tbuckley/cabot-search huggingface dataset:
An open-label, multicenter, phase IIIb study of patients with urinary tract carcinoma (UTC) (STRONG): Interim safety results for fixed-dose durvalumab (D) monotherapy (module A).
Authors: Guru Sonpavde, Cora N. Sternberg, Jae-Lyun Lee, Paulo Andre Palhares de Miranda, Ana Rita Lima, Makan Sarkeshik, Sebastien J. Hotte
Journal: Journal of Clinical Oncology (2020)

484 Background: Patients (pts) with advanced UTC who fail first-line therapy have a poor prognosis and limited treatment options, with only modest benefit from chemotherapy. D (anti-PD-L1 antibody) is approved for the treatment of metastatic urothelial carcinoma after progression on platinum-based chemotherapy. Methods: Module A of the phase IIIb STRONG study (NCT03084471) will determine the short- and long-term safety of a fixed dose of D monotherapy (1500 mg, every 4 weeks) in pts with urothelial and non-urothelial carcinoma of the UT who progressed on or after prior chemotherapy. The primary endpoint is to determine the number of pts with adverse events of special interest (AESIs). This analysis included AEs with onset date on or after the date of first dose and up to 90 days after discontinuation of study treatment. Interim results from module A are reported. Results: A total of 700 pts received D monotherapy. Median age was 68.2 yr and 79.6% were male; 88.6% had an ECOG PS 0 or 1 and 11.3% an ECOG PS 2. Most (88.4%) had urothelial (transitional cell) carcinoma. Tumor PD-L1 expression was high (tumor or immune cell membrane positivity ≥25%) in 183/436 (42%) pts with PD-L1 data. Median treatment duration was 11.7 weeks (range, 1-73). AEs of any grade were reported in 86.9% of pts (Table), and in 89.0%, 86.9%, and 78.5% of pts with ECOG PS 0, 1, or 2, respectively. The most common grade ≥3 AESI was increased lipase (1.4%). Deaths related to study treatment occurred in 10 pts (1.4%). Conclusions: Fixed-dose D monotherapy has an acceptable safety profile as second-line therapy for UTC. Long-term safety data reported here are consistent with published studies of D monotherapy. Clinical trial information: NCT03084471.
Nanotechnology approaches in the current therapy of skin cancer
Authors: Livia Neves Borgheti-Cardoso, Juliana Santos Rosa Viegas, Ana Vitoria Pupo Silvestrini, Angelo Luis Caron, Fabiola Garcia Praça, Marcelo Kravicz, Maria Vitória Lopes Badra Bentley
Journal: Advanced Drug Delivery Reviews (2020)
Quantitative analysis of airway obstruction in lymphangioleiomyomatosis
Authors: Stijn E. Verleden, Arno Vanstapel, Laurens De Sadeleer, Birgit Weynand, Matthieu Boone, Erik Verbeken, Davide Piloni, Dirk Van Raemdonck, Maximilian Ackermann, Danny D. Jonigk, Johny Verschakelen, Wim A. Wuyts
Journal: European Respiratory Journal (2020)

Lymphangioleiomyomatosis (LAM) is a rare, cystic lung disease with progressive pulmonary function loss caused by progressively proliferating LAM cells. The degree of airway obstruction has not been well investigated within the pathogenesis of LAM. Using a combination of ex vivo computed tomography (CT), microCT and histology, the site and nature of airway obstruction in LAM explant lungs was compared with matched control lungs (n=5 each). The total number of airways per generation, total airway counts, terminal bronchioles number and surface density were compared in LAM versus control. Ex vivo CT analysis demonstrated a reduced number of airways from generation 7 on (p&lt;0.0001) in LAM compared with control, whereas whole-lung microCT analysis confirmed the three- to four-fold reduction in the number of airways. Specimen microCT analysis further demonstrated a four-fold decrease in the number of terminal bronchioles (p=0.0079) and a decreased surface density (p=0.0079). Serial microCT and histology images directly showed the loss of functional airways by collapse of airways on the cysts and filling of the airway by exudate. LAM lungs show a three- to four-fold decrease in the number of (small) airways, caused by cystic destruction which is the likely culprit for the progressive loss of pulmonary function.
The impact of age on general and bladder cancer-specific quality of life among bladder cancer survivors.
Authors: Pauline Filippou, Sean McCabe, Hannah McCloskey, Kathryn Gessner, Judy Hamad, Allison Mary Deal, Angela Smith, John L. Gore
Journal: Journal of Clinical Oncology (2020)

