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Phase I Study of Ixazomib Added to Chemotherapy in the Treatment of Acute Lymphoblastic Leukemia in Older Adults

BLOOD 2020年 136卷 41-42页

作者： Amrein, Philip C. Ballen, Karen K. Stevenson, Kristen E. Blonquist, Traci M. Brunner, Andrew M. Hobbs, Gabriela S. Hock, Hanno R. McAfee, Steven L. Moran, Jenna A. Bergeron, Meghan Foster, Julia E. Bertoli, Christina McGregor, Kristin Macrae, Molly Burke, Meghan Behnan, Tanya T. Som, Tina T. Ramos, Aura Y. Vartanian, Megan K. Story, Jennifer Lombardi Connolly, Christine Graubert, Timothy A. Neuberg, Donna S. Fathi, Amir T. Leukemia Center/MGH Cancer Center Massachusetts General Hospital Belmont MA Division of Hematology/Oncology University of Virginia Health Center Charlottesville VA Department of Data Science Dana-Farber Cancer Institute Boston MA Data Science Dana-Farber Cancer Institute Boston MA Center for Leukemia Massachusetts General Hospital Boston MA Leukemia Center Massachusetts General Hospital Boston MA Leukemia Center Massachusetts General Hospital / Harvard Medical School Boston MA Massachusetts General Hospital Blood and Marrow Transplant Program Boston MA Leukemia Center Massachusetts General Hospital Center for Leukemia Cambridge MA

Introduction: While progress has been made in the treatment of childhood leukemia, the outlook for patients >60 years of age with acute lymphoblastic leukemia (ALL) is poor with complete remission rates (CR) of approximately 60% and 3-year survivals (OS) of less than 15%. Intensified treatment in a later CALGB trial showed little improvement with a CR=61% and 5-year OS=6% (Stock, cancer 2013). Ixazomib is an oral proteasome inhibitor, which has shown single agent activity and promising combination activity in pediatric ALL patients (Messinger, Blood 2012). We sought to assess the safety and tolerability, as well as early efficacy of adding ixazomib to a current MGH-DFCI/HCC multi-agent regimen for older adults with ALL. Methods: Patients aged 51 to 75 years of age with newly diagnosed B-ALL and T-ALL were screened for eligibility. Patients with mature ALL (including Burkitt's) were excluded. Patients with Philadelphia chromosome positive ALL (BCR-ABL1+) were eligible, and dasatinib was added to the chemotherapy on Day 10 for these patients. The chemotherapy treatment schedule from induction through maintenance is outlined in Table 1. A standard 3 + 3 patient cohort dose escalation design was used to determine the maximum tolerated dose (MTD) of ixazomib during induction for these patients, the primary objective of the trial. After consolidation I, patients in complete remission (CR) with a suitable donor were offered a hematopoietic stem cell transplantation (HSCT) as per institutional guidelines. Those not going to HSCT continued therapy as noted in the table. Results: There were 19 patients with B-ALL enrolled, none with T-ALL. Among these patients, 7 harbored BCR-ABL1 rearrangements. The median age was 65 years, 74% were male, and 90% had a performance status 0 or 1. The MTD was 2.3 mg of ixazomib, as 2 patients at 3.0 mg developed DLT's: a grade 3 peripheral neuropathy and a grade 5 acute kidney injury (Table 2). Grade 3 and 4 toxicities encountered at any time

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Choosing between HLA-Mismatched Unrelated and Haploidentical Donors: Donor Age Considerations

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Transplantation and Cellular Therapy 2025年第2期31卷 S258-S259页

