bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electron flash-RT program in clinical setting for human translation.
Authors: Zhang Rongxiao , Rahman Mahbubur , Bruza Petr , Thomas Charles R. , Jarvis Lesley A. , Hoopes P. Jack , Gladstone David J. , Pogue Brian W. 
Published: June 2022

e13596 Background: A FLASH-RT program was established at Dartmouth-Hitchcock Medical Center in minimally-modified clinical setting by joint efforts of biomedical engineering, radiation oncology, radiation biology and medical physics teams. Various projects on dosimetry, chemical sensing, molecular profiling, software/hardware development, and translational studies have been conducted. The aim is to share logistical considerations and experience on running a FLASH-RT program to support institution-wide academic activities with an ultimate goal of treating human patients with FLASH-RT in 2022. Methods: A linac was converted in the clinical setting by qualified engineers to deliver an ultra-high dose rate (UHDR) electron beam. Routine safety and dosimetry checks were done by physicists for every reversible conversion. Long-term record-keeping and retrospective surveys were carried out to demonstrate the feasibility, safety, stability and accuracy of this dual-purpose (FLASH and conventional RT) approach. Comprehensive failure mode and effects analysis (FMEA) has been completed to systematically evaluate safety related considerations. A treatment planning system (TPS) has been developed in Varian Eclipse to facilitated comparative studies. The FLASH-capable linac has been utilized as shared resource to support institution-wide academic activities as well as normal clinical treatments. Results: With its safety (no accident or FLASH-related malfunction), flexibility (> 100 conversions in 2 years), reliability (̃6000 hours in flash mode and ̃5x105 Gy accumulative dose delivered at isocenter) and accuracy (̃5% conversion-to-conversion variations) demonstrated by commissioning, long-term user experience and comprehensive FMEA analysis, the FLASH-RT platform has been actively utilized for researches in six major categories 1) FLASH beam dosimetry; 2) real-time beam delivery monitoring and control; 3) oximetry and chemical sensing; 4) preclinical/translational small/large animal treatment with tumor control and normal tissue complication endpoints, 5) treatment plan and delivery optimization; 6) the design of phase I/II trials. Key findings in each category will be reported. Conclusions: A FLASH-RT program in clinical setting is established at Dartmouth with joint efforts, promoting collaborative projects to advance FLASH-RT to clinical treatment. The system has been reliably utilized for over two years for mechanistic as well as translational studies and support a phase I/II trial treating cutaneous lymphoma with eFLASH-RT.
Association of enrollment duration on trial outcome in phase 3 randomized controlled trials: A pancancer analysis spanning 67 years.
Authors: Li Xuanyi , Warner Jeremy Lyle 
Published: June 2022

e13597 Background: Randomized controlled trials (RCTs) inform the standard of care in clinical oncology, yet a substantial proportion yield negative results. Difficulty with patient enrollment is a problem commonly encountered in the conduct of large multicenter RCTs, leading to slow enrollment. Slow enrollment can lead to increased financial costs, delayed reporting, and decreased relevance of trial results if standards of care shift. The effects of slow enrollment on trial success are understudied. We hypothesized that longer enrollment periods would be inversely correlated with trial success, after adjustment for year of study. Methods: Phase 3 RCTs studying malignant hematologic and solid tumor conditions available on the HemOnc.org website through December 31, 2021, were included in the analysis. HemOnc.org contains nearly all phase 3 RCTs of systemic anticancer therapy registered on ClinicalTrials.gov (with results) or with publications indexed in PubMed. Start year and end year of enrollment and comparative efficacy of control and experimental arms of RCTs were extracted. RCTs were deemed positive if the experimental arms were superior in superiority trials or non-inferior in non-inferiority trials, or if control arms were inferior in superiority trials. The remaining RCTs were deemed negative. Logistic regression was used to analyze the relationship between length of enrollment period and trial outcome, adjusted for year of study enrollment start. Results: The analysis included 3072 phase 3 RCTs spanning 99 different cancer types, enrolling from 1955-2019. Breast cancer was the most studied condition (n=554 trials) followed by non-small cell lung cancer (n=314 trials). 1513 (49.2%) of RCTs reported positive trial outcomes. The overall median enrollment period was 4 years (range 1-16 years). Negative trials took 1 year longer, on average, to complete enrollment (Table). The logistic regression model showed that shorter enrollment periods were associated with trial success. Later enrollment start year was also independently associated with trial success (Table). Conclusions: Our study showed that shorter enrollment period was significantly associated with positive trial outcomes. The success rate of trials has also increased over time; this could reflect both more efficacious drugs as well as more conservative enrollment criteria. Our main limitation is that we do not have data on early termination or closure for futility; these two issues might arise in both fast and slow accruing studies, which would bias results towards the null. The results of this analysis emphasize the importance of rapid phase 3 trial enrollment.[Table: see text]
Digital patient-reported outcomes and serological response to SARS-COV-2 vaccines in patients with cancer.
Authors: Sandoval Jose L. , Bugeia Sebastien , Mentu Santeri , Gutknecht Garance , Ekström Jussi , Battagin Anna , Friedlaender Alex , Metso-Lintula Mari , Kataja Vesa V , Dietrich Pierre-Yves , Mach Nicolas , Addeo Alfredo 
Published: June 2022

