tbuckley/cabot-search huggingface dataset:
Growth in eligibility criteria content and failure to accrue among National Cancer Institute (NCI)-affiliated clinical trials.
Authors: John Stuart Peterson, Deborah Plana, Danielle Sara Bitterman, Skyler B Johnson, Benjamin Harris Kann
Journal: Journal of Clinical Oncology (2021)

1515 Background: Cancer clinical trial accrual across diverse socioeconomic and demographic groups is a national priority, yet up to 20% of trials fail due to poor accrual. Eligibility criteria content may contribute to poor accrual, but effects are challenging to measure. We sought to evaluate growth of eligibility criteria within NCI-affiliated cancer trials and the impact on trial accrual over the past decade. Methods: We conducted a retrospective study with the Aggregate Analysis of ClinicalTrials.gov (AACT) (abstracted: 02/02/2021). We included NCI-affiliated, interventional Phase II or III trials that initiated between 01/01/2008 and 12/13/2018. We excluded active and recruiting trials that lacked accrual data on the Cancer Trials Support Unit website. Trials whose status was “Withdrawn”, “Terminated”, or “Suspended” due to low accrual, or had less than 50% target accrual after two years active were deemed accrual failures. Eligibility criteria were extracted from inclusion and exclusion criteria and complexity was estimated by the number of unique content words, calculated by removing duplicates and stop words from the word count. Association of unique word count with accrual failure was evaluated by univariable and multivariable logistic regressions, adjusting for other predictors of low accrual identified in earlier research. Results: Of 1197 trials included, 231 (19.3%) failed due to low accrual. Eligibility criteria increased in length from a median of 214 (IQR [23, 282]) unique content words in 2008 to 417 (IQR [289, 514]) in 2018. The rate of trial accrual failure increased with unique word count decile from 11.8% in the first decile (12 to 112 words) to 29.4% in the tenth decile (445 to 750 words) (P = 0.004). On multivariable analysis, unique word count remained independently associated with low accrual (OR: 1.07 per decile, 95%CI [1.01-1.13], P = 0.02), as did Phase III and metastatic disease settings (Table). Conclusions: Eligibility criteria content has increased dramatically in the last decade in NCI-affiliated trials. Increasing eligibility criteria content associates strongly with accrual failure, even after adjusting for multiple known predictors of accrual. These findings underscore the need for efforts to simplify eligibility criteria to improve trial accrual. Further investigation is ongoing to determine specific criteria qualities that portend accrual failure.[Table: see text]
Increasing underrepresented minority cancer patient enrollment into cancer clinical trials: A systematic review.
Authors: Rosa Nouvini, Patricia A. Parker, Charlotte Malling, Kendra Godwin, Rosario Costas-Muñiz
Journal: Journal of Clinical Oncology (2021)

e18574 Background: Minorities continue to be underrepresented in clinical trials despite the National Institute of Health’s Revitalization Act, passed in 1993, mandating the representation of women and underrepresented minority groups in clinical trials. Studies have shown that although Blacks represent 15% and Hispanics 13% of the cancer population, their clinical trial enrollment rates in are disproportionately low at 4-6% and 3-6% respectively. We conducted a systematic review exploring interventions aimed at improving clinical trial enrollment for racial and ethnic minorities. Methods: A systematic search of PubMed, Cochrane CENTRAL, and Ovid PsycINFO was conducted for English-language studies of humans since 1993. Inclusion criteria included peer-reviewed, U.S.-based studies with interventions aimed to recruit underrepresented minority adult cancer patients into cancer clinical trials. We defined underrepresented minority groups as Black, Hispanic/Latino, Asian, American Indian/Alaska Native and Native Hawaiian/other Pacific Islander. Results: A total of 2471 titles and abstracts were identified and 2324 were excluded based on the eligibility criteria. A full text review was conducted of the remaining 147 articles, of which only 9 met criteria for our review. The interventions included patient navigation/coaching (n = 4), a clinical trial educational video (n = 2), institutional research infrastructure changes (n = 1), a relationship building and social marketing recruitment model (n = 1) and cultural competency training for providers (n = 1). Studies were conducted in a variety of practice settings including national cancer institutes and community practices. The quality of evidence was limited by the heterogeneity of study methods, patient representation and bias. Several studies had a homogeneous population of Black patients. Most studies (n = 7) were single arm trials that compared results to either historical controls or those cited in the existing literature; two studies were randomized controlled trials. A statistically significant improvement in accrual was shown in three of the patient navigation interventions, one of the clinical trial educational videos, the institutional research infrastructure change and the relationship building and social marketing recruitment model. The common threads to many of these successful interventions were support through the cancer care continuum, cultural congruency of research staff and culturally catered clinical trial educational materials. Conclusions: This systematic review illustrates several mechanisms by which to increase cancer clinical trial recruitment for cancer patients of underrepresented minority backgrounds in a variety of clinical settings. Randomized controlled trials with representation of multiple races/ethnicities are needed to further explore the benefits of these interventions.
