tbuckley/cabot-search huggingface dataset:
Activated interferon-γ (IFN-γ) pathway associated with clinical benefit to programmed cell death protein-1 (PD-1)/PD ligand 1 (PD-L1)-based therapy in esophageal squamous cell carcinoma (ESCC).
Authors: Jhe-Cyuan Guo, Min-Shu Hsieh, Chia-Chi Lin, Ta-Chen Huang, Chun-Jung Chang, Chih-Hung Hsu
Journal: Journal of Clinical Oncology (2019)

67 Background: Previous studies indicate a preexisting T cell response and the associated “adaptive immune resistance” are critical for the clinical efficacy of anti-PD-1/PD-L1 immunotherapy. The study explored the activated IFN-γ pathway and the expression of interferon regulatory factor 1 (IRF-1), as surrogates of preexisting T cell response, as potential biomarkers associated with clinical benefit (CB) for ESCC patients receiving anti-PD-1/PD-L1 therapy. Methods: Thirty-one ESCC patients treated with PD-1/PD-L1 blockade antibody, alone or in combination, were enrolled. Tumor response evaluation was made according to Response Evaluation Criteria in Solid Tumours 1.1, and CB was defined as complete response, partial response or stable disease at least 6 months. Formalin-fixed paraffin-embedded tissues from 31 patients were analyzed for the expression of PD-L1 and IRF-1 by immunohistochemistry; 13 tissues were analyzed for the expression of immune-related genes by NanoString nCounter Human PanCancer Immune Profiling. Results: Of 31 enrolled patients (M: F= 30: 1, median age of 58), 23 and 8 were of recurrent and de novo metastatic ESCC. Sixteen and 15 received PD-1/PD-L1 blockade alone and PD-1/PD-L1-based combination therapy, respectively; 13 had received at least 2 lines of systemic therapy for advanced disease. The response rate was 10%, and the CB rate was 16%. The median progression-free-survival (PFS) and overall survival are 1.8 and 5.6 months, respectively. The 25-gene IFN-γ signature was significant higher in patients with CB than in patients without CB ( P = 0.020). Neither PD-L1 expression on tumor cells (TC) nor on immune cells (IC) was associated with CB ( P = 0.489 and 0.646, respectively). However, the IRF-1 expression on TC or on IC was significantly associated with CB ( P &lt; 0.001 and 0.005, respectively). Conclusions: Activated IFN-γ pathway determined by 25-gene IFN-γ signature and high IHC-expression of IRF-1 were associated with CB in advanced ESCC patients receiving anti-PD-1/PD-L1-based therapy. (Supported by the grant of MOST 105-2314-B-002 -186 -MY3).
microRNA-142–mediated repression of phosphodiesterase 3B critically regulates peripheral immune tolerance
Authors: Nelomi Anandagoda, Joanna C.D. Willis, Arnulf Hertweck, Luke B. Roberts, Ian Jackson, M. Refik Gökmen, Richard G. Jenner, Jane K. Howard, Graham M. Lord
Journal: Journal of Clinical Investigation (2019)

Tregs play a fundamental role in immune tolerance via control of self-reactive effector T cells (Teffs). This function is dependent on maintenance of a high intracellular cAMP concentration. A number of microRNAs are implicated in the maintenance of Tregs. In this study, we demonstrate that peripheral immune tolerance is critically dependent on posttranscriptional repression of the cAMP-hydrolyzing enzyme phosphodiesterase-3b (Pde3b) by microRNA-142-5p (miR-142-5p). In this manner, miR-142-5p acts as an immunometabolic regulator of intracellular cAMP, controlling Treg suppressive function. Mir142 was associated with a super enhancer bound by the Treg lineage–determining transcription factor forkhead box P3 (FOXP3), and Treg-specific deletion of miR-142 in mice (TregΔ142) resulted in spontaneous, lethal, multisystem autoimmunity, despite preserved numbers of phenotypically normal Tregs. Pharmacological inhibition and genetic ablation of PDE3B prevented autoimmune disease and reversed the impaired suppressive function of Tregs in TregΔ142 animals. These findings reveal a critical molecular switch, specifying Treg function through the modulation of a highly conserved, cell-intrinsic metabolic pathway. Modulation of this pathway has direct relevance to the pathogenesis and treatment of autoimmunity and cancer.
Symptom burden of patients with advanced pancreas cancer (APC): A provincial cancer institute observational study.
Authors: Julie Ward, Christina Kim, Pascal J Lambert
Journal: Journal of Clinical Oncology (2019)

