tbuckley/cabot-search huggingface dataset:
Venetoclax Consolidation in Patients with High-Risk CLL Who Have Been on Ibrutinib More Than a Year Achieves a High Rate of Undetectable Minimal Residual Disease
Authors: Philip A. Thompson, Yan Wang, Michael J. Keating, Alessandra Ferrajoli, Nitin Jain, Christine B. Peterson, Naveen Garg, Chongjuan Wei, Ana Ayala, Tapan M. Kadia, Prithviraj Bose, Naveen Pemmaraju, Nicholas J. Short, William G. Wierda
Journal: Blood (2021)
Combined Inhibition of Bcl-2 and Mcl-1 Circumvents Resistance of TP53 Deficient/Mutant AML to BH3 Mimetics
Authors: Bing Z Carter, Po Yee Mak, Wenjing Tao, Lauren B Ostermann, Steffen Boettcher, Yuki Nishida, Edward Ayoub, Vivian Ruvolo, Elias J. Jabbour, Paul Hughes, PK Morrow, Michael Andreeff
Journal: Blood (2021)
Effect of Age on Outcomes of Allogeneic Transplantation in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome
Authors: Audrey M. Sigmund, Justin Jiang, Qiuhong Zhao, Patrick Elder, Ashley E. Rosko, Maria Chaudhry, Naresh Bumma, Abdullah Khan, Srinivas Devarakonda, Sumithira Vasu, Samantha Jaglowski, Alice S. Mims, Hannah Choe, Karilyn Larkin, Jonathan E Brammer, Sarah A Wall, Nicole Grieselhuber, Ayman Saad, Sam Penza, Marcos J.G. de Lima, Don M Benson, Yvonne A. Efebera, Nidhi Sharma
Journal: Blood (2021)
Eptacog Beta Efficacy in Children and Adolescents with Hemophilia A or B and Inhibitors: Subset Analysis Suggests Improved Caregiver Capacity to Assess Bleeding Episode Resolution with Subject Age
Authors: Guy Young, Steven W Pipe, Cédric Hermans, Manuel Carcao, Giancarlo Castaman, Joanna A. Davis, Jonathan M. Ducore, Amy L. Dunn, Miguel A. Escobar, Janna Journeycake, Osman Khan, Johnny Mahlangu, Shannon Meeks, Ismail Haroon Mitha, Claude Négrier, Ulrike Nowak-Göttl, Michael Recht, Tammuella Chrisentery-Singleton, Oleksandra Stasyshyn, Kateryna V. Vilchevska, Laura Villarreal Martinez, Michael Wang, Jerzy Windyga, W. Allan Alexander, Ahmad Al-Sabbagh, Daniel Bonzo, Christopher Macie, Ian S. Mitchell, Thomas A. Wilkinson, Amy D. Shapiro
Journal: Blood (2021)
Abstract 9234: Effects of a 26-Week Randomized, Controlled Exercise Intervention on Arterial Stiffness, Endothelial Function, and Cognition in Adults Atrisk for Alzheimer Disease
Authors: Ryan Pewowaruk, Julian M Gaitan, Carol Mitchell, Sarah Lose, Ryan Dougherty, Elizabeth Boots, Dane B Cook, Ozioma C Okonkwo, Adam D Gepner
Journal: Circulation (2021)

Introduction: Arterial stiffness progresses with age and is associated with cardiovascular disease (CVD) events and cognitive decline. Alzheimer’s disease (AD) risk factors like physical inactivity overlap significantly with progression of arterial stiffness. Aerobic exercise training reduces arterial stiffness and may bolster cognition at a time of life when the risk of AD heightens. Hypothesis: Following a 26-week aerobic exercise intervention, improvements in cognitive function will be significantly correlated with improvements in carotid artery stiffness and endothelial function. Methods: Late-middle-aged adults with normal cognition and parental history of AD were randomized to a 26-week exercise training intervention designed to increase physical activity (PA) levels (Enhanced PA; n=11) or maintain Usual PA (n=12). At baseline and following the intervention we used ultrasound to measure local stiffness of the right common carotid artery, brachial artery flow mediated dilation, and tested cognitive function. Pre- and post- intervention changes in outcome variables were compared between groups using independent sample t-tests or ANCOVA and results are presented as mean ± standard deviation. The association between pre-post intervention changes in arterial stiffness and cognitive function were assessed using Pearson correlation coefficients. Results: The pre-post intervention changes for Usual PA vs Enhanced PA were not different for carotid artery stiffness (Young’s Elastic Modulus: (219 ± 1088 mmHg vs -131 ± 384, p=0.12) or endothelial function (0.49 ± 1.69 vs 0.47 ± 1.71, p=0.32). Improvements in cognitive function were not significantly correlated with changes in arterial stiffness or endothelial function (r = -.27-.25, p = .24-.81). Conclusions: The findings of this pilot study do not support the hypothesis that improved cognition following exercise would be associated with improved carotid artery stiffness and endothelial function.