A Phase Ib Open-Label, Multicenter Study of Inhaled DV281, a TLR9 Agonist, in Combination with Nivolumab in Patients with Advanced or Metastatic Non–small Cell Lung Cancer
Authors: Edward B. Garon, Alexander I. Spira, Melissa Johnson, Lyudmila Bazhenova, Joseph Leach, Amy L. Cummings, Albert Candia, Robert L. Coffman, Mary J. Janatpour, Robert Janssen, Erick Gamelin, Laura Q.M. Chow
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Although PD-(L)1 inhibitors have shown efficacy in advanced/metastatic non–small cell lung cancer (NSCLC), many patients do not respond to this treatment and more effective combinations with acceptable toxicities are needed. To assess the potential benefit of combining localized innate immune stimulation with checkpoint blockade, the TLR9 agonist DV281 was combined with nivolumab in a phase Ib study. Patients and Methods: Patients after one or two prior lines of systemic therapy were enrolled in a dose-escalation study with a 3+3 design. DV281 was administered via inhalation in five dose cohorts at 1 to 25 mg; nivolumab 240 mg was administered intravenously every 2 weeks. Safety, tolerability, pharmacodynamics, and response to treatment were assessed. Results: Twenty-six patients with advanced NSCLC enrolled. Baseline programmed death ligand 1 (PD-L1) expression was present in 16 patients (61.5%); 21 (80.7%) had received previous anti–PD-1/PD-L1. Thirteen patients (50%) had stable disease, nine (34.6%) had progressive disease, and four (15.4%) were not evaluable. Median duration of disease control was 124 days. Adverse events were seen in 16 patients (61.5%), mostly grade 1/2 chills, fatigue, flu-like symptoms, diarrhea, and rash; there was only one grade 3 adverse event (dyspnea). Pharmacodynamic assessment, measured by IFN- inducible gene expression, showed target engagement in all dose cohorts. Systemic pharmacodynamic responses plateaued in the 2 highest dose cohorts. Conclusions: DV281 with nivolumab was well tolerated with target engagement observed at every dose. Pharmacodynamic advantages at doses above 10 mg were unclear. The long duration of disease control in 50% of patients suggests clinically relevant activity in this population of heavily pretreated patients.
Association of use of remote patient monitoring (RPM) with reduced hospitalizations in cancer patients with COVID-19.
Authors: Joshua Pritchett, Aakash Desai, Bijan J Borah, Zhuoer Xie, Antoine N Saliba, Konstantinos Leventakos, Jordan Coffey, Kristin Pearson, Leigh Speicher, Robert Orenstein, Abinash Virk, Ravindra Ganesh, Jonas Paludo, Tufia C. Haddad
Journal: Journal of Clinical Oncology (2021)

1503 Background: Patients with cancer and COVID-19 are at risk for poor clinical outcomes. An established multi-site remote patient monitoring (RPM) service was rapidly adapted to support a novel, interdisciplinary COVID-19 program for outpatient management of patients at high-risk for severe illness. The goal of this study was to assess the impact of the RPM program on clinical outcomes and acute care utilization in cancer patients diagnosed with COVID-19. Methods: This is a cross-sectional analysis following a multi-site prospective observational study performed at Mayo Clinic Cancer Center (MCCC). All adult patients with active cancer – defined as currently receiving cancer-directed therapy or in recent remission on active surveillance – and PCR-confirmed SARS-CoV-2 infection between March 18 and July 31, 2020 were included. RPM was comprised of in-home technology to assess symptoms and physiologic data with centralized nurse and physician oversight. Results: During the study timeframe 224 cancer patients were diagnosed with COVID-19 at MCCC. Initial management included urgent hospitalization (within 48 hours of diagnosis) in 34 patients (15%). Of the remaining 190 patients (85%) initially managed in the outpatient setting, those who did not receive RPM were significantly more likely to experience hospitalization than those receiving RPM (OR 3.6, 95% CI 1.036 to 12.01, P = 0.044). Following balancing of patient characteristics by inverse propensity weighting, rates of hospital admission for RPM and non-RPM patients were 3.1% and 11% respectively, implying that RPM was associated with an 8% reduction in hospital admission rate (-0.077; 95% CI: -0.315 to -0.019, P = 0.009). Use of RPM was also associated with lower rates of prolonged hospitalization, ICU admission, and mortality, though these trends did not reach statistical significance. Conclusions: In the midst of a global pandemic associated with inpatient bed, ventilator, and PPE shortages, the RPM program provided an effective strategy for outpatient clinical management and was associated with decreased rates of hospitalization, ICU admission, and mortality in cancer patients with COVID-19. This care model enabled simultaneous opportunity to mitigate the increased risks of exposure, transmission, and resource utilization associated with conventional care.
