bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of real-world data to understand barriers to interventional clinical trial enrollment in community oncology clinics (COC).
Authors: Blakely Johnetta , Gordan Lucio N. , Schwartzberg Lee S. , Gutman Jacqueline , Adamson Blythe J.S. , Bourla Ariel B. , Meropol Neal J. , Ramsey Scott David , Green Robert J. 
Published: May 2020

2061 Background: Increasing enrollment in clinical trials remains a national priority, yet there are limited data from COCs on the degree to which common trial exclusion criteria (EC) and socioeconomic factors play a role in low enrollment rates. Methods: We analyzed data from the nationwide Flatiron Health electronic health record (EHR) derived de-identified database. COC were eligible if they had given a clinical trial study drug to ≥2 patients (pts)/year. We included pts with one of eight advanced or metastatic solid tumors who received ≥1 line of systemic anticancer therapy between 1/1/2014 and 11/30/2019. We defined EC as either: creatinine > 1.5 mg/dl or Ccl < 45 ml/min, Hb < 9 g/dL, ANC < 1500/ul, plts < 100,000/ul, bilirubin > 1.5 upper limit of normal (uln) or AST/ALT > 2.5 uln within 30 days or ECOG performance status (PS) ≥ 2 within 60 days prior to start of therapy. We calculated the percentage of pts with ≥1 EC relative to the group of candidate pts, stratified by therapy line (1L, 2L, 3L+). We used multivariate logistic regression models to evaluate the effect of EC and socioeconomic factors (age, race, Medicaid) on the likelihood of receiving a clinical study drug for each line of therapy. Results: In this sample of 35 COCs, 26,988 pts received ≥1 systemic therapy. Pts with ≥ 1 EC: 28.4% in 1L, 34.2% in 2L, 37.4% in 3L. Percentages of pts with an ECOG PS ≥ 2 were: 15.6% (1L), 18.2% (2L), 19.8% (3L). Pts receiving a clinical study drug: 1.7% of 26,988 in 1L, 2.0% of 12,738 in 2L, 2.9% of 5,333 in 3L+, and 3.1% in any line. Excluding pts with ≥1 EC from the denominator modestly improved overall accrual: 2.0% of 19,729 in 1L, 2.3% of 8,588 in 2L, 3.7% of 3,470 in 3L+. In multivariate logistic regression, ECOG PS ≥ 2 was strongly associated with not receiving a study drug [odds ratio (95% CI); 1L: 0.25 (0.16-0.4); 2L: 0.28 (0.17-0.49); 3L: 0.21 (0.1-0.44)]. The likelihood of receiving a clinical study drug (any line) was lower for pts who are Black [0.63 (0.48-0.82)], Latino [0.49 (0.32-0.75)], and pts older than 70 years [0.63 (0.54-0.72)]. Medicaid pts were not significantly less likely to receive study drug [0.83 (0.64-1.07)]. Conclusions: In COC, common trial EC reduce pt availability for trials by > 25%. Poor PS is highly prevalent and influential. These EC and complex trial requirements challenge COC’s ability to recruit representative pt populations. Future efforts to increase enrollment in trials must consider common EC along with well known barriers to enrollment of unrepresented groups.
A pilot study of a wearable monitoring system as an adjunct to geriatric assessment in older adults with cancer.
Authors: Wong Karlton , Shen John , Ramezani Ramin , Zhang Wenhao , Xie Zhuoer , Naeim Arash , Elashoff David 
Published: May 2020

