tbuckley/cabot-search huggingface dataset:
Expression of CD44 and CD133 markers in regional metastases from breast cancer.
Authors: Aleksandr B. Sagakyants, Elena P. Ulianova, Elena Yu. Zlatnik, Inna A. Novikova, Oksana G. Shulgina, Nikolay S. Karnaukhov, Marina A. Kuznetsova, Inna R. Petriashvili, Yakha S. Gaysultanova, Liubov Yu Vladimirova, Iuliana S. Shatova, Larisa N. Vashchenko, Aleksandr E. Lisutin, Oleg I. Kit
Journal: Journal of Clinical Oncology (2020)

e13087 Background: High incidence and mortality of breast cancer (BC) require a constant search for the most informative and effective methods of diagnosis and treatment evaluation. The purpose of the study was to analyze phenotypic characteristics of cancer stem cells in tumor tissues and regional metastases of breast cancer (BC). Methods: The study included 20 BC patients with regional metastases (lymph nodes) aged 32-74 years, mean age 56.1±3.3 years. IHC analysis was performed on sections from paraffin blocks of tumors using monoclonal mouse antibodies to CD44 (156-3C11 Thermo Scientific) at a dilution of 1:2500 and polyclonal rabbit antibodies to CD133 (Cloud-Clone Corp.) at a dilution of 1:700 using the Thermo Scientific automated stainer. Membrane staining and staining intensity were evaluated: 0, 1+ weak, 2+ moderate, 3+ strong staining. CD44 expression was considered positive when staining was detected in more than 10% (cut-off) tumor cells. CD133 expression was considered positive when staining was detected in more than 5% (cut-off) of the tumor. Results: CD44 + expression was detected in 80% of breast tumor tissues (16 samples), while in 20% this marker was not determined. The average CD44 expression was 27.2±13.9%. The expression of CD44 in regional metastases (RM) from BC was 35% (from 0 to 30%), on average 17.0±6.8%. When distributed according to the χ2 criterion in the tumor and RM, an association between factorial and resultant signs was statistically significant (8.286, at p &lt; 0.004). CD133+ expression in tumor tissues was detected in 80%, with an average expression level of 56.0±14.6%, with a predominance of positive cytoplasmic staining in 60%. Determination of this marker in BC RM gave a positive result in 15% (3 samples), with expression fluctuations from 0 to 60%, the average level was 33.0±15.4%. When distributed according to the χ2 criterion in the tumor and RM, an association between factorial and resultant signs was statistically significant (16.942, at p &lt; 0.001). Conclusions: Determination of tumor cells with the stem phenotype directly in the tissue of primary BC tumors and in tissues of regional metastases demonstrated that the percentage of CD44+ and CD133+ cells in the primary BC tumor was higher.
Cost-effectiveness of novel antiandrogens (AAs) for treatment of nonmetastatic castrate-resistant prostate cancer (nmCRPC).
Authors: Irbaz Bin Riaz, Abdulaali Almutairi, Daenielle K. Lang, Noureen Asghar, Anum Riaz, Yuan Yao, Qurat Ul Ain Riaz Sipra, Alexander J. Ryu, Nimer S Alkhatib, Mok Oh, Ivo Abraham, M. Hassan Murad, Manish Kohli
Journal: Journal of Clinical Oncology (2020)

5583 Background: FDA has approved three novel AAs [Apalutamide(A), Darolutamide(D) and Enzalutamide(E)] in combination with Androgen deprivation therapy ( ADT) for treatment of (nmCRPC) patients (pts). We report the cost-effectiveness of these drugs from the US perspective to help facilitate the choice of these agents for clinical practice. Methods: A life time Markov state-transition model was constructed with three health states (Metastasis-Free Survival[MFS], Metastatic disease, and Death) to compare cost-effectiveness of AA therapies for treatment of nmCRPC based on US healthcare payer perspective. A network meta-analysis of MFS and OS was conducted due to the lack of head to head trials. An approximation of the original individual-level patient time-to-event data were derived from digitized Kaplan-Meier curves for OS and MFS. Weibull distributions was selected as the best fitted model fitted and extrapolated as per the NICE decision support unit recommendations. Medication costs were based on wholesale acquisition cost. Adverse event (AE) grades 3/4 management costs were incorporated in the model. Discount rate of 3% per year was applied to costs and effects. Life years (LYs) and quality adjusted life years (QALYs) for each treatment as well as the incremental cost effectiveness (ICER) and cost utility (ICUR) ratios were estimated. Base case analyses (BCA) and probabilistic sensitivity analyses (PSA) were estimated. Results: The table summarizes the results form BCA analyses. A+ADT offers best gain in LYs (8.37yrs) and QALYs (5.30 yrs) but at higher cost. Conclusions: Apalutamide was associated with gains in LYs and QALYs traded off with higher lifetime cost relative to other AA alternatives. ADT was associated with lower gains in LYs and QALYs traded off with lower lifetime cost relative to other alternatives. Based on a $150,000/QALY threshold pay off, A+ADT is likely more cost effective compared to E+ADT or ADT alone; while E+ ADT may be more cost effective compared to D+ ADT. [Table: see text]
Marker of lipid peroxidation TBARS predicts survival in patients with metastaticurothelial carcinoma (MUC).
Authors: Jan Slopovsky, Jarmila Kucharska, Jana Obertova, Michal Mego, Katarina Kalavska, Anna Gvozdjakova, Patrik Palacka
Journal: Journal of Clinical Oncology (2020)

