tbuckley/cabot-search huggingface dataset:
Frontline treatment with the combination obinutuzumab ± chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group
Authors: Yair Herishanu, Adir Shaulov, Riva Fineman, Sandra Bašić‐Kinda, Ariel Aviv, Ewa Wasik‐Szczepanek, Ozren Jaksic, Mihnea Zdrenghea, Uri Greenbaum, Inga Mandac, Martin Simkovic, Marta Morawska, Ohad Benjamini, Martin Spacek, Anatoly Nemets, Osnat Bairey, Livio Trentin, Rosa Ruchlemer, Luca Laurenti, Oana Stanca Ciocan, Michael Doubek, Lev Shvidel, Nagib Dali, Fátima Mirás, Anne De Meûter, Maria Dimou, Francesca R. Mauro, Marta Coscia, Horia Bumbea, Róbert Szász, Tamar Tadmor, Odit Gutwein, Massimo Gentile, Lydia Scarfò, Alessandra Tedeschi, Paolo Sportoletti, Eva Gimeno Vázquez, Juan Marquet, Sarit Assouline, Maria Papaioannou, Andrei Braester, Luciano Levato, Michael Gregor, Gian M. Rigolin, Javier Loscertales, Angeles Medina Perez, Marten R. Nijziel, Viola M. Popov, Rosa Collado, Irma Slavutsky, Gilad Itchaki, Shimrit Ringelstein, Neta Goldschmidt, Chava Perry, Shai Levi, Aaron Polliack, Paolo Ghia
Journal: American Journal of Hematology (2020)

In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O ± Clb in unfit patients with CLL, in a "real-world" setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a "real-world" setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease.
Double SVCの患者にペースメーカー植え込み術を行った1例 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: 竹中創, 藤井理樹, 光藤和明, 井上勝美, 後藤剛, 門田一繁, 加藤晴美, 山本浩之, 福康志, 廣野明寿, 田中裕之, 田場正直, 池田篤史, 前川潤平, 前川祐子, 羽原誠二, 中村幸伸, 宮地剛, 山田千夏, 岡本陽地, 大鶴優
Journal: Circulation (2006)
CLINICAL ACCURACY OF ACOUSTIC RHINOMETRY AND SYMPTOMS SCORE TO DETECT ALLERGIC REACTIVITY IN NASAL ALLERGEN CHALLENGE
Authors: Almudena Testera-Montes, MarÃa Salas, Ibon Eguiluz-Gracia, Francisca Gomez Perez, Ana Prieto del Prado, Maria Auxiliadora Guerrero, Carmen Rondon Segovia
Journal: Journal of Allergy and Clinical Immunology (2020)
Evaluation of 124I-JS001 for hPD1 immuno-PET imaging using sarcoma cell homografts in humanized mice
Authors: Haifeng Huang, Hua Zhu, Quan Xie, Xiaobin Tian, Xianteng Yang, Fan Feng, Qiyu Jiang, Xinan Sheng, Zhi Yang
Journal: Acta Pharmaceutica Sinica B (2020)

JS001 (toripalimab) is a humanized IgG monoclonal antibody which strongly inhibits programmed cell death protein 1 (PD1). In this study, we used a different iodine isotype (nat/124/125I) to label JS001 probes to target the human PD1 (hPD1) antigen. In vitro, the half maximal effective concentration (EC50) value of natI-JS001 did not significantly differ from that of JS001. The uptake of 125I-JS001 by activated T cells was 5.63 times higher than that by nonactivated T cells after 2 h of incubation. The binding affinity of 125I-JS001 to T cells of different lineages after phytohemagglutinin (PHA) stimulation reached 4.26 nmol/L. Humanized PD1 C57BL/6 mice bearing mouse sarcoma S180 cell tumors were validated for immuno-positron emission tomography (immuno-PET) imaging. Pathological staining was used to assess the expression of PD1 in tumor tissues. The homologous 124I-human IgG (124I-hIgG) group or blocking group was used as a control group. Immuno-PET imaging showed that the uptake in the tumor area of the 124I-JS001 group at different time points was significantly higher than that of the blocking group or the 124I-hIgG group in the humanized PD1 mouse model. Taken together, these results suggest that this radiotracer has potential for noninvasive monitoring and directing tumor-specific personalized immunotherapy in PD1-positive tumors.
Clinical presentation and outcomes of patients with testicular tumors in cryptorchid testis.
Authors: Amit Joshi, Vijai Simha, Kumar Prabhash, Vanita Noronha, Santosh Menon, Vedang Murthy, Ganesh Bakshi, Gagan Prakash, Archi Agrawal, Palak Popat, Nilesh Sable, Rahul Krishnatry
Journal: Journal of Clinical Oncology (2020)

