tbuckley/cabot-search huggingface dataset:
Seminomatous and non-seminomatous mediastinal germ cell tumors (MGCT): A real-world analysis from two tertiary care centers in India.
Authors: Aparna Sharma, Bivas Biswas, Rohit Reddy, Robin Thumbudorai, Sandip Ganguly, Deepak Dabkara, Raja Pramanik, Sunil Kumar, Ranjit Kumar Sahoo, Atul Sharma, Lalit Kumar, Atul Batra
Journal: Journal of Clinical Oncology (2021)

e18726 Background: Mediastinal germ cell tumor (MGCT) is a rare entity and comprises 10-15% of all mediastinal tumors. We describe the real-world treatment patterns and outcomes of MGCT treated at two tertiary care centres in India. Methods: Patients diagnosed with GCT (any site) at two large tertiary care centres from January 2010 to December 2020 in India were identified using the ICD-09 code (C-62) from prospectively kept databases. From these databases, a manual search was performed to identify MGCT patients. A chart review was done to retrieve demographic, tumor-related (serum tumor marker levels as per International germ cell cancer consensus (IGCCC)) and treatment details. Relapse free survival (RFS) and overall survival (OS) were estimated and compared for seminomatous and non-seminomatous MGCT. Results: A total of 54 patients were identified and all were males with a median age of 25 years (interquartile range, 18-45). Common presenting symptoms included cough (81.4%) shortness of breath (64.8%), chest pain (25.9%), superior vena cava obstruction (20.3%), pleural effusion (18.5%) and pericardial effusion (5.6%). Approximately one-thirds (n = 17) were seminomatous, while two-thirds were non-seminomatous (n = 37). Serum tumors markers levels were S0 (7.4%),S1 (42.6%),S2 (29.6%) and S3 (20.4%). Treatment was primarily by multiagent chemotherapy [ Bleomycin/Etoposide/cisplatin(BEP) 63.0%, EP (Etoposide/Cisplatin) 18.5%, VIP (etoposide/ifosfamide/cisplatin) 13.0%). Median number of cycles administered was 3 (Range 1-6). Three patients did not receive chemotherapy (all seminoma) and were treated with upfront surgery. In total, 11 patients (20.4%) underwent surgery, and eight (14.8%) received radiation. Three patients were not evaluable for response, 33.3% achieved complete response (CR),44.4% achieved partial response (PR), 9.3% had SD (stable disease) and 7.4% progressed on first line chemotherapy. Median follow up was 14.4 months (95% confidence interval [CI] 9.03 -26.16). Three year relapse free survival was 64.0% in overall population, and 100% in seminoma vs 41.5% in non-seminoma (P &lt; 0.001). Three year OS was 80.2% in all patients and 94.1% for seminoma versus 70.0% in non-seminoma (P = 0.178). Conclusions: In this largest real-world analysis of MGCT, we found excellent long-term survival rates for patients with seminomatous MGCT, while further optimization of treatment is needed for those with non-seminomatous MGCT.
Molecular mechanisms of chemo‐ and radiotherapy resistance and the potential implications for cancer treatment
Authors: Ya‐Ping Liu, Can‐Can Zheng, Yun‐Na Huang, Ming‐Liang He, Wen Wen Xu, Bin Li
Journal: MedComm (2021)

Cancer is a leading cause of death worldwide. Surgery is the primary treatment approach for cancer, but the survival rate is very low due to the rapid progression of the disease and presence of local and distant metastasis at diagnosis. Adjuvant chemotherapy and radiotherapy are important components of the multidisciplinary approaches for cancer treatment. However, resistance to radiotherapy and chemotherapy may result in treatment failure or even cancer recurrence. Radioresistance in cancer is often caused by the repair response to radiation-induced DNA damage, cell cycle dysregulation, cancer stem cells (CSCs) resilience, and epithelial-mesenchymal transition (EMT). Understanding the molecular alterations that lead to radioresistance may provide new diagnostic markers and therapeutic targets to improve radiotherapy efficacy. Patients who develop resistance to chemotherapy drugs cannot benefit from the cytotoxicity induced by the prescribed drug and will likely have a poor outcome with these treatments. Chemotherapy often shows a low response rate due to various drug resistance mechanisms. This review focuses on the molecular mechanisms of radioresistance and chemoresistance in cancer and discusses recent developments in therapeutic strategies targeting chemoradiotherapy resistance to improve treatment outcomes.
