Cancers

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4 pages, 180 KiB

Open AccessEditorial

What Is the Role of Imaging in Cancers?

by Laura Evangelista and Stefano Fanti

Cancers 2020, 12(6), 1494; https://doi.org/10.3390/cancers12061494 - 8 Jun 2020

Cited by 1 | Viewed by 1972

Abstract

In the issue entitled “Role of Medical Imaging in Cancers”, 33 papers have been collected (23 original articles, 8 reviews, 1 brief report and 1 perspective) [...] Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

Research

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17 pages, 5213 KiB

Open AccessArticle

Gold Nanoparticle Mediated Multi-Modal CT Imaging of Hsp70 Membrane-Positive Tumors

by Melanie A. Kimm, Maxim Shevtsov, Caroline Werner, Wolfgang Sievert, Wu Zhiyuan, Oliver Schoppe, Bjoern H. Menze, Ernst J. Rummeny, Roland Proksa, Olga Bystrova, Marina Martynova, Gabriele Multhoff and Stefan Stangl

Cancers 2020, 12(5), 1331; https://doi.org/10.3390/cancers12051331 - 22 May 2020

Cited by 29 | Viewed by 4541

Abstract

Imaging techniques such as computed tomographies (CT) play a major role in clinical imaging and diagnosis of malignant lesions. In recent years, metal nanoparticle platforms enabled effective payload delivery for several imaging techniques. Due to the possibility of surface modification, metal nanoparticles are [...] Read more.

Imaging techniques such as computed tomographies (CT) play a major role in clinical imaging and diagnosis of malignant lesions. In recent years, metal nanoparticle platforms enabled effective payload delivery for several imaging techniques. Due to the possibility of surface modification, metal nanoparticles are predestined to facilitate molecular tumor targeting. In this work, we demonstrate the feasibility of anti-plasma membrane Heat shock protein 70 (Hsp70) antibody functionalized gold nanoparticles (cmHsp70.1-AuNPs) for tumor-specific multimodal imaging. Membrane-associated Hsp70 is exclusively presented on the plasma membrane of malignant cells of multiple tumor entities but not on corresponding normal cells, predestining this target for a tumor-selective in vivo imaging. In vitro microscopic analysis revealed the presence of cmHsp70.1-AuNPs in the cytosol of tumor cell lines after internalization via the endo-lysosomal pathway. In preclinical models, the biodistribution as well as the intratumoral enrichment of AuNPs were examined 24 h after i.v. injection in tumor-bearing mice. In parallel to spectral CT analysis, histological analysis confirmed the presence of AuNPs within tumor cells. In contrast to control AuNPs, a significant enrichment of cmHsp70.1-AuNPs has been detected selectively inside tumor cells in different tumor mouse models. Furthermore, a machine-learning approach was developed to analyze AuNP accumulations in tumor tissues and organs. In summary, utilizing mHsp70 on tumor cells as a target for the guidance of cmHsp70.1-AuNPs facilitates an enrichment and uniform distribution of nanoparticles in mHsp70-expressing tumor cells that enables various microscopic imaging techniques and spectral-CT-based tumor delineation in vivo. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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15 pages, 1960 KiB

Open AccessArticle

¹⁸F-FDG Pet Parameters and Radiomics Features Analysis in Advanced Nsclc Treated with Immunotherapy as Predictors of Therapy Response and Survival

by Giulia Polverari, Francesco Ceci, Valentina Bertaglia, Maria Lucia Reale, Osvaldo Rampado, Elena Gallio, Roberto Passera, Virginia Liberini, Paola Scapoli, Vincenzo Arena, Manuela Racca, Andrea Veltri, Silvia Novello and Désirée Deandreis

Cancers 2020, 12(5), 1163; https://doi.org/10.3390/cancers12051163 - 5 May 2020

Cited by 80 | Viewed by 5131

Abstract

Objectives: (1.1) to evaluate the association between baseline 18F-FDG PET/CT semi-quantitative parameters of the primary lesion with progression free survival (PFS), overall survival (OS) and response to immunotherapy, in advanced non-small cell lung carcinoma (NSCLC) patients eligible for immunotherapy; (1.2) to evaluate the [...] Read more.

Objectives: (1.1) to evaluate the association between baseline 18F-FDG PET/CT semi-quantitative parameters of the primary lesion with progression free survival (PFS), overall survival (OS) and response to immunotherapy, in advanced non-small cell lung carcinoma (NSCLC) patients eligible for immunotherapy; (1.2) to evaluate the application of radiomics analysis of the primary lesion to identify features predictive of response to immunotherapy; (1.3) to evaluate if tumor burden assessed by 18F-FDG PET/CT (N and M factors) is associated with PFS and OS. Materials and Methods: we retrospectively analyzed clinical records of advanced NCSLC patients (stage IIIb/c or stage IV) candidate to immunotherapy who performed 18F-FDG PET/CT before treatment to stage the disease. Fifty-seven (57) patients were included in the analysis (F:M 17:40; median age = 69 years old). Notably, 38/57 of patients had adenocarcinoma (AC), 10/57 squamous cell carcinoma (SCC) and 9/57 were not otherwise specified (NOS). Overall, 47.4% patients were stage IVA, 42.1% IVB and 8.8% IIIB. Immunotherapy was performed as front-line therapy in 42/57 patients and as second line therapy after chemotherapy platinum-based in 15/57. The median follow up after starting immunotherapy was 10 months (range: 1.5–68.6). Therapy response was assessed by RECIST 1.1 criteria (CT evaluation every 4 cycles of therapy) in 48/57 patients or when not feasible by clinical and laboratory data (fast disease progression or worsening of patient clinical condition in nine patients). Radiomics analysis was performed by applying regions of interest (ROIs) of the primary tumor delineated manually by two operators and semi-automatically applying a threshold at 40% of SUVmax. Results: (1.1) metabolic tumor volume (MTV) (p = 0.028) and total lesion glycolysis (TLG) (p = 0.035) were significantly associated with progressive vs. non-progressive disease status. Patients with higher values of MTV and TLG had higher probability of disease progression, compared to those patients presenting with lower values. SUVmax did not show correlation with PD status, PFS and OS. MTV (p = 0.027) and TLG (p = 0.022) also resulted in being significantly different among PR, SD and PD groups, while SUVmax was confirmed to not be associated with response to therapy (p = 0.427). (1.2) We observed the association of several radiomics features with PD status. Namely, patients with high tumor volume, TLG and heterogeneity expressed by “skewness” and “kurtosis” had a higher probability of failing immunotherapy. (1.3) M status at 18F-FDG PET/CT was significantly associated with PFS (p = 0.002) and OS (p = 0.049). No significant associations were observed for N status. Conclusions: 18F-FDG PET/CT performed before the start of immunotherapy might be an important prognostic tool able to predict the disease progression and response to immunotherapy in patients with advanced NSCLC, since MTV, TLG and radiomics features (volume and heterogeneity) are associated with disease progression. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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13 pages, 1332 KiB

Open AccessArticle

Predictive Role of MRI and ¹⁸F FDG PET Response to Concurrent Chemoradiation in T2b Cervical Cancer on Clinical Outcome: A Retrospective Single Center Study

by Anna Myriam Perrone, Giulia Dondi, Manuela Coe, Martina Ferioli, Silvi Telo, Andrea Galuppi, Eugenia De Crescenzo, Marco Tesei, Paolo Castellucci, Cristina Nanni, Stefano Fanti, Alessio G. Morganti and Pierandrea De Iaco

Cancers 2020, 12(3), 659; https://doi.org/10.3390/cancers12030659 - 12 Mar 2020

Cited by 10 | Viewed by 3774

Abstract

Tumor response in locally advanced cervical cancer (LACC) is generally evaluated with MRI and PET, but this strategy is not supported by the literature. Therefore, we compared the diagnostic performance of these two techniques in the response evaluation to concurrent chemoradiotherapy (CCRT) in [...] Read more.

Tumor response in locally advanced cervical cancer (LACC) is generally evaluated with MRI and PET, but this strategy is not supported by the literature. Therefore, we compared the diagnostic performance of these two techniques in the response evaluation to concurrent chemoradiotherapy (CCRT) in LACC. Patients with cervical cancer (CC) stage T2b treated with CCRT and submitted to MRI and PET/CT before and after treatment were enrolled in the study. All clinical, pathological, therapeutic, radiologic and follow-up data were collected and examined. The radiological response was analyzed and compared to the follow-up data. Data of 40 patients with LACC were analyzed. Agreement between MRI and PET/CT in the evaluation response to therapy was observed in 31/40 (77.5%) of cases. The agreement between MRI, PET/CT and follow-up data showed a Cohen kappa coefficient of 0.59 (95% CI = 0.267–0.913) and of 0.84 (95% CI = 0.636–1.00), respectively. Considering the evaluation of primary tumor response, PET/CT was correct in 97.5% of cases, and MRI in 92.5% of cases; no false negative cases were observed. These results suggest the use of PET/CT as a unique diagnostic imaging tool after CCRT, to correctly assess residual and progression disease. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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11 pages, 2498 KiB

Open AccessArticle

Detection of Glioblastoma Subclinical Recurrence Using Serial Diffusion Tensor Imaging

by Yan Jin, James W. Randall, Hesham Elhalawani, Karine A. Al Feghali, Andrew M. Elliott, Brian M. Anderson, Lara Lacerda, Benjamin L. Tran, Abdallah S. Mohamed, Kristy K. Brock, Clifton D. Fuller and Caroline Chung

Cancers 2020, 12(3), 568; https://doi.org/10.3390/cancers12030568 - 29 Feb 2020

Cited by 16 | Viewed by 4351

Abstract

Glioblastoma is an aggressive brain tumor with a propensity for intracranial recurrence. We hypothesized that tumors can be visualized with diffusion tensor imaging (DTI) before they are detected on anatomical magnetic resonance (MR) images. We retrospectively analyzed serial MR images from 30 patients, [...] Read more.

