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Bregni G, Adams R, Bale R, Bali MA, Bargellini I, Blomqvist L, Brown G, Cremolini C, Demetter P, Denecke T, Dohan A, Dopazo C, Elez E, Evrard S, Feakins R, Guckenberger M, Guren MG, Hawkins M, Hoorens A, Huguet E, Intven M, Koessler T, Kunz WG, Lordick F, Lucidi V, Mahnken AH, Malik H, Martinive P, Mauer M, Romero AM, Nagtegaal I, Orsi F, Oyen WJ, Pellerin O, Rengo M, Ricke J, Ricoeur A, Riddell A, Ronot M, Scorsetti M, Seligmann J, Sempoux C, Sheahan K, Stättner S, Svrcek M, Taieb J, West N, Wyrwicz L, Zech CJ, Moehler M, Sclafani F. EORTC consensus recommendations on the optimal management of colorectal cancer liver metastases. Cancer Treat Rev 2025; 136:102926. [PMID: 40179590 DOI: 10.1016/j.ctrv.2025.102926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2025] [Revised: 03/22/2025] [Accepted: 03/24/2025] [Indexed: 04/05/2025]
Abstract
Patients with colorectal cancer liver metastases have long represented a unique and thoroughly investigated population. Nevertheless, the optimal management of these is still controversial with a number of open questions which are only partially addressed by available studies and existing guidelines. The European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Tract Cancer Group (GITCG) sought to fill this knowledge gap and promoted the development of a European consensus on this subject. By using the Delphi methodology and leveraging a multidisciplinary team of 43 international experts, including gastrointestinal oncologists, hepatobiliary surgeons, interventional radiologists, radiation oncologists, radiologists, nuclear medicine physicians and pathologists from 12 European countries, 34 practical recommendations and two consensus statements were proposed. These cover varying aspects of the optimal management of colorectal cancer liver metastases such as baseline imaging, selection criteria for liver-directed therapies, treatment strategies, assessment of treatment response, follow-up, care delivery, clinical research and future perspectives. This roadmap document is intended to complement national and international guidelines, and to provide practical guidance for clinicians and multidisciplinary teams, ultimately promoting practice standardisation, optimal management and better patient outcomes across Europe. Also, it provides a unique opportunity to highlight grey areas and unmet needs, and to give a strategic direction to future research in the field by identifying topics where there is no consensus among experts.
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Affiliation(s)
- Giacomo Bregni
- Department of Gastrointestinal Oncology, Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet, Brussels, Belgium
| | - Richard Adams
- Velindre Cancer Centre, Cardiff University, Cardiff, UK
| | - Reto Bale
- Interventional Oncology, Stereotaxy and Robotics, Department of Radiology, Medical University Innsbruck, Innsbruck, Austria
| | - Maria A Bali
- Department of Radiology, Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet, Brussels, Belgium
| | - Irene Bargellini
- Candiolo Cancer Institute FPO-IRCCS, Department of Surgical Sciences, University of Turin, Italy
| | - Lennart Blomqvist
- Department of Nuclear Medicine/Hospital Physics, Karolinska University Hospital, Stockholm, Sweden
| | | | - Chiara Cremolini
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Pieter Demetter
- Cerba Path, Division CMP, Brussels, Belgium; Laboratory for Experimental Gastroenterology, Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Timm Denecke
- Department of Diagnostic and Interventional Radiology, University of Leipzig Medical Center, University Cancer Center (UCCL), Leipzig, Germany
| | - Anthony Dohan
- Department of Diagnostic and Interventional Radiology, Hôpital Cochin, AP-HP Centre, Université de Paris Cité, Paris, France
| | - Cristina Dopazo
- Department of HPB Surgery and Transplants, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Elena Elez
- Vall d'Hebron Hospital Universitari, and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Serge Evrard
- Institut Bergonié, University of Bordeaux, Bordeaux, France
| | | | | | - Marianne Gronlie Guren
- Department of Oncology, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Maria Hawkins
- University College London, Medical Physics and Biomedical Engineering, NIHR University College London Hospitals Biomedical Research Centre, London, UK
| | | | - Emmanuel Huguet
- Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Martijn Intven
- University Medical Center Utrecht, Utrecht, the Netherlands
| | | | - Wolfgang G Kunz
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Florian Lordick
- Department of Oncology, Gastroenterology, Hepatology and Pulmonology, University of Leipzig Medical Center, University Cancer Center (UCCL), Leipzig, Germany
| | - Valerio Lucidi
- Department of Surgical Oncology, Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Hôpital Erasme, Brussels, Belgium
| | | | | | - Philippe Martinive
- Department of Radiation Oncology, Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet, Brussels, Belgium
| | - Murielle Mauer
- European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium
| | - Alejandra Méndez Romero
- Department of Radiotherapy, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands
| | | | - Franco Orsi
- IRCCS Istituto Europeo di Oncologia, Milan, Italy
| | - Wim Jg Oyen
- Humanitas University, Department of Biomedical Sciences, and IRCCS Humanitas Research Hospital, Department of Nuclear Medicine, Milan, Italy; Rijnstate, Department of Radiology and Nuclear Medicine, Arnhem, the Netherlands; Radboudumc, Department of Radiology and Nuclear Medicine, Nijmegen, the Netherlands
| | - Olivier Pellerin
- Department of Interventional Radiology, Georges Pompidou European Hospital SIRIC-CARPEM, Université Paris Cité, Paris, France
| | | | - Jens Ricke
- University Hospital, LMU Munich, Munich, Germany
| | - Alexis Ricoeur
- Radiology Division, Geneva University Hospitals, Geneva, Switzerland
| | | | - Maxime Ronot
- Beaujon University Hospital, APHP Nord, Clichy, AND Université Paris Cité, Paris, France
| | - Marta Scorsetti
- Department of Radiotherapy and Radiosurgery, IRCCS Humanitas Research Hospital, and Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Jenny Seligmann
- Division of Oncology, Leeds Institute of Medical Research, University of Leeds, Leeds UK
| | - Christine Sempoux
- Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Kieran Sheahan
- Department of Pathology, St Vincent's University Hospital, and UCD School of Medicine, Dublin, Ireland
| | | | - Magali Svrcek
- Saint-Antoine Hospital, Sorbonne Université, Paris, France
| | - Julien Taieb
- Department of GI Oncology, Georges Pompidou European Hospital SIRIC-CARPEM, Université Paris Cité, Paris, France
| | - Nick West
- Division of Pathology and Data Analytics, Leeds Institute of Medical Research, University of Leeds, Leeds UK
| | - Lucjan Wyrwicz
- Maria Sklodowska Curie National Cancer Research Institute, Warsaw, Poland
| | | | | | - Francesco Sclafani
- Department of Gastrointestinal Oncology, Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet, Brussels, Belgium.
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Verona F, Di Bella S, Schirano R, Manfredi C, Angeloro F, Bozzari G, Todaro M, Giannini G, Stassi G, Veschi V. Cancer stem cells and tumor-associated macrophages as mates in tumor progression: mechanisms of crosstalk and advanced bioinformatic tools to dissect their phenotypes and interaction. Front Immunol 2025; 16:1529847. [PMID: 39981232 PMCID: PMC11839637 DOI: 10.3389/fimmu.2025.1529847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Accepted: 01/17/2025] [Indexed: 02/22/2025] Open
Abstract
Cancer stem cells (CSCs) are a small subset within the tumor mass significantly contributing to cancer progression through dysregulation of various oncogenic pathways, driving tumor growth, chemoresistance and metastasis formation. The aggressive behavior of CSCs is guided by several intracellular signaling pathways such as WNT, NF-kappa-B, NOTCH, Hedgehog, JAK-STAT, PI3K/AKT1/MTOR, TGF/SMAD, PPAR and MAPK kinases, as well as extracellular vesicles such as exosomes, and extracellular signaling molecules such as cytokines, chemokines, pro-angiogenetic and growth factors, which finely regulate CSC phenotype. In this scenario, tumor microenvironment (TME) is a key player in the establishment of a permissive tumor niche, where CSCs engage in intricate communications with diverse immune cells. The "oncogenic" immune cells are mainly represented by B and T lymphocytes, NK cells, and dendritic cells. Among immune cells, macrophages exhibit a more plastic and adaptable phenotype due to their different subpopulations, which are characterized by both immunosuppressive and inflammatory phenotypes. Specifically, tumor-associated macrophages (TAMs) create an immunosuppressive milieu through the production of a plethora of paracrine factors (IL-6, IL-12, TNF-alpha, TGF-beta, CCL1, CCL18) promoting the acquisition by CSCs of a stem-like, invasive and metastatic phenotype. TAMs have demonstrated the ability to communicate with CSCs via direct ligand/receptor (such as CD90/CD11b, LSECtin/BTN3A3, EPHA4/Ephrin) interaction. On the other hand, CSCs exhibited their capacity to influence immune cells, creating a favorable microenvironment for cancer progression. Interestingly, the bidirectional influence of CSCs and TME leads to an epigenetic reprogramming which sustains malignant transformation. Nowadays, the integration of biological and computational data obtained by cutting-edge technologies (single-cell RNA sequencing, spatial transcriptomics, trajectory analysis) has significantly improved the comprehension of the biunivocal multicellular dialogue, providing a comprehensive view of the heterogeneity and dynamics of CSCs, and uncovering alternative mechanisms of immune evasion and therapeutic resistance. Moreover, the combination of biology and computational data will lead to the development of innovative target therapies dampening CSC-TME interaction. Here, we aim to elucidate the most recent insights on CSCs biology and their complex interactions with TME immune cells, specifically TAMs, tracing an exhaustive scenario from the primary tumor to metastasis formation.
