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Cancers
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Biomarkers in Interventional Oncology
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Biomarkers in Interventional Oncology

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 23390

Special Issue Editors

Dr. Marianna Alunni-Fabbroni

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Guest Editor
Department of Radiology, University Hospital, LMU Munich, 81377 München, Germany
Interests: integrated diagnostics; liquid biopsy; minimal residual disease; circulating tumor cell
Prof. Dr. Moritz Wildgruber

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Guest Editor
Department of Radiology, University Hospital, LMU Munich, 81377 München, Germany
Interests: integrated diagnostics; interventional radiology; molecular imaging
Special Issues, Collections and Topics in MDPI journals
Prof. S. Nahum Goldberg

E-Mail Website
Guest Editor
Department of Radiology, Hadassah Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel
Interests: tumor ablation; interventional oncology; minimally invasive therapy

Special Issue Information

Dear Colleagues,

Targeted minimally invasive procedures are being increasingly used in multimodality concepts of personalized cancer treatment. Interventional oncology applies thermal energy, radiation, or local delivery of chemotherapeutic agents at a high dosage directly into the tumor under image guidance in order to treat cancer more effectively. Interventional oncology plays an increasing role and is now considered the fourth pillar of oncology particularly for oligometastases where patients with limited metastatic disease are still considered curable. Response assessment of those minimally invasive therapies is nevertheless limited. Traditional imaging criteria, such as the response evaluation criteria in solid tumors (RECIST), frequently fail to assess, in a timely manner, the effect of minimally invasive cancer treatment. Liquid biopsies (i.e., blood analyses) can greatly supplement response assessment by non-invasively providing very specific biomarkers of tumor biology and its spread, or response to treatment. The role of biomarkers to gauge the response to minimally invasive tumor treatments is the primary topic of this Special Issue. We aim to procure high-quality research, as well as review articles, that address the available kinds of biomarkers to improve therapy monitoring in interventional oncology. Reports of studies combining biomarkers from solid or liquid biopsy together with Radiomics within an integrated diagnostics approach are particularly welcome.

Dr. Marianna Alunni-Fabbroni
Prof. Moritz Wildgruber
Prof. S. Nahum Goldberg
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • integrated diagnostics
  • interventional oncology
  • tumor biomarkers
  • liquid biopsy
  • radiofrequency ablation
  • microwave ablation
  • chemoembolization
  • radioembolization
  • brachytherapy
  • imaging

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Published Papers (7 papers)

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Research

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19 pages, 1550 KiB  
Article
The Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio for Small Renal Cell Carcinomas after Image-Guided Cryoablation or Radio-Frequency Ablation
by Aqua Asif, Vinson Wai-Shun Chan, Filzah Hanis Osman, Jasmine Sze-Ern Koe, Alexander Ng, Oliver Edward Burton, Jon Cartledge, Michael Kimuli, Naveen Vasudev, Christy Ralph, Satinder Jagdev, Selina Bhattarai, Jonathan Smith, James Lenton and Tze Min Wah
Cancers 2023, 15(7), 2187; https://doi.org/10.3390/cancers15072187 - 6 Apr 2023
Cited by 1 | Viewed by 2028
Abstract
There is a lack of cheap and effective biomarkers for the prediction of renal cancer outcomes post-image-guided ablation. This is a retrospective study of patients with localised small renal cell cancer (T1a or T1b) undergoing cryoablation or radiofrequency ablation (RFA) at our institution [...] Read more.
There is a lack of cheap and effective biomarkers for the prediction of renal cancer outcomes post-image-guided ablation. This is a retrospective study of patients with localised small renal cell cancer (T1a or T1b) undergoing cryoablation or radiofrequency ablation (RFA) at our institution from 2003 to 2016. A total of 203 patients were included in the analysis. In the multivariable analysis, patients with raised neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) pre-operatively, post-operatively and peri-operatively are associated with significantly worsened cancer-specific survival, overall survival and metastasis-free survival. Furthermore, an increased PLR pre-operatively is also associated with increased odds of a larger than 25% drop in renal function post-operatively. In conclusion, NLR and PLR are effective prognostic factors in predicting oncological outcomes and peri-operative outcomes; however, larger external datasets should be used to validate the findings prior to clinical application. Full article
(This article belongs to the Special Issue Biomarkers in Interventional Oncology)
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10 pages, 1212 KiB  
Article
Selective Intra-Arterial Doxorubicin Eluting Microsphere Embolization for Desmoid Fibromatosis: A Combined Prospective and Retrospective Study
by Eldad Elnekave, Eytan Ben Ami, Sivan Shamai, Idit Peretz, Shlomit Tamir, Elchanan Bruckheimer, Amos Stemmer, Joseph Erinjeri, Abed Abu Quider, Max Seidensticker, Moritz Wildgruber, Jens Ricke, Antoinette Anazodo, Kin Fen Fung, Alona Zer and Shifra Ash
Cancers 2022, 14(20), 5045; https://doi.org/10.3390/cancers14205045 - 14 Oct 2022
Cited by 7 | Viewed by 2359
Abstract
Desmoid fibromatoses (DFs) are locally aggressive tumors composed of monoclonal fibroblasts within an abundant extracellular matrix. Systemic doxorubicin treatment is effective, but toxic. We investigated arterial doxorubicin eluting embolization (DEE), an approach characterized by high drug concentrations in the tumor alongside limited systemic [...] Read more.
Desmoid fibromatoses (DFs) are locally aggressive tumors composed of monoclonal fibroblasts within an abundant extracellular matrix. Systemic doxorubicin treatment is effective, but toxic. We investigated arterial doxorubicin eluting embolization (DEE), an approach characterized by high drug concentrations in the tumor alongside limited systemic drug exposure. The primary and secondary endpoints were radiological response using MRI and RECIST 1.1, respectively. The study included 24 patients (median age, 24; interquartile range, 16–34 years). Data were collected prospectively for 9 patients and retrospectively for 15 patients. The most frequent tumor locations were chest/abdomen wall and neck/shoulder/axilla (29% each). Of 24 patients, 7 (24%) were treatment naïve, and 17 (71%) had received one or two prior treatments. Patients underwent a median of two treatments (range, 1–4), with a median of 49 mg (range, 8–75) doxorubicin/treatment. Efficacy outcomes were available for 23 patients. With a median follow-up of 8 months (interquartile range, 3–13), median tumor volumes decreased by 59% (interquartile range, 40–71%) and T2 signal intensity decreased by 36% (interquartile range, 19–55%). Of 23 patients, 9 (39%), 12 (52%), and 2 (9%) had a partial response, stable disease, and progressive disease, respectively. DEE was safe and well tolerated, with one reported grade 3–4 adverse event (cord injury). In conclusion, DEE was safe and achieved rapid clinical/volumetric responses in DFs. Full article
(This article belongs to the Special Issue Biomarkers in Interventional Oncology)
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23 pages, 3753 KiB  
Article
An Exploratory Analysis of Changes in Circulating Plasma Protein Profiles Following Image-Guided Ablation of Renal Tumours Provides Evidence for Effects on Multiple Biological Processes
by Tze Min Wah, Jim Zhong, Michelle Wilson, Naveen S. Vasudev and Rosamonde E. Banks
Cancers 2021, 13(23), 6037; https://doi.org/10.3390/cancers13236037 - 30 Nov 2021
Cited by 4 | Viewed by 2298
Abstract
Further biological understanding of the immune and inflammatory responses following ablation is critical to the rational development of combination ablation-immunotherapies. Our pilot exploratory study evaluated the circulating plasma protein profiles after image-guided ablation (IGA) of small renal masses to determine the resultant systemic [...] Read more.
Further biological understanding of the immune and inflammatory responses following ablation is critical to the rational development of combination ablation-immunotherapies. Our pilot exploratory study evaluated the circulating plasma protein profiles after image-guided ablation (IGA) of small renal masses to determine the resultant systemic effects and provide insight into impact both on the tumour and immune system. Patients undergoing cryotherapy (CRYO), radiofrequency ablation (RFA) or microwave ablation (MWA) for small renal tumours were recruited. Blood samples were obtained at four timepoints; two baselines prior to IGA and at 24 h and 1–3 months post-IGA, and a panel of 164 proteins measured. Of 55 patients recruited, 35 underwent ablation (25 CRYO, 8 RFA, 2 MWA) and biomarker measurements. The most marked changes were 24 h post-CRYO, with 29 proteins increasing and 18 decreasing significantly, principally cytokines and proteins involved in regulating inflammation, danger-associated molecular patterns (DAMPs), cell proliferation, hypoxic response, apoptosis and migration. Intra-individual variation was low but inter-individual variation was apparent, for example all patients showed increases in IL-6 (1.7 to 29-fold) but only 50% in CD27. Functional annotation analysis highlighted immune/inflammation and cell proliferation/angiogenesis-related clusters, with interaction networks around IL-6, IL-10, VEGF-A and several chemokines. Increases in IL-8, IL-6, and CCL23 correlated with cryoprobe number (p = 0.01, rs = 0.546; p = 0.009, rs = 0.5515; p = 0.005, rs = 0.5873, respectively). This initial data provide further insights into ablation-induced biological changes of relevance in informing trial design of immunotherapies combined with ablation. Full article
(This article belongs to the Special Issue Biomarkers in Interventional Oncology)
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13 pages, 2375 KiB  
Article
Multiparametric Magnetic Resonance Imaging for Immediate Target Hit Assessment of CD13—Targeted Tissue Factor tTF-NGR in Advanced Malignant Disease
by Mirjam Gerwing, Tobias Krähling, Christoph Schliemann, Saliha Harrach, Christian Schwöppe, Andrew F. Berdel, Sebastian Klein, Wolfgang Hartmann, Eva Wardelmann, Walter L. Heindel, Georg Lenz, Wolfgang E. Berdel and Moritz Wildgruber
Cancers 2021, 13(23), 5880; https://doi.org/10.3390/cancers13235880 - 23 Nov 2021
Cited by 5 | Viewed by 2272
Abstract
Early assessment of target hit in anti-cancer therapies is a major task in oncologic imaging. In this study, immediate target hit and effectiveness of CD13-targeted tissue factor tTF-NGR in patients with advanced malignant disease enrolled in a phase I trial was assessed using [...] Read more.
Early assessment of target hit in anti-cancer therapies is a major task in oncologic imaging. In this study, immediate target hit and effectiveness of CD13-targeted tissue factor tTF-NGR in patients with advanced malignant disease enrolled in a phase I trial was assessed using a multiparametric MRI protocol. Seventeen patients with advanced solid malignancies were enrolled in the trial and received tTF-NGR for at least one cycle of five daily infusions. Tumor target lesions were imaged with multiparametric MRI before therapy initiation, five hours after the first infusion and after five days. The imaging protocol comprised ADC, calculated from DWI, and DCE imaging and vascular volume fraction (VVF) assessment. DCE and VVF values decreased within 5 h after therapy initiation, indicating early target hit with a subsequent decrease in tumor perfusion due to selective tumor vessel occlusion and thrombosis induced by tTF-NGR. Simultaneously, ADC values increased at five hours after tTF-NGR administration. In four patients, treatment had to be stopped due to an increase in troponin T hs, with subsequent anticoagulation. In these patients, a reversed effect, with DCE and VVF values increasing and ADC values decreasing, was observed after anticoagulation. Changes in imaging parameters were independent of the mean vessel density determined by immunohistochemistry. By using a multiparametric imaging approach, changes in tumor perfusion after initiation of a tumor vessel occluding therapy can be evaluated as early as five hours after therapy initiation, enabling early assessment of target hit. Full article
(This article belongs to the Special Issue Biomarkers in Interventional Oncology)
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17 pages, 893 KiB  
Article
NMR-Based Lipid Metabolite Profiles to Predict Outcomes in Patients Undergoing Interventional Therapy for a Hepatocellular Carcinoma (HCC): A Substudy of the SORAMIC Trial
by Thomas Geyer, Johannes Rübenthaler, Marianna Alunni-Fabbroni, Regina Schinner, Sabine Weber, Julia Mayerle, Eric Schiffer, Sebastian Höckner, Peter Malfertheiner and Jens Ricke
Cancers 2021, 13(11), 2787; https://doi.org/10.3390/cancers13112787 - 3 Jun 2021
Cited by 6 | Viewed by 3020
Abstract
Background: This exploratory study aimed to evaluate lipidomic and metabolomic profiles in patients with early and advanced HCCs and to investigate whether certain metabolic parameters may predict the overall survival in these patients. Methods: A total of 60 patients from the prospective, randomized-controlled, [...] Read more.
Background: This exploratory study aimed to evaluate lipidomic and metabolomic profiles in patients with early and advanced HCCs and to investigate whether certain metabolic parameters may predict the overall survival in these patients. Methods: A total of 60 patients from the prospective, randomized-controlled, multicenter phase II SORAMIC trial were included in this substudy; among them were 30 patients with an early HCC who underwent radiofrequency ablation combined with sorafenib or a placebo and 30 patients with an advanced HCC who were treated with a selective internal radiation therapy (SIRT) plus sorafenib vs. sorafenib alone. The blood serum of these patients was analyzed using a standardized nuclear magnetic resonance (NMR) platform. All tested metabolites were correlated with the overall survival. Results: The overall survival (OS) was significantly higher in patients with an early HCC (median OS: 34.0 months) compared with patients with an advanced HCC (median OS: 12.0 months) (p < 0.0001). Patients with high serum concentrations of myo-inositol (MI) had a higher overall survival compared with patients with low concentrations (21.6 vs. 13.8 months) with a Pearson correlation coefficient of 0.331 (p = 0.011). Patients with high serum concentrations of dimethylamine had a higher overall survival compared with patients with low concentrations (25.1 vs. 19.7 months) with a Pearson correlation coefficient of 0.279 (p = 0.034). High concentrations of total cholesterol, LDL-cholesterol and LDL particles (LDL-P) were associated with a decreased overall survival. Conclusions: NMR-based lipidomic and metabolomic profiling has the potential to identify individual metabolite biomarkers that predict the outcome of patients with an HCC exposed to non-invasive therapeutic management. Full article
(This article belongs to the Special Issue Biomarkers in Interventional Oncology)
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Review

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34 pages, 1920 KiB  
Review
Techniques for Profiling the Cellular Immune Response and Their Implications for Interventional Oncology
by Tushar Garg, Clifford R. Weiss and Rahul A. Sheth
Cancers 2022, 14(15), 3628; https://doi.org/10.3390/cancers14153628 - 26 Jul 2022
Cited by 5 | Viewed by 3452
Abstract
In recent years there has been increased interest in using the immune contexture of the primary tumors to predict the patient’s prognosis. The tumor microenvironment of patients with cancers consists of different types of lymphocytes, tumor-infiltrating leukocytes, dendritic cells, and others. Different technologies [...] Read more.
In recent years there has been increased interest in using the immune contexture of the primary tumors to predict the patient’s prognosis. The tumor microenvironment of patients with cancers consists of different types of lymphocytes, tumor-infiltrating leukocytes, dendritic cells, and others. Different technologies can be used for the evaluation of the tumor microenvironment, all of which require a tissue or cell sample. Image-guided tissue sampling is a cornerstone in the diagnosis, stratification, and longitudinal evaluation of therapeutic efficacy for cancer patients receiving immunotherapies. Therefore, interventional radiologists (IRs) play an essential role in the evaluation of patients treated with systemically administered immunotherapies. This review provides a detailed description of different technologies used for immune assessment and analysis of the data collected from the use of these technologies. The detailed approach provided herein is intended to provide the reader with the knowledge necessary to not only interpret studies containing such data but also design and apply these tools for clinical practice and future research studies. Full article
(This article belongs to the Special Issue Biomarkers in Interventional Oncology)
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18 pages, 2673 KiB  
Review
Phosphatidylserine: The Unique Dual-Role Biomarker for Cancer Imaging and Therapy
by Ahmet Kaynak, Harold W. Davis, Andrei B. Kogan, Jing-Huei Lee, Daria A. Narmoneva and Xiaoyang Qi
Cancers 2022, 14(10), 2536; https://doi.org/10.3390/cancers14102536 - 21 May 2022
Cited by 17 | Viewed by 6570
Abstract
Cancer is among the leading causes of death worldwide. In recent years, many cancer-associated biomarkers have been identified that are used for cancer diagnosis, prognosis, screening, and early detection, as well as for predicting and monitoring carcinogenesis and therapeutic effectiveness. Phosphatidylserine (PS) is [...] Read more.
Cancer is among the leading causes of death worldwide. In recent years, many cancer-associated biomarkers have been identified that are used for cancer diagnosis, prognosis, screening, and early detection, as well as for predicting and monitoring carcinogenesis and therapeutic effectiveness. Phosphatidylserine (PS) is a negatively charged phospholipid which is predominantly located in the inner leaflet of the cell membrane. In many cancer cells, PS externalizes to the outer cell membrane, a process regulated by calcium-dependent flippases and scramblases. Saposin C coupled with dioleoylphosphatidylserine (SapC-DOPS) nanovesicle (BXQ-350) and bavituximab, (Tarvacin, human–mouse chimeric monoclonal antibodies) are cell surface PS-targeting drugs being tested in clinical trial for treating a variety of cancers. Additionally, a number of other PS-selective agents have been used to trigger cytotoxicity in tumor-associated endothelial cells or cancer cells in pre-clinical studies. Recent studies have demonstrated that upregulation of surface PS exposure by chemodrugs, radiation, and external electric fields can be used as a novel approach to sensitize cancer cells to PS-targeting anticancer drugs. The objectives of this review are to provide an overview of a unique dual-role of PS as a biomarker/target for cancer imaging and therapy, and to discuss PS-based anticancer strategies that are currently under active development. Full article
(This article belongs to the Special Issue Biomarkers in Interventional Oncology)
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