tbuckley/cabot-search huggingface dataset:
COVID-19 and exacerbation of screening mammography inequities.
Authors: Gary X. Wang, Jarvis Chen, Leslie Lamb, Christian Testa, Pamela Waterman, Constance Dobbins Lehman, Nancy Krieger
Journal: Journal of Clinical Oncology (2021)

6543 Background: After state-mandated cessation of screening mammography (SM) in Spring 2020 due to COVID-19, centers were urged to resume screening, particularly of patients at increased risk. As our tertiary-care medical center’s screening program provides SM at four sites across our metropolitan area, we examined whether sites that historically served more patients from more disadvantaged areas returned slower to pre-COVID volumes. Methods: Patient records were linked by ZIP code of residence to ZIP Code Tabulation Area (ZCTA)-level area-based social metrics (ABSMs) from the 2014-2018 American Community Survey. We compared baseline pre-COVID (May-October, 2015-2019) SM population ABSMs between our four imaging sites for: % persons below poverty (≥ vs &lt; 10%), % persons of color (POC) (quintiles: top 2 vs bottom 3), index of racialized economic segregation (quintiles: bottom 2 [more POC low-income households] vs top 3 [more white non-Hispanic (WNH) high-income households]); and race/ethnicity (% WNH vs POC). We modeled weekly SM volumes per screening day by site using Poisson regression and tested for weekly differences at each site, COVID-era (May-October 2020) vs pre-COVID; and tested for monthly differences in SM population composition by logistic regression modeling. Results: There were 89,082 pre-COVID and 16,220 COVID-era SM exams. At pre-COVID baselines the four sites differed in population composition by ABSMs and race/ethnicity (all chi-square P values &lt;.001) (Table). The two sites that served more disadvantaged populations (A, B) returned slower to pre-COVID volumes (site-specific weekly screening volume no longer different [ P &gt;.05] vs pre-COVID) (Table). As a result, compositions of the aggregate SM population across all sites showed a smaller proportion of patients from the most disadvantaged ZCTAs by ABSMs (all P values &lt;.001) before returning to pre-COVID compositions three months after SM resumption. Conclusions: SM was slower to return to pre-COVID volumes at imaging sites that historically served lower-income communities of color. As a result, our COVID-era SM population skewed away from patients in disadvantaged ZCTAs. Our findings highlight the need to monitor for emergent disparities in the pandemic era. Future work will focus on understanding causes of inequitable SM engagement across our imaging sites to mitigate care disparities for our most vulnerable patients.[Table: see text]
Abstract 2847: Impact of Primary PCI as Compared to Thrombolysis on Hospital Mortality of STEMI in the High Risk Population of Diabetics in Clinical Practice. Results of the ACOS Registry
Authors: Anselm K Gitt, Uwe Zeymer, Harm Wienbergen, Tobias Heer, Frank Towae, Martin G Gottwik, Jochen Senges
Journal: Circulation (2006)
Measurement of treatment dependent glioblastoma cell density in T1- weighted contrast enhancement at autopsy.
Authors: Allison Lowman, Samuel Bobholz, Jennifer Marie Connelly, Elizabeth Cochran, Wade Mueller, Michael Brehler, Fitzgerald Kyereme, John Sherman, Savannah Duenweg, Peter S LaViolette
Journal: Journal of Clinical Oncology (2021)