2062 Background: Advances in health technology provide potential tools that can aid in assessing and monitoring the functional status of the growing older adult population diagnosed with cancer. We piloted a novel wearable monitoring platform, Sensing in At-Risk Populations (SARP), which consists of a smartwatch, software application for health monitoring, and a central data processing and analytics engine. Methods: This is a prospective single center, single arm study, utilizing the SARP platform to risk stratify older adults with cancer and determine correlation with treatment-related adverse events and healthcare utilization. Pts age ≥60 undergoing active treatment, were offered participation. Pts were instructed to wear the smartwatch for ≥7 days. We used Kruskal-Wallis to correlate wearable data with clinical outcomes: toxicity, ED visits, hospitalizations, and mortality. We also compared SARP data to independently collected ECOG PS, CARG score, ADLs, and IADLs. Results: From 8/2016 to 8/2017, 54 older adults were consented, and 26 had wearable data available for analysis. The average age was 72 years, with 18 males and 8 females. 12 pts had ECOG PS of 0, 12 with ECOG of 1, and 2 with ECOG of 2. 4 pts had CARG score of low, 17 intermediate, and 3 high. Energy intensity was significantly correlated with ED visits, with an effect size of 0.95 (p = 0.04). Similarly, energy intensity and hospitalizations had an effect size of 0.87 (p = 0.06). The CARG scores were noted to be significantly correlated with dose delay and dose reduction with an effect size 0.45 (p = 0.05) and 0.4 (p = 0.05), respectively. Spearman correlation analysis demonstrated that walking time, active time, and energy intensity positively correlate with ADLs and IADLs, and inversely correlated with ECOG PS and CARG risk. Conclusions: Though this is a limited study due to sample size, the overall trend demonstrated that the SARP platform offers an adjunct tool in assessing and risk stratifying older patients with cancer undergoing active therapy. Additional cohorts are now enrolled with an at-home monitoring system. [Table: see text]
Physician whistle-blower’s experiences in hematology-oncology safety litigation against pharmaceutical companies.
Authors: Godwin Ashley Caitlin , Hoque Shamia , Vemula Jayanth , Ausdenmoore Henry C , Zhu Michael , Bennett Charles L. 
Published: May 2020

2074 Background: Some clinicians have reported initial series of severe or fatal adverse drug reactions (ADRs) that affected large hematology-oncology patient numbers and for which pharmaceutical manufacturers subsequently paid large settlements or fines for allegedly failing to inform physicians about such ADRs. Based on their large human costs ( > 1,000 serious illnesses or deaths) and large financial costs ( > $100 million in settlements or fines), we have termed these ADRs as titanic ADRs. At a Senate hearing on one titanic, Vioxx, (a COX-2 inhibitor that was evaluated for colorectal cancer prevention), the clinician reporter was termed a “whistleblower” by a senator although this individual had not filed a formal whistleblower lawsuit. We identified physicians who would fit this characterization of whistleblowers and had published titanic hematology-oncology ADR reports in high impact journals. Methods: Hematology-oncology titanic ADRs were identified by collaborators with two NIH-funded drug safety networks (RADAR and SONAR (1998-2019)). Exclusion criteria included having also filed a whistleblower lawsuit. Qualitative research analyses evaluated content of statements made by whistleblowers to national reporters or at congressional hearings. Results: 18 physicians who reported titanic hematology/oncology-associated ADRs in peer-reviewed literature and discussed their findings in national news media outlets are included. Titanic ADRs included death, nephrogenic systemic fibrosis, coronary artery disease, and venous thromboembolism related to COX-2 inhibitors, heparin, gadolinium dye, thalidomide, lenalidomide, epoetin, and darbepoetin. Related financial settlements ranged from $100 million to $4.85 billion. Whistleblowers were from the United States, Denmark, and Germany. Primary motivations were public health and medical awareness. Whistleblowers reported having gone through lawsuits and having had executives request that the whistleblowers’ university terminate employment. One whistleblower was quoted saying “I believe that the lawsuit is an attempt to silence me.” Conclusions: Clinician whistleblowers of titanic hematology-oncology ADRs experienced reputational, financial, and personal threats. Motivations for reporting titanic ADRs were mainly public health and medical awareness focused. This differs from our previous study on clinicians publishing on non-titanic ADRs, where the primary motivation was scientific curiosity.
Annual trends in opioid prescribing for patients (Pts) with metastatic non-small cell lung cancer (mNSCLC): Cancerlinq data analysis, 2010 to 2017.
Authors: Paice Judith A. , Chen Li , Garrett-Mayer Elizabeth , Hagerty Karen S , Maletz Novick Kristina Lynne , Potter Danielle , Riffon Mark , Rhodes Whitney , Wang Liya , Bruinooge Suanna S. 
Published: May 2020

