bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of baseline lesion selection on reader performance in oncologic clinical trials.
Authors: Bansal Anu , Mantri Ninad , McCracken Paul 
Published: May 2020

e14082 Background: Blinded independent central radiology review is integral to modern clinical trials in oncology. Based on previously published data based on overall adjudication rates, it is generally accepted that selection of a larger and more complete number of target and non-target lesions at baseline results in greater reader concordance and therefore improved data fidelity. Methods: A retrospective database review was performed across 27 trials spanning 15 clinical indications and 4 response criteria involving a total of 20,942 independent reads across numerous timepoints in 10,471 subjects by 119 readers. Adjudication rates and adjudication selection rates were calculated across and within all trials. Results: Readers selected a mean of 2.3 target lesions and 1.2 non-target lesions in each subject. The mean adjudication rate across all trials was 33%. However, adjudication selection rate should be a more accurate representation of reader performance. Within any one trial, 44% of readers who selected the greatest number of target and non-target lesions at baseline actually had adjudication selection rates below average. Conclusions: Readers who select more target and non-target lesions than their peers at baseline do not demonstrate significantly higher adjudication selection rates. This suggests that the number of lesions chosen at baseline may not be as strong a contributer to reader performance and data quality as previously surmised.
The joint i3+3 (Ji3+3) design for phase I / II adoptive cell therapy clinical trials.
Authors: Ji Yuan 
Published: May 2020

e14083 Background: Adoptive cell therapy (ACT), such as chimeric antigen receptor (CAR) T-cell therapy, have demonstrated promising therapeutic effects. However, it has been shown by previous studies that dose-response of ACTs may be complex and non-monotonic. For example, a ten-fold increase in dose level may not necessarily lead to higher anti-cancer response. This creates a new challenge for dose-finding trials with ACTs since higher dose may not lead to higher probability of efficacy. Methods: We propose a novel statistical design called the joint i3+3 design (Ji3+3) which extends our previous work of the i3+3 design (ASCO 2019 abstract 268979) and addresses the dose-finding challenge for ACT trials. In particular, Ji3+3 is a rule-based method that can be easily understood, visualized, and implemented by clinicians. It uses a set of smart rules based on observed efficacy and toxicity outcomes, and conducts up-and-down dose escalation decisions based on dose-response intervals. The entire dose-finding algorithm and decision rules can be presented as a precalculated table, which can be examined, discussed, modified, and approved as part of trial design. Results: Motivated by a CAR T trial (NCT03971799) we demonstrate the superiority of the Ji3+3 design through extensive computer simulations. Compared with the 3+3 design and i3+3 design, we show that Ji3+3 has a much higher chance finding the BOD and allocates more patients to desirable doses. The impact of these results will be to help investigators and drug developers identify a dose that is efficacious and safe, thereby increasing the probability of success to market the ACT and improving patient care. Conclusions: The Ji3+3 design is a novel, simple, and effective method that can potentially significantly improve the dose finding for ACT clinical trials.
Harnessing tumor immunity with chemotherapy: Mathematical modeling for decision-making in combinatorial regimen with immune-oncology drugs.
Authors: Cuplov Vesna , Sicard Guillaume , Barbolosi Dominique , Ciccolini Joseph , Barlesi Fabrice 
Published: May 2020

e14095 Background: Combining chemotherapy and immune checkpoint inhibitors (ICI) is challenging due to the near-infinite choice of dosing, scheduling and sequencing between drugs. The aim of this work is to develop a phenomenological model that describes the synergistic effect between cytotoxics and immune check point inhibitors in patients with cancer. Methods: Inspired from literature, we have developed an integrative mathematical model that includes tumor cells, cytotoxic T cells (CTLs) and regulatory T cells (TREGs) plus pharmacokinetics (PK) inputs. Loss in tumor mass is due to combined effect of direct chemotherapy-induced cytotoxicity and CTLs immune response, which is in turn inhibited by the tumor and mitigated by TREGs in the tumor micro-environment. The model describes as well the impact of chemotherapy-induced lymphodepletion on immune tolerance, whereas ICIs protect CTLs against tumor inhibition. Identification of model’s parameters and simulations of various scheduling were performed using Mlxplore software and a Python standalone code. In vitro and in vivo experiments using lung cancer models generate experimental data to adjust model parameters. Results: Complex interplays between cytotoxics and immune cells were best described by a 10-parameters model so as to ensure better identifiability. PK/PD relationships were integrated using compartmental modeling. In silico simulations show how changes in dosing and scheduling impact efficacy endpoints, an observation in line with data from the literature. Ongoing in vitro and in vivo experiments with pemetrexed-cisplatin doublet and anti-PD1 pembrolizumab help optimizing the model’s parameters in a self-learning loop. Conclusions: This work is at the frontier between mathematical modeling and experimental therapeutics with ICIs. In silico modeling and simulations could help narrow down the treatment choices and define optimal combinations prior to running clinical trials. Such model will help identify optimal dosing and scheduling, so as to achieve better synergism and efficacy.
Pilot study for the use of wearable devices for patients undergoing oral chemotherapy.
Authors: Patel Monaliben , Cooney Matthew M. , Caimi Paolo Fabrizio , Randall Rory Eric , Metheny Leland L. , Mendiratta Prateek , Bruno Debora S. , Silverman Paula 
Published: May 2020