e14035 Background: With an average overall survival of 12-18 months, glioblastoma has a particularly grim diagnosis. Standard treatment of glioblastoma, following detection on MRI, is surgical resection followed by radiation therapy and chemotherapy and is monitored through MR imaging. Glioblastoma has a unique heterogenous nature that complicates visualization of subtly enhancing tumor. This study used autopsy tissue samples taken from glioblastoma patients with varying treatment, to examine the effects of treatment on cell density within regions of contrast enhancement, using T1-weighted subtraction maps (T1S) from the last MR images to death. Methods: Eight patients diagnosed with glioblastoma at autopsy were recruited for this study. Two patients had no treatment and six received a combination of chemo-radiation and other treatments, including but not limited to bevacizumab (Bev) and TTFields therapy. At autopsy, whole brain samples were sliced axially aligned to the patient’s final MRI to death. Time between last MRI and death ranged from 4-27 days (mean 16 days). Overall survival (OS) ranged from 4-538 days (mean 307 days). Large tissue samples were taken from regions of suspected tumor or treatment effect, for a total of 18 tissue samples. Tissue samples were processed, H&amp;E stained, and digitized at 40X resolution (Huron Slide Scanner). Cell density (cells/mm 2 ) was calculated using digital histology. T1S were created for each patient by subtracting intensity normalized T1 weighted images from T1 post contrast images (T1C). Digital histology was aligned and resampled into MRI space using manual control point registration. Mixed effect models were used to compare differences in cell density across contrast enhancement (T1SE vs. NE) as well as across treatment groups (treatment vs. no treatment). Results: Cellularity was compared across regions of T1S enhancement (T1SE) and non-enhancement (NE) within manually selected regions of interest. Cell density compared between regions of T1SE and NE was not different (p=0.219). Total cell density was increased in patients who had received treatment compared to no treatment in both regions of T1SE and NE (p=0.014). Conclusions: Overall, cell density was increased in patients who had received treatment after diagnosis of glioblastoma. Additional research is needed to examine the extent of treatment’s effect on cellularity of glioblastoma. This work begins to characterize the use of T1S in evaluating glioblastoma tumor burden in patients with varying treatment histories.[Table: see text]
EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial
Authors: Quan Zhou, Nynke S van den Berg, Eben L Rosenthal, Michael Iv, Michael Zhang, Johana C M Vega Leonel, Shannon Walters, Naoki Nishio, Monica Granucci, Roan Raymundo, Grace Yi, Hannes Vogel, Romain Cayrol, Yu-Jin Lee, Guolan Lu, Marisa Hom, Wenying Kang, Melanie Hayden Gephart, Larry Recht, Seema Nagpal, Reena Thomas, Chirag Patel, Gerald A Grant, Gordon Li
Journal: Theranostics (2021)

: First-line therapy for high-grade gliomas (HGGs) includes maximal safe surgical resection. The extent of resection predicts overall survival, but current neuroimaging approaches lack tumor specificity. The epidermal growth factor receptor (EGFR) is a highly expressed HGG biomarker. We evaluated the safety and feasibility of an anti-EGFR antibody, panitumuab-IRDye800, at subtherapeutic doses as an imaging agent for HGG.
ACC/AHA 2007 Methodology for the Development of Clinical Data Standards
Authors: Martha J. Radford, Paul A. Heidenreich, Steven R. Bailey, David C. Goff, Frederick L. Grover, Edward P. Havranek, Richard E. Kuntz, David J. Malenka, Eric D. Peterson, Rita F. Redberg, Veronique Lee Roger
Journal: Journal of the American College of Cardiology (2007)
Ipilimumab, nivolumab and tocilizumab as first-line therapy for advanced melanoma.
Authors: Inderjit Mehmi, Omid Hamid, F. Stephen Hodi, Melinda Vassalo, Saundra Malatyali, Swathi Krishnarajapet, Nan O’Donnell, Angeli Castrence, Eunice Lim, Jill Gormley, Jeffrey S. Weber
Journal: Journal of Clinical Oncology (2021)