e13606 Background: SARS-CoV-2 vaccines have changed the course of the current global pandemic. Cancer patients were identified as highrisk of adverse infection outcomes. We have previously characterised the serological response to SARS-CoV-2 vaccines in 220 cancer patients treated at our institution. In addition these patients were given the possibility to report their symptoms (patient-reported outcomes, PROs) weekly using a digital platform (ePROs). We sought to determine if, in cancer patients, the prospectively recorded post-vaccination ePROs could predict the serological response to SARS-CoV-2 vaccines. Methods: We used a pre-existing digital platform that allows monitoring of PROs using weekly questionnaires sent to patients and available on their desktop computers, tablets or smartphones. Serial serologies were performed at 28, 50 and 115 days after vaccination. Results: We observed that at day 50 after the first vaccination dose, coinciding with three weeks after the second dose, patients could be divided into two groups according to their serological response (low – below 1500 U/ml and high – above or equal 1500 U/ml). A peak in symptom burden could be observed after the second dose, as previously described. Omitting ePRO features decreased prediction performance of all models, whereas omitting baseline symptom scores had inconsistent effects. Among all models and feature constructions, the top performance metrics were given by the nearest centroid model7 with baseline symptoms omitted and 20 features chosen with the aforementioned procedure. The model achieved an accuracy of 0.704, an F1-score of 0.759 and an MCC of 0.398. Conclusions: we were able to identify the patients who achieved higher antibody levels against SARS-COV-2 based on the symptom burden reported through ePROs. This represents the first model showing that symptoms, assessed through ePRO can be predictive of response to vaccines. Our results could also be useful information for patients, as they could assuage their fears about adverse -effects, through the knowledge that toxicity could predict better protection against SARS-COV-2. The same toxicity-based prediction of efficacy has been identified with immunotherapy in cancer and is now a routine part of clinical discussions with patients.
Advancing digital health innovation in oncology to improve the lives of cancer patients.
Authors: Patel Smit , Van De Keere Isabel , Goldsack Jennifer , Rollison Dana Elise , Robinson Edmondo 
Published: June 2022

