tbuckley/cabot-search huggingface dataset:
Post-intervention lung cancer screening compliance among internal medicine resident physicians at a primary care clinic in Hartford, Connecticut.
Authors: Nerea Lopetegui-Lia, Daniel Condit, Gian Carlo Castor Lima, Dimitrios Drekolias, Jasmin Hundal, Syed Imran Mustafa Jafri, James Vredenburgh
Journal: Journal of Clinical Oncology (2021)

6569 Background: Lung cancer (ca) screening has shown to reduce mortality by up to 20%. Despite this, only 4% of eligible patients in the US undergo screening. Our initial analysis revealed that 18.3% of patients who met screening criteria had an appropriately ordered LDCT scan, with an 8.7% completion rate. The aim of this study was to improve lung ca screening compliance following the USPSTF guidelines among residents from the University of Connecticut Internal Medicine (IM) residency program at a Clinic in Hartford, Connecticut. Methods: Care provided to patients by an IM resident at the Gengras Clinic were included. After initial data was gathered, we implemented an intervention to improve screening compliance between October 2019 and March 2020, when SARS-CoV-2 pandemic occurred and routine services were interrupted. USPSTF screening guidelines were emailed monthly to residents and attendings; they were reminded of the importance of lung ca screening; updating the pack-year smoking history; as well as instructions on correctly ordering LDCT and documenting shared decision making, which is needed for insurance approval. In-person reminders also occurred at the clinic. Results: Post-intervention, 601 charts were reviewed. 168/601 (27%) patients met screening criteria. 433 patients were excluded due to unclear pack-year, did not meet screening criteria, were deceased or last seen at the clinic prior to the intervention. 63/168 (37.5%) met the criteria and had an appropriately ordered LDCT; 51/168 (30.35%) had a completed LDCT in chart. The remaining 12/168 (7.14%) with an appropriately ordered LDCT, had it scheduled at the time of data collection or it had been cancelled for unclear reasons. 20 patients’ LDCT was ordered by their pulmonologist. 94 (62.5%) who met screening criteria did not have a LDCT ordered. 11 patients with a smoking history, who did not meet screening criteria had a LDCT ordered because of clinical suspicion for cancer. Lastly, 4/168 (2.4%) had a diagnosis of personal history of lung ca. Conclusions: After our educational intervention, patients who qualified had an increase of LDCT being ordered (37.5% from 18.3%) and completed (30.3% from 8.7%). This is, to our knowledge, the first study of its kind. We identified areas of improvement that were key to achieving higher screening rates: educating all residents and attendings on lung ca screening guidelines; educating patients on the importance of undergoing screening tests; creating a best practice advisory in the electronic medical record system that reminds provider to input pack-year smoking history and if the criteria for screening is met, a pop-up prompting the provider to order LDCT; obtaining insurance approval; and lastly, stressing the importance on screening and overall outcomes.
Conflicts of interest (COI) among the UpToDate oncology management authors.
