bluuebunny/crossref_metadata_2025_split huggingface dataset:
Code status discussions in outpatient setting.
Authors: Prasad Sonika , Jain Nikita , Tahir Nayha 
Published: June 2022

e13539 Background: In the face of the COVID 19 pandemic, goal-concordant care has been gaining further significance. Discussions about the care goals are best when they are exploratory, conversational, and longitudinal. Complex information processing is best done outside of a crisis. Ideally, these conversations should start with the primary care clinician who has a longitudinal clinical relationship with the patient. Methods: A quality initiative project was conducted at the Internal Medicine Residency Clinic located in Northwestern Medicine Woodstock Hospital. Review of order entry in electronic medical records and charts for code status was assessed for data gathering. Patients above the age of 65 years presenting for their annual physical visit were included in the study. Various interventions were done, including educating residents through didactic lectures, sending electronic reminders to the residents and formatting a template note including code status documentation. Pre and post-intervention data was gathered. Results: A total of 104 patients were in the pre-intervention group and 94 patients in the post-intervention group. Pre-intervention, code status was addressed in 33% of total patients interviewed during their annual physical visit. Post intervention, code status was addressed in 48% of the patients. Conclusions: This project was undertaken to increase awareness on a crucial aspect of the addressing code status in outpatient setting. Post intervention studies showed that addressing code status significantly increased. In order to fill the gap, we propose that addressing code status be a mandatory process or a reminder be generated in electronic health records.
Predicting immune checkpoint inhibitor-related hepatitis using electronic health records of patients.
Authors: Horváth Gergely , Kiss Zoltán , Csernai Eszter , Lippenszky Levente , Napan-Molina Pablo , LeNoue-Newton Michele , Mittendorf Kathleen , Smith David , Park Ben Ho , Wolber Jan , Osterman Travis John 
Published: June 2022

e13564 Background: Immune checkpoint inhibitor (ICI) therapies have shown impressive results in treating oncology patients. However, some patients exhibit immune-related adverse events (irAE-s), one significant irAE is autoimmune hepatitis. Oncologists routinely screen for hepatic toxicity with a complete metabolic panel prior to each ICI administration. Predictive modeling of irAE-s based on patient factors has the potential to help guide treatment selection and monitoring protocols. We have developed a widely usable model based on patient history and routinely collected standard blood panels that can predict whether a patient will experience hepatitis with ICI administration. Methods: We defined irAE hepatitis as any single value of AST, ALT, or alkaline phosphatase three-times the upper limit of normal (ULN) as following ICI treatment. The goal was to determine whether the level of the biomarkers exceed this threshold within certain, pre-defined time-windows, as determined by medical experts. We used feature engineering to compress the time-series of lab panels into single meaningful statistical descriptors, such as mean or maximum of these vectors. The dataset was highly unbalanced with many more negative cases (out of the 3231 patients, depending on the window length used for feature generation, 100-400 positives were found), which warranted the application of synthetic resampling methods. Finally, we trained various ensemble models ( e.g., random forest, gradient boosting), on both the resampled and original dataset, to obtain the final, predictive model for the likelihood of irAE hepatitis. Models were tuned to favor high recall and lower precision (identification of patients for increased monitoring) or moderate recall and moderate precision (maximizing F1-score). Results: We explored several modelling methods, such as KNN, Logistic Regression, Random Forests (RF), Gradient Boosting (GB), and stacking. GB without resampling produced the best model with the moderate recall and precision. To achieve high recall with low precision, we needed to resample the dataset with random majority class under sampling and then use RF (see table below for exact results). Conclusions: In this study, we show contemporary machine learning methods can be used as a screening tool for patients at risk for irAE hepatitis. This method could be used to identify patients who would benefit from additional laboratory monitoring between ICI administrations or guide clinical decisions about therapy cessation in advance of toxicity. Additionally, these methods may be further developed and adapted to improve clinical trial exclusion criteria for patients most likely to develop irAE hepatitis.[Table: see text]
Prospective evaluation of an affordable and portable artificial intelligence-based modality for breast cancer screening in women across breast densities.