e13609 Background: Oncology is renowned for leading innovation in research and in care. However, digital innovation in cancer care and research appears to be limited relative to other therapeutic areas. Methods: A multi-stakeholder roundtable, co-hosted by the Digital Medicine Society (DiMe) and Moffitt Cancer Center, convened experts from 35 leading organizations in life science R&D, regulators, payers, innovators, and with core representation from cancer patients and patient experts. Discussions addressed the current state of digital innovation in cancer care, root causes of digital health innovation challenges in oncology, and identifying action-oriented approaches to collaborative solutions needed to advance the safe, effective, ethical, and equitable use of digital innovations in oncology. Results: There was consensus among roundtable attendees that digital innovation lags behind in oncology relative to other therapeutic areas. Challenges identified as ‘low hanging fruit’ for digital innovation include reducing patient administrative burden, supporting care navigation, optimizing decision making in care and research, optimizing clinical pathways, and improving how we monitor both performance status and safety. Reducing financial toxicity and disparities in disease burden must be imperatives of digital innovation in oncology. Access to care and health outcomes for all patients must also be improved. Impediments to digital innovation in oncology include a proliferation of digital point solutions as opposed to system level innovations; transactional digital solutions that do not promote ongoing engagement and reengagement for the lifetime of the patient journey; lack of trust among patients and clinicians; the absence of data sharing incentives and infrastructure; and business and payer disincentives to digital transformation. Conclusions: Digital innovation frameworks can support more effective and equitable approaches to care that are accessible, scalable, and inclusive, thereby reducing the burden of cancer. To achieve this, clinical, technical, and operational best practices necessary to develop, design, and deploy high-quality digital interventions into cancer care must be established. There is no reason for the successful adoption of digital interventions in oncology to lag behind other therapeutic areas. Intentional action with urgency is required by the multi-stakeholder community through a collaborative effort to realize the full promise of digital innovation for patients and the systems that support those who care for them.
Physical activity levels in patients with melanoma during treatment with immune checkpoint inhibitors: Fitbit results from the CAMP-IT trial.
Authors: Kos Milan , Buffart Laurien M. , de Groot Jan Willem , Westgeest Hans M. , Boers-Sonderen Marye J. , Van Laarhoven Hanneke W.M. , van Oijen Martijn G.H. 
Published: June 2022

e13610 Background: Wearable activity trackers offer possibilities to harness real-time patient data for predicting clinical outcomes in patients with cancer during treatment with immune checkpoint inhibitors (ICIs). As a first step towards this purpose, we aimed to assess the feasibility of using wearable activity trackers to objectively measure physical activity levels during the course of treatment. Methods: Patients with advanced melanoma, scheduled to receive treatment with ICIs were eligible to participate in the Comprehensive Ambulatory Monitoring Platform during ImmunoTherapy (CAMP-IT) trial. Participants were instructed to wear a Fitbit Versa 2.0 during waking hours for 12 weeks after start of immunotherapy. Feasibility of Fitbit use was assessed using predefined goals regarding compliance (> 75% participants with > 75% wear days) and acceptability (satisfaction score > 75%). Weekly averages of daily steps were calculated. A valid wear week was defined as a week with a minimum of 4 valid wear days (> 100 steps) including at least 1 weekend day. Linear mixed models were used to examine the changes in mean daily steps during 12 weeks after treatment initiation. We currently analyzed data of the first 30 of the 50 patients that will be included in the trial. Results: Of the 30 patients that were currently included 57% was female and mean age was 57,3 (SD 9,7). Forty percent had metastatic disease, and 30% received treatment with combination ICI therapy. Ninety-six percent of patients was compliant with Fitbit use. Moreover, Fitbit use was rated as satisfactory by 86% of patients. Mean steps per day in week 1 was 6728 (SD 3405). Mean daily steps per week did not change significantly over time during the observation period (b = -13,3 (95% CI: -85,7 - 59,1); p = 0.72). Conclusions: This is the first prospective study that reports on the use of consumer-grade wearable activity trackers to objectively measure physical activity in advanced melanoma patients during treatment with ICIs. Our results suggest that the use of wearable activity trackers in these patients is feasible and that treatment with ICI does not impact physical activity levels during the first 12 weeks. Future research should investigate whether our results hold true for specific subgroups (e.g., patients that receive combination ICI therapy). Clinical trial information: NL8827.
Immunogenicity of the vaccine against Sars-Cov-2 in cancer patients under active treatment.
Authors: Fernandez-Murga María Leonor , Serrano-Garcia Lucia , Garde-Noguera Javier , Portero Maria , García-Sánchez José , Regal Lorena , Dominguez-Martinez Victoria , Llombart-Cussac Antonio 
Published: June 2022