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Affiliation(s)
- Francesco Verona
- Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, Palermo, Italy
| | - Sebastiano Di Bella
- Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, Palermo, Italy
| | - Roberto Schirano
- Department of Molecular Medicine, University La Sapienza, Rome, Italy
| | - Camilla Manfredi
- Department of Molecular Medicine, University La Sapienza, Rome, Italy
| | - Francesca Angeloro
- Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Giulia Bozzari
- Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, Palermo, Italy
| | - Matilde Todaro
- Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
- Azienda Ospedaliera Universitaria Policlinico “Paolo Giaccone” (AOUP), Palermo, Italy
| | - Giuseppe Giannini
- Department of Molecular Medicine, University La Sapienza, Rome, Italy
- Istituto Pasteur, Fondazione Cenci-Bolognetti, Sapienza University of Rome, Rome, Italy
| | - Giorgio Stassi
- Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, Palermo, Italy
| | - Veronica Veschi
- Department of Molecular Medicine, University La Sapienza, Rome, Italy
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Davis JMK, Niazi MKK, Ricker AB, Tavolara TE, Robinson JN, Annanurov B, Smith K, Mantha R, Hwang J, Shrestha R, Iannitti DA, Martinie JB, Baker EH, Gurcan MN, Vrochides D. Predicting response to neoadjuvant chemotherapy for colorectal liver metastasis using deep learning on prechemotherapy cross-sectional imaging. J Surg Oncol 2024; 130:93-101. [PMID: 38712939 DOI: 10.1002/jso.27673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 04/13/2024] [Accepted: 04/28/2024] [Indexed: 05/08/2024]
Abstract
BACKGROUND AND OBJECTIVES Deep learning models (DLMs) are applied across domains of health sciences to generate meaningful predictions. DLMs make use of neural networks to generate predictions from discrete data inputs. This study employs DLM on prechemotherapy cross-sectional imaging to predict patients' response to neoadjuvant chemotherapy. METHODS Adult patients with colorectal liver metastasis who underwent surgery after neoadjuvant chemotherapy were included. A DLM was trained on computed tomography images using attention-based multiple-instance learning. A logistic regression model incorporating clinical parameters of the Fong clinical risk score was used for comparison. Both model performances were benchmarked against the Response Evaluation Criteria in Solid Tumors criteria. A receiver operating curve was created and resulting area under the curve (AUC) was determined. RESULTS Ninety-five patients were included, with 33,619 images available for study inclusion. Ninety-five percent of patients underwent 5-fluorouracil-based chemotherapy with oxaliplatin and/or irinotecan. Sixty percent of the patients were categorized as chemotherapy responders (30% reduction in tumor diameter). The DLM had an AUC of 0.77. The AUC for the clinical model was 0.41. CONCLUSIONS Image-based DLM for prediction of response to neoadjuvant chemotherapy in patients with colorectal cancer liver metastases was superior to a clinical-based model. These results demonstrate potential to identify nonresponders to chemotherapy and guide select patients toward earlier curative resection.
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Affiliation(s)
- Joshua M K Davis
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
| | - Muhammad Khalid Khan Niazi
- Center for Artificial Intelligence Research and the Clinical Image Analysis Lab, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Ansley B Ricker
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
| | - Thomas E Tavolara
- Center for Artificial Intelligence Research and the Clinical Image Analysis Lab, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Jordan N Robinson
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
| | - Bayram Annanurov
- Center for Artificial Intelligence Research and the Clinical Image Analysis Lab, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Kaylee Smith
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
| | - Rohit Mantha
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
| | - Jimmy Hwang
- Department of Medical Oncology, Atrium Health Carolinas Medical Center, Levine Cancer Institute, Charlotte, North Carolina, USA
| | - Ruchi Shrestha
- Department of Radiology, Atrium Health, Charlotte, North Carolina, USA
| | - David A Iannitti
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
| | - John B Martinie
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
| | - Erin H Baker
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
| | - Metin N Gurcan
- Center for Artificial Intelligence Research and the Clinical Image Analysis Lab, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Dionisios Vrochides
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
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Pei W, Wei K, Wu Y, Qiu Q, Zhu H, Mao L, Shi X, Zhang S, Shi Y, Tao S, Mao H, Pang S, Wang J, Liu M, Wang W, Yang Q, Chen C. Colorectal cancer tumor cell-derived exosomal miR-203a-3p promotes CRC metastasis by targeting PTEN-induced macrophage polarization. Gene 2023; 885:147692. [PMID: 37562585 DOI: 10.1016/j.gene.2023.147692] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 07/25/2023] [Accepted: 08/03/2023] [Indexed: 08/12/2023]
Abstract
(1) Background: Tumor-associated macrophages (TAMs) are important immunocytes associated with liver metastasis of colorectal cancer (CRLM). However, the molecular processes underpinning the interaction between the TME and the tumour-derived exosomal miRNAs in CRLM are not being fully understood; (2) Methods: Transmission electron microscopy was utilized to confirm the existence of exosomes after differential ultracentrifugation. To determine the roles of exosomal miR-203a-3p, an in vivo and in vitro investigation was conducted. The mechanism by which exosomal miR-203a-3p governs the interaction between CRC cells and M2 macrophages was investigated using a dual-luciferase reporter assay, western blot, and other techniques; (3) Results: Overexpression of miR-203a-3p was associated with poor prognosis and liver metastasis in CRC patients. Exosomal miR-203a-3p was upregulated in the plasma of CRC patients and highly metastatic CRC cells HCT116, and it could be transported to macrophages via exosomes. Exosomal miR-203a-3p induced M2 polarization of macrophages by controlling PTEN and activating the PI3K/Akt signaling pathway. M2-polarized macrophages secreted the CXCL12, which increased cancer metastasis and resulted in pre-metastatic niches in CRLM by CXCL12/CXCR4/NF-κB signaling pathway. Co-culture of macrophages with miR-203a-3p-transfected or exosome-treated cells increased the ability of HCT116 cells to metastasize both in vitro and in vivo; (4) Conclusions: Exosomes produced by highly metastatic CRC cells and rich in miR-203a-3p may target PTEN and alter the TME, promoting liver metastasis in CRC patients. These findings offer fresh understanding of the liver metastatic process in CRC.
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Affiliation(s)
- Wenhao Pei
- Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China; Department of Life Sciences, Bengbu Medical College, Bengbu, China.
| | - Ke Wei
- Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China; School of Laboratory Medicine, Bengbu Medical College, Bengbu, China
| | - Yulun Wu
- Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China; Department of Life Sciences, Bengbu Medical College, Bengbu, China
| | - Quanwei Qiu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Haitao Zhu
- Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China; School of Laboratory Medicine, Bengbu Medical College, Bengbu, China
| | - Lingyu Mao
- Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China; Department of Life Sciences, Bengbu Medical College, Bengbu, China
| | - Xiuru Shi
- Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China; School of Laboratory Medicine, Bengbu Medical College, Bengbu, China
| | - Shiwen Zhang
- Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China; Department of Life Sciences, Bengbu Medical College, Bengbu, China
| | - Yingxiang Shi
- Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China; School of Laboratory Medicine, Bengbu Medical College, Bengbu, China
| | - Shuang Tao
- Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China; School of Laboratory Medicine, Bengbu Medical College, Bengbu, China
| | - Huilan Mao
- Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China; Department of Life Sciences, Bengbu Medical College, Bengbu, China
| | - Siyan Pang
- Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China; Department of Life Sciences, Bengbu Medical College, Bengbu, China
| | - Jing Wang
- Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China; School of Laboratory Medicine, Bengbu Medical College, Bengbu, China
| | - Mulin Liu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
| | - Wenrui Wang
- Department of Biotechnology, Bengbu Medical College, Bengbu, China.
| | - Qingling Yang
- Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu, China.
| | - Changjie Chen
- Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu, China.
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Maino C, Vernuccio F, Cannella R, Cortese F, Franco PN, Gaetani C, Giannini V, Inchingolo R, Ippolito D, Defeudis A, Pilato G, Tore D, Faletti R, Gatti M. Liver metastases: The role of magnetic resonance imaging. World J Gastroenterol 2023; 29:5180-5197. [PMID: 37901445 PMCID: PMC10600959 DOI: 10.3748/wjg.v29.i36.5180] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 08/28/2023] [Accepted: 09/11/2023] [Indexed: 09/20/2023] Open
Abstract
The liver is one of the organs most commonly involved in metastatic disease, especially due to its unique vascularization. It's well known that liver metastases represent the most common hepatic malignant tumors. From a practical point of view, it's of utmost importance to evaluate the presence of liver metastases when staging oncologic patients, to select the best treatment possible, and finally to predict the overall prognosis. In the past few years, imaging techniques have gained a central role in identifying liver metastases, thanks to ultrasonography, contrast-enhanced computed tomography (CT), and magnetic resonance imaging (MRI). All these techniques, especially CT and MRI, can be considered the non-invasive reference standard techniques for the assessment of liver involvement by metastases. On the other hand, the liver can be affected by different focal lesions, sometimes benign, and sometimes malignant. On these bases, radiologists should face the differential diagnosis between benign and secondary lesions to correctly allocate patients to the best management. Considering the above-mentioned principles, it's extremely important to underline and refresh the broad spectrum of liver metastases features that can occur in everyday clinical practice. This review aims to summarize the most common imaging features of liver metastases, with a special focus on typical and atypical appearance, by using MRI.
