tbuckley/cabot-search huggingface dataset:
MECPAT: A critical appraisal tool for assessing molecular epidemiologic studies of cancer prognosis
Authors: Jessica Hopkins, David Cescon, Darren Tse, Penny Bradbury, Wei Xu, Clement Ma, Paul Wheatley-Price, John Waldron, David Goldstein, Francois Meyer, Isabelle Bairati, Geoffrey Liu
Journal: Cancer Research (2008)

3866  Background: There is growing interest in evaluating the role of genetic polymorphisms in the prognosis and survival of cancer patients (molecular epidemiology of cancer prognosis). There have been several recent reviews and consensus statements providing lists of criteria for assessing the quality of such analyses. The standard criteria used by epidemiologists for risk studies are not synonymous with these polymorphism-outcomes criteria. Our goal was to develop a practical tool based on these criteria that could be used by both clinicians and epidemiologists to critically appraise the literature in this rapidly expanding field. We applied the tool when reviewing the literature of two different cancer sites, obtaining expert opinion along the way to modify and refine the tool.  Method: We first collated criteria from published sources commenting on how to assess the quality of molecular epidemiologic (prognosis) studies. Using well-known critical appraisal tools in other topics as a guide, we developed a prototype tool. We applied our prototype first to the head and neck cancer literature, and compared our results to expert assessments. After refining the tool, we then applied the more refined version of the tool, known as MECPAT v1.0 (Molecular Epidemiologic Cancer Prognosis Appraisal Tool) to the head and neck cancer literature, and separately to the esophageal cancer polymorphism-outcomes literature. Three users with differing levels of molecular epidemiologic and clinical backgrounds used the tools and provided feedback on its utility. Further, we also assessed the utility of using MECPAT in assessing two grant proposals in development.  Results: In both head and neck and esophageal cancers, heterogeneity or lack of detail in describing study populations (65%), lack of adjustment for important known disease prognostic factors (44%), and lack of accounting for multiple comparisons (88%) were cited as consistent and common deficiencies in published articles. Most studies were exploratory analyses rather than validation or replication studies. Our tool was effective in identifying areas for improvement in study design and reporting. MECPAT was felt by users to be relatively easy to learn, easy to apply, and helpful in focusing on important elements of each polymorphism-outcomes study. It was also judged to be useful in developing and reviewing new study proposals.  Conclusions: The majority of studies we assessed in these two sites had deficiencies in study design, analysis, or result reporting. Applying MECPAT highlighted the areas requiring improvement. MECPAT may be helpful to researchers and reviewers in assessing molecular epidemiologic prognosis studies.
Preoperative differentiation of chromophobe renal cell carcinoma from oncocytoma: Aorta-lesion-attenuation difference on multiphasic multidetector computed tomography.
Authors: Melina Hosseiny, Justin Ching, Soheil Kooraki, Steven Raman
Journal: Journal of Clinical Oncology (2020)

