tbuckley/cabot-search huggingface dataset:
Sarcomatoid (srcRCC) versus clear cell (ccRCC) renal cell carcinoma: A comparative comprehensive genomic profiling (CGP) study.
Authors: Gennady Bratslavsky, Joseph M Jacob, Andrea Necchi, Philippe E. Spiess, Petros Grivas, Natalie Danziger, Richard Huang, Douglas A Mata, Brennan James Decker, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2021)

349 Background: srcRCC is a well-described histologic entity often featuring rapid progression and aggressive clinical course when compared with classic ccRCC. We queried whether CGP would uncover opportunities for targeted and immunotherapy (IO) for srcRCC patients that could individualize their treatment and entry into clinical trials. Methods: Using a hybrid capture-based CGP assay to evaluate all classes of genomic alterations (GA), 160 cases of srcRCC and 1,664 cases of ccRCC were sequenced from FFPE tissue samples. Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on up to 114 loci. PD-L1 expression was determined by IHC (Dako 22C3) with low tumor cell positive staining set at 1-49% and high staining &gt;50% expression. Results: Gender and age distributions for both tumor types were similar. srcRCC featured significantly higher GA/tumor than ccRCC (P &lt; .0001). CGP revealed major differences with ccRCC associated more frequently with tumor suppressor gene (TSG) losses in VHL, PBRM1, TSC2 and SETD2 (all P &lt; .0001). In contrast, srcRCC is associated with cell proliferation with increased inactivation of cell cycle regulatory genes including TP53, CDKN2A/B, MDM2 and TERT (all P &lt; .0001). RB1 GA in srcRCC may reflect neuroendocrine differentiation occasionally found in these tumors. NF2 GA were more frequent in srcRCC (P &lt; .0001). Conclusions: CGP reveals striking differences between srcRCC and ccRCC which may in part explain the differing histologic appearances and typical clinical course of these 2 aggressive malignancies. ccRCC is driven more by TSG loss and srcRCC is driven more by cell cycle dysregulation. Targeted therapy opportunities were uncommon for both tumor types although each featured biomarkers potentially predictive of mTOR inhibitor responses ( TSC2 in ccRCC and NF2 in srcRCC). Although the higher PBRM1 GA frequency in ccRCC may explain the IO benefit well-known for this tumor type, the srcRCC group features significantly increased TMB, CD274 amplification and PD-L1 staining which may also create IO opportunities for srcRCC patients. [Table: see text]
Abstract 1809: Increased eNOS Coupling Protects Against Vein Graft Accelerated Atherosclerosis in ApoE-KO Mice
Authors: Ziad A Ali, Marianna Papaspyridonos, Christina A Bursill, Amy L Tatham, Joseph P deBono, Jennifer K Bendall, David Greaves, Nicholas J Alp, Keith M Channon
Journal: Circulation (2006)

Accelerated atherosclerosis, a principal cause of vein graft (VG) failure, is associated with eNOS uncoupling and increased vascular superoxide (O2−). Tetrahydrobiopterin (BH4) is a required cofact...
Social disparities in the diagnosis and management of bladder cancer.
Authors: Shaakir Hasan, Stanislav Lazarev, Madhur Garg, Robert H. Press, Arpit Chhabra, Isabelle Choi, Charles B. Simone, Daniel Gorovets, Keyur J. Mehta
Journal: Journal of Clinical Oncology (2021)