Authors: Madhuri Chengappa, Aakash Desai, Ronald S. Go, Thejaswi K. Poonacha
Journal: Journal of Clinical Oncology (2021)

e13573 Background: UpToDate is an evidence based clinical resource designed to provide current clinical information. It is a widely used clinical practice tool providing evidenced based recommendations for diagnosis, management, and therapy. The extent of COI among the UpToDate authors has not been well studied. Our study evaluated the extent of COI of UpToDate authors involved in medical management recommendations for the 10 most common cancers in United States. Methods: We examined the latest November 2020 version of the UpToDate clinical management recommendations for 10 most common cancers. Using disclosure lists, we catalogued COIs for participants in each work group. The categories included: Category I- Grant/Research/Clinical Trial Support; Category II- Consultant/Scientific Advisory Boards/Expert witness; Category III- Speakers Bureau; Category IV- Equity Ownership/Stock Options/Patent holder/Employment/Other Financial Interest; and Category V- Spouse/Domestic Partner/Dependent Potential Conflict. We cataloged the companies/institutions involved in each disclosure. An “episode” describes 1 instance of participation of an individual in 1 company in 1 category for each cancer section. Results: There was a total of 207 authors including section and deputy editors of oncology management section. All authors completed their COI disclosures (100%). 128 (62%) of a total of 207 individuals reported COIs. A total of 1343 episodes were disclosed. We found that each author had an average of 10.49 episodes overall. Authors involved in Category I, II, III, IV &amp; V were 6.3%, 13.5%, 3.2%, 4.7% and 1.6% respectively. 29.36% authors were involved both in Category I and II. A total of 672 company affiliations were associated with COI disclosure. AstraZeneca (6.10%), Merck (4.31%) and Novartis (2.68%) were the companies most frequently reported. The guideline with the maximum episodes (223) was prostate cancer. Conclusions: COIs are prevalent among authors of UpToDate clinical management recommendations. More than ½ of the participants disclosed at least 1 COI, but there appears to be a substantial number of experienced experts without COIs. Further research studies are necessary to determine the impact of these COIs on clinical practice patterns and resource utilization. Distribution of COI and total episodes.[Table: see text]
Phase I Study of Entinostat and Nivolumab with or without Ipilimumab in Advanced Solid Tumors (ETCTN-9844)
Authors: Evanthia T. Roussos Torres, Christine Rafie, Chenguang Wang, David Lim, Adam Brufsky, Patricia LoRusso, Joseph Paul Eder, Vincent Chung, Melinda Downs, Molly Geare, Richard Piekarz, Howard Streicher, Leslie Anforth, Michelle A. Rudek, Qingfeng Zhu, Sepideh Besharati, Ashley Cimino-Mathews, Robert A. Anders, Vered Stearns, Elizabeth M. Jaffee, Roisin M. Connolly
Journal: Clinical Cancer Research (2021)

Epigenetic modulators improve immune checkpoint inhibitor (ICI) efficacy and increase CD8+ effector:FoxP3+ regulatory T cell ratios in preclinical models. We conducted a multicenter phase I clinical trial combining the histone deacetylase inhibitor entinostat with nivolumab ± ipilimumab in advanced solid tumors.Patients received an entinostat run-in (5 mg, weekly × 2) prior to the addition of ICIs. Dose escalation followed a modified 3+3 design [dose level (DL)1/2: entinostat + nivolumab; DL 3/4: entinostat + nivolumab + ipilimumab]. Blood and tissue samples were collected at baseline, after entinostat run-in, and after 8 weeks of combination therapy. Primary endpoints included safety and tolerability, and the recommended phase II dose (RP2D). Secondary endpoints included antitumor activity and change in tumor CD8/FoxP3 ratio pre- and post-therapy.Thirty-three patients were treated across four dose levels. Treatment-related adverse events (AE) included fatigue (65%), nausea (41%), anemia (38%), diarrhea (26%), and anorexia (26%). Grade 3/4 AEs included fatigue (n = 7, 21%), anemia (n = 9, 27%), and neutropenia (n = 4, 12%). The RP2D was 3 mg entinostat weekly, 3 mg/kg every 2 weeks nivolumab, and 1 mg/kg every 6 weeks ipilimumab (max four doses). The objective response rate by RECIST 1.1 was 16%, including a complete response in triple-negative breast cancer. A statistically significant increase in CD8/FoxP3 ratio was seen following the addition of ICIs to entinostat, but not post-entinostat alone.The combination of entinostat with nivolumab ± ipilimumab was safe and tolerable with expected rates of immune-related AEs. Preliminary evidence of both clinical efficacy and immune modulation supports further investigation.