627 Background: Differentiation of benign oncocytoma from chromophobe renal cell carcinoma (chRCC) remains a challenge. This study aimed to investigate whether Aorta-lesion-attenuation difference (ALAD) on multiphasic multidetector CT scan (MDCT) can aid to distinguish oncocytoma from chRCC. Methods: This IRB-approved, HIPAA-compliant study consisted MDCT of 111 patients with pathologically proven chRCC (N: 37) or oncocytoma (N: 74). Regions of interest (ROIs) were placed over the renal mass and Aorta on the same axial MDCT slice of un-enhanced (UE), corticomedullary (CM), nephrographic (NP) and excretory (EX) phases. ROIs were devoid of calcification, necrosis and hemorrhage in lesion or atherosclerotic plaque in Aorta. The difference between Aorta and renal mass Hounsfield unit was calculated in all available phases. SPSS v.18 was used to draw receiver-operating characteristic (ROC) curve to calculate accuracy and optimal cutoff values for differentiation of chRCC from oncocytoma. Results: Mean ALAD was significantly higher in chRCC compared to oncocytoma in CM(P: 0.04), NP (P&lt;0.01) and EX (P&lt;0.01) phases. The area under the curves for ALAD in UE, CM, NP and EX phases were 0.47 (95% CI: 0.36- 0.59, p: 0.68), 0.64 (95% CI: 0.51-0.77, p: 0.03), 0.87 (95% CI: 0.79- 0.95, p&lt; 0.01) and 0.80 (0.70-0.90, P&lt;0.001), respectively. ALAD threshold of 19 in nephrographic phase had sensitivity and specificity of 79% and 78%, respectively, for differentiation of chRCC from oncocytoma. Conclusions: ALAD measured in the nephrogenic phase showed the highest accuracy for differentiation of chRCC from oncocytoma on multidetector CT scan. If validated prospectively, ALAD may act as a useful imaging biomarker to distinguish chRCC from oncocytoma.
Combined preclosure technique and traction method facilitating endoscopic full-thickness resection of a gastric fundal gastrointestinal stromal tumor
Authors: Xiao-gang Liu, Zi-yang Chen, Yun-chao Yang, Ren-yi Zhang, Wei-hui Liu
Journal: Endoscopy (2020)

We describe the case of a 47-year-old man with a gastric fundal mass found on upper gastrointestinal endoscopy ([Fig. 1 a]). Endosonography showed a 2.5-cm subepithelial mass originating from the muscularis propria, without lymph node involvement ([Fig. 1 b]). A diagnosis of a gastrointestinal stromal tumor (GIST) was made by fine-needle biopsy, and the patient was referred for endoscopic full-thickness resection (EFTR) of the mass.
Analysis of small non-coding RNAs in urinary exosomes to classify prostate cancer into low-grade (GG1) and higher-grade (GG2-5).
Authors: Laurence Klotz, Derya Tilki, Neil Eric Fleshner, Albert Gregory DiRienzo, Wei-Lin Winnie Wang, Martin Tenniswood
Journal: Journal of Clinical Oncology (2020)

277 Background: To develop a new predictive test for prostate cancer, based on the interrogation of small non-coding RNAs (sncRNA) isolated from urinary exosomes. We report the development and performance of the miR Sentinel PCa Test, that distinguishes patients with prostate cancer from those with no evidence of prostate cancer (NEPC) and the miR Sentinel CS Test, that distinguishes low grade from higher grade disease. Methods: Affymetrix miR 4.0 arrays were used to identify informative sncRNAs isolated from urinary exosomes. sncRNA from 233 subjects undergoing a prostate biopsy [89 men with benign biopsies, 88 with grade group 1 (GG1) cancer and 56 patients with grade group 2-5 (GG2-5)] were interrogated on these arrays. A custom OpenArray platform was designed to interrogate the 280 most informative sncRNAs, identified using a data-driven selection algorithm. The platform was designed to categorize patients as either no cancer or cancer using the miR Sentinel PCa Test, and subclassify the patients with cancer into GG1 or GG2-5 cancer using the miR Sentinel CS Test. The performance of the miR Sentinel PCa and CS Tests was validated in an independent cohort. Results: In 233 men, theSentinel PCa Test correctly classified 89/89 subjects with no cancer and 144/144 with cancer. The Sentinel CS Test correctly identified 55/56 patients with GG2-5 and 87/88 patients with GG1. Sensitivity was 98%, Specificity 98%, NPV 98% and PPV 93%. For validation, a prospective observational study of 329 subjects (NEPC = 139; GG1= 88; GG2-5 = 102) with elevated PSA correctly classified 134/139 as no cancer [Sensitivity 98% (195/199); Specificity 96% (134/139), PPV 98% and NPV 97%]. The Sentinel CS Test classified 87/88 as GG1 and 102/102 as GG2-5 [Sensitivity 100% (102/102), Specificity 99% (87/88), PPV 99%, and NPV=100%]. Conclusions: Initial evaluation of the miR Sentinel PCa and CS Tests demonstrated the high precision of these tests to detect prostate cancer and distinguish high grade (GG2-5) disease. Further validation is ongoing.[Table: see text]
Prefrontal Cortex Corticotropin-Releasing Factor Neurons Control Behavioral Style Selection under Challenging Situations
Authors: Peng Chen, Shihao Lou, Zhao-Huan Huang, Zhenni Wang, Qing-Hong Shan, Yu Wang, Yupeng Yang, Xiangning Li, Hui Gong, Yan Jin, Zhi Zhang, Jiang-Ning Zhou
Journal: Neuron (2020)
High-dimensional single cell-based immune profiling of the tumor immune microenvironment in prostate cancer.
Authors: Michela Masetti, Federica Portale, Roberta Carriero, Bianca Partini, Nicolò Morina, Andrea Ponzetta, Piergiuseppe Colombo, Maria Grazia Elefante, Alberto Saita, Giovanni Lughezzani, Nicolo' Buffi, Paolo Casale, Clelia Peano, Paolo Kunderfranco, Javier Cibella, Giorgio Ferruccio Guazzoni, Massimo Lazzeri, Diletta Di Mitri
Journal: Journal of Clinical Oncology (2020)