403 Background: The socioeconomic characteristics associated with the diagnosis and management of bladder cancer are not well described. Methods: We utilized the National Cancer Database (NCDB) to stratify cases of urothelial cell carcinoma of the bladder by the National Comprehensive Cancer Network (NCCCN) guidelines: early (Tis, Ta, T1), muscle invasive (T2-T3, N0), locally advanced (T4, N1-3), and metastatic. We then used multivariate binomial and multinomial logistic regression analyses to identify demographic characteristics associated with stage at diagnosis and receipt of cancer-directed therapies. Hazard ratios (HR) are reported with 95% confidence intervals. Results: After exclusions, we identified 331,714 early, 72,154 muscle invasive, 15,579 locally advanced, and 15,161 metastatic cases. Relative to diagnosis at early stage, the two strongest independent predictors of diagnosis at muscle invasive, locally advanced, and metastatic disease included black race (HR = 1.19 [1.15-1.23], HR = 1.49 [1.40-1.59], HR = 1.66 [1.56-1.76], respectively), and female gender (HR = 1.21 [1.18-1.21], HR = 1.16 [1.12-1.20], and HR = 1.34 [1.29-1.38], respectively). Additional demographic factors associated with diagnosis at a more advanced stage on multivariable analysis included older age, treatment at an academic center (except for metastasis), Medicaid insurance, and patients from lower income/ less educated/more rural areas (all p &lt; 0.01). The following demographic factors were less likely to receive cancer-directed therapies, signified by odds ratios, per multivariable binomial regression analysis: Additionalyl, female patients (HR = 1.03, 1.02-1.05) and black patients (HR = 1.13, 1.11-1.16) were the only demographic correlates of reduced survival in the entire cohort with multivariable cox regression analysis. Conclusions: In the largest study of its kind, we report that several socioeconomic, racial, and gender factors are associated with the diagnosis of bladder cancer at a later stage, as well as the use of less cancer-directed treatments. Further investigation is warranted to better characterize, and ultimately improve upon, health disparities in bladder cancer. Research Sponsor: None[Table: see text]
Prognostic association between common laboratory tests and overall survival in men with <i>de novo</i> metastatic castration-sensitive prostate cancer: A population-based study.
Authors: Shawn Malone, Christopher J.D. Wallis, Scott Carlyle Morgan, Robert James Hamilton, Ilias Cagiannos, Naveen S. Basappa, Cristiano Ferrario, Geoffrey Gotto, Ricardo Fernandes, Krista Noonan, Tamim Niazi, Sebastien J. Hotte, Fred Saad, Katherine Chan, Huong Hew, Laura Park-Wyllie, Bobby Shayegan
Journal: Journal of Clinical Oncology (2021)

149 Background: Despite significant advancements in the treatment of metastatic prostate cancer, a validated prognostic tool for patients with de novo metastatic castration-sensitive prostate cancer (mCSPC) is still lacking. Using population-based data from Ontario, Canada, we sought to examine the prognostic association between common laboratory tests and survival for patients with mCSPC. Methods: A population-based cohort of men aged 66 years and older diagnosed with de novo metastatic prostate cancer between 2014-2019 were included. We assessed the association between laboratory tests at the time of cancer diagnosis and overall survival (OS). Utilizing a complete case analysis, we used Cox proportional hazards models to assess the association between these laboratory tests and OS while adjusting for patient and disease characteristics. Results: A total of 3,556 men with de novo mCSPC were included. On multivariable analysis, there were significant associations between OS and neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, albumin, hemoglobin, PSA decrease and PSA nadir &lt;0.1 ng/mL (please see table). Conclusions: Commonly available laboratory tests provide important prognostic information for patients with newly diagnosed mCSPC given demonstrated associations to overall survival. Apart from PSA kinetics, none of these baseline tests were performed in more than 57% of patients indicating underutilization of these low-cost prognostic biomarkers. [Table: see text]
Abstract 10139: Uterine Fibroids Affect the Harmonic Characteristics of Radial Pulse Waves
Authors: Chih-Yu Chen, Chi-Wei Chang, Yi-Ting Chang, Sheng-Hung Wang, gin-chung wang
Journal: Circulation (2019)

Introduction: Uterine fibroids are the most common pelvic tumors and have been shown to be associated with several cardiovascular risk markers. However, the conclusions of different studies on whet...
Abstract 15585: Sex Dimorphism in Prostaglandins’ Role in Thromboxane-dependent Contraction in the Rat Middle Cerebral Artery
Authors: Victor M Pulgar, Ibrahim Elsaangeedy, Liliya M Yamaleyeva
Journal: Circulation (2020)

