tbuckley/cabot-search huggingface dataset:
Mental perception of prostate cancer (PCa) disease in patients aged 60 years and older initiating gonadotropin-releasing hormone agonist (GnRHa) therapy.
Authors: Christophe Hennequin, Francois Rozet, Pierre Mongiat-Artus, Nathalie Pello Leprince Ringuet, Aude Houchard, Morgan Roupret
Journal: Journal of Clinical Oncology (2020)

67 Background: PCa mostly affects elderly men and impacts their health-related quality of life (HRQOL), but little is known on differences by age groups. Our purpose was to analyze HRQOL with EORTC QLQ-ELD-14 questionnaire, a 7-dimension questionnaire specific of elderly cancer patients. Methods: From March 2018, a prospective, multicenter, non-interventional study was conducted in France (PRISME, NCT03516110). Urologists, radiation oncologists and medical oncologists recruited, as part as the normal consultation process, patients who met the following inclusion criteria: aged 60 years and older, with histologically confirmed PCa, candidate for GnRHa therapy. Patients were included (1:2:1) in prespecified age groups ([60-70[, [70-75[, ≥ 75 years). They reported HRQOL using ELD-14. Results: Overall, 528 patients were included in the interim analysis of baseline results. Mean (±SD) age was 72.9±6.5 years. There were 145, 207 and 176 patients, respectively, in the [60-70[, [70-75[ and ≥ 75 years groups. 93.8% of patients had a Karnofsky score ≥ 80%; 73.4% had at least one comorbidity at baseline and 67.9% were receiving at least one concomitant systemic treatment. Reason for GnRHa initiation was high risk localized or locally advanced tumor in 57.6%, metastatic stage in 19.8%, biochemical recurrence after local treatment in 14.7%. ELD-14 results on dimensions were as follows: “Mobility” was significantly worse in the 75y+ group (21.2±25.0) than in the [60-70[ (8.8±18.0) and [70-75[ (11.1±17.4) groups. “Burden of illness” decreased with age, with mean scores of 37.7±27.7, 31.0±25.3, and 28.3±25.1 (significantly different between [60-70[and 75y+ groups). No difference were observed on “Worries about future”, “Worries about others”, “Family support” and “Maintaining purpose” (motivation and positive outlook), however there was a large variability (SD &gt; 34) within each group for the last two dimensions. Conclusions: HRQOL interim analysis through ELD-14 showed few differences between age groups, and noticed variability within groups instead of between groups, meaning that mental perception of the disease could be more subject- than age-related.
Treatment response comparisons between <i>ATM</i> and <i>BRCA2</i> germline carriers for mCRPC.
Authors: Alexandra Sokolova, Catherine Handy Marshall, Rebeca Lozano, Petros Grivas, Celestia S. Higano, Tamara L. Lotan, Robert B. Montgomery, Peter Nelson, David Olmos, Michael Thomas Schweizer, Todd Yezefski, Evan Y. Yu, Channing Judith Paller, Elena Castro, Emmanuel S. Antonarakis, Heather H. Cheng
Journal: Journal of Clinical Oncology (2020)

63 Background: Over 10% of men with metastatic prostate cancer (PC) have germline DNA damage response gene alterations; most studies have reported BRCA2 alone or an aggregate of BRCA1, BRCA2 and ATM. Emerging data suggest ATM mutations have distinct effects and warrant individual gene evaluation. We hypothesize that, compared to patients (pts) carrying germline BRCA2 mutations (g BRCA2mut), pts carrying germline ATM mutations (g ATMmut) may have different treatment response to androgen-receptor-targeted agents, docetaxel, platinum therapy and PARP inhibitors (PARPi). Methods: This is an international, multicenter, retrospective case-control study of pts with PC who underwent clinical germline genetic testing between 2014-2019. We identified pts with g ATMmut and matched pts with g BRCA2mut by stage at diagnosis and year of testing. IRB-approved medical records review, χ² and log rank tests were performed. Results: 39 g ATMmut cases and 39 matched g BRCA2mut cases were identified for total of 78. A third (13/39) of pts in each cohort had metastases at diagnosis. Of those diagnosed with localized stage, 81% (21/26) of gATMmut and 73% (19/26) of g BRCA2mut developed metastasis (median times to metastasis 69 vs 49 months, respectively (p=0.1)). Pts in g ATMmut and g BRCA2mut cohorts had similar age, Gleason grade, and PSA at diagnosis. We did not observe a difference in PSA 50 response rates to abiraterone, enzalutamide, docetaxel, or carboplatin for mCRPC (Table). g BRCA2mut pts were more likely to respond to PARPi for mCRPC; where available, somatic loss of heterozygosity (LOH) data will be reported at final presentation. Conclusions: While response to standard therapies appears similar between g ATMmut and g BRCA2mut cohorts, response to PARPi in g ATMmut appears to be attenuated compared to g BRCA2mut. More studies are needed and pts with g ATMmut warrant prioritization for novel treatment strategies.[Table: see text]
Abstract 12102: Hypoxia-Inducible Factor-2α Activation in Vascular Smooth Muscle Cells Accelerates Atherogenesis in ApoE-/- Mice
Authors: Dan Qi, Yanting Song, Xia Wang, Shiyu Jiao, Ming Wei, Baoqi Yu, Aijuan Qu
Journal: Circulation (2018)

