early breast cancer therapy). Using claims, we identified receipt of and factors associated with biopsy, biomarker re-assessment, and treatment administered at recurrence. Results: We identified 715 patients with recurrent MBC (any ER or HER2 status) with median age of 62 (range 52-73). The majority of the cohort were Caucasian (89%) with the rest comprising of Asian, Black, American Indian, and Hispanic patients. Based on the Rural Urban Commuting Area (RUCA) classification, patients predominantly lived in metropolitan neighborhoods (97%). Approximately 13% of patients lived in areas of high deprivation (area of deprivation index, ADI, 8-10). Patients had either Commercial (53.1%), Medicaid (4.2%), Medicare (29.7%) or multiple (13.0%) insurance. Patients were primarily treated at high volume centers (70.9%), though 23% of patients were seen at low volume centers (<25 breast cancer patients/year). Of the patients with recurrent MBC, 49.5% received a biopsy to confirm metastatic diagnosis. Similarly, 48.7% of recurrent MBC patients underwent biomarker reassessment. Patients with highest co-morbidity index (>2) were more likely to undergo biopsy confirmation (20.3% vs 13.0%, p = 0.02). Biopsy was more often performed in patients receiving care at a high-volume center compared to low-volume center (74.3% vs 18.6%, p = 0.03). First line treatment selection was directly associated with receipt of biopsy and biomarker testing. Hormone therapy only was more common in patients who did not undergo biopsy (62.3% vs 37.7%, p <0.001) or biomarker reassessment (62.7% vs 37.3%, p <0.001). Conclusions: Our study shows there is variation across Washington state in biopsy and biomarker assessment in the diagnosis of recurrent metastatic breast cancer. Nearly half of cases had metastatic biopsy omitted. Our findings demonstrate downstream implications for treatment selection and support the need for quality initiatives to improve adherence to guidelines.
The impact of virtual oncology care on chemotherapy continuity and clinical outcomes in patients treated for colorectal cancer: A pre-post analysis of the COVID-19 pandemic.
Authors: Phillips William James , Leung Macyn , Thavorn Kednapa , Asmis Timothy R. 
Published: June 2022

e13649 Background: The coronavirus (COVID-19) pandemic has resulted in an abrupt transition to virtual oncology care at most cancer centres worldwide. A pillar of the American Medical Association’s proposed framework for digitally enabled care is assessing clinical quality, safety, and outcomes. This study’s objective is to evaluate chemotherapy quality and clinical outcomes in patients receiving intravenous chemotherapy for colorectal cancer before and during the COVID-19 pandemic. Methods: This is an observational study assessing patients treated with intravenous chemotherapy for colorectal cancer consecutively at the Ottawa Hospital Cancer Centre from June 2019 to September 2021. Patients with non-metastatic rectal cancer were excluded. Patient were stratified by whether they were started on chemotherapy pre-pandemic (June 2019 – Jan 2020) versus intra-pandemic (Feb 2020 – Sept 2021). Baseline characteristics and treatment data were collected from the electronic medical records. Outcomes of interest included chemotherapy delays, dose reductions, emergency department (ED) visits and hospitalizations. We used generalized linear and binary logistic regression modelling to compare outcomes between pre- and intra-pandemic periods. Results: There were 220 patients included in this study with 108 (49%) diagnosed with metastatic disease. In total, there were 66 (30%) patients treated in the pre-pandemic and 154 (70%) in the intra-pandemic period. As expected, virtual care consultations increased during the pandemic from 1.5% to 43.5% (p < 0.001). Likewise, the proportion of follow-up visits also increased from 37% to 84% (p < 0.001). There was no difference in the incidence of treatment delays (odds ratio [OR] = 1.01, p = 0.78), dose reductions (OR = 0.99, p = 0.69), ED visits (OR = 1.23, p = 0.37), hospitalizations (OR = 0.73, p = 0.43) or the total length of time off treatment (OR = 0.85, p = 0.17) between the pre- and intra-pandemic periods by multivariable analysis. A subgroup analysis was performed based on stage, which showed no difference in outcomes independent of the presence of metastases. Conclusions: This study demonstrates no significant difference in chemotherapy interruptions, dose intensity, or clinical outcomes in patients treated for colorectal cancer during the COVID-19 pandemic. These findings serve as an important quality-care indictor and demonstrate that virtual oncology care appears safe in a cohort of high-risk colorectal cancer patients. Future work dedicated to other tumor sites would allow for broader application of these findings.
Integration of traditional molecular diagnostic tools and targeted next generation sequencing for the precise diagnosis and management of adult gliomas.
Authors: Kanan Duaa , Safı Şebnem , Kanan Tarek , Celik Serkan , Öven Bala Başak , Yapicier Ozlem 
Published: June 2022