e14103 Background: The rapid development of digital technology holds enormous potential to transform the delivery of cancer care. Despite these digital innovations, we still face significant challenges in healthcare in using these emerging digital technologies in the clinical setting. Clinicians generally underestimate the severity and extent of chemotherapy toxicity of patients. This project seeks to conduct an exploratory field study to collect patient feedback on their experiences, and the design/functionality of the prototype of the digital health service platform designed to monitor their symptoms. Methods: Using the National Cancer Institute item library addressing the most common symptoms for chemotherapy toxicity, a digital health platform was designed by Samsung Research America (SRA) and University Hospitals. Patients age ≥ 18 years old, willingness to agree to the consent document, ability to understand use of wearable device and willingness to answer patient reported outcomes questions were included in this study. Patients who are not undergoing oral chemotherapy treatment for their cancer were excluded. Patients were given a phone that had our designed platform along with a watch. The watch had the capability of tracking blood pressure, heart rate, and pulse oximetry. Patients were set up with an electronic account that queried them on patient Reported Outcomes (PRO) regarding potential toxicity they may be experiencing. They were also able to track medication consumption and input their weight. Subjects were be asked to use the wearable device and phone for at least 28 days and no more than 90 days. At the end of the study, a phone survey was attempted. Results: Total patients enrolled: 21. 18/21 (85.7%) patients completed the 90 days of the study. Only 9 patients provided PRO with total number of side effects reported 28 times. Watch device was only utilized by 15/21 (71.4%) patients. On an average across 90 days, these patients wore the watch 430 minutes per day. At the end of the treatment, 5 patients agreed to participate in the phone survey. Three patients stated that they would do similar study in the future noting that the digital platform helped them stay on track and monitor symptoms accurately. Every patient questioned had a complaint regarding the watch functionality. Patients also found it difficult to carry a second phone in addition to their personal phone. Conclusions: Improving our digital health service platform will get us closer to achieving effective bi-lateral patient communication and ultimately improving patient care.
Continuous monitoring of mobility performance trajectory in patients receiving chemotherapy.
Authors: Yarlagadda Sudha , Najafi Bijan , Chu Jinna , Wang Changhong , Sada Yvonne 
Published: May 2020

e14104 Background: Accurate performance status (PS) assessment is important for chemotherapy decisions, but current tools such as the Eastern Cooperative Oncology Group (ECOG) PS assessment are subjective, static, and prone to inter-observer and recall biases. Continuous patient monitoring technology can enhance PS assessment by providing an objective and dynamic measurement of mobility performance (MP), defined as mobility in real-life situations. This study examined the feasibility of a pendant sensor to continuously track MP during a 4-week period of chemotherapy. Methods: Patients on chemotherapy were recruited from a single center. Patients were asked to continuously wear a water-resistant pendant sensor (PAMSys, Biosensics, USA) for 4-weeks during the day and night. Patients completed psychosocial surveys (cognitive, depression, and fatigue) and a technology acceptance survey measured on a Likert scale from 1 (strongly disagree) to 5 (strongly agree). Chart review was completed for demographics, medical history, and baseline ECOG PS. Using a validated algorithm, postures (lying and sitting postures: LSP) and walking parameters (cadence, longest walking bout, total steps per day) were extracted from the pendant. We also calculated percent change from baseline activity to the lowest activity level during the 4-week period. To determine clinically meaningful digital biomarkers, we compared these MP measures between two groups: ECOG 0 or ECOG ≥1. Results: Fifteen patients (median age 68), with either a solid (n = 14) or hematologic (n = 1) malignancy, stages II-IV, with ECOG 0 (n = 7) and ECOG ≥1 (n = 8) were evaluated. Baseline psychosocial parameters were not significantly different. ECOG ≥1 tend to have poorer baseline walking compared to ECOG 0 with the largest effect size observed for cadence (79.2 ± 10.0 vs 73.3±3.7, Cohen’s d effect size d = 0.78). The percentage of MP decline was higher in ECOG 0 compared to ECOG ≥1 (89.0±22.9% vs 79.9±34.5%). None of the observed trends reached statistical significance. Patients reported that the pendant was comfortable to wear (4.9±0.30) and did not interfere with activities (4.9±0.25). Conclusions: This study showed the feasibility of a pendant sensor to continuously monitor MP and its trajectory during chemotherapy. Results suggest continuous MP monitoring may provide objective information to enhance PS assessment. Larger studies are needed to confirm statistical significance of digital MP metrics and its potential effect on clinical decisions such as dose reduction, rehabilitation, and palliative care.
Using a bi-directional digital health platform for cancer care coordination and monitoring to enhance the cancer care continuum between patients, clinicians and caregivers.
Authors: Hensley Alford Sharon , Mahatma Shilpa , Mahatma Rohit , Amode Sagar , Sethia Rupal , Mahatma Kartik , Mahatma Hitesh , Mahatma Varun , Sonawane Nayan , Chawla Kanchan , Patil Pooja , Solankar Pravin , Belote Shital , Wasu Sneha , Mahatma Srishti , Kumar Tarun 
Published: May 2020