Glioblastoma is an aggressive brain tumor with a propensity for intracranial recurrence. We hypothesized that tumors can be visualized with diffusion tensor imaging (DTI) before they are detected on anatomical magnetic resonance (MR) images. We retrospectively analyzed serial MR images from 30 patients, including the DTI and T1-weighted images at recurrence, at 2 months and 4 months before recurrence, and at 1 month after radiation therapy. The diffusion maps and T1 images were deformably registered longitudinally. The recurrent tumor was manually segmented on the T1-weighted image and then applied to the diffusion maps at each time point to collect mean FA, diffusivities, and neurite density index (NDI) values, respectively. Group analysis of variance showed significant changes in FA (p = 0.01) and NDI (p = 0.0015) over time. Pairwise t tests also revealed that FA and NDI at 2 months before recurrence were 11.2% and 6.4% lower than those at 1 month after radiation therapy (p < 0.05), respectively. Changes in FA and NDI were observed 2 months before recurrence, suggesting that progressive microstructural changes and neurite density loss may be detectable before tumor detection in anatomical MR images. FA and NDI may serve as non-contrast MR-based biomarkers for detecting subclinical tumors. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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25 pages, 5593 KiB

Open AccessArticle

The Impact of Normalization Approaches to Automatically Detect Radiogenomic Phenotypes Characterizing Breast Cancer Receptors Status

by Rossana Castaldo, Katia Pane, Emanuele Nicolai, Marco Salvatore and Monica Franzese

Cancers 2020, 12(2), 518; https://doi.org/10.3390/cancers12020518 - 24 Feb 2020

Cited by 41 | Viewed by 6110

Abstract

In breast cancer studies, combining quantitative radiomic with genomic signatures can help identifying and characterizing radiogenomic phenotypes, in function of molecular receptor status. Biomedical imaging processing lacks standards in radiomic feature normalization methods and neglecting feature normalization can highly bias the overall analysis. [...] Read more.

In breast cancer studies, combining quantitative radiomic with genomic signatures can help identifying and characterizing radiogenomic phenotypes, in function of molecular receptor status. Biomedical imaging processing lacks standards in radiomic feature normalization methods and neglecting feature normalization can highly bias the overall analysis. This study evaluates the effect of several normalization techniques to predict four clinical phenotypes such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and triple negative (TN) status, by quantitative features. The Cancer Imaging Archive (TCIA) radiomic features from 91 T1-weighted Dynamic Contrast Enhancement MRI of invasive breast cancers were investigated in association with breast invasive carcinoma miRNA expression profiling from the Cancer Genome Atlas (TCGA). Three advanced machine learning techniques (Support Vector Machine, Random Forest, and Naïve Bayesian) were investigated to distinguish between molecular prognostic indicators and achieved an area under the ROC curve (AUC) values of 86%, 93%, 91%, and 91% for the prediction of ER+ versus ER−, PR+ versus PR−, HER2+ versus HER2−, and triple-negative, respectively. In conclusion, radiomic features enable to discriminate major breast cancer molecular subtypes and may yield a potential imaging biomarker for advancing precision medicine. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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16 pages, 2547 KiB

Open AccessArticle

Usefulness of Hybrid PET/MRI in Clinical Evaluation of Head and Neck Cancer Patients

by Natalia Samolyk-Kogaczewska, Ewa Sierko, Dorota Dziemianczyk-Pakiela, Klaudia Beata Nowaszewska, Malgorzata Lukasik and Joanna Reszec

Cancers 2020, 12(2), 511; https://doi.org/10.3390/cancers12020511 - 22 Feb 2020

Cited by 35 | Viewed by 4246

Abstract

(1) Background: The novel hybrid of positron emission tomography/magnetic resonance (PET/MR) examination has been introduced to clinical practice. The aim of our study was to evaluate PET/MR usefulness in preoperative staging of head and neck cancer (HNC) patients (pts); (2) Methods: Thirty eight [...] Read more.

(1) Background: The novel hybrid of positron emission tomography/magnetic resonance (PET/MR) examination has been introduced to clinical practice. The aim of our study was to evaluate PET/MR usefulness in preoperative staging of head and neck cancer (HNC) patients (pts); (2) Methods: Thirty eight pts underwent both computed tomography (CT) and PET/MR examination, of whom 21 pts underwent surgical treatment as first-line therapy and were further included in the present study. Postsurgical tissue material was subjected to routine histopathological (HP) examination with additional evaluation of p16, human papillomavirus (HPV), Epstein-Barr virus (EBV) and Ki67 status. Agreement of clinical and pathological T staging, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of CT and PET/MR in metastatic lymph nodes detection were defined. The verification of dependences between standardized uptake value (SUV value), tumor geometrical parameters, number of metastatic lymph nodes in PET/MR and CT, biochemical parameters, Ki67 index, p16, HPV and EBV status was made with statistical analysis of obtained results; (3) Results: PET/MR is characterized by better agreement in T staging, higher specificity, sensitivity, PPV and NPV of lymph nodes evaluation than CT imaging. Significant correlations were observed between SUVmax and maximal tumor diameter from PET/MR, between SUVmean and CT tumor volume, PET/MR tumor volume, maximal tumor diameter assessed in PET/MR. Other correlations were weak and insignificant; (4) Conclusions: Hybrid PET/MR imaging is useful in preoperative staging of HNC. Further studies are needed. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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15 pages, 3866 KiB

Open AccessArticle

Circulating Tumor Cells and Metabolic Parameters in NSCLC Patients Treated with Checkpoint Inhibitors

by Angelo Castello, Francesco Giuseppe Carbone, Sabrina Rossi, Simona Monterisi, Davide Federico, Luca Toschi and Egesta Lopci

Cancers 2020, 12(2), 487; https://doi.org/10.3390/cancers12020487 - 19 Feb 2020

Cited by 35 | Viewed by 3910

Abstract

Circulating tumor cells (CTC) count and characterization have been associated with poor prognosis in recent studies. Our aim was to examine CTC count and its association with metabolic parameters and clinical outcomes in non-small cell lung carcinoma (NSCLC) patients treated with immune checkpoint [...] Read more.

Circulating tumor cells (CTC) count and characterization have been associated with poor prognosis in recent studies. Our aim was to examine CTC count and its association with metabolic parameters and clinical outcomes in non-small cell lung carcinoma (NSCLC) patients treated with immune checkpoint inhibitors (ICI). For this prospective study, data from 35 patients (23 males, 12 females) were collected and analyzed. All patients underwent an 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) scan and CTC detection through Isolation by Size of Tumor/Trophoblastic Cells (ISET) from peripheral blood samples obtained at baseline and 8 weeks after ICI initiation. Association of CTC count with clinical and metabolic characteristics was studied. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and the log-rank test. Median follow-up was 13.2 months (range of 4.9–21.6). CTC were identified in 16 out of 35 patients (45.7%) at baseline and 10 out of 24 patients at 8 weeks (41.7%). Mean CTC numbers before and after 8 weeks were 15 ± 28 and 11 ± 19, respectively. Prior to ICI, the mean CTC number was significantly higher in treatment-naïve patients (34 ± 39 vs. 9 ± 21, p = 0.004). CTC count variation (ΔCTC) was significantly associated with tumor metabolic response set by European Organization for Research and Treatment of Cancer (EORTC) criteria (p = 0.033). At the first restaging, patients with a high tumor burden, that is, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), had a higher CTC count (p = 0.009). The combination of mean CTC and median MTV at 8 weeks was associated with PFS (p < 0.001) and OS (p = 0.024). Multivariate analysis identified CTC count at 8 weeks as an independent predictor for PFS and OS, whereas ΔMTV and maximum standardized uptake value variation (ΔSUVmax) was predictive for PFS and OS, respectively. Our study confirmed that CTC number is modulated by previous treatments and correlates with metabolic response during ICI. Moreover, elevated CTC count, along with metabolic parameters, were found to be prognostic factors for PFS and OS. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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21 pages, 1150 KiB

Open AccessArticle

PSA and PSA Kinetics Thresholds for the Presence of ⁶⁸Ga-PSMA-11 PET/CT-Detectable Lesions in Patients with Biochemical Recurrent Prostate Cancer

by Manuela Andrea Hoffmann, Hans-Georg Buchholz, Helmut J. Wieler, Matthias Miederer, Florian Rosar, Nicolas Fischer, Jonas Müller-Hübenthal, Ludwin Trampert, Stefanie Pektor and Mathias Schreckenberger

Cancers 2020, 12(2), 398; https://doi.org/10.3390/cancers12020398 - 8 Feb 2020

Cited by 22 | Viewed by 3566

Abstract

⁶⁸Ga-PSMA-11 positron-emission tomography/computed tomography (PET/CT) is commonly used for restaging recurrent prostate cancer (PC) in European clinical practice. The goal of this study is to determine the optimum time for performing these PET/CT scans in a large cohort of patients by identifying [...] Read more.