376 Background: Genetic lesions that drive prostate cancer (PCa) development are able to modify the immune response and tumor infiltrating immune subsets, resulting in tumor progression. We investigated the profile of the immune microenvironment in PCa by high dimensional single cell analysis. Methods: We conducted an immune profiling study based on integrated RNA single cell sequencing and multiparametric flow cytometry in order to dissect the immune landscape of PCa. CD45+ immune cells infiltrating tumoral and adjacent non tumoral tissues were isolated from patients with PCa who underwent software assisted fusion biopsy, based on MRI, and/or radical prostatectomy, and analyzed by single cell sequencing. The primary endpoint was to evaluate the effectiveness of single cell RNA sequencing on CD45+ cell sorted from tumoral and adjacent non-tumoral tissues. Secondary endpoint was the identification of tumor-driven immune changes in prostatic lesions. Results: The cohort consisted of 3 patients who underwent radical prostatectomy (RP) and 45 patients with positive prostate biopsy; the negative control was checked by pathological assessment. In patients who underwent RP the gene expression analysis identified a modulation in the abundance of several immune subsets infiltrating the tumoral tissue, when compared with the non tumoral, evident for Tumor associated macrophages (TAMs), Natural Killer cells (NK) and T regulatory cells. We then implemented a 22 parameters flow cytometry panel that we tested on fresh prostatic tissue and peripheral blood from positive PCa biopsies. We identified a subset of tumor infiltrating macrophages showing an altered gene expression profile when compared with macrophages infiltrating the non-tumoral tissue. Importantly we derived a genetic signature from this subset of tumoral TAMs that resulted to be associated with cancer progression. Conclusions: Our findings support the effectiveness of single cell RNA sequencing in the dissection of the immune landscape in PCa and identified immune changes in patients when comparing neoplastic tissue with non tumoral areas. Such data may be useful for understanding the role of immune system in PCa carcinogenesis.
Extension of bone marrow involvement and cytopenias in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Daniel D Almeida Preto, Marcella de Oliveira Gonçalves Prince Soares, Wilson Eduardo Furlan Matos Alves, Marcos Alves de Lima, Joao Antonio Junior Neif, Luis Eduardo Rosa Zucca, Flavio Mavignier Carcano
Journal: Journal of Clinical Oncology (2020)

222 Background: Most of bone metastatic castration-resistant prostate cancer (mCRPC) patients present variable extension of bone marrow involvement which in some cases may influence hematopoiesis. Cytopenias may hinder clinical practice, especially in decision making, regarding the use of myelotoxic drugs. The aim of this study was to assess whether the extension of bone marrow involvement in mCRPC patients is a prognostic factor for developing cytopenias. Methods: We retrospectively reviewed 1649 hemograms from 103 bone mCRPC cases. Patients were pooled in two groups, according to the extension of bone metastasis assessed by skeletal scintigraphy: ≤10 lesions (group A) and &gt;10 lesions or superscan (group B). Time for cytopenia event (event-free survival) and overall survival (time from first cytopenia event until death) were calculated using the Kaplan-Meier method and differences between survivals were tested using the log-rank test. Univariable analysis were performed to determine any significant prognostic factor. Results: The median event-free survival (EFS) was longer in patients with ≤10 bone lesions (group A) on the margin of significance (41.9 vs 23.6 months; p=0.051). The exploratory analyses for severe cytopenia events (grade 3-4) also showed a longer EFS for group A (51.8 vs 31.7 months; p=0.050). When group B was stratified into two subgroups (11-20 bone lesions vs &gt;20 or superscan), there was no significant difference in EFS (19.1 vs 24.2 months; p=0.14). The median overall survival (OS) was 3.3 (1.9-4.6) months, regardless the extension of bone involvement. Patients in the group with more bone lesions showed higher mean PSA levels (55.5 vs 40.3 ng/mL; p=0.01). ECOG, stage disease, Gleason score, visceral metastases, types of cytopenia event (anemia, neutropenia or thrombocytopenia), number of chemotherapy lines, and antialgic radiotherapy did not show difference between groups. Conclusions: The extension of bone metastasis in mCRPC seems to be a prognostic factor for developing cytopenias, but is not related to OS. Additional analyzes with a larger sample are needed to assess whether any clinical variables may be associated with cytopenia event.
Design and Conduct of Early Clinical Studies of Immunotherapy: Recommendations from the Task Force on Methodology for the Development of Innovative Cancer Therapies 2019 (MDICT)
Authors: Martin Smoragiewicz, Alex A. Adjei, Emiliano Calvo, Josep Tabernero, Aurélien Marabelle, Christophe Massard, Jun Tang, Elisabeth G.E. de Vries, Jean-Yves Douillard, Lesley Seymour
Journal: Clinical Cancer Research (2020)

To review key aspects of the design and conduct of early clinical trials (ECT) of immunotherapy agents.The Methodology for the Development of Innovative Cancer Therapies Task Force 2019 included experts from academia, nonprofit organizations, industry, and regulatory agencies. The review focus was on methodology for ECTs testing immune-oncology therapies (IO) used in combination with other IO or chemotherapy.Although early successes have been seen, the landscape continues to be very dynamic, and there are ongoing concerns regarding the capacity to test all new drugs and combinations in clinical trials.Optimization of drug development methodology is required, taking into account early, late, and lower grade intolerable toxicities, novel response patterns, as well as pharmacodynamic data.
Changes in Therapeutic Alliance and in Social Inhibition as Mediators of the Effect of the Cognitive Behavioral Analysis System of Psychotherapy: A Secondary Analysis from a Randomized Clinical Trial
Authors: Jan Philipp Klein, Thomas Probst, Levente Kriston, Nele Assmann, Josef Bailer, Hannah Eich, Ulrich Schweiger, Nikola Maria Stenzel, Katrin Wambach, Martin Hautzinger, Martin Härter, Elisabeth Schramm
Journal: Psychotherapy and Psychosomatics (2020)
Predicting radiation-induced immune trafficking and activation in localized prostate cancer.
Authors: Scott Williams, Simon P. Keam, Heloise Halse, Thu Nguyen, Catherine Mitchell, Franco Caramia, David Byrne, Sue Haupt, Georgina Ryland, Phillip K. Darcy, Shahneen Kaur Sandhu, Piers Blombery, Ygal Haupt, Paul J. Neeson
Journal: Journal of Clinical Oncology (2020)

340 Background: Prostate cancer is frequently cured with high-dose rate brachytherapy as a front-line treatment. However, a significant number unfortunately develop intrinsic resistance. Although considered to be an immune-excluded tissue, immune responses are implicated in driving tumour-eradication in prostate cancer. This has not been proven, and yet is used as the rationale for numerous clinical trials combining radiation and immunotherapies. We hypothesise that there is a predictable but differential relationship between radiation and the immune responses in prostate cancer that could be used to fulfil a clinical need - identifying patients that would benefit from immune intervention in conjunction with radiation. Methods: We present here the results of comprehensive immunological profiling of a cohort of world-unique pre- and post-radiation tissues from 24 patients (RadBank cohort). These were assessed using pathological classification, tissue segmentation (cancer/surrounding stroma), multiplex IHC, gene expression profiling, T-cell receptor sequencing, and spatial computational analysis. Results: Our data resolved three classes of prostate cancer tissue based on immune infiltrate level, immune-activation and -checkpoint gene signatures, spatial clustering and T cell clone sequencing: We have begun to resolve clear patient and clinical classifiers based on immune responses to radiation, and identified patients groups likely to benefit from immune therapy alongside radiation. Conclusions: Importantly, these classifications are associated with baseline gene expression profiles that may be used for pre-clinical stratification and more sophisticated treatment paradigms.
Case 7-2020: A 52-Year-Old Man with a Mass in the Left Breast
Authors: Steven J. Isakoff, Constance D. Lehman, Kristen M. Shannon, Kristen M. Basnet
Journal: New England Journal of Medicine (2020)

A 52-year-old man was referred to the hospital for management of a lump in the left breast. Mammography confirmed a round mass with irregular margins; ultrasonography of the left axilla revealed an abnormal lymph node. Biopsies showed intermediate-grade invasive ductal carcinoma and metastatic adenocarcinoma. Management decisions were made.
Efficiency in patch testing: the number needed to test to get one relevant result as a new approach in the evaluation of baseline series
Authors: J. García‐Gavín, P. Mercader, M.A. Descalzo, I. Garcia‐Doval, J.F. Silvestre, J. Sánchez‐Pérez, V. Fernández‐Redondo, J.C. Armario‐Hita, I. Ruiz‐González, A. Giménez Arnau
Journal: British Journal of Dermatology (2020)
Reply
Authors: Martin Aringer, Karen H. Costenbader, Thomas Dörner, Sindhu R. Johnson
Journal: Arthritis & Rheumatology (2020)