TPS9589 Background: Interleukin 6 (IL-6) functions in the maintenance of hepatocytes, haemotopoietic progenitor cells, a variety of other tissues, and regulates the innate and adaptive immune system. IL-6 may play a role as a chronic inflammatory mediator in altering levels of acute phase proteins synthesized by the liver and circulating myeloid cells which have been shown to be associated with short survival with checkpoint inhibition and which are immune suppressive. The immunomodulatory properties of interleukin-6 may in part also be responsible for immune related adverse events, given the reversal of those toxicities observed with IL-6 receptor blockade in clinical practice. To assess if blockade of IL-6 binding is associated with a decrease in irAEs and/or an increase in efficacy defined as overall response rate (ORR) at week 24 in patients receiving ICB, we added tocilizumab to ipilimumab and nivolumab therapy. Methods: The current phase II trial is a two-stage design to assess the safety, tolerability, and grades 3-5 immune related toxicities of tocilizumab administered every 6 weeks up to week 24 in combination with ipilimumab at 1 mg/kg and nivolumab at 3 mg/kg every 3 weeks for 4 doses each during a 12 week induction period, then administered every 6 weeks with nivolumab at 240 mg flat dose every 2 weeks in maintenance for up to 24 weeks, and nivolumab alone will be given at 480 mg flat dose every 4 weeks thereafter for up to 2 years. Eligible patients include those age 18 or older with measurable and unresectable stages III/IV melanoma (cutaneous, acral, mucosal), without prior systemic treatment for metastatic disease. Adjuvant therapy (IFN-alpha, ipilimumab and/or nivolumab, or pembrolizumab) is allowed. Patients with metastatic melanoma of brain are allowed, if neurologically stable and off immunosuppressive steroids. A total of 18 patients will be treated in the first stage, and 49 additional patients in the second stage for a total of 67. The comparator data are from the N3I1 arm of Checkmate-511 trial, in which treatment-related grades 3-5 irAEs were 33.9% with a 45.6% response rate (1). Prespecified activity goal for the first stage of accrual has been met; second stage accrual began in January 2021. References: (1) Lebbé C, Meyer N, Mortier L, Marquez-Rodas I, et al. Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial. Journal of Clinical Oncology 2019 37:11, 867-875. Clinical trial information: NCT03999749.
Implications of Ridesharing on Alcohol-Associated Motor Vehicle Crashes
Authors: Adil Haider, Hamna Shahbaz
Journal: JAMA Surgery (2021)

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Availability, reading level, quality, and accessibility of online cancer center smoking cessation materials.
Authors: Dalia Littman, Fumiko Chino
Journal: Journal of Clinical Oncology (2021)

e18662 Background: Smoking cessation after a cancer diagnosis improves cancer outcomes. Therefore, it is important for cancer centers to provide educational resources to encourage patients to quit smoking. The NIH recommends that patient reading materials be written at a grade 6-7 reading level to maximize comprehension. As smokers on average have lower educational attainment than the general population, they may have particular difficulty comprehending smoking cessation materials written at advanced grade levels. Methods: This study evaluated the reading level of online resources via textual analysis of smoking cessation webpages associated with 63 NCI-Designated Cancer Centers or their affiliated medical centers or universities. Reading level was assessed using the WebFx Readability Test Tool. Differences in grade level were calculated by Mood’s Median Test. Content was evaluated for the quality of information, including textual analysis of print-out pamphlets. Non-English content and ease of navigation to webpages was documented. Results: Availability: Of 63 cancer centers, 42 (67%) had smoking cessation webpages. Among centers that did not have their own webpages, 14 had smoking cessation webpages hosted by affiliated medical centers and the remaining 7 had webpages hosted by affiliated universities. Reading Level: The median grade level for online smoking cessation materials was 9 (interquartile range IQR 8-10). There was no significant difference in grade level based on cancer center region, ranking, or whether the webpage was hosted by the cancer center, medical center or university. 17 webpages (27%) had print out pamphlets available, which had a median reading level of 8.5 (IQR 7-10). Information Quality: 27 webpages (43%) explicitly stated that smoking cessation improves cancer outcomes, 15 (24%) included details about smoking cessation medications, 16 (25%) provided information on behavioral counseling, and 14 (22%) described the risks/benefits of e-cigarette use. Only 4 (6%) had information on all four topics, while 21 (33%) did not have information on any of these four topics. Accessibility: Only 3 webpages (5%) were available in multiple languages. 12 webpages (19%) were inaccessible by search from the homepage with common terms (i.e. smoking, quit smoking, tobacco, etc). 38 webpages (60%) required 3 or more clicks to reach from the center homepage. Conclusions: Online smoking cessation materials at leading cancer centers exceed recommended reading levels, which can inhibit comprehension for patients trying to quit smoking. These webpages do not routinely include information on cancer outcomes or on evidence-based medications and behavioral change interventions to assist patients in quitting. Given the survival benefit found in cancer patients who quit smoking, it is imperative that educational materials from cancer centers maximize comprehension and accessibility.
The genomic landscape of Chinese patients with upper tract urothelial carcinoma.
Authors: Shengming Jin, Yu Wei, Junlong Wu, Chengyuan Gu, Wenqi Gao, Bing Li, Yao Zhu, Dingwei Ye
Journal: Journal of Clinical Oncology (2021)