⁶⁸Ga-PSMA-11 positron-emission tomography/computed tomography (PET/CT) is commonly used for restaging recurrent prostate cancer (PC) in European clinical practice. The goal of this study is to determine the optimum time for performing these PET/CT scans in a large cohort of patients by identifying the prostate-specific-antigen (PSA) and PSA kinetics thresholds for detecting and localizing recurrent PC. This retrospective analysis includes 581 patients with biochemical recurrence (BC) by definition. The performance of ⁶⁸Ga-PSMA-11 PET/CT in relation to the PSA value at the scan time as well as PSA kinetics was assessed by the receiver-operating-characteristic-curve (ROC) generated by plotting sensitivity versus 1-specificity. Malignant prostatic lesions were identified in 77%. For patients that were treated with radical prostatectomy (RP) a PSA value of 1.24 ng/mL was found to be the optimal cutoff level for predicting positive and negative scans, while for patients previously treated with radiotherapy (RT) it was 5.75 ng/mL. In RP-patients with PSA value <1.24 ng/mL, 52% scans were positive, whereas patients with PSA ≥1.24 ng/mL had positive scan results in 87%. RT-patients with PSA <5.75 ng/mL had positive scans in 86% and for those with PSA ≥5.75 ng/mL 94% had positive scans. This study identifies the PSA and PSA kinetics threshold levels for the presence of ⁶⁸Ga-PSMA-11 PET/CT-detectable PC-lesions in BC patients. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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11 pages, 832 KiB

Open AccessArticle

Multiparametric MRI for Prostate Cancer Detection: New Insights into the Combined Use of a Radiomic Approach with Advanced Acquisition Protocol

by Serena Monti, Valentina Brancato, Giuseppe Di Costanzo, Luca Basso, Marta Puglia, Alfonso Ragozzino, Marco Salvatore and Carlo Cavaliere

Cancers 2020, 12(2), 390; https://doi.org/10.3390/cancers12020390 - 7 Feb 2020

Cited by 25 | Viewed by 6828

Abstract

Prostate cancer (PCa) is a disease affecting an increasing number of men worldwide. Several efforts have been made to identify imaging biomarkers to non-invasively detect and characterize PCa, with substantial improvements thanks to multiparametric Magnetic Resonance Imaging (mpMRI). In recent years, diffusion kurtosis [...] Read more.

Prostate cancer (PCa) is a disease affecting an increasing number of men worldwide. Several efforts have been made to identify imaging biomarkers to non-invasively detect and characterize PCa, with substantial improvements thanks to multiparametric Magnetic Resonance Imaging (mpMRI). In recent years, diffusion kurtosis imaging (DKI) was proposed to be directly related to tissue physiological and pathological characteristic, while the radiomic approach was proven to be a key method to study cancer imaging phenotypes. Our aim was to compare a standard radiomic model for PCa detection, built using T2-weighted (T2W) and Apparent Diffusion Coefficient (ADC), with an advanced one, including DKI and quantitative Dynamic Contrast Enhanced (DCE), while also evaluating differences in prediction performance when using 2D or 3D lesion segmentation. The obtained results in terms of diagnostic accuracy were high for all of the performed comparisons, reaching values up to 0.99 for the area under a receiver operating characteristic curve (AUC), and 0.98 for both sensitivity and specificity. In comparison, the radiomic model based on standard features led to prediction performances higher than those of the advanced model, while greater accuracy was achieved by the model extracted from 3D segmentation. These results provide new insights into active topics of discussion, such as choosing the most convenient acquisition protocol and the most appropriate postprocessing pipeline to accurately detect and characterize PCa. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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14 pages, 1162 KiB

Open AccessArticle

Role of Baseline and Post-Therapy 18F-FDG PET in the Prognostic Stratification of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Treated with Radium-223

by Matteo Bauckneht, Selene Capitanio, Maria Isabella Donegani, Elisa Zanardi, Alberto Miceli, Roberto Murialdo, Stefano Raffa, Laura Tomasello, Martina Vitti, Alessia Cavo, Fabio Catalano, Manlio Mencoboni, Marcello Ceppi, Cecilia Marini, Giuseppe Fornarini, Francesco Boccardo, Gianmario Sambuceti and Silvia Morbelli

Cancers 2020, 12(1), 31; https://doi.org/10.3390/cancers12010031 - 20 Dec 2019

Cited by 33 | Viewed by 3873

Abstract

Radium-223 dichloride (Ra223) represents the unique bone-directed treatment option that shows an improvement in overall survival (OS) in metastatic castrate resistant prostate cancer (mCRPC). However, there is an urgent need for the identification of reliable biomarkers to non-invasively determine its efficacy (possibly improving [...] Read more.

Radium-223 dichloride (Ra223) represents the unique bone-directed treatment option that shows an improvement in overall survival (OS) in metastatic castrate resistant prostate cancer (mCRPC). However, there is an urgent need for the identification of reliable biomarkers to non-invasively determine its efficacy (possibly improving patients’ selection or identifying responders’ after therapy completion). 18F-Fluorodeoxyglucose (FDG)-avidity is low in naïve prostate cancer, but it is enhanced in advanced and chemotherapy-refractory mCRPC, providing prognostic insights. Moreover, this tool showed high potential for the evaluation of response in cancer patients with bone involvement. For these reasons, FDG Positron Emission Tomography (FDG-PET) might represent an effective tool that is able to provide prognostic stratification (improving patients selection) at baseline and assessing the treatment response to Ra223. We conducted a retrospective analysis of 28 mCRPC patients that were treated with Ra223 and submitted to bone scan and FDG-PET/CT for prognostic purposes at baseline and within two months after therapy completion. The following parameters were measured: number of bone lesions at bone scan, SUVmax of the hottest bone lesion, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). In patients who underwent post-therapy 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT), (20/28), PET Response Criteria in Solid Tumors (PERCIST), and European Organization for Research and Treatment of Cancer (EORTC) criteria were applied to evaluate the metabolic treatment response. The difference between end of therapy and baseline values was also calculated for Metabolic Tumor Volume (MTV), TLG, prostate-specific antigen (PSA), alkaline phosphatase (AP), and lactate dehydrogenase (LDH) (termed deltaMTV, deltaTLG, deltaPSA, deltaAP and deltaLDH, respectively). Predictive power of baseline and post-therapy PET- and biochemical-derived parameters on OS were assessed by Kaplan–Meier, univariate and multivariate analyses. At baseline, PSA, LDH, and MTV significantly predicted OS. However, MTV (but not PSA nor LDH) was able to identify a subgroup of patients with worse prognosis, even after adjusting for the number of lesions at bone scan (which, in turn, was not an independent predictor of OS). After therapy, PERCIST criteria were able to capture the response to Ra223 by demonstrating longer OS in patients with partial metabolic response. Moreover, the biochemical parameters were outperformed by PERCIST in the post-treatment setting, as their variation after therapy was not informative on long term OS. The present study supports the role of FDG-PET as a tool for patient’s selection and response assessment in mCRPC patients undergoing Ra223 administration. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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12 pages, 1952 KiB

Open AccessArticle

The Role of 18F-FDG PET/CT in Staging and Prognostication of Mantle Cell Lymphoma: An Italian Multicentric Study

by Domenico Albano, Riccardo Laudicella, Paola Ferro, Michela Allocca, Elisabetta Abenavoli, Ambra Buschiazzo, Alessia Castellino, Agostino Chiaravalloti, Annarosa Cuccaro, Lea Cuppari, Rexhep Durmo, Laura Evangelista, Viviana Frantellizzi, Sofya Kovalchuk, Flavia Linguanti, Giulia Santo, Matteo Bauckneht and Salvatore Annunziata

Cancers 2019, 11(12), 1831; https://doi.org/10.3390/cancers11121831 - 21 Nov 2019

Cited by 18 | Viewed by 5298

Abstract

Mantle cell lymphoma (MCL) is an aggressive lymphoma subtype with poor prognosis in which 18F-FDG-PET/CT role in treatment response evaluation and prediction of outcome is still unclear. The aim of this multicentric study was to investigate the role of 18F-FDG-PET/CT in staging MCL [...] Read more.

Mantle cell lymphoma (MCL) is an aggressive lymphoma subtype with poor prognosis in which 18F-FDG-PET/CT role in treatment response evaluation and prediction of outcome is still unclear. The aim of this multicentric study was to investigate the role of 18F-FDG-PET/CT in staging MCL and the prognostic role of Deauville criteria (DC) in terms of progression-free survival (PFS) and overall survival (OS). We retrospectively enrolled 229 patients who underwent baseline and end-of-treatment (eot) 18F-FDG-PET/CT after first-line therapy. EotPET/CT scans were visually interpreted according to DC. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of PET/CT for evaluation of bone marrow (BM) were 27%, 100%, 100%, 48% and 57%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of PET/CT for evaluation of the gastrointestinal (GI) tract were 60%, 99%, 93%, 90% and 91%, respectively. At a median follow-up of 40 months, relapse occurred in 104 cases and death in 49. EotPET/CT results using DC significantly correlated with PFS, not with OS. Instead, considering OS, only MIPI score was significantly correlated. In conclusion, we demonstrated that MCL is an FDG-avid lymphoma and 18F-FDG-PET/CT is a useful tool for staging purpose, showing good specificity for BM and GI evaluation, but suboptimal sensitivity. EotPET/CT result was the only independent significant prognostic factor that correlated with PFS. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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12 pages, 235 KiB

Open AccessArticle

Consensus Procedures in Oncological Imaging: The Case of Prostate Cancer

by Stefano Fanti, Wim Oyen and Elisabetta Lalumera

Cancers 2019, 11(11), 1788; https://doi.org/10.3390/cancers11111788 - 14 Nov 2019

Cited by 3 | Viewed by 2508

Abstract

Recently, there has been increasing interest in methodological aspects of advanced imaging, including the role of guidelines, recommendations, and experts’ consensus, the practice of self-referral, and the risk of diagnostic procedure overuse. In a recent Delphi study of the European Association for Nuclear [...] Read more.

