bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methodology, results, and publication of oncology clinical trials: Insights from all the world’s randomized controlled trials (RCTs) 2014-2017.
Authors: Sharma Shubham , Wells Connor , Del Paggio Joey C. , Hopman Wilma M. , Gyawali Bishal , Pramesh C S. , Sullivan Richard , Booth Christopher M. 
Published: May 2020

2019 Background: Clinical cancer research is now a global effort. Most published overviews of oncology trials are restricted to a specific disease site or cohort of high-profile journals. Here we describe authorship, trial characteristics, design, and results of all oncology RCTs published globally during 2014-2017. Methods: A structured literature search was designed using PUBMED to identify all RCTs evaluating anti-cancer therapies published during 2014-2017. Data were captured regarding authorship, participants, study characteristics, design, and results. Among superiority RCTs that met the primary endpoint (i.e. statistically “positive”), we calculated the ESMO-MCBS to identify trials with substantial clinical benefit (MCBS scores 4/5 or A/B). Outcomes were compared with Chi Square or Fisher’s Exact tests. Results: The study cohort included 694 RCTs. The most common cancers evaluated were breast (17%, 121/694), lung (15%, 104/694) and colorectal (8%, 58/694). Treatment intent was curative, adjuvant/neoadjuvant, and palliative in 10% (68/694), 25% (176/694), and 65% (448/694) of trials respectively. Median sample size was 443 (IQR 246-718). Seventy percent (488/694) of RCTs were supported by industry; 87% (601/694) of experimental arms tested systemic therapy. Ninety-two percent (636/694) of RCTs were led by investigators in 28 high-income countries; the most common countries leading these trials were US (27%, 174/636), France (10%, 64/636), Germany (10%, 62/636), Japan (9%, 59/636), and UK (9%, 57/636). The most common primary endpoints were PFS (32%, 220/694), OS (31%, 215/694), and DFS (11%, 79/694); Forty-six percent of all trials (318/694) met their primary endpoint. Among superiority trials with “positive” results, 33% met ESMO-MCBS threshold for substantial clinical benefit. The median impact factor (IF) of journals which published the overall study cohort of trials was 21 (IQR 7-27); trials meeting their primary endpoint were published in higher profile journals (median IF 25 vs 18, p < 0.001). Conclusions: At the global level, oncology clinical trials are dominated by high-income countries and study diseases which do not necessarily reflect the global burden of cancer. The vast majority of trials are funded by industry and only one third of “positive” trials meet ESMO-MCBS threshold for substantial clinical benefit.
Association of hospital type and patient volume growth with timely cancer treatment.
Authors: Frosch Zachary AK , Illenberger Nicholas , Mitra Nandita , Boffa Daniel J. , Facktor Matthew A. , Nelson Heidi , Bekelman Justin E. , Shulman Lawrence N. , Takvorian Samuel U 
Published: May 2020

2022 Background: Studies have suggested superior outcomes for patients with cancer treated at National Cancer Institute (NCI) and academic hospitals, leading some to advocate for complex cancer care to be delivered at regional referral centers. However, growing demand at such centers may exceed their capacity to provide timely treatment, which could be detrimental to patient outcomes. We evaluated the relationship between hospital type, the average annual growth rate in patient volume (PV), and time to treatment initiation (TTI) trends. Methods: We used the National Cancer Database to identify patients undergoing initial treatment for a new diagnosis of cancer (breast, lung, prostate, colorectal, melanoma, bladder, non-Hodgkin lymphoma, renal, uterine or pancreatic) in 2007-2016. The exposure was hospital type (NCI, academic, community or integrated network). The primary outcome was TTI over time. We estimated both the average annual growth rate for PV and adjusted TTI trends by hospital type using linear mixed effects models, including a hospital type-by-time interaction and, when modeling TTI, a patient volume-by-time interaction. Results: We identified 4,218,577 patients treated at 1351 hospitals (49% at 897 community, 23% at 177 academic, 14% at 50 NCI and 14% at 227 integrated network hospitals). Over the study period, PV grew by 40% at NCI and 25% at academic hospitals, compared to 8% at community hospitals (p-value for trend both < 0.001). Meanwhile, mean TTI increased by 3.2 days at community, remained stable at academic (+0.3 days) and decreased by 4.3 days at NCI hospitals (p-value for trend both < 0.001 vs community). A higher annual PV growth rate was associated with a statistically but not clinically significant TTI increase (0.05 days for each 100 patient/year increase in the growth rate, p = 0.001). Conclusions: Patients with newly diagnosed cancer are increasingly receiving treatment at NCI and academic hospitals. While TTI at NCI and academic hospitals is longer than in the community, PV growth has been possible without delaying cancer treatment. Further study is needed to determine whether continued growth at this rate is sustainable. [Table: see text]
Impact of an immuno-oncology (IO) education/monitoring program on patient’s self-efficacy and adverse event reporting from immune checkpoint inhibitors (ICIs).
Authors: Cheema Parneet Kaur , Nematollahi Massey , Berco FeRevelyn , Papadakos Janet , Kaushik Deepanjali , Matthews Priscilla , Iafolla Marco , Perdrizet Kirstin , Balcewicz Margaret , Raskin William , Reingold Stephen , Husain Juhi , Kuruvilla Philip , Conter Henry Jacob 
Published: May 2020

