bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Tempus TIME trial portal and clinical trial enrollment.
Authors: Rao Amol , Miller Kevin , Huynh Chanh Trung , Luedtke Rachel , Anderson Mary Alice , Harris Melissa , Johnstone Michael , Murphy Lauren , Morgan Nicholas , Harmon Rachel , Ward AnnaJane , Donovan Blathnaid , Rice Christie , Sherrin Scott , Darmofal Annie , Skelly Danielle , Cooney Matthew M. 
Published: June 2023

1583 Background: The TIME Trial Program is a research network that screens > 1 million patients daily via EMR integrations and NGS testing through an automated trial matching platform and human review. There are enormous complexities following patients longitudinally as their clinical status changes while accurately matching them with hundreds of studies. The TIME Trials Portal, which stores both clinical trial documents and patient status updates, allows for real-time communication between the TIME team and Clinical Sites. Methods: After both an automated and nursing review, eligible trial patients are uploaded into the TIME Trials Portal. This database tracks the patient’s name, date of birth, biomarkers, clinical status, trial matches, free text comments, and upcoming physician, radiology, and laboratory appointments. To protect Personal Health Information, each Clinical Site can only view their own patients. Patient status is classified as Needs Review, Monitoring, Enrolled, Inactive. Each update is time-stamped and tracked. Enrolled patients have the trial name, consent date, and other pertinent information documented. Results: The data from 2020 to 2022 includes 71 TIME Sites. Over this period, 6,816 patients were added to the TIME Trials Portal for an average of 219 per month. Of these, 1,891 patients were no longer eligible due to worsening performance status, trial closure, death, and other causes. The TIME team provided 8,643 patient updates compared to 7,442 Clinical Site updates. Clinical Sites spent 1,231.7 hours using the TIME Therapies Portal resulting in 623 total consents. Data from 2022 alone, demonstrated that 30 (42.3%) Clinical Sites with EMR integrations were responsible for 4,491 (76.3% of the total) patient updates translating into 288 (82.1%) of all consents. Also in 2022, of the 27 (38%) Clinical Sites that updated their patient’s status > 50 times consented 291 (82.9% of the total) patients. Conclusions: By 2022, the TIME Trials Portal was averaging approximately 400 new patients monthly resulting in a 13.1X increase in patients added from the program’s inception. Clinical Sites updated the patient status over 7,400 times spending over 1,200 hours using the TIME Trials Portal. The highest-performing Clinical Sites, which enrolled approximately 80% of the total patients, included those with EMR integrations and/or > 50 patient updates yearly. The TIME Trials Portal enabled patient tracking and communication to facilitate clinical trial enrollment.[Table: see text]
Comparison of publications between cancer sites in high impact factor journals.
Authors: Sinha Nikita , McDonald Amanda , Barry Danika , Barber Emma Longley 
Published: June 2023

1588 Background: Prior studies have shown disparities in federal funding allocation by cancer site after accounting for mortality, incidence, and person-years of life lost. Whether disparities exist in publications in high impact factor journals is unknown. The aim of this study is to analyze research publications in high impact factor journals by cancer site relative to their burden from 2000 to 2018. Methods: Abstracts from the top 55 impact factor journals from 2000 to 2018 were extracted from PubMed. We developed an algorithm to search the title of the abstract to determine whether the abstract was about cancer and identify the cancer type. The algorithm was validated against the gold standard of human review in 1143 abstracts and yielded a sensitivity and a specificity of >95%. An article proportion for each cancer site was calculated (abstracts for a cancer site / total cancer abstracts). Article proportion was compared to cancer site-specific incidence, mortality and lethality from NCI’s SEER database using scatter plots and non-parametric Wilcoxon signed rank test. Results: We identified 128,377 articles; 31,045 (24%) were about cancer. Cancers with the most publications in high impact factor journals were breast (22%), lung (11%), and colorectal (10%) cancer. Breast, lung and colorectal cancer were also well represented in high impact factor journals compared to their incidence, mortality, and lethality. Gynecologic (ovarian, cervical, and endometrial), pancreatic, hepatobiliary, and prostate cancers were poorly represented in all 3 metrics. Breast, lung, and colorectal cancer ranked in the top half of Article to Lethality scores, while the gynecologic, pancreatic, and hepatobiliary cancers were in the bottom half (p <0.05 for all comparisons). Comparison of rankings by lethality versus by funding indicates relative underfunding of the gynecologic, pancreatic, hepatobiliary, and prostate cancers. Conclusions: Research publications in high impact factor journals by cancer site are not proportionate to individual societal cancer burden. Significant disparities exist between breast, lung, and colorectal cancer when compared to gynecologic, pancreatic, hepatobiliary, and prostate cancers relative to their disease burden. Underfunding of these cancer sites likely contributes to this publication gap.[Table: see text]
Cost-effectiveness of trastuzumab deruxtecan in HER2 low metastatic breast cancer.