A Novel Strategy for Off-the-Shelf T Cell Therapy Which Evades Allogeneic T Cell and NK Cell Rejection
Authors: Yong Zhang, Surbhi Goel, Aaron Prodeus, Utsav Jetley, Yiyang Tan, John Averill, Utkarsha Ranade, Ishina Balwani, Ivy Dutta, Palak Sharma, Priya Venkatesan, Dai Liu, Matthew Roy, Daniel O′Connell, Simo M Arredouani, Marie Keenan, Reynald Lescarbeau, Birgit C Schultes
Journal: Blood (2021)
Between a Rock and a Hard Place: Paraproteinemia Associated with Chronic Myeloid Leukemia
Authors: Tamar Berger, Adi Shacham Abulafia, Shai Shimony, Oren Pasvolsky, Iuliana Vaxman, Yifat Miron, Shimrit Feldman, Avi Leader, Pia Raanani
Journal: Blood (2021)
Association between serum urate and flares in people with gout and evidence for surrogate status: a secondary analysis of two randomised controlled trials
Authors: Lisa K Stamp, Christopher Frampton, Melanie B Morillon, William J Taylor, Nicola Dalbeth, Jasvinder A Singh, Michael Doherty, Weiya Zhang, Helen Richardson, Aliya Sarmanova, Robin Christensen
Journal: The Lancet Rheumatology (2021)
Early Clinical Evaluation of Potential Synergy of Targeted Radiotherapy with Lintuzumab-Ac225 and Venetoclax in Relapsed/Refractory AML
Authors: Gary J. Schiller, Laura Finn, Gail J. Roboz, Johnnie J. Orozco, Tiffany Lin, Mary M Chen, Mohamed M. Hegazi
Journal: Blood (2021)
The Increased Burden of Sickle Cell Disease in Italy: Findings from the Greatalys (Generating Real world Evidence Across ITALy In SCD) Study
Authors: Lucia de Franceschi, Gian Luca Forni, Chiara Castiglioni, Claudia Condorelli, Diletta Valsecchi, Eleonora Premoli, Valentina Perrone, Luca Degli Esposti, Carina Andrea Fiocchi
Journal: Blood (2021)
Comparison of Clinical and Thrombotic Outcomes in Sars-Cov-2- Pneumonia Versus Other Viral Pneumonia in an Urban Academic Medical Center
Authors: Rachel N. Goldberg, Kevin Johns, William Ye, Jeff J. Mucksavage, John G. Quigley, Nancy L. Shapiro, Scott T. Benken, Neha Atal, Jeffrey R. Jacobson, Keri S. Kim
Journal: Blood (2021)
Abstract IA-003: Proteogenomic characterizations of pancreatic ductal adenocarcinoma
Authors: Liwei Cao, Chen Huang, Daniel Cui Zhou, Yingwei Hu, Mamie Lih, Sara R. Savage, Karsten Krug, David J. Clark, Michael Schnaubelt, Lijun Chen, Felipe da Veiga Leprevost, Rodrigo Vargas Eguez, Alexey I. Nesvizhskii, D.R. Mani, Gilbert S. Omenn, Emily S. Boja, Mehdi Mesri, Ana I. Robles, Henry Rodriguez, Oliver F. Bathe, Daniel W. Chan, Ralph H. Hruban, Li Ding, Bing Zhang, Hui Zhang
Journal: Cancer Research (2021)

Abstract Pancreatic cancer is one of the deadliest cancers and the five-year survival rate is less than 10%. Pancreatic ductal adenocarcinoma (PDAC) represents more than 90% of all pancreatic malignancies, and is responsible for the majority of pancreatic cancer-related deaths. Towards understanding the underlying molecular alterations that drive PDAC oncogenesis and identify therapeutic targets for personalized treatments, we comprehensively characterized 140 pancreatic cancers and 67 normal adjacent tissues. To ensure robust, downstream analyses, tumor neoplastic cellularity was assessed via multiple, orthogonal strategies