2032 Background: ICIs have unique side effects of immune related adverse events (irAEs). For early detection and management of irAEs, at a large community hospital we implemented a standard IO nursing baseline assessment, education and monitoring program. We studied it’s impact on a patient’s irAE reporting and self-efficacy (confidence to manage symptoms) of ICIs. Methods: Prospective study conducted at William Osler Health System, Brampton, Canada from May 2018-December 2019. Patients aged > = 18, English speaking that received an ICI for cancer were included. Patients underwent a standardized baseline nursing assessment and education class. Patients identified at the assessment as high risk (risk of grade 3/4 irAE >20%) had weekly nurse proactive calls. Cancer Behaviour Inventory – Brief Version (CBI-B) (Heitzmann et al, 2011) was used to evaluate patient’s self-efficacy. Results: Eighty patients were enrolled. Median follow up of 4.1 months. Baseline demographics: median age 69, 70% males, 77% Caucasian, 81% ECOG 0/1, 66% had English as their first language and 19% highest education was elementary, 30% high school, 26% trade diploma and 21% post-secondary. Fourty-one percent had limited cancer health literacy (measured by CHLT6 (Dumenci et al, 2014)). ICIs prescribed were 70% monotherapy anti-PD1/PDL1, 13% combination nivolumab/ipilimumab, 17% anti-PD1/PDL1 + chemotherapy/other therapies. Majority had a diagnosis of non-small cell lung cancer (55%), melanoma (19%) and renal cell carcinoma (9%). A statistically significant improvement in the average CBI-B scores were found pre and post baseline assessment/education (p < 0.001) and this improvement was maintained over time at follow-up visits (non-significant change in scores from post education results). Fourty-three percent of patient’s experienced > 1 irAE. Most were grade 1/2 at time of detection (65%). Method of detection was mainly by patient self-reporting (62%), followed by proactive calls (27%). Only 3 patients had detection of an irAE with an ER visit. Rate of discontinuation of ICIs due to toxicity was 8.8%. Conclusions: In this diverse patient population with almost half of patients having limited cancer health literacy, a standardized IO baseline assessment, education and monitoring program resulted in improved patient self-efficacy with most irAEs detected by self-reporting and proactive calls. Our IO program can be a model for other oncology programs.
Affordable Care Act Medicaid expansion does not reduce guideline concordant cancer care disparities in vulnerable populations.
Authors: Ju Michelle , Blackwell James-Michael , Polanco Patricio , Mansour John C. , Wang Sam C. , Porembka Matthew R. , Zeh Herbert , Yopp Adam Charles 
Published: May 2020