Authors: Dickerson James , Moen Marcus , Nielsen Perry , Tran Edward , Suen Wesley , Goldhaber-Fiebert Jeremy D , Alarid-Escudero Fernando 
Published: June 2023

1593 Background: In recent years, metastatic breast cancer treatment has been revolutionized by new therapies that improve overall survival in phase three randomized clinical trials. These drugs are often more expensive than traditional cytotoxics. In 2022, the Destiny-Breast04 trial results showed that trastuzumab deruxtecan (T-DXd) improved survival in HER2 low metastatic breast cancer patients; FDA approval shortly thereafter greatly expanded the potential market capitalization of T-DXd. While the trial demonstrated T-DXd’s clinical efficacy, its cost-effectiveness remains unknown. Methods: We developed a decision-analytic state transition Markov model to simulate a hypothetical cohort of HER2 low metastatic breast cancer patients to assess the cost-effectiveness of T-DXd compared to a physician's choice chemotherapy from a US healthcare payer perspective over a lifetime horizon. Each month, simulated patients could remain progression-free, progress, have a non-interstitial lung disease (ILD) treatment-related adverse event leading to drug discontinuation (TRAE), have ILD leading to drug discontinuation, progress after either a TRAE or ILD, or die. Patients with either a TRAE or ILD were presumed to be progression free directly after discontinuation of the offending agent, and hence eligible for a different therapy. We calibrated the model to outcome data from the Destiny-Breast04 trial, supplemented with data from other relevant metastatic breast cancer clinical trials. Health-related quality-of-life weights were derived from studies of metastatic breast cancer patients. Drug prices (2020 USD) were extracted from the Federal Supply Schedule. Outcomes included discounted (3% annual) quality-adjusted life years (QALYs), life years, lifetime costs, and incremental cost-effectiveness ratios (ICER). We varied T-DXd price and efficacy in a two-way sensitivity analysis to assess our findings’ robustness. Results: Modeled life expectancies with T-DXd and chemotherapy were 26.5 and 21.5 months, respectively (T-DXd: 1.19 QALYs; chemotherapy: 0.93 QALYs). Discounted lifetime costs were 315,000 for T-DXd and 203,000 for chemotherapy; T-DXd cost 431,000 per QALY gained, surpassing a cost effectiveness threshold of 150,000 per QALY gained. The two-way sensitivity analysis showed that, across a range of plausible efficacies, T-DXd would need a price reduction of approximately 50% to be cost-effective at the $150,000 threshold. Conclusions: While providing clinical benefits, our model-based analysis finds that at current prices, T-DXd for HER2 low metastatic breast cancer is not cost-effective at traditional thresholds. Substantial price reduction for T-DXd to a level much closer to prices of comparator cytotoxics could greatly increase the value for money T-DXd provides patients.
Association of participation in Medicare’s Oncology Care Model with spending, utilization, and quality outcomes among commercially insured and Medicare Advantage members: A national difference-in-differences analysis.