作者： Mehta, Rohtesh S., MD Wang, Tao, PhD Schmidt, Gabrielle, MPH Gadalla, Shahinaz M., MD, PhD Betts, Brian Christopher, MD Benjamin, Cara L., PhD Arrieta-Bolaños, Esteban, MQC, PhD Bolon, Yung-Tsi Lee, Stephanie J, MD, MPH Department of Stem Cell Transplantation and Cellular Therapy The University of Texas MD Anderson Cancer Center Houston TX CIBMTR® (Center for International Blood and Marrow Transplant Research) Medical College of Wisconsin Milwaukee WI Division of Biostatistics Data Science Institute Medical College of Wisconsin Milwaukee WI Center for International Blood and Marrow Transplant Research (CIBMTR) National Marrow Donor Program/Be The Match Minneapolis MN Clinical Genetics Branch； Division of Cancer Epidemiology and Genetics National Cancer Institute NIH Bethesda MD Roswell Park Comprehensive Cancer Center Buffalo NY Department of Medicine Univeristy of Miami Miller School of Medicine Miami FL Institute for Experimental Cellular Therapy University Hospital Essen Essen Düsseldorf Germany CIBMTR® (Center for International Blood and Marrow Transplant Research) NMDP Minneapolis MN Clinical Research Division Fred Hutchinson Cancer Center Seattle WA

BACKGROUNDHLA-mismatched unrelated donor (mmURD) and haploidentical donor (haplo) are the two most common mismatched donor options for hematopoietic cell transplantation (HCT). Substantial evidence suggests that donor age significantly influences HCT outcomes. However, a direct comparison of these two donor choices while accounting for donor age is lacking. METHODSWe compared the outcomes of mmURD and haplo donor HCT with post-transplantation cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis using data from the Center for International Blood and Marrow Transplant Research. Donors in each group were categorized as younger (<30 years) vs. older (≥30 years) based on the maximal likelihood ratio test. The groups compared were: ‘younger’ haplo (n=1870) vs. ‘older’ mmURD (n=460), and ‘older’ haplo (n=4186) vs. ‘younger’ mmURD (n=600). All patients received PTCy; in vivo or ex vivo T cell depletion was excluded. Most patients had acute leukemia in all groups (65-73%), intermediate disease risk index (58-66%) and received peripheral blood graft (76-82%) [Baseline characteristics, Fig 1]. The primary outcome was GVHD-free relapse-free survival (GRFS), a composite of death, relapse, grade III-IV acute GVHD (aGVHD), and systemic therapy-requiring chronic GVHD (cGVHD). Secondary endpoints were aGVHD, cGVHD, relapse, non-relapse mortality (NRM), progression-free survival, and overall survival. To adjust for multiple testing, a significance level of 0.01 was used for statistical association of the main variable. RESULTSYounger haplo (ref) vs. older mmURD: The 3-year GRFS was 33% (95% confidence interval 31-36) vs. 24% (20-29), respectively. In multivariate analyses [Fig 2], the older mmURD group had significantly worse GRFS (HR 1.20, p=.003) [Fig 3], higher risk of NRM (HR 1.49, p=.005), and grade III-IV aGVHD (HR 2.88, p=.003). Older haplo (ref) vs. younger mmURD: The 3-year GRFS was 24% (23-26) vs. 29% (25-33), respectively, with HR 0.87, p=.02 in multi

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Whole slide images are 2D point clouds: Context-aware survival prediction using patch-based graph convolutional networks

arXiv

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arXiv 2021年

作者： Chen, Richard J. Lu, Ming Y. Shaban, Muhammad Chen, Chengkuan Chen, Tiffany Y. Williamson, Drew F.K. Mahmood, Faisal Department of Pathology Brigham and Women's Hospital Department of Biomedical Informatics Harvard Medical School Cancer Data Science Program Dana-Farber Cancer Institute Cancer Program Broad Institute of Harvard MIT

cancer prognostication is a challenging task in computational pathology that requires context-aware representations of histology features to adequately infer patient survival. Despite the advancements made in weakly-supervised deep learning, many approaches are not context-aware and are unable to model important morphological feature interactions between cell identities and tissue types that are prognostic for patient survival. In this work, we present Patch-GCN, a context-aware, spatially-resolved patch-based graph convolutional network that hierarchically aggregates instance-level histology features to model local- and global-level topological structures in the tumor microenvironment. We validate Patch-GCN with 4,370 gigapixel WSIs across five different cancer types from the cancer Genome Atlas (TCGA), and demonstrate that Patch-GCN outperforms all prior weakly-supervised approaches by 3.58-9.46%. Our code and corresponding models are publicly available at https://***/mahmoodlab/Patch-GCN. Copyright © 2021, The Authors. All rights reserved.