2039 Background: The receipt of timely, guideline concordant cancer amongst racial/ethnic and socioeconomic vulnerable populations remains a significant health policy issue. The Affordable Care Act (ACA) with implementation of Medicaid Expansion sought to reduce cancer disparities by reducing uninsured rates, theoretically improving healthcare access and delivery. We assessed the impact of Medicaid expansion on racial/ethnic disparities in the receipt of timely guideline concordant cancer care. Methods: We identified patients between 40-64 years of age with all stages of cancer (lung, colorectal, breast, uterine, and cervical) in the National Cancer Database, 2012-2015. Patients were assigned to Medicaid expansion cohort based on state of residence and whether Medicaid expansion was enacted at date of diagnosis in that state. Guideline concordant care was defined based on NCCN guidelines. We constructed an ecological model with multivariate regression analysis on rate of guideline concordant care receipt with covariates including race/ethnicity, Medicaid expansion, SES, gender, Charlson-Deyo score, and treatment facility type. Results: We identified 445,952 patients, 12% Black, 6% Hispanic white, median age 55 years. Patients in the lowest SES quartile following Medicaid expansion had the greatest increase in rates of insured status, although all SES quartiles had increased insured rates compared to non-Medicaid expansion regardless of race/ethnicity. In our ecological model, the rate of receipt of guideline concordant care declined by 0.5% per year between 2012-2015. After adjusting for covariates, Asians were 2.8% less likely to receive guideline concordant care than non-Hispanic whites, Blacks 3.8% less likely, and Hispanics 6.3% less likely (p < 0.0001). Racial/ethnic disparities in receipt of guideline concordant cancer care remained after Medicaid expansion with no differential benefit. Conclusions: Insurance gains under the ACA Medicaid expansion did not affect the rate of guideline concordant care receipt. Significant racial disparities persist in the likelihood of receiving guideline concordant care, particularly among Hispanics. Further studies are needed to determine additional barriers to cancer care access/delivery and identify key targets aimed at improving equity.
Novel artificial intelligence (AI)-based technology to improve oncology clinical trial fulfillment.
Authors: Bowen TJ , Stephens Laura , Vance Mark , Huang Yancui , Fridman Deborah , Nabhan Chadi 
Published: May 2020

2052 Background: Less than 5% of US adult cancer pts are enrolled on clinical trials. Challenges in clinical trial fulfillment limit available treatment options, slow enrollment and ultimately delay new therapies from reaching market. Pt screening requires multiple clinical team members to find pts that meet strict inclusion/exclusion criteria. We evaluated the impact of new technology, Deep Lens VIPER, in identifying more qualified pts for clinical studies, and reduction of staff burden. Methods: We implemented Deep Lens VIPER at Hoag Hospital (Newport Beach, California), accessing the electronic medical records and pathology systems (EMR/LIS) to effectively identify pts who are candidates for 20 ongoing recruiting clinical studies. VIPER was fed pt data from 5,706 surgical pathology pts over a 4-month period (October 1, 2019 - January 31, 2020). Proprietary AI identification and matching technology was configured to align cancer pts with those 20 clinical studies, each with unique study criteria. Following an initial machine-assisted triage step, a research coordinator was alerted when pts who met protocol criteria were ready for final approval steps. Results were analyzed and a qualitative assessment of usability was also performed. Results: VIPER was able to triage all 5,706 surgical pathology cases (100%), identifying 1,045 pts (18.3%) with malignant neoplasms that would qualify for further analysis for clinical trials enrollment. Further triage based on inclusion and exclusion criteria led to the identification of 150 previously unidentified pts for 16 of the 20 studies. The 16 different studies for which potential pts were identified, included 11 tumor types, 12 biomarkers and 3 basket studies. Working with the VIPER system, 1 novice care team member performed initial identification of all 150 previously unidentified pts. The VIPER system increased monthly candidate pt catchment for 16 of the 20 studies under investigation, which is approximately 600 patients annually added for final triage for studies being conducted. Conclusions: We demonstrate the use of an AI-based platform to identify pts for clinical trial enrollment who would be missed using traditional recruiting methods. One staff member effectively triaged participants from 20 different studies with unique inclusion/exclusion criteria. These studies were previously managed by 6 different care team members with limited time for recruitment. Scaling this platform to additional institutions and more studies is ongoing to validate these findings.
Trends in FDA cancer registration trial design over time, 1969-2020.
Authors: Warner Jeremy Lyle , Sethi Tarsheen Kaur , Rivera Donna R , Venepalli Neeta K. , Osterman Travis John , Khaki Ali Raza , Rubinstein Sam 
Published: May 2020