e14105 Background: It has been recognized that current electronic medical record (EMR) systems detract from the patient-provider relationship and that an innovative technology is needed to re-center medical encounters on the patient-provider engagement. This is especially important in oncology during new patient onboarding, care coordination in between medical visits and survivorship planning. Methods: We built a HIPAA compliant role-based digital health platform to support providers in patient engagement and care coordination. In this pilot at a non-profit oncology center in India, nurse navigators onboarded the patients using the mobile application. The technology was used to digitize past medical records and parse the clinical history. In addition, self-reported patient past medical history, family history, as well as social, reproductive and surgical history was collected as needed. The system collated the information into an easy to consume case summary for the oncologists. The system was tested with 3 clinicians and consented cancer patients. Results: Nearly 200 cancer patients participated in the pilot study. Patients’ medical records were digitized by oncology nurse navigators. The summarized longitudinal view of the patient’s medical history was used by oncologists for diagnosis and treatment planning. Participating clinicians noted that the digital case summary saved time and effort in treatment planning. In addition, it was noted that collaboration between nursing staff, medical oncologist, surgical oncologist and radiation oncologist was substantially improved. Conclusions: We demonstrate the value of using digital health technology to support the care coordination of cancer patients in a low-resource, non-profit clinical center in India.
Adherence to remote versus clinic-based collection of patient-reported outcomes in patients with advanced lung cancer.
Authors: Gabriel Peter Edward , Kaufmann Tara L. , Blauch Abigail N. , Pucci Donna A. , Jacobs Linda A. , Bekelman Justin E. , Shulman Lawrence N. , Takvorian Samuel U 
Published: May 2020

e14109 Background: Routine collection of patient-reported outcomes (PROs) is an evidence-based practice to improve communication, symptom management, and health outcomes in cancer care. However, optimal implementation strategies are poorly understood. Previous studies have mostly assessed PROs collected during clinic visits, which may be less actionable and more subject to recall bias than those collected in real time. Behavioral economics-informed digital approaches have shown increasing promise as sustainable and scalable strategies for remote patient monitoring. We compared remote text-messaging versus usual clinic-based PRO collection approaches. Methods: Between September 2018 and May 2019, we conducted a prospective pilot feasibility study of remote PRO monitoring via text-messaging among 20 patients with advanced non-small cell lung cancer (NSCLC). Pilot participants consented to enroll in a HIPAA-compliant, bidirectional text-messaging platform, which allowed for direct reporting of PRO measures at home. Data were integrated into the electronic health record in real time, and clinicians were notified of severe or escalating symptoms. We compared patient-level adherence over 12 weeks among: 1) pilot participants and 2) patients with advanced NSCLC reporting via usual clinic-based collection methods. We identified predictors of adherence using multivariable logistic regression, and surveyed pilot participants on feasibility outcomes. Results: During the study period, 20 patients with advanced NSCLC participated in the remote text-messaging pilot study (mean age, 63y; 60% male; 85% white), and 328 patients with advanced NSCLC participated in usual clinic-based PRO collection (mean age, 66y; 48% male; 69% white). Baseline characteristics were similar between groups. Mean adherence was 88.4% for remote text-messaging vs 71.2% for clinic-based collection (p < 0.001). Pilot participation predicted > 80% adherence after adjusting for age, sex, race, and marital status (OR 3.5, p = 0.029). Pilot participants reported high levels of usability (97%) and satisfaction (96%) with text-messaging, and 90% noted that text messages reminded them to report symptoms to their clinical team. Conclusions: Among patients with advanced NSCLC, remote PRO monitoring via text-messaging was feasible and enabled significantly higher adherence to reporting than usual clinic-based collection. These results are based on a small pilot study, and further research on text messaging as a PRO implementation strategy is warranted. Clinical trial information: NCT03616522.
The changing atlas of clinical research in cancer: Measuring accessibility to clinical trials.
Authors: Mazzarella Luca , Tini Giulia , Fabio Pammolli , Lorenzo Righetto , Curigliano Giuseppe , Pelicci Pier Giuseppe 
Published: May 2020