Recent studies suggest that hypoxia may exist in the process of atherosclerosis. However, the contribution of hypoxia to the development of atherosclerosis and the underlying mechanisms remain unkn...
The impact of time-to-castration resistance on survival in patients with metastatic hormone-naïve prostate cancer: A multicenter retrospective study.
Authors: Teppei Okamoto, Shingo Hatakeyama, Masahiro Takahashi, Shintaro Narita, Masanori Ishida, Senji Hoshi, Sadafumi Kawamura, Shigeto Ishidoya, Jiro Shimoda, Toshiaki Kawaguchi, Tatsuo Tochigi, Koji Mitsuzuka, Norihiko Tsuchiya, Yoichi Arai, Tomonori Habuchi, Chikara Ohyama
Journal: Journal of Clinical Oncology (2020)

213 Background: To evaluate the prognostic impact of time to castration resistance (TCR) in patients with metastatic hormone-naïve prostate cancer (mHNPC). Methods: We retrospectively evaluated 283 mHNPC patients with metastatic castration-resistant prostate cancer (mCRPC) who were initially treated with androgen deprivation therapy as metastatic hormone-naïve prostate cancer in 14 hospitals between September 2008 and October 2018. Overall survival (OS) and OS after castration resistance (OS-CR) were compared between the &lt;12 months (TCR &lt;12M) and ≥12 months (TCR ≥12M). The association between the first-line life-prolonging therapy (docetaxel or new androgen receptor-targeted agents: ART) and TCR on OS-CR was investigated using multivariate Cox regression analysis via inverse probability of treatment weighting (IPTW) model. Results: Median age and time to CRPC were 72 years and 12 months, respectively. The number of patients in the TCR&lt;12M and ≥12M groups were 137 and 146, respectively. Of 283, baseline parameters such as age, extent of disease (EOD), hemoglobin (Hgb), lactate dehydrogenase (LDH), and serum albumin levels were significantly differences in between the groups. We observed significantly poor OS and OS-CR in the TCR &lt;12M group than those in the TCR ≥12M group. First-line docetaxel therapy did not significantly improved OS-CR regardless of TCR. Background (age, ECOG PS, GS, Hgb, tumor volume, serum data, and TCR)-adjusted multivariate Cox regression analyses showed that first-line docetaxel therapy was significantly associated with shorter OS-CR than first-line ART therapy in the TCR &lt;12M group. Conclusions: The prognostic impact of TCR on OS was significant. However, the association between the first-line life-prolonging therapy and TCR on OS need further study.
Trends and current spectrum of contact allergy in Central Europe: results of the Information Network of Departments of Dermatology (IVDK) 2007–2018*
Authors: W. Uter, O. Gefeller, V. Mahler, J. Geier
Journal: British Journal of Dermatology (2020)