关键词： Pathology

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Prognosis of Breast cancer in European female adolescents and young adults (AYAs): EUROCARE-6 retrospective cohort results

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The Breast 2025年 82卷

作者： Alice Bernasconi Angela Toss Emma Zattarin Seyed Mohsen Mousavi Marcel Blum Claudia E. Kuehni Alexander Katalinic Jan Trallero Elisabetta Rapiti Luigino Dal Maso Laura Botta Silvia Rossi Fedro Peccatori Annalisa Trama Evaluative Epidemiology Unit Department of Epidemiology and Data Science Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy Department of Oncology and Hematology Azienda Ospedaliero-Universitaria di Modena Modena Italy Department of Medical and Surgical Sciences University of Modena and Reggio Emilia Modena Italy Cancer Registry of Eastern Switzerland St.Gallen Switzerland Childhood Cancer Registry and Childhood Cancer Research Group Institute of Social and Preventive Medicine University of Bern Bern Switzerland Division of Pediatric Hematology/Oncology Inselspital Bern University Hospital University of Bern Bern Switzerland University of Lübeck Institute for Social Medicine and Epidemiology Lübeck Germany Cancer Registry of Girona Girona Spain Geneva Cancer Registry University of Geneva Geneva Switzerland Cancer Epidemiology Unit Centro di Riferimento Oncologico (CRO) IRCCS Aviano Italy Department of Oncology and Molecular Medicine Istituto Superiore di Sanità Rome Italy Gynaecology Oncology Program European Institute of Oncology IRCCS Milan Italy

Background Breast cancer (BC) is the most common malignancy in AYA (15–39 years) females and is more aggressive than in adult women (40–69 years). However, an updated overview on BC in AYAs and how it differs from BC in adult women is lacking. Methods We used data from the EUROCARE-6 study to calculate incidence rates (IRs) of BC in AYA and adult women over the period 2001–2013 in Europe. We estimated 5-year and 10-year relative survival (RS) using period analysis. Stage at diagnosis distribution and conditional RS (CS) were used to investigate survival differences. We also reported cumulative incidence of multiple primary neoplasms (MPNs) in AYAs. Results The IR of BC in Europe was ∼18 per 100,000 in AYA females and more than ten-fold higher in adult women. Most BC cases were diagnosed at Stages I-II (74 % in AYAs vs 77 % in adults). Overall, AYAs had lower 5-year RS than adult women (85.0 % vs 89.5 %, respectively); the survival gap slightly decreased in CS. AYAs had worse survival than adult women for early stage and Stage III but better RS for Stage IV (5-year RS 31.5 % vs. 26.3 %). Cumulative incidence of all MPNs in AYAs was ∼6 % at 14 years from BC diagnosis. Conclusions Our findings support the more aggressive behavior of BC in AYAs. The high proportion of early stage at diagnosis is reassuring considering that organized BC screening is not available for AYAs in Europe. Conversely, the incidence of MPNs in AYAs is relevant and might deserve a revision of follow-up strategies.

关键词： Breast cancer Survival Adolescents and young adults Stage at diagnosis Population-based cancer registries

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Comparative analyses for plant virus-based cancer immunotherapy drug development

Cell Biomaterials

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Cell Biomaterials 2025年

作者： Anthony O. Omole Hannah S. Newton Edward Cedrone Kimia Nematpour Shaojun Xie Yongmei Zhao Bao Tran Marina A. Dobrovolskaia Nicole F. Steinmetz Aiiso Yufeng Li Family Department of Chemical and Nano Engineering University of California San Diego La Jolla San Diego CA 92093 USA Shu and K.C. Chien and Peter Farrell Collaboratory University of California San Diego La Jolla San Diego CA 92093 USA Center for Nano-ImmunoEngineering University of California San Diego La Jolla San Diego CA 92093 USA Moores Cancer Center University of California San Diego La Jolla San Diego CA 92093 USA Nanotechnology Characterization Lab Cancer Research Technology Program Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute Frederick MD 21702 USA Sequencing Facility Bioinformatics Group Biomedical Informatics and Data Science Directorate Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute Frederick MD 21702 USA CCR Sequencing Facility Cancer Research Technology Program Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute Frederick MD 21702 USA Department of Bioengineering University of California San Diego La Jolla San Diego CA 92093 USA Department of Radiology University of California San Diego La Jolla San Diego CA USA Institute for Materials Discovery and Design University of California San Diego La Jolla San Diego CA 92093 USA Center for Engineering in Cancer Institute of Engineering Medicine University of California San Diego La Jolla San Diego CA 92093 USA