To the Editor: Dr. Weinstein expresses disappointment that the new European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for SLE do not include CB-CAPs. We find the concept of CB-CAPs interesting in that low complement proteins C3 and C4 can be masked, as they are part of the acute-phase response. We also appreciate that the cited work had prominent involvement of colleagues who also played an active role in the EULAR/ACR SLE classification project 1, 2. However, we do not share Dr. Weinstein's disappointment with the EULAR/ACR 2019 classification criteria and believe that it is due, in part, to misunderstanding of the criteria. Development of new classification criteria takes several years, is unidirectional, and is based on robust evidence. The expert Delphi exercise, which supported the primary choice of candidate criteria, was completed and presented in abstract form in 2017 and published in 2018 3. Therefore, 2 of the 3 CB-CAP studies cited by Dr. Weinstein 1, 2 could not have been taken into consideration. Complement fragments (elevated EC4d and BC4d levels) were considered 3 as were many other more novel laboratory parameters, but, as with these other assays, there was insufficient consensus in the expert Delphi exercise. Many laboratory parameters (including CB-CAPs and type I interferon signature) were not selected due to insufficient evidence or unavailability worldwide. This problem is not resolved for CB-CAPs, as of today. Inclusion, in classification criteria approved by EULAR and ACR, of a test that is not broadly available in clinical practice would limit access to scientific studies. This precludes inclusion of potentially interesting tests that have not been proven robust in independent patient cohorts and hence are not fully established for clinical use in different regions of the world. There is another distinction between diagnosis and classification that appears relevant regarding CB-CAPs. CB-CAP testing was apparently optimized for sensitivity, which at 61% is much higher than the sensitivity of low C4 or C3 levels (23%) 1. This is important in a diagnostic setting, where it is often relevant to exclude an SLE diagnosis. Classification, on the other hand, aims to positively define the disease with high specificity. Therefore, low C3 and C4 complement levels, with a higher specificity (98%) compared to CB-CAPs (86%) 1, are advantageous for classification. Whether the CB-CAP assay becomes available for routine clinical use worldwide and whether its specificity for SLE will be proven to be high remain to be seen, and we would welcome validated demonstrations of improved laboratory test characteristics.
30P Prognostic Impact of Basal, Mesenchymal and Stem Cell Markers in Breast Cancer
Authors: A. Zaczek, A. Markiewicz, T. Ahrends, P. Nowialis, B. Seroczynska, J. Skokowski, J. Szade, M. Welnicka-Jaskiewicz, P. Nastaly, N. Bednarz-Knoll
Journal: Annals of Oncology (2012)
A phase II study of lenvatinib plus everolimus in patients with advanced non-clear cell renal cell carcinoma (nccRCC).
Authors: Thomas E. Hutson, M Dror Michaelson, Timothy M. Kuzel, Neeraj Agarwal, Ana M. Molina, James J Hsieh, Ulka N. Vaishampayan, Sharon Xie, Urmi Bapat, Rohit K. Jain, Mayer N. Fishman
Journal: Journal of Clinical Oncology (2020)

685 Background: Non-clear cell renal cell carcinoma (nccRCC) is an umbrella term that encompasses multiple RCC histological subtypes, including papillary, chromophobe, and undetermined RCC. Both increased expression of the vascular endothelial growth factor (VEGF) and dysregulation of the mammalian target of rapamycin (mTOR) pathway occur in nccRCC. Lenvatinib (LEN) is a multitarget tyrosine kinase inhibitor that inhibits the VEGF receptor and other targets; everolimus (EVE) is a mTOR inhibitor. LEN + EVE is approved for the treatment of patients with advanced RCC following 1 prior antiangiogenic therapy. This phase 2 study examined the efficacy and tolerability of LEN + EVE in patients with nccRCC. Methods: This single-arm, multicenter, phase 2 trial assessed the safety and efficacy of LEN (18 mg once daily) + EVE (5 mg once daily) in patients with unresectable advanced or metastatic nccRCC who had not received any chemotherapy for advanced disease. The primary objective was objective response rate (ORR) as assessed by investigators using RECIST v1.1. Secondary objectives included progression-free survival (PFS), overall survival (OS), and safety assessments. Results: At the time of data cutoff (July 17, 2019), 31 patients with nccRCC (papillary, n = 20; chromophobe, n = 9; unclassified, n = 2) were enrolled and treated. The ORR was 25.8% (95% confidence interval [CI]: 11.9–44.6%); 8 patients achieved a partial response (PR; papillary, n = 3; chromophobe, n = 4; unclassified, n = 1) and no patients had a complete response (CR). The median duration of response was not reached. Additionally, 18 patients (58.1%) had stable disease (SD) and the clinical benefit rate (CR + PR + durable SD [duration ≥ 23 weeks]) was 61.3% (95% CI: 42.2–78.2%). The median PFS was 9.23 months (95% CI: 5.49- not estimable [NE]) and median OS was 15.64 months (95% CI: 9.23–NE). The safety profile observed in this study was similar to the established profile of the study drug combination (LEN + EVE). Conclusions: The combination of LEN + EVE showed promising antitumor activity as first-line therapy in patients with advanced nccRCC. The ORR was 25.8%, which compares favorably to historical reports with EVE monotherapy. Clinical trial information: NCT02915783.