Background Changing patterns of exposure lead to changes in the spectrum of contact allergy in the general population and in patients patch tested for suspected contact allergy. The main contact allergens (haptens) are assembled in the so-called 'baseline series'. Objectives To present the current spectrum of contact allergy to baseline series allergens, and its temporal development over the last 12 years, based on data collected by the 56 active departments of the trinational Information Network of Departments of Dermatology (IVDK). Methods Patch-test data, along with core demographic and clinical information, subdivided into 4-year periods for all patients patch tested with the baseline series in the IVDK, were analysed descriptively. Moreover, log-binomial regression analysis addressed temporal trends of specific contact allergies, adjusted for potentially confounding factors. Results Among the 125 436 patients tested with the German baseline series, the most common allergens were nickel (14·7%), fragrance mix I (8·1%), Myroxylon pereirae resin (7·5%) and cobalt (5·2%), with no conclusive trend. The rise and fall of contact allergy to methylchloroisothiazolinone/methylisothiazolinone (MI), following (self-) regulation in the European Union, reflected the MI contact allergy epidemic. Propolis showed a marked upward trend with a prevalence of 3·94% during the period 2015–2018. Conclusions Decreases in sensitization prevalence likely reflect reduced exposure, with some lag, as seen with hydroxyisohexyl 3-cyclohexene carboxaldehyde. If no (sufficient) decrease can be observed despite interventions, such as for nickel and chromium, affected subgroups should be identified and their causative exposures explored. Finally, increases such as that observed with propolis, certainly warrant targeted investigation of the exposures driving sensitization, and possibly intervention. What is already known about this topic? Contact allergy is prevalent in the general population. Surveillance based on clinical data offers timely information on trends concerning certain allergens or subgroups at risk. What does this study add? This analysis provides an update of the current contact allergy prevalence in Central Europe, including time trends. This study describes the demographic and clinical profile of patients tested from 2007 to 2018. This research identifies contact allergens that require (further) preventive efforts. Linked Comment: Schuttelaar. Br J Dermatol 2020; 183:800–801.
Phase II trial of a DNA vaccine encoding prostatic acid phosphatase (pTVG-HP) and nivolumab (Nivo) in patients (pts) with nonmetastatic, PSA-recurrent prostate cancer (PCa).
Authors: Hamid Emamekhoo, Christos Kyriakopoulos, Glenn Liu, Douglas G. McNeel
Journal: Journal of Clinical Oncology (2020)

TPS273 Background: Radical prostatectomy (RP) and radiation therapy (RT) are the gold standard, curative intent treatment for pts with presumed organ-confined PCa. However, about one third of these pts will have progressive or metastatic disease at 10 years (yr). Pts with PSA recurrence without radiographic evidence of metastatic (m) PCa (stage M0) will ultimately develop radiographically apparent mPCa within a median of 8 yr. Pts with rapid PSA doubling time (DT) have a markedly shorter time to mPCa and death. Utilizing an immunotherapeutic approach could utilize the sensitivity and specificity of the immune system to treat microscopic disease and potentially avoid or postpone androgen deprivation therapy (ADT) and its unwanted side effects. Methods: In this single arm, two-stage phase II trial, a total of 21-41 PCa pts with PSA only progression (4 rising PSA with final PSA ≥ 2 ng/mL) after initial RP for presumed organ-confined disease who have no radiographic evidence of mPCa in conventional imaging (CT and bone scan) will be enrolled. Pts with small cell or other variant PCa, or history of ADT other than concurrent with RT are excluded. All pts will be treated with pTVG-HP 100 μg intradermally (id) and Nivo 240 mg IV every (Q) 2 weeks (w) x6, and then pTVG-HP 100 μg id and Nivo 480 mg IV Q4w x9 beginning w12 on study. Pts with PSA on w4 &gt; PSA on day 1 will additionally receive rhGM-CSF 208 μg id, as a vaccine adjuvant, Q2w x4 beginning w4 on study. Pts will be treated until progression or up to a total of 1 yr. Response will be monitored by CT and bone scan Q6 months or as clinically indicated. Primary endpoints are safety and tolerability of this combination and PSA complete response rate (PSA &lt; 0.2 ng/mL). Key secondary endpoints are 2-yr metastasis-free survival, median radiographic progression-free survival, PSA response rate (≤50% of baseline), and changes in PSA DT. Elicited antigen-specific T-cell and/or IgG response and its correlation with PSA response will be explored. Bone mets not detected by conventional imaging and their association with response will be evaluated by Quantitative Total Bone Imaging (QTBI) by NaF PET/CT. Updated enrollment will be presented. Clinical trial information: NCT03600350.
New guidelines for the diagnosis of epidermolysis bullosa
Authors: C. Has, L. Liu, M.C. Bolling, A.V. Charlesworth, M. El Hachem, M.J. Escámez, I. Fuentes, S. Büchel, R. Hiremagalore, G. Pohla‐Gubo, P.C. Akker, K. Wertheim‐Tysarowska, G. Zambruno
Journal: British Journal of Dermatology (2020)