e14123 Background: The recent global economic growth produced dramatic social changes that impacted healthcare. Private industries, low and middle income countries increased their interest in clinical research. How these changes impact on accessibility to clinical trials has not been sufficiently studied, an issue becoming more relevant as trials increasingly constitute a relevant source of access to innovative drugs. Methods: We analyzed changes related to funding source, phase and locations involved in all interventional clinical trials on cancer extracted from clinicaltrials.gov from 2005 to 2019. We studied the evolution of accessibility to clinical trials on worldwide scale, by developing a family of indexes weighted on population, distance from the site location, numbers of trials. These indexes were also used to simulate different resource allocation models. Results: The absolute involvement of industry in clinical trials consistently increased (~6 fold over 2005), with a significant bias for phase 1 trials; however, its relative impact has globally remained the same. The geographical distribution of trial sites changed dramatically: some nations (China, Korea) increased their total number of trials 50 fold. The number of countries with ≥10 multicentric studies grew from 3 to 16. Our accessibility index (Table, relative increment on 2005 in parenthesis) shows that Asia had the highest improvement, with Korea and Taiwan as leading countries. The analysis captures significant trends associated with changing policies on trial conduct, such as the introduction in 2012 and abandonment in 2015 of centralized ethical committees in Brazil, or the introduction of EUdract in Europe in 2015. Simulations allowed to identify specific resource allocations to maximize accessibility. Conclusions: Accessibility to clinical trials is improving worldwide, but with important differences across continents and countries, which follow social, economic and political changes. Our accessibility indexes can inform national and continental healthcare/research policies, as they predict the impact of different resource allocation models, representing useful tools to facilitate access to innovative treatments. [Table: see text]
The validity of VALID act: Cost modeling cancer diagnostics regulation by the FDA.
Authors: Huang Richard , Lasiter Laura , Young Christina , Allen Jeff , Lennerz Jochen K 
Published: May 2020

e14124 Background: VALID Act is a bipartisan draft legislation proposing to ensure the quality and safety of diagnostic tests through direct FDA oversight. Currently, FDA exercises enforcement discretion and exempts from premarket review tests that are developed and used in the same clinical laboratory. Many stakeholders have pointed out that the lack of direct FDA oversight has led to erroneous results that have serious patient consequences. However, the maintenance cost after the implementation of the Act is unknown. Thus, we estimate the additional financial burden of genotyping all new late stage cancer patients under a fully implemented VALID Act precertification framework. Methods: Based on our laboratory with 36 high-complexity clinical assays, we modeled the cost increase by dividing the total anticipated cost for annual FDA precertification by our 2019 patient volume. To model the stringency of complying with the Act, we calculated either 3, 6, or 9 assays as representative of the laboratory’s test complexity. To make the estimated additional annual national healthcare cost relatable, we expressed the increase as a distributed cost per newly diagnosed late stage cancer patient in 2019 (NCI SEER) or per employed person in 2019 (Bureau of Labor Statistics). Results: FDA precertification for 3 assays was estimated at $638,310.13, or when divided by our annual late stage patient volume (n = 10,232), an increased cost of $62.38/patient. Precertification for 6 or 9 assays costs $684,751.60 (+$66.92/patient) or $1,253,717.25 (+$122.53/patient), respectively. If only 1 cancer center per state/DC/PR got precertified (n = 52), multiplied by the cost of precertifying 3 assays, then the annual national healthcare cost would increase by $33,192,126.50, or +$42.37/new late stage patient (n = 783,476) or +$0.21/employed (n = 158,803,000). Precertification for 52 centers for 6 or 9 assays would cost $35,607,083.20 (+$45.45/patient, +$0.22/employed) or $65,193,297.00 (+$83.21/patient, +$0.41/employed), respectively. Nationally, there are ~886 centers and the increased cost was estimated at < $7/employed. Even though the VALID Act will affect more than late stage cancer patients, thus costs will vary, our data show how a specific change of the Act will impact oncology practice. Conclusions: We provided a concrete cost model for late stage cancer patients under the proposed VALID Act. Cost modeling is important in informing the balanced legislative language needed to ensure patient access to validated cancer diagnostics, while supporting continued innovation by clinical laboratories.