Authors: Mullangi Samyukta , Ukert Benjamin , Sylwestrzak Gosia , DeVries Andrea , Schauder Stephanie , Andreyeva Elena , Debono David Joseph , Fisch Michael Jordan , Schleicher Stephen Matthew , Navathe Amol S. , Schwartz Aaron L , Bekelman Justin E. , Parikh Ravi Bharat 
Published: June 2023

1596 Background: Medicare’s Oncology Care Model (OCM) was a voluntary, episode-based model between 2016 and 2021 that provided participating practices with additional payments to fund care enhancements such as extended clinical hours and urgent care. While it resulted in net losses for traditional Medicare beneficiaries, the OCM may have had “spillover” improvements on spending, utilization, and quality for commercially insured (CM) and Medicare Advantage (MA) members who were not targeted by the program. Methods: This retrospective analysis used claims from Elevance Health, a large national payer, to identify commercially insured and Medicare Advantage members diagnosed with breast, colorectal, lung, prostate, and pancreatic cancer initiating systemic therapy between 2014 to 2021. We identified 85 OCM practices and 581 matched non-OCM practices based on episode, practice, demographic, and market factors. The exposure variable was participation in the OCM model. All outcomes were defined in 6-month episodes; the primary outcome was overall inflation-adjusted spending; secondary outcomes included hospitalization and emergency room visits, and end-of-life acute care utilization. We utilized adjusted difference-in-differences linear probability models, with state-level fixed effects to control for market price variability, to estimate the association between OCM participation and all outcomes. Results: We studied 45,296 episodes of care in OCM practices and 122,231 episodes in non-OCM practices among CM and MA members during the post-implementation period. OCM participation was associated with a $5,275 (SE $749.40) reduction in total allowed spending (p<0.001), driven by reductions in outpatient and systemic therapy spending. OCM was associated with improvements in end-of-life utilization and ED visits but none in hospitalizations and timely chemotherapy initiation. Conclusions: Participation in the OCM was associated with modest spillover spending benefit onto CM and MA members, but minimal utilization and quality benefits. Resultant practice innovations may have benefited non-targeted patients. Evaluations limited to targeted patients may have underestimated the full impact of the OCM.[Table: see text]
Telemedicine-supervised cancer therapy for patients with an aggressive lymphoma and metastatic lung cancer in the U.S. Veterans Affairs National TeleOncology Service.
Authors: Lin Chenyu , Zhou Katherine I. , Burningham Zachary R. , Rowe Kerry G. , Anglin-Foote Tori , Maddox Mark , Friedman Daphne Ruth , Halwani Ahmad Sami , Passero Vida Almario , Kelley Michael J. , Rodgers Thomas David 
Published: June 2023

1602 Background: Telemedicine is increasingly used in cancer care but has mostly been applied to surveillance and oral therapy rather than parenteral treatments. In the U.S. Veterans Affairs National TeleOncology service (NTO), patients receive intravenous cancer treatments locally under remote supervision from a disease-specialized oncologist. We analyzed care delivered by the NTO for patients with an aggressive lymphoma (AL) and metastatic lung cancer (mLC). Methods: The demographics of veterans with AL and mLC enrolled in NTO between 2020-2023 were compared to patients receiving in-person care at the VA. From these NTO cohorts, two subsets of patients receiving 1st line therapy for diffuse large B cell lymphoma (DLBCL) and stage IV non-small cell lung cancer (NSCLC) were extracted and compared to control arms of in-person care matched 1:4 by stage, age, PDL1 (NSCLC), and cytogenetics (DLBCL). Fisher’s exact test was used for categorical variables, t test for continuous variables, log rank for survival, and negative binomial for count outcomes. Results: 140 patients with AL or mLC (40 DLBCL, 13 Hodgkin, 2 Burkitt, 61 NSCLC, 24 SCLC) were enrolled in NTO, spanning 12 U.S. states. Compared to in-person care ( n = 7,561), NTO had more rural (56% vs. 34%, p < 0.001) and white patients (89% vs. 77%, p = 0.002). With a median follow-up of 256 days (IQR, 154 - 415), NTO mLC and AL patients had a median of 15 and 17 telemedicine visits, respectively. 13 of 55 AL (24%) and 56 of 85 mLC (66%) patients received systemic therapy of any line, while 38 (69%) of AL were on surveillance. 7 mLC and 2 AL patients were referred externally for care. 11 patients with DLBCL and 30 patients with stage IV NSCLC started 1st line therapy while in NTO, which were compared to matched controls. NTO and matched control had similar mean time from referral to first appointment and from diagnosis to first treatment. There were no significant differences in progression-free survival between NTO and matched controls for NSCLC (HR 1.1, 95% CI 0.7-1.8) or DLBCL (HR 0.5, 95% CI 0.1-2.3). COVID infections in the first 12 months and number of ED visits in the first 3 months of treatment were not statistically different from controls. Conclusions: The NTO service demonstrates the feasibility of infusional chemoimmunotherapy administration under the direction of a remote tele-oncologist. This model has the potential to improve access to specialized oncology care for rural populations and provides a framework for decentralized clinical trials.[Table: see text]
Use and value of self-management (SM) recommendations in a real-world evidence study evaluating digital patient monitoring (DPM) of patients (pts) receiving cancer care.