HGG-06. EARLY GABAERGIC NEURONAL LINEAGE DEFINES DEPENDENCIES IN HISTONE H3 G34R/V GLIOMA
Authors: Ilon Liu, Lynn Bjerke, Gustavo Alencastro Veiga Cruzeiro, Rebecca F Rogers, Yura Grabovska, Eshini Panditharatna, Alan Mackay, Tara Barron, McKenzie Shaw, Samantha E Hoffman, Olivia A Hack, Michael A Quezada, Joshua Dempster, Sara Temelso, Bernhard Englinger, Valeria Molinari, Hafsa M Mire, Li Jiang, Sibylle Madlener, Lisa Mayr, Christian Dorfer, Rene Geyeregger, Christopher Rota, Gerda Ricken, Sanda Alexandrescu, Emelie Braun, Miri Danan-Gotthold, Lijuan Hu, Kimberly Siletti, Erik Sundstroem, Rebecca Hodge, Ed Lein, Sameer Agnihotri, David D Eisenstat, Fernando Carceller, Simon Stapleton, Cristina Bleil, Angela Mastronuzzi, Kristina A Cole, Angela J Waanders, Angel Montero Carcaboso, Maria Vinci, Darren Hargrave, Christine Haberler, Johannes Gojo, Irene Slavc, Sten Linnarsson, Michelle Monje, Chris Jones, Mariella G Filbin
Journal: Neuro-Oncology (2021)

Abstract High-grade gliomas harboring H3 G34R/V mutations exclusively occur in the cerebral hemispheres of adolescents and young adults, suggesting a distinct neurodevelopmental origin. Combining multimodal bulk and single-cell genomics with unbiased genome-scale CRISPR/Cas9 approaches, we here describe a GABAergic interneuron progenitor lineage as the most likely context from which these H3 G34R/V mutations drive gliomagenesis, conferring unique and tumor-selective gene targets essential for glioma cell survival, as validated genetically and pharmacologically. Phenotypically, we demonstrate that while H3 G34R/V glioma cells harbor the neurotransmitter GABA, they are developmentally stalled, and do not induce the neuronal hyperexcitability described in other glioma subtypes. These findings offer a striking counter-example to the prevailing view of glioma origins in glial precursor cells, resulting in distinct cellular, microenvironmental, and therapeutic consequences.
ATRT-01. IDENTIFICATION OF MICRORNA-BASED PROGNOSTIC BIOMARKERS AND CANDIDATE THERAPEUTIC AGENTS FOR ATYPICAL TERATOID/RHABDOID TUMOR
Authors: Yang Zhang
Journal: Neuro-Oncology (2021)

Abstract Background MicroRNA (miRNA) has been found to be involved in development of many malignant pediatric brain tumors, including atypical teratoid/rhabdoid tumor (AT/RT) that is highly aggressive and carries a dismal prognosis. The current study investigated the potential value of miRNAs and pivotal genes associated with AT/RT using bioinformatics analysis, aiming to identify new prognostic biomarkers and candidate drugs for AT/RT patients. Methods Differentially expressed miRNAs (DEMs) and genes (DEGs) between AT/RT and normal control samples were obtained from GEO database. The target genes of DEMs were predicted via TargetScanHuman7.2 and miRDB, and then intersected with DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of overlapping genes were conducted, followed by construction of protein-protein interaction network. Hub genes were determined by Cytoscape software, and their prognostic values were evaluated using Kaplan-Meier analysis. Connectivity Map database was used to identify latent therapeutic agents. Results A total of 11 DEMs (hsa-miR-1224-5p, hsa-miR-128-3p, hsa-miR-17-5p, hsa-miR-18b-5p, hsa-miR-29c-5p, hsa-miR-329-3p, hsa-miR-379-5p, hsa-miR-433-3p, hsa-miR-488-5p, hsa-miR-656-3p and hsa-miR-885-5p) were screened. By intersecting 3275 predicted target genes and 925 DEGs, we finally identified 226 overlapping genes that were enriched in pathways in cancer and MAPK signaling pathway. Four hub genes (GRIA2, NRXN1, SLC6A1 and SYT1) were significantly associated with the overall survival of AT/RT patients. Candidate drugs included histone deacetylase inhibitor (givinostat), DNA synthesis inhibitor (floxuridine), cyclin-dependent kinase inhibitor (purvalanol) and janus kinase inhibitor (lestaurtinib). Conclusion In summary, this study systematically analyzed AT/RT-related miRNAs and pivotal genes to provide novel prognostic biomarkers and potential therapeutic agents.