New guidelines for the diagnosis of epidermolysis bullosa SummaryEpidermolysis bullosa (EB) is a group of rare inherited disorders in which the skin is more fragile than usual, and outside forces like minor injury or rubbing cause blisters or ulcers that may be slow to heal and often leave scars.EB comprises four main types, with more than 30 subtypes.The diagnosis is based on clinical manifestations, meaning how it looks, mode of inheritance, level of skin splitting and the genetic defect.A group of experts from countries all over the world developed these guidelines on behalf of the charity DEBRA International, to provide information on the laboratory diagnosis of EB.Publications (i.e.scientific studies about EB that had been published in journals) were identified in public databases.Sixty-four papers were appraised, and their quality rated.Based on this, the authors recommend the following:• If EB is suspected, laboratory diagnosis is always required, after informed consent.If available and affordable, both genetic (DNA) testing and analysis of a skin sample (by a process called immunofluorescence) should be performed to allow complete diagnosis.However, this is not always possible.Prioritisation can shorten the time to diagnosis and save resources but requires expertise.For example, in a new-born, analysis of a skin sample should be the first diagnostic step since it delivers the results within a few days.In parallel, genetic testing should always be performed.If the EB type can be clinically recognized or the disease is mild, genetic testing by a process called next-generation sequencing is recommended, because no valuable information is expected by analysis of the skin. •If the genetic defect is detected in one affected person, parents and other family members can be tested for confirmation and genetic counselling. •If no genetic defect is detected, research methods must be employed, or the diagnosis reconsidered.Precise diagnosis of EB enables early prediction of the disease severity and its management, genetic counselling and prenatal diagnosis, and inclusion in therapy trials.This is a summary of the study: Clinical practice guidelines for laboratory diagnosis of epidermolysis bullosa
Efficacy and safety of lenvatinib in combination with everolimus in metastatic renal cell carcinoma resistant to antiangiogenic targeted therapy: Russian multicenter observational study ROSLERCM.
Authors: Maria Volkova, Ahmed Abdelgafur, Zurab Amoev, Magomed Aivazov, Ksenia Gennadievna Babina, Pavel S. Borisov, Irina Evstigneeva, Olga Igorevna Samuseva, Alexei Kalpynsky, Elena Karabina, Natalia Kirdakova, Evgeniya Kuzmina, Dilorom H. Latipova, Elena G. Ovchinnikova, Anna Sergeevna Olshanskaya, Svetlana Protsenko, Tatiana Semiglazova, Roman Smirnov, Evgeny Usynin, Irina Chernyakova
Journal: Journal of Clinical Oncology (2020)

644 Background: an assessment of efficacy and safety of lenvatinib in combination with everolimus in unselected patients with metastatic renal cell carcinoma (mRCC) progressed during or following ≥1 line of antiangiogenic targeted therapy. Methods: Russian multicenter observational study included 73 consecutive patients with morphologically verified mRCC progressed during or following ≥1 line of antiangiogenic targeted therapy, treated with lenvatinib (18 mg/d) and everolimus (5 mg/d) in 20 Russian centers. Median age of the patients was 59 (23-73) years, a male-to-female ratio - 3:1. Most common histological type of kidney cancer was clear-cell RCC (71 (95.8%)). More than 2 lines of previous treatment were administered in 45 (61.6%) cases. Most patients were diagnosed with multiple metastases (71 (97.3%)) in &gt;1 site (61 (83.6%)). Nephrectomy was performed in 87.7% (64/73) of cases. At the combined therapy start ECOG PS 2-4 was registered in 16 (20.5%), poor prognosis according to IMDC score – in 33 (45.2%) patients. Median follow-up was 9.7 (1-26) months. Results: objective response rate was 11% (8/73); tumor control was reached in 93.2% (68/73) of cases. Median objective response duration was 10.5 (4.3-16.8) months, tumor control duration – 10.0 (2.5-17.5) months. Median progression-free survival (PFS) achieved 16.9 (95% confidence intervals (CI): 12.1-20.6), overall survival (OS) – 20.8 (95% CI: 15.7-25.9) months. Any adverse events (AE) developed in 83.6% (61/73), AE grade 3-5 - in 23.3% (17/73) of cases. Most frequent AE grade 3-4 were diarrhea (10 (13.6%)) and arterial hypertension (6 (8.2%)). Unacceptable toxicity demanded treatment cancellation in 4.2% (3/73), therapy interruption – in 30.1% (22/73) and dose reduction – in 32.9% (24/73) of patients. Conclusions: unselected mRCC patients administered with combined targeted therapy in the real world practice were registered with lower objective response rate, similar survival and better tolerability comparing with population assigned for lenvatinib plus everolimus in the randomized phase II trial.
Clinicopathologic Features of Never-Smoking Women Lung Cancer (WLC): A Review from the Spanish World07 Database
Authors: J. De Castro, D. Isla Casado, M. Provencio Pulla, M. Majem Tarruella, N. Vinolas Segarra, E. Felip, A. Artal-Cortes, R. García-Campelo, M. Domine, P. Garrido Lopez
Journal: Annals of Oncology (2012)
A 6 bp deletion polymorphism in the 3’UTR of the human thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels
Authors: Michael V. Mandola, Jan Stoehlmacher, Wu Zhang, Susan Groshen, Mimi C. Yu, Syma Iqbal, Heinz-Josef Lenz, Robert D. Ladner
Journal: Cancer Research (2004)