Distinct Biomarkers Reflect Pathophysiological Differences of Sickle Cell Disease Sub-Phenotypes: Viscosity-Vaso-Occlusion Vs. Hemolysis-Endothelial Dysfunction
Authors: Ioannis Papassotiriou, Christos Poziopoulos, Katerina Larissi, Alexandra Margeli, Marianna Politou, Evangelos Terpos, Ersi Voskaridou
Journal: Blood (2017)
Patient navigation plus hospital at home to improve COVID-19 outcomes for cancer patients.
Authors: Brittany K. Ragon, Ashley Love Sumrall, Kris Blackley, Ify Osunkwo, Tamara Kay Moyo, Laura Kabrich, Kelly Leonard, Ben Masten, Beth York, Stephanie Murphy, Brian Kersten, Thomas Batchelor, Carly Rivet, Armida Parala-Metz, Zainab Shahid, Seungjean Chai, Laura W. Musselwhite, Declan Walsh
Journal: Journal of Clinical Oncology (2021)

1524 Background: Reports suggested cancer patients were at greater risk for increased morbidity and mortality from COVID-19. A process to mitigate these risks was established at Levine Cancer Institute (LCI) in partnership with Atrium Health’s (AH) Hospital at Home (HAH) initiative. This virtual health navigation process employed expertise from the departments of Hematologic Oncology and Blood Disorders, Oncology, and Supportive Oncology, including a specialized nurse navigation team, to rapidly identify COVID-19 positive LCI patients, monitor them under physician supervision, and escalate care as needed with AH HAH program. Methods: AH Information Services created an automated list of LCI COVID-19 positive patients with a daily database. Each patient was reviewed by a nurse navigator. Review included hematologic or oncologic diagnosis, outpatient or inpatient status, and any COVID-19 symptoms. Once a malignant diagnosis was confirmed, a diagnosis-specific navigator contacted and screened the patient with a COVID assessment tool. Documentation was forwarded to the primary oncologist/hematologist. The tool scored patients for surveillance and treatment needs. A score of 0-2 prompted phone assessment every 48-72 hours, and score of 3-5 required every 24-48 hour calls with physician involvement when appropriate. If score of ≥6, care was escalated to LCI nurse/physician for admission to AH acute care HAH or conventional inpatient admission. Results: From inception on 3/20/2020 to data review date of 12/2/2020, 974 LCI patients were identified as COVID-19 positive and reviewed for nurse navigation (Table). Of the 974, 488 were navigated. Given limited resources, patients with benign conditions were not assigned a navigator, though a similar process was created for sickle cell disease. Of the 974, 75 are now deceased. Only 25 are deceased among the 488 navigated. Conclusions: The COVID-19 pandemic presented unprecedented circumstances to our patients and their clinicians. LCI expeditiously put policies and procedures in place to mitigate the intersection of COVID-19 and cancer. The multidisciplinary response strategy liaising between AH HAH and LCI followed, assessed, and assisted LCI COVID-19 positive patients. With our embedded nurse navigation team’s specialized attention along with enhanced physician oversight and close collaboration with AH HAH, opportunities for care escalation or adjustments in cancer-focused care were promptly identified. Analysis is ongoing to elucidate the lower mortality rate observed among navigated patients.[Table: see text]
The Impact of Adding Aspirin to Warfarin without an Apparent Indication: An Exploration of Patients Anticoagulated for Atrial Fibrillation or Venous Thromboembolic Disease
Authors: Jordan K. Schaefer, Nicole M. Souphis, Suman L. Sood, Brian Haymart, Xiaokui Gu, Eva Kline-Rogers, Steven L. Almany, Jay H. Kozlowski, Gregory D. Krol, Scott Kaatz, James B. Froehlich, Geoffrey D. Barnes
Journal: Blood (2017)
Differential role of residual metabolic tumor volume in patients with inoperable stage III NSCLC after chemoradiotherapy ± immune checkpoint inhibition.