Recently, there has been increasing interest in methodological aspects of advanced imaging, including the role of guidelines, recommendations, and experts’ consensus, the practice of self-referral, and the risk of diagnostic procedure overuse. In a recent Delphi study of the European Association for Nuclear Medicine (EANM), panelists were asked to give their opinion on 47 scientific questions about imaging in prostate cancer. Nine additional questions exploring the experts’ attitudes and opinions relating to the procedure of consensus building itself were also included. The purpose was to provide insights into the mechanism of recommendation choice and consensus building as seen from the experts’ point of view. Results: Regarding the factors likely to influence the willingness to refer a patient for imaging, the most voted were incorporation into guidelines and data from scientific literature, while personal experience and personal relationship were chosen by a small minority. Regarding the recommendations more relevant to prescribe an imaging procedure, it resulted the incorporation into guidelines promoted by scientific societies (59% of votes); these guidelines also resulted the more trusted. With respect to patients’ preferences considered when prescribing an imaging procedure, the most voted was accuracy, resulted more important than easy access and time to access to the procedure. The majority of the experts expressed the opinion that there is a scarce use of imaging procedures in prostate cancer. With respect to the most relevant factor to build consensus, it resulted the transparency of the process (52% of votes), followed by multidisciplinarity of contributors. The main obstacle to incorporation of modern imaging procedures into guidelines resulted the lack of primary literature on clinical impact. Conclusions: Firstly, the panelists portray themselves as having Evidence-Based Medicine oriented and scientifically inclined attitudes and preferences. Secondly, guidelines and recommendations from scientific societies, especially clinical ones, are positively taken into account as factors influencing decisions, but panelists tend to consider their own appraisal of the scientific literature as more relevant. Thirdly, in respect of overuse, panelists do not think that advanced diagnostic procedures are overutilized in the specific case of Prostate Cancer, but rather they are underutilized. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

15 pages, 1261 KiB

Open AccessArticle

Hybrid ¹⁸F-FDG-PET/MRI Measurement of Standardized Uptake Value Coupled with Yin Yang 1 Signature in Metastatic Breast Cancer. A Preliminary Study

by Concetta Schiano, Monica Franzese, Katia Pane, Nunzia Garbino, Andrea Soricelli, Marco Salvatore, Filomena de Nigris and Claudio Napoli

Cancers 2019, 11(10), 1444; https://doi.org/10.3390/cancers11101444 - 26 Sep 2019

Cited by 25 | Viewed by 3753

Abstract

Purpose: Detection of breast cancer (BC) metastasis at the early stage is important for the assessment of BC progression status. Image analysis represents a valuable tool for the management of oncological patients. Our preliminary study combined imaging parameters from hybrid ¹⁸F-FDG-PET/MRI and [...] Read more.

Purpose: Detection of breast cancer (BC) metastasis at the early stage is important for the assessment of BC progression status. Image analysis represents a valuable tool for the management of oncological patients. Our preliminary study combined imaging parameters from hybrid ¹⁸F-FDG-PET/MRI and the expression level of the transcriptional factor Yin Yang 1 (YY1) for the detection of early metastases. Methods: The study enrolled suspected n = 217 BC patients that underwent ¹⁸F-FDG-PET/MRI scans. The analysis retrospectively included n = 55 subjects. n = 40 were BC patients and n = 15 imaging-negative female individuals were healthy subjects (HS). Standard radiomics parameters were extracted from PET/MRI image. RNA was obtained from peripheral blood mononuclear cells and YY1 expression level was evaluated by real time reverse transcription polymerase chain reactions (qRT-PCR). An enzyme-linked immuosorbent assay (ELISA) was used to determine the amount of YY1 serum protein. Statistical comparison between subgroups was evaluated by Mann-Whitney U and Spearman’s tests. Results: Radiomics showed a significant positive correlation between Greg-level co-occurrence matrix (GLCM) and standardized uptake value maximum (SUVmax) (r = 0.8 and r = 0.8 respectively) in BC patients. YY1 level was significant overexpressed in estrogen receptor (ER)-positive/progesteron receptor-positive/human epidermal growth factor receptor2-negative (ER+/PR+/HER2-) subtype of BC patients with synchronous metastasis (SM) at primary diagnosis compared to metachronous metastasis (MM) and HS (p < 0.001) and correlating significantly with ¹⁸F-FDG-uptake parameter (SUVmax) (r = 0.48). Conclusions: The combination of functional ¹⁸F-FDG-PET/MRI parameters and molecular determination of YY1 could represent a novel integrated approach to predict synchronous metastatic disease with more accuracy than ¹⁸F-FDG-PET/MRI alone. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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15 pages, 2537 KiB

Open AccessArticle

Prognostic Significance of CT-Attenuation of Tumor-Adjacent Breast Adipose Tissue in Breast Cancer Patients with Surgical Resection

by Jeong Won Lee, Sung Yong Kim, Hyun Ju Lee, Sun Wook Han, Jong Eun Lee and Sang Mi Lee

Cancers 2019, 11(8), 1135; https://doi.org/10.3390/cancers11081135 - 8 Aug 2019

Cited by 18 | Viewed by 3718

Abstract

The purpose of this study was to evaluate the prognostic significance of computed tomography (CT)-attenuation of tumor-adjacent breast adipose tissue for predicting recurrence-free survival (RFS) in patients with breast cancer. We retrospectively enrolled 287 breast cancer patients who underwent pretreatment ¹⁸F-fluorodeoxyglucose (FDG) [...] Read more.

The purpose of this study was to evaluate the prognostic significance of computed tomography (CT)-attenuation of tumor-adjacent breast adipose tissue for predicting recurrence-free survival (RFS) in patients with breast cancer. We retrospectively enrolled 287 breast cancer patients who underwent pretreatment ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. From non-contrast-enhanced CT images of PET/CT, CT-attenuation values of tumor-adjacent breast adipose tissue (TAT HU) and contralateral breast adipose tissue (CAT HU) were measured. Difference (HU difference) and percent difference (HU difference %) in CT-attenuation values between TAT HU and CAT HU were calculated. The relationships of these breast adipose tissue parameters with tumor factors and RFS were assessed. TAT HU was significantly higher than CAT HU (p < 0.001). TAT HU, HU difference, and HU difference % showed significant correlations with T stage and estrogen receptor and progesterone receptor status (p < 0.05), whereas CAT HU had no significant relationships with tumor factors (p > 0.05). Patients with high TAT HU, HU difference, and HU difference % had significantly worse RFS than those with low values (p < 0.001). In multivariate analysis, TAT HU and HU difference % were significantly associated with RFS after adjusting for clinico-pathologic factors (p < 0.05). CT-attenuation of tumor-adjacent breast adipose tissue was significantly associated with RFS in patients with breast cancer. The findings seem to support the close contact between breast cancer cells and tumor-adjacent adipocytes observed with imaging studies. Full article

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13 pages, 2649 KiB

Open AccessArticle

In Vivo Assessment of VCAM-1 Expression by SPECT/CT Imaging in Mice Models of Human Triple Negative Breast Cancer

by Christopher Montemagno, Laurent Dumas, Pierre Cavaillès, Mitra Ahmadi, Sandrine Bacot, Marlène Debiossat, Audrey Soubies, Loic Djaïleb, Julien Leenhardt, Nicolas De Leiris, Maeva Dufies, Gilles Pagès, Sophie Hernot, Nick Devoogdt, Pascale Perret, Laurent Riou, Daniel Fagret, Catherine Ghezzi and Alexis Broisat

Cancers 2019, 11(7), 1039; https://doi.org/10.3390/cancers11071039 - 23 Jul 2019

Cited by 6 | Viewed by 5458

Abstract

Recent progress in breast cancer research has led to the identification of Vascular Cell Adhesion Molecule-1 (VCAM-1) as a key actor of metastatic colonization. VCAM-1 promotes lung-metastases and is associated with clinical early recurrence and poor outcome in triple negative breast cancer (TNBC). [...] Read more.

Recent progress in breast cancer research has led to the identification of Vascular Cell Adhesion Molecule-1 (VCAM-1) as a key actor of metastatic colonization. VCAM-1 promotes lung-metastases and is associated with clinical early recurrence and poor outcome in triple negative breast cancer (TNBC). Our objective was to perform the in vivo imaging of VCAM-1 in mice models of TNBC. The Cancer Genomic Atlas (TCGA) database was analyzed to evaluate the prognostic role of VCAM-1 in TNBC. MDA-MB-231 (VCAM-1+) and control HCC70 (VCAM-1-) TNBC cells were subcutaneously xenografted in mice and VCAM-1 expression was assessed in vivo by single-photon emission computed tomography (SPECT) imaging using ^99mTc-cAbVCAM1-5. Then, MDA-MB-231 cells were intravenously injected in mice and VCAM-1 expression in lung metastasis was assessed by SPECT imaging after 8 weeks. TCGA analysis showed that VCAM-1 is associated with a poor prognosis in TNBC patients. In subcutaneous tumor models, ^99mTc-cAbVCAM1-5 uptake was 2-fold higher in MDA-MB-231 than in HCC70 (p < 0.01), and 4-fold higher than that of the irrelevant control (p < 0.01). Moreover, ^99mTc-cAbVCAM1-5 uptake in MDA-MB-231 lung metastases was also higher than that of ^99mTc-Ctl (p < 0.05). ^99mTc-cAbVCAM1-5 is therefore a suitable tool to evaluate the role of VCAM-1 as a marker of tumor aggressiveness of TNBC. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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22 pages, 3849 KiB

Open AccessArticle

Circulating miRNAs in Untreated Breast Cancer: An Exploratory Multimodality Morpho-Functional Study

by Mariarosaria Incoronato, Anna Maria Grimaldi, Peppino Mirabelli, Carlo Cavaliere, Chiara Anna Parente, Monica Franzese, Stefania Staibano, Gennaro Ilardi, Daniela Russo, Andrea Soricelli, Onofrio Antonio Catalano and Marco Salvatore

Cancers 2019, 11(6), 876; https://doi.org/10.3390/cancers11060876 - 22 Jun 2019

Cited by 42 | Viewed by 5754

Abstract

The aim of this study was to identify new disease-related circulating miRNAs with high diagnostic accuracy for breast cancer (BC) and to correlate their deregulation with the morpho-functional characteristics of the tumour, as assessed in vivo by positron emission tomography/magnetic resonance (PET/MR) imaging. [...] Read more.