428 Background: Undescended testis which occurs in 2-4% of all boys confers a natural risk for development of testicular cancer. Cryptorchidism accounts for 10% of all testicular germ cell tumours. The presentation, natural history and outcomes of testicular tumours occurring in cryptorchid testis has not been described in literature so far. Methods: Case records of patients enlisted in the prospectively maintained ‘ testicular cancer database’ at our tertiary cancer care hospital were retrospectively reviewed. Any patient who presented with testicular germ cell tumour with the testis being absent in the scrotum was considered as ‘undescended testis’. Results: From our database of 490 patients with testicular tumours presenting from the year 2014 -2018, 42 patients had testicular cancer in cryptorchid testis. The mean age was 32.9 years (Range:17-56). 24(57.14%) had seminoma and 18(42.86%) had non seminomatous tumors. Orchidopexy was done in 22(52.3%) patients at median age of 30 yrs (Range 2-33). 23 patients had prior undescended testis underwent high inguinal orchidectomy, 13 patients had testis located in pelvis and 6 patient had testis located in the upper abdomen. The average maximum size of tumours presenting with after orchidopexy was 7.34cm (4-10.5cm), in those presenting with pelvic tumours was 9.86cm (7-12.6cm) and in those with intraabdominal tumours was 14.3cm (9-20cm). The median follow-up for these patients was 36 months (3-64 months). There were 6 patients who relapsed after front line therapy whom 3 were salvaged with second line chemotherapy and 2 patients had residual disease at their last follow up. There was one death due to disseminated tumour with brain metastasis. The disease free survival for the whole cohort was 92.85%. Conclusions: The tumours developing in intraabdominal location of testis presented with a larger size and orchiopexy apart from its role in prevention of testicular cancer also helps in surveillance and early detection leading to effective treatment of these highly curable cancers. In the first of its series on testicular tumours in the cryptorchid, we show that they are also as curable as the germ cell tumours developing in the descended testis.
Safety, dose tolerance, pharmacokinetics, and pharmacodynamics of fosciclopirox (CPX-POM) in patients with advanced solid tumors.
Authors: Manish R. Patel, Susanna Varkey Ulahannan, Scott James Weir, Robyn Wood, Tammy Ham, Crista Casey, Greg Reed, Prasad Dandawate, Prabhu Ramamoorthy, Michael Jay Baltezor, Roy A. Jensen, Benjamin L. Woolbright, John Arthur Taylor, Shrikant Anant, Michael Dalton, Valentina Zhukova-Harrill, William McCulloch, Suzanne Fields Jones, Howard A. Burris, Gerald Steven Falchook
Journal: Journal of Clinical Oncology (2020)