e17023 Background: Oxidative stress plays a significant role in cancer development and progression. A marker of lipid peroxidation TBARS is upregulated in various diseases. The objective of this prospective study was to explore predictive and prognostic values of TBARS in MUC patients (pts.) before the first-line platinum-based chemotherapy. Methods: Seventy-two consecutive pts. (57 men) with MUC (58 bladder, 14 upper GU tract) were enrolled into this study. Performance status ECOG ≥ 2 had 11 pts., visceral metastases were present in 34 pts. Most common type of treatment regimen was gemcitabine and cisplatin (65 pts.), gemcitabine and carboplatin received 7 pts. Based upon TBARS mean of 6,06 μmol/L, pts. were dichotomized into low and high groups. Progression-free survival (PFS), overall survival (OS) and their 95% CI were estimated by Kaplan-Meier method and compared with log-rank test. Results: At median follow-up of 9.6 months, 65 pts. experienced progression and 64 pts. died. Pts. with low TBARS had significantly better survival opposed to pts. with high TBARS (HR 0.44, 95% CI 0.27-0.74; P = 0,0009 for OS and HR 0.51; 95% CI 0.31-0.84; P = 0,006 for PFS, respectively). Pts. with ECOG ≤ 1 had significantly better both, OS and PFS in comparison to pts. with ECOG &gt; 2. Conclusions: In this study, high plasma TBARS levels in patients with MUC before chemotherapy initiation were associated with poor survival. Therefore, this biomarker could be used for identification of patients with worse prognosis and could lead to better patient stratification and treatment decision making. The study was supported by VEGA 1/0614/12. Key Words: Metastatic Urothelial Carcinoma. Platinum-Based Chemotherapy. Lipid Peroxidation. TBARS. Survival.
Immune checkpoint inhibition-induced myocarditis in cancer patients: Proposal of a detection and management strategy.
Authors: Anjali Rao, Vlad Zaha, Bonnie Bermas, John Lohrey, Kevin Dale Courtney, Hans J. Hammers, David E. Gerber, Sonia Garg, Pradeep P Mammen
Journal: Journal of Clinical Oncology (2020)

e15116 Background: Monoclonal antibodies against the immune checkpoint inhibitors (ICI) programmed cell death protein-1 (PD-1), its ligand (PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4) have had a transformative effect on the field of oncology. Autoimmune myocarditis (AIM) is a rare but potentially severe complication associated with these medications, without specific management guidelines. The aim of this observational report is to present four cases of AIM following ICI and propose a detection and treatment strategy. Methods: Four patients who received anti-PD-1 or anti-PD-L1 immune checkpoint inhibitors (ICI) developed severe cardiac manifestations within two weeks to several months after initiation. Demographic, historical, laboratory, and imaging data were collected by retrospective chart review. Results: Manifestations included LV systolic dysfunction, ventricular arrhythmias, and elevated cardiac enzymes. Myocardial ischemia was ruled out by coronary catheterization. Abnormal myocardial tissue characteristics on CMRI and biopsy were used to establish the diagnosis of myocarditis. Patients had endocrine, rheumatologic and neurologic irAEs (Table) and were managed by a multi-disciplinary team including oncology, rheumatology and cardiology. Management included prompt administration of high-dose steroids with rapid taper. Steroid sparing and escalation therapies included mycophenolate mofetil, methotrexate, rituximab, abatacept (CTLA4 agonist), as well as plasma exchange. This combination of tiered therapies resulted in substantial improvement in AIM. Conclusions: Clinical improvements seen in these cases highlight potential key elements for controlling autoimmune myocarditis response to ICI. We propose rapid diagnosis including CMRI and biopsy and initiation of high dose prednisone. We also recommend prompt initiation of steroid sparing agent within one month of diagnosis. Importantly, these patients should be managed by a multi-disciplinary team. [Table: see text]
银屑病的识别与治疗
Authors: 陈周
Journal: BMJ (2010)