The aim of this study was to identify new disease-related circulating miRNAs with high diagnostic accuracy for breast cancer (BC) and to correlate their deregulation with the morpho-functional characteristics of the tumour, as assessed in vivo by positron emission tomography/magnetic resonance (PET/MR) imaging. A total of 77 untreated female BC patients underwent same-day PET/MR and blood collection, and 78 healthy donors were recruited as negative controls. The expression profile of 84 human miRNAs was screened by using miRNA PCR arrays and validated by real-time PCR. The validated miRNAs were correlated with the quantitative imaging parameters extracted from the primary BC samples. Circulating miR-125b-5p and miR-143-3p were upregulated in BC plasma and able to discriminate BC patients from healthy subjects (miR-125-5p area under the receiver operating characteristic ROC curve (AUC) = 0.85 and miR-143-3p AUC = 0.80). Circulating CA15-3, a soluble form of the transmembrane glycoprotein Mucin 1 (MUC-1) that is upregulated in epithelial cancer cells of different origins, was combined with miR-125b-5p and improved the diagnostic accuracy from 70% (CA15-3 alone) to 89% (CA15-3 plus miR-125b-5p). MiR-143-3p showed a strong and significant correlation with the stage of the disease, apparent diffusion coefficient (ADC_mean), reverse efflux volume transfer constant (Kep_mean) and maximum standardized uptake value (SUV_max), and it might represent a biomarker of tumour aggressiveness. Similarly, miR-125b-5p was correlated with stage and grade 2 but inversely correlated with the forward volume transfer constant (Ktrans_mean) and proliferation index (Ki67), suggesting a potential role as a biomarker of a relatively more favourable prognosis. In situ hybridization (ISH) experiments revealed that miR-143-3p was expressed in endothelial tumour cells, miR-125-5p in cancer-associated fibroblasts, and neither in epithelial tumour cells. Our results suggested that miR-125-5p and miR-143-3p are potential biomarkers for the risk stratification of BC, and Kaplan-Maier plots confirmed this hypothesis. In addition, the combined use of miR-125-b-5p and CA15-3 enhanced the diagnostic accuracy up to 89%. This is the first study that correlates circulating miRNAs with in vivo quantified tumour biology through PET/MR biomarkers. This integration elucidates the link between the plasmatic increase in these two potential circulating biomarkers and the biology of untreated BC. In conclusion, while miR-143-3b and miR-125b-5p provide valuable information for prognosis, a combination of miR-125b-5p with the tumour marker CA15-3 improves sensitivity for BC detection, which warrants consideration by further validation studies. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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13 pages, 2429 KiB

Open AccessArticle

Automated Definition of Skeletal Disease Burden in Metastatic Prostate Carcinoma: A 3D Analysis of SPECT/CT Images

by Francesco Fiz, Helmut Dittmann, Cristina Campi, Matthias Weissinger, Samine Sahbai, Matthias Reimold, Arnulf Stenzl, Michele Piana, Gianmario Sambuceti and Christian la Fougère

Cancers 2019, 11(6), 869; https://doi.org/10.3390/cancers11060869 - 21 Jun 2019

Cited by 1 | Viewed by 4649

Abstract

To meet the current need for skeletal tumor-load estimation in castration-resistant prostate cancer (CRPC), we developed a novel approach based on adaptive bone segmentation. In this study, we compared the program output with existing estimates and with the radiological outcome. Seventy-six whole-body single-photon [...] Read more.

To meet the current need for skeletal tumor-load estimation in castration-resistant prostate cancer (CRPC), we developed a novel approach based on adaptive bone segmentation. In this study, we compared the program output with existing estimates and with the radiological outcome. Seventy-six whole-body single-photon emission computed tomographies/x-ray computed tomography with 3,3-diphosphono-1,2-propanedicarboxylic acid from mCRPC patients were analyzed. The software identified the whole skeletal volume (S_Vol) and classified the voxels metastases (M_Vol) or normal bone (B_Vol). S_Vol was compared with the estimation of a commercial software. M_Vol was compared with manual assessment and with prostate specific antigen (PSA) levels. Counts/voxel were extracted from M_Vol and B_Vol. After six cycles of ²²³RaCl2-therapy every patient was re-evaluated as having progressive disease (PD), stable disease (SD), or a partial response (PR). S_Vol correlated with that of the commercial software (R = 0.99, p < 0.001). M_Vol correlated with the manually-counted lesions (R = 0.61, p < 0.001) and PSA (R = 0.46, p < 0.01). PD had a lower counts/voxel in M_Vol than PR/SD (715 ± 190 vs. 975 ± 215 and 1058 ± 255, p < 0.05 and p < 0.01) and B_Vol (PD 275 ± 60, PR 515 ± 188 and SD 528 ± 162 counts/voxel, p < 0.001). Segmentation-based tumor load correlated with radiological/laboratory indices. Uptake was linked with the clinical outcome, suggesting that metastases in PD patients have a lower affinity for bone-seeking radionuclides and might benefit less from bone-targeted radioisotope therapies. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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10 pages, 2226 KiB

Open AccessArticle

Diffusion-Weighted Imaging Can Differentiate between Malignant and Benign Pleural Diseases

by Katsuo Usuda, Shun Iwai, Aika Funasaki, Atsushi Sekimura, Nozomu Motono, Munetaka Matoba, Mariko Doai, Sohsuke Yamada, Yoshimichi Ueda and Hidetaka Uramoto

Cancers 2019, 11(6), 811; https://doi.org/10.3390/cancers11060811 - 12 Jun 2019

Cited by 20 | Viewed by 4298

Abstract

It is not clear whether magnetic resonance imaging (MRI) is useful for the assessment of pleural diseases. The aim of this study is to determine whether diffusion-weighted magnetic resonance imaging (DWI) can differentiate malignant pleural mesothelioma (MPM) from pleural dissemination of lung cancer, [...] Read more.

It is not clear whether magnetic resonance imaging (MRI) is useful for the assessment of pleural diseases. The aim of this study is to determine whether diffusion-weighted magnetic resonance imaging (DWI) can differentiate malignant pleural mesothelioma (MPM) from pleural dissemination of lung cancer, empyema or pleural effusion. The DWI was calibrated with the b value of 0 and 800 s/mm². There were 11 MPMs (8 epithelioid and 3 biphasic), 10 pleural disseminations of lung cancer, 10 empyemas, and 12 pleural effusions. The apparent diffusion coefficient (ADC) of the pleural diseases was 1.22 ± 0.25 × 10⁻³ mm²/s in the MPMs, 1.31 ± 0.49 × 10⁻³ mm²/s in the pleural disseminations, 2.01 ± 0.45 × 10⁻³ mm²/s in the empyemas and 3.76 ± 0.62 × 10⁻³ mm²/s in the pleural effusions. The ADC of the MPMs and the pleural disseminations were significantly lower than the ADC of the empyemas and the pleural effusions. Concerning the diffusion pattern of DWI, all 11 MPMs showed strong continuous diffusion, 9 of 10 pleural disseminations showed strong scattered diffusion and 1 pleural dissemination showed strong continuous diffusion, all 10 empyemas showed weak continuous diffusion, and all 12 pleural effusions showed no decreased diffusion. DWI can evaluate pleural diseases morphologically and qualitatively, and thus differentiate between malignant and benign pleural diseases. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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12 pages, 2410 KiB

Open AccessArticle

Machine-Learning-Based Prediction of Treatment Outcomes Using MR Imaging-Derived Quantitative Tumor Information in Patients with Sinonasal Squamous Cell Carcinomas: A Preliminary Study

by Noriyuki Fujima, Yukie Shimizu, Daisuke Yoshida, Satoshi Kano, Takatsugu Mizumachi, Akihiro Homma, Koichi Yasuda, Rikiya Onimaru, Osamu Sakai, Kohsuke Kudo and Hiroki Shirato

Cancers 2019, 11(6), 800; https://doi.org/10.3390/cancers11060800 - 10 Jun 2019

Cited by 41 | Viewed by 4930

Abstract

The purpose of this study was to determine the predictive power for treatment outcome of a machine-learning algorithm combining magnetic resonance imaging (MRI)-derived data in patients with sinonasal squamous cell carcinomas (SCCs). Thirty-six primary lesions in 36 patients were evaluated. Quantitative morphological parameters [...] Read more.

The purpose of this study was to determine the predictive power for treatment outcome of a machine-learning algorithm combining magnetic resonance imaging (MRI)-derived data in patients with sinonasal squamous cell carcinomas (SCCs). Thirty-six primary lesions in 36 patients were evaluated. Quantitative morphological parameters and intratumoral characteristics from T2-weighted images, tumor perfusion parameters from arterial spin labeling (ASL) and tumor diffusion parameters of five diffusion models from multi-b-value diffusion-weighted imaging (DWI) were obtained. Machine learning by a non-linear support vector machine (SVM) was used to construct the best diagnostic algorithm for the prediction of local control and failure. The diagnostic accuracy was evaluated using a 9-fold cross-validation scheme, dividing patients into training and validation sets. Classification criteria for the division of local control and failure in nine training sets could be constructed with a mean sensitivity of 0.98, specificity of 0.91, positive predictive value (PPV) of 0.94, negative predictive value (NPV) of 0.97, and accuracy of 0.96. The nine validation data sets showed a mean sensitivity of 1.0, specificity of 0.82, PPV of 0.86, NPV of 1.0, and accuracy of 0.92. In conclusion, a machine-learning algorithm using various MR imaging-derived data can be helpful for the prediction of treatment outcomes in patients with sinonasal SCCs. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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13 pages, 3247 KiB

Open AccessArticle

Neoadjuvant Pazopanib Treatment in High-Risk Soft Tissue Sarcoma: A Quantitative Dynamic ¹⁸F-FDG PET/CT Study of the German Interdisciplinary Sarcoma Group

by Christos Sachpekidis, Ioannis Karampinis, Jens Jakob, Bernd Kasper, Kai Nowak, Lothar Pilz, Ulrike Attenberger, Timo Gaiser, Hans-Günter Derigs, Matthias Schwarzbach, Peter Hohenberger, Antonia Dimitrakopoulou-Strauss and Ulrich Ronellenfitsch

Cancers 2019, 11(6), 790; https://doi.org/10.3390/cancers11060790 - 8 Jun 2019

Cited by 13 | Viewed by 4087

Abstract

The outcome of high-risk soft tissue sarcoma (STS) is poor with radical surgery being the only potentially curative modality. Pazopanib is a multikinase inhibitor approved for the treatment of metastatic STS. Herein, in terms of the German Interdisciplinary Sarcoma Group (GISG-04/NOPASS) trial, we [...] Read more.