Clinical performance of artificial intelligence-powered annotation of tumor cell PD-L1 expression for treatment of immune-checkpoint inhibitor (ICI) in advanced non-small cell lung cancer (NSCLC).
Authors: Hyojin Kim, Sangjoon Choi, Seokhwi Kim, Jaehong Aum, Sergio Pereira, Seonwook Park, Minuk Ma, Seunghwan Shin, Kyunghyun Paeng, Donggeun Yoo, Wonkyung Jung, Chan-Young Ock, Se-Hoon Lee, Jin-haeng Chung, Yoon-La Choi, Tony S. K. Mok
Journal: Journal of Clinical Oncology (2021)

9026 Background: Programmed death ligand 1 (PD-L1) expression is the standard biomarker for first line ICI in advanced NSCLC. However, manual evaluation of tumor proportion score (TPS) by pathologists has practical limitations including intra/inter-observer bias, variation in subjectivity on area of interest and intensive labor. We developed an artificial intelligence (AI)-powered TPS analyzer, namely Lunit SCOPE PD-L1, for objective annotation of tumor cell PD-L1 expression for prediction of ICI response in advanced NSCLC. Methods: Lunit SCOPE PD-L1 was developed by a total of 393,565 tumor cells annotated by board-certified pathologists for PD-L1 expression in 802 whole-slide images (WSI) stained by 22C3 pharmDx immunohistochemistry. A After excluding the in-house control tissue regions, the WSI were divided into patches, from which a deep learning-based model detected the location and PD-L1 positivity of tumor cells. The patch-level cell predictions were aggregated for TPS estimation. Clinical performance of the model was validated in an external cohort of 430 NSCLC tumor slides from patients treated with ≥ ICI at Seoul National University Bundang Hospital and Samsung Medical Center. Independent control TPS annotation of this external validation cohort was performed by three pathologists, and their consensus TPS was calculated by mean value of such. Results: AI-model (Lunit SCOPE PD-L1) predicts PD-L1-positive tumor cell with the area under the curves of 0.889 and PD-L1-negative tumor cells with that of 0.809 at cell-level analysis. At WSI-level, significant positive correlation was observed between TPS by AI model and control TPS by pathologists (Spearman coefficient = 0.9247, P &lt; 0.001). Concordance rate between AI-model and control TPS by pathologists according to expression level of PD-L1 ≥ 50%, 1-49%, and &lt; 1% status was 85.7%, 89.3%, and 52.4%, respectively. Median progression-free survival (mPFS) according to TPS by AI model ≥ 1% vs. &lt; 1% were 2.8 vs. 1.7 months (hazard ratio, HR, 0.52, 95% confidence interval, CI, 0.38-0.71, P &lt; 0.001). In contrast, mPFS according to control TPS was 2.8 vs. 2.1 months (HR 0.70, 95% CI 0.55-0.91, P &lt; 0.001). Forty out of 84 patients (47.6%) annotated as control TPS &lt; 1% by pathologists were considered as TPS ≥ 1% by AI-model and mPFS of this subgroup was 2.7 months. Conclusions: PD-L1 expression by AI-model correlates with PD-L1 expression by pathologists. Clinical performance of AI-model in WSI-level is comparable with assessment by pathologists. The AI-model can accurately predict tumor response and progression-free survival of ICI in advanced NSCLC.