Innate immune pathways and inflammation in hematopoietic aging, clonal hematopoiesis, and MDS
Authors: Jennifer J. Trowbridge, Daniel T. Starczynowski
Journal: The Journal of Experimental Medicine (2021)

With a growing aged population, there is an imminent need to develop new therapeutic strategies to ameliorate disorders of hematopoietic aging, including clonal hematopoiesis and myelodysplastic syndrome (MDS). Cell-intrinsic dysregulation of innate immune- and inflammatory-related pathways as well as systemic inflammation have been implicated in hematopoietic defects associated with aging, clonal hematopoiesis, and MDS. Here, we review and discuss the role of dysregulated innate immune and inflammatory signaling that contribute to the competitive advantage and clonal dominance of preleukemic and MDS-derived hematopoietic cells. We also propose how emerging concepts will further reveal critical biology and novel therapeutic opportunities.
Phase 2 trial of gemcitabine, cisplatin, plus nivolumab with selective bladder sparing in patients with muscle- invasive bladder cancer (MIBC): HCRN GU 16-257.
Authors: Matt D. Galsky, Siamak Daneshmand, Kevin G. Chan, Tanya B. Dorff, Jeremy Paul Cetnar, Brock O Neil, Anishka D'souza, Ronac Mamtani, Christos Kyriakopoulos, Philip Garcia, Sudeh Izadmehr, Menggang Yu, Qianqian Zhao, Reza Mehrazin, Sara C Lewis, John Sfakianos, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2021)

4503 Background: Transurethral resection of bladder tumor (TURBT) plus systemic therapy has been known for decades to achieve durable bladder-intact survival in a subset of patients with MIBC but efforts to advance this paradigm have been complicated by (a) lack of prospective studies exclusively testing cisplatin-based neoadjuvant chemotherapy, (b) lack of rigorous methods to define clinical complete response (cCR) and its association with long term outcomes and (c) limited understanding of the role of “salvage” cystectomy. Methods: Eligible patients were cisplatin-eligible with cT2-T4aN0M0 urothelial bladder cancer. Patients received 4 cycles of gemcitabine, cisplatin, plus nivolumab followed by clinical restaging including urine cytology, MRI/CT of the bladder, cystoscopy and bladder/prostatic urethral biopsies. Patients achieving a cCR (normal cytology, imaging, and cT0/Ta) were eligible to proceed without cystectomy and receive nivolumab q2 weeks x 8 followed by surveillance; otherwise, patients underwent cystectomy. Coprimary endpoints included (1) cCR rate and (2) ability of cCR to predict 2-year metastasis-free survival (MFS). The key secondary endpoint was the impact of genomic alterations in baseline TURBT (TMB, ERCC2, FANCC, RB1, ATM) on performance of cCR for predicting MFS. The cCR rate coprimary endpoint, and interim analysis of 1-year outcomes, are reported. Results: Between 8/2018-11/2020, 76 patients were enrolled at 7 sites (male 79%, median age 69; cT2 = 56%, cT3 = 32%, cT4 = 12%) and 64 (84%) have completed post-cycle 4 restaging; 31/64 achieved a cCR (48%; 95% CI 36%, 61%). The median follow-up of cCR patients is 13.7 months (range, 2.5-24 months). One cCR patient opted for immediate cystectomy (pTaN0M0). Outcomes for the entire cohort are summarized in the table below. Local recurrence has occurred in 8/31 cCR patients and 6 underwent cystectomy (pT0N0 = 1, pTaN0 = 1, pTisN0 =1, pT2N0 = 2, pT4N1 = 1). TMB ≥ 10 mut/Mb (p=0.02) or mutant ERCC2 (p=0.02) were associated with cCR or pT0. Conclusions: TURBT + gemcitabine, cisplatin, plus nivolumab achieves stringently defined cCR in a large subset of patients with MIBC. 1-year bladder intact survival is possible though the durability of responses, and role of genomic biomarkers in management algorithms, requires longer follow-up. Clinical trial information: NCT03558087. [Table: see text]
Significant decline in cancer diagnostic testing in U.S. CMS population during the COVID-19 pandemic.