2076 Background: Despite opioid misuse and abuse, opioids remain a mainstay for management of cancer pain. Government, payers, and institutions have implemented policies to reduce opioid use. The impact of these restrictions on oncologist prescriptions (Rx) of opioids and management of cancer pain in pts with cancer is not well known. Methods: A retrospective, observational analysis used deidentified EHR data from ASCO’s CLQ Discovery database. Study cohort included pts with mNSCLC diagnosis and >1 clinical encounter (including opioid Rx) from CLQ clinician during 2010-2017. Opioids included DEA schedule II and III opioid drugs prescribed for cancer pain, excluding cough suppressants. Annual Rx rates were defined as the number of mNSCLC pts who had ≥ 1 opioid Rx dated 2010-2017 per CLQ total mNSCLC pts who had ≥1 clinical encounter in the year. Annual rates demonstrate trends in opioid prescribing patterns over time. Results: 18,106 pts with mNSCLC clinical activity between 2010 and 2017 were identified. Overall, 39.8% of pts had opioid Rx in 2010-2017. Annual Rx rates increased from 2010-2015 and fell 2016-2017 (see table). Hydrocodone was the second most frequently prescribed opioid overall (N=4211 pts), but Rx rates began to decline in 2012. Tramadol and acetaminophen + codeine Rx rates gradually increased throughout the time period. DEA initially scheduled Tramadol as schedule IV in 2014. Conclusions: Opioids are commonly prescribed by oncologists for patients with mNSCLC. Rx rates have declined since 2015, likely due to increased government, payer, and institutional restrictions on access. Hydrocodone Rx declined since 2012, perhaps exacerbated by reclassification from schedule III to schedule II by the DEA (October 2014). Rxs for schedule IV and III opioids (known to be of lower potency) increased modestly, likely due to comparatively fewer prescribing restrictions. Additional research is needed to understand whether the decline continues and the impact on management of cancer pain, particularly among metastatic patients. [Table: see text]
Pivotal trial endpoints and prices of cancer drugs in the US and Europe.
Authors: Vokinger Kerstin Noëlle , Daniore Paola , Hwang Thomas J , Lee ChangWon C , Kesselheim Aaron S 
Published: May 2020

2077 Background: A key clinical outcome for new cancer drugs is improvement in overall survival (OS), defined as time from the date of randomization to the death from any cause. However, many cancer drugs are approved by regulators based on changes to surrogate measures of OS, such as progression-free survival or overall response rate. When surrogate measures are not validated, they can provide misleading information about drug efficacy. We categorized pivotal trial endpoints for recently-approved cancer drugs in the US and Europe as showing improvements in OS vs non-OS surrogates, and evaluated the correlation with drug prices. Methods: We identified new drugs FDA-approved between 2009 and 2018 that were indicated to treat solid and hematologic tumors in adults and that had also been approved by the EMA and Swissmedic by December 2019. Launch prices were extracted and adjusted to average sales prices for monthly treatment costs in the US and compared to currency-adjusted ex-factory monthly treatment costs in Germany, Switzerland, and England. Pivotal clinical trial primary endpoints were collected from the drug labeling and FDA medical reviews for the US, and the EMA public assessment reports for Europe, and categorized as OS in any trial vs. not. Pearson’s correlation tests assessed the association between launch prices and OS vs non-OS endpoints in each country. Results: 54 drugs were approved by the FDA, EMA, and Swissmedic during the study period. In the US, 30 (56%) were approved based on OS by contrast to 35 (65%) in the EMA. The number of cancer drugs approved by the FDA based on OS decreased in the past years. By contrast, the number of approved cancer drugs by the EMA based on OS were stable. There was no association for the US (p = 0.05), Germany (p = 0.13) and England (p = 0.12), while Switzerland revealed an association (p = 0.03) between OS endpoint and price. Conclusions: Reductions in use of OS endpoints as the basis for cancer drug approval in the US is concerning. Drug pricing should be better aligned with the benefit that drugs provide to patients, as measured by clinical trial outcomes such as OS.
Understanding practice variation with a clinical pathways system: Differences by physician and practice factors, and changes in practice over time.
Authors: Foster Emily , Stuver Sherri Oliver , Tremonti Carole Kathleen , Bunnell Craig A. , Hamilton Joanna M. , Jacobson Joseph O. , Jackman David Michael 
Published: May 2020