518 Background: Fosciclopirox (CPX-POM) is being developed for the treatment of non-muscle invasive and muscle invasive bladder cancer. CPX-POM selectively delivers its active metabolite, ciclopirox (CPX), to the entire urinary tract following systemic administration. In a chemical carcinogen mouse model of bladder cancer, CPX-POM treatment resulted in significant decreases in bladder weight, migration to lower stage tumors, inhibition of cell proliferation as well as Notch 1 and Wnt signaling pathways. Methods: Study CPX-POM-001 (NCT03348514) is US multi-site, Phase I, open-label, dose escalation study characterizing the safety, dose tolerance, pharmacokinetics (PK) and pharmacodynamics of IV CPX-POM in advanced solid tumor patients. The PK of CPX-POM, CPX and ciclopirox glucuronide (CPX-G), were characterized in plasma and urine. Circulating biomarkers of Wnt and Notch, IL-6, IL-8 and VEGF were determined. Results: Nineteen patients were enrolled in the study. The starting dose of 30 mg/m 2 was administered once daily on Days 1-5 of each 21-day treatment cycle. Doses were escalated to 1200 mg/m 2 . The MTD was determined to be 900 mg/m 2 . Overall, the number of treatment-related AE's tended to increase in frequency with dose, nausea and vomiting being the most common. Grade 3 confusion was observed in the 1200 mg/m 2 cohort. Four AE's of Grade 1 confusion at 600 and 900 mg/m 2 . There was no evidence of QTc prolongation or other ECG abnormality. One patient in the 240 mg/m 2 dose cohort, with a diagnosis of indolent primary fallopian tube tumor, achieved a partial response per RECIST 1.1. Metabolism of CPX-POM was rapid and complete. The clearance of CPX was dose proportional and time-independent. At MTD, steady-state 24-hour urine CPX concentrations of 215 µM were achieved. Evidence of Notch and Wnt inhibition was observed. Conclusions: IV CPX-POM was well tolerated with treatment-related AEs primarily CNS-related. At MTD, systemic and urinary CPX exposures exceeding in vitro IC 50 values by several-fold. The 900 mg/m 2 dose is currently being evaluated in an expansion cohort study in cisplatin-ineligible muscle invasive bladder cancer patients scheduled for cystectomy. Clinical trial information: NCT03348514.
Oral Prophylaxis with Berotralstat (BCX7353) Reduces Use of Standard of Care (SOC) On-demand Medication in Patients with Hereditary Angioedema (HAE): APeX-2 Study Results
Authors: Jonathan Bernstein, Bruce Zuraw, Emel Aygoren-Pursun, Huamin Li, Paula Busse, Douglas Johnston, Marcus Maurer, William Lumry, Marc Riedl, Joshua Jacobs, Karl Sitz, Remi Gagnon, Desiree Clemons, Sylvia Dobo, Eniko Nagy, Sharon Murray, Philip Collis, William Sheridan, Aleena Banerji
Journal: Journal of Allergy and Clinical Immunology (2020)
Long-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1‒Positive, Advanced Non‒Small-Cell Lung Cancer in the KEYNOTE-010 Study
Authors: Roy S. Herbst, Edward B. Garon, Dong-Wan Kim, Byoung Chul Cho, Jose L. Perez-Gracia, Ji-Youn Han, Catherine Dubos Arvis, Margarita Majem, Martin D. Forster, Isabelle Monnet, Silvia Novello, Zsuzsanna Szalai, Matthew A. Gubens, Wu-Chou Su, Giovanni Luca Ceresoli, Ayman Samkari, Erin H. Jensen, Gregory M. Lubiniecki, Paul Baas
Journal: Journal of Clinical Oncology (2020)

PURPOSE In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in previously treated, programmed death-ligand 1 (PD-L1)‒expressing advanced non‒small-cell lung cancer (NSCLC) in patients with a tumor proportion score (TPS) ≥ 50% and ≥ 1%. We report KEYNOTE-010 long-term outcomes, including after 35 cycles/2 years or second-course pembrolizumab. METHODS Of 1,033 patients randomly assigned (intention to treat), 690 received up to 35 cycles/2 years of pembrolizumab 2 mg/kg (n = 344) or 10 mg/kg (n = 346) every 3 weeks, and 343 received docetaxel 75 mg/m 2 every 3 weeks. Eligible patients with disease progression after 35 cycles/2 years of pembrolizumab could receive second-course treatment (up to 17 cycles). Pembrolizumab doses were pooled because no between-dose difference was observed at primary analysis. RESULTS Pembrolizumab continued to improve OS over docetaxel in the PD-L1 TPS ≥ 50% and ≥ 1% groups (hazard ratio [HR], 0.53; 95% CI, 0.42 to 0.66; P &lt; .00001; and HR, 0.69; 95% CI, 0.60 to 0.80; P &lt; .00001, respectively) after a 42.6-month (range, 35.2-53.2 months) median follow-up. Estimated 36-month OS rates were 34.5% versus 12.7% and 22.9% versus 11.0%, respectively. Grade 3-5 treatment-related adverse events occurred in 16% versus 37% of patients, respectively. Seventy-nine of 690 patients completed 35 cycles/2 years of pembrolizumab; 12-month OS and progression-free survival rates after completing treatment were 98.7% (95% CI, 91.1% to 99.8%) and 72.5% (95% CI, 59.9% to 81.8%), respectively. Seventy-five patients (95%) had objective response (RECIST v1.1, blinded independent central review) and 48 (64%) had ongoing response. Grade 3-5 treatment-related adverse events occurred in 17.7% of patients. Fourteen patients received second-course pembrolizumab: 5 completed 17 cycles, 6 (43%) had partial response, and 5 (36%) had stable disease. CONCLUSION Pembrolizumab provided long-term OS benefit over docetaxel, with manageable safety, durable responses among patients receiving 2 years of treatment, and disease control with second-course treatment, further supporting pembrolizumab for previously treated, PD-L1‒expressing advanced NSCLC.
Availability of Fractional Exhaled Nitric Oxide (FeNO) and Eosinophil (EOS) Count Data Among Patients with Severe Asthma in Five European Countries
Authors: Siddhesh Kamat, Imène Gouia, Jingdong Chao, Mark Small, Asif Khan, James Siddall
Journal: Journal of Allergy and Clinical Immunology (2020)
Predicting Survival After Hepatocellular Carcinoma Resection Using Deep Learning on Histological Slides
Authors: Charlie Saillard, Benoit Schmauch, Oumeima Laifa, Matahi Moarii, Sylvain Toldo, Mikhail Zaslavskiy, Elodie Pronier, Alexis Laurent, Giuliana Amaddeo, Hélène Regnault, Daniele Sommacale, Marianne Ziol, Jean‐Michel Pawlotsky, Sébastien Mulé, Alain Luciani, Gilles Wainrib, Thomas Clozel, Pierre Courtiol, Julien Calderaro
Journal: Hepatology (2020)