The outcome of high-risk soft tissue sarcoma (STS) is poor with radical surgery being the only potentially curative modality. Pazopanib is a multikinase inhibitor approved for the treatment of metastatic STS. Herein, in terms of the German Interdisciplinary Sarcoma Group (GISG-04/NOPASS) trial, we evaluate the potential role of kinetic analysis of fludeoxyglucose F-18 (¹⁸F-FDG) data derived from the application of dynamic positron emission tomography/computed tomography (PET/CT) in response assessment to pazopanib of STS patients scheduled for surgical resection. Sixteen STS patients treated with pazopanib as neoadjuvant therapy before surgery were enrolled in the analysis. All patients underwent dynamic PET/CT prior to and after pazopanib treatment. Data analysis consisted of visual (qualitative) analysis of the PET/CT scans, semi-quantitative evaluation based on standardized uptake value (SUV) calculations, and quantitative analysis of the dynamic ¹⁸F-FDG PET data, based on two-tissue compartment modeling. Resection specimens were histopathologically assessed and the percentage of regression grade was recorded in 14/16 patients. Time to tumor relapse/progression was also calculated. In the follow-up, 12/16 patients (75%) were alive without relapse, while four patients (25%) relapsed, among them one patient died. Median histopathological regression was 20% (mean 26%, range 5–70%). The studied population was dichotomized using a histopathological regression grade of 20% as cut-off. Based on this threshold, 10/14 patients (71%) showed partial remission (PR), while stable disease (SD) was seen in the rest 4 evaluable patients (29%). Semi-quantitative evaluation showed no statistically significant change in the widely used PET parameters, SUV_average and SUV_max. On the other hand, ¹⁸F-FDG kinetic analysis revealed a significant decrease in the perfusion-related parameter K₁, which reflects the carrier-mediated transport of ¹⁸F-FDG from plasma to tumor. This decrease can be considered as a marker in response to pazopanib in STS and could be due to the anti-angiogenic effect of the therapeutic agent. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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11 pages, 1174 KiB

Open AccessArticle

Potential Prognostic Role of ¹⁸F-FDG PET/CT in Invasive Epithelial Ovarian Cancer Relapse. A Preliminary Study

by Anna Myriam Perrone, Giulia Dondi, Giacomo Maria Lima, Paolo Castellucci, Marco Tesei, Sara Coluccelli, Giuseppe Gasparre, Anna Maria Porcelli, Cristina Nanni, Stefano Fanti and Pierandrea De Iaco

Cancers 2019, 11(5), 713; https://doi.org/10.3390/cancers11050713 - 23 May 2019

Cited by 11 | Viewed by 4425

Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, with relapse occurring in about 70% of advanced cases with poor prognosis. Fluorine-18-2-fluoro-2-deoxy-d-glucose PET/CT (¹⁸F-FDGPET/CT) is the most specific radiological imaging used to assess recurrence. Some intensity-based and volume-based PET parameters, [...] Read more.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, with relapse occurring in about 70% of advanced cases with poor prognosis. Fluorine-18-2-fluoro-2-deoxy-d-glucose PET/CT (¹⁸F-FDGPET/CT) is the most specific radiological imaging used to assess recurrence. Some intensity-based and volume-based PET parameters, maximum standardized uptake values (SUV_max), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), are indicated to have a correlation with treatment response. The aim of our study is to correlate these parameters with post relapse survival (PRS) and overall survival (OS) in Epithelial Ovarian Cancer (EOC) relapse. The study included 50 patients affected by EOC relapse who underwent ¹⁸F-FDGPET/CT before surgery. All imaging was reviewed and SUV_max, MTV and TLG were calculated and correlated to PRS and OS. PRS and OS were obtained from the first relapse and from the first diagnosis to the last follow up or death, respectively. SUV_max, MTV and TLG were tested in a univariate logistic regression analysis, only SUV_max demonstrated to be significantly associated to PRS and OS (p = 0.005 and p = 0.024 respectively). Multivariate analysis confirmed the results. We found a cut-off of SUV_max of 13 that defined worse or better survival (p = 0.003). In the first relapse of EOC, SUV_max is correlated to PRS and OS, and when SUV_max is greater than 13, it is an unfavorable prognostic factor. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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14 pages, 1905 KiB

Open AccessArticle

¹⁸F-FDG PET/CT and Urothelial Carcinoma: Impact on Management and Prognosis—A Multicenter Retrospective Study

by Fabio Zattoni, Elena Incerti, Fabrizio Dal Moro, Marco Moschini, Paolo Castellucci, Stefano Panareo, Maria Picchio, Federico Fallanca, Alberto Briganti, Andrea Gallina, Stefano Fanti, Riccardo Schiavina, Eugenio Brunocilla, Ilaria Rambaldi, Val Lowe, R. Jeffrey Karnes and Laura Evangelista

Cancers 2019, 11(5), 700; https://doi.org/10.3390/cancers11050700 - 20 May 2019

Cited by 24 | Viewed by 5060

Abstract

Objectives: To evaluate the ability of ¹⁸F-labeled fluoro-2-deoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) to predict survivorship of patients with bladder cancer (BC) and/or upper urinary tract carcinoma (UUTC). Materials: Data from patients who underwent FDG PET/CT for [...] Read more.

Objectives: To evaluate the ability of ¹⁸F-labeled fluoro-2-deoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) to predict survivorship of patients with bladder cancer (BC) and/or upper urinary tract carcinoma (UUTC). Materials: Data from patients who underwent FDG PET/CT for suspicion of recurrent urothelial carcinoma (UC) between 2007 and 2015 were retrospectively collected in a multicenter study. Disease management after the introduction of FDG PET/CT in the diagnostic algorithm was assessed in all patients. Kaplan-Meier and log-rank analysis were computed for survival assessment. A Cox regression analysis was used to identify predictors of recurrence and death, for BC, UUTC, and concomitant BC and UUTC. Results: Data from 286 patients were collected. Of these, 212 had a history of BC, 38 of UUTC and 36 of concomitant BC and UUTC. Patient management was changed in 114/286 (40%) UC patients with the inclusion of FDG PET/CT, particularly in those with BC, reaching 74% (n = 90/122). After a mean follow-up period of 21 months (Interquartile range: 4–28 mo.), 136 patients (47.4%) had recurrence/progression of disease. Moreover, 131 subjects (45.6%) died. At Kaplan-Meier analyses, patients with BC and positive PET/CT had a worse overall survival than those with a negative scan (log-rank < 0.001). Furthermore, a negative PET/CT scan was associated with a lower recurrence rate than a positive examination, independently from the primary tumor site. At multivariate analysis, in patients with BC and UUTC, a positive FDG PET/CT resulted an independent predictor of disease-free and overall survival (p < 0,01). Conclusions: FDG PET/CT has the potential to change patient management, particularly for patients with BC. Furthermore, it can be considered a valid survival prediction tool after primary treatment in patients with recurrent UC. However, a firm recommendation cannot be made yet. Further prospective studies are necessary to confirm our findings. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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9 pages, 909 KiB

Open AccessArticle

¹⁸F-FDG-PET Can Predict Microvessel Density in Head and Neck Squamous Cell Carcinoma

by Alexey Surov, Hans Jonas Meyer, Anne-Kathrin Höhn, Andreas Wienke, Osama Sabri and Sandra Purz

Cancers 2019, 11(4), 543; https://doi.org/10.3390/cancers11040543 - 15 Apr 2019

Cited by 7 | Viewed by 3536

Abstract

Aim: Positron emission tomography (PET) with ¹⁸F-fluordeoxyglucose (¹⁸F-FDG) plays an essential role in the staging and tumor monitoring of head and neck squamous cell carcinoma (HNSCC). Microvessel density (MVD) is one of the clinically important histopathological features in HNSCC. [...] Read more.

Aim: Positron emission tomography (PET) with ¹⁸F-fluordeoxyglucose (¹⁸F-FDG) plays an essential role in the staging and tumor monitoring of head and neck squamous cell carcinoma (HNSCC). Microvessel density (MVD) is one of the clinically important histopathological features in HNSCC. The purpose of this study was to analyze possible associations between ¹⁸F-FDG-PET findings and MVD parameters in HNSCC. Materials and Methods: Overall, 22 patients with a mean age of 55.2 ± 11.0 and with different HNSCC were acquired. In all cases, whole-body ¹⁸F-FDG-PET was performed. For each tumor, the maximum and mean standardized uptake values (SUV_max; SUV_mean) were determined. The MVD, including stained vessel area and total number of vessels, was estimated on CD105 stained specimens. All specimens were digitalized and analyzed by using ImageJ software 1.48v. Spearman’s correlation coefficient (r) was used to analyze associations between investigated parameters. p-values of <0.05 were taken to indicate statistical significance. Results: SUV_max correlated with vessel area (r = 0.532, p = 0.011) and vessel count (r = 0.434, p = 0.043). Receiver operating characteristic analysis identified a threshold SUV_max of 15 to predict tumors with high MVD with a sensitivity of 72.7% and specificity of 81.8%, with an area under the curve of 82.6%. Conclusion: ⁸F-FDG-PET parameters correlate statistically significantly with MVD in HNSCC. SUV_max may be used for discrimination of tumors with high tumor-related MVD. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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Review

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19 pages, 446 KiB

Open AccessReview

Novel Nuclear Medicine Imaging Applications in Immuno-Oncology

by Stefano Frega, Alessandro Dal Maso, Giulia Pasello, Lea Cuppari, Laura Bonanno, PierFranco Conte and Laura Evangelista

Cancers 2020, 12(5), 1303; https://doi.org/10.3390/cancers12051303 - 21 May 2020

Cited by 7 | Viewed by 3937

Abstract

The global immuno-oncology pipeline has grown progressively in recent years, leading cancer immunotherapy to become one of the main issues of the healthcare industry. Despite their success in the treatment of several malignancies, immune checkpoint inhibitors (ICIs) perform poorly in others. Again, ICIs [...] Read more.