Authors: Bansal Richa , Aggarwal Bharat 
Published: June 2022

e13585 Background: Mammography is known to be less effective in women with dense breast. Thermalytix is a radiation-free technique for breast screening which uses artificial intelligence over thermal images and has shown promising results in early clinical results. Methods: A prospective, cross-sectional study was conducted from December 2018 to January 2020 to compare the performance of Thermalytix with Mammography in women with dense and non-dense breast tissue. Women aged between 30 and 80 years who presented for a routine health check-up to the hospital and provided informed written consent for the study were included in the evaluation. All women took both Thermalytix and 2D-mammography tests. The output of the Thermalytix tool was blinded to the radiologist interpreting mammograms and the Thermalytix technician did not have access to any other imaging reports of the patient . For participants who were reported as positive on either or both of the tests, confirmatory diagnostic investigations were recommended; the outcome of which was used as the ground truth for comparison. Sensitivity and specificity of the two tests were calulated across age-groups, menopausal status, and breast densities.. Results: Among the 687 women invited for the study, 459 women fulfilled the inclusion criteria for the study analysis. Overall, 21 women were diagnosed with breast malignancies in the study. Thermalytix demonstrated an overall sensitivity of 95·24% (95% CI, 76·18-99·88) and a specificity of 88·58% (95% CI, 85·23-91·41). In 168 women (36·6%) who had ACR categories ‘c’ or ‘d’ dense breasts, Thermalytix showed a sensitivity of 100% (95% CI, 69·15-100) and specificity of 81·65% (95% CI, 74·72-87·35). Among these 168 women, 37 women had an incomplete assessment (BI-RADS 0) of their mammograms with a single reader (trained radiologist), while all 3 malignancies in these women were identified by Thermalytix tool. Conclusions: Thermalytix has the potential to be a radiation-free, privacy-conscious modality for breast cancer screening. Particularly in women with dense breast tissue, it can be a supplemental modality to mammography. As an automated, portable and affordable solution, Thermalytix test could be used alone for large-scale breast cancer screening programmes in resource-constrained settings. Clinical trial information: NCT04688086.
Combination dose finding trials for targeted/immuno oncology agents in early development: Lessons learned.
Authors: Zhou Li , Reddy Micaela , Mittapalli Rajendar K. , Yang Jing , Yin Donghua 
Published: June 2022

e13595 Background: Combination therapy is commonly evaluated in clinical development of oncology investigational agent (IA). An IA may be combined with an approved agent (AA), or with another IA. The aim of this landscape analysis was to 1) summarize and evaluate the different dose finding study design options used in early clinical development for oncology targeted/immuno therapy combinations; 2) propose best-fit application scenarios for each trial designs. Methods: The data sources included 1) FDA approved oncology combination therapies from 2010 to 2021; 2) registered early-stage oncology combination trials in the US with protocol available at clinicaltrial.gov from 2015 to mid-2021; 3) Pfizer internal programs. This analysis focused on “IA + IA” and “IA + AA” combinations. We extracted data on modality type, target, starting dose rationale, trial design and approved dose (if applicable) of the combination. Starting dose considerations and pros/cons of different trial designs were assessed. Results: Both external and internal in scope trials were summarized, including 8 approved non-Pfizer oncology combinations, 32 clinicaltrial.gov registered external trials and 14 Pfizer internal programs. Most surveyed combination trials included an AA. Selection of starting doses and dose escalation design for the combination were the two critical factors influencing the efficiency of clinical development (time, cost and resources). Overlapping toxicities are key concerns resulting in more conservative combination starting doses. The combination dose finding was generally performed with one of the following designs: sequential design, parallel (staggered) design, healthy volunteer first-in-human single ascending dose before first-in-patient combination and monotherapy lead-in (intra-patient “crossover”). A comparison of the characteristics of these dose finding designs indicate that the choice of a particular design should consider factors including exposure-response relationships for efficacy and safety of both monotherapy and combination, the benefit/risk to trial participants, study population, etc. We proposed application scenarios for each trial designs by incorporating the above considerations and analyzing the collected trial examples in the database. The dose finding for combinations between two IAs should consider additional factors including the relative contributions of the two agents to efficacy and safety, the anticipated minimal dose/exposure level for efficacy, and potential pharmacokinetic/pharmacodynamic drug-drug interactions. Conclusions: Multiple design options for dose finding exist for oncology targeted/immuno therapy combinations involving IA. The choice of a suitable design should consider properties and available data of each agents involved, trial efficiency, as well as benefit/risk of trial participants and target indication.