Standardized and robust risk-stratification systems for patients with hepatocellular carcinoma (HCC) are required to improve therapeutic strategies and investigate the benefits of adjuvant systemic therapies after curative resection/ablation.In this study, we used two deep-learning algorithms based on whole-slide digitized histological slides (whole-slide imaging; WSI) to build models for predicting survival of patients with HCC treated by surgical resection. Two independent series were investigated: a discovery set (Henri Mondor Hospital, n = 194) used to develop our algorithms and an independent validation set (The Cancer Genome Atlas [TCGA], n = 328). WSIs were first divided into small squares ("tiles"), and features were extracted with a pretrained convolutional neural network (preprocessing step). The first deep-learning-based algorithm ("SCHMOWDER") uses an attention mechanism on tumoral areas annotated by a pathologist whereas the second ("CHOWDER") does not require human expertise. In the discovery set, c-indices for survival prediction of SCHMOWDER and CHOWDER reached 0.78 and 0.75, respectively. Both models outperformed a composite score incorporating all baseline variables associated with survival. Prognostic value of the models was further validated in the TCGA data set, and, as observed in the discovery series, both models had a higher discriminatory power than a score combining all baseline variables associated with survival. Pathological review showed that the tumoral areas most predictive of poor survival were characterized by vascular spaces, the macrotrabecular architectural pattern, and a lack of immune infiltration.This study shows that artificial intelligence can help refine the prediction of HCC prognosis. It highlights the importance of pathologist/machine interactions for the construction of deep-learning algorithms that benefit from expert knowledge and allow a biological understanding of their output.
What Dose of Epinephrine? Safety and Pharmacokinetics of 0.5mg versus 0.3mg Epinephrine by Autoinjector in Food-allergic Teenagers: a Randomized Cross-over Trial
Authors: Nandinee Patel, Emily Isaacs, Bettina Duca, Haadiya Mohammed, Nanthagopan Nagaratnam, Jackie Donovan, Paul Turner
Journal: Journal of Allergy and Clinical Immunology (2020)
Is bigger always better?
Authors: Joan B. Gornals
Journal: Endoscopy (2020)

In the management of symptomatic walled-off necrosis (WON), the available minimally therapeutic interventions include surgical, percutaneous, and endoscopic drainage. Nowadays, the endoscopic approach is considered the first-line treatment for WON owing to various advantages over surgical or percutaneous approaches, and recent trials have shown that endoscopic drainage offers better clinical outcomes, with improvement in quality of life, shorter hospital stays, and lower costs [1].
Phase I study of pasotuxizumab (AMG 212/BAY 2010112), a PSMA-targeting BiTE (Bispecific T-cell Engager) immune therapy for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Horst-Dieter Hummel, Peter Kufer, Carsten Grüllich, Barbara Deschler-Baier, Manik Chatterjee, Maria-Elisabeth Goebeler, Kurt Miller, Maria De Santis, Wolfgang C. Loidl, Andreas Buck, Sabine Wittemer-Rump, Goekben Koca, Oliver Boix, Wolf-Dietrich Doecke, Sabine Stienen, Cyrus Sayehli, Ralf C. Bargou
Journal: Journal of Clinical Oncology (2020)