using molecular features, and verified via pathological estimation of tumor cellularity based on histological review to select tumors with sufficient tumor cellularity. We also included the analysis of 9 normal pancreatic ductal tissues. Proteomic, phosphoproteomic, and glycoproteomic analyses were used to characterize proteins and their modifications. In addition, whole genome sequencing, whole exome sequencing, methylation, RNA-seq, and miRNA-seq were performed on the same tissues to facilitate an integrated proteogenomic analysis and determine the impact of genomic alterations on protein expression, signaling pathways, and post-translational modifications. These characterizations revealed functional impacts of genomic and epigenomic alterations on proteins and protein modifications, delineated PDAC cell microenvironment compositions and the immune signatures for immunotherapy, also uncovered putative kinase inhibitors that could be tested for therapy. This integrated proteogenomic characterization of PDAC will serve as a valuable resource for the community, paving the way for early detection and identification of novel therapeutic targets. Citation Format: Liwei Cao, Chen Huang, Daniel Cui Zhou, Yingwei Hu, Mamie Lih, Sara R. Savage, Karsten Krug, David J. Clark, Michael Schnaubelt, Lijun Chen, Felipe da Veiga Leprevost, Rodrigo Vargas Eguez, Alexey I. Nesvizhskii, D.R. Mani, Gilbert S. Omenn, Emily S. Boja, Mehdi Mesri, Ana I. Robles, Henry Rodriguez, Oliver F. Bathe, Daniel W. Chan, Ralph H. Hruban, Li Ding, Bing Zhang, Hui Zhang, Clinical Proteomic Tumor Analysis Consortium. Proteogenomic characterizations of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr IA-003.
Midostaurin in Patients (Pts) with Newly Diagnosed <i>FLT3</i>-Mutation Negative Acute Myeloid Leukemia (AML): Final Results and Measurable Residual Disease (MRD) Analyses from the Unify Trial
Authors: Jacqueline J Cloos, Pau Montesinos, Walter Fiedler, Rouven Müller, Jürgen Krauter, Simona Sica, Jörg Westermann, Maaike E Heidinga, Lok Lam Ngai, Yvonne J.M Oussoren-Brockhoff, Hartmut Döhner, Mark Levis, Gert J. Ossenkoppele, Richard M. Stone, Giedre Koenen, Bourras-Rezki Bengoudifa, Yuan Cheng, Thierry Medts, Valerie Heidinger, Carolin Sachs, Jorge Sierra
Journal: Blood (2021)
Clinical Characteristics and Outcome of Patients with <i>EZH2</i>- Mutant Myelodysplastic Syndromes
Authors: Somedeb Ball, Luis E. E. Aguirre, Akriti G Jain, Mohammad O Hussaini, Najla Al Ali, Sara Marie Tinsley-Vance, Onyee Chan, Andrew T. Kuykendall, Kendra Sweet, Jeffrey E. Lancet, David A. Sallman, Eric Padron, Rami S. Komrokji
Journal: Blood (2021)
Efficiency and Safety of Eltrombopag for Multi-Line Failed Chinese Patients with Immune Thrombocytopenia: Cases with Decreased Megakaryocyte Response Well from Single Center Experience
Authors: Qi Liu, Yingying Shen, Yuzhu Li, Huijing Hu, Wenbin Liu, Yuechao Zhao, Huijie Dong, Yiping Shen, Yuhong Zhou, Baodong Ye, Dijiong Wu
Journal: Blood (2021)
Frontline Venetoclax (ven) Based Combination Therapy in Older Adults with Acute Myeloid Leukemia Treated in the Real-World Setting; A Multi-Institutional Retrospective Study