A remote evaluation of NAVIFY guidelines using simulation-based research methods.
Authors: Halligan Jack , Prime Matthew Stewart , Fontana Gianluca , Guo Chaohui , Andoni Anna , Ghafur Saira 
Published: June 2022

e13605 Background: This pilot study was designed to explore the use of remote simulation-based research methods to assess NAVIFY Guidelines, including data collection procedures. NAVIFY Guidelines is a software application that digitizes NCCN Guidelines and allows the user to navigate guidelines in a stepwise manner to support clinical decisions. The application has been designed to simplify access and improve adherence to guidelines in the management of oncology patients. Methods: A total of 10 board-certified oncologists were recruited to participate from large academic centers (5), community hospitals (3) and specialist oncology centers (2). Each oncologist reviewed clinical information for 10 synthetic breast cancer patient cases (i.e., 100 case reviews). The cases were developed by a medical oncologist, a surgical oncologist, a radiologist and a histopathologist. Participants were tasked to select the most appropriate clinical decision as per guidelines in two conditions: 1) using a PDF of the NCCN Guidelines (control), and 2) using NAVIFY Guidelines (experimental). Outcome measures were compared across conditions. Sessions were conducted via Google Meet, with participants using the share screen feature to allow the session to be recorded. The cognitive burden of each method was measured via a psychometric test conducted before and after each method (the Stroop Colour and Word Test). After each session, a post-simulation survey gathered feedback on 1) study methods, 2) use of synthetic patient cases, 3) workload effort required (via the NASA Task Load Index), and 4) usability of NAVIFY Guidelines (via the System Usability Scale). A short interview was conducted after each session to gather feedback on the benefits and challenges of using NAVIFY Guidelines and to discuss the participant’s experience of the simulation session. Results: All data collection procedures were successful including 1) assessment of time taken to reach a clinical decision, 2) psychometric testing, 3) survey data, and 4) user feedback. All participants felt the synthetic patient cases were either ‘very similar’ (7 of 10) or ‘somewhat similar’ (3 of 10) to cases seen in routine clinical practice, and the majority felt the task completed during the sessions was ‘very similar’ (3 of 10) or ‘somewhat similar’ (4 of 10). Conclusions: Remote evaluations can be conducted quickly helping to keep pace with product development cycles. The method is easily repeated therefore supporting evaluation of product development over time. In addition, managing simulations remotely enables the possibility of simultaneous evaluations across multiple geographies, and the use of synthetic patient data eliminates data protection concerns. This study suggests that simulation-based research can be used to assess digital health solutions remotely in a timely fashion.
Feasibility study of integrated ePROs in routine care during radiation therapy for head and neck cancer.