银屑病俗称牛皮癣,是常见的慢性复发性皮肤病,其发病机制主要与异常免疫相关.遗传因素和环境因素共同致病,遗传因素是基础,环境因素对遗传易感个体起触发作用.感染、精神紧张、居住潮湿、吸烟、饮酒、外伤等都是银屑病的危险因素。
Survey on the usage of antiasthmatic drugs in community hospitals in Shanghai
Authors: Xiaofen Ye, Zhigang Pan, Yingyun Cai, Lubiao Bu, Qianzhou Lü
Journal: BMJ (2015)

Objective
To observe the usage of antiasthmatic drugs and seek problems of following the guidelines of asthma and COPD prevention & treatment in community hospitals.


Methods
The prescribed quantity in 2013 of antiasthmatic drugs was recorded for 5 community hospitals in a district of Shanghai. Basing on the defined daily dose (DDD), the dosing frequency of drugs (DDDs) and the percentages of each category of drugs were calculated. Then comparisons were made with the data of a grade Ⅱ hospital and a grade Ⅲ hospital in the same district.


Results
Among three level hospitals, no significant difference existed in the percentages of oral antiasthmatic drugs. But the major category of oral drugs at grades Ⅱ-Ⅲ hospitals was leukotriene receptor antagonist whereas only oral theophylline and oral β2-receptor agonists were available at community hospitals. Among inhaled drugs, inhaled corticosteroids (ICS) dominated at grades Ⅱ-Ⅲ hospitals. But at community hospitals, inhaled short-acting beta-agonists (SABA) predominated. Among inhalants, dry powder inhaler (DPI) dominated at grades Ⅱ-Ⅲ hospitals and metered dose inhaler (MDI) at community hospitals.


Conclusions
The usage of antiasthmatics at community hospitals is not consistent with the guidelines. Optimizing drug purchasing at hospitals, strengthening continued medical education, modifying the medication concept of patients and boosting the production of domestic inhalants should be urgently undertaken.


Key words: 
Community health centers; Anti-asthmatic agents; Medication systems, hospital
Hcrn GU15-215: A phase II trial of atezolizumab (atezo) and bevacizumab (bev) in cisplatin-ineligible patients (pts) with advanced/unresectable urothelial cancer (UC).
Authors: Arjun Vasant Balar, Samuel Aaron Funt, Shilpa Gupta, Arkadiusz Z. Dudek, Alejandro Recio Boiles, Daniel A. Vaena, Deepak Kilari, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2020)

TPS5098 Background: Atezolizumab is a standard of care in selected cisplatin-ineligible pts with advanced UC. VEGF targeted therapies have activity in advanced UC and may lead to immune synergy when combined with anti-PD-1/L1 therapy. This phase II study is investigating the combination of bevacizumab and atezolizumab in untreated cisplatin-ineligible pts with advanced UC. Methods: HCRN GU15-215 (NCT03272217) is a phase 2, multicenter single arm trial to evaluate the efficacy and safety of atezolizumab and bevacizumab in pts with advanced UC. Cisplatin-ineligible pts (defined as any of estimated CrCl &lt; 60 cc/min, Grade ≥ 2 hearing loss or neuropathy, ECOG PS 2 or solitary kidney) with untreated, histologically confirmed locally advanced or metastatic UC irrespective of PD-L1 expression status and with sufficient pre-treatment tumor tissue available for biomarker analysis are eligible. Pts who have received perioperative chemotherapy are eligible, however prior treatment with a checkpoint inhibitor is excluded. Pts with NYHA Class II or greater heart failure, significant cerebrovascular or cardiac disease within 3 months, uncontrolled HTN, persistent gross hematuria, and GI obstruction or perforation within 6 months are excluded. 70 pts will receive treatment with atezolizumab 1200 mg IV plus bevacizumab 15 mg/kg IV every 21 days. All pts will undergo an on-treatment biopsy before cycle 2 if safe and feasible. Peripheral blood samples and stool samples will be collected before treatment and on-treatment for immune-relevant biomarker analyses. Cross-sectional imaging will be performed every 9 weeks on therapy for the first 12 months and then every 12 weeks thereafter to assess for response. Subjects will be eligible to continue treatment until RECIST v1.1 defined progression or unacceptable toxicity for up to 24 months. The primary endpoint is overall survival rate at 1 year and will be analyzed by the Kaplan Meier method. Key secondary endpoints include objective response rate, duration of response, disease control rate, progression-free survival and safety and toxicity as defined by CTCAE version 4.0. Clinical trial information: NCT03272217 .
IMMUNOSARC: a collaborative Spanish (GEIS) and Italian (ISG) sarcoma groups phase I/II trial of sunitinib and nivolumab in advanced soft tissue and bone sarcoma: Results from the phase II part, bone sarcoma cohort.
Authors: Emanuela Palmerini, Antonio Lopez-Pousa, Giovanni Grignani, Andres Redondo, Nadia Hindi, Silvia Stacchiotti, Ana Sebio, Jose A. Lopez-Martin, Claudia Maria Valverde Morales, Javier Martinez-Trufero, Antonio Gutierrez, Enrique de Alava, Lorenzo D'Ambrosio, Paola Collini, Piero Picci, Paolo Giovanni Casali, Javier Martin Broto
Journal: Journal of Clinical Oncology (2020)