Authors: Prapti A. Patel, Yazan F. Madanat, Andrew J. Belli, Eric Hansen, Heidi Foss, Molly Schulte, Ching-Kun Wang
Journal: Blood (2021)
活性化誘導シチジンデアミナーゼにおける高IgM症候群変異はG四重鎖結合およびゲノムワイドクロマチン局在化を破壊する【JST・京大機械翻訳】
Authors: T Yewdell William, Kim Youngjun, Chowdhury Priyanka, M Lau Colleen, M Smolkin Ryan, T Belcheva Kalina, C Fernandez Keith, Cols Montserrat, Yen Wei-Feng, Vaidyanathan Bharat, Angeletti Davide, B McDermott Adrian, W Yewdell Jonathan, C Sun Joseph, Chaudhuri Jayanta
Journal: Immunity (2020)
A Propensity Score-Matched Comparison of Axi-Cel and Tisa-Cel for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Real-Life: A Lysa Study from the Descar-T Registry
Authors: Emmanuel Bachy, Steven Le Gouill, Roberta Di Blasi, Pierre Sesques, Guillaume Cartron, David Beauvais, Louise Roulin, Francois Xavier Gros, Choquet Sylvain, Pierre Bories, Marie Thérèse Rubio, Rene-Olivier Casasnovas, Jacques-Olivier Bay, Mohamad Mohty, Magalie Joris, Thomas Gastinne, Jean Jacques Tudesq, Isabelle Chaillol, Florence Broussais, Catherine Thieblemont, Roch Houot, Franck Morschhauser
Journal: Blood (2021)
Clinical, Cytogenetic Characteristics and Survival of Acute Leukemia in a National Research Center Database, 10-Year Real-World Data Review
Authors: Yan Li, Junping Zhang, Hui Wei, Ying Wang, Bingcheng Liu, Dong Lin, Chunlin Zhou, Kaiqi Liu, Benfa Gong, Shuning Wei, Guangji Zhang, Yuntao Liu, Xiaoyuan Gong, Shaowei Qiu, Runxia Gu, Qiuyun Fang, Jingjing Jin, Zhulin Ma, Xuan Liang, Yingchang Mi, Jianxiang Wang
Journal: Blood (2021)
A Comparison of Incomplete Resection Rate of Large and Small Colorectal Polyps by Cold Snare Polypectomy
Authors: Xianzong Ma, Xiutang Feng, Yangjie Li, Yongqiang Du, Jiheng Wang, Yanmei Wu, Hua Jin, Xiaoli Xie, Xin Wang, Peng Jin, Lang Yang, Haihong Wang, Joseph Leung, Jianqiu Sheng, Yuqi He
Journal: Clinical Gastroenterology and Hepatology (2021)
Most ASH Abstracts Reporting Phase II Studies Lead to Peer-Reviewed Publications, but Less Than 50% of "Positive" Abstracts Lead to Phase III Investigations: An Analysis of 371 Abstracts 2013 - 2015
Authors: David Cucchi, Tobias Polak, Gert J. Ossenkoppele, Jacob M. Rowe, Elihu H. Estey
Journal: Blood (2021)
Using Spatial Transcriptomics to Reveal Fetal Liver Hematopoietic Stem Cell-Niche Interactions
Authors: Ruochen Dong, Jonathon Russell, Seth Malloy, Kate Hall, Sarah E Smith, Hua Li, Yongfu Wang, Anoja Perera, Sean McKinney, Brian Slaughter, Jay Unruh, Xi C He, Linheng Li
Journal: Blood (2021)
MGUS and Chip: Two Faces, but Not of the Same Medal
Authors: Matteo Claudio Da Via, Marta Lionetti, Antonio Matera, Erica Travaglino, Ugo Lucca, Emma Riva, Mauro Tettamanti, Luca Baldini, Antonino Neri, Matteo G. Della Porta, Niccolo Bolli
Journal: Blood (2021)
Drive to tackle surgical backlog could backfire, leading surgeon warns
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Government pressure on surgeons to work harder to reduce waiting lists, against a background of bed shortages and a lack of support staff, could lead to an exodus from the profession, the president of the Royal College of Surgeons of England has warned.