Authors: Katzel Jed Abraham , VanDenEeden Stephen K. , Liu Raymond , Leimpeter Amethyst D. , Briones Cecilia B. , Lewis Dionne L. , Lee-Enriquez Nancy M. , Yan Jennifer M. , Altschuler Andrea , Gillis Amy M. , Patel Deep , Patel Milan Dilip , Kaufman Marcy Ann , Shan Jun , Basch Ethan 
Published: June 2022

e13612 Background: Use of electronic Patient Reported Outcomes (ePRO) tools in the routine care of cancer patients remains challenging despite data showing that they can improve resource utilization and patient outcomes. Patients with head and neck cancer during intensive therapy with radiation therapy (RT) may particularly benefit from interventions focused on early symptom management. Methods: 34 patients with head and neck cancer were enrolled in an implementation study and received ePROs integrated within the electronic medical record (EMR) weekly during radiation therapy (RT) within a large integrated health care delivery system. ePROs consisted of the FACT G7 and FACT-HN. After completion of each survey on the patient portal, a radiation oncology RN documented any abnormal findings and subsequent interventions using a standardized format within the EMR. If patients did not have access to the patient portal or had language barriers, they could complete ePROs with a translator by phone or video. Results: Between January and December of 2021, 34 patients with head and neck cancer receiving curative RT were enrolled. The median age 65 years (range 46-84). 74% of patients were male. 59% were white, 26% Asian/PI, 5% Black, and 5% Hispanic. The most common primary cancer sites were: oropharynx (32%), nasopharynx (24%), larynx (18%), oral cavity (9%). 65% of patients received concurrent chemotherapy with RT and 35% received RT alone. 97.4% of patients had access to the online portal. The total number of surveys completed was 194 with a median of 7 per patient (range 1-8). There was a total of 887 abnormal findings reported and 887 documented and corresponding interventions resulting in a 100% intervention rate. Over the course of RT the mean number of abnormal findings increased from 2.26 at baseline (n = 34) to 6.27 at week 7 (n = 24), P < 0.0001. Hospitalizations and Emergency Department (ED) visit data were collected during the study and up to 30 days from last day of RT. There was a total of 2 hospitalizations and 8 ED visits. Conclusions: ePROs integrated within the patient portal and EMR are feasible during RT for patients with head and neck cancer within a large integrated health care system. The use of ePROs integrated within the patient portal and EMR can lead to a high rate of intervention. The increasing number of abnormal findings on ePRO during intensive treatment for head and neck cancer is consistent with known patterns of toxicity and confirm the value of studying methods for improving quality of life in this patient population.[Table: see text]
Seroconversion following first and second dose of COVID-19 vaccination among cancer patients: A prospective longitudinal observational study from India on the effectiveness of COVID vaccines.
Authors: Kalpathi Krishnamani Iyer , Pappala Raj Kishore , Nawaz Ayesha , Krishnamani Mithra , Mathi Kavita 
Published: June 2022

e13629 Background: Cancer patients are at high risk of infections and vaccination against SARS CoV-2 virus is essential to reduce the risk of COVID-19 and its complications. Different types of vaccines against SARS CoV-2 have been developed at record speed, followed by emerging efficacy studies of these vaccines. Our aim is to assess the efficacy of these vaccines in Indian cancer patients, along with factors such as intervals between doses impacting a robust immune response. Methods: A longitudinal observational study was done to evaluate the seroconversion post one and/or two doses of ChAdOx1 nCoV-19 (Covishield) and BBV152 (Covaxin) vaccine in adult cancer patients. Patients received 0.5 ml of vaccine 4 – 12 weeks apart based on existing Government regulations. A minimum gap of four weeks post vaccination for sample collection was followed. Samples were collected during patient follow up or treatment schedules. The control group comprised of healthy volunteers. Our primary endpoint was to assess seroconversion rates to SARS COV-2 spike protein after first and/or second dose. Our secondary endpoint was to explore the factors influencing seroconversion and to compare the two available vaccines in India, Covishield and Covaxin. Results: Between May 1, 2021 and January 16, 2022, antibody levels were measured in 219 patients