Cowpea mosaic virus (CPMV) is a plant virus with potent anti-tumor efficacy. Intratumoral CPMV, but not cowpea chlorotic mottle virus (CCMV), reprograms the tumor microenvironment priming durable, systemic anti-tumor immunity. Here, we performed a side-by-side mechanism of action comparison between CPMV and CCMV. Through immune-multiplexing and trafficking studies we observed that CPMV and CCMV are taken up by innate immune cells at similar rates but are processed differently. While CCMV induces proinflammatory interleukins 22, 23, and 27, CPMV is a strong inducer of type I, II, and III interferons, which contribute to the activation and enhancement of immune cell function. We observed that CPMV RNAs activate Toll-like receptor (TLR) 7 upon delivery—and not CCMV RNAs; CPMV RNAs persist longer within cells compared with CCMV. Taken together, this work identifies determinants for CPMV’s unique mechanism for intratumoral immunotherapy. It also broadens our understanding of the utility of plant viruses for biomedical applications.

关键词： plant viruses intratumoral immunotherapy cowpea mosaic virus cowpea chlorotic mottle virus cancer nanotechnology

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Treatment Outcomes By Duffy Genotype in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) Receiving Lenalidomide, Bortezomib, and Dexamethasone (RVd) Alone or Rvd Plus Autologous Stem Cell Transplantation (ASCT) in the Determination Phase 3 Trial

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Transplantation and Cellular Therapy 2025年第2期31卷 S406-S407页

作者： Merz, Lauren E., MD Zon, Rebecca L., MD Jacobus, Susanna J, MSc, MBA Samur, Mehmet K., PhD Zonder, Jeffrey, MD Khan, Dr. Abdullah Mohammad Hassoun, Hani, MD Anderson, Larry D., MD, PhD Efebera, Yvonne, MD Buck, Tondre, MD Shelton, Racquel D. Innis Hartley-Brown, Monique A., MD Lonial, Sagar, MD, FACP Campagnaro, Erica L., MD Voorhees, Peter M. Orlowski, Robert Z., MD, PhD Libby, Edward N., MD Hurd, David D, MD Costello, Caitlin, MD Raje, Noopur S., MD Medvedova, Eva, MD McCarthy, Philip L., MD Milner, Carter P., MD Gasparetto, Cristina, MD Agha, Mounzer E., MD Gowin, Krisstina, DO Kamble, Rammurti T., MD Jagannath, Sundar, MD Nathwani, Nitya, MD Alsina, Melissa, MD Giralt, Sergio A., MD Laubach, Jacob P., MD Nadeem, Omar, MD Ghobrial, Irene M., MD Mo, Clifton C., MD Anderson, Kenneth C., MD Munshi, Nikhil C., MD Richardson, Paul G., MD Department of Medical Oncology Dana-Farber Cancer Institute Harvard Medical School Boston MA Division of Hematology/Oncology Mass General Brigham Boston MA Department of Data Science Dana-Farber Cancer Institute Harvard Medical School Boston MA Barbara Ann Karmanos Cancer Institute / Wayne State University School of Medicine Detroit MI Division of Hematology The Ohio State University Comprehensive Cancer Center Columbus OH Myeloma Service Memorial Sloan Kettering Cancer Center New York NY Myeloma Waldenstrom's and Amyloidosis Program Simmons Comprehensive Cancer Center UT Southwestern Medical Center Dallas TX Division of Blood and Marrow Transplant/Hematology OhioHealth Columbus OH Gibbs Cancer Center & Research Institute Spartanburg SC Alabama Oncology University of Alabama at Birmingham Birmingham AL Winship Cancer Institute of Emory University Atlanta GA Division of Hematology and Oncology Department of Internal Medicine University of Michigan Ann Arbor MI Levine Cancer Institute Atrium Health Wake Forest University School of Medicine Charlotte NC Department of Lymphoma and Myeloma The University of Texas MD Anderson Cancer Center Houston TX Division of Medical Oncology University of Washington and Fred Hutchinson Cancer Center Seattle WA Section of Hematology and Oncology Atrium Health Wake Forest Baptist Medical Center Winston-Salem NC Moores Cancer Center at University of California San Diego San Diego CA Center for Multiple Myeloma Massachusetts General Hospital Harvard Medical School Boston MA