Introduction: Recent evidences suggest that sex and estrogen can influence cerebrovascular reactivity. We investigated the role of prostanoids and the estrogen receptor (ER) ex vivo in isolated middle cerebral arteries from male (M-MCA) and female (F-MCA) rats. Methods: MCA segments isolated from 20-week-old male and female Sprague-Dawley rats were mounted on a wire Multi Myograph (DMT) to measure isometric tone. Acetylcholine (ACh) was used to assess endothelium integrity. Concentration response curves to the thromboxane analog U46619 (U4, 10 -11 -10 -5 M) were performed in arteries intact or pre-treated with indomethacin (I,10 -5 M) or the ER antagonist G15 (G, 10 -6 M). Data were acquired with Powerlab 8 (ADInstruments) and recorded with LabChart v8 (ADInstruments). Response to K + was expressed in mN/mm whereas U4 maximal contraction as percent of maximal response to 75mM K + (%K MAX ) and sensitivity as pD 2 (-LogEC 50 ). Results: M-MCA (n=10) and F-MCA (n=13) displayed similar optimal diameters (M vs. F; 214±12 vs. 218±5 μm, p&gt;0.05) and ACh-dependent relaxation (M vs. F; 71±11 vs. 78±10 % pre-constricted tone; 7.3±0.4 vs. 7.2±0.2, p&gt;0.05). A greater contraction to K + was observed in M-MCA (M vs. F; 1±0.2 vs. 0.6±0.1 mN/mm, p&lt;0.05). M- and F-MCA showed similar maximal contraction (M vs. F; 116±6 vs. 109±10 %K MAX ) and sensitivity (M vs. F; 7.2±0.2 vs. 7.3±0.2) to U4. Pre-incubation with Indomethacin lowered maximal response and sensitivity (M vs. M-I; 116±6 vs. 97±5%K MAX, p&lt;0.05; 7.2±0.2 vs. 6.8±0.1, p&lt;0.05) to U4 in M-MCA, with no effect on F-MCA (F vs. F-I; 109±9 vs. 113±7%K MAX ; 7.3±0.2 vs. 7.3±0.2). Pre-treatment with G15 increased U4 sensitivity in M-MCA (M vs. M-G; 7.3±0.2 vs. 7.8±0.2, p&lt;0.05), with no effect in F-MCA (F vs. F-G; 7.3±0.2 vs. 7.4±0.3). Conclusions: Our data demonstrate sex differences in thromboxane-dependent contraction of MCA in middle-aged rats. Hormonal changes during the estrous cycle may contribute to a greater variability of F-MCA responses.
Diffuse Large B-Cell Lymphoma
Authors: Laurie H. Sehn, Gilles Salles
Journal: New England Journal of Medicine (2021)

DLBCL, an aggressive cancer, accounts for about 30% of all lymphomas. Empirical combination chemotherapy cures about 65% of patients initially, with another 20 to 25% cured with salvage therapy. Efforts are ongoing to tailor therapy to particular genetic lesions.
Replacement Myocardial Fibrosis in Patients With Mitral Valve Prolapse
Authors: Anne-Laure Constant Dit Beaufils, Olivier Huttin, Antoine Jobbe-Duval, Thomas Senage, Laura Filippetti, Nicolas Piriou, Caroline Cueff, Clément Venner, Damien Mandry, Jean-Marc Sellal, Solena Le Scouarnec, Romain Capoulade, Marie Marrec, Aurélie Thollet, Marine Beaumont, Gabriella Hossu, Claire Toquet, Jean-Baptiste Gourraud, Jean-Noël Trochu, Karine Warin-Fresse, Pierre-Yves Marie, Jean-Jacques Schott, Jean-Christian Roussel, Jean-Michel Serfaty, Christine Selton-Suty, Thierry Le Tourneau
Journal: Circulation (2021)

Background: Mitral valve prolapse (MVP) is a frequent disease that can be complicated by mitral regurgitation (MR), heart failure, arterial embolism, rhythm disorders, and death. Left ventricular (LV) replacement myocardial fibrosis, a marker of maladaptive remodeling, has been described in patients with MVP, but the implications of this finding remain scarcely explored. We aimed at assessing the prevalence, pathophysiological and prognostic significance of LV replacement myocardial fibrosis through late gadolinium enhancement (LGE) by cardiac magnetic resonance in patients with MVP. Methods: Four hundred patients (53±15 years of age, 55% male) with MVP (trace to severe MR by echocardiography) from 2 centers, who underwent a comprehensive echocardiography and LGE cardiac magnetic resonance, were included. Correlates of replacement myocardial fibrosis (LGE+), influence of MR degree, and ventricular arrhythmia were assessed. The primary outcome was a composite of cardiovascular events (cardiac death, heart failure, new-onset atrial fibrillation, arterial embolism, and life-threatening ventricular arrhythmia). Results: Replacement myocardial fibrosis (LGE+) was observed in 110 patients (28%; 91 with myocardial wall including 71 with basal inferolateral wall, 29 with papillary muscle). LGE+ prevalence was 13% in trace-mild MR, 28% in moderate MR, and 37% in severe MR, and was associated with specific features of mitral valve apparatus, more dilated LV and more frequent ventricular arrhythmias (45% versus 26%, P &lt;0.0001). In trace-mild MR, despite the absence of significant volume overload, abnormal LV dilatation was observed in 16% of patients and ventricular arrhythmia in 25%. Correlates of LGE+ in multivariable analysis were LV mass (odds ratio, 1.01 [95% CI, 1.002–1.017], P =0.009) and moderate-severe MR (odds ratio, 2.28 [95% CI, 1.21–4.31], P =0.011). LGE+ was associated with worse 4-year cardiovascular event–free survival (49.6±11.7 in LGE+ versus 73.3±6.5% in LGE–, P &lt;0.0001). In a stepwise multivariable Cox model, MR volume and LGE+ (hazard ratio, 2.6 [1.4–4.9], P =0.002) were associated with poor outcome. Conclusions: LV replacement myocardial fibrosis is frequent in patients with MVP; is associated with mitral valve apparatus alteration, more dilated LV, MR grade, and ventricular arrhythmia; and is independently associated with cardiovascular events. These findings suggest an MVP-related myocardial disease. Last, cardiac magnetic resonance provides additional information to echocardiography in MVP.
Referral patterns and treatment preferences in patients with advanced prostate cancer (aPC): Differences between medical oncologists and urologists.
Authors: Ajeet Gajra, Skyler Hime, Yolaine Jeune-Smith, Amy Russell, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2021)