after second dose and 56 patients after each dose. The mean age was 57.6+12.2 years (24-85 years) with 52% above 60 years age, and 68% being women. Most common cancer was breast (39.3%) followed by GIT (17.4%), while 44% had metastatic disease. Overall, 54.3% had not received any systemic therapy in the past 6 months, while 22.4% had received chemotherapy and 14.2% had received biologics. Three fourth of the patients had received Covishield and the rest Covaxin. Amongst the 56 patients who had antibody testing after both doses, seroconversion after first and second dose were 85.7% and 96.4% respectively. Higher seroconversion was seen in younger age group, treated with biologics without chemotherapy. In 219 patients, post second dose, seroconversion was marginally higher in women compared to men (96.6% vs 91.4%), on biologics (96.8%) when compared to patients taking chemotherapy (89.8 %), although not statistically significant. Overall patients on Covishield vaccine showed higher seroconversion, compared to Covaxin (P = 0.002) (OR- 5.9). Timing of antibody sample had no effect on seroconversion. Conclusions: Both Covishield and Covaxin are immunogenic in cancer patients. Seroconverison after first and second doses were 85.7% and 96.4%with higher rates amongst patients on biologics compared to chemotherapy. We are hoping to continue our study longitudinally to further explore factors impacting efficacy amongst these two vaccines.
Consensus on the utility of breast cancer multigene signatures in routine clinical practice: Results of the PROCURE Project.
Authors: Curigliano Giuseppe , Cardoso Fatima , Gnant Michael , Harbeck Nadia , King Judy W. , Laenkholm Anne-Vibeke , Penault Llorca Frederique , Prat Aleix 
Published: June 2022

e13639 Background: Several Breast Cancer Multigene Signatures (BCMS) are available to profile early breast cancer (eBC) that according to current evidence, can provide reliable information on the risk of recurrence but the knowledge regarding their real use in clinical practice is scarce. The PROCURE Project aims to establish recommendations on the use of BCMS in clinical practice. Methods: A Scientific Committee consisting of 8 European experts in BC, including oncologists, pathologists, and surgeons, developed a Delphi questionnaire that was administered twice to clinicians across different European centers. The questionnaire included 5 sections: 1) Panelists’ profile and experience with BCMS, 2) Current clinical practice in eBC and use of BCMS, 3) Panelists’ opinion on the utility of the BCMS in eBC according to patient profiles, 4) Agreement with a set of recommendations on the use of BCMS in clinical practice and 5) Identification of unmet needs and future applications of BCMS. 70% agreement was used to determine consensus on a topic. Results: 133 panelists from 11 European countries completed both rounds of the survey. Most of the panelists worked in a teaching hospital (86.5%) and 72.2% of them were medical oncologists. 93.6% of the panelists used BCMS routinely or in selected patients and 73.4% had more than 5 years of experience using BCMS. According to panelists, for being useful in clinical practice BCMS should consider clinical and pathological features of the disease (91%). Additionally, BCMS must provide both, prognostic and predictive information (82%), and information on the risk of late distant recurrence from 5 to 10 years (74%), all based on prospective randomized clinical trials (85%). BCMS must also provide accurate results to guide adjuvant chemotherapy decision (81%). Regarding recommendations for improving BCMS utility, 76% of the panelists agreed that hospitals policies on the use of BCMS must be based on clinical practice guidelines. Panelists also agreed that patients should have the right to access their BCMS results to take part in the treatment decision (86%) and more training is needed for patients (79%) as well as oncologists (84%) and pathologists (82%). Finally, panelists mostly disagree on the fact that BCMS must be performed in all patients when BC is suspected (76%). Conclusions: The high degree of importance that panelists attributed to the fact that a BCMS should provide both prognostic and predictive information, reflects a misconception on the utility of BCMS as they are primarily prognostic tools but not predictive about the effect of a therapeutic intervention. Also, consensus reached on the need of providing risk of late recurrence from 5 to 10 years shows that panelists evaluate the long-term treatment even in the early setting.