124 Background: mCRPC has a poor prognosis and immunotherapies are largely ineffective. PSMA is a promising therapeutic target in mCRPC. Pasotuxizumab is a PSMA x CD3 BiTE immune therapy that mediates killing of tumor cells by T cells. Methods: NCT01723475 was a first-in-human, multicenter, dose-escalation study in patients (pts) with mCRPC refractory to standard therapy. Pts received continuous IV infusion of pasotuxizumab in cohorts of 3–4 pts. Dose-escalation followed a continuous reassessment methodology. The primary objective was to determine safety and maximum tolerated dose (MTD); secondary objectives included pharmacokinetics, biomarkers, and tumor response. Results: 16 pts were enrolled into 5 dosing cohorts (5 µg/d, n=3; 10 µg/d, n=4; 20 µg/d, n=3; 40 µg/d, n=4; 80 µg/d, n=2). All pts had ≥1 AE of any grade; most common were fever (94%), chills (69%), and fatigue (50%). 13 pts (81%) had ≥1 AE of grade ≥3; most common were decreased lymphocytes and infections (both 44%). No grade 5 AE occurred. A serious drug-related AE was reported for 1 pt (fatigue, 20 µg/d). No antidrug antibodies were observed. Recruitment was stopped before MTD was reached to allow initiation of a new study sponsored by Amgen. Antitumor activity as indicated by PSA serum level decline was dose dependent, with a mean best PSA change per dosing cohort vs baseline of +0.74% (5 µg/d), −17.9% (10 µg/d), −37.4% (20 µg/d), −42.5% (40 µg/d) and −54.9% (80 µg/d). PSA decreases ≥50% occurred in 3 pts (n=1 each in 20 µg/d, 40 µg/d, 80 µg/d cohorts). One long-term PSA responder was treated for 14 months (40 µg/d) and one for 19.4 months (80 µg/d). The latter pt showed a complete regression of soft-tissue metastases and marked regression of bone metastases by PSMA-PET/CT, &gt;90% reduction in PSA and alkaline phosphatase, and a significant and durable improvement in disease related symptoms. Conclusions: Pasotuxizumab had an acceptable safety profile and dose-dependent clinical activity in mCRPC pts. There were two long term responders in the dose escalation. This is the first clinical study showing that a BiTE immune therapy can be efficacious in solid tumors. Clinical trial information: NCT01723475.
Validation and implementation of a mobile app decision support system for quality assurance of tumor boards: Analyzing the concordance rates for testis cancer at a multidisciplinary tumor board of a tertiary referral center.
Authors: Yasemin Ural, Axel Heidenreich, Thomas Elter, Yasemin Yilmaz, David A. Pfister
Journal: Journal of Clinical Oncology (2020)

399 Background: Guideline-compliance in the management of GCT is suboptimal concerning and it results in significantly impaired long-term survival. To facilitating guideline concordant decisions even in less experienced MTD, we developed an algorithm-driven and validated mobile App to provide evidence-based recommendations. This App contains latest guideline versions and it is continuously updated to include practice changing clinical trials. It is the purpose of this study to analyse treatment decision made by MTD compared to guideline recommended therapy. Methods: 302 patients with GCT and MTD decision were randomly selected from our database. Concordance rates of MTD recommendations were compared to query results of the digital APP “Easy Oncology” performed by 2 independent, blinded reviewers. Descriptive statistics and data analysis included IBM´s statistics software SPSS Version 25. Correlation analysis of cancer case characteristics was performed by Kendalls Tau, Gamma, Pearson and Spearman tests. Results: Median age was 35 (18-82) years. Clinical stages I, IIA-C, and III were identified in 32%, 37%, and 31%, resp. According to IGCCCG 56%, 18%, and 25% demonstrated good, intermediate, and poor prognosis, resp. 56% were non-seminomas and 44% were seminomas. 60%, 16%, and 7% of MTD decisions were related to 1st-line, 2nd, and 3rd line therapy and 18% dealt with follow up. Overall concordance rate was 99% (301/302). Concordance rates in CS I, IIA-C, and III were 100%, 98% and 99%, resp. Concordance rates with regard to 1st, 2nd and 3rd line therapy were 99% (135/136), 100%, and 88% (13/14). Conclusions: Our validated expert-created mobile decision support system demonstrates easy and reliable application in daily routine in an expert tertiary referral centre. The APP relies on guideline and trial based information and avoids MTD decisions by expert opinions. It might improve the MTD decision in less experienced MTDs which is currently evaluated in a prospective study.