11522 Background: Herein, we present the results of the cohort on advanced bone sarcoma patients of the phase II part of the IMMUNOSARC study (NCT03277924), a European multicentre phase I-II trial aimed at investigating the activity of the combination of sunitinib (SU) and nivolumab (NI) in selected advanced sarcoma subtypes. Methods: Adult, pre-treated, progressing patients, ECOG 0-1, with a diagnosis of osteosarcoma, high-grade bone sarcoma, Ewing sarcoma, chondrosarcoma or dedifferentiated chondrosarcoma were eligible. SU 37.5 mg/day as induction was given days 1-14 and then reduced to 25mg/day continuously. NI was administered at 3 mg/Kg every 2 weeks from week 3. SU-NI was maintained up to progression or intolerance. Primary end-point was progression-free survival rate (PFSR) at 6 months (H1: PFSR 6-months: 15%). Secondary end-points: overall survival (OS), objective response rate (ORR) by RECIST v 1.1 and toxicity. Results: From Nov 2017 to Dec 2018, 40 eligible patients were included: (M/F = 27/13), median age 47 years (range 21-74), ECOG 0 in 11 (27%) cases, 36 (90%) were metastatic, 4 (10%) locally advanced. Histology: 17 osteosarcomas (43%), 14 chondrosarcomas (35%) (4 dedifferentiated), 8 Ewing sarcomas (20%), 1 bone undifferentiated pleomorphic sarcoma (2%). PFSR at 6 months based on local evaluation was 32%. At a median FU of 12.5 months (2-26), median PFS was 3.7 months (95% IC 3.4-4) while median OS was 14.2 months (95%CI: 7.1-21.3). OS rate at 3 and 6 months were 87% and 73%, respectively. ORR by RECIST: 1 CR (2.5%) (1 patient with dedifferentiated chondrosarcoma, lasting 22 months and on going), 1 PR (2.5%) (1 patient with osteosarcoma, lasting 5.7 months), 22 SD (55%, lasting &gt; 6 months in 45% of the cases) and 16 PD (40%). G3/5 toxicities are detailed in Table. Conclusions: The trial met its primary endpoint in the cohort of patients with advanced bone sarcoma, with &gt; 30% of patients free from progression at 6 months. Pre-planned tumor microenvironment genomic, exploratory analysis on pre and post-treatment tumor samples is on going. Clinical trial information: NCT03277924 . [Table: see text]
Phase II study of olaparib in malignant mesothelioma (MM) to correlate efficacy with germline and somatic mutations in DNA repair genes.
Authors: Raffit Hassan, Idrees Mian, Cathy Wagner, Yvonne Mallory, Maria Agra, Emerson Padiernos, Manjistha Sengupta, Betsy Morrow, Jun S. Wei, Anish Thomas, Seth M. Steinberg, Javed Khan, Azam Ghafoor
Journal: Journal of Clinical Oncology (2020)