384 Background: Patients (pts) with advanced pancreatic cancer (APC) experience many disease-related symptoms. The Edmonton Symptom Assessment System (ESAS) measures the severity of 9 separate domains, and is completed by pts at each visit at our provincial cancer institute. The aim of this study was to describe symptom burden at baseline and over time for chemotherapy (CT) treated pts with APC, using ESAS. Methods: Pts diagnosed with APC between 2012-2016 and treated with at least 1 cycle of CT were identified. ESAS scores were extracted from the electronic medical record. Descriptive statistics were used to report the most common symptoms of pts with APC. A joint model was used to describe the trajectory of ESAS during follow-up while controlling for death. Multivariable Cox regression was used to identify independent predictors of death. Results: Of 123 pts identified, 61% had metastatic disease, 82.1% had a baseline ECOG of 0-1, with an average age of 64.8. 1608 clinic visits had an ESAS score documented and 87% of pts completed ≥ 2 ESAS assessments. Median overall survival was 10.2 months. Median progression free survival was 6.7 months. At baseline, the 10 th percentile, median and 90 th percentile for total symptom distress (TSD) score were 6.2, 24 and 53 respectively. 86% of pts had at least one ESAS score of ≥ 4 at baseline, with the most common being: fatigue, nausea, anxiety, and shortness of breath. Using a joint model, average TSD scores for the cohort improved for the first 4 to 5 months after starting CT and started to rise after 6 months. Average TSD scores at 15 to 18 months were similar to scores at baseline. Controlling for metastatic disease and CT type, for every increase of 10 in baseline TSD score, there was a 5% increased risk of death. Conclusions: The ESAS tool reflects the heavy burden of cancer-associated symptoms in APC. Symptoms improve months after starting CT and eventually worsen. The impact of early intervention to address symptom management is an important area of investigation in APC.
Abstract B06: Targeted radiopeptide therapy re188-P2045 to treat neuroendocrine lung cancer
Authors: Chris Adams, Ajit Shinto, Wasif Saif
Journal: Clinical Cancer Research (2018)

Abstract Background: Despite the recent success of checkpoint inhibitors, there continues to be a significant medical need for lung cancer therapies that can be directed to the patients most likely to respond. Somatostatin receptor subtype 2 (SSTR2) is the most widely upregulated subtype in both small and non-small cell lung cancers and is also expressed in tumoral (but not mature) blood vessels. Peptide-targeted radiotherapy has advantages over traditional targeted therapies in that targeted tumor cells as well as surrounding cancer cells and supporting stroma are selectively killed. This study was conducted to determine the ability of Rhenium Re 188 P2045, a radiolabeled somatostatin analog specific for SSTR2 to both image (to select the most appropriate patients) and treat lung and neuroendocrine cancer patients who overexpress somatostatin receptors. Methods: In an open-label, single-arm study, refractory lung cancer and metastatic neuroendocrine patients to standard-of-care therapy were identified by image analysis using Rhenium Re 188 P2045, a radiolabeled somatostatin analog. Twenty-five patients received the imaging dose of 10uCi of Re188 and 265ng of peptide by intravenous injection. Three patients were selected based on high SSTR expression levels to receive 30uCi of Re188 P2045 as a therapeutic dose 14 days after imaging. Patients were followed for 8 weeks post treatment. Results: The imaging study revealed a high density of expression of the somatostatin receptor in the lungs of patients. Patients in the imaging and therapeutic treatment groups reported no adverse advents or signs of toxicity. The image analysis using Re188 P2045 was compared to CT images and demonstrated accurate detection of lung and neuroendocrine tumor lesions. The patients who received R188 P2045 at the therapeutic dose had a 25% reduction in tumor mass based on image analysis versus typical results of stable disease from standard of care. The images obtained using Re188 P2045 were of sufficiently high quality to enable identification of receptor expression at the tumor site as shown in Figures 1 and 2 (figures not available). Conclusions: Rhenium Re 188 P2045, a radiolabeled somatostatin analog, may be used to both identify and treat lung and neuroendocrine cancer tumors. The ability to image and dose patients with the same targeted molecule enables a personalized medicine approach, and this highly targeted patient therapy may significantly improve treatment of tumors that overexpress somatostatin receptors. Citation Format: Chris Adams, Ajit Shinto, Wasif Saif. Targeted radiopeptide therapy re188-P2045 to treat neuroendocrine lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr B06.
A retrospective study of hepatic arterial infusion (HAI) FUDR/Dex and mitomycin C (MMC) for chemotherapy refractory unresectable intrahepatic cholangiocarcinomas (ICC).
Authors: Gustavo Dos Santos Fernandes, Nancy E. Kemeny, Haley Hauser, James J. Harding, Thomas Boerner, Anna M. Varghese, Peter Kingham, Michael Ian D'Angelica, Ronald P. DeMatteo, Jeffrey A. Drebin, Vinod P. Balachandran, William R. Jarnagin, Andrea Cercek
Journal: Journal of Clinical Oncology (2019)