e16583 Background: Upper tract urothelial carcinoma (UTUC) is known to have a distinct aggressive clinical phenotype and its genomic characterization is poorly understood, especially in Asian population. In this study, we aimed to characterize the genomic landscape of Chinese UTUC patients and explore the clinical relevance, which is the largest cohort of UTUC to date. Methods: Overall, 122 Chinese patients with UTUC were enrolled. Tumor and germline DNA from patients were analyzed using a targeted next-generation sequencing assay to identify somatic mutations in 520 cancer associated genes. Mutations like deletion, amplification and gene fusion were included. Tumor mutational burden (TMB) and microsatellite instability (MSI) status were also evaluated. The frequency of genomic alterations in patients with UTUC was compared with that of the Western counterpart from previous studies. Results: In total, 13 low-grade and 109 high-grade UTUC patients were included in this study. The most frequent genomic alterations were identified in genes like TERT (50.0%; 61.5% low-grade vs 48.6% high-grade), KMT2D (48.4%; 61.5% vs 46.8%), FGFR3 (41.0%; 69.2% vs 37.6%), TP53 (37.7%; 7.7% vs 41.3%), CDKN2A (22.1%; 23.1% vs 22.0%), KDM6A (20.5%; 15.4% vs 21.1%) with different mutation frequencies in the two subgroups of patients. Despite the overall similarity (including FGFR3, ARID1A and CDKN2A), the comparison between our cohort and the two Western UTUC cohorts (n = 119, 24 low-grade and 95 high-grade) revealed significant differences in mutation frequencies of KMT2D (48.4% vs 36.1%), TERT (50.0% vs 26.9%), TP53 (37.7% vs 21.9%) and KDM6A (20.5% vs 32.8%) . Chi-square analysis revealed that patients with history of other cancers (4/17 vs. 3/105, P = 0.001) were more likely to have a MSI-high status. In addition, females (9/44 vs. 6/78, P = 0.039) and patients with cancer history (6/17 vs. 9/105, P = 0.002) were more likely to have high TMB (≥20 mutations/Mb; median: 6.48 mutations/Mb). At last, the frequency of germline P/LP variants were also similar but different in the spectrum between our cohort and the Western UTUC population. Differences in mutation frequency of APC (0 vs 2.6%), BRAC2 (2.6% vs 0.9%), CHEK2 (0.3% vs 1.8%), MSH2 (2.6% vs 5.3%) and MSH6 (0 vs 1.8%) were significant. Conclusions: This study revealed that Chinese UTUC patients had a similar frequency of genomic alterations with western patients. However, there were significant differences in the prevalence of several mutated genes including KMT2D, TERT, TP53 and KDM6A, suggesting the ethnicity differences between the two populations. Our findings laid the foundation of a deeper understanding of UTUC biology and will provide potential targets for the development of precision therapies in UTUC.
EPEN-02. FUNCTION AND DEPENDENCY OF NF-KB ACTIVITY IN C11ORF95-RELA FUSION EPENDYMOMA
Authors: Austin Stuckert, Amir Arabzade, Yanhua Zhao, Hsiao-Chi Chen, Stephen Mack
Journal: Neuro-Oncology (2021)

Abstract Introduction Ependymoma is an aggressive type of pediatric brain tumor resistant to chemotherapy, with treatment to date limited to surgical resection and radiation. Thus, identification and validation of molecular targets that can translate into clinical trials in ependymoma is desperately needed to improve patient outcomes. Over 70% of supratentorial ependymoma are driven by an oncogenic fusion between C11orf95 and Rela (denoted CRFUS). CRFUS expression initiates ependymoma development in mice by potentially acting as an oncogenic transcription factor and disrupting gene expression programs. We hypothesized that specific CRFUS interacting proteins are required for tumor formation and could represent lead therapeutic targets. Methods To study CRFUS ependymoma, a natively-forming tumor model of CRFUS generated by in utero electroporation of the developing mouse brain was utilized. Tumor cells were isolated and then subjected to nuclear Rapid Immunoprecipitation and Mass Spectrometry Analysis of Endogenous Proteins (RIME) of HA-tagged CRFUS protein. Immunoprecipitation and Western Blot (IP-WB) were utilized to probe for leading protein interactions. Results We identified NF-kB proteins consistent with canonical Rela mediated transcription (NFKB1 and NFKB2) as well as novel protein interactomes that converged on RNA splicing and translational regulation. In addition, we identified a large series of novel chromatin-binding proteins as candidates potentially required for CRFUS mediated tumorigenesis. Conclusions Further study is ongoing to validate key CRFUS protein interaction dependency on tumor development. ChIP-Seq (chromatin immunoprecipitation with massively parallel DNA sequencing) and CUT&amp;RUN (cleavage under target and release using nuclease) assays have been employed to further analyze the functional role of canonical Rela pathway members. By interrogating these mechanisms, novel therapeutic targets and pathways may be identified in parallel with dissecting the molecular basis of CRFUS driven ependymoma.
Associations of coping strategies with quality of life (QOL) and mood in patients with acute myeloid leukemia (AML).
Authors: Matthew J. Reynolds, Mitchell W. Lavoie, Bailey T. Jones, Ashley M. Nelson, Hermioni L. Amonoo, Thomas William LeBlanc, Areej El-Jawahri
Journal: Journal of Clinical Oncology (2021)

e19012 Background: Patients with AML who receive intensive chemotherapy experience immense physical and psychological symptoms, which can result in a substantial deterioration of QOL. As data on the relationship between AML patient coping strategies and patient-reported outcomes are lacking, we aimed to determine the associations between patients’ coping strategies and their quality of life and mood. Methods: We conducted a secondary analysis of cross-sectional data from a multi-site randomized supportive care trial for hospitalized patients diagnosed with AML and receiving intensive chemotherapy. Within 72 hours of initiating chemotherapy, patients completed baseline assessments of QOL (FACT-Leu), anxiety and depression symptoms (HADS), and symptom burden (ESAS). Patients also completed subscales from the Brief Cope to assess baseline use of coping strategies. We created high-order factors (approach-oriented coping vs. avoidant-oriented coping) from the coping subscales and utilized the median split method to identify the proportions of patients with high use of approach and avoidant-oriented coping strategies, respectively. We used linear regression models adjusting for age, gender and diagnosis type (newly diagnosed vs. relapsed/refractory AML) to examine the relationships between patients’ use of coping strategies and their baseline QOL, mood and symptom burden. Results: A total of 160 patients were enrolled in the study (60.0% male; median age 64.4 years [range 19.7-80.1]). Overall, 47.5% (76/160) of patients reported high use of approach-oriented coping strategies, while 38.8% (62/160) reported high use of avoidant-oriented strategies. In regression models, the greater use of approach-oriented coping strategies at baseline was associated with higher baseline QOL (β = 1.33, SE = 0.44, P= 0.003), lower depression (β = -0.28, SE = 0.07, P&lt; 0.001) and anxiety symptoms (β = -0.24, SE = 0.08, P= 0.002), and lower symptom burden (β = -0.96, SE = 0.34, P= 0.006). By contrast, the greater use of avoidant-oriented coping strategies at baseline was associated with lower baseline QOL (β = -4.98, SE = 0.81, P&lt; 0.001), higher depression (β = 0.60, SE = 0.13, P&lt; 0.001) and anxiety symptoms (β = 0.79, SE = 0.14, P&lt; 0.001), and worse symptom burden (β = 2.30, SE = 0.64, P&lt; 0.001). Conclusions: Newly hospitalized patients with AML who utilize approach-oriented coping strategies experience better baseline QOL and mood, and a lower symptom burden. These findings underscore the need for supportive care interventions that promote effective coping in patients with AML, to improve patients’ QOL and reduce their physical and psychological distress.