The NHS is currently facing extreme pressure from ongoing covid-19 cases, winter pressure, the backlog of routine care caused by the pandemic, and an influx of patients who delayed seeking help.

In the autumn budget the NHS was tasked with providing around 30% more elective activity by 2024-25 than before the pandemic.1 But Neil Mortensen is concerned that increased pressure from targets could drive staff away.

“I fear that an attention to targets and to fulfilling capacity in order to be able to reduce the waiting list will have a significant effect on the staff, both recruitment and retention,” Mortensen said, adding that “the Department of Health and Care’s aim of getting back capacity plus and NHS England’s system …
A Phase I/II Study of Twice Weekly Ixazomib Plus Pomalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma
Authors: Omar Nadeem, Robert A. Redd, Peter Barth, Clifton C Mo, Jacob P. Laubach, Giada Bianchi, Trevor J. Bayliss, Vaishali Sanchorawala, Leyla Shune, Alexandra Distaso, Virginia Dalton, Mary McKenney, Sarah Patches, Isabella Hou, Lindsay Issokson, Anna Barrell, Kelly Masone, Adam S. Sperling, Nikhil C. Munshi, Irene M. Ghobrial, Kenneth C. Anderson, Paul G. Richardson
Journal: Blood (2021)
A Biomimetic Nonantibiotic Nanoplatform for Low‐Temperature Photothermal Treatment of Urinary Tract Infections Caused by Uropathogenic <i>Escherichia coli</i>
Authors: Shi Wenjie, An Jinxia, Tan He, Jia Mengran, Gao Hui
Journal: Advanced Healthcare Materials (2021)

Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) remain a matter of concern, as the clinical use of multiple antibiotics induces antibiotic resistance in bacteria, resulting in the failure of treatments. Despite the emergence of anti-adhesion strategies that can prevent the development of bacterial drug resistance, these strategies are mainly used for disease prevention rather than effective treatment. Photothermal therapy (PTT) has emerged as an efficient alternative for the elimination of bacteria. Nevertheless, high local temperatures related to PTT probably cause damage to surrounding healthy tissue. Herein, a biomimetic nonantibiotic nanoplatform for low-temperature photothermal treatment of UTIs is developed. The nanoplatform comprises polydopamine (PDA) photothermal core and biphenyl mannoside (Man) shell with multivalent high-affinity to UPEC. Scanning electron microscope (SEM) shows PDA-Man possessed ultra-strong targeting binding ability toward UPEC. It is the fact that this impulse UPEC to form a large bacterial cluster. Consequently, the high photothermal energy of the PDA-Man appears predominantly in the affected bacterial area, while the overall environment remains at a low temperature. The fabricated nanoplatform shows excellent photothermal bactericidal effects, approximately 100% in a UTI model. Overall, this low-temperature photothermal nanoplatform provides an appropriate strategy for the elimination of bacteria in clinical applications.