BackgroundErythrocyte Duffy null phenotype, seen in ∼66% of African American (AA) and 0, and pts with elevated LDH. Treatment duration was longer than in ITT pts: median duration from randomization (RVd-alone vs RVd+...

BackgroundErythrocyte Duffy null phenotype, seen in ∼66% of African American (AA) and <1% of White pts, is associated with lower absolute neutrophil count (ANC) and has a key role in cytokine and chemokine homeostasis, which may influence MM pathobiology, response to proinflammatory stressors, and treatment effect. The DETERMINATION trial of RVd-alone vs RVd+ASCT in NDMM showed significantly improved progression-free survival (PFS; median 46.2 vs 67.5 mos; hazard ratio [HR] 1.53, 95% CI 1.23–1.91) with RVd+ASCT. PFS was improved with RVd+ASCT in White pts (n=540, 74.8%; median 44.3 vs 67.2 mos; HR 1.67, 95% CI 1.29–2.15), but in AA pts (n=132, 18.3%) median PFS was not reached (NR) vs 61.4 mos (HR 1.07, 95% CI 0.61–1.89). Race is an inadequate explanation for differences in outcomes; we hypothesized that Duffy null phenotype may influence outcomes and magnitude of benefit with these treatment modalities in NDMM. MethodsPts received RVd-alone or RVd+ASCT followed by R maintenance until progression. Peripheral blood samples underwent genomics analysis for SNP rs2814778 and were classified as C/C (Duffy null) or non-C/C (Duffy non-null). ResultsDuffy status is currently available for 295 pts (Fig 1). The cohort is broadly representative of the ITT population but has fewer AA pts, pts with ECOG PS >0, and pts with elevated LDH. Treatment duration was longer than in ITT pts: median duration from randomization (RVd-alone vs RVd+ASCT) was 62.2 vs 36.5 mos in Duffy null and 44.7 vs 45.5 mos in Duffy non-null pts; median duration of R maintenance was 55.2 vs 30.4 mos in Duffy null and 38.5 vs 42.9 mos in Duffy non-null pts. Median (IQR) baseline ANC was 2.8 (2.1–4.2) in Duffy null and 3.3 (2.5–4.7) x 10 9/L in Duffy non-null pts. Rates of grade ≥3 hematologic adverse events (AEs) during all treatment (RVd-alone vs RVd+ASCT) were 69.2% vs 93.8% in Duffy null and 58.7% vs 96.6% in Duffy non-null pts; rates of grade ≥3 hematologic AEs during R maintenance were 23.1% vs 57.1% in

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Through the Lens of Patient Partners: Challenges in Accrual of Older Adults to NCI Clinical Trials

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Journal of the National cancer Institute - Monographs 2022年第60期2022卷 125-134页

作者： BrintzenhofeSzoc, Karlynn Canin, Beverly Casas-Silva, Esmeralda Denicoff, Andrea Braun-Inglis, Christa Okado, Izumi Bakos, Alexis Oncology Social Work Kent School of Social Work University of Louisville Louisville KY United States SCOREboard Patient Advocate Board The Cancer and Aging Research Group United States Center for Biomedical Informatics and Information Technology Informatics and Data Science Program National Institutes of Health National Cancer Institute Rockville MD United States Division of Cancer Treatment and Diagnosis Cancer Therapy and Evaluation Program National Institutes of Health National Cancer Institute Rockville MD United States Clinical Faculty UH Nancy Atmospera-Walch School of Nursing University of Hawaii Cancer Center Hawaii M U NCORP Honolulu HI United States University of HawaiiCancer Center Honolulu HI United States Division of Cancer Prevention Community Oncology and Prevention Trials Research Group National Institutes of Health National Cancer Institute Rockville MD United States