Scaling Up Pharmacist-Led Blood Pressure Control Programs in Black Barbershops: Projected Population Health Impact and Value
Authors: Dhruv S. Kazi, Pengxiao C. Wei, Joanne Penko, Brandon K. Bellows, Pamela Coxson, Kelsey B. Bryant, Valy Fontil, Ciantel A. Blyler, Courtney Lyles, Kathleen Lynch, Joseph Ebinger, Yiyi Zhang, Gabriel S. Tajeu, Ross Boylan, Mark J. Pletcher, Florian Rader, Andrew E. Moran, Kirsten Bibbins-Domingo
Journal: Circulation (2021)
Hospitalization of Adolescents Aged 12–17 Years with Laboratory-Confirmed COVID-19 — COVID-NET, 14 States, March 1, 2020–April 24, 2021
Authors: Fiona P. Havers, Michael Whitaker, Julie L. Self, Shua J. Chai, Pam Daily Kirley, Nisha B. Alden, Breanna Kawasaki, James Meek, Kimberly Yousey-Hindes, Evan J. Anderson, Kyle P. Openo, Andrew Weigel, Kenzie Teno, Maya L. Monroe, Patricia A. Ryan, Libby Reeg, Alexander Kohrman, Ruth Lynfield, Kathryn Como-Sabetti, Mayvilynne Poblete, Chelsea McMullen, Alison Muse, Nancy Spina, Nancy M. Bennett, Maria Gaitán, Laurie M. Billing, Jess Shiltz, Melissa Sutton, Nasreen Abdullah, William Schaffner, H. Keipp Talbot, Melanie Crossland, Andrea George, Kadam Patel, Huong Pham, Jennifer Milucky, Onika Anglin, Dawud Ujamaa, Aron J. Hall, Shikha Garg, Christopher A. Taylor, Gretchen Rothrock, Arthur Reingold, Millen Tsegaye, Sarah McLafferty, Amber Maslar, Paula Clogher, Adam Misiorski, Christina Parisi, Maria Correa, Tessa Carter, Carol Lyons, Daewi Kim, Gaggan Brar, Emily Fawcett, Allison Roebling, Katelyn Ward, Jana Manning, Asmith Joseph, Chandler Surell, Daniel Pizarro, Jeremiah Williams, Rayna Ceaser, Stephanie Lehman, Taylor Eisenstein, Gracie Chambers, Grayson Kallas, Lauren Russell, Suzanne Segler, David Blythe, Alicia Brooks, Erica Bye, Richard Danila, Cory Cline, Susan Ropp, Chad Smelser, Daniel Sosin, Salina Torres, Kathy Angeles, Melissa Christian, Nancy Eisenberg, Kristina Flores, Caroline Habrun, Emily Hancock, Sarah Khanlian, Meaghan Novi, Erin Phipps, Dominic Rudin, Yadira Salazar-Sanchez, Judith Segall, Sarah Shrum Davis, Grant Barney, Christina Felsen, Sophrena Bushey, Kevin Popham, Virginia Cafferky, Christine Long, RaeAnne Kurtz, Nicole West, Ama Owusu-Dommey, Breanna McArdle, Emily Youngers, Kylie Seeley, Tiffanie Markus, Amanda Carter, Andrea Price, Andrew Haraghey, Ashley Swain, Caitlin Shaw, Ian Buchta, Jake Ortega, Laine McCullough, Ryan Chatelain, Tyler Riedesel
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

COVID-19 adolescent hospitalization rates peaked at 2.1 per 100,000 in early January 2021, declined to 0.6 in mid-March, and rose to 1.3 in April. Among hospitalized adolescents, nearly one-third required intensive care unit admission and 5% required invasive mechanical ventilation, but no associated deaths occurred.
Efficacy of immunotherapy in hepatocholangiocarcinoma (HCC-CC): Proof of concept.