Smart NIR-II croconaine dye-peptide for enhanced photo-sonotheranostics of hepatocellular carcinoma
Authors: Shuang Li, Yang Zhang, Xue Liu, Ye Tian, Yi Cheng, Longguang Tang, Huirong Lin
Journal: Theranostics (2021)

Hepatocellular carcinoma (HCC) is associated with high morbidity and mortality rates. The development of novel nanomaterials represents an important direction for precise HCC theranostics. The combination of photothermal and sonodynamic therapy has provided great benefits for HCC therapy. Theranostic agents in the second near-infrared window (NIR-II, 1000-1700 nm) show great prospects because of their extraordinarily high detection sensitivity, resolution, and deep penetration.
抑制性受容体TIM-3は細胞外DNA取込の抑制により腫瘍内樹状細胞におけるcGAS-STING経路の活性化を制限する【JST・京大機械翻訳】
Authors: de Mingo Pulido Alvaro, Haenggi Kay, P Celias Daiana, Gardner Alycia, Li Jie, Batista-Bittencourt Bruna, Mohamed Eslam, Trillo-Tinoco Jimena, Osunmakinde Olabisi, Pena Reymi, Onimus Alexis, Kaisho Tsuneyasu, Kaufmann Johanna, McEachern Kristen, Soliman Hatem, C Luca Vincent, C Rodriguez Paulo, Yu Xiaoqing, Ruffell Brian
Journal: Immunity (2021)
Impact of Specific Adverse Cytogenetic Features on Outcomes after Allogeneic Hematopoietic Cell Transplantation in Myelodysplastic Syndrome with Very Poor Risk Cytogenetics: A Study from the Chronic Malignancies Working Party of EBMT
Authors: Xavier Poiré, Diderik-jan Eikeman, Linda Koster, Johan A. Maertens, Jan J. Cornelissen, Nathalie Fegueux, Jennifer Byrne, Urpu Salmenniemi, Goda Choi, Patrice Chevallier, Francesca A Kinsella, Thomas Schroeder, Yves Beguin, Didier Blaise, Jean-Henri Bourhis, Jurgen H.E. Kuball, Hendrik Veelken, Jakob R. Passweg, Arancha Bermudez Rodriguez, Micha Srour, Patrick John Hayden, Francesco Onida, Christof Scheid, Marie Robin, Ibrahim Yakoub-Agha
Journal: Blood (2021)
Abstract 9075: Long-Term Prognostic Value of Cardiac MIBG Imaging and 6-Minute Walk Distance for Ventricular Tachyarrhythmias in Patients With Implantable Cardioverter Defibrillator
Authors: Masato Kawasaki, Takahisa Yamada, Tetsuya Watanabe, Takashi Morita, Atsushi Kikuchi, Tsutomu Kawai, Masahiro Seo, Jun Nakamura, Kiyomi Kayama, Kunpei Ueda, Daisuke Sakamoto, Takehiro Kogame, Yuto Tamura, Takeshi Fujita, Keisuke Nishigaki, Yuki Kokubu, Yuto Fukuda, Masatake Fukunami
Journal: Circulation (2021)

Backgrounds: Cardiac MIBG imaging provides prognostic information in patients with chronic heart failure (CHF). Recent studies showed that the highest occurrence of severe arrhythmic events (SAE) was seen in CHF patients with an intermediate decrease in MIBG uptake rather than the lowest values. On the other hand, 6-minute walk distance (6MWD) has been shown to be associated with poor prognostic outcome in CHF patients. However, there is little information available on long-term prognostic value of intermediate decrease in MIBG uptake and 6MWD for the prediction of ventricular tachyarrhythmias in implantable cardioverter defibrillator (ICD) patients. Methods and Results: We prospectively enrolled 232 consecutive outpatients with ICD (age: 65±14 years, male: 81%, NYHA class: 1.7±0.7, LVEF: 47±17%). At entry, all patients underwent cardiac MIBG imaging and 6-minute walk test. An intermediate decrease in heart-to-mediastinum ratio on delayed planar image (H/M) was defined as 1.40-1.89. During a follow-up period of 4.4±2.8 years, 73 patients had appropriate ICD discharge for ventricular tachyarrhythmias. At multivariate Cox analysis, intermediate decrease in H/M and 6MWD were significantly and independently associated with appropriate ICD discharge after adjustment for age, sex, NYHA class and LVEF. Appropriate ICD discharge was significantly more frequently observed in patients with both intermediate decrease in H/M and shorter 6MWD (≤300m) and with either intermediate decrease in H/M or shorter 6MWD than with none of them (49 % vs 35% vs 18%, p&lt;0.0001). Conclusion: Combination of cardiac MIBG imaging and 6MWD would be more strongly associated with an increased risk for ventricular tachyarrhythmias in ICD patients.