The global immuno-oncology pipeline has grown progressively in recent years, leading cancer immunotherapy to become one of the main issues of the healthcare industry. Despite their success in the treatment of several malignancies, immune checkpoint inhibitors (ICIs) perform poorly in others. Again, ICIs action depends on such a multitude of clinico-pathological features, that the attempt to predict responders/long-responders with ad-hoc built immunograms revealed to be quite complex. In this landscape, the role of nuclear medicine might be crucial, with first interesting evidences coming from small case series and pre-clinical studies. Positron-emission tomography (PET) techniques provide functional information having a predictive and/or prognostic value in patients treated with ICIs or adoptive T-cell therapy. Recently, a characterization of the tumor immune microenvironment (TiME) pattern itself has been shown to be feasible through the use of different radioactive tracers or image algorithms, thus adding knowledge about tumor heterogeneity. Finally, nuclear medicine exams permit an early detection of immune-related adverse events (irAEs), with on-going clinical trials investigating their correlation with patients’ outcome. This review depicts the recent advances in molecular imaging both in terms of non-invasive diagnosis of TiME properties and benefit prediction from immunotherapeutic agents. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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11 pages, 745 KiB

Open AccessFeature PaperReview

The Role of Positron Emission Tomography in Clinical Management of Intraductal Papillary Mucinous Neoplasms of the Pancreas

by Simone Serafini, Cosimo Sperti, Alessandra Rosalba Brazzale, Diego Cecchin, Pietro Zucchetta, Elisa Sefora Pierobon, Alberto Ponzoni, Michele Valmasoni and Lucia Moletta

Cancers 2020, 12(4), 807; https://doi.org/10.3390/cancers12040807 - 27 Mar 2020

Cited by 14 | Viewed by 3042

Abstract

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas represent a heterogeneous group of tumors, increasingly diagnosed in clinical practice. An early differential diagnosis between malignant and benign lesions is crucial to patient management and the choice of surgery or observation. The therapeutic approach [...] Read more.

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas represent a heterogeneous group of tumors, increasingly diagnosed in clinical practice. An early differential diagnosis between malignant and benign lesions is crucial to patient management and the choice of surgery or observation. The therapeutic approach is currently based on a patient’s clinical, biochemical, and morphological characteristics. The latest published International Consensus Guidelines (ICG) make no mention of the role of metabolic assessments of IPMNs. The aim of this study was to review the current literature, examining the role of 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in IPMN management. An extensive literature review was conducted according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and 10 articles were analyzed in detail, focusing on the value of PET as opposed to other standard imaging criteria. Data were retrieved on 419 patients. The 18-FDG-PET proved more sensitive, specific, and accurate than the ICG criteria in detecting malignant IPMNs (reaching 80%, 95%, and 87% vs. 67%, 58%, and 63%, respectively). Metabolic assessments may be used as an additional tool for the appropriate management of patients with doubtful imaging findings. Full article

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15 pages, 1126 KiB

Open AccessReview

FDG-PET Imaging for Hodgkin and Diffuse Large B-Cell Lymphoma—An Updated Overview

by Conrad-Amadeus Voltin, Jasmin Mettler, Jirka Grosse, Markus Dietlein, Christian Baues, Christine Schmitz, Peter Borchmann, Carsten Kobe and Dirk Hellwig

Cancers 2020, 12(3), 601; https://doi.org/10.3390/cancers12030601 - 5 Mar 2020

Cited by 32 | Viewed by 9653

Abstract

Since the mid-1990s, ¹⁸F-fluorodeoxglucose (FDG)-positron emission tomography (PET) in combination with computed tomography has come to play a prominent role in the management of malignant lymphomas. One of the first PET applications in oncology was the detection of lymphoma manifestations at staging, [...] Read more.

Since the mid-1990s, ¹⁸F-fluorodeoxglucose (FDG)-positron emission tomography (PET) in combination with computed tomography has come to play a prominent role in the management of malignant lymphomas. One of the first PET applications in oncology was the detection of lymphoma manifestations at staging, where it has shown high sensitivity. Nowadays, this imaging modality is also used during treatment to evaluate the individual chemosensitivity and adapt further therapy accordingly. If the end-of-treatment PET is negative, irradiation in advanced-stage Hodgkin lymphoma patients can be safely omitted after highly effective chemotherapy. Thus far, lymphoma response assessment has mainly been performed using visual criteria, such as the Deauville five-point scale, which became the international standard in 2014. However, novel measures such as metabolic tumor volume or total lesion glycolysis have recently been recognized by several working groups and may further increase the diagnostic and prognostic value of FDG-PET in the future. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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22 pages, 2891 KiB

Open AccessReview

Immunotherapy by Immune Checkpoint Inhibitors and Nuclear Medicine Imaging: Current and Future Applications

by Pierre Decazes and Pierre Bohn

Cancers 2020, 12(2), 371; https://doi.org/10.3390/cancers12020371 - 6 Feb 2020

Cited by 57 | Viewed by 8293

Abstract

Immunotherapy by using immune checkpoint inhibitors is a revolutionary development in oncology. Medical imaging is also impacted by this new therapy, particularly nuclear medicine imaging (also called radionuclide imaging), which uses radioactive tracers to visualize metabolic functions. Our aim was to review the [...] Read more.

Immunotherapy by using immune checkpoint inhibitors is a revolutionary development in oncology. Medical imaging is also impacted by this new therapy, particularly nuclear medicine imaging (also called radionuclide imaging), which uses radioactive tracers to visualize metabolic functions. Our aim was to review the current applications of nuclear medicine imaging in immunotherapy, along with their limitations, and the perspectives offered by this imaging modality. Method: Articles describing the use of radionuclide imaging in immunotherapy were researched using PubMed by April 2019 and analyzed. Results: More than 5000 articles were analyzed, and nearly 100 of them were retained. Radionuclide imaging, notably ¹⁸F-FDG PET/CT, already has a major role in many cancers for pre-therapeutic and therapeutic evaluation, diagnoses of adverse effects, called immune-related adverse events (IrAE), and end-of-treatment evaluations. However, these current applications can be hindered by immunotherapy, notably due to atypical response patterns such as pseudoprogression, which is defined as an increase in the size of lesions, or the visualization of new lesions, followed by a response, and hyperprogression, which is an accelerated tumor growth rate after starting treatment. To overcome these difficulties, new opportunities are offered, particularly therapeutic evaluation criteria adapted to immunotherapy and immuno-PET allowing us to predict responses to immunotherapy. Moreover, some new technological solutions are also promising, such as radiomic analyses and body composition on associated anatomical images. However, more research has to be done, notably for the diagnosis of hyperprogression and pseudoprogression. Conclusion: Immunotherapy, by its major impact on cancer and by the new patterns generated on images, is revolutionary in the field of medical images. Nuclear medicine imaging is already established and will be able to help meet new challenges through its plasticity. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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22 pages, 2271 KiB

Open AccessReview

Recent Advances in Nuclear Imaging of Receptor Expression to Guide Targeted Therapies in Breast Cancer

by Barbara Salvatore, Maria Grazia Caprio, Billy Samuel Hill, Annachiara Sarnella, Giovanni Nicola Roviello and Antonella Zannetti

Cancers 2019, 11(10), 1614; https://doi.org/10.3390/cancers11101614 - 22 Oct 2019

Cited by 9 | Viewed by 4097

Abstract

Breast cancer remains the most frequent cancer in women with different patterns of disease progression and response to treatments. The identification of specific biomarkers for different breast cancer subtypes has allowed the development of novel targeting agents for imaging and therapy. To date, [...] Read more.

Breast cancer remains the most frequent cancer in women with different patterns of disease progression and response to treatments. The identification of specific biomarkers for different breast cancer subtypes has allowed the development of novel targeting agents for imaging and therapy. To date, patient management depends on immunohistochemistry analysis of receptor status on bioptic samples. This approach is too invasive, and in some cases, not entirely representative of the disease. Nuclear imaging using receptor tracers may provide whole-body information and detect any changes of receptor expression during disease progression. Therefore, imaging is useful to guide clinicians to select the best treatments for each patient and to evaluate early response thus reducing unnecessary therapies. In this review, we focused on the development of novel tracers that are ongoing in preclinical and/or clinical studies as promising tools to lead treatment decisions for breast cancer management. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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20 pages, 2819 KiB

Open AccessReview

Theragnostic Use of Radiolabelled Dota-Peptides in Meningioma: From Clinical Demand to Future Applications

by Riccardo Laudicella, Domenico Albano, Salvatore Annunziata, Diletta Calabrò, Giovanni Argiroffi, Elisabetta Abenavoli, Flavia Linguanti, Domenico Albano, Antonio Vento, Antonio Bruno, Pierpaolo Alongi and Matteo Bauckneht

Cancers 2019, 11(10), 1412; https://doi.org/10.3390/cancers11101412 - 22 Sep 2019

Cited by 20 | Viewed by 5523

Abstract

Meningiomas account for approximately 30% of all new diagnoses of intracranial masses. The 2016 World Health Organization’s (WHO) classification currently represents the clinical standard for meningioma’s grading and prognostic stratification. However, watchful waiting is frequently the chosen treatment option, although this means the [...] Read more.