Authors: Eicher Manuela , Bana Marika , Ribi Karin , Schneider Sophie , Ammann Johannes 
Published: June 2023

1603 Background: SM includes pts’ abilities and activities to manage symptoms, treatment (tx), and any problems inherent to a chronic condition. Tailored SM support is recommended in cancer care. DPM enables pts to systematically self-report disease- or tx-related symptoms, communicate directly with healthcare professionals (HCPs), and access support materials. This observational study evaluated the real-world use of the Symptom Navi Program (SNP; Bern, Switzerland) SM materials on the Kaiku Health DPM platform (Helsinki, Finland) in collaboration with F. Hoffmann-La Roche Ltd (Roche; Basel, Switzerland). Methods: Adults diagnosed with locally advanced or metastatic non-small/small cell lung cancer, or any stage HER2-positive breast cancer being treated with locally approved and reimbursed drugs with an expected tx duration of >3 months, had access to a DPM solution that provided disease- and tx-tailored modules, including SNP SM recommendations for selected mild or moderate symptoms. The co-primary endpoints were DPM adoption and adherence. Here we report secondary endpoints; the perceived clinical impact, DPM module and service experience (assessed via Customer Effort Score [CES] and Customer Satisfaction Score [CSS]), and use of DPM features such as SM recommendations, via a DPM tool questionnaire. Results: Of the 89 enrolled pts, 66 had completed the DPM tool questionnaire at Week 6 of DPM use (data cutoff: June 9, 2022). Among the educational content, the symptom feedback library was accessed most. Pts spent up to a median of 12 minutes on Roche educational or SNP SM materials. The majority of pts (45/66 [68%]) considered the symptom questionnaires to cover all/most of the symptoms they experienced; 18/66 (27%) experienced only fair/partial symptom coverage; 49% (25/51) of pts whose symptoms were not covered contacted their HCP team. 34 pts (52%) took action based on the symptom questionnaire feedback; the most common action was SM recommendations applied according to symptom level (21/66 [32%]), followed by sending a message via the platform to the care team (8/66 [12%]). Half of pts found the SNP SM recommendations helpful/very helpful and 22 pts agreed that the SNP SM recommendations almost always/sometimes supported them in delaying contacting an HCP at an emergency room. At Week 6, the CES was 80%, CSS was 71%, and 48% (32/66) of pts felt that this service improved their care. Conclusions: Pt feedback showed that SNP SM recommendations were the most used action in response to the symptom questionnaire feedback and were perceived by most to be helpful/very helpful. These results support the use of SM recommendations in pts with cancer to help them self-manage tx-related symptoms experienced; future studies are needed to further explore their impact and usefulness, and to form recommendations for routine use in clinical practice.
INB-200 phase I study of gene modified autologous gamma-delta (γδ) T cells in patients with newly diagnosed glioblastoma multiforme (GBM) receiving maintenance temozolomide (TMZ).
Authors: Lobbous Mina , Goswami Trishna , Lamb Lawrence S. , Rochlin Kate , Pillay Thriumaine , Youngblood Samantha , ter Haak Mariska , Nabors Louis B. 