e14011 Background: It is known that gliomas represent a wide variety of entities with varying biological features and clinical outcomes (Neuropathol Exp Neurol 2019, 78). Hence, optimal tumor classification that aids in the diagnosis and management of patients and which supports the use of specific treatment modalities is of critical importance in neuro-oncology. Targeted next-generation sequencing (NGS) has proven to be an efficient and reliable tool for identifying prognostic biomarkers for the diagnosis of CNS tumors (Neurooncol Adv 2020, 2). Here, an analysis of the impact of using NGS in addition to traditional molecular tools on tumor classification and therapy selection was analyzed; and the overall concordance was evaluated. Methods: Patients with glial tumors who were seen at our clinic between 2019-2020 and had an NGS analysis in addition to traditional molecular studies were included. All clinical data, histopathological findings and genetic reports were retrieved from the electronic medical record. We retrospectively studied each of the patients’ findings with regards to their clinical diagnosis, grade, anatomic localization; ki67 (%); TP53, IDH and ATRX mutations; as well as microsatellite instability (MSI) and additional mutational studies such as HER2 and BRAF for some patients. The concordance between the genetic and molecular data regarding TP53 and IDH mutations was also analyzed. Results: 9 patients (66.7% male) with grade 3-4 gliomas were identified at our single-center oncology institution. Most patients had a diagnosis of glioblastoma (55.6%), with a median age of 43 years at the time of diagnosis. 22.2% (2/9) had a genetic analysis through FoundationOneCDx. The concordance of the identification of mutations by NGS and immunohistochemistry (IHC) was 77.8% (7/9) for IDH mutations, and 55.6% (5/9) for TP53 mutations. NGS led to the identification of TP53 mutation in 1 patient (11%) which IHC failed to show. NGS also supported the use of targeted therapy [dabrafenib] in 1 patient (11.1%) with BRAF positivity. Conclusions: Traditional molecular diagnostic tools and targeted NGS are not perfectly concordant, but when integrated together can lead to a more comprehensive identification of genetic mutations and potential biomarkers. This can have significant implications on the precise diagnosis and potential use of targeted therapies of adult gliomas in the future.
Real-world analysis of outcomes of patients receiving bevacizumab for recurrent glioblastoma in British Columbia.
Authors: Chahal Manik , Harrison Rebecca A. , Thiessen Brian Arthur 
Published: June 2022

e14017 Background: Bevacizumab (Bev) has been publicly funded in British Columbia (BC) since 2011 for treatment of recurrent glioblastoma (rGBM). We performed a retrospective outcomes assessment of patients with rGBM treated with Bev to evaluate treatment practices and outcomes. Methods: Patients with rGBM treated at BC Cancer centers with Bev between January 2011 and December 2017 were reviewed. Patient demographics, tumor characteristics, treatment regimens, and dates of radiographic progression and death were collected. Kaplan-Meier method was used to assess survival, and comparisons were made using the log-rank test. Results: 182 patients were reviewed. There were 180 reported deaths with median PFS 3 months (CI95 = 2.5 - 3.5) and OS 7 months (CI95 = 6.2-7.8) from Bev initiation. Higher corticosteroid dose prior to Bev initiation was associated with worse OS on univariate and multivariate analysis ( p = 0.40 and 0.01, respectively). 67% of patients on corticosteroids reduced their dose shortly after Bev initiation. Most patients (68%) were treated with multiple lines of therapy prior to Bev, with a median time from chemoradiation to Bev initiation of 8 months (range 1-67). Patients started on Bev < 6 months from completion of chemoradiation (prior to adjuvant temozolomide completion) had improved PFS ( p = 0.02) and OS compared to those who started Bev later ( p = 0.05), but there was no association between extent of treatment prior to Bev and outcomes ( p = 0.09). Addition of chemotherapy to Bev did not improve survival over Bev monotherapy ( p = 0.10). Conclusions: Bev combinations with chemotherapy did not confer survival advantage over Bev monotherapy. Furthermore, our results show that patients receiving Bev before completion of adjuvant chemotherapy have better outcomes, suggesting pseudoprogression may have prompted the therapeutic switch. Despite limited benefits to overall survival, Bev is associated with reduction in corticosteroid use and likely improvement in quality of life. Therefore, further research is required to optimize patient selection for and administration of Bev. Additional analysis of rGBM patients prescribed Bev until 2020 in BC is currently underway.