e13632 Background: Coranavirus disease 2019 (COVID-19) has affected more than 220 millon people worldwide. The establishment of safe and effective vaccine coverage is crucial in these patients. We aim to investigate the safety, adverse effects and immune response (cellular and humoral) in cancer patients under active treatment and risk criteria. Methods: 56 samples from cancer patients under active treatment for cancer were collected before and after vaccination Demographic, clinical and biochemical data were collected and a post-vaccination symptomatology questionnaire was performed. For the determination of anti-SARS-Cov-2 antibodies (Immunoglobulin G and immunoglobulin M) we used the ELISA technique (LIASON SARS-CoV-2 S1/S2 IgG test and LIASON SARS-CoV-2 IgM test, DiaSorin, Saluggia, Italy). A study of the lymphocyte population was performed by flow cytometry. Results: We enrolled 52 patients with cancer who received mRNA vaccines (mRNA-1273 and BNT162b2), 2 patients with AZD1222vaccine and 2 with Ad26.COV2.S vaccine. All patients were SARS-COV-2 naive as determined by a negative anti-SARS-COVID-2 IgG test baseline. The median follow-up time was 50 days after receip of a second vaccine dosis. All subject received anti- cancer therapy. The most common anti-cancer treatment received by this cohort of patients was cytotoxic chemoterapy (44.6%), immunotherapy (25%), and monoclonal antibody therapy (14.3%). Overall, a high rate of seroconvertion(anti–IgG) (94,5%) was observed in our cohort, 1 patients with chemotherapy (1,8%) and 2 patients with immunotherapy (3,6%) were negatives. No significant differences in antibody titer were observed according to therapy. Thirty percent presented an antibody titer lower than 1000 U/ml, 27 (48%) patients developed an anti-SARS-CoV2 titer between 1000-4000 U/ml, and only 9 (16%) subjects presented a titer higher than 4000 U/ml. Studies of the lymphocyte profile of vaccinated patients showed no significant changes in the subtypes, except for peripheral memory CD3+ CD8+ lymphocytes which were significantly increased (p = 0.0001) after the second dose of anti-SARS-CoV-2 vaccine. Interestingly, cell apoptosis was significantly reduced in almost all T lymphocyte subtypes studied in vaccinated patients. Finally, analysis of blood cells showed a statistically significant increase (p = 0.0402) of eosinophils in vaccinated patients compared to baseline data. Conclusions: A personalized approach to vaccination can be proposed to cancer patients, especially depending on the type of tumor and the specific oncological treatments received. We are currently recruiting patients (n = 150) who have received the third dose of vaccine and plan to follow up at 6 months for humoral and cellular immune response. Final results will be reported at the ASCO meeting.
Factors associated with U.S. hospital payer-specific negotiated mammography charges.
Authors: Hsieh Kristin , Huang Hsin-Hui , Tarras Elizabeth Stieglitz , Weber Ellerie , Marshall Deborah Catherine 
Published: June 2022

e13633 Background: The Hospital Price Transparency Rule, effective 1/1/2021, requires hospitals to publish payer-specific negotiated charges and cash prices. Given differences in insurance coverage for screening versus diagnostic mammography, we evaluate factors associated with these payer-negotiated charges. Methods: We conducted a cross-sectional study of U.S. acute care and critical access hospitals in CMS’ Care Compare linked to Turquoise Health (payer-negotiated charges), Healthcare Cost Report Information System (hospital characteristics) and Social Vulnerability Indices by county. Negotiated charges for mammography (CPT: screening 77067; diagnostic unilateral 77065, bilateral 77066) were estimated by payer type (self-pay, managed Medicare/Medicaid, or commercial). Adjusted models estimated commercial charges accounting for hospital factors. Results: Most hospitals (N=4212) were non-profits (61%) and acute care hospitals (69%). Median operating margin was .03 (IQR:-.03, .09), asset-to-liability ratio was 1.79 (1.06, 2.96), and social vulnerability index was .53 (.29, .74). 48-50% reported mammography charges. Charges were greater for commercial insurance compared to Medicare/Medicaid (+$55-$82 screening, +$122-$132 bilateral diagnostic; P<.001, all tests). Charges for commercial insurance were similar to self-pay for bilateral screening (p=.41) and diagnostic (p=.08) mammography. See Table for adjusted analysis of commercial charges. Conclusions: Our analysis showed U.S. negotiated mammography charges are similar for self-pay and commercial payers. Commercial charges are higher at private hospitals and those with higher operating margins for diagnostic exams, and lower in socially vulnerable areas. Price transparency may promote competition to lower healthcare prices and highlight any financial toxicity associated with self-pay charges. [Table: see text]
Analysis of a post covid multi-disciplinary meeting operating in a digitally supportive virtual platform.
Authors: van Loggerenberg Dominic , Benn Carol 
Published: June 2022