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Affiliation(s)
- Cesare Maino
- Department of Radiology, Fondazione IRCCS San Gerardo dei Tintori, Monza 20900, Italy
| | - Federica Vernuccio
- University Hospital of Padova, Institute of Radiology, Padova 35128, Italy
| | - Roberto Cannella
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Palermo 90127, Italy
| | - Francesco Cortese
- Unit of Interventional Radiology, F Miulli Hospital, Acquaviva delle Fonti 70021, Italy
| | - Paolo Niccolò Franco
- Department of Radiology, Fondazione IRCCS San Gerardo dei Tintori, Monza 20900, Italy
| | - Clara Gaetani
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Valentina Giannini
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Riccardo Inchingolo
- Unit of Interventional Radiology, F Miulli Hospital, Acquaviva delle Fonti 70021, Italy
| | - Davide Ippolito
- Department of Radiology, Fondazione IRCCS San Gerardo dei Tintori, Monza 20900, Italy
- School of Medicine, University of Milano Bicocca, Milano 20100, Italy
| | - Arianna Defeudis
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Giulia Pilato
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Palermo 90127, Italy
| | - Davide Tore
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Riccardo Faletti
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Marco Gatti
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
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Zhang M, Wang Y, Yu L, Zhang Y, Wang Y, Shang Z, Xin Y, Li X, Ning N, Zhang Y, Zhang X. Fusobacterium nucleatum promotes colorectal cancer metastasis by excretion of miR-122-5p from cells via exosomes. iScience 2023; 26:107686. [PMID: 37694140 PMCID: PMC10485600 DOI: 10.1016/j.isci.2023.107686] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 07/23/2023] [Accepted: 08/17/2023] [Indexed: 09/12/2023] Open
Abstract
Fusobacterium nucleatum (Fn) infection and microRNAs (miRNAs) are closely associated with colorectal cancer (CRC) development, but the mechanism by which Fn regulates tumor-suppressive miRNAs via exosomes and facilitates CRC metastasis remains unclear. Here, we identified that Fn infection significantly increased exosomal miR-122-5p levels in the serum of CRC patients and CRC cell culture supernatants through two miRNA panels of high-throughput sequencing and RT-qPCR analysis. In Fn-infected patients, the serum exosomal levels of miR-122-5p were negatively associated with their expression levels of tissues. Downregulated miR-122-5p was demonstrated to enhance the migration, invasion, and metastasis abilities of CRC cells in vivo and in vitro. Secretion of miR-122-5p into exosomes is mediated by hnRNPA2B1. Mechanistically, Fn activated the TGF-β1/Smads signaling pathway to promote EMT by regulation of the miR-122-5p/FUT8 axis. In conclusion, Fn infection may stimulate CRC cells to excrete exosome-wrapped miR-122-5p, and activate the FUT8/TGF-β1/Smads axis to promote metastasis.
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Affiliation(s)
- Mengjiao Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan 250012, China
- Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, China
| | - Yifeng Wang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan 250012, China
- Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, China
| | - Longchen Yu
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan 250012, China
- Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, China
| | - Yanli Zhang
- Department of Clinical Laboratory, Shandong Provincial Third Hospital, Jinan 250031, China
| | - Yanlei Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Ziqi Shang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan 250012, China
- Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, China
| | - Yiwei Xin
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan 250012, China
- Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, China
| | - Xinyang Li
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan 250012, China
- Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, China
| | - Nannan Ning
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan 250012, China
- Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, China
| | - Yi Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan 250012, China
- Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, China
| | - Xin Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan 250012, China
- Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, China
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7
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Jackson A, Pathak R, deSouza NM, Liu Y, Jacobs BKM, Litiere S, Urbanowicz-Nijaki M, Julie C, Chiti A, Theysohn J, Ayuso JR, Stroobants S, Waterton JC. MRI Apparent Diffusion Coefficient (ADC) as a Biomarker of Tumour Response: Imaging-Pathology Correlation in Patients with Hepatic Metastases from Colorectal Cancer (EORTC 1423). Cancers (Basel) 2023; 15:3580. [PMID: 37509240 PMCID: PMC10377224 DOI: 10.3390/cancers15143580] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 06/29/2023] [Accepted: 06/30/2023] [Indexed: 07/30/2023] Open
Abstract
Background: Tumour apparent diffusion coefficient (ADC) from diffusion-weighted magnetic resonance imaging (MRI) is a putative pharmacodynamic/response biomarker but the relationship between drug-induced effects on the ADC and on the underlying pathology has not been adequately defined. Hypothesis: Changes in ADC during early chemotherapy reflect underlying histological markers of tumour response as measured by tumour regression grade (TRG). Methods: Twenty-six patients were enrolled in the study. Baseline, 14 days, and pre-surgery MRI were performed per study protocol. Surgical resection was performed in 23 of the enrolled patients; imaging-pathological correlation was obtained from 39 lesions from 21 patients. Results: There was no evidence of correlation between TRG and ADC changes at day 14 (study primary endpoint), and no significant correlation with other ADC metrics. In scans acquired one week prior to surgery, there was no significant correlation between ADC metrics and percentage of viable tumour, percentage necrosis, percentage fibrosis, or Ki67 index. Conclusions: Our hypothesis was not supported by the data. The lack of meaningful correlation between change in ADC and TRG is a robust finding which is not explained by variability or small sample size. Change in ADC is not a proxy for TRG in metastatic colorectal cancer.
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Affiliation(s)
- Alan Jackson
- Centre for Imaging Sciences, University of Manchester, Manchester M20 4GJ, UK
| | - Ryan Pathak
- Centre for Imaging Sciences, University of Manchester, Manchester M20 4GJ, UK
| | - Nandita M deSouza
- CRUK Cancer Imaging Centre, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Downs Road, London SW7 3RP, UK
| | - Yan Liu
- European Organisation for Research and Treatment of Cancer, 1200 Brussels, Belgium
| | - Bart K M Jacobs
- European Organisation for Research and Treatment of Cancer, 1200 Brussels, Belgium
| | - Saskia Litiere
- European Organisation for Research and Treatment of Cancer, 1200 Brussels, Belgium
| | | | - Catherine Julie
- EA 4340 BECCOH, UVSQ, Universite Paris-Saclay, 92104 Boulogne-Billancourt, France
- Department of Pathology, APHP-Hopital Ambroise Pare, 92100 Boulogne-Billancourt, France
| | - Arturo Chiti
- Nuclear Medicine Unit, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
- Department of Bio-Medical Sciences, Humanitas University, 20072 Milan, Italy
| | - Jens Theysohn
- Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany
| | - Juan R Ayuso
- Radiology Department-CDI, Hospital Clinic Universitari de Barcelona, 08036 Barcelona, Spain
| | - Sigrid Stroobants
- Molecular Imaging and Radiology, University of Antwerp, 2000 Antwerp, Belgium
| | - John C Waterton
- Centre for Imaging Sciences, University of Manchester, Manchester M20 4GJ, UK
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8
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Caruso M, Stanzione A, Prinster A, Pizzuti LM, Brunetti A, Maurea S, Mainenti PP. Role of advanced imaging techniques in the evaluation of oncological therapies in patients with colorectal liver metastases. World J Gastroenterol 2023; 29:521-535. [PMID: 36688023 PMCID: PMC9850941 DOI: 10.3748/wjg.v29.i3.521] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 11/25/2022] [Accepted: 01/03/2023] [Indexed: 01/12/2023] Open
Abstract
In patients with colorectal liver metastasis (CRLMs) unsuitable for surgery, oncological treatments, such as chemotherapy and targeted agents, can be performed. Cross-sectional imaging [computed tomography (CT), magnetic resonance imaging (MRI), 18-fluorodexoyglucose positron emission tomography with CT/MRI] evaluates the response of CRLMs to therapy, using post-treatment lesion shrinkage as a qualitative imaging parameter. This point is critical because the risk of toxicity induced by oncological treatments is not always balanced by an effective response to them. Consequently, there is a pressing need to define biomarkers that can predict treatment responses and estimate the likelihood of drug resistance in individual patients. Advanced quantitative imaging (diffusion-weighted imaging, perfusion imaging, molecular imaging) allows the in vivo evaluation of specific biological tissue features described as quantitative parameters. Furthermore, radiomics can represent large amounts of numerical and statistical information buried inside cross-sectional images as quantitative parameters. As a result, parametric analysis (PA) translates the numerical data contained in the voxels of each image into quantitative parameters representative of peculiar neoplastic features such as perfusion, structural heterogeneity, cellularity, oxygenation, and glucose consumption. PA could be a potentially useful imaging marker for predicting CRLMs treatment response. This review describes the role of PA applied to cross-sectional imaging in predicting the response to oncological therapies in patients with CRLMs.
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Affiliation(s)
- Martina Caruso
- Department of Advanced Biomedical Sciences, University of Naples "Federico II", Napoli 80131, Italy
| | - Arnaldo Stanzione
- Department of Advanced Biomedical Sciences, University of Naples "Federico II", Napoli 80131, Italy
| | - Anna Prinster
- Institute of Biostructures and Bioimaging, National Research Council, Napoli 80131, Italy
| | - Laura Micol Pizzuti
- Institute of Biostructures and Bioimaging, National Research Council, Napoli 80131, Italy
| | - Arturo Brunetti
- Department of Advanced Biomedical Sciences, University of Naples "Federico II", Napoli 80131, Italy
| | - Simone Maurea
- Department of Advanced Biomedical Sciences, University of Naples "Federico II", Napoli 80131, Italy
| | - Pier Paolo Mainenti
- Institute of Biostructures and Bioimaging, National Research Council, Napoli 80131, Italy
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9
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Jiang Q, Tan XP, Zhang CH, Li ZY, Li D, Xu Y, Liu YX, Wang L, Ma Z. Non-Coding RNAs of Extracellular Vesicles: Key Players in Organ-Specific Metastasis and Clinical Implications. Cancers (Basel) 2022; 14:cancers14225693. [PMID: 36428785 PMCID: PMC9688215 DOI: 10.3390/cancers14225693] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/17/2022] [Accepted: 11/17/2022] [Indexed: 11/22/2022] Open
Abstract
Extracellular vesicles (EVs) are heterogeneous membrane-encapsulated vesicles released by most cells. They act as multifunctional regulators of intercellular communication by delivering bioactive molecules, including non-coding RNAs (ncRNAs). Metastasis is a major cause of cancer-related death. Most cancer cells disseminate and colonize a specific target organ via EVs, a process known as "organ-specific metastasis". Mounting evidence has shown that EVs are enriched with ncRNAs, and various EV-ncRNAs derived from tumor cells influence organ-specific metastasis via different mechanisms. Due to the tissue-specific expression of EV-ncRNAs, they could be used as potential biomarkers and therapeutic targets for the treatment of tumor metastasis in various types of cancer. In this review, we have discussed the underlying mechanisms of EV-delivered ncRNAs in the most common organ-specific metastases of liver, bone, lung, brain, and lymph nodes. Moreover, we summarize the potential clinical applications of EV-ncRNAs in organ-specific metastasis to fill the gap between benches and bedsides.
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Affiliation(s)
- Qian Jiang
- Department of Gastroenterology, First Affiliated Hospital of Yangtze University, Health Science Center, Yangtze University, Jingzhou 434023, China
- Digestive Disease Research Institution of Yangtze University, Yangtze University, Jingzhou 434023, China
- Department of Cardiovascular Medicine, Honghu Hospital of Traditional Chinese Medicine, Honghu 433200, China
| | - Xiao-Ping Tan
- Department of Gastroenterology, First Affiliated Hospital of Yangtze University, Health Science Center, Yangtze University, Jingzhou 434023, China
- Digestive Disease Research Institution of Yangtze University, Yangtze University, Jingzhou 434023, China
| | - Cai-Hua Zhang
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China
| | - Zhi-Yuan Li
- Department of Cardiovascular Medicine, Honghu Hospital of Traditional Chinese Medicine, Honghu 433200, China
| | - Du Li
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China
| | - Yan Xu
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China
| | - Yu Xuan Liu
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
| | - Lingzhi Wang
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
- Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
- NUS Centre for Cancer Research (N2CR), National University of Singapore, Singapore 117599, Singapore
- Correspondence: (Z.M.); (L.W.)
| | - Zhaowu Ma
- Department of Gastroenterology, First Affiliated Hospital of Yangtze University, Health Science Center, Yangtze University, Jingzhou 434023, China
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China
- Correspondence: (Z.M.); (L.W.)
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10
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Alshohoumi F, Al-Hamdani A, Hedjam R, AlAbdulsalam A, Al Zaabi A. A Review of Radiomics in Predicting Therapeutic Response in Colorectal Liver Metastases: From Traditional to Artificial Intelligence Techniques. Healthcare (Basel) 2022; 10:2075. [PMID: 36292522 PMCID: PMC9602631 DOI: 10.3390/healthcare10102075] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 10/12/2022] [Accepted: 10/13/2022] [Indexed: 12/12/2024] Open
Abstract
An early evaluation of colorectal cancer liver metastasis (CRCLM) is crucial in determining treatment options that ultimately affect patient survival rates and outcomes. Radiomics (quantitative imaging features) have recently gained popularity in diagnostic and therapeutic strategies. Despite this, radiomics faces many challenges and limitations. This study sheds light on these limitations by reviewing the studies that used radiomics to predict therapeutic response in CRCLM. Despite radiomics' potential to enhance clinical decision-making, it lacks standardization. According to the results of this study, the instability of radiomics quantification is caused by changes in CT scan parameters used to obtain CT scans, lesion segmentation methods used for contouring liver metastases, feature extraction methods, and dataset size used for experimentation and validation. Accordingly, the study recommends combining radiomics with deep learning to improve prediction accuracy.
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Affiliation(s)
- Fatma Alshohoumi
- Department of Computer Science, College of Science, Sultan Qaboos University, P.O. Box 36, Muscat 123, Oman
| | - Abdullah Al-Hamdani
- Department of Computer Science, College of Science, Sultan Qaboos University, P.O. Box 36, Muscat 123, Oman
| | - Rachid Hedjam
- Department of Computer Science, College of Science, Sultan Qaboos University, P.O. Box 36, Muscat 123, Oman
| | - AbdulRahman AlAbdulsalam
- Department of Computer Science, College of Science, Sultan Qaboos University, P.O. Box 36, Muscat 123, Oman
| | - Adhari Al Zaabi
- Department of Human and Clinical Anatomy, College of Medicine & Health Sciences, Sultan Qaboos University, P.O. Box 36, Muscat 123, Oman
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11
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De Cobelli F, Calandri M, Della Corte A, Sirovich R, Gazzera C, Della Vigna P, Bonomo G, Varano GM, Maiettini D, Mauri G, Camisassi N, Steidler S, Ratti F, Gusmini S, Ronzoni M, Aldrighetti L, Odisio BC, Racca P, Fonio P, Veltri A, Orsi F. Multi-institutional analysis of outcomes for thermosphere microwave ablation treatment of colorectal liver metastases: the SMAC study. Eur Radiol 2022; 32:4147-4159. [PMID: 35092474 PMCID: PMC9123066 DOI: 10.1007/s00330-021-08497-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 10/29/2021] [Accepted: 11/17/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Oligometastatic colorectal cancer benefits of locoregional treatments but data concerning microwave ablation (MWA) are limited and interactions with systemic therapy are still debated. The aim of this study is to evaluate safety and effectiveness of Thermosphere™ MWA (T-MWA) of colorectal liver metastases (CLM) and factors affecting local tumor progression-free survival (LTPFS). METHODS In this multi-institutional retrospective study (January 2015-September 2019), patients who underwent T-MWA for CLM were enrolled. Complications according to SIR classification were collected, primary efficacy and LTP were calculated. Analyzed variables included CLM size at diagnosis and at ablation, CLM number, ablation margins, intra-segment progression, chemotherapy before ablation (CBA), variations in size (ΔSDIA-ABL), and velocity of size variation (VDIA-ABL) between CLM diagnosis and ablation. Uni/multivariate analyses were performed using mixed effects Cox model to account for the hierarchical structure of data, patient/lesions. RESULTS One hundred thirty-two patients with 213 CLM were evaluated. Complications were reported in 6/150 procedures (4%); no biliary complications occurred. Primary efficacy was achieved in 204/213 CLM (95.7%). LTP occurred in 58/204 CLM (28.4%). Six-, twelve-, and eighteen-month LTPFS were 88.2%, 75.8%, and 69.9%, respectively. At multivariate analysis, CLM size at ablation (p = 0.00045), CLM number (p = 0.046), ablation margin < 5 mm (p = 0.0035), and intra-segment progression (p < 0.0001) were statistically significant for LTPFS. ΔSDIA-ABL (p = 0.63) and VDIA-ABL (p = 0.38) did not affect LTPFS. Ablation margins in the chemo-naïve group were larger than those in the CBA group (p < 0.0001). CONCLUSION T-MWA is a safe and effective technology with adequate LTPFS rates. Intra-segment progression is significantly linked to LTPFS. CBA does not affect LTPFS. Anticipating ablation before chemotherapy may take the advantages of adequate tumor size with correct ablation margin planning. KEY POINTS • Thermosphere™-Microwave ablation is a safe and effective treatment for colorectal liver metastases with no registered biliary complications in more than 200 ablations. • Metastases size at time of ablation, intra-segment progression, and minimal ablation margin < 5 mm were found statistically significant for local tumor progression-free survival. • Chemotherapy before ablation modifies kinetics growth of the lesions but deteriorates ablation margins and does not significantly impact local tumor progression-free survival.
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Affiliation(s)
- Francesco De Cobelli
- Department of Radiology, IRCCS San Raffaele Hospital, Milan, Italy ,Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy ,School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Marco Calandri
- Department of Oncology, University of Torino, Turin, Italy ,Interventional Radiology Unit, AOU San Luigi Gonzaga, Orbassano, Turin, Italy
| | - Angelo Della Corte
- Department of Radiology, IRCCS San Raffaele Hospital, Milan, Italy ,Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy ,School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Roberta Sirovich
- Department of Mathematics “Giuseppe Peano”, University of Torino, Turin, Italy
| | - Carlo Gazzera
- Radiology Unit, AOU Città Della Salute E Della Scienza, Turin, Italy
| | - Paolo Della Vigna
- Divisione Di Radiologia Interventistica, Istituto Europeo Di Oncologia, Istituto Di Ricovero E Cura a Carattere Scientifico (IRCCS), Milan, Italy
| | - Guido Bonomo
- Divisione Di Radiologia Interventistica, Istituto Europeo Di Oncologia, Istituto Di Ricovero E Cura a Carattere Scientifico (IRCCS), Milan, Italy
| | - Gianluca Maria Varano
- Divisione Di Radiologia Interventistica, Istituto Europeo Di Oncologia, Istituto Di Ricovero E Cura a Carattere Scientifico (IRCCS), Milan, Italy
| | - Daniele Maiettini
- Divisione Di Radiologia Interventistica, Istituto Europeo Di Oncologia, Istituto Di Ricovero E Cura a Carattere Scientifico (IRCCS), Milan, Italy
| | - Giovanni Mauri
- Divisione Di Radiologia Interventistica, Istituto Europeo Di Oncologia, Istituto Di Ricovero E Cura a Carattere Scientifico (IRCCS), Milan, Italy ,Dipartimento Di Oncologia Ed Emato-Oncologia, Università Degli Studi Di Milano, Milan, Italy
| | - Nicola Camisassi
- Divisione Di Radiologia Interventistica, Istituto Europeo Di Oncologia, Istituto Di Ricovero E Cura a Carattere Scientifico (IRCCS), Milan, Italy
| | - Stephanie Steidler
- Department of Radiology, IRCCS San Raffaele Hospital, Milan, Italy ,Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesca Ratti
- Hepatobiliary Surgery Division, IRCCS San Raffaele Hospital, Milan, Italy
| | - Simone Gusmini
- Department of Radiology, IRCCS San Raffaele Hospital, Milan, Italy
| | - Monica Ronzoni
- Unit of Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Luca Aldrighetti
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy ,Hepatobiliary Surgery Division, IRCCS San Raffaele Hospital, Milan, Italy
| | - Bruno C. Odisio
- The University of Texas, Department of Interventional Radiology, MD Anderson Cancer Center, Houston, TX USA
| | - Patrizia Racca
- ColoRectal Cancer Unit, Department of Oncology, AOU Città Della Salute E Della Scienza, Turin, Italy
| | - Paolo Fonio
- Radiology Unit, AOU Città Della Salute E Della Scienza, Turin, Italy ,Department of Surgical Sciences, University of Torino, Turin, Italy
| | - Andrea Veltri
- Department of Oncology, University of Torino, Turin, Italy ,Interventional Radiology Unit, AOU San Luigi Gonzaga, Orbassano, Turin, Italy
| | - Franco Orsi
- Divisione Di Radiologia Interventistica, Istituto Europeo Di Oncologia, Istituto Di Ricovero E Cura a Carattere Scientifico (IRCCS), Milan, Italy
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12
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Zhao S, Mi Y, Zheng B, Wei P, Gu Y, Zhang Z, Xu Y, Cai S, Li X, Li D. Highly-metastatic colorectal cancer cell released miR-181a-5p-rich extracellular vesicles promote liver metastasis by activating hepatic stellate cells and remodelling the tumour microenvironment. J Extracell Vesicles 2022; 11:e12186. [PMID: 35041299 PMCID: PMC8765330 DOI: 10.1002/jev2.12186] [Citation(s) in RCA: 113] [Impact Index Per Article: 37.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 11/21/2021] [Accepted: 12/29/2021] [Indexed: 01/11/2023] Open
Abstract
Liver metastasis of colorectal cancer (CRLM) is the most common cause of CRC-related mortality, and is typically caused by interactions between CRC cells and the tumour microenvironment (TME) in the liver. However, the molecular mechanisms underlying the crosstalk between tumour-derived extracellular vesicle (EV) miRNAs and the TME in CRLM have yet to be fully elucidated. The present study demonstrated that highly metastatic CRC cells released more miR-181a-5p-rich EVs than cells which exhibit a low metastatic potential, in-turn promoting CRLM. Additionally, we verified that FUS mediated packaging of miR-181a-5p into CRC EVs, which in-turn persistently activated hepatic stellate cells (HSCs) by targeting SOCS3 and activating the IL6/STAT3 signalling pathway. Activated HSCs could secrete the chemokine CCL20 and further activate a CCL20/CCR6/ERK1/2/Elk-1/miR-181a-5p positive feedback loop, resulting in reprogramming of the TME and the formation of pre-metastatic niches in CRLM. Clinically, high levels of serum EV containing miR-181a-5p was positively correlated with liver metastasis in CRC patients. Taken together, highly metastatic CRC cells-derived EVs rich in miR-181a-5p could activate HSCs and remodel the TME, thereby facilitating liver metastasis in CRC patients. These results provide novel insight into the mechanism underlying liver metastasis in CRC.
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Affiliation(s)
- Senlin Zhao
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiChina
- Department of OncologyShanghai Medical CollegeFudan UniversityShanghaiChina
| | - Yushuai Mi
- Department of Gastrointestinal SurgeryThe Second HospitalCheeloo College of MedicineShandong UniversityJinanChina
| | - Binbin Zheng
- Department of General SurgeryShanghai General HospitalSchool of MedicineShanghai Jiaotong UniversityShanghaiChina
| | - Ping Wei
- Department of OncologyShanghai Medical CollegeFudan UniversityShanghaiChina
- Cancer InstituteFudan University Shanghai Cancer CenterShanghaiChina
- Department of PathologyFudan University Shanghai Cancer CenterShanghaiChina
| | - Yanzi Gu
- Department of BiobankFudan University Shanghai Cancer CenterShanghaiChina
| | - Zhengxiang Zhang
- Department of OncologyYijishan Hospital of Wannan Medical CollegeWuhuAnhuiChina
| | - Ye Xu
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiChina
- Department of OncologyShanghai Medical CollegeFudan UniversityShanghaiChina
| | - Sanjun Cai
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiChina
- Department of OncologyShanghai Medical CollegeFudan UniversityShanghaiChina
| | - Xinxiang Li
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiChina
- Department of OncologyShanghai Medical CollegeFudan UniversityShanghaiChina
| | - Dawei Li
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiChina
- Department of OncologyShanghai Medical CollegeFudan UniversityShanghaiChina
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13
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Freitas PS, Janicas C, Veiga J, Matos AP, Herédia V, Ramalho M. Imaging evaluation of the liver in oncology patients: A comparison of techniques. World J Hepatol 2021; 13:1936-1955. [PMID: 35069999 PMCID: PMC8727197 DOI: 10.4254/wjh.v13.i12.1936] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/26/2021] [Accepted: 11/28/2021] [Indexed: 02/06/2023] Open
Abstract
The liver is commonly affected by metastatic disease. Therefore, it is essential to detect and characterize liver metastases, assuming that patient management and prognosis rely on it. The imaging techniques that allow non-invasive assessment of liver metastases include ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)/CT, and PET/MRI. In this paper, we review the imaging findings of liver metastases, focusing on each imaging modality's advantages and potential limitations. We also assess the importance of different imaging modalities for the management, follow-up, and therapy response of liver metastases. To date, both CT and MRI are the most appropriate imaging methods for initial lesion detection, follow-up, and assessment of treatment response. Multiparametric MRI is frequently used as a problem-solving technique for liver lesions and has evolved substantially over the past decade, including hardware and software developments and specific intravenous contrast agents. Several studies have shown that MRI performs better in small-sized metastases and moderate to severe liver steatosis cases. Although state-of-the-art MRI shows a greater sensitivity for detecting and characterizing liver metastases, CT remains the chosen method. We also present the controversial subject of the "economic implication" to use CT over MRI.
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Affiliation(s)
- Patrícia S Freitas
- Department of Radiology, Centro Hospitalar Universitário de Lisboa Central, Lisbon 1150-199, Portugal
| | - Catarina Janicas
- Department of Radiology, Centro Hospitalar de Lisboa Ocidental, Lisbon 1449-005, Portugal
| | - José Veiga
- Department of Radiology, Centro Hospitalar Universitário de Lisboa Central, Lisbon 1150-199, Portugal
| | - António P Matos
- Department of Radiology, Hospital Garcia de Orta, EPE, Almada 2805-267, Portugal
- Department of Radiology, Hospital CUF Tejo, Lisbon 1350-352, Portugal
| | - Vasco Herédia
- Department of Radiology, Hospital Garcia de Orta, EPE, Almada 2805-267, Portugal
- Department of Radiology, Hospital Espírito Santo de Évora-EPE, Évora 7000-811, Portugal
| | - Miguel Ramalho
- Department of Radiology, Hospital Garcia de Orta, EPE, Almada 2805-267, Portugal
- Department of Radiology, Hospital da Luz, Lisbon 1500-650, Portugal.
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14
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Radiomics as a New Frontier of Imaging for Cancer Prognosis: A Narrative Review. Diagnostics (Basel) 2021; 11:diagnostics11101796. [PMID: 34679494 PMCID: PMC8534713 DOI: 10.3390/diagnostics11101796] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 09/15/2021] [Accepted: 09/23/2021] [Indexed: 12/12/2022] Open
Abstract
The evaluation of the efficacy of different therapies is of paramount importance for the patients and the clinicians in oncology, and it is usually possible by performing imaging investigations that are interpreted, taking in consideration different response evaluation criteria. In the last decade, texture analysis (TA) has been developed in order to help the radiologist to quantify and identify parameters related to tumor heterogeneity, which cannot be appreciated by the naked eye, that can be correlated with different endpoints, including cancer prognosis. The aim of this work is to analyze the impact of texture in the prediction of response and in prognosis stratification in oncology, taking into consideration different pathologies (lung cancer, breast cancer, gastric cancer, hepatic cancer, rectal cancer). Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. This paper contains a narrative report and a critical discussion of radiomics approaches related to cancer prognosis in different fields of diseases.
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15
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Walker BS, Sutton TL, Zarour L, Hunter JG, Wood SG, Tsikitis VL, Herzig DO, Lopez CD, Chen EY, Mayo SC, Wong MH. Circulating Hybrid Cells: A Novel Liquid Biomarker of Treatment Response in Gastrointestinal Cancers. Ann Surg Oncol 2021; 28:8567-8578. [PMID: 34365557 DOI: 10.1245/s10434-021-10379-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 06/17/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Real-time monitoring of treatment response with a liquid biomarker has potential to inform treatment decisions for patients with rectal adenocarcinoma (RAC), esophageal adenocarcinoma (EAC), and colorectal liver metastasis (CRLM). Circulating hybrid cells (CHCs), which have both immune and tumor cell phenotypes, are detectable in the peripheral blood of patients with gastrointestinal cancers, but their potential as an indicator of treatment response is unexplored. METHODS Peripheral blood specimens were collected from RAC and EAC patients after neoadjuvant therapy (NAT) or longitudinally during therapy and evaluated for CHC levels by immunostaining. Receiver operating characteristics (ROCs) and the Kaplan-Meier method were used to analyze the CHC level as a predictor of pathologic response to NAT and disease-specific survival (DSS), respectively. RESULTS Patients with RAC (n = 23) and EAC (n = 34) were sampled on the day of resection, and 11 patients (32%) demonstrated a pathologic complete response (pCR) to NAT. On ROC analysis, CHC levels successfully discriminated pCR from non-pCR with an area under the curve of 0.82 (95% confidence interval [CI], 0.71-0.92; P < 0.001). Additionally, CHC levels in the EAC patients correlated with residual nodal involvement (P = 0.026) and 1-year DSS (P = 0.029). The patients with RAC who were followed longitudinally during NAT (n = 2) and hepatic arterial infusion therapy for CRLM (n = 2) had CHC levels that decreased with therapy response and increased before clinical evidence of disease progression. CONCLUSION Circulating hybrid cells are a novel blood-based biomarker with potential for monitoring treatment response and disease progression to help guide decisions for further systemic therapy, definitive resection, and post-therapy surveillance. Additional validation studies of CHCs are warranted.
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Affiliation(s)
- Brett S Walker
- Department of Surgery, Oregon Health and Science University (OHSU), Portland, OR, USA
| | - Thomas L Sutton
- Department of Surgery, Oregon Health and Science University (OHSU), Portland, OR, USA
| | - Luai Zarour
- Department of Surgery, Oregon Health and Science University (OHSU), Portland, OR, USA
| | - John G Hunter
- Department of Surgery, Oregon Health and Science University (OHSU), Portland, OR, USA.,Knight Cancer Institute, Portland, OR, USA
| | - Stephanie G Wood
- Department of Surgery, Oregon Health and Science University (OHSU), Portland, OR, USA
| | - V Liana Tsikitis
- Department of Surgery, Oregon Health and Science University (OHSU), Portland, OR, USA.,Knight Cancer Institute, Portland, OR, USA
| | - Daniel O Herzig
- Department of Surgery, Oregon Health and Science University (OHSU), Portland, OR, USA
| | - Charles D Lopez
- Knight Cancer Institute, Portland, OR, USA.,Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University (OHSU), Portland, OR, 97239, USA
| | - Emerson Y Chen
- Knight Cancer Institute, Portland, OR, USA.,Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, 2720 South Moody Aveune, Mailcode KC-CDCB, Portland, OR, 97201, USA
| | - Skye C Mayo
- Department of Surgery, Oregon Health and Science University (OHSU), Portland, OR, USA.,Knight Cancer Institute, Portland, OR, USA
| | - Melissa H Wong
- Knight Cancer Institute, Portland, OR, USA. .,Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, 2720 South Moody Aveune, Mailcode KC-CDCB, Portland, OR, 97201, USA.
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16
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Zhang G, Chen L, Liu A, Pan X, Shu J, Han Y, Huan Y, Zhang J. Comparable Performance of Deep Learning-Based to Manual-Based Tumor Segmentation in KRAS/NRAS/BRAF Mutation Prediction With MR-Based Radiomics in Rectal Cancer. Front Oncol 2021; 11:696706. [PMID: 34395262 PMCID: PMC8358773 DOI: 10.3389/fonc.2021.696706] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 07/15/2021] [Indexed: 12/22/2022] Open
Abstract
Radiomic features extracted from segmented tumor regions have shown great power in gene mutation prediction, while deep learning–based (DL-based) segmentation helps to address the inherent limitations of manual segmentation. We therefore investigated whether deep learning–based segmentation is feasible in predicting KRAS/NRAS/BRAF mutations of rectal cancer using MR-based radiomics. In this study, we proposed DL-based segmentation models with 3D V-net architecture. One hundred and eight patients’ images (T2WI and DWI) were collected for training, and another 94 patients’ images were collected for validation. We evaluated the DL-based segmentation manner and compared it with the manual-based segmentation manner through comparing the gene prediction performance of six radiomics-based models on the test set. The performance of the DL-based segmentation was evaluated by Dice coefficients, which are 0.878 ± 0.214 and 0.955 ± 0.055 for T2WI and DWI, respectively. The performance of the radiomics-based model in gene prediction based on DL-segmented VOI was evaluated by AUCs (0.714 for T2WI, 0.816 for DWI, and 0.887 for T2WI+DWI), which were comparable to that of corresponding manual-based VOI (0.637 for T2WI, P=0.188; 0.872 for DWI, P=0.181; and 0.906 for T2WI+DWI, P=0.676). The results showed that 3D V-Net architecture could conduct reliable rectal cancer segmentation on T2WI and DWI images. All-relevant radiomics-based models presented similar performances in KRAS/NRAS/BRAF prediction between the two segmentation manners.
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Affiliation(s)
- Guangwen Zhang
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Lei Chen
- Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd., Shanghai, China
| | - Aie Liu
- Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd., Shanghai, China
| | - Xianpan Pan
- Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd., Shanghai, China
| | - Jun Shu
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Ye Han
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Yi Huan
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jinsong Zhang
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
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17
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Shen H, Huang C, Wu J, Li J, Hu T, Wang Z, Zhang H, Shao Y, Fu Z. SCRIB Promotes Proliferation and Metastasis by Targeting Hippo/YAP Signalling in Colorectal Cancer. Front Cell Dev Biol 2021; 9:656359. [PMID: 33937255 PMCID: PMC8084105 DOI: 10.3389/fcell.2021.656359] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 03/24/2021] [Indexed: 12/24/2022] Open
Abstract
The complex in which scribble planar cell polarity protein (SCRIB) is located is one of the three main polar protein complexes that play an important role in maintaining epithelial polarity and affecting tumour growth. However, the role of SCRIB in colorectal cancer (CRC) remains largely unknown. This study used date from The Cancer Genome Atlas (TCGA) and clinical samples to determine the expression of SCRIB in CRC and explored its mechanism through bioinformatics analysis and in vivo and in vitro experiments. In this study, SCRIB was found to be highly expressed in CRC patients, and it was often associated with malignant characteristics, such as proliferation, apoptosis, and epithelial-mesenchymal transition (EMT). Furthermore, we found that SCRIB may interact with the Hippo signalling pathway and affect the phosphorylation of YAP and its distribution inside and outside of the nucleus. We concluded that increased expression of SCRIB is likely to inhibit the Hippo signalling pathway by promoting YAP phosphorylation. This role of SCRIB in the progression of CRC provides an important information for the treatment of CRC.
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Affiliation(s)
- Hengyang Shen
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Changzhi Huang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Jingyu Wu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Jie Li
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Tao Hu
- Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Zhenling Wang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Hongqiang Zhang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Yu Shao
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Zan Fu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
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18
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Zhao S, Mi Y, Guan B, Zheng B, Wei P, Gu Y, Zhang Z, Cai S, Xu Y, Li X, He X, Zhong X, Li G, Chen Z, Li D. Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer. J Hematol Oncol 2020; 13:156. [PMID: 33213490 PMCID: PMC7678301 DOI: 10.1186/s13045-020-00991-2] [Citation(s) in RCA: 507] [Impact Index Per Article: 101.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Accepted: 11/03/2020] [Indexed: 12/24/2022] Open
Abstract
Background Mounting evidence has demonstrated the vital importance of tumor-associated macrophages (TAMs) and exosomes in the formation of the premetastatic niche. However, the molecular mechanisms by which tumor-derived exosomal miRNAs interact with TAMs underlying premetastatic niche formation and colorectal cancer liver metastasis (CRLM) remain largely unknown. Methods Transmission electron microscopy and differential ultracentrifugation were used to verify the existence of exosomes. In vivo and in vitro assays were used to identify roles of exosomal miR-934. RNA pull-down assay, dual-luciferase reporter assay, etc. were applied to clarify the mechanism of exosomal miR-934 regulated the crosstalk between CRC cells and M2 macrophages. Results In the present study, we first demonstrated the aberrant overexpression of miR-934 in colorectal cancer (CRC), especially in CRLM, and its correlation with the poor prognosis of CRC patients. Then, we verified that CRC cell-derived exosomal miR-934 induced M2 macrophage polarization by downregulating PTEN expression and activating the PI3K/AKT signaling pathway. Moreover, we revealed that hnRNPA2B1 mediated miR-934 packaging into exosomes of CRC cells and then transferred exosomal miR-934 into macrophages. Interestingly, polarized M2 macrophages could induce premetastatic niche formation and promote CRLM by secreting CXCL13, which activated a CXCL13/CXCR5/NFκB/p65/miR-934 positive feedback loop in CRC cells. Conclusions These findings indicate that tumor-derived exosomal miR-934 can promote CRLM by regulating the crosstalk between CRC cells and TAMs. These findings reveal a tumor and TAM interaction in the metastatic microenvironment mediated by tumor-derived exosomes that affects CRLM. The present study also provides a theoretical basis for secondary liver cancer.
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Affiliation(s)
- Senlin Zhao
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 200032, China
| | - Yushuai Mi
- Department of Gastrointestinal Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, No. 247 Beiyuan Street, Jinan, 250033, China
| | - Bingjie Guan
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 85 Wujin Road, Shanghai, 200080, China
| | - Binbin Zheng
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 85 Wujin Road, Shanghai, 200080, China
| | - Ping Wei
- Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 200032, China.,Cancer Institute, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.,Department of Pathology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China
| | - Yanzi Gu
- Department of Biobank, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China
| | - Zhengxiang Zhang
- Department of Oncology, Yijishan Hospital of Wannan Medical College, No. 2 Zheshan Road, Wuhu, 241001, Anhui, China
| | - Sanjun Cai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 200032, China
| | - Ye Xu
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 200032, China
| | - Xinxiang Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 200032, China
| | - Xuefeng He
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 200032, China
| | - Xinyang Zhong
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 200032, China
| | - Guichao Li
- Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 200032, China. .,Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.
| | - Zhiyu Chen
- Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 200032, China. .,Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.
| | - Dawei Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China. .,Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 200032, China.
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Giannini V, Defeudis A, Rosati S, Cappello G, Mazzetti S, Panic J, Regge D, Balestra G. An innovative radiomics approach to predict response to chemotherapy of liver metastases based on CT images. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2020; 2020:1339-1342. [PMID: 33018236 DOI: 10.1109/embc44109.2020.9176627] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Liver metastases (mts) from colorectal cancer (CRC) can have different responses to chemotherapy in the same patient. The aim of this study is to develop and validate a machine learning algorithm to predict response of individual liver mts. 22 radiomic features (RF) were computed on pretreatment portal CT scans following a manual segmentation of mts. RFs were extracted from 7x7 Region of Interests (ROIs) that moved across the image by step of 2 pixels. Liver mts were classified as non-responder (R-) if their largest diameter increased more than 3 mm after 3 months of treatment and responder (R+), otherwise. Features selection (FS) was performed by a genetic algorithm and classification by a Support Vector Machine (SVM) classifier. Sensitivity, specificity, negative (NPV) and positive (PPV) predictive values were evaluated for all lesions in the training and validation sets, separately. On the training set, we obtained sensitivity of 86%, specificity of 67%, PPV of 89% and NPV of 61%, while, on the validation set, we reached a sensitivity of 73%, specificity of 47%, PPV of 64% and NPV of 57%. Specificity was biased by the low number of R- lesions on the validation set. The promising results obtained in the validation dataset should be extended to a larger cohort of patient to further validate our method.Clinical Relevance- to personalize treatment of patients with metastastic colorectal cancer, based on the likelihood of response to chemotherapy of each liver metastasis.
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20
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Impact of Size and Location of Metastases on Early Tumor Shrinkage and Depth of Response in Patients With Metastatic Colorectal Cancer: Subgroup Findings of the Randomized, Open-Label Phase 3 Trial FIRE-3/AIO KRK-0306. Clin Colorectal Cancer 2020; 19:291-300.e5. [PMID: 32917529 DOI: 10.1016/j.clcc.2020.06.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 06/01/2020] [Accepted: 06/13/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND The Response Evaluation Criteria in Solid Tumors (RECIST) are used to define degrees of response to chemotherapy. For accelerated response evaluation, early tumor shrinkage (ETS) of ≥ 20% has been suggested as a predictor for outcome in metastatic colorectal cancer (mCRC). Together with depth of response (DpR), new alternative metrics have been provided, yielding promising outcome parameters. In this analysis, we aimed to further characterize ETS and DpR. PATIENTS AND METHODS This analysis was based on FIRE-3, a randomized phase 3 trial comparing first-line FOLFIRI plus either cetuximab or bevacizumab in KRAS exon 2 wild-type mCRC. ETS and DpR were determined on the basis of RECIST 1.1 in a blinded radiologic review. ETS was evaluated as a categorized (≥ 20% shrinkage) and continuous parameter. The impact of baseline location and size of metastases on ETS and DpR were evaluated by univariate and multivariate analyses. RESULTS Of 592 patients, 395 (66.7%) had data available for radiologic review. Median continuous ETS for lung, liver, and suspected lymph node metastases was 20%, 23%, and 30%, respectively. The median DpR was -32%, -44%, and -50%, respectively (all P < .01). In multivariate analysis, lung metastases were significantly associated with inferior DpR (P = .021), whereas hepatic metastases led to higher DpR (P = .024). Large metastases were associated with favorable ETS, whereas small metastases were correlated with higher DpR (P < .001). CONCLUSION ETS and DpR depend on the location and size of metastases in mCRC. These associations may establish the basis for further research to optimize the predictive accuracy of both parameters. This may help basing treatment decisions on ETS and DpR.
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21
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Hazhirkarzar B, Khoshpouri P, Shaghaghi M, Ghasabeh MA, Pawlik TM, Kamel IR. Current state of the art imaging approaches for colorectal liver metastasis. Hepatobiliary Surg Nutr 2020; 9:35-48. [PMID: 32140477 DOI: 10.21037/hbsn.2019.05.11] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
One of the most common cancers worldwide, colorectal cancer (CRC) has been associated with significant morbidity and mortality and therefore represents an enormous burden to the health care system. Recent advances in CRC treatments have provided patients with primary and metastatic CRC a better long-term prognosis. The presence of synchronous or metachronous metastasis has been associated, however, with worse survival. The most common site of metastatic disease is the liver. A variety of treatment modalities aimed at targeting colorectal liver metastases (CRLM) has been demonstrated to improve the prognosis of these patients. Loco-regional approaches such as surgical resection and tumor ablation (operative and percutaneous) can provide patients with a chance at long-term disease control and even cure in select populations. Patient selection is important in defining the most suitable treatment option for CRLM in order to provide the best possible survival benefit while avoiding unnecessary interventions and adverse events. Medical imaging plays a crucial role in evaluating the characteristics of CRLMs and disease resectability. Size of tumors, proximity to adjacent anatomical structures, and volume of the unaffected liver are among the most important imaging parameters to determine the suitability of patients for surgical management or other appropriate treatment approaches. We herein provide a comprehensive overview of current-state-of-the-art imaging in the management of CRLM, including staging, treatment planning, response and survival assessment, and post-treatment surveillance. Computed tomography (CT) scan and magnetic resonance imaging (MRI) are two most commonly used techniques, which can be used solely or in combination with functional imaging modalities such as positron emission tomography (PET) and diffusion weighted imaging (DWI). Providing up-to-date evidence on advantages and disadvantages of imaging modalities and tumor assessment criteria, the current review offers a practice guide to assist providers in choosing the most suitable imaging approach for patients with CRLM.
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Affiliation(s)
- Bita Hazhirkarzar
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Pegah Khoshpouri
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Mohammadreza Shaghaghi
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Mounes Aliyari Ghasabeh
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Ihab R Kamel
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Gültekin MA, Türk HM, Beşiroğlu M, Toprak H, Yurtsever I, Yilmaz TF, Sharifov R, Uysal Ö. Relationship between KRAS mutation and diffusion weighted imaging in colorectal liver metastases; Preliminary study. Eur J Radiol 2020; 125:108895. [PMID: 32109834 DOI: 10.1016/j.ejrad.2020.108895] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 01/24/2020] [Accepted: 02/10/2020] [Indexed: 01/02/2023]
Abstract
PURPOSE We aimed to investigate whether there are any differences in apparent diffusion coefficient (ADC) values obtained from colorectal liver metastases (CRLM) according to Kirsten rat sarcoma (KRAS) gene mutation status. METHOD In this retrospective study, we included 22 patients with 65 liver metastases due to colorectal cancer and performed KRAS gene mutation tests. We divided the patients into two groups as KRAS mutation positive (+) (n:10, 30 lesions) and the wild-type group (n:12, 35 lesions). Mann-Whitney U test was used to compare ADC and ADC mean values of the two groups. In addition, we performed receiver-operating characteristic (ROC) analysis to discriminate the two groups in terms of their ADC and ADCmean values. RESULTS The ADC and ADCmean values were found to be statistically significantly lower in the KRAS (+) group compared to the wild-type group. ROC curve analysis revealed a statistically significant difference in terms of ADC and ADCmean with area under the curve (AUC) values of 0.680 and 0.760, respectively. The cut-off values for ADC and ADCmean were 986 × 10-6 mm2/s and 823 × 10-6 mm2/s, respectively. CONCLUSION In our study, the lower ADC and ADCmean values of CRLM are associated with presence of KRAS mutation. ADC and ADCmean values derived from liver metastases due to the colorectal cancer can be used to differentiate KRAS mutation status.
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Affiliation(s)
- Mehmet Ali Gültekin
- Department of Radiology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.
| | - Hacı Mehmet Türk
- Department of Medical Oncology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Mehmet Beşiroğlu
- Department of Medical Oncology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Hüseyin Toprak
- Department of Radiology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Ismail Yurtsever
- Department of Radiology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Temel Fatih Yilmaz
- Department of Radiology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Rasul Sharifov
- Department of Radiology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Ömer Uysal
- Department of Biostatistics, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
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Zamboni G, Mazzaro A, Mansueto G. How to Best Image Colorectal Liver Metastases. CURRENT COLORECTAL CANCER REPORTS 2020. [DOI: 10.1007/s11888-019-00447-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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El-Husseiny NG, Mehana SM, El Zawawy SF. Assessment of the percentage of apparent diffusion coefficient value changes as an early indicator of the response of colorectal hepatic metastases to chemotherapy. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2019. [DOI: 10.1186/s43055-019-0070-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Colorectal cancer is considered one of the most common causes of cancer-related deaths worldwide. We aim to evaluate the efficacy of DWI-MRI in predicting response to chemotherapy in this cohort.
The study included 30 lesions in 20 biopsy proven-colorectal cancer patients with hepatic metastasis larger than 1 cm. All patients underwent both triphasic CT with intravenous contrast, pre-chemotherapy MRI (axial T2 and DW sequences) which was repeated 21 days following chemotherapy. A follow-up CT was done 2 months later. The response of the lesions was evaluated using the RESCIST criteria. On MRI, the lesions corresponding to the ones chosen on CT were identified and the apparent diffusion coefficient (ADC) values of pre- and post-chemotherapy images were recorded and correlated with the CT results.
Results
In the study, 17 (56.7%) of the lesions showed response to chemotherapy while 13 (43.3%) were non-responding. There was no significant difference in pretreatment ADC values between responding and non-responding lesions (p = 0.14). The mean percentage increase in ADC values in responding lesions was 42% compared to 18% in non-responding lesions (p < 0.001). Lesions that showed less than 18% increase were all found to be non-responsive
Conclusion
DWI-MRI has an emerging role in early assessment of early treatment response that can be detected before morphological response for patients with hepatic metastasis from colorectal cancer. Based on our study, the use of 25 % as the cutoff point of percent difference in ADC for detection of non-responding lesions proved to be successful only 21 days after the 1st chemotherapy cycle.
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25
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Badia S, Picchia S, Bellini D, Ferrari R, Caruso D, Paolantonio P, Carbone I, Laghi A, Rengo M. The Role of Contrast-Enhanced Imaging for Colorectal Cancer Management. CURRENT COLORECTAL CANCER REPORTS 2019. [DOI: 10.1007/s11888-019-00443-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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26
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[Role of the radiologist in surgery of colorectal liver metastases : What should be removed and what must remain]. Radiologe 2019; 59:791-798. [PMID: 31410495 DOI: 10.1007/s00117-019-0577-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The radical resection of colorectal liver metastases is the only curative option for affected patients. If properly performed, surgery provides the chance of long-term tumor-free survival. OBJECTIVE Summary of the critical interaction points between radiology and surgery in the planning and performance of (complex) liver resections. RESULTS There are many interaction points between radiology and surgery in the treatment of patients with colorectal liver metastases. Radiology supports surgery by providing detailed information of the localization of metastases, information on liver inflow and outflow as well as basic information on liver quality and function. Perioperatively, it provides interventional treatment options for postoperative complications as well as ablation of non-resectable metastases. CONCLUSION Complex liver resections can only be performed properly and successfully after thorough planning by an interdisciplinary board of surgeons, radiologists and associated disciplines.
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27
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Ravanelli M, Agazzi GM, Tononcelli E, Roca E, Cabassa P, Baiocchi G, Berruti A, Maroldi R, Farina D. Texture features of colorectal liver metastases on pretreatment contrast-enhanced CT may predict response and prognosis in patients treated with bevacizumab-containing chemotherapy: a pilot study including comparison with standard chemotherapy. LA RADIOLOGIA MEDICA 2019; 124:877-886. [PMID: 31172448 DOI: 10.1007/s11547-019-01046-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Accepted: 05/13/2019] [Indexed: 02/06/2023]
Abstract
PURPOSE Bevacizumab added to chemotherapy can improve survival in patients with metastatic colorectal cancer, but no predictive factors of efficacy are available in clinical practice. The aim of this study is to assess the predictive and prognostic value of texture analysis on pretreatment contrast-enhanced CT in patients affected by colorectal liver metastases. MATERIALS AND METHODS Forty-three patients with colorectal liver metastases were retrospectively included in the study: 23 treated with bevacizumab-containing chemotherapy (group A), and 20 with standard chemotherapy (group B). Target liver lesions were analyzed by texture analysis of pretreatment contrast-enhanced CT. Texture analysis produced the parameter uniformity, describing lesion heterogeneity. Radiological response was classified after 3 months according to RECIST-1.1. Overall survival (OS) and progression-free survival (PFS) were considered to be outcome indicators. Multivariable logistic regression and survival analysis were performed. RESULTS Uniformity was lower in responders than in nonresponders (p < 0.001) in group A but not in group B. Lesion CT density was lower in nonresponders in both groups (p = 0.03 and 0.02, respectively). In group A, uniformity was independently correlated with radiological response (odds ratio = 20, p = 0.01), OS and PFS (relative risks 6.94 and 5.05, respectively; p = 0.005 and p = 0.004, respectively). In group B, no variables were correlated with radiological response, OS or PFS. CONCLUSION Texture analysis on contrast-enhanced CT stratified response probability and prognosis in patients with colorectal liver metastases treated with bevacizumab-containing therapy. This result was specific for the bevacizumab group.
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Affiliation(s)
- Marco Ravanelli
- Department of Radiology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy.
| | - Giorgio Maria Agazzi
- Department of Radiology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy
| | - Elena Tononcelli
- Department of Radiology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy
| | - Elisa Roca
- Department of Oncology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy
| | - Paolo Cabassa
- Department of Radiology, Mellino Mellini Hospital, Viale Mazzini 4, 25032, Chiari, Italy
| | - Gianluca Baiocchi
- Department of Surgery, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy
| | - Alfredo Berruti
- Department of Oncology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy
| | - Roberto Maroldi
- Department of Radiology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy
| | - Davide Farina
- Department of Radiology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy
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Mao R, Zhao JJ, Bi XY, Zhang YF, Li ZY, Huang Z, Zhou JG, Zhao H, Cai JQ. A Low Neutrophil to Lymphocyte Ratio Before Preoperative Chemotherapy Predicts Good Outcomes After the Resection of Colorectal Liver Metastases. J Gastrointest Surg 2019; 23:563-570. [PMID: 30066069 DOI: 10.1007/s11605-018-3796-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 04/23/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND The neutrophil to lymphocyte ratio (NLR) is a marker of inflammation and is associated with poor outcomes. We aimed to evaluate the role of the pretreatment NLR in predicting the outcomes after preoperative chemotherapy in patients with colorectal liver metastases (CRLM). METHODS A retrospective review was performed for 183 patients with CRLM. The NLR was measured before chemotherapy, and a receiver operating characteristic (ROC) curve was used to estimate the cutoff value. Logistic regressions were applied to analyze potential predictors of the pathological response. The Cox proportional hazard method was used to analyze survival. RESULTS The pre-chemotherapy NLR was 2.4 ± 1.1, whereas the post-chemotherapy NLR was 2.1 ± 1.6 (p < 0.001). The pretreatment NLR of 2.3 was a significant predictive marker for the pathological response. The pathological response rates were 67.1% in the patients with an NLR ≤ 2.3 and 48.1% in patients with an NLR > 2.3 (p = 0.01). Multivariate analysis revealed that the factors independently associated with pathological responses were a low pretreatment NLR (p = 0.043), radiological response to chemotherapy (p < 0.001), first-line chemotherapy (p = 0.001), and targeted therapy (p = 0.002). The median overall survival (OS) and recurrence-free survival (RFS) were worse in the increased NLR cohort than in the low NLR cohort (OS: 31.1 vs. 43.1 months, p = 0.012; RFS: 6.5 vs. 9.4 months, p = 0.06). According to multivariate analyses, a high pretreatment NLR was a significant predictor for both worse OS (HR = 2.43, 95%CI = 1.49-3.94, p < 0.001) and RFS (HR = 1.53, 95%CI = 1.08-2.18, p = 0.017). CONCLUSIONS An increased pretreatment NLR was a significant predictor of a poor pathological response and worse prognosis after preoperative chemotherapy. The NLR is a simple biomarker for assessing chemotherapy efficacy.
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Affiliation(s)
- Rui Mao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 10021, China
| | - Jian-Jun Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 10021, China
| | - Xin-Yu Bi
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 10021, China
| | - Ye-Fan Zhang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 10021, China
| | - Zhi-Yu Li
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 10021, China
| | - Zhen Huang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 10021, China
| | - Jian-Guo Zhou
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 10021, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 10021, China.
| | - Jian-Qiang Cai
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 10021, China.
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29
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Esser M, Kloth C, Thaiss WM, Reinert CP, Fritz J, Kopp HG, Horger M. CT-response patterns and the role of CT-textural features in inoperable abdominal/retroperitoneal soft tissue sarcomas treated with trabectedin. Eur J Radiol 2018; 107:175-182. [PMID: 30292263 DOI: 10.1016/j.ejrad.2018.09.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Revised: 08/06/2018] [Accepted: 09/05/2018] [Indexed: 01/18/2023]
Abstract
PURPOSE To evaluate CT patterns and textural features of soft tissue sarcomas following trabectedin therapy as well as their suitability for predicting therapeutic response. MATERIAL AND METHODS A total of 31 patients (18 female, 13 male; mean age, 58.0years; range, 38-79years) with sarcoma under trabectedin as a third-line therapy between October 2008 and July 2017 underwent baseline and follow-up contrast-enhanced CT. Response evaluation was based on modifiedCHOI-criteria and RECIST1.1, classified as partial response(PR), stable disease(SD), progressive disease(PD). For CT-texture analysis (CTTA), mean, entropy and uniformity of intensity/skewness/entropy of co-occurrence matrix (COM) and contrast of neighboring-grey-level-dependence-matrix (NGLDM) were calculated. RESULTS Following CHOI-criteria, 9 patients achieved PR, 10 SD and 12 PD. RECIST1.1. classified patients into 5 PR, 15 SD and 11 PD. A frequent (n = 6/31; 19.3%) pattern of response was tumor liquefaction. In responders differences in entropy of entropy-NGLDM(p = 0.028) and uniformity-NGLDM(p = 0.021), in non-responders entropy of average(p = 0.039), deviation(p = 0.04) and uniformity of deviation(p = 0.013) occured between baseline and follow-up. Mean intensity and average were higher when liquefication occured(p = 0.03; p = 0.02), whereas mean deviation was lower(p = 0.02) at baseline compared to other response patterns. Differences in mean(p = 0.023), entropy(p = 0.049) and uniformity(p = 0.023) of entropy-NGLDM were found between responders and non-responders at follow-up. For the mean of heterogeneity a cut-off value was calculated for prediction of response in baseline CTTA (0.12; sensitivity 89%; specificity 77%). CONCLUSION A frequent pattern of response to trabectedin was tumor liquefication being responsible for pseudoprogression, therefore modifiedCHOI should be preferred. Single CT-textural features can be used complementarily for prediction and monitoring response to trabectedin.
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Affiliation(s)
- Michael Esser
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls- University, Hoppe-Seyler-Str.3, 72076, Tübingen, Germany.
| | - Cristopher Kloth
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls- University, Hoppe-Seyler-Str.3, 72076, Tübingen, Germany.
| | - Wolfgang Maximilian Thaiss
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls- University, Hoppe-Seyler-Str.3, 72076, Tübingen, Germany.
| | - Christian Philipp Reinert
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls- University, Hoppe-Seyler-Str.3, 72076, Tübingen, Germany.
| | - Jan Fritz
- Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology and Radiological Science, 601 N. Caroline Street, JHOC 3140A, Baltimore, MD, 21287, United States.
| | - Hans-Georg Kopp
- Department of Internal Medicine II, Eberhard-Karls- University, Otfried-Müller-Str. 10, 72076, Tübingen, Germany; Department of Molecular Oncology, Robert-Bosch-Hospital, Auerbacherstr. 110, Stuttgart, 70736, Germany.
| | - Marius Horger
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls- University, Hoppe-Seyler-Str.3, 72076, Tübingen, Germany.
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