71 Background: With the advent of newer non-cytotoxic therapies for aPC, early integration of hormonal therapies (HT), and expansion of services within urology practices [e.g., radiation therapy (RT) and immunotherapy], urology practices are playing a larger role in the management of patients with aPC. In this descriptive study, we sought to assess the differences between medical oncologists (oncs) and urologists (uros) as they pertain to referral patterns and treatment decisions of men with aPC. Methods: Virtual meetings held in August 2020 convened oncs and uros of diverse US regions and practice types with experience treating prostate cancer (PC) to better understand perceptions around the management of patients with PC. Participants submitted responses via web-based pre-meeting surveys and real-time polling. All responses are summarized using descriptive statistics. Results: 66 oncs and 69 uros participated. The advisors were mostly community-based and see on average 20+ patients per day. 75% of uros estimated they refer ≤25% of all of their patients with PC to oncs and 75% of oncs reported that &gt; 50% of their patients with PC referrals are from uros. Other referring physicians identified include primary care (76%), radiation oncs (46%), or hospitalists (40%). Uros perceive oncs as co-managers (86%) for their patients with aPC and rarely (9%) transfer the care of their patients completely to oncs. Referrals from uros to oncs are driven by the need for chemotherapy (chemo) (52%) or progression to metastatic castration-resistant PC (mCRPC) (22%). Oncs reported that upon referral, these patients with PC have already been exposed to HT (75%), RT (66%), and/or surgery (43%). For second-line treatment of asymptomatic patients with mCRPC, oncs most commonly prescribe HT (60%) and chemo (23%), while uros most commonly prescribe sipuleucel-T (45%) and HT (38%). For second-line treatment of patients with mCRPC and symptomatic bony disease, oncs most commonly prescribe chemo (44%) and radium-223 (34%), while uros most commonly prescribe radium-223 (47%) and HT (22%). Conclusions: Uros refer patients with aPC to oncs for chemo. Uros prefer to treat with non-chemo options when possible and retain oncologic care for most of the patients’ cancer journey. The need for chemo is a major reason for referral from uros to oncs. The impact of these provider preferences upon patient outcomes in the real world needs further research. [Table: see text]
Safety and efficacy outcomes in immune checkpoint inhibitor (ICI)-treated metastatic urothelial carcinoma (mUC) patients (pts) requiring treatment interruption (TI) due to immune-related adverse events (irAEs).
Authors: Amanda Nizam, Iris Yeong- Fung Sheng, Kimberly D. Allman, Allison Martin, Timothy D. Gilligan, Shilpa Gupta, Moshe Chaim Ornstein
Journal: Journal of Clinical Oncology (2021)