2079 Background: Clinical oncology pathways aim to support clinical decision-making and reduce unwarranted practice variation across an enterprise. The Dana-Farber Cancer Institute (DFCI) implemented web-based oncology pathways with DFCI-customized content in each disease center and at each of its satellites. Our pre-specified aim was an on-pathway rate of 70-85%. Methods: Treatment decisions were electronically captured as on- or off- pathway. Monthly metrics about usage and on-pathway rate were shared with users on a monthly basis. Physicians were categorized into quintiles based on the calculated on-pathway performance during the first 90 days of each individual’s use of the platform. On-pathway rates were then calculated for days 91-360 to study changes in behavior over time. Physician and practice factors were examined to determine any differences by initial on-pathway quintile classification. Results: 122 physicians were eligible for inclusion in this analysis (minimum 5 navigations in each study period). On-pathway rates showed significant variability in the initial 90-day period: quintile 1 median 100%, quintiles 2-4 80.2%, and quintile 5 50% (Table). In the follow-up period, median on-pathway rates shifted into the pre-specified goal range for all groups. Physicians in quintiles 1 or 5 of initial on-pathway rate were more likely to have fewer total navigations than were physicians in quintiles 2-4 (p=0.003). While no other physician or practice characteristic differed significantly by on-pathway rate group, physicians in the first or last quintile were more likely to be in an academic setting, have a PhD, or navigate fewer pathways. Conclusions: Over time, the deployment of a web-based clinical pathways program resulted in greater uniformity in physician practice, based on on-pathway rate. Familiarity with the pathways platform and its navigation, monthly feedback about usage, and evolution of content over time are some factors that might have played a role. [Table: see text]
Association of financial conflicts of interest with academic success among junior faculty in hematology and oncology.
Authors: Fought Angela J. , Davis Andrew A. , Shaw Melissa M. , Prasad Vinay , Kamath Suneel Deepak 
Published: May 2020

2080 Background: Financial conflict of interest (COI) represents a complex issue in hematology and oncology. Little is known about when COIs develop during a career and if these correlate with early career success. We evaluated self-reported COIs for junior faculty members at 10 academic cancer centers and examined if these financial relationships with industry correlated with measures of academic career success. Methods: The study evaluated 229 assistant professors from the top 10 cancer centers based on the 2018 US News Cancer rankings. Faculty characteristics were determined from hospital websites including the number of years since completing fellowship. Data regarding National Institute of Health (NIH) funding were obtained. Industry funds (Sunshine Act funds; SAF) were identified from the Centers for Medicare & Medicaid Services (CMS) Open Payments database from 2013-2017. Self-reported COIs were obtained from the American Society of Clinical Oncology (ASCO) or American Society of Hematology (ASH) disclosures databases, and through review of disclosures from recent publications. Measures of academic success included h-index and number of publications. We assessed the influence of number of COIs and SAF received on measures of academic success. Results: Of the 229 included faculty, 45% were female, 39% graduated fellowship in 2015 or later, 35% were double-boarded, 40% had dual degrees and 15% received NIH funding. Approximately 46% of faculty had at least 1 COI. COIs (ASCO/ASH) were positively correlated with COIs self-reported in publications and total SAF (Spearman correlations 0.57 and 0.54, both P < 0.01). The development of COIs and the number of SAF increased with years in practice (Spearman correlations 0.37 and 0.28, both P < 0.01). COIs and SAF correlated with h-index (Spearman correlation 0.40 and 0.41, both P < 0.01). After adjusting for years since fellowship, linear regression demonstrated that log-transformed h-index and number of publications were associated with SAF (P < 0.01) and COIs (ASCO/ASH) (P = 0.01). Conclusions: Financial COIs were present in nearly half of the faculty and increased with more time since completing fellowship. Measures of academic success were positively correlated with COIs (ASCO/ASH) and SAF. These data suggest that cultivating industry relationships may aid faculty in establishing early academic success.
Telemedicine visits reduce time to biopsy, travel time and costs for interventional radiology patients.
Authors: Shah Suken , Erinjeri Joseph , Guan Qiu Xia , Otto Christian , Solomon Stephen Barnett 
Published: May 2020