Authors: Marcus Unterrainer, Julian Taugner, Lukas Käsmann, Chukwuka Eze, Wolfgang G. Kunz, Amanda Tufman, Niels Reinmuth, Claus Belka, Farkhad Manapov
Journal: Journal of Clinical Oncology (2021)

e20558 Background: PET-derived metabolic-tumor-volume (MTV) has shown to be an independent prognosticator in non-small cell lung cancer (NSCLC) patients treated with chemoradiotherapy (CRT). We analysed the prognostic value of residual MTV after completion of thoracic irradiation (TRT) in inoperable stage III NSCLC patients treated with CRT with and without immune check-point inhibition (ICI). Methods: Fifty-six inoperable stage III NSCLC patients (16 female, median age: 65 years) underwent 18 F-FDG PET/CT at the same institution before and after completion of CRT. MTV was delineated on 18 F-FDG PET/CT using a standard threshold (hepatic SUV mean + 2 x standard-deviation). Patients were divided in volumetric subgroups using median split dichotomization (residual MTV ≤4.0 ml &amp; &gt; 4.0 ml). Residual MTV, clinical features and ICI maintenance (RCT-IO; 21/56 (37.5%) patients) were correlated with clinical outcome (progression-free survival (PFS), local PFS (LPFS), metastasis-free survival (MFS), and overall survival (OS). Results: Median follow-up was 52.0 months. 52 (93%) patients were treated with CRT, 12 (21%) patients with CRT followed by durvalumab, and 9 (16%) patients treated with CRT plus nivolumab (concurrent and sequential). In the entire cohort, smaller residual MTV was associated with longer PFS (median 29.3 vs. 10.5 months, p = 0.015); PFS in patients treated with CRT and ICI was also significantly longer compared to the CRT-only subgroup (median 29.3 vs. 11.2 months, p = 0.010). However, residual MTV was predictive for longer PFS in CRT-only (median 33.5 vs. 8.6 months, p = 0.001), but not in the CRT-ICI patients (p = 0.909). Analogously, patients with smaller MTV had a longer LPFS (median 49.9 vs. 16.3 months, p = 0.002); CRT-ICI patients showed a significantly longer LPFS compared to CRT-only patients (median not reached vs. 16.9 months, p = 0.016). Residual MTV remained a significant prognosticator for LPFS in the CRT-only (median 49.9 vs. 10.1 months, p = 0.01), but not in CRT-ICI patients (p = 0.291). Again, smaller residual MTV remained a significant prognosticator for OS in the CRT-only subgroup (median 63.0 vs. 16.3 months, p = 0.004), but not in CRT-ICI patients (p = 0.720). Even in patients with larger residual MTV, the application of ICI significantly improved OS compared to CRT-only subgroup (median not reached vs. 22.9 months, p = 0.004). Conclusions: Smaller residual MTV is associated with superior clinical outcome in inoperable stage III NSCLC, especially in patients undergoing CRT-only. In contrast, in patients undergoing concurrent or sequential consolidation clinical outcome was independent of residual MTV. Hence, even patients with extensive residual MTV might significantly profit from ICI consolidation.
Artificial intelligence (AI)–powered pathologic response (PathR) assessment of resection specimens after neoadjuvant atezolizumab in patients with non-small cell lung cancer: Results from the LCMC3 study.