Authors: Osama Diab, Maloree Khan, Saqib Abbasi, Anwaar Saeed, Anup Kasi, Joaquina Celebre Baranda, Weijing Sun, Raed Moh'd Taiseer Al-Rajabi
Journal: Journal of Clinical Oncology (2021)

e16194 Background: Hepatocholangiocarcinoma (HCC-CC) is a rare form of cancer with a poor prognosis. Of all primary liver cancers, the incidence of HCC-CC ranges from 0.4 to 14.2%. HCC-CC is a mixed carcinoma with findings of both hepatocellular carcinoma and cholangiocarcinoma. Immune checkpoint inhibitors are a potent first line treatment in hepatocellular carcinoma with multiple clinical trial showing effectiveness in cholangiocarcinoma. HCC-CC has limited proven treatment options as patients are generally excluded from clinical trials. In this study we reviewed outcomes of patients with HCC-CC who received immune checkpoint inhibitor in a single center. Methods: Records of patients who had a pathological confirmed HCC-CC by a subspecialized hepatic pathologist at the University of Kansas medical center were reviewed. We identified 6 patients with locally advanced unresectable or metastatic HCC-CC that received immune checkpoint inhibitor between February 2017 and January 2021. Baseline characteristics were obtained, as well as best response, line of therapy, and duration of response. Results: Of the six patients 4 (66%) received PD-1 inhibitor alone and 2 (34%) received combination therapy with CTLA-4 inhibitor for the treatment of HCC-CC. There were 3 (50%) females and 6 (100%) with prior hepatitis C infection. four (66%) patients had metastatic disease and 2 had locally unresectable advanced disease. Objective response rate was 83.3%. One patient achieved complete response and had a treatment holiday after receiving treatment for 2 years, and restarted immunotherapy upon relapse. Four patients had a partial response, of which two passed away after disease progression. One patient had stable disease on 2 different lines of immunotherapy then progressed. Of those who responded, one patient received immunotherapy, 3 (50%) received liver directed therapy and two received chemotherapy or Lenvatinib as first line treatment (Table). Conclusions: Immune checkpoint inhibitors demonstrate potential activity in patients with HCC-CC without unexpected side effect in this unmet need high-risk population. Larger studies are needed to confirm activity and efficacy in this setting.[Table: see text]
Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: A phase 3, multicenter, randomized controlled trial.
Authors: Jun Ma, Yu-Pei Chen, Ying Sun, Qin Zhou, Kun-Yu Yang, Feng Jin, Xiao-Dong Zhu, Mei Shi, Guoqing Hu, Yan Sun, Hong-Fen Wu, Hui Wu, Qin Lin, Hui Wang, Ye Tian, Ning Zhang, Xicheng Wang, Liangfang Shen, Fangyun Xie, Xu Liu
Journal: Journal of Clinical Oncology (2021)

6003 Background: Patients suffering from locoregionally advanced nasopharyngeal carcinoma (NPC) commonly develop disease recurrence, despite a high rate of complete clinical remission after standard of care (concurrent cisplatin-radiotherapy, with or without induction chemotherapy). The benefit of additional adjuvant chemotherapy remains unclear. Methods: Patients with high-risk locoregionally advanced NPC (stage III to IVA, excluding T3-4N0 and T3N1), and with no locoregional disease or distant metastasis after definitive chemoradiotherapy, were eligible. They were randomly assigned (1:1) within 12 to 16 weeks after the last radiation dose to receive either capecitabine at a dose of 650 mg/m 2 twice daily for 1 year (metronomic capecitabine group) or observation (standard-therapy group). The primary end point was recurrence-free survival (RFS). The calculated sample size was 201 per group, with an 80% power (two-sided α 0.05) to detect a target hazard ratio (HR) of 0.52. Results: A total of 406 patients underwent randomization, comprising 204 in the metronomic capecitabine group and 202 in the standard-therapy group. After a median follow-up of 36 months (corresponding to 43 months when calculated from the start of standard therapy), the estimated 3-year RFS was 85.9% in the metronomic capecitabine group, as compared with 76.5% in the