432 Background: ICC are aggressive tumors with approximately 6,000 cases a year in US. The 5-year survival rate is less than 30% even for localized disease. There is only one approved line of systemic (SYS) treatment and further treatment options are necessary. HAI chemotherapy is an option to treat liver predominant cancers. Methods: After obtaining IRB approval, we retrospectively reviewed patients (pts) with ICC chemo refractory unresectable liver limited (LL) or liver dominant (LD) disease who received intrahepatic chemotherapy with HAI MMC. Baseline characteristics, previous lines of therapy, toxicity profile, combinations and radiographic responses were reviewed. Tumor genomic analyses were performed on samples using an on-site next generation sequencing (NGS) assay. Results: Between January 2011 and October 2018, 19 patients ICC with LL or LD disease were treated with HAI FUDR/Dex/MMC at Memorial Sloan Kettering Cancer Center. Disease was confined to the liver in 58% of the pts. All pts had previous chemotherapy (1-4 lines) and 14 (74%) previously had HAI FUDR/Dex. Of the 19 pts, 56% had HAI with FUDR/Dex and MMC, 43% had FUDR/Dex, MCC and SYS and 5% had HAI MMC and SYS. Seventeen patients were evaluable for response, two are being treated and will have response assessment for the meeting. Response was noted in 4 (23.5%), stable disease in 6 (35.5%) and progressive disease in 7 (41%) pts. Median overall survival from treatment was 6.1months (0.36-26). Median progression free survival was 3.65 months (0.36-9.53). Four patients had dose reductions. Common toxicity attributed to MMC was grade (G) one fatigue (32%), thrombocytopenia G1(16%) and G2 (5%). Of the 12 tumors analyzed to date the most 92% of tumors harbored at least one (0-10) genomic alteration. Common genomic alterations were ARID1 (25%), RASA1 (25%), IDH1(16.6%), NTRK (16.6%), TERT (16.6%), NRAS (16.6%), CDKN2 (16. 6%). FGFR2-FOXP1 and GTL2MEt fusions were found in one patient each. Conclusions: HAI FUDR/Dex/MMC containing regimens are active in pts with heavily pretreated refractory unresectable ICC. This strategy should be further investigated. Translational data will be presented.
A lobulated mass in the left lower lobe: not what it seems
Authors: Naoki Kadota, Tsutomu Shinohara, Keishi Naruse, Hiroyuki Hino, Fumitaka Ogushi
Journal: Thorax (2019)

A 43-year-old asymptomatic woman with no history of smoking was referred to our hospital because of decreased radiolucency in the left lower lung field (figure 1A), which was found by chest X-ray performed as part of a routine investigation during a medical check-up. No abnormal shadow was recognised by chest X-ray performed two years previously (figure 1B). Initial laboratory data included a white blood cell count of 4710/μl (neutrophils, 48.6%) and a C-reactive protein level of 0.03 mg/dL. Chest enhanced CT revealed a solitary lobulated low attenuation mass with septal enhancement, approximately 6 cm in diameter, across the left lateral and posterior basal segments (figure 1C-D). The internal structure appeared multilocular and was filled with fluid. A small part of the margin of the mass was accompanied by stippled calcification (figure 1D-E). Bronchoscopic examination was performed on suspicion of pulmonary mucinous cystadenocarcinoma (PMCAC). However, the forceps could not reach the mass. Bronchial lavage bacterial culture, acid-fast bacillus smear (Ziehl-Neelsen stain) and PCR tests for …
Evaluating the prognostic significance of lymphovascular invasion in stage II and III colon cancer.
Authors: Dorotea Mutabdzic, Shalana BL O'Brien, Elizabeth A. Handorf, Karthik Devarajan, Sanjay S. Reddy, Elin R. Sigurdson, Crystal S. Denlinger, Joshua E. Meyer, Jeffrey M. Farma
Journal: Journal of Clinical Oncology (2019)

685 Background: Presence of lymphovascular invasion (LVI) is known to be a predictor of lymph node involvement in colon adenocarcinoma (CA). Lymph node involvement is associated with poorer prognosis necessitating adjuvant therapy. While some studies have suggested that LVI is a predictor of worse overall survival in early stage colon cancer, the significance of LVI on prognosis has not been tested in a comprehensive North American data set. Methods: Patients with stage II and III CA with LVI data available and those who received predefined standard of care treatment were identified from the National Cancer Data Base (NCDB) from 2011 to 2015. The relationship between LVI and overall survival was tested using Kaplan-Meier survival curves and Cox proportional hazards regression analysis after adjusting for relevant clinical and demographic variables. Hazard ratios and 95% confidence intervals are reported along with median overall survival (OS) where available. Results: The dataset included 93,070 patients with stage II and 66,701 patients with stage III CA. The proportion of patients with LVI was 13% in stage II and 47% in stage III CA. After adjusting for age, sex, gender, race, comorbidities, socioeconomic status, T, and N stage, LVI was associated with worse OS in stage II, HR 1.2 (1.15-1.25, p &lt; 0.001), and in stage III, HR 1.25 (1.21-1.30, p &lt; 0.001), CA. Median OS was 6.51 years with LVI versus. 6.85 years without LVI in stage II compared with 6.57 years with LVI versus not reached without LVI in stage III CA. Of the stage II patients with LVI, 20% received adjuvant chemotherapy (CT) and median OS was 6.91 years for those who did versus 6.07 years for those who did not receive CT. Conclusions: Our data suggest that LVI is an important predictor of OS in stage II and III CA. There is evidence that adjuvant chemotherapy improves OS in advanced CA but there remains uncertainty as to the benefit in stage II. Despite this uncertainty, guidelines suggest consideration of adjuvant CT in patients with high-risk stage II disease. Our data support the recommendation that LVI be considered a high-risk feature in stage II disease. Further studies are necessary to examine whether the type or duration of CT should differ for patients with CA and LVI.
The incidence of infusion reactions associated with monoclonal antibody drugs targeting the epidermal growth factor receptor in metastatic colorectal cancer patients: A systematic literature review and meta-analysis.
Authors: Kimberly Lowe, Lauren C Bylsma, Rebecca Dean, Christina Gillezeau, Laura Sangaré, Dominik D Alexander, Jon Fryzek
Journal: Journal of Clinical Oncology (2019)

526 Background: Infusion reactions have been reported in studies of metastatic colorectal cancer (mCRC) patients treated with anti-EGFR therapies, including cetuximab and panitumumab, with incidences ranging from 0-33%. A systematic literature review and meta-analysis were conducted to estimate the incidence of infusion reactions in this population and identify variations in this incidence by patient and study characteristics. Methods: Multiple scientific databases were searched to identify observational studies or clinical trials of mCRC patients treated with anti-EGFR therapies that reported rates of infusion reactions, hypersensitivity, or allergy/anaphylaxis. Random effects models were used to meta-analyze the incidence of infusion reactions overall and stratified by therapy, study design, geographic location, KRAS mutation status, and grade of reaction severity. Results: Among 48 studies included in this meta-analysis, the pooled estimate for infusion reaction incidence was 0.049 (95% CI: 0.036 – 0.065), or nearly 5%. Reactions of grades 1 or 2 were more common than reactions of grades 3-5 (0.089 vs. 0.028) No significant variations in infusion reaction incidence were observed by study design, KRAS status, or study location. Conclusions: Infusion reactions occur in approximately 5% of mCRC patients treated with anti-EGFR therapies and the incidence varies significantly by grade and severity. Future studies should consider investigating survival outcomes for only those patients with infusion reactions to determine its prognostic relevance.
A novel method for detecting the cellular stemness state in normal and leukemic human hematopoietic cells can predict disease outcome and drug sensitivity
Authors: Muhammad Yassin, Nasma Aqaqe, Abed Alkader Yassin, Peter van Galen, Eitan Kugler, Bradley E. Bernstein, Maya Koren-Michowitz, Jonathan Canaani, Arnon Nagler, Eric R. Lechman, John E. Dick, Erno Wienholds, Shai Izraeli, Michael Milyavsky
Journal: Leukemia (2019)
Desensitization rates to peanut protein during OIT among children, adolescents, and adults
Authors: Andrew J. Long, Natasha Purington, Margaret Woch, Katherine O'Laughlin, Tiffany Tan, Laurie Kost, Susan Hijazi, Melanie Shojinaga, Olivia Raeber, Andres Alvarez, Sandra Andorf, Robert Tibshirani, Stephen J. Galli, Kari C. Nadeau, R. Sharon Chinthrajah
Journal: Journal of Allergy and Clinical Immunology (2019)
Baseline PET-Derived Metabolic Tumor Volume Metrics Did Not Predict Outcomes in Follicular Lymphoma Patients Treated with First-Line Immunochemotherapy and Antibody Maintenance in the Phase III GALLIUM Study
Authors: Sally F Barrington, Judith Trotman, Deniz Sahin, David Belada, Andrew Davies, Robert MacEwan, Carolyn Owen, Václav Ptáčník, András Rosta, Wolfgang Hiddemann, Robert Marcus, Tina Nielsen, Federico Mattiello, Harald Zeuner, Michel Meignan
Journal: Blood (2018)
Annals Graphic Medicine - What It Is Like
Authors: Gazi M. Rashid
Journal: Annals of Internal Medicine (2019)

Web Exclusives5 February 2019Annals Graphic Medicine - What It Is LikeFREEGazi M. Rashid, BSGazi M. Rashid, BSEmory University School of Medicine, Marietta, Georgia (G.M.R.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G18-0027 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Emory University School of Medicine, Marietta, Georgia (G.M.R.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G18-0027.Author/Illustrator Information: Gazi M. Rashid, MS, is a fourth-year medical student at Emory University (e-mail, [email protected]edu). He is applying for a general surgery residency, during which he hopes to continue storytelling and teaching. He collects his works on his Web site: www.gazirashid.com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoReimagining the Cape: Exploring New Metaphors for Emerging Medical Professionals Michael J. Green Annals Graphic Medicine - The Tale of a Wannabe Superhero Michelle Sayad Reimagining the Cape: Exploring New Metaphors for Emerging Medical Professionals Michael J. Green Annals Graphic Medicine - The Med Student Mollie Kotzen Annals Graphic Medicine - Team Doctor Shruti Sudhakar Metrics Cited byReimagining the Cape: Exploring New Metaphors for Emerging Medical ProfessionalsMichael J. Green, MD, MS 5 February 2019Volume 170, Issue 3Page: W68-W72KeywordsConflicts of interestDisclosureHealth careResidencySurgery ePublished: 5 February 2019 Issue Published: 5 February 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Life course approach to prevention and control of non-communicable diseases
Authors: Bente Mikkelsen, Julianne Williams, Ivo Rakovac, Kremlin Wickramasinghe, Anselm Hennis, Hai-Rim Shin, Mychelle Farmer, Martin Weber, Nino Berdzuli, Carina Borges, Manfred Huber, João Breda
Journal: BMJ (2019)

A successful approach to reducing the burden of non-communicable disease requires action at all stages of life, argue Bente Mikkelsen and colleagues
Prognostic Value of IPSS-R Score, Cytogenetic Aberrations, and Cytopenias on Outcome of Allogeneic Hematopoietic Stem Cell Transplant in Myelodysplastic Syndrome in GATA2 Deficiency
Authors: Julia Scheiermann, Robert West, Lisa J. Embree, Katherine R. Calvo, Nirali N. Shah, Laura Tuschong, Mark Parta, Dennis D. Hickstein
Journal: Blood (2018)