463 Background: Quality of life among cancer survivors has been shown to vary by age. Our objective was to evaluate differences in general and bladder cancer-specific quality of life based on age among a large cross-sectional bladder cancer cohort. Methods: We performed a cross-sectional survey of bladder cancer patients using the Bladder Cancer Advocacy Network Patient Survey Network and Inspire platforms to determine general and bladder cancer-specific quality of life (QOL) using the EORTC QLQ-C30 and Bladder Cancer Index. Patients were also queried regarding demographic, socioeconomic and clinical characteristics. We present descriptive statistics and a multiple linear regression model to identify factors independently associated with QOL domain score. Results: 972 respondents self-identified as patients with bladder cancer, of whom 41% were female and 97 % were white. The mean age was 67.6 years (range 29 to 93 years). Respondents were highly educated (67% completed college). 63% of patients identified as having non-invasive (NMIBC) cancer (n=578), 30% had MIBC (n=270), and 7% had metastatic bladder cancer (n=63). On multivariable analysis, older age was significantly associated with better generic QOL and urinary function ( Table), but not sexual function (p=0.19) or bowel function (p=0.73), controlling for sex, race, stage, comorbidity and years since diagnosis. Conclusions: Higher general and domain-specific QOL scores are more common among older bladder cancer patients. Differential impact by age may be important for the development of tailored interventions to improve QOL for bladder cancer patients. [Table: see text]
Oligopelvis-GETUG P07: A multicenter phase II trial of combined salvage radiotherapy and hormone therapy in oligorecurrent pelvic node relapses of prostate cancer.
Authors: Stephane Supiot, David Pasquier, Xavier Buthaud, Nicolas Magné, Veronique Beckendorf, Paul Sargos, Gilles Crehange, Pascal Pommier, Genevieve Loos, Ali Hasbini, Igor Latorzeff, Marlon Silva, Fabrice Denis, Jean-Leon Lagrange, Loic Campion, Loig Vaugier, Audrey Blanc-Lapierre
Journal: Journal of Clinical Oncology (2020)

93 Background: Oligorecurrent pelvic nodal relapse of prostatic cancer is a challenge for regional salvage treatments. We conducted OLIGOPELVIS – GETUG P07, a phase II trial of combined salvage radiotherapy and hormone therapy in oligorecurrent pelvic node relapses of prostate cancer (NCT02274779). Methods: OLIGOPELVIS–GETUG P07 was a prospective multi-center phase II trial investigating high-dose salvage pelvic irradiation with an additional dose to the fluorocholine-based positron-emission-tomography (FCH- PET)-positive pelvic lymph nodes (PLN), combined with six-month androgen blockade (LH-RH agonist or antagonist injections). The prescribed dose was 54 Gy in 1.8 Gy fractions with up to 66 Gy in 2.2 Gy fractions to the pathological PLN. Toxicity (CTCAE v4) and complete response rates (PSA &lt; 0.20 ng/ml) were analyzed. The main objective was to assess biochemical-clinical failure defined by a cluster of events including PSA progression (≥25 % and ≥ 2 ng/ml above the nadir) or clinical evidence of local or metastatic progression or post- treatment initiation of hormonal therapy or prostate cancer-related death. We hypothesized that salvage treatment would achieve a 2-year relapse-free survival of 70 %. Results: Seventy-four patients were recruited in fifteen French radiation oncology departments between August 2014 and July 2016. Seven were excluded before treatment because of violation of the inclusion criteria. The intention-to-treat analysis therefore included sixty-seven patients. Half of them had received prior prostatic/prostate bed irradiation. Median age was 67.7. Grade 2+ two-year urinary and intestinal toxicity were 10% and 2% respectively. At 2 and 3 years, 73.1 and 45.9% of patients achieved a persisting complete response respectively. After a median follow-up of 34 months, the 2-year progression-free survival rate was 77.6%. Median progression-free survival was 40.1 months. Conclusions: Combined pelvic salvage radiotherapy and hormone therapy allowed for prolonged tumor control in oligorecurrent pelvic node relapses of prostate cancer with limited toxicity. Clinical trial information: NCT02274779.
Abstract 13298: Usefulness of Heart Rate Efficiency as a New Indicator to Replace a Chronotropic Incompetence in Patients With Chronic Heart Failure
Authors: Ayumi Date, Yuto Koizumi, Taiki Hayasaka, Kiwamu Horiuchi, Shohei Hosoguchi, Akiho Minoshima, Naka Sakamoto, Naoyuki Hasebe
Journal: Circulation (2018)