2060 Background: The FDA has issued hundreds of cancer drug indications, with many new drugs, expanded indications, and biosimilars approved in recent years. While the gold standard for regulatory approval is the randomized controlled trial (RCT), RCT design including selection of control arms can differ considerably. We sought to investigate trends and patterns in RCT trial design used to support FDA approvals in oncology. Methods: We reviewed the available FDA package inserts of oncology drugs (N=258) for RCTs cited to support initial and expanded indication approvals as of January 2020; biosimilars were excluded. RCTs were linked to the HemOnc ontology, which contains trial-level metadata including publication year, endpoints, and trial design. Log-linear regression was performed to evaluate trends in approvals over time by endpoint. Study drugs were categorized as cytotoxic therapy, targeted therapy, or immunotherapy. RCTs were categorized by four designs: escalation (adding a drug or increasing the drug dose in an established regimen), in-class comparison (comparing two drugs in the same therapeutic class), out-of-class switch (comparing drugs in distinct therapeutic classes), and de-escalation (removing a drug or reducing the drug dose in an established regimen). Results: We identified 556 registration trials, 372 (67%) of which were RCTs. Approvals have been increasing exponentially over time (R2 0.9, p<0.001), both for RCTs reporting overall survival (OS) endpoints (R2 0.77, p<0.001), and non-OS endpoints (R2 0.67, p<0.001). Of the three most common trial designs (Table), in-class comparisons were least likely to report OS (28%; escalations 47%; out-of-class switches 43%, p=0.01 by Chi-squared). Class switches were common in immunotherapy trials compared to targeted or cytotoxic therapy. Conclusions: Despite growth in FDA approvals, a minority of registration trials report paradigmatic shifts in therapeutic approach (out-of-class switches), with the relative exception of immunotherapy trials. Escalation is the most common route to FDA approval, even though this design inevitably increases cost and toxicity. This suggests that new oncology drug approvals are not alone a useful metric of practice-changing innovation. [Table: see text]
Self-reported overall wellbeing (OWb), physical function (PFn), and PRO-CTCAE symptom scores in post-operative and chemotherapy patients.
Authors: Hazard Hannah , Osarogiagbon Raymond U. , Wong Sandra L. , Bian Jessica J , Dizon Don S. , Wedge Jason , Mallow Jennifer , Basch Ethan M. , Enzinger Andrea Catherine , Wright Alexi A. , Remick Scot C. , Bradford Leslie Siriya , Cass Ilana , Phillips Joseph D. , Ivatury Srinivas J , Bandera Christina A. , Faris Nicholas Ryan , Cronin Christine , Hassett Michael J. , Schrag Deborah ,   eSyM Project Managers
Published: May 2020

2064 Background: A standardized, validated tool for capturing symptoms from cancer patients, PRO-CTCAE, has been used to reduce symptom burden, decrease acute care needs, and preserve quality of life. The association between specific PRO-CTCAE symptom scores and single item measures of OWb and PFn were characterized to understand symptom constellations. Methods: A novel Epic-based symptom management program (eSyM) was deployed for GI, GYN, and thoracic cancer patients starting chemotherapy (Memphis Baptist) or having surgery (WVU Medicine). Patients received automated prompts to complete surveys via the patient portal (MyChart) on a fixed schedule, approximately twice/week. Each survey included one OWb item, one PFn item, and at least 6 PRO-CTCAE items (pain, nausea, vomiting, fatigue, anxiety, insomnia). The OWb and PFn items, which were created de novo, included 5 ordinal response options with corresponding pictograms (emojis from very happy to very sad for OWb; a figure walking to one prone in bed for PFn). Composite scores were generated: 0 for no symptoms, 1-2 for mild/moderate symptoms, and 3 for severe symptoms. We describe OWb and PFn and analyze associations between these items and PRO-CTCAE symptom scores. Results: Between 9/10/19-1/22/20, we collected 908 eSyM responses from 166 chemotherapy patients at Baptist (Age, M = 65), and 480 eSyM responses from 97 postoperative patients at WVU (Age, M = 57). The OWb and PFn scores demonstrated moderate correlation with PRO-CTCAE symptom scores (Baptist r = 0.63; WVU r = 0.75), and moderate correlation with mean symptom scores among surgery patients at WVU (r = 0.74); but lower correlation among chemotherapy patients at Baptist (r = 0.53-0.55). Scores improved over time following surgery, but not after initiation of chemotherapy. Among the 730 eSyM responses with none/mild values for both OWb and PFn (52.9% of all responses), only 4.5% reported any severe symptom; among 651 responses with impairment of OWb and/or PFn, 45.2% reported at least one severe symptom. Conclusions: Integration of eSyM into the Epic EHR enabled tracking of OWb, PFn, and PRO-CTCAE items. When asked alongside PRO-CTCAE symptom items, two single item OWb and PFn measures provided distinct information and correlated with symptom burden. These results demonstrate the feasibility of integrating ePRO collection into routine post-operative and medical oncology care and that PRO-CTCAE items provide information that is distinct from that obtained from global metrics of well-being. Clinical trial information: NCT03850912.
Administration of immune checkpoint inhibitors using teleoncology model of care in Far North Queensland: A multicenter review of safety outcomes.
Authors: Fletcher James , Kang Sebastian , Brown Amy , Sabesan Sabe S. , Lyle Megan , Pandey Ritwik , Lui Andrew , Rainey Natalie , Kelly Barbara , Schmidt Andrew Lachlan , Joshi Abhishek Jagdish 
Published: May 2020