Use of Granulocyte Transfusions in Two National Cohorts and Association between Transfusion Dose and Patient Outcomes: The Best Collaborative Study
Authors: Suzy Morton, Claire Boulat, Emma Laing, Joseph Parsons, Elisa Allen, Domenico Francis-Radice, Ruth Keogh, Jennifer A Thompson, Lorna Cain, Monica B. Pagano, Jeffrey McCullough, Pierre Tiberghien, Simon J. Stanworth
Journal: Blood (2021)
42 The role of tissue stiffness in predicting the immunotherapy response in hepatocellular carcinoma
Authors: Betul Gok Yavuz, Elshad Hasanov, Lianchun Xiao, Yehia Mohamed, Sunyoung Lee, Asif Rashid, Ahmed Kaseb, Aliya Qayyum
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Currently, there is no standard biomarker that predict immunotherapy response in hepatocellular carcinoma (HCC). Here, we aim to investigate the role of tissue stiffness measured by magnetic resonance elastography (MRE) in predicting neoadjuvant immunotherapy response in patients with resectable HCC. Methods This was a study of 15 patients with HCC treated with immune checkpoint blockade (ICB) therapy, nivolumab ± ipilimumab, followed by surgical resection. HCC MRE assessment was performed at baseline and after 6 weeks of therapy. HCC stiffness (kPa) was measured on MRE elastograms (liver stiffness maps). Baseline stiffness and changes in stiffness were compared with treatment response to ICB. Treatment response was defined as a tumor with more than 60% necrosis which was the major pathological response. Analysis was performed using descriptive statistics, Fisher’s exact test, and Wilcoxon rank sum test; p-value &lt;0.05 was considered statistically significant. Results Fifteen patients were evaluable for MRE assessment. The median age was 67 years. Etiology of liver disease was NASH (n=4), HCV (n=3), HBV (n=2) and unknown (n=6). Three out of 15 patients (20%) achieved a major pathological response (MPR). Median baseline HCC stiffness and change in stiffness were 4.6 kPa and –0.2 kPa, respectively. Among the 4 patients with stiffness increase, 3 (75%) of them achieved MPR and 1 (25%) did not achieve MPR. Among the patients without stiffness increase, none of them achieved MPR. Fisher’s exact test indicates that increase in stiffness was associated with a higher chance to achieve MPR than patients without stiffness increase (p=0.0088). Median baseline HCC stiffness for responders and non-responders was 6.8 (5.4, 9) kPa and 3.9 (2.2, 9.7) kPa, respectively (p=0.09). The median change in HCC stiffness for responders and non-responders was 1 (1, 1.4) kPa and -0.4 (-2.2, 0.7) kPa, respectively (p=0.02). Conclusions Patients who achieved MPR inclined to have a higher baseline stiffness than patients who did not achieve MPR. Regarding the changes in stiffness between the two arms, patients with MPR group had a greater increase than that in the non-MPR group. In conclusion, baseline and change in MRE stiffness may be a useful biomarkers in predicting response to ICB therapy in HCC. Ethics Approval This was an Institutional Review Board approved study (MDACC 2017–0972). All patients provided written informed consent.