Salvatore Annunziata

The Role of Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in Aggressive Histological Subtypes of Thyroid Cancer: An Overview

Aggressive histological subtypes of thyroid cancer are rare and have a poor prognosis. The most important aggressive subtypes of thyroid cancer are Hürthle cell carcinoma (HCTC) and anaplastic and poorly differentiated carcinoma (ATC and PDTC). The American Thyroid Association recently published guidelines for the management of patients with ATC, but no specific guidelines have been done about HCTC. We performed an overview of the literature about the role of Fluorine-18-Fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (FDG-PET or PET/CT) in aggressive histological subtypes of thyroid cancer. Only few original studies about the role of FDG-PET or PET/CT in HCTC, PDTC, and ATC have been published in the literature. FDG-PET or PET/CT seems to be useful in staging or followup of invasive and metastatic HCTC. FDG-PET or PET/CT should be used in patients with ATC in initial staging and in the followup after surgery to evaluate metastatic disease. Some authors suggest the use of FDG-PET/CT in staging of PDTC, but more studies are needed to define the diagnostic use of FDG-PET/CT in this setting. Limited experience suggests the usefulness of FDG-PET or PET/CT in patients with more aggressive histological subtypes of DTC. However, DTC presenting as radioiodine refractory and FDG-PET positive should be considered aggressive tumours with poor prognosis.

The role of 18F-FDG-PET and PET/CT in patients with sarcoidosis: an updated evidence-based review.

RATIONALE AND OBJECTIVES To provide an updated evidence-based review of the literature on the role of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) or PET/computed tomography (PET/CT) in patients with sarcoidosis. MATERIALS AND METHODS A comprehensive literature search of PubMed/MEDLINE, Scopus, and Embase databases was conducted to find relevant published articles on FDG-PET or PET/CT in patients with sarcoidosis. Only those studies that satisfied all the following criteria were included: (1) FDG-PET or PET/CT performed in patients with histologically confirmed sarcoidosis, (2) sample size of at least 10 patients, and (3) whole-body PET studies performed. Information was collected concerning basic study, patient characteristics, and technical aspects. The main findings of the articles included have been described. RESULTS Reviewing titles and abstracts, 21 articles were selected. The role of FDG-PET or PET/CT was analyzed in assessing disease extent and activity and in treatment response evaluation. Comparison with other tracers had also been investigated. Recent studies evaluated the influence of these methods in the clinical management and their role as predictive tools in patients with sarcoidosis. CONCLUSIONS FDG-PET and PET/CT seem to be useful in staging, evaluating disease activity, and monitoring treatment response in patients with sarcoidosis. PET appears to have higher diagnostic accuracy compared to Gallium-67-citrate scintigraphy. Conversely, there is not enough evidence about the use of other PET tracers in patients with sarcoidosis. FDG-PET and PET/CT seem to have a role as predictive tools and may influence the clinical management in patients with sarcoidosis, but more studies are needed in this regard.

Diagnostic performance of Fluorine-18-Fluorodeoxyglucose positron emission tomography for the diagnosis of osteomyelitis related to diabetic foot: A systematic review and a meta-analysis

OBJECTIVE To systematically review and meta-analyse published data about the diagnostic performance of Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in osteomyelitis related to diabetic foot. METHODS A comprehensive literature search of studies on (18)F-FDG-PET and PET/CT in patients with diabetic foot was performed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odds ratio (DOR) and area under the summary ROC curve of (18)F-FDG-PET and PET/CT in patients with osteomyelitis related to diabetic foot were calculated. RESULTS Nine studies comprising 299 patients with diabetic foot were included in the qualitative analysis (systematic review) and discussed. The quantitative analysis (meta-analysis) of four selected studies provided the following results on a per patient-based analysis: sensitivity was 74% [95% confidence interval (95%CI): 60-85%], specificity 91% (95%CI: 85-96%), LR+ 5.56 (95%CI: 2.02-15.27), LR- 0.37 (95%CI: 0.10-1.35), and DOR 16.96 (95%CI: 2.06-139.66). The area under the summary ROC curve was 0.874. CONCLUSIONS In patients with suspected osteomyelitis related to diabetic foot (18)F-FDG-PET and PET/CT demonstrated a high specificity, being potentially useful tools if combined with other imaging methods such as MRI. Nevertheless, the literature focusing on the use of (18)F-FDG-PET and PET/CT in this setting remains still limited.

Diagnostic Accuracy of Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in the Evaluation of the Primary Tumor in Patients with Cholangiocarcinoma: A Meta-Analysis

Objective. To meta-analyze published data about the diagnostic accuracy of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) or PET/computed tomography (PET/CT) for primary tumor evaluation in patients with cholangiocarcinoma (CCa). Methods. A comprehensive literature search of studies published through December 31, 2013, was performed. Pooled sensitivity and specificity were calculated on a per patient based analysis. Subgroup analyses considering the device used (PET versus PET/CT) and the localization of the primary tumor (intrahepatic cholangiocarcinoma (IH-CCa), extrahepatic cholangiocarcinoma (EH-CCa), and hilar cholangiocarcinoma (H-CCa)) were carried out. Results. Twenty-three studies including 1232 patients were included in the meta-analysis. Pooled sensitivity and specificity of 18F-FDG-PET or PET/CT were 81% and 82%, respectively. Pooled sensitivity and specificity, respectively, were 80% and 89% for PET, 82% and 75% for PET/CT, 95% and 83% for IH-CCa, 84% and 95% for H-CCa, and 76% and 74% for EH-CCa. Conclusions.   18F-FDG-PET and PET/CT were demonstrated to be accurate diagnostic imaging methods for primary tumor evaluation in patients with CCa. These tools have a better diagnostic accuracy in patients with IH-CCa