Background: In chronic heart failure (CHF) patients, chronotropic incompetence (CI) suggests a poor prognosis. However, the determination of CI was affected by the factors such as patient effort du...
Low Use of Epinephrine for the Treatment of Anaphylaxis in Restaurants
Authors: Jordan Trevisonno, Sofianne Gabrielli, Ann Clarke, Judy Morris, Harley Eisman, Jocelyn Gravel, Paul Enarson, Edmond Chan, Andrew O'Keefe, Robert Porter, Rodrick Lim, Susan Elliott, Moshe Ben-Shoshan
Journal: Journal of Allergy and Clinical Immunology (2020)
Genomic determinants of nested variant urothelial carcinoma.
Authors: Timothy Nguyen Clinton, Karissa Whiting, Vitor Silva, Qiang Li, Nima Almassi, Eugene Pietzak, Aditya Bagrodia, Eugene K. Cha, Guido Dalbagni, Gopa Iyer, Bernard H. Bochner, Maria E. Arcila, Irina Ostrovnaya, Anuradha Gopalan, Ying-Bei Chen, Samson Fine, Satish Tickoo, Victor E. Reuter, David B. Solit, Hikmat Al-Ahmadie
Journal: Journal of Clinical Oncology (2020)

538 Background: Nested variant urothelial carcinoma (NVUC) is a historically aggressive variant of bladder cancer with management reliant on radical cystectomy given unclear effectiveness of chemotherapy. Given the aggressive behavior of NVUC, the identification of pathogenic and potentially targetable genomic alterations could suggest novel treatment paradigms for this rare histologic variant. Methods: Query of our institutional database identified 81 cases of clinically localized NVUC. Each case was re-reviewed by GU pathologists to confirm the histology. Targeted capture sequencing was performed to define the spectrum of genomic alterations in known and putative cancer genes. Clinical and sequencing data was then compared between the nested variant cases and a prospective cohort of clinically localized high-grade urothelial carcinomas, not otherwise specified (UC NOS). Results: On central re-review, tumors were classified as either classic NVUC (N=53) or high-grade urothelial carcinoma with nested features (N=28). A cohort of UC NOS patients (N=600) was used as a comparator. Median follow-up of the overall cohort was 4.3 years. Classic NVUC was associated with higher risk of cancer specific mortality compared to UC NOS on multivariate analysis (HR 1.76, p=0.04). Tumor mutational burden was lower in classic NVUC tumors versus UC NOS. Evaluation of 136 cancer-associated genes identified differences in mutational frequencies across the 3 cohorts (Table) with RhoA and FOXA1 alterations enriched in NVUC. Conclusions: Patients with NVUC have significantly higher risk of cancer specific mortality than patients with UC NOS. While there was significant overlap between the landscape of genomic alterations in NVUC and UC NOS tumors, NVUC tumors were enriched for RhoA and FOXA1 alterations among others.[Table: see text]
Survival outcomes of patients with extranodal natural-killer T-cell lymphoma: a prospective cohort study from the international T-cell Project
Authors: Christopher P Fox, Monica Civallero, Young-Hyeh Ko, Martina Manni, Tetiana Skrypets, Stefano Pileri, Seok Jin Kim, Maria Elena Cabrera, Andrei R Shustov, Carlos S Chiattone, Steven M Horwitz, Ivan Dlouhy, Michele Spina, Felicitas Hitz, Silvia Montoto, Arnon Nagler, Virginia Martinez, Carmino A De Souza, Ruben Fernandez-Alvarez, Veronika Ballova, Raul Gabús, Giorgio Inghirami, Massimo Federico, Won Seog Kim
Journal: The Lancet Haematology (2020)
Assembly of hundreds of novel bacterial genomes from the chicken caecum
Authors: Laura Glendinning, Robert D. Stewart, Mark J. Pallen, Kellie A. Watson, Mick Watson
Journal: Genome biology (2020)

Abstract Background Chickens are a highly important source of protein for a large proportion of the human population. The caecal microbiota plays a crucial role in chicken nutrition through the production of short-chain fatty acids, nitrogen recycling, and amino acid production. In this study, we sequence DNA from caecal content samples taken from 24 chickens belonging to either a fast or a slower growing breed consuming either a vegetable-only diet or a diet containing fish meal. Results We utilise 1.6 T of Illumina data to construct 469 draft metagenome-assembled bacterial genomes, including 460 novel strains, 283 novel species, and 42 novel genera. We compare our genomes to data from 9 European Union countries and show that these genomes are abundant within European chicken flocks. We also compare the abundance of our genomes, and the carbohydrate active enzymes they produce, between our chicken groups and demonstrate that there are both breed- and diet-specific microbiomes, as well as an overlapping core microbiome. Conclusions This data will form the basis for future studies examining the composition and function of the chicken caecal microbiota.
Pachyonychia congenita, a paradigm for rare skin disorders
Authors: L. Steele, E.A. O'Toole
Journal: British Journal of Dermatology (2020)

Linked Articles: Soon et al. Br J Dermatol 2020; 182:789–790. Simpson et al. Br J Dermatol 2020; 182:729–737. Angwin et al. Br J Dermatol 2020; 182:698–707. Samuelov et al. Br J Dermatol 2020; 182:738–746. Weinberg et al. Br J Dermatol 2020; 182:543–551. Koren et al. Br J Dermatol 2020; 182:671–677. Funk et al. Br J Dermatol 2020; 182:788–789.
Stereotactic pelvic radiotherapy with HDR boost for dose escalation in intermediate and high-risk prostate cancer (SPARE): Efficacy, survival, and late toxicity outcomes.
Authors: Andrew Loblaw, Bindu Musunuru, Patrick Cheung, Danny Vesprini, Stanley K. Liu, William Chu, Hans T. Chung, Gerard Morton, Andrea Deabreu, Melanie Davidson, Ananth Ravi, Joelle Helou, Ling Ho, Liying Zhang
Journal: Journal of Clinical Oncology (2020)

328 Background: The ASCO/CCO guidelines recommend brachytherapy boost for all eligible intermediate- or high-risk localized prostate cancer patients. We present efficacy, survival and late toxicity outcomes in patients treated on a prospective, single institutional protocol of MRI dose painted HDR brachytherapy boost (HDR-BT) followed by pelvic stereotactic body radiotherapy (SBRT) and androgen deprivation therapy (ADT). Methods: A phase I/II study was performed where intermediate (IR) or high-risk (HR) prostate cancer patients received HDR-BT 15Gy x 1 to the prostate and up to 22.5Gy to the MRI nodule and followed by gantry-based SBRT 25Gy in 5 weekly fractions delivered to pelvis, seminal vesicles and prostate. ADT was used for 6-18 months. CTCAEv3 was used to assess toxicities and was captured q6months x 5 years. Biochemical failure (BF; nadir + 2 definition), nadir PSA, proportion of patients with PSA &lt; 0.4 ng/ml at 4 years (4yPSARR), incidence of salvage therapy, cause specific survival and overall survival were calculated. Day 0 was HDR-BT date for all time-to-event analyses. Results: Thirty-two patients (NCCN 3% favorable IR, 47% unfavorable IR and 50% HR) completed the planned treatment with a median follow-up of 50 months; 31 of these had an MRI nodule. Four patients had BF with actuarial 4-year BF rate of 11.5%; 3 of these received salvage ADT. Median nPSA was 0.02 ng/ml; 4yPSARR was 68.8%. One patient died (of prostate cancer) at 45 months. For late toxicities, grade 1, 2 and 3+ GU and GI toxicities were: 40.6%, 37.5%, 3% and 28.1%, 0%, 0%, respectively. Conclusions: This novel treatment protocol incorporating MRI-dose painted HDR brachytherapy boost and SBRT pelvic radiation for intermediate- and high-risk prostate cancer in combination with ADT is feasible, effective and well tolerated. Clinical trial information: 12345678. [Table: see text]
Results of a phase I/II prospective dose-escalation trial evaluating safety and efficacy of combination 177LuPSMA-617 and NOX66 in men with mCRPC post androgen signalling inhibition and two lines of taxane chemotherapy (LuPIN trial).
Authors: Louise Emmett, Sarennya Pathmanandavel, Andrew Nguyen, Megan Crumbaker, Andrew On Wah Yam, Wai Ling Chan, Karen Fullard, Bao Ho, Arun Azad, Anthony M. Joshua
Journal: Journal of Clinical Oncology (2020)

120 Background: Despite treatment advances, metastatic castrate resistant prostate cancer (mCRPC) remains a lethal disease. Trials in 177 LuPSMA-617 have demonstrated good efficacy and safety, but synergistic combinations may further improve treatment responses. NOX66 inhibits external NADH oxidase type 2 with downstream pro-apoptotic actions including radio-sensitization. We present results of a prospective open label single arm phase 1/2 dose escalation/expansion trial of 177 LuPSMA-617 and NOX66 in mCRPC. Methods: Men with progressive mCRPC post androgen signalling inhibition (ASI) and taxane chemotherapy were eligible. Inclusion criteria included PSMA PET/CT intensity &gt; SUV max 15, with no discordant disease on FDG PET/CT, Hb &gt; 100 g/L, Platelets &gt; 90 x 10 6 /L and GFR &gt; 40 mL/min. Protocol allowed up to 6 doses of 177 Lu-PSMA 617 (7.5Gbq) on day 1 with NOX66 (suppository) given day 1-10 at 6-weekly intervals; the first 8 men received 400mg NOX66. After safety review, dose was escalated to 800mg. Data regarding safety, efficacy, pain scores, and QOL were collected. Results: 32/43 (26% imaging screen failures) screened men were enrolled (November 2017 – June 2019), of whom 100% had prior docetaxel and ASI, and 94% (30/32) cabazitaxel. All men received ≥ 2 cycles, with 12/32 completing 6 cycles, and 16/32 2 - 5 cycles, while 4/32 remain on treatment. Any PSA response was seen in 84% (27/32), with a PSA response &gt; 50% in 62.5% (20/32). Median PSA PFS was 6.5 months (95%CI 3.54-9.3). To date, 72% (23/32) of patients have progressed. 34% (11/32) men have died with median OS not reached. 50% (12/24) of men with baseline pain scores ≥3 (24/32) had significant reduction in pain. Adverse events are summarized below. Conclusions: Combination 177 LuPSMA-617 with NOX66 appears safe and efficacious in men with heavily pre-treated mCRPC. Clinical trial information: ACTRN12618001073291. [Table: see text]
A randomized phase II trial comparing switch to nivolumab with TKI continuation after 12 weeks of TKI induction therapy in metastatic renal cell carcinoma patients (NIVOSWITCH).
Authors: Viktor Grünwald, Carsten Grüllich, Philipp Ivanyi, Manfred Wirth, Peter Staib, Martin Schostak, Philip Dargatz, Lothar Müller, Michael Metz, Lothar Bergmann, Thomas Steiner, Manfred Welslau, Anja Lorch, Mohammad-Reza RAFIYAN, Eva Hellmis, Axel Hinke, Johannes Meiler, Thomas Kretz, Wolfgang C. Loidl, Anne Flörcken
Journal: Journal of Clinical Oncology (2020)