2084 Background: The Teleoncology model of care, as developed and implemented across health services in Far North Queensland (Australia), improves access to specialist oncology services, including telehealth supervised administration of Oncology drugs for patients in rural/remote towns. There is limited published data regarding the safety of checkpoint inhibitor immunotherapy when it is administered via Teleoncology. Aim: Evaluate safety of immunotherapy administration via Teleoncology, including immune-related adverse events (irAE), treatment delays, hospital admissions and interhospital transfers, in comparison to a retrospective control population. Methods: Retrospective review of all patients treated with immunotherapy via Teleoncology as part of Cairns and Hinterland Hospital and Health Service (CHHHS) and the Townsville Teleoncology Network (TTN) between January 2015 and April 2019. A retrospective cohort treated at Townsville Cancer Centre over the same time period was used as a control group. Results: Fifty-one patients received a total of 624 cycles of immunotherapy (all single agent anti-PD-1/L-1) via Teleoncology. The control population included 142 patients who received 1697 cycles of immunotherapy. Baseline characteristics were well matched between groups. Compared to the control population, patients treated via telehealth did not have statistically significant differences in the rate of Grade 3+ irAE (13.7% v 8%), hospital admissions (13.7% v 7.4%) or protocol suspensions due to immune toxicity (16% v 10%). One patient with Grade 3+ irAE required interhospital transfer for investigation and management, which occurred within 24 hours of presentation to hospital. There were no treatment-related mortalities in either group. Conclusions: Checkpoint inhibitor immunotherapy can safely be delivered using the Teleoncology model of care in rural and remote centres. The incidence of toxicity for single agent immunotherapy was predictably low and not significantly different between groups, however the numbers in this retrospective study were small. The time to recognition and management of immune mediated toxicity in rural and remote centres is an important factor that was not assessed in this study and will be considered in future work.
Temozolomide-induced hypermutation is associated with high-grade transformation, distant recurrence, and reduced survival after transformation in initially low-grade IDH-mutant diffuse gliomas.
Authors: Oberheim Bush Nancy Ann , Yu Yao , Villanueva-Meyer Javier , Grimmer Matthew , Hilz Stephanie , Solomon David , Choi Serah , Mazor Tali , Hong Chibo , Shai Anny , Phillips Joanna J. , McDermott Mike , Haas-Kogan Daphne A. , Taylor Jennie , Butowski Nicholas A. , Clarke Jennifer , Berger Mitchel , Molinaro Annette , Chang Susan Marina , Costello Joseph 
Published: May 2020

2506 Background: Temozolomide, a commonly used alkylating agent to treat gliomas, can induce somatic hypermutation. The prevalence and clinical implications of this phenomenon are not well characterized. Methods: We used targeted and whole exome sequencing from a cohort of 82 patients with recurrent IDH-mutant low grade gliomas undergoing re-operation to evaluate the prevalence as well as the clinical implications of hypermutation. Results: Hypermutation was identified at transformation in 57% of recurrent gliomas exposed to Temozolomide, 94% of which were transformed to higher WHO grades. All patients who developed hypermutation were exposed to Temozolomide. Hypermutation was associated with transformation to higher WHO grade (OR 12.0 95% CI 2.5 – 115.5, p = 0.002) and shorter survival after transformation (HR 2.1, 95% CI 1.1-4.0, p = 0.018) compared with non-hypermutated transformed tumors, controlling for grade, molecular subtype, age, and prior radiotherapy. Patients with transformation to glioblastoma had poor survival regardless of hypermutation (p = 0.78). Hypermutated tumors were associated with development of discontiguous disease at a significantly higher frequency (p = 0.003), including four cases with spinal dissemination. Conclusions: TMZ-induced hypermutation is associated with high grade transformation, unique patterns of dissemination and shortened survival after transformation. Next generation sequencing should be considered in this patient population. These data have important implications for the management of newly diagnosed and recurrent IDH-mutant low grade gliomas.