9054 Background: BRCA1 associated protein 1 ( BAP1), a nuclear deubiquitinase involved in DNA double-strand break repair is frequently mutated in MM. Because poly(ADP-ribose) polymerase inhibitors (PARPIs) induce synthetic lethality in BRCA1/2 mutant cancers, we sought to evaluate efficacy of olaparib in patients with MM and correlate it with pathogenic germline and somatic mutations in DNA repair genes. Methods: Phase II single-center study (NCT03531840) enrolled patients with advanced pleural or peritoneal mesothelioma who had progressed on prior therapies, age &gt;18 years, ECOG performance status &lt;1, adequate organ and bone marrow function. Olaparib 300mg was given twice daily orally in 3 week cycles until disease progression or toxicity. Efficacy was assessed by CT scan every 6 weeks using RECIST criteria. Whole exome sequencing (WES) was performed on blood and tumor samples to identify pathogenic germline and somatic mutations in DNA repair genes. Primary objective was to determine response rate based on germline or somatic mutation status of DNA repair genes. Results: Between July 2018 to May 2019, 23 patients were enrolled, 15 pleural and 8 peritoneal MM [14 male; median age 63 (range 41-75 years); median number of prior treatments 3 (range 1-5)]. Median olaparib cycles received was 4 (2-21). WES to identify pathogenic mutations in the germline and tumor was performed in 23 and 17 patients respectively. Four patients had germline BAP1, 1 germline MRE11A, and 5 had somatic BAP1 mutations. Of 22 evaluable patients, 1(4%) had partial response (PR), 17 (77%) had stable disease at 6 weeks and 4 (18%) had progressive disease. Patient with PR had a germline mutation in MRE11A. Median progression free survival (PFS) and overall survival (OS) for all patients was 3.4 months (95% CI: 2.7 – 4.8 months) and 8.1 months (95% CI: 4.5 months – not estimable) respectively. Median PFS of germline BAP1 mutant patients (n = 4) was 2.3 months (95% CI: 1.3 – 3.6 months) compared to 4.1 months (95% CI: 2.7 – 5.5 months) for BAP1wild type patients (n = 18;P = 0.026). Median OS was 4.6 months (95% CI: 3.1 – 4.9 months) for patients with germline BAP1 mutation versus not reached for those without germline BAP1 mutation (P = 0.0058). The most common side effects of olaparib were anemia (16%), lymphopenia (24%), nausea (14%), and increased creatinine (9%). Conclusions: Olaparib has limited anti-tumor activity in previously treated MM patients including those with germline or somatic BAP1 mutations. Presence of germline BAP1 mutations was associated with decreased PFS and OS. Clinical trial information: NCT03531840.
Does neoadjuvant FOLFOX chemotherapy improve the oncological prognosis of high-risk stage II and III colon cancers ? Three years’ follow-up results of the Prodige 22 phase II randomized multicenter trial.
Authors: Medhi Karoui, Claire Gallois, Guillaume Piessen, Jean-Louis Legoux, Emilie Barbier, Cecile De Chaisemartin, Cedric Lecaille, Olivier Bouché, Hanifa Ammarguellat, Francesco Brunetti, Michel Prudhomme, Jean-Marc Regimbeau, Olivier Glehen, Astrid Lièvre, Guillaume Portier, Johannes Hartwig, Gael Goujon, Benoît Romain, Come Lepage, Julien Taieb
Journal: Journal of Clinical Oncology (2020)

4110 Background: Neoadjuvant chemotherapy in a perioperative setting has proven valuable in locally advanced resectable colon cancer (CC) in terms of toxicity, postoperative morbidity and downstaging, but its effect on oncological outcomes remains uncertain. Methods: Prodige 22 was a randomized multicenter phase II trial in patients with resectable high-risk T3, T4 and/or N2 CC on baseline CT-scan. Patients were randomized to receive either 6 months of adjuvant FOLFOX after colectomy (control) or perioperative FOLFOX for 4 cycles before surgery and 8 cycles after (FOLFOX peri-op). In RAS wild-type (wt) patients a third arm testing perioperative FOLFOX-cetuximab was added. Primary endpoint was the Tumor Regression Grade. Secondary endpoints were 3-years overall (OS), disease-free survival (DFS) and time to recurrence (TTR). Results: 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped for futility. The remaining 104 patients (control, n = 52; FOLFOX peri-op n = 52) represented our intention-to-treat population. In the FOLFOX peri-op group, 96% received the schedule 4 cycles prior to surgery and all but one underwent adjuvant FOLFOX for a total of 12 cycles. In the control arm, 38 patients received adjuvant FOLFOX (1 postoperative death and 13 low-risk stage II patients). Median follow-up was 54.3 months [48.5-57.2]. Nineteen deaths and 26 disease recurrences were observed leading to a 3 years-OS of 90.3% in both arms (p = 0.7) and to a 3-years DFS of 76.8% and 69.2% in the peri-op and control arm respectively (p = 0.6). A trend to a better TTR in the peri-op arm was observed with a 3-years TTR of 82% as compared to 72% in the control arm (p = 0.3). No benefit from adding Cetuximab was observed in the 16 RAS-wt treated patients. Conclusions: In this pilot randomized study, perioperative FOLFOX chemotherapy has no detrimental effect on long term oncological outcomes and may be an option for some patients with locally advanced CC. A pooled analysis of randomized trials testing peri-operative strategies in this setting is warranted. Clinical trial information: NCT01675999 .