678 Background: Tyrosine kinase inhibitors (TKI) and Nivolumab (NIVO) are standard treatment options for mRCC. We tested whether TKI followed by early switch to NIVO improved outcome in mRCC patients (pts). Methods: Main inclusion criteria: measurable advanced or metastatic clear cell RCC, ECOG PS 0-2, adequate organ function, PR or SD to induction therapy with sunitinib (50 mg, 4-2 regime) or pazopanib (800 mg OD). 1:1 randomization at 12 wks.: TKI continuation vs. switch to NIVO (240 or 480 mg IV q2-4wks). Strata were MSKCC risk, TKI used and response to TKI. Imaging was performed q12w. 49 of 244 planned pts were randomized between Dec 2016 and Aug 2018, which led to premature closure of the trial. We report the second interim analysis with data base lock on 31.07.19. ORR was assessed according to RECIST 1.1. Efficacy and safety analyses were performed in ITT and safety population, respectively. Log-Rank analyses were used for survival analyses. Results: 25 and 24 pts received NIVO or TKI, respectively. Median age was 65 y (range: 35-79), 82% were male and 4% had ECOG PS 2. Metastases occurred predominantly in lung (47%), lymph nodes (27%) and liver (24%). MSKCC risks were: favorable (31%), intermediate (65%), and poor (4%), which were balanced between arms. 55% received sunitinib. ORR for NIVO vs. TKI differed when assessed from start of induction therapy (64 vs. 70%, P=0.76) or from time of randomization (16 vs. 48%; P=0.032). Accordingly, PFS from randomization was 3.0 vs. 11.9 mo. (HR = 1.72 [95% CI: 1.19 – 2.48]; P=0.0026) in favor of TKI continuation. At a median follow-up of 12.9 mo. median OS was not reached, but HR = 1.86 (95% CI: 0.85 – 4.07) P=0.10 showed a trend for TKI continuation. All grades AE for NIVO vs. TKI occurred in 96% vs. 100%, grade 3-5 48% vs. 71% and serious AE 40% vs. 46%. Conclusions: In TKI-sensitive pts, continuation of TKI is more efficacious than early switch to NIVO. The major limitation of our trial is the premature closure and its limited sample size. Clinical trial information: NCT02959554.
Posterior Neocortex-Specific Regulation of Neuronal Migration by CEP85L Identifies Maternal Centriole-Dependent Activation of CDK5
Authors: Andrew Kodani, Connor Kenny, Abbe Lai, Dilenny M. Gonzalez, Edward Stronge, Gabrielle M. Sejourne, Laura Isacco, Jennifer N. Partlow, Anne O’Donnell, Kirsty McWalter, Alicia B. Byrne, A. James Barkovich, Edward Yang, R. Sean Hill, Pawel Gawlinski, Wojciech Wiszniewski, Julie S. Cohen, S. Ali Fatemi, Kristin W. Baranano, Mustafa Sahin, David G. Vossler, Christopher J. Yuskaitis, Christopher A. Walsh
Journal: Neuron (2020)
Hypertensive Disorders of Pregnancy and Recurrent Wheezing: 18 Month Follow-up Of A Birth Cohort Study
Authors: Beatriz Yazbek, Mariana Rahal, Júlia Mello, Luiza Magalhaes, Fernanda Falleiros, Juliana Silva, Etienne Duim, Francisco Sousa, MARIA CELIA CIACCIA, Vera Rullo
Journal: Journal of Allergy and Clinical Immunology (2020)