standard-therapy group (intention-to-treat population; HR 0.51, 95% confidence interval 0.32–0.81; P = 0.003). The incidence of grade 3 adverse events was 17.4% in the metronomic capecitabine group and 5.5% in the standard-therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (9.0%). One grade 4 neutropenia occurred in the metronomic capecitabine group. Neither group sufferd from treatment-related deaths. During treatment, there was no clinically meaningful deterioration of health-related quality of life associated with the use of metronomic adjuvant capecitabine. Conclusions: The addition of metronomic capecitabine as adjuvant therapy to chemoradiotherapy significantly improved RFS in locoregionally advanced NPC, with a manageable safety profile and no compromise to quality of life. Clinical trial information: NCT02958111. [Table: see text]
Risk Stratification of Smoldering Multiple Myeloma in the Light of the Revised IMWG Diagnostic Criteria
Authors: Arjun Lakshman, S. Vincent Rajkumar, Angela Dispenzieri, Martha Q Lacy, Morie A. Gertz, Francis K Buadi, David Dingli, Lisa Hwa, Amie Fonder, Miriam Hobbs, Suzanne R. Hayman, Steven Zeldenrust, John A. Lust, Stephen J. Russell, Nelson Leung, Prashant Kapoor, Ronald S. Go, Yi Lin, Wilson I Gonsalves, Taxiarchis Kourelis, Rahma Warsame, Robert A Kyle, Shaji K Kumar
Journal: Blood (2017)
S100A4 enhances protumor macrophage polarization by control of PPAR-γ-dependent induction of fatty acid oxidation
Authors: Shuangqing Liu, Huilei Zhang, Yanan Li, Yana Zhang, Yangyang Bian, Yanqiong Zeng, Xiaohan Yao, Jiajia Wan, Xu Chen, Jianru Li, Zhaoqing Wang, Zhihai Qin
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background The peroxisome proliferator-activated receptor γ (PPAR-γ)-dependent upregulation of fatty acid oxidation (FAO) mediates protumor (also known as M2-like) polarization of tumor-associated macrophages (TAMs). However, upstream factors determining PPAR-γ upregulation in TAM protumor polarization are not fully identified. S100A4 plays crucial roles in promotion of cancer malignancy and mitochondrial metabolism. The fact that macrophage-derived S100A4 is major source of extracellular S100A4 suggests that macrophages contain a high abundance of intracellular S100A4. However, whether intracellular S100A4 in macrophages also contributes to cancer malignancy by enabling TAMs to acquire M2-like protumor activity remains unknown. Methods Growth of tumor cells was evaluated in murine tumor models. TAMs were isolated from the tumor grafts in whole-body S100A4-knockout (KO), macrophage-specific S100A4-KO and transgenic S100A4 WT−EGFP mice (expressing enhanced green fluorescent protein (EGFP) under the control of the S100A4 promoter). In vitro induction of macrophage M2 polarization was conducted by interleukin 4 (IL-4) stimulation. RNA-sequencing, real-time quantitative PCR, flow cytometry, western blotting, immunofluorescence staining and mass spectrometry were used to determine macrophage phenotype. Exogenous and endogenous FAO, FA uptake and measurement of lipid content were used to analyze macrophage metabolism. Results TAMs contain two subsets based on whether they express S100A4 or not and that S100A4 + subsets display protumor phenotypes. S100A4 can be induced by IL-4, an M2 activator of macrophage polarization. Mechanistically, S100A4 controls the upregulation of PPAR-γ, a transcription factor required for FAO induction during TAM protumor polarization. In S100A4 + TAMs, PPAR-γ mainly upregulates CD36, a FA transporter, to enhance FA absorption as well as FAO. In contrast, S100A4-deficient TAMs exhibited decreased protumor activity because of failure in PPAR-γ upregulation-dependent FAO induction. Conclusions We find that macrophagic S100A4 enhances protumor macrophage polarization as a determinant of PPAR-γ-dependent FAO induction. Accordingly, our findings provide an insight into the general mechanisms of TAM polarization toward protumor phenotypes. Therefore, our results strongly suggest that targeting macrophagic S100A4 may be a potential strategy to prevent TAMs from re-differentiation toward a protumor phenotype.