The workshop “Engaging Older Adults in cancer Clinical Trials Conducted in the NCI Clinical Trials Network: Challenges and Opportunities” included a Patient Stakeholder Workgroup that explored the needs and concerns of older adults with cancer regarding clinical trials. To accomplish this, the workgroup conducted patient focus groups in which participants were interviewed, recorded conversations were analyzed and coded, and salient themes were identified. The focus groups identified general barriers to accrual such as complex consent forms, general communication, restrictive eligibility, nonreferrals, patient costs, cultural insensitivity, limited accessibility in community settings, and transportation issues. They also identified the influence of knowledgeable information presenters, improved care, family or caregiver support, and the desire to help others as drivers or reasons to participate in clinical trials. The workshop concluded that multi-level interventions could be used to increase the accrual of older adults to National cancer Institute clinical trials as well as others. © The Author(s) 2022. Published by Oxford University Press. All rights reserved.

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Nivolumab plus low-dose ipilimumab in hypermutated HER2-negative metastatic breast cancer: a phase II trial (NIMBUS)

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Nature Communications 2025年第1期16卷 1-13页

作者： Barroso-Sousa, Romualdo Zanudo, Jorge Gomez Tejeda Li, Tianyu Reddy, Sangeetha M. Emens, Leisha A. Kuntz, Thomas M. Silva, Carolina Alves Costa AlDubayan, Saud H. Chu, Hoyin Overmoyer, Beth Lange, Paulina DiLullo, Molly K. Montesion, Meagan Kasparian, Julie Hughes, Melissa E. Attaya, Victoria Basta, Ameer Lin, Nancy U. Tayob, Nabihah Jeselsohn, Rinath Mittendorf, Elizabeth A. Tolaney, Sara M. Hospital Brasília Rede Américas Brasilia Brazil Medical Oncology Dana-Farber Cancer Institute Boston MA United States Breast Oncology Program Dana-Farber Brigham Cancer Center Boston MA United States Harvard Medical School Boston MA United States Data Science Dana-Farber Cancer Institute Boston MA United States University of Texas Southwestern Medical Center Dallas TX United States University of Pittsburgh Medical Center Pittsburgh PA United States Department of Biostatistics Harvard T. H. Chan School of Public Health Boston MA United States Gustave Roussy Cancer Campus (GRCC) Clinicobiome Cedex Villejuif France Foundation Medicine Inc. Boston MA United States Division of Breast Surgery Department of Surgery Brigham and Women’s Hospital Boston MA United States

In the phase II NIMBUS trial, patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) and high tumor mutational burden (TMB ≥ 9 mut/Mb) received nivolumab (3 mg/kg biweekly) and low-dose ipilimumab (1 mg/kg every 6 weeks) for 2 years or until progression. The primary endpoint was objective response rate (ORR) per RECIST 1.1 criteria. Among 30 patients enrolled, the median TMB was 10.9 mut/Mb (range: 9–110) and the confirmed objective response rate was 20%. Secondary endpoints included progression-free survival, overall survival, clinical benefit rate, and safety and tolerability, including immune-related adverse events (irAEs). A prespecified correlative outcome was to evaluate the ORR in patients with a TMB ≥ 14 mut/Mb. Patients with TMB ≥ 14 mut/Mb (n = 6) experienced higher response rates (60% vs 12%;p = 0.041) and showed a trend towards improved progression-free survival and overall survival compared to patients with TMB < 14 mut/Mb. Exploratory genomic analyses suggested that ESR1 and PTEN mutations may be associated with poor response, while clinical benefit was associated with a decrease or no change in tumor fraction by serial circulating tumor DNA during treatment. Stool microbiome analysis revealed that baseline blood TMB, PD-L1 positivity, and immune-related diarrhea are associated with distinct taxonomic profiles. In summary, some patients with hypermutated HER2-negative MBC experience extended clinical benefit with a dual immunotherapy regimen;a higher TMB, and additional genomic and microbiome biomarkers may optimize patient selection for therapy with nivolumab plus low-dose ipilimumab. (Funded by Bristol Myers Squibb;*** identifier, NCT03789110). © The Author(s) 2025.

