tbuckley/cabot-search huggingface dataset:
Development and validation of circulating tumor cell (Epic Sciences) enumeration as a prognostic biomarker in men with metastatic castration-resistant prostate cancer.
Authors: Howard I. Scher, Andrew J. Armstrong, Joseph D. Schonhoft, Audrey Gill, Jimmy Zhao, Ethan Barnett, Emily Carbone, James Lu, Emmanuel S. Antonarakis, Jun Luo, Scott T. Tagawa, Qian Yang, Daniel J. George, Russell Zelig Szmulewitz, Daniel Costin Danila, Rick Wenstrup, Mithat Gonen, Susan Halabi
Journal: Journal of Clinical Oncology (2021)

157 Background: We evaluated the prognostic significance of circulating tumor cell (CTC) number as determined on the Epic Sciences platform in men with metastatic castration resistant prostate cancer (mCRPC) treated with an androgen receptor signaling inhibitor (ARSI). Methods: A pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a 1st, 2nd or 3rd line systemic therapy at Memorial Sloan Kettering Cancer Center (Discovery cohort, N=175) or as a 1st and 2nd line therapy as part of the multi-center PROPHECY trial (NCT02269982) (Validation cohort, N=107). Enumeration was performed on the Epic Sciences platform and associated with overall survival (OS) in the Discovery cohort, and progression-free survival (PFS) and OS in the Validation cohort. Matched blood samples from the Validation cohort were to CTC counts measured on the CellSearch Circulating Tumor Cell kit. Results: In the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous (&lt; 3 CTCs/mL versus ≥ 3 CTCs/mL; HR = 1.8, (1.3-3.0, 95% CI)) and as a continuous variable when adjusting for line of therapy, presence of visceral metastases, PSA, lactate-dehydrogenase, and alkaline-phosphatase. The findings were validated in an independent dataset (PROPHECY trial) - (HR (95% CI) = 1.8, (1.1-3.0) for OS and 1.7 (1.1-2.9), for PFS). A strong correlation was observed between CTC counts determined in matched samples on the CellSearch and Epic platforms (r = 0.84). Conclusions: The findings validate the prognostic significance of pretreatment CTC number determined on the Epic Sciences platform for predicting OS in men with progressing mCRPC starting an ARSI.
COVID‐19 pandemic and allergen immunotherapy—an EAACI survey
Authors: Oliver Pfaar, Ioana Agache, Matteo Bonini, Helen Annaruth Brough, Tomás Chivato, Stefano R. Del Giacco, Radoslaw Gawlik, Aslı Gelincik, Karin Hoffmann‐Sommergruber, Marek Jutel, Ludger Klimek, Edward F. Knol, Antti Lauerma, Markus Ollert, Liam O’Mahony, Charlotte G. Mortz, Oscar Palomares, Carmen Riggioni, Jürgen Schwarze, Isabel Skypala, María José Torres, Eva Untersmayr, Jolanta Walusiak‐Skorupa, Adam Chaker, Mattia Giovannini, Enrico Heffler, Erika Jensen‐Jarolim, Cristina Quecchia, Mónica Sandoval‐Ruballos, Umit Sahiner, Vesna Tomić Spirić, Montserrat Alvaro‐Lozano
Journal: Allergy (2021)

As in many fields of medical care, the coronavirus disease 2019 (COVID-19) resulted in an increased uncertainty regarding the safety of allergen immunotherapy (AIT). Therefore, the European Academy of Allergy and Clinical Immunology (EAACI) aimed to analyze the situation in different countries and to systematically collect all information available regarding tolerability and possible amendments in daily practice of sublingual AIT (SLIT), subcutaneous AIT (SCIT) for inhalant allergies and venom AIT.Under the framework of the EAACI, a panel of experts in the field of AIT coordinated by the Immunotherapy Interest Group set-up a web-based retrospective survey (SurveyMonkey® ) including 27 standardized questions on practical and safety aspects on AIT in worldwide clinical routine.417 respondents providing AIT to their patients in daily routine answered the survey. For patients (without any current symptoms to suspect COVID-19), 60% of the respondents informed of not having initiated SCIT (40% venom AIT, 35% SLIT) whereas for the maintenance phase of AIT, SCIT was performed by 75% of the respondents (74% venom AIT, 89% SLIT). No tolerability concern arises from this preliminary analysis. 16 physicians reported having performed AIT despite (early) symptoms of COVID-19 and/or a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).This first international retrospective survey in atopic diseases investigated practical aspects and tolerability of AIT during the COVID-19 pandemic and gave no concerns regarding reduced tolerability under real-life circumstances. However, the data indicate an undertreatment of AIT, which may be temporary, but could have a long-lasting negative impact on the clinical care of allergic patients.
Shorter Diagnosis-to-Treatment Interval in Diffuse Large B-Cell Lymphoma is Associated With Inferior Overall Survival in a Large, Population-Based Registry
Authors: Danielle N. Blunt, Liam Smyth, Chenthila Nagamuthu, Evgenia Gatov, Ruth Croxford, Lee Mozessohn, Matthew C. Cheung
Journal: Journal of the National Comprehensive Cancer Network (2021)

Background: Because of prolonged screening requirements, patient and time-dependent selection have been proposed as potential biases in clinical trials. The screening process may exclude patients with a need for emergent treatment (and a short period from diagnosis to treatment initiation [DTI]). We explored the impact of DTI on overall survival (OS) in a population-based cohort of patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods: Using population-based administrative databases in Ontario, Canada, we identified adults aged ≥18 years with DLBCL treated with rituximab-based chemotherapy for curative intent between January 2005 and December 2015. Cox regression and multivariable analyses were presented to evaluate the impact of time from DTI on OS, controlling for relevant covariates. Results: We identified 9,441 patients with DLBCL in Ontario; median age was 66 years, 53.6% were male, median number of comorbidities (Johns Hopkins aggregated diagnosis groups) was 10 (interquartile range [IQR], 8–13), and median DTI was 37 days (IQR, 22–61). Between treatment initiation and study end, 43% of patients died (median OS, 1 year; IQR, 0.4–2.8 years). Shorter DTI was a significant predictor of mortality ( P &lt;.001). Compared with the shortest DTI period of 0–18 days, those who commenced therapy at 19–29 days (hazard ratio [HR], 0.75; 95% CI, 0.68–0.84), 30–41 days (HR, 0.70; 95% CI, 0.63–0.78), 42–57 days (HR, 0.52; 95% CI, 0.46–0.58), and 58–180 days (HR, 0.52; 95% CI, 0.47–0.58) had improved survival. Increasing age (HR, 1.03; 95% CI, 1.03–1.04), male sex (HR, 1.23; 95% CI, 1.14–1.32), and increasing number of comorbidities (HR, 1.12; 95% CI, 1.11–1.13) were associated with inferior survival. Conclusions: Among patients with DLBCL, shorter DTI was associated with inferior OS. Therefore, DTI may represent a surrogate marker for aggressive biology. Clinical trials with lengthy screening periods are likely creating a time-dependent patient selection bias.
Letter to the Editor: Serum Albumin in COVID‐19: A Good Example in Which Analytical and Clinical Performance of a Laboratory Test Are Strictly Intertwined
Authors: Sara Pasqualetti, Elena Aloisio, Mauro Panteghini
Journal: Hepatology (2021)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with interest the paper by Hundt et al. describing the behavior of common liver tests in Coronavirus disease 2019 (COVID‐19) and their association with poor outcomes.(1) Among the presented data, we were surprised to see that serum albumin (ALB) concentrations during hospitalization did not significantly predict patient death at the multivariate analysis (MA), even if 86.6% of patients showed ALB values < 35 g/L (i.e., the lower reference limit). In a similar COVID‐19 population enrolled in our national reference center for infectious diseases, we recently analyzed a group of common biochemistry tests, including ALB, as major predictor of COVID‐19 severity.(2) Although the patient rate showing an ALB < 35 g/L was quite similar (89%) to that of Hundt et al.'s study, at MA, low ALB concentrations remained significantly associated (P = 0.003) with higher odds of death, ALB values ≤ 18 g/L giving a positive likelihood ratio of 12.2 for predicting in‐hospital death. In terms of absolute ALB levels in the respective populations, it is somewhat difficult to compare our results with those of Hundt et al., however, as the authors do not mention the methodology used to determine ALB in their hospital network. It is known that immunoturbidimetric assays for ALB determination, such as the one in use at our institution, are specific for the ALB measurement, contrary to nonspecific colorimetric methods, which are in use in most US health‐care institutions, also reacting with proteins other than ALB.(3) The well‐known lack of specificity of the latter methods, especially at low ALB and high globulin (including "acute phase reactants") concentrations (i.e., the typical COVID‐19 situation) may have influenced Hundt et al.'s results. Figure 1 depicts ALB distribution in our patients with COVID‐19, showing that even survivors displayed a median (interquartile range) of 28 g/L (25‐32), which is quite lower than patients with severe COVID‐19 enrolled by Hundt et al. Therefore, we cannot exclude that the inability of ALB to predict death in the Hundt et al. study was due to spuriously higher ALB values measured with nonspecific methods in the evaluated patients with COVID‐19. The accuracy of ALB methods may become critical in COVID‐19 cases, in which ALB is decreased but acute‐phase proteins are increased; thus, use of immunological assays should be preferred in this condition.(4)FIG. 1: Box and whisker plots showing the distribution of results of serum ALB in a cohort of 390 patients with COVID‐19, according to death during hospitalization (nonsurvivors) versus hospital discharge after clinical recovery (survivors). Adapted from Aloisio et al.( 2 )
Plasmacytoid urothelial carcinoma (UC) are luminal tumors with similar immune microenvironment as compared to conventional UC.
Authors: Myriam Kossai, Camélia Radulescu, Julien Adam, Anaïs Dziegielewski, Nicolas Signolle, Mathilde Sibony, Thierry Lebret, Yves Allory, Mathieu Rouanne
Journal: Journal of Clinical Oncology (2021)

477 Background:Plasmacytoid urothelial carcinoma (UC) is a rare pathological variant of UC with low chemotherapeutic sensitivity and dismal outcomes. The molecular and immune profiles of such tumors remain poorly investigated. Herein, we investigated the phenotypical features of a cohort of plasmacytoid UC (n = 32) by comparison to a control group of conventional high-grade UC with matched clinicopathological characteristics (n = 30). Methods: Histopathological analysis included the following antibodies: p63, GATA3, CK5/6, CK20 and HER2. In addition, the density of intra-tumor CD8 + lymphocytes, and PD-L1 expression in tumor (TC) and immune cells (IC) were evaluated. Clinical data were collected. Results: Plasmacytoid UC expressed GATA3 (97% vs 86% p = 0.18), CK20 (59% vs 36% p = 0.08) markers and showed a significantly higher rate of HER2 overexpression (2+ and 3+ score: 25% vs 0%, p &lt; 0.01) compared to controls. A significantly lower expression of CK5/6 (22% vs 56%, p &lt; 0.05) and p63 (41% vs 80%, p &lt; 0.05) was observed in plasmacytoid UC compared to controls. The density of tumor-infiltrating CD8+ cells was similar between plasmacytoid and conventional UC (p = 0.5). PD-L1 expression on IC was similar compared to conventional UC (p = 0.3). Overall survival at 5 years was significantly lower among patients with plasmacytoid UC compared to patients with conventional UC (p = 0.02). Conclusions: Together, our study demonstrated that plasmacytoid UC belong to the luminal subtype and display a rather inflamed microenvironment similar to conventional UC. These data support the inclusion of plasmacytoid variant of UC in clinical trials evaluating immune checkpoint inhibitors monotherapy or combination immunotherapeutic strategies.
Abstract IA-15: Platforms to improve reproducibility in artificial intelligence research
Authors: Benjamin Haibe-Kains, Anthony Mammoliti, Minoru Nakano
Journal: Clinical Cancer Research (2021)

Abstract As artificial intelligence (AI) becomes a method of choice to analyze biomedical data, the field is facing multiple challenges around research reproducibility and transparency. Given the proliferation of studies investigating the applications of AI in research and clinical studies, it is essential for independent researchers to be able to scrutinize and reproduce the results of a study using its materials, and build upon them in future studies. Computational reproducibility is achievable when the data can easily be shared and the required computational resources are relatively common. However, the complexity of AI algorithms and their implementation, the need for specific computer hardware and the use of sensitive biomedical data represent major obstacles in healthy-related AI research. In this talk, I will describe the various aspects of an AI biomedical study that are necessary for reproducibility and the platforms that exist for sharing these materials with the scientific community. Citation Format: Benjamin Haibe-Kains, Anthony Mammoliti, Minoru Nakano. Platforms to improve reproducibility in artificial intelligence research [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr IA-15.
Abstract PO-076: Unsupervised learning of image embeddings enables new opportunities to extract novel information from digital pathology H&amp;E images
Authors: Jason Hipp, Mona Xu, Lucas Bordeaux, Feng Gu, Carlos Pedrinaci, Khan Baykaner
Journal: Clinical Cancer Research (2021)

Abstract Introduction: In digital pathology, large amounts of time and money are spent annotating whole slide images (WSIs). By using an AI algorithm trained on thousands of WSIs, it is possible to remove the process of annotating from the workflow whilst simultaneously finding potential imaging features that correlate with drug response, molecular phenotypes, histologic features (e.g. Tertiary Lymphoid Structures), inflammation at the tumor-stroma interface, artifacts, etc. Method: A pipeline was constructed for ingesting WSI from the set of diagnostic slides available in the cancer genome archive (TCGA). The WSIs were masked for tissue areas and divided into patches extracted at multiple magnification levels. These patches were used to train a U-Net (initialised with a pre-trained ResNet34) to complete a self-supervised in-painting task and evaluated with perceptual loss using VGG16. After training, embeddings were extracted from the bottleneck layer of the U-Net, and these were evaluated for their capacity to cluster according to tissue type and magnification level. Results: The trained embeddings showed strong clustering by tissue type, magnification level, and separation of artefacts. The results were qualitatively evaluated by pathologist with consensus and exceeded the performance of a baseline pre-trained ImageNet model. Conclusion: These results highlight a novel methodology for AI algorithm development that removes the need for numerous pathologists to annotate pathology images by hand and converts their role to reviewing and quality-checking images. AI algorithms based on this approach can have a significant impact in the pathologic evaluation of tissue for oncology clinical trials by extracting a richer set of features than glass microscopy alone would permit. Furthermore, self-supervised methods, such as in-painting allow for the training of embeddings that encapsulate a richer understanding of the data and are consequently more repurposable than supervised/labelled approaches. Citation Format: Jason Hipp, Mona Xu, Lucas Bordeaux, Feng Gu, Carlos Pedrinaci, Khan Baykaner. Unsupervised learning of image embeddings enables new opportunities to extract novel information from digital pathology H&amp;E images [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-076.
Higher Rates of Processed Pseudogene Acquisition in Humans and Three Great Apes Revealed by Long-Read Assemblies
Authors: Xiaowen Feng, Heng Li
Journal: Molecular Biology and Evolution (2021)

Abstract LINE-1-mediated retrotransposition of protein-coding mRNAs is an active process in modern humans for both germline and somatic genomes. Prior works that surveyed human data mostly relied on detecting discordant mappings of paired-end short reads, or exon junctions contained in short reads. Moreover, there have been few genome-wide comparisons between gene retrocopies in great apes and humans. In this study, we introduced a more sensitive and accurate method to identify processed pseudogenes. Our method utilizes long-read assemblies, and more importantly, is able to provide full-length retrocopy sequences as well as flanking regions which are missed by short-read based methods. From 22 human individuals, we pinpointed 40 processed pseudogenes that are not present in the human reference genome GRCh38 and identified 17 pseudogenes that are in GRCh38 but absent from some input individuals. This represents a significantly higher discovery rate than previous reports (39 pseudogenes not in the reference genome out of 939 individuals). We also provided an overview of lineage-specific retrocopies in chimpanzee, gorilla, and orangutan genomes.
Abstract IA026: Activating a collaborative innate-adaptive immune response to control metastasis
Authors: Mikala Egeblad
Journal: Cancer Research (2021)

Abstract Tumor-associated macrophages (TAMs) promote metastasis and inhibit cytotoxic T cells. Yet, macrophages can be polarized to kill cancer cells. Macrophage polarization could therefore be a strategy for controlling cancer. We have found that monophosphoryl lipid A (MPLA, a derivative of lipopolysaccharide [LPS]) with IFNγ can polarize macrophages isolated from metastatic pleural effusions of breast cancer patients to kill cancer cells in vitro. Injecting tumors with MPLA+IFNγ reduced primary tumor growth, greatly suppressed metastasis, and enhanced the response to chemotherapy in breast and ovarian cancer mouse models. Both macrophages and T cells were critical for the anti-metastatic effects of MPLA+IFNγ. Mechanistically, the combined MPLA+IFNγ treatment stimulated type I interferon signaling, reprogramed TAMs (CD206+) to tumoricidal macrophages (iNOS+), and activated cytotoxic T cells through macrophage-secreted interleukin 12 (IL-12) and tumor necrosis factor α (TNFα). MPLA and IFNγ are already used individually in clinical practice and together represent a previously unexplored approach to engage a systemic anti-tumor immune response. Citation Format: Mikala Egeblad. Activating a collaborative innate-adaptive immune response to control metastasis [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA026.
Abstract 10424: Impact of Non-alcoholic Fatty Liver Disease on Coronary High-risk Plaque Assessed by Coronary Computed Tomography and Its Long-term Prognosis
Authors: Keishi Ichikawa, Toru Miyoshi, Takashi Miki, Kazufumi Nakamura, Hiroshi Ito
Journal: Circulation (2019)

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases and is independently associated with an increased risk of cardiovascular (CV) events. To date, the asso...
Inhibition of Progression of Acrodermatitis Continua of Hallopeau With Baricitinib
Authors: Guang-Ming Han, Wan-Shan Yang, Bin Yang
Journal: JAMA Dermatology (2021)

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Sleep Disruption, Fatigue, and Depression as Predictors of 6-Year Clinical Outcomes Following Allogeneic Hematopoietic Cell Transplantation
Authors: Kelly E Rentscher, Judith E Carroll, Mark B Juckett, Christopher L Coe, Aimee T Broman, Paul J Rathouz, Peiman Hematti, Erin S Costanzo
Journal: JNCI Journal of the National Cancer Institute (2021)

Allogeneic hematopoietic cell transplantation (HCT) is a widely used treatment for hematologic cancers, with survival rates ranging from 25% to 78%. Known risk factors for chronic graft-versus-host disease (cGVHD), a serious and common long-term complication, disease relapse, and mortality following HCT have been identified, but much of the variability in HCT outcomes is unexplained. Biobehavioral symptoms including depression, sleep disruption, and fatigue are some of the most prevalent and distressing for patients; yet research on biobehavioral risk factors for HCT outcomes is limited. This study evaluated patient-reported depression, sleep disruption, and fatigue as risk factors for cGVHD, disease relapse, and mortality.Adults receiving allogeneic HCT for a hematologic malignancy (N = 241) completed self-report measures of depression symptoms, sleep quality, and fatigue (severity, interference) pre-HCT and 100 days post-HCT. Clinical outcomes were monitored for up to 6 years.Cox proportional hazard models (2-tailed) adjusting for patient demographic and medical characteristics revealed that high pre-HCT sleep disruption (Pittsburgh Sleep Quality Index >9; hazard ratio [HR] = 2.74, 95% confidence interval [CI] = 1.27 to 5.92) and greater post-HCT fatigue interference (HR = 1.32, 95% CI = 1.05 to 1.66) uniquely predicted increased risk of mortality. Moderate pre-HCT sleep disruption (Pittsburgh Sleep Quality Index 6-9) predicted increased risk of relapse (HR = 1.99, 95% CI = 1.02 to 3.87). Biobehavioral symptoms did not predict cGVHD incidence.Biobehavioral symptoms, particularly sleep disruption and fatigue interference, predicted an increased risk for 6-year relapse and mortality after HCT. Because these symptoms are amenable to treatment, they offer specific targets for intervention to improve HCT outcomes.