411 Background: Most patients (pts) with metastatic urothelial carcinoma (mUC) will receive immune checkpoint inhibitors (ICI) at some point during treatment. As such, understanding of immune-mediated toxicity is integral to optimal patient management. We describe the clinical characteristics, treatment, and outcomes of ICI-treated mUC pts who experienced irAEs requiring treatment interruption (TI). Methods: ICI-treated mUC pts who developed &gt; grade 2 (per CTCAEv5) irAEs leading to &gt;2 week TI were retrospectively reviewed. Patient-, disease-, treatment-, and toxicity-related data were evaluated. Toxicity was graded per CTCAEv5. Time to treatment interruption (TTI), treatment-free interval (TFI), time to next treatment (TTNT), and duration of response (DoR) were assessed descriptively. Results: Of 200 ICI-treated mUC pts, 18 (9%) experienced irAEs necessitating TI. 12 (43%) were male; median age at diagnosis was 72.5 (range, 45-80); 15 (83%) had KPS &gt; 80. 8 (44%) had pure UC histology, 14 (78%) had prior cystectomy or nephroureterectomy, and 11 (61%) received platinum-based chemotherapy in the perioperative setting. 4 (22%) received 1L platinum-based Tx for mUC. ICI therapy was distributed evenly between atezolizumab (50%, n = 9) and pembrolizumab (50%, n = 9). Median TTI was 6.5 months (mos) (range, 1-19). The most common irAEs were dermatitis (22%, n = 4), colitis (17%, n = 3), and transaminitis (17%, n = 3); the majority were grade 2 (72%, n = 13). No grade 4/5 events occurred. 14 pts (78%) were treated with methylprednisolone and/or prednisone. Median initial prednisone-equivalent steroid dose was 45 mg/day (range, 30-1,250) with a median steroid duration of 42 days (range, 4-198). ICI were held and later re-challenged in 10 pts (56%), permanently discontinued in 7 pts (39%), and transitioned to a subsequent Tx in 1 pt (5%). Of 10 pts re-challenged with ICI, 7 (70%) experienced an irAE upon re-challenge (4 with recurrent irAEs, 3 with new irAEs); ICI was permanently discontinued in 3 of these pts. For pts receiving subsequent Tx, median TFI was 1 month (range, 0-12) and median TTNT was 5 mos (range, 2-31). Median DoR among all pts with initial response to ICI therapy was 15.5 mos (range, 2-52). Of 7 pts who permanently discontinued ICI and received no further Tx, 6 (86%) demonstrated an ongoing sustained therapy response with median DoR of 22.5 mos (range, 12-52). Conclusions: In this cohort, ICI-treated mUC pts who developed irAEs requiring treatment interruption had a high rate of subsequent irAEs upon ICI re-challenge. Importantly, pts who discontinue ICI due to irAE can have durable responses off treatment, consistent with data from other cancers.
High-risk nonmetastatic prostate cancer in the elderly: Does adjuvant chemotherapy affect survival?
Authors: Komal Akhtar, Margaret K Formica, Bhaskara Madhira, Alina Basnet
Journal: Journal of Clinical Oncology (2021)

229 Background: RTOG0521 and STAMPEDE showed improved Overall survival (OS) and progression free survival (PFS) respectively, of ACT (adjuvant chemotherapy) to ADT (androgen deprivation therapy) and RT (adjuvant radiotherapy) in HrPC (High Risk localized Prostate Cancer). The median age of males in these trials is in 60’s. We present an observational study reporting OS on addition of ACT to ADT and RT in male age &gt; 65 with HrPC. Methods: A retrospective national cancer center database (NCDB) (2004-2015) analysis was done. Patients aged &gt;65 years with non-metastatic HrPC who underwent ADT and RT with or without ACT were included. Group1 included RT+ ADT+ ACT, Group2 included RT+ ADT. OS was estimated using Kaplan Meier analysis, reported for sub groups based on age. An adjusted hazard ratio (aHR) was calculated utilizing a Cox proportional hazard regression model. Results: 1,380,357 patients with HrPC were identified. 11734 met our inclusion criteria; 128 in Group1 and 11606 in Group2. Median Age, Gleason and PSA were: Group1- 72, 9, 14.6, Group2- 74, 9 and 14. Patients who received ACT were more likely to be younger and treated in an academic setting. OS stratified by age is depicted in table. Among patients ≥ 75, OS was uniformly worse with ACT with non-significant p value (p=0.08). The aHR, group 1 vs group 2 is 1.22, 95% CI = 0.96-1.57, p=0.11, when adjusted for Age, Facility Type, Insurance, and Charlson-Deyo Score (CDS). Conclusions: Very elderly patients ≥75 years were not likely to get ACT. OS was not improved by addition of chemotherapy, at age ≥ 65yrs and more prominent at age ≥ 75. Limitations of observational database study are lack of randomizations, missing information, physician bias on choices of ACT, RT and ADT. [Table: see text]