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Association of Risk Factors For Venous Thromboembolism and Overall Survival in Lung cancer

Blood Vessels, Thrombosis & Hemostasis

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Blood Vessels, Thrombosis & Hemostasis 2025年

作者： Thomas E. Plate Asaad Trabolsi Rachel S. Kronenfeld Leticia E. Campoverde Dan Morgenstern-Kaplan Alyssa J. Mercadel Michael Caballero Wei Zhao Gerald A. Soff Sylvester Comprehensive Cancer Center University of Miami Miller School of Medicine Miami Fl USA Hematology Oncology Fellowship Program Jackson Memorial Health System/ University of Miami Miami Fl USA Division of Pediatric Hematology/Oncology University of Miami/Jackson Memorial Hospital Miami FL Internal Medicine Residency program division of internal medicine Department of Medicine University of Miami/ Jackson Memorial Hospital Miami Division of Gynecologic Oncology Department of Obstetrics Gynecology and Reproductive Sciences University of Miami Leonard M. Miller School of Medicine Miami Data Science and Engineering UHealth Information Technology University of Miami Miami FL Biostatistics and Bioinformatics Shared Resource Sylvester Comprehensive Cancer Center University of Miami Miami FL Division of Hematology Department of Medicine University of Miami Miller School of Medicine Miami Fl USA

Venous thromboembolism (VTE) is a frequent complication in patients with lung cancer, but the risk factors and incidence in different lung cancer subtypes have not been fully characterized. Despite multiple studies supporting the use of VTE prophylaxis in patients with cancer at increased risk of VTE by the Khorana score (KS), routine use of VTE prophylaxis is uncommon in clinical practice for these patients. This study further characterizes the risk factors and incidence of VTE and in patients with lung cancer at a university cancer center. Further, we assessed the association of KS and its individual components with overall survival in this same group of patients with lung cancer. Utilizing natural language processing and human review to detect thrombotic events in the electronic medical record, a 12-month incidence of 10.1% was identified in the 632 lung cancer patients analyzed. Significant risk factors included age <60 years and white blood cell count (WBC) ≥ 11× 10 9 /L, but KS itself was not significantly associated with VTE. The median overall survival was 12 months with VTE. The KS, age ≥ 60 years, stage III-IV, WBC ≥ 11× 10 9 /L, Hgb <10 gm/dL, BMI, surgery and VTE were identified as significant predictors of death. These findings warrant further validation, as the KS and two of its individual components in this study of lung cancer were significantly associated with reduced overall survival.

关键词： Lung cancer thrombosis Khorana Score cancer associated thrombosis

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Roles of Cellular Neighborhoods in Hepatocellular Carcinoma Pathogenesis

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Pathology: Mechanisms of Disease 1000年第1期20卷 169-192页

作者： Lichun Ma Cherry Caiyi Li Xin Wei Wang 2Liver Cancer Program Center for Cancer Research National Cancer Institute Bethesda Maryland USA 1Cancer Data Science Laboratory Center for Cancer Research National Cancer Institute Bethesda Maryland USA email: lichun.ma@nih.gov 3Laboratory of Human Carcinogenesis Center for Cancer Research National Cancer Institute Bethesda Maryland USA

The development of hepatocellular carcinoma (HCC) involves an intricate interplay among various cell types within the liver. Unraveling the orchestration of these cells, particularly in the context of various etiologies, may hold the key to deciphering the underlying mechanisms of this complex disease. The advancement of single-cell and spatial technologies has revolutionized our ability to determine cellular neighborhoods and understand their crucial roles in disease pathogenesis. In this review, we highlight the current research landscape on cellular neighborhoods in chronic liver disease and HCC, as well as the emerging computational approaches applicable to delineate disease-associated cellular neighborhoods, which may offer insights into the molecular mechanisms underlying HCC pathogenesis and pave the way for effective disease interventions.

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