2082 Background: Telemedicine has been utilized to increase access to care for patients in primary care practices and more recently, specialty practices. The purpose of the study was to test the hypothesis that adding a telemedicine clinic practice could decrease the time to biopsy, travel time and cost for interventional radiology (IR) clinic patients. Methods: Telemedicine visits were performed by a physician or advanced practice provider (PA or NP) at a single institution, academic medical center to patients at 3 MSK regional locations in NY and NJ. Total patient encounters and data from November 2017 to October 2019 were analyzed. Primary outcome measures were wait time from the IR referral to biopsy procedure visits, patient travel time and travel cost, stratified by in-person vs telemedicine visit. Round-trip travel distance and costs for patients were calculated by determining the offset travel. Cost (economic) benefit was the sum of: Federal cost per mile for travel, toll and parking costs, and doctor visit lost wages. Results: There were 172 MSK Regional site telemedicine visits. There was a significant reduction in time from referral to biopsy for telemedicine visits compared to in-person visits (12 vs 17 days, p < 0.0001). Additionally, there was a significant reduction in travel time for telemedicine visits vs travel time to Manhattan for an in-person visit (p < 0.0001). Telemedicine visit patients had to travel 367 less hours than an in-person visit and saved a total of 11,222 in miles that they did not have to travel. Telemedicine patients accrued $14,652 in economic benefits due to reduced travel costs and lost wages from work. Conclusions: Telemedicine significantly reduced the time to biopsy, travel time and cost for Interventional Radiology patients compared to in-person visits. Telemedicine for IR patients increases access to care for patients and allow for more efficient use of physician time and resources.
Controlled IL-12 in combination with a PD-1 inhibitor subjects with recurrent glioblastoma.
Authors: Chiocca E. Antonio , Lukas Rimas Vincas , Chen Clark C , Rao Ganesh , Amidei Christina , Buck Jill Yannetti , Hadar Nira , Demars Nathan A. , Miao John , Estupinan Taylor , Loewy John W. , Wang Yunxia , Gelb Arnold Bruce , Cooper Laurence JN 
Published: May 2020

2510 Background: Monotherapy with intratumoral Ad-RTS-hIL-12 (Ad), a gene therapeutic conditionally expressing IL-12 under the transcriptional control of oral veledimex (“Controlled IL-12”), was shown in a phase 1 study (NCT02026271) to elicit a new and sustained intra-tumoral infiltration of T cells with co-expression of PD-1. We report updated findings following completion of enrollment (with follow-up ongoing) for a phase 1 substudy (NCT03636477) evaluating safety and tolerability of local, Controlled IL-12 in combination with nivolumab (nivo) in adults with recurrent glioblastoma (rGBM). Methods: Multicenter, open label, dose-escalation phase 1 trial to evaluate safety and tolerability of local, Controlled IL-12 with nivo in adult subjects with rGBM. Ad was administered by single intratumoral injection (2 x 1011 viral particles, Day 0 at time of resection) plus V (10 or 20 mg) PO QD x 15 with nivo (1 or 3 mg/kg) IV on Days -7, 15, then Q2W. Results: 21 subjects were treated (Cohort 1: V 10 mg, nivo 1 mg/kg, n = 3; Cohort 2: V 10 mg, nivo 3 mg/kg, n = 3; and Cohort 3: V 20 mg, nivo 3 mg/kg, n = 3 + 12 expansion). Safety data were similar to Ad+V monotherapy. Adverse reactions during follow-on nivo dosing were consistent with anti-PD-1 labeling, manageable, and generally reversible with no synergistic toxicities. Focusing on the 20mg V cohort (recommended phase 2 dose), serum IL-12 mean ± SEM (screening, 0.4 ± 0.1 pg/mL; Day 0, 0.6 ± 0.1 pg/mL), increased after Ad+V to 8.7 ± 3.3 pg/mL on Day 3. Similarly, serum IFN-g levels did not increase due to nivo alone (screening, 0 ± 0 pg/mL; Day 0, 0 ± 0 pg/mL), increasing after Ad+V to 6.2 ± 2.3 pg/mL on Day 7. Additionally, nivo alone did not significantly increase circulating T cells (CD3+ CD8+%) (paired differences comparison, Day 0 to screening) 3.1%, p =0.13, whereas Ad+V significantly increased peripheral T cells (Day 28 - Day 0) 3.6%, p =0.02. Pseudoprogression followed by a decrease in size (SPD) has been shown as evidenced by serial MRIs in a subgroup of subjects. Preliminary overall survival findings will be presented. Conclusions: Controlled IL-12 with PD-1 inhibition is a rational combination with initial data consistent with immune-mediated effects, a favorable safety profile, and early evidence of anti-tumor effects. An additional phase 2 study combining Controlled IL-12 with cemiplimab-rwlc in adults with rGBM is ongoing. Clinical trial information: NCT03636477 .