Authors: Sanja Dacic, William D. Travis, Jennifer Margaret Giltnane, John Abel, Filip Kos, Stephanie Hilz, Stephanie Hennek, Junya Fujimoto, Lynette M. Sholl, Farah Khalil, Jon Ritter, Massimo D'Apuzzo, Jay M. Lee, Valerie W. Rusch, David Paul Carbone, Alan Nicholas, Ann Johnson, Katja Schulze, Mark G. Kris, Ignacio Ivan Wistuba
Journal: Journal of Clinical Oncology (2021)

106 Background: PathR is an efficacy endpoint in Phase II and III neoadjuvant trials and is proposed as a surrogate for disease-free survival (DFS) and overall survival. Machine learning (ML)–based, automated approaches standardize quantification of areas of tumor bed and residual viable tumor. Here we show that automation may provide a scalable alternative to or complementary tool for manual assessment. Methods: We determined inter-reader variability for PathR among pathologists in the LCMC3 (NCT02927301) study and developed an AI-powered digital PathR assessment tool in line with manual consensus recommendations. Study cases were reviewed for PathR by a local site pathologist and 3 central expert pathologists (n = 127). When determined manually, major PathR (MPR) was defined as ≤10% viable tumor averaged per case. ML models were trained and validated by the PathAI research platform using digitized H&amp;E-stained tumor sections. The digital PathR model predicted percent viable tumor for each case as the sum of the cancer epithelium area from each slide divided by the sum of tumor bed area for each slide. DFS (clinical cutoff: Oct 23, 2020) was reported for patients with manual and digital PathR assessment (n = 135). For digital MPR, we used a prevalence-matched cutoff that maintained the same proportion of patients as manual MPR. Results: Inter-reader agreement among 1 local and 3 central pathologists for manual PathR was good (n = 127; ICC = 0.87; 95% CI: 0.84-0.90). Agreement was 91% (κ = 0.82) on manual MPR and 98% (κ = 0.88) on pathologic complete response (pCR). 6 patients had unanimous pCR. Digital and manual PathR were strongly correlated (n = 135, Pearson r = 0.78) and digital PathR demonstrated an outstanding predictability for manual MPR (AUROC = 0.975). The range was 0%-60% for digital PathR and 0%-100% for manual PathR with a regression line slope &lt; 1.0 (m = 0.303) indicating systematic differences between the methods, consistent with digital PathR using a high-resolution segmentation of cancer epithelium from stroma across each slide. Longer DFS was observed for MPR yes vs no with both digital and manual assessment (Table). Conclusions: This analysis showed good inter-reader agreement for manual and strong correlation of AI-powered digital and manual PathR. Comparable DFS rates for manual MPR and digital MPR are encouraging in the preliminary data. These data support further studies of digital PathR as a standardized and scalable tool to determine PathR. Clinical trial information: NCT02927301. [Table: see text]
O- and N-Glycosylation of Serum Immunoglobulin A is Associated with IgA Nephropathy and Glomerular Function
Authors: Viktoria Dotz, Alessia Visconti, Hannah J. Lomax-Browne, Florent Clerc, Agnes L. Hipgrave Ederveen, Nicholas R. Medjeral-Thomas, H. Terence Cook, Matthew C. Pickering, Manfred Wuhrer, Mario Falchi
Journal: Journal of the American Society of Nephrology (2021)

IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and is a leading cause of renal failure. The disease mechanisms are not completely understood, but a higher abundance of galactose-deficient IgA is recognized to play a crucial role in IgAN pathogenesis. Although both types of human IgA (IgA1 and IgA2) have several N-glycans as post-translational modification, only IgA1 features extensive hinge-region O-glycosylation. IgA1 galactose deficiency on the O-glycans is commonly detected by a lectin-based method. To date, limited detail is known about IgA O- and N-glycosylation in IgAN.To gain insights into the complex O- and N-glycosylation of serum IgA1 and IgA2 in IgAN, we used liquid chromatography-mass spectrometry (LC-MS) for the analysis of tryptic glycopeptides of serum IgA from 83 patients with IgAN and 244 age- and sex-matched healthy controls.Multiple structural features of N-glycosylation of IgA1 and IgA2 were associated with IgAN and glomerular function in our cross-sectional study. These features included differences in galactosylation, sialylation, bisection, fucosylation, and N-glycan complexity. Moreover, IgA1 O-glycan sialylation was associated with both the disease and glomerular function. Finally, glycopeptides were a better predictor of IgAN and glomerular function than galactose-deficient IgA1 levels measured by lectin-based ELISA.Our high-resolution data suggest that IgA O- and N-glycopeptides are promising targets for future investigations on the pathophysiology of IgAN and as potential noninvasive biomarkers for disease prediction and deteriorating kidney function.