4744  A 6 bp deletion polymorphism in the thymidylate synthase (TS) gene that is encoded into the 3’-untranslated region (3’UTR) of TS mRNA was investigated in order to determine its function. Insertion of the TS-3’UTR containing the +6 bp/1494 polymorphism into the luciferase 3’UTR resulted in a ∼35% decrease in luciferase activity, and a similar decrease in mRNA levels, compared to the empty pGL3-control vector. Insertion of the TS-3’UTR containing the –6 bp/1494 deletion polymorphism resulted in a ∼70% decrease in luciferase activity and a ∼60% decrease in mRNA levels compared to the empty pGL3-control vector, suggesting that the deletion polymorphism caused a decrease in mRNA stability. Moreover, the TS-3’UTR containing the –6 bp/1494 deletion polymorphism had a significantly higher rate of message degradation compared to the +6 bp/1494 construct. Measurement of intratumoral TS mRNA levels demonstrated that individuals homozygous for the insertion (+6 bp/+6 bp) polymorphism had significantly higher intratumoral TS mRNA levels compared to individuals that were homozygous for the deletion (-6 bp/-6 bp) polymorphism (p
Protein velocity and acceleration from single-cell multiomics experiments
Authors: Gennady Gorin, Valentine Svensson, Lior Pachter
Journal: Genome biology (2020)

Abstract The simultaneous quantification of protein and RNA makes possible the inference of past, present, and future cell states from single experimental snapshots. To enable such temporal analysis from multimodal single-cell experiments, we introduce an extension of the RNA velocity method that leverages estimates of unprocessed transcript and protein abundances to extrapolate cell states. We apply the model to six datasets and demonstrate consistency among cell landscapes and phase portraits. The analysis software is available as the protaccel Python package.
Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial
Authors: Richard T. Penson, Ricardo Villalobos Valencia, David Cibula, Nicoletta Colombo, Charles A. Leath, Mariusz Bidziński, Jae-Weon Kim, Joo Hyun Nam, Radoslaw Madry, Carlos Hernández, Paulo A.R. Mora, Sang Young Ryu, Tsveta Milenkova, Elizabeth S. Lowe, Laura Barker, Giovanni Scambia
Journal: Journal of Clinical Oncology (2020)

PURPOSE A phase II study (ClinicalTrials.gov identifier: NCT00628251 ) showed activity of olaparib capsules versus pegylated liposomal doxorubicin in patients with germline BRCA-mutated platinum-resistant or partially platinum-sensitive relapsed ovarian cancer. We conducted a phase III trial (SOLO3) of olaparib tablets versus nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy. PATIENTS AND METHODS In this randomized, open-label trial, patients were randomly assigned 2:1 to olaparib 300 mg twice a day or physician’s choice single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). The primary end point was objective response rate (ORR) in the measurable disease analysis set assessed by blinded independent central review (BICR). The key secondary end point was progression-free survival (PFS) assessed by BICR in the intent-to-treat population. RESULTS Of 266 randomly assigned patients, 178 were assigned to olaparib and 88 to chemotherapy. In patients with measurable disease (olaparib, n = 151; chemotherapy, n = 72), the BICR-assessed ORR was significantly higher with olaparib than with chemotherapy (72.2% v 51.4%; odds ratio [OR], 2.53 [95% CI, 1.40 to 4.58]; P = .002). In the subgroup who had received 2 prior lines of treatment, the ORR was 84.6% with olaparib and 61.5% with chemotherapy (OR, 3.44 [95% CI, 1.42 to 8.54]). BICR-assessed PFS also significantly favored olaparib versus chemotherapy (hazard ratio, 0.62 [95% CI, 0.43 to 0.91]; P = .013; median, 13.4 v 9.2 months). Adverse events were consistent with the established safety profiles of olaparib and chemotherapy. CONCLUSION Olaparib resulted in statistically significant and clinically relevant improvements in ORR and PFS compared with nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy.