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Systematic Review and Meta-Analysis of Imaging Biomarkers for Breakthrough Cancer...
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Systematic Review and Meta-Analysis of Imaging Biomarkers for Breakthrough Cancer Therapies

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Medical Imaging and Theranostics".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 14102

Special Issue Editors

Dr. Kyung Won Kim

E-Mail Website
Guest Editor
Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
Interests: cancer imaging; clinical trial; immunotherapy; response criteria; precision medicine; imaging biomarker
Dr. Hyo Jung Park

E-Mail Website
Guest Editor
Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
Interests: abdominal imaging; cancer imaging; immunotherapy; response criteria; precision medicine; imaging biomarker

Special Issue Information

Dear Colleagues,

Breakthrough therapy is a new treatment demonstrating substantial improvement over existing therapies. The Food and Drug Administration (FDA) supports the rapid approval of these breakthrough therapies if there is evidence demonstrating significant clinical benefit over currently available ones based on clinical or surrogate endpoints. In the oncology field, the use of imaging biomarkers as objective indicators of significant endpoints such as therapeutic efficacy, drug toxicity, or prognosis has been increasing. To increase the level of evidence indicating the clinical benefits of a therapy, a systematic summary of scattered research through systematic review and meta-analysis is very helpful. In this Special Issue, we aim to improve readers’ understanding of how imaging biomarkers are utilized to assess the clinical benefit of breakthrough therapies through systematic reviews and/or meta-analyses. Systematic review papers on, but not limited to, the following topics are welcome:

  • Imaging endpoints for anticancer efficacy in breakthrough cancer therapies;
  • Typical and atypical response patterns during immunotherapy including pseudoprogression and hyperprogression;
  • Predictive value of imaging biomarkers for therapeutic response or prognosis;
  • Imaging utilization for safety evaluation.

Dr. Kyung Won Kim
Dr. Hyo Jung Park
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 short 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. Diagnostics 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 2600 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

  • Antitumor efficacy
  • Response criteria
  • Toxicity
  • Prediction
  • Prognosis
  • Pseudoprogression
  • Hyperprogression
  • Molecular targeted therapy
  • Immunotherapy
  • Cell therapy
  • Functional and molecular imaging

Published Papers (6 papers)

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Research

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8 pages, 1856 KiB  
Article
Additional Value of [18F]FDG PET or PET/CT for Response Assessment of Patients with Gastrointestinal Stromal Tumor Undergoing Molecular Targeted Therapy: A Meta-Analysis
by Kota Yokoyama, Junichi Tsuchiya, Yuji Nakamoto and Ukihide Tateishi
Diagnostics 2021, 11(3), 475; https://doi.org/10.3390/diagnostics11030475 - 8 Mar 2021
Cited by 5 | Viewed by 1728
Abstract
To assess the additional value of 2-deoxy-2-[18F] fluoro-d-glucose ([18F]FDG) positron emission tomography (PET) or PET/CT over conventional morphological imaging techniques in the treatment response assessment of gastrointestinal stromal tumor (GIST) to molecular targeted therapy (MTT), we performed a meta-analysis [...] Read more.
To assess the additional value of 2-deoxy-2-[18F] fluoro-d-glucose ([18F]FDG) positron emission tomography (PET) or PET/CT over conventional morphological imaging techniques in the treatment response assessment of gastrointestinal stromal tumor (GIST) to molecular targeted therapy (MTT), we performed a meta-analysis of all the available studies to compare the predictive value of [18F]FDG PET or PET/CT and conventional imaging techniques for assessing the response to MTT in GIST. We determined the sensitivities and specificities across studies, we calculated the positive and negative likelihood ratios (LR) and made summary receiver operating characteristic curves (SROC) using hierarchical regression models. Pooled analysis included 4 studies comprising 88 patients. The performance characteristics in [18F]FDG PET or PET/CT and CT were as follows: sensitivity, 89% (95% confidence interval (CI) 78, 95), 52% (39, 64); specificity, 65% (44, 83), 92% (75, 99); diagnostic odds ratios (DOR), 5.8 (2.0, 16.8 4.9 (1.5, 16.1); positive LR, 1.9 (1.1, 3.4), 3.0 (1.1, 8.1); and negative LR, 0.23 (0.03, 1.6), 0.66 (0.42, 1.0), respectively. In SROC curves, the area under the curve (AUC) was 0.81 (SE, 0.11) and 0.71 (SE, 0.13) and the Q* index was 0.74 and 0.66, respectively. [18F]FDG PET/CT had higher sensitivity, while DOR and SROC curves showed better diagnostic performance in [18F]FDG PET and PET/CT studies as compared to CT. Full article
(This article belongs to the Special Issue Systematic Review and Meta-Analysis of Imaging Biomarkers for Breakthrough Cancer Therapies)
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Review

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11 pages, 1389 KiB  
Review
Comparison of [18F]FDG PET/CT and MRI for Treatment Response Assessment in Multiple Myeloma: A Meta-Analysis
by Kota Yokoyama, Junichi Tsuchiya and Ukihide Tateishi
Diagnostics 2021, 11(4), 706; https://doi.org/10.3390/diagnostics11040706 - 15 Apr 2021
Cited by 8 | Viewed by 2457
Abstract
The present study was designed to assess the additional value of 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) to magnetic resonance imaging (MRI) in the treatment response assessment of multiple myeloma (MM). We performed a meta-analysis of all available [...] Read more.
The present study was designed to assess the additional value of 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) to magnetic resonance imaging (MRI) in the treatment response assessment of multiple myeloma (MM). We performed a meta-analysis of all available studies to compare the detectability of treatment response of [18F]FDG PET/CT and MRI in treated MM. We defined detecting a good therapeutic effect as positive, and residual disease as negative. We determined the sensitivities and specificities across studies, calculated the positive and negative likelihood ratios (LR), and made summary receiver operating characteristic curves (SROC) using hierarchical regression models. The pooled analysis included six studies that comprised 278 patients. The respective performance characteristics (95% confidence interval (CI)) of [18F]FDG PET/CT and MRI were as follows: sensitivity of 80% (56% to 94%) and 25% (19% to 31%); specificity of 58% (44% to 71%) and 83% (71% to 91%); diagnostic odds ratio (DOR) of 6.0 (3.0–12.0) and 1.7 (0.7–2.7); positive LR of 1.8 (1.3–2.4) and 1.4 (0.7–2.7); and negative LR of 0.33 (0.21–0.53) and 0.81 (0.62–1.1). In the respective SROC curves, the area under the curve was 0.77 (SE, 0.038) and 0.59 (SE, 0.079) and the Q* index was 0.71 and 0.57. Compared with MRI, [18F]FDG PET/CT had higher sensitivity and better DOR and SROC curves. Compared with MRI, [18F]FDG PET/CT had greater ability to detect the treatment assessment of MM. Full article
(This article belongs to the Special Issue Systematic Review and Meta-Analysis of Imaging Biomarkers for Breakthrough Cancer Therapies)
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14 pages, 1881 KiB  
Review
Concordance between Response Assessment Using Prostate-Specific Membrane Antigen PET and Serum Prostate-Specific Antigen Levels after Systemic Treatment in Patients with Metastatic Castration Resistant Prostate Cancer: A Systematic Review and Meta-Analysis
by Sangwon Han, Sungmin Woo, Yong-il Kim, Jae-Lyun Lee, Andreas G. Wibmer, Heiko Schoder, Jin-Sook Ryu and Hebert Alberto Vargas
Diagnostics 2021, 11(4), 663; https://doi.org/10.3390/diagnostics11040663 - 7 Apr 2021
Cited by 17 | Viewed by 2597
Abstract
Prostate-specific membrane antigen positron emission tomography (PSMA PET) has recently gained interest as a promising tool for treatment response evaluation in metastatic castration-resistant prostate cancer (CRPC). We performed a systematic review and meta-analysis assessing the concordance between response evaluation using PSMA PET and [...] Read more.
Prostate-specific membrane antigen positron emission tomography (PSMA PET) has recently gained interest as a promising tool for treatment response evaluation in metastatic castration-resistant prostate cancer (CRPC). We performed a systematic review and meta-analysis assessing the concordance between response evaluation using PSMA PET and serum prostate-specific antigen (PSA) level after systemic treatment and the association between PSMA PET and overall survival in metastatic CRPC patients. PubMed, Embase, and Cochrane library databases were searched until August 2020. Studies that reported the concordance between PSMA PET and PSA response were included. PSMA PET and PSA response evaluation were dichotomized into response vs. non-response to construct two-by-two contingency tables; an ≥30% increase in PSMA PET according to PET Response Criteria in Solid Tumors 1.0 and as an increase in serum PSA level of ≥25% as per Prostate Cancer Working Group 3 guidelines were defined as non-response. The percent agreement rates were pooled using random-effect model. Ten studies (268 patients) were included. The concordance rates ranged 0.50–0.84 with a pooled proportion of 0.73 (95% confidence interval 0.67–0.79). Patients were treated with 177Lu-PSMA therapy in five, chemotherapy in three, 223Ra in one, and more than one type in one study. Various PET parameters were used: the most widely evaluated was PSMA tumor volume (PSMA-TV). Similar proportions were found across different therapeutic agents, PET response parameters, and regarding directionality of discordance (PSA response/PSMA non-response vs. PSMA response/PSA non-response). Two studies reported that a decrease in PSMA-TV was associated with better overall survival. PSMA PET and PSA response assessments were discordant in nearly a fourth of metastatic CRPC patients. Further studies are warranted to establish the clinical meaning of this discordance and define appropriate management for such clinical situation. Full article
(This article belongs to the Special Issue Systematic Review and Meta-Analysis of Imaging Biomarkers for Breakthrough Cancer Therapies)
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12 pages, 2545 KiB  
Review
Interreader Reliability of Liver Imaging Reporting and Data System Treatment Response: A Systematic Review and Meta-Analysis
by Dong Wook Kim, Sang Hyun Choi, Ji Sung Lee, So Yeon Kim, So Jung Lee and Jae Ho Byun
Diagnostics 2021, 11(2), 237; https://doi.org/10.3390/diagnostics11020237 - 4 Feb 2021
Cited by 4 | Viewed by 1755
Abstract
Background: For a proper management strategy in patients with locoregionally treated hepatocellular carcinoma (HCC), it is essential that the Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (LR-TR) has high interreader reliability. We aimed to systematically evaluate the interreader reliability of [...] Read more.
Background: For a proper management strategy in patients with locoregionally treated hepatocellular carcinoma (HCC), it is essential that the Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (LR-TR) has high interreader reliability. We aimed to systematically evaluate the interreader reliability of LR-TR and sources of any study heterogeneity. Methods: Original studies reporting the interreader reliability of LR-TR were identified in MEDLINE and EMBASE up to 20 September 2020. The pooled kappa coefficient (κ) was calculated using the DerSimonian–Laird random effects model. Subgroup analyses were performed according to imaging modality (magnetic resonance imaging (MRI) or computed tomography (CT)). Meta-regression analyses were performed to explore study heterogeneity. Results: Eight studies with 851 HCCs were finally included. Pooled κ was 0.70 (95% CI, 0.58–0.82) for CT/MRI LR-TR, and those of MRI and CT were 0.71 (95% CI, 0.53–0.89) and 0.71 (95% CI, 0.65–0.78), respectively. Study design (p < 0.001) and type of treatment (p = 0.02) were significantly associated with substantial study heterogeneity. Conclusion: LR-TR showed substantial interreader reliability regardless of the imaging modality. Because of substantial study heterogeneity, which was significantly associated with study design and type of treatment, published values for the interreader reliability of LR-TR should be interpreted with care. Full article
(This article belongs to the Special Issue Systematic Review and Meta-Analysis of Imaging Biomarkers for Breakthrough Cancer Therapies)
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13 pages, 1756 KiB  
Review
Immune Checkpoint Inhibitors with or without Radiotherapy in Non-Small Cell Lung Cancer Patients with Brain Metastases: A Systematic Review and Meta-Analysis
by Dong Yeong Kim, Pyeong Hwa Kim, Chong Hyun Suh, Kyung Won Kim and Ho Sung Kim
Diagnostics 2020, 10(12), 1098; https://doi.org/10.3390/diagnostics10121098 - 16 Dec 2020
Cited by 8 | Viewed by 2829
Abstract
This study aimed to evaluate the radiologic response and adverse event rates of immune checkpoint inhibitor (ICI) therapy with or without radiotherapy for the treatment of non-small cell lung cancer (NSCLC) brain metastases. A systematic literature search was performed up to January 3, [...] Read more.
This study aimed to evaluate the radiologic response and adverse event rates of immune checkpoint inhibitor (ICI) therapy with or without radiotherapy for the treatment of non-small cell lung cancer (NSCLC) brain metastases. A systematic literature search was performed up to January 3, 2020. Studies evaluating the intracranial objective response rates (ORR) and/or disease control rates (DCR) of ICI with or without radiotherapy for treating NSCLC brain metastases were included. Consequently, twelve studies satisfied inclusion criteria. ICI combined with radiotherapy (pooled ORR, 95%; DCR, 97%) showed better local efficacy compared to ICI monotherapy (pooled ORR, 24%; DCR, 44%; p < 0.01 for both ORR and DCR). Grade 3 or 4 central nervous system (CNS)-related adverse event rates were not different (5% vs. 4%; p = 0.93). In conclusion, ICI combined with radiotherapy showed better intracranial efficacy than ICI monotherapy for treating NSCLC brain metastases. CNS-related grade 3 or 4 adverse event rate was not statistically different between the two groups. Several prospective trials are needed to compare the efficacy of ICI combined with radiotherapy and ICI monotherapy. Full article
(This article belongs to the Special Issue Systematic Review and Meta-Analysis of Imaging Biomarkers for Breakthrough Cancer Therapies)
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Other

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14 pages, 1809 KiB  
Systematic Review
Magnetic Resonance Imaging for Surveillance of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis
by Dong Hwan Kim, Sang Hyun Choi, Ju Hyun Shim, So Yeon Kim, Seung Soo Lee, Jae Ho Byun, Kyung Won Kim and Joon-Il Choi
Diagnostics 2021, 11(9), 1665; https://doi.org/10.3390/diagnostics11091665 - 12 Sep 2021
Cited by 7 | Viewed by 1986
Abstract
Our meta-analysis aimed to evaluate the diagnostic performance of surveillance magnetic resonance imaging (sMRI) for detecting hepatocellular carcinoma (HCC), and to compare the diagnostic performance of sMRI between different protocols. Original articles about the diagnostic accuracy of sMRI for detecting HCC were found [...] Read more.
Our meta-analysis aimed to evaluate the diagnostic performance of surveillance magnetic resonance imaging (sMRI) for detecting hepatocellular carcinoma (HCC), and to compare the diagnostic performance of sMRI between different protocols. Original articles about the diagnostic accuracy of sMRI for detecting HCC were found in major databases. The meta-analytic pooled sensitivity and specificity of sMRI for detecting HCC were determined using a bivariate random effects model. The pooled sensitivity and specificity of full MRI and abbreviated MRI protocols were compared using bivariate meta-regression. In the total seven included studies (1830 patients), the pooled sensitivity of sMRI for any-stage HCC and very early-stage HCC were 85% (95% confidence interval, 79–90%; I2 = 0%) and 77% (66–85%; I2 = 32%), respectively. The pooled specificity for any-stage HCC and very early-stage HCC were 94% (90–97%; I2 = 94%) and 94% (88–97%; I2 = 96%), respectively. The pooled sensitivity and specificity of abbreviated MRI protocols were 87% (80–94%) and 94% (90–98%), values that were comparable with those of full MRI protocols (84% [76–91%] and 94% [89–99%]; p = 0.83). In conclusion, sMRI had good sensitivity for detecting HCC, particularly very early-stage HCC. Abbreviated MRI protocols for HCC surveillance had comparable diagnostic performance to full MRI protocols. Full article
(This article belongs to the Special Issue Systematic Review and Meta-Analysis of Imaging Biomarkers for Breakthrough Cancer Therapies)
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