Abstract 16362: The Right Heart is Specifically Targeted by Intravenous Administration of Treprostinil: Implications for Our Understanding of How Prostacyclin Drugs Work to Treat Pulmonary Arterial Hypertension
Authors: Nicholas S Kirkby, Dmitry Akhmedov, Fisnik Shala, Rebecca Berdeaux, Jane A Mitchell
Journal: Circulation (2018)

Background: Pulmonary arterial hypertension (PAH) is a devastating disease with no cure. In PAH elevated pulmonary artery pressures increase workload on the right heart leading to right heart failu...
The comparative efficacy of atezolizumab and bevacizumab versus lenvatinib in patients with unresectable hepatocellular carcinoma (uHCC).
Authors: David Trueman, Yifeng Liu, Melanie Lucero, Genevieve Meier
Journal: Journal of Clinical Oncology (2021)

e16151 Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer, comprising 90% of all cases. In the phase III IMbrave150 trial, combination of atezolizumab and bevacizumab (atezo+bev) resulted in improved overall survival (OS) and progression-free survival (PFS) compared with sorafenib for patients with unresectable hepatocellular carcinoma (uHCC). In the phase III REFLECT trial, lenvatinib met the primary endpoint of non-inferiority in OS versus sorafenib, and demonstrated superiority in secondary endpoints; PFS, time to progression and objective response rate (ORR). Furthermore, post-hoc analyses strongly suggest that the original non-inferiority trial likely underestimated the true effect of lenvatinib on OS due to imbalances in baseline prognostic covariates and the comparatively greater use of post-treatment anti-cancer therapies in the sorafenib arm. In the absence of a head-to-head comparison between atezo+bev and lenvatinib, the objective of this analysis was to estimate their comparative efficacy as first-line treatments for patients with uHCC. Methods: A network meta-analysis (NMA) was conducted based on a de novo systematic literature review which identified evidence for licensed therapies in first-line uHCC. This was supplemented with data from the extended IMbrave150 study findings (clinical cut-off on 31 August 2020). Median hazard ratios (HR) with corresponding 95% credible intervals (CrI) were estimated for OS and PFS. HRs for OS and PFS from REFLECT were taken from multivariable analyses which adjusted imbalances in baseline prognostic covariates. All analyses were conducted in a Bayesian generalised linear model framework. Model selection was based on deviance information criterion (DIC). Results: Four eligible phase III studies (REFLECT, SHARP, Asia-Pac and IMbrave150) were included. Using a fixed-effects model, the estimated median HRs for atezo+bev compared with lenvatinib were 0.81 (95%CrI: 0.61, 1.08; posterior p=0.078) and 0.99 (95%CrI: 0.76, 1.28; posterior p=0.454) for OS and PFS, respectively. The results obtained were similar to those observed by Vogel et al, who reported an OS HR of 0.63 (95% CI: 0.32, 1.25), and a PFS HR of 0.91 (95% CI: 0.23, 3.65). Conclusions: While the NMA respects the randomization of the included studies, it does not represent direct evidence and should therefore be considered exploratory in nature. The results of this NMA suggest that the benefit of atezo+bev is not statistically significant compared to lenvatinib, as the differences between atezo+bev and lenvatinib fell within the Bayesian range of equivalence (upper limit of Crl ≥ 1 for OS and PFS) and were subject to a high degree of uncertainty. The results of the NMA were consistent for all the publicly available data cuts from IMbrave150.