Meningiomas account for approximately 30% of all new diagnoses of intracranial masses. The 2016 World Health Organization’s (WHO) classification currently represents the clinical standard for meningioma’s grading and prognostic stratification. However, watchful waiting is frequently the chosen treatment option, although this means the absence of a certain histological diagnosis. Consequently, MRI (or less frequently CT) brain imaging currently represents the unique available tool to define diagnosis, grading, and treatment planning in many cases. Nonetheless, these neuroimaging modalities show some limitations, particularly in the evaluation of skull base lesions. The emerging evidence supporting the use of radiolabelled somatostatin receptor analogues (such as dota-peptides) to provide molecular imaging of meningiomas might at least partially overcome these limitations. Moreover, their potential therapeutic usage might enrich the current clinical offering for these patients. Starting from the strengths and weaknesses of structural and functional neuroimaging in meningiomas, in the present article we systematically reviewed the published studies regarding the use of radiolabelled dota-peptides in surgery and radiotherapy planning, in the restaging of treated patients, as well as in peptide-receptor radionuclide therapy of meningioma. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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17 pages, 853 KiB

Open AccessReview

¹⁸F-Facbc in Prostate Cancer: A Systematic Review and Meta-Analysis

by Riccardo Laudicella, Domenico Albano, Pierpaolo Alongi, Giovanni Argiroffi, Matteo Bauckneht, Sergio Baldari, Francesco Bertagna, Michele Boero, Giuseppe De Vincentis, Angelo Del Sole, Giuseppe Rubini, Lorenzo Fantechi, Viviana Frantellizzi, Gloria Ganduscio, Priscilla Guglielmo, Anna Giulia Nappi, Laura Evangelista and on the behalf of Young AIMN Working Group

Cancers 2019, 11(9), 1348; https://doi.org/10.3390/cancers11091348 - 11 Sep 2019

Cited by 36 | Viewed by 5150

Abstract

Trans-1-amino-3-¹⁸F-fluorocyclobutanecarboxylic-acid (anti-[¹⁸F]-FACBC) has been approved for the detection of prostate cancer (PCa) in patients with elevated prostate-specific-antigen following prior treatment. This review and meta-analysis aimed to investigate the diagnostic performance of ¹⁸F-FACBC positron emission tomography/computed-tomography (PET/CT) in the [...] Read more.

Trans-1-amino-3-¹⁸F-fluorocyclobutanecarboxylic-acid (anti-[¹⁸F]-FACBC) has been approved for the detection of prostate cancer (PCa) in patients with elevated prostate-specific-antigen following prior treatment. This review and meta-analysis aimed to investigate the diagnostic performance of ¹⁸F-FACBC positron emission tomography/computed-tomography (PET/CT) in the detection of primary/recurrent PCa. A bibliographic search was performed including several databases, using the following terms: “FACBC”/“fluciclovine” AND “prostate cancer”/“prostate” AND “PET”/“Positron Emission Tomography”. Fifteen and 9 studies were included in the systematic reviews and meta-analysis, respectively. At patient-based analysis, the pooled sensitivity and specificity of ¹⁸F-FACBC-PET/CT for the assessment of PCa were 86.3% and 75.9%, respectively. The pooled diagnostic odds-ratio value was 16.453, with heterogeneity of 30%. At the regional-based-analysis, the pooled sensitivity of ¹⁸F-FACBC-PET/CT for the evaluation of primary/recurrent disease in the prostatic bed was higher than in the extra-prostatic regions (90.4% vs. 76.5%, respectively); conversely, the pooled specificity was higher for the evaluation of extra-prostatic region than the prostatic bed (89% vs. 45%, respectively). ¹⁸F-FACBC-PET/CT seems to be promising in recurrent PCa, particularly for the evaluation of the prostatic bed. Additional studies to evaluate its utility in clinical routine are mandatory. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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14 pages, 1725 KiB

Open AccessFeature PaperReview

Detection Rate of ¹⁸F-Labeled PSMA PET/CT in Biochemical Recurrent Prostate Cancer: A Systematic Review and a Meta-Analysis

by Giorgio Treglia, Salvatore Annunziata, Daniele A. Pizzuto, Luca Giovanella, John O. Prior and Luca Ceriani

Cancers 2019, 11(5), 710; https://doi.org/10.3390/cancers11050710 - 23 May 2019

Cited by 83 | Viewed by 6815

Abstract

Background: The use of radiolabeled prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) for biochemical recurrent prostate cancer (BRPCa) is increasing worldwide. Recently, ¹⁸F-labeled PSMA agents have become available. We performed a systematic review and meta-analysis regarding the detection rate [...] Read more.

Background: The use of radiolabeled prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) for biochemical recurrent prostate cancer (BRPCa) is increasing worldwide. Recently, ¹⁸F-labeled PSMA agents have become available. We performed a systematic review and meta-analysis regarding the detection rate (DR) of ¹⁸F-labeled PSMA PET/CT in BRPCa to provide evidence-based data in this setting. Methods: A comprehensive literature search of PubMed/MEDLINE, EMBASE, and Cochrane Library databases through 23 April 2019 was performed. Pooled DR was calculated on a per-patient basis, with pooled proportion and 95% confidence interval (95% CI). Furthermore, pooled DR of ¹⁸F-PSMA PET/CT using different cut-off values of prostate-specific antigen (PSA) was obtained. Results: Six articles (645 patients) were included in the meta-analysis. The pooled DR of ¹⁸F-labeled PSMA PET/CT in BRPCa was 81% (95% CI: 71–88%). The pooled DR was 86% for PSA ≥ 0.5 ng/mL (95% CI: 78–93%) and 49% for PSA < 0.5 ng/mL (95% CI: 23–74%). Statistical heterogeneity was found. Conclusions: ¹⁸F-labeled PSMA PET/CT demonstrated a good DR in BRPCa. DR of ¹⁸F-labeled PSMA PET/CT is related to PSA values with significant lower DR in patients with PSA < 0.5 ng/mL. Prospective multicentric trials are needed to confirm these findings. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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8 pages, 1313 KiB

Open AccessBrief Report

^99mTc-A1 as a Novel Imaging Agent Targeting Mesothelin-Expressing Pancreatic Ductal Adenocarcinoma

by Christopher Montemagno, Shamir Cassim, Dimitry Trichanh, Clara Savary, Jacques Pouyssegur, Gilles Pagès, Daniel Fagret, Alexis Broisat and Catherine Ghezzi

Cancers 2019, 11(10), 1531; https://doi.org/10.3390/cancers11101531 - 10 Oct 2019

Cited by 12 | Viewed by 4791

Abstract

Mesothelin is a membrane-associated protein overexpressed in pancreatic ductal adenocarcinoma (PDAC). Some mesothelin-targeted therapies are in clinical development but the identification of patients eligible for such therapies is still challenging. The objective of this study was to perform the imaging of mesothelin in [...] Read more.

Mesothelin is a membrane-associated protein overexpressed in pancreatic ductal adenocarcinoma (PDAC). Some mesothelin-targeted therapies are in clinical development but the identification of patients eligible for such therapies is still challenging. The objective of this study was to perform the imaging of mesothelin in mice models of PDAC with a technetium-labeled anti-mesothelin single-domain antibody (^99mTc-A1). Methods: The Cancer Genomic Atlas (TCGA) database was used to determine the prognostic role of mesothelin in PDAC. ^99mTc-A1 was evaluated both in vitro in PDAC cells (SW1990 and AsPC-1) and in vivo in an experimental model of mesothelin-expressing PDAC (AsPC-1) in mice. Results: TCGA analysis showed that PDAC patients with high mesothelin expression had a shorter overall survival (P = 0.00066). The binding of ^99mTc-A1 was 2.1-fold greater in high-mesothelin-expressing AsPC-1 cells when compared to moderate-mesothelin-expressing SW1990 cells (p < 0.05). In vivo, the ^99mTc-A1 uptake was 3.5-fold higher in AsPC-1-derived tumors as compared to a technetium-labeled irrelevant antibody (^99mTc-Ctl) (p < 0.01). Conclusions: ^99mTc-A1 accurately allows imaging of mesothelin-expressing experimental PDAC tumors. Our experiments paved the way for the development of a companion test for mesothelin-targeted therapies. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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13 pages, 9316 KiB

Open AccessPerspective

FDG-PET/CT for Response Monitoring in Metastatic Breast Cancer: Today, Tomorrow, and Beyond

by Malene Grubbe Hildebrandt, Jeppe Faurholdt Lauridsen, Marianne Vogsen, Jorun Holm, Mie Holm Vilstrup, Poul-Erik Braad, Oke Gerke, Mads Thomassen, Marianne Ewertz, Poul Flemming Høilund-Carlsen and The Centre for Personalized Response Monitoring in Oncology (PREMIO)

Cancers 2019, 11(8), 1190; https://doi.org/10.3390/cancers11081190 - 15 Aug 2019

Cited by 12 | Viewed by 6964

Abstract

While current international guidelines include imaging of the target lesion for response monitoring in metastatic breast cancer, they do not provide specific recommendations for choice of imaging modality or response criteria. This is important as clinical decisions may vary depending on which imaging [...] Read more.

While current international guidelines include imaging of the target lesion for response monitoring in metastatic breast cancer, they do not provide specific recommendations for choice of imaging modality or response criteria. This is important as clinical decisions may vary depending on which imaging modality is used for monitoring metastatic breast cancer. FDG-PET/CT has shown high accuracy in diagnosing metastatic breast cancer, and the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) have shown higher predictive values than the CT-based Response Evaluation Criteria in Solid Tumors (RECIST) for prediction of progression-free survival. No studies have yet addressed the clinical impact of using different imaging modalities or response evaluation criteria for longitudinal response monitoring in metastatic breast cancer. We present a case study of a patient with metastatic breast cancer who was monitored first with conventional CT and then with FDG-PET/CT. We retrospectively applied PERCIST to evaluate the longitudinal response to treatment. We used the one-lesion PERCIST model measuring SULpeak in the hottest metastatic lesion on consecutive scans. This model provides a continuous variable that allows graphical illustration of disease fluctuation along with response categories. The one-lesion PERCIST approach seems able to reflect molecular changes and has the potential to support clinical decision-making. Prospective clinical studies addressing the clinical impact of PERCIST in metastatic breast cancer are needed to establish evidence-based recommendations for response monitoring in this disease. Full article

(This article belongs to the Special Issue Role of Medical Imaging in Cancers)

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