e13645 Background: The BCCE is an NAPBC internationally accredited unit operating around a surgical oncology breast specialist surgeon, three reconstructive surgeons; four radiological units four pathology labs; 8 medical oncologists and 3 radiation oncologists. Whilst the centre was affected by the SARS Covid-19 pandemic, a rapid restructuring of the MDM procedure allowed for a return to -pre-pandemic service delivery and optimum time-to-treatment of 21days. Methods: Over the 2021 period the BCCE saw 778 newly diagnosed cancer patients, these are all reviewed at a 25 member MDM with 308 patients having full radiological review during the meetings and 609 full pathological reviews prior to treatment discussion amongst the members. These MDM discussions occurred within 6 days of clinical examination due to the integration of multiple specialists and facilities resulting in rapid appointments. Further pathological analysis of 203 patients occurred beyond initial presentation as well as over 350 OncotypeDx reviews. Five hundred and seventy-one individual patient treatment feedback discussions occurred directly postoperatively and 459 treatment plans were reviewed prior to secondary treatment pathways. Results: Digital MDM’s resulted in a full return to the centre’s optimum level of care, a 7 day MDM review with a 21-day treatment pathway plan proposal, whilst still under the effect of pandemic lockdown regulations. A 6-month comparison (during lockdown regulations) showed a 15% increase in patients seen whilst supported with virtual consultation platforms and digitally supported MDM decisions. Conclusions: Whilst the SARS Covid-19 pandemic affected service delivery. Medical IT transference to full digital MDM allowed for improved review and treatment planning. This improved service delivery to patients with physician and navigator knowledge transfer, resulting in growth of the unit.
Whole brain radiotherapy and association with rapid brain aging as determined by anatomic surface morphology.
Authors: Rammohan Nikhil , Ho Alexander , Kruser Tim J. , Besson Pierre , Bandt S Kathleen 
Published: June 2022

e14007 Background: Brain metastases are the most common intracranial tumors in adults and are associated with significant morbidity and mortality. Whole brain radiotherapy (WBRT) is used frequently in patients for palliation, but can result in neurocognitive deficits. While dose-dependent injury to individual areas such as the hippocampus have been demonstrated, global structural changes after WBRT remain to be studied. Our group previously published a magnetic resonance imaging (MRI) deep learning model based on anatomic brain surface morphology to accurately predict brain age in healthy subjects. We now report the effect of WBRT on aging pace of the irradiated brain. Methods: We studied patients with brain metastases and examined MRI brain anatomic surface data before and after WBRT. We implemented a graph convolutional neural network model to estimate patient’s brain age. We further developed a mixed-effects linear model to compare age of whole brain and substructures before and after WBRT, written as follows: ΔAge = c + β(ΔScan) + 1|patient_ID; where for each patient, ΔAge = [(model_predicted_age_at_follow up – actual_age_at_follow up) – (model_predicted_age_pre_treatment – actual_age_pre_treatment)], ΔScan = time interval between pre-and post-treatment MRI scans, β = aging coefficient (β =0 corresponds to normal aging), and c = intercept (model_predicted_age_pre_treatment – actual_age_pre_treatment). Results: 56 patients were analyzed. The median age was 62 (range 32 – 85). Two-thirds of patients were female. Primary organ site was breast or lung in 87% of cases and 77% of patients had five or more metastases. Median radiation dose was 30Gy (range 25 – 37.5Gy). Results of aging analysis are presented in Table. Small c values demonstrate that model accurately predicted age pre-treatment. The whole brain and substructures underwent rapid aging compared to normal aging pace (β>>0). Based on median follow up of 6.3 months, the whole brain aged approximately 4.94 years, the cortex aged approximately 4.53 years, the subcortical structures aged approximately 5.94 years, and the hippocampus aged approximately 5.17 years. Conclusions: Our findings suggest that WBRT causes the brain and its substructures to age at a pace of 9-11x of the normal aging pace, mirroring deficits in long-term neurocognition seen post-treatment. Given post-treatment aging pace and increasing survival for many patients with brain metastases, WBRT needs to be used judiciously. [Table: see text]