Published: June 2023

2007 Background: MHC unrestricted γδ T cells target NKG2D ligands upregulated on tumor cells. IN8bio’s DeltEx chemotherapy resistant cell therapy (CRCT), is a novel γδ T cell genetically engineered to express MGMT to convey temozolomide (TMZ) resistance and allow combination therapy. NCT04165941, a Phase 1 trial assessing the safety of single and multiple infusions of autologous CRCT cells presents updated safety and efficacy data. Methods: Adult newly diagnosed GBM patients with adequate organ function and KPS≥70% are enrolled. Cells engineered from apheresis were infused through a Rickham catheter placed during surgery. Cohorts (C) 1, 2 and 3 each receive 1, 3 and6 doses of cells respectively on day (D) 1 of each 28-day maintenance cycle. Patients receive 1 x 107 γδ T cells intratumorally with 150 mg/m2 of TMZ intravenously on D1 of maintenance with the standard Stupp maintenance regimen on D2-5. Primary endpoint is safety; secondary endpoints include progression free and overall survival. Immunologic and genomic correlative analyses are being conducted. Dose limiting toxicities (DLTs) are defined as treatment related ≥ grade 3 cardiopulmonary or hepatic toxicity, grade 4 toxicity exceeding 72 hours or neurologic deterioration that exceeds 2 weeks. Results: 15 patients (53% male; median age 69 (range: 21-76); 80% IDH-WT, 66.7% MGMT unmethylated) were enrolled with 8 dosed (N=3 in C1, 4 in C2, 1 in C3). No patients experienced DLTs, cytokine release syndrome (CRS), or neurotoxicity (ICANS). The most common adverse events (AEs) were Grade 1/2 events including fever, fatigue, nausea, headache, platelet count decreased, incision site pain attributable to TMZ, radiotherapy or disease. One subject had Grade 3 treatment related AEs of UTI, dehydration, and thrombocytopenia. Three evaluable C1 patients have PFS of 8.3, 11.9, 7.4 months and OS of 15.6, 17.7 and 9.6 months respectively. In C2, four patients have been dosed, with no DLTs in 3 evaluable patients; 2 remain progression free at 18.9 and 14.8 months, while a third died without relapse due to pulmonary embolus at 8.7 months. One C3 patient has completed 5 of 6 planned doses without DLT. Patient recruitment continues with anticipated completion in 2023. Conclusions: Data demonstrates that single, repeat doses of CRCT gamma delta T cells have manageable toxicity with continued encouraging trend in PFS and warrants further assessment. Clinical trial information: NCT04165941 .
A genomic score to predict local control among patients with brain metastases managed with radiation.
Authors: Lamba Nayan , Cagney Daniel , Catalano Paul J. , Elhalawani Hesham Magdy Mohammad , Kim Dewey , Haas-Kogan Daphne A. , Wen Patrick Y. , Wagle Nikhil , Aizer Ayal 
Published: June 2023

2011 Background: Clinical predictors of local recurrence following radiation among patients with brain metastases (BrM) provide limited explanatory power. As a result, radiation doses and fractionation schemes are prescribed with a “one-size-fits-all” approach. We sought to develop a DNA-based signature of radiation-based efficacy among patients with BrM, utilizing readily testable genes, to identify subpopulations at greater vs. lesser risk of recurrence. Methods: We retrospectively identified 570 patients with 1,487 distinct BrM managed with whole-brain (WBRT) or stereotactic radiation therapy (SRS/SRT) at a tertiary cancer center (2013-2020) for whom next-generation sequencing panel data (OncoPanel, 239 genes) were available on at least one tumor specimen. Local recurrence was assessed in a manner consistent with Response Assessment in Neuro-Oncology – Brain Metastases guidelines (i.e., radiographic enlargement of >20% in maximal cross-sectional diameter). Enlarging lesions managed with salvage treatment prior to >20% enlargement were considered to have recurred on the date of salvage therapy. Fine/Gray’s competing risks regression was utilized to compare local recurrence on a per-metastasis level among patients with vs. without somatic alterations of likely biological significance across 84 OncoPanel genes with a mutational frequency >0.5%. Genes with a q-value<0.10 were utilized to develop a numeric “Brain-Radiation Prediction Score” (“Brain-RPS”) to quantify local recurrence risk. Results: Genomic alterations of potential biological relevance in 11 ( ATM, MYCL, PALB2, FAS, PRDM1, PAX5, CDKN1B, EZH2, NBN, DIS3, MDM4) and two genes ( FBXW 7 and AURKA) were associated with a decreased or increased risk of local recurrence, respectively (q-value<0.10). Weighted scores corresponding to the strength of association with local failure for each gene were summed to calculate a patient-level RPS. On multivariable Fine/Gray’s competing risks regression, RPS [1.66 (1.44-1.92, p<0.001)], metastasis-associated edema [1.89 (1.38-2.59), p<0.001] and receipt of WBRT without SRS/SRT or neurosurgical resection [2.73 (1.78-4.20), p<0.001] were independent predictors of local failure. Conclusions: We developed a genomic score that can be calculated from an extracranial or intracranial site to quantify local recurrence risk following brain-directed radiation. Prior attempts to develop a biomarker-based radiation response signature have not been BrM-specific and have primarily relied on RNA-based measures of radiosensitivity, limiting their utility in clinical practice. To our knowledge, this represents the first study to systemically correlate DNA-based alterations with radiation-based outcomes among patients with BrM. If validated, Brain-RPS has potential to facilitate clinical trials aimed at genomic personalization of radiation treatment among patients with BrM.