Authors: Dave Smart, Peter Riccelli, Keith Kerr, Jordan Clark, Susanne Munksted Fosvig, Mark Lawler
Journal: Journal of Clinical Oncology (2021)

6536 Background: The COVID-19 pandemic has caused &gt;400,000 infection related deaths in the US to January 2021. Actions taken to limit COVID-19 infection and mortality could potentially lead to unintended consequences, precipitating excess mortality due to other causes. One such cause is delayed cancer diagnosis. Significant decreases in presentation for cancer diagnosis at the primary care level have been noted in the UK. This study aimed to look for evidence of a similar effect in the US. Methods: CMS claims data from JAN18-JUN20 associated with primary diagnosis across 11 cancers (bladder, breast, cervical, colorectal, endometrial, lung, ovarian, pancreatic, prostate, sarcoma and thyroid) were analyzed for use of surgical pathology (SP), a procedure associated with initial diagnosis, and immunohistochemistry (IHC). Test volumes varied widely by test and cancer so were normalized to enable comparison across indications. This was done by dividing the month-on-month difference for the period JAN19-JUN19 vs JAN20-JUN20 by the median monthly test volume for the period JAN18-DEC19 (“pre-COVID period”). Extent and duration of declines in test rates and number of missing patients as the sum of these declines were then determined. The ratio of IHC to SP testing was taken to determine any decline in likely post-initial diagnosis testing. Results: There were significant (&gt;10%) declines in test volumes for SP for all 11 cancers at some time in Q1-Q2 2020. Table. Extent, duration and return to pre-COVID levels for SP testing across 11 cancers Median extent and duration of the decline was 56% (range 41.1%-80.4%) and 2 months (range 1- &gt;4). This equates to 32,192 missing diagnoses across all cancers. SP test volumes for all cancers except lung and breast had returned to around pre-COVID levels by JUN20. There was no significant (&gt;10%) increase in normalized SP test volume after the COVID dip for any cancer. While SP showed decreased test volumes across all cancers at some point during the first half of 2020, test volume ratios of IHC to SP showed increases for most cancers in the same time period. Conclusions: These data highlight that the decline in patients presenting to their primary care physicians with suspicion of cancer for diagnostic investigation was linked to COVID-19 prevention strategies. No evidence for increased, “catch up” testing to address presentational/diagnostic backlog was observed. Thus, it is predicted that these patients may subsequently present with a more advanced cancer. Potential excess morbidity, mortality and cost associated with absent or delayed diagnosis should be factored into cancer control programs going forward.[Table: see text]
A randomized controlled trial of cognitive behavior therapy for reducing anxiety and depressive symptoms in patients with locoregional advanced nasopharyngeal carcinoma.
Authors: Feng Liu, Shengnan Fu, Yanzhu Chen, Ouying Yan, Xiangwei Wu, Yaqian Han, Cuihong Jiang, Fei Tong, Ran Zou, Wanglian Peng, Hui Wang, Xiaohong Liu
Journal: Journal of Clinical Oncology (2021)

12121 Background: The purpose of this randomized trial was to compare the efficacy of cognitive behavioral therapy (CBT) versus treatment as usual (TAU) on anxiety and depression, response rates and acute adverse events in patients with locoregional advanced nasopharyngeal carcinoma (NPC) receiving chemoradiotherapy. To the best of our knowledge, this is the first randomized trial evaluating the effect of CBT for depression and anxiety in patients with locoregional advanced NPC treated with chemoradiotherapy. Methods: A total of 202 patients with diagnosis of stage III-IVa (8 th AJCC) NPC were randomly assigned to receive CBT plus chemoradiotherapy (CBT group, n = 101) or treatment as usual (TAU) plus chemoradiotherapy (TAU group, n = 101). Patients in the CBT group received a series of six CBT sessions for 6 weeks during concurrent chemoradiotherapy. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale (HADS) score at baseline, the completion of chemoradiotherapy, 1 and 3 months after chemoradiotherapy. Response rates and adverse events were also evaluated. This trial is registered with chictr.org.cn, number ChiCTR2000034701. Results: Patients in the CBT group showed significantly less depression and anxiety than patients in the TAU group after the completion of CBT (P &lt; 0.01). Complete response (CR) rate was significantly higher in CBT group than in TAU group (100% vs. 93.1%，P = 0.014). Compared with the TAU group, the CBT group showed a significantly lower incidence of acute adverse events including anemia, fatigue, mucositis, insomnia and weight losing (P &lt; 0.05). Conclusions: The addition of CBT to chemoradiotherapy significantly reduced depressive and anxiety symptoms. CBT combined with chemoradiotherapy is associated with improved response rates, with reduced incidence of acute toxic effects in patients with locoregional advanced nasopharyngeal carcinoma. Clinical trial information: ChiCTR2000034701.
Mobile low-dose computerized tomography (LDCT): Three-year follow up of solution for early diagnosis of lung cancer in under-served populations.
Authors: Derek Raghavan, Darcy L. Doege, Mellisa S Wheeler, Kia Dungan, Lauren Davis, John Doty, Glenn Hickman, Brooke Weatherford, Stephanie White, Kathryn Finch Mileham, Daniel R. Carrizosa
Journal: Journal of Clinical Oncology (2021)

6507 Background: Randomized trials have proven that screening high-risk patients with LDCT of chest reduces lung cancer mortality compared to screening with chest x-ray. Under-served patients lack access to this test due to geographic and socio-economic factors. We hypothesized that a mobile screening unit would improve access and increase survival in this group, which is most at risk of lung cancer deaths. Methods: We installed a BodyTom portable 32 slice low-dose CT scanner (Samsung Inc) into a 35 foot coach (Frazier Inc), reinforced to avoid equipment damage during road travel. It includes waiting area, high speed wireless internet connection for rapid image transfer, and electronic tablets to deliver smoking cessation and health education programs and shared decision-making video aids. We used LUNG RADS approach to lesion classification, yielding high sensitivity and specificity in assessment. All films were reviewed by a central panel. This is certified as a lung cancer screening Center of Excellence by the Lung Cancer Alliance. Protocol was approved by Advarra IRB. Medicare pts excluded as insurance covered them for LDCT, although this reduced potential number of cases diagnosed as this is highest risk population. Results: We screened 1200 uninsured or under-insured subjects, mean age 61 years (range 55-64), with average pack year history of 47.8 (30-150); 61% male; 18% Black, 3% Hispanic/Latino; 78% rural. We found 97 pts with LUNG RADS 4 lesions, 30 lung cancers (2.5%), including 15 at stage I-II treated with curative intent; 5 incidental non-lung cancers (renal CA 2, head &amp; neck CA 1, pancreas CA 2); more than 50% with cardiovascular disease or COPD seen on LDCT. Of eligible first-screen subjects (J. Clin. Oncol., 2019, 37, 383S), 440 attended Year 1 repeat LDCT and 161 attended Year 2 LDCT. Only one pt with surgically resected CA lung has relapsed to date. Conclusions: Mobile LDCT yields higher screening rate for under-served pts than prior international studies, with strong protocol adherence and paucity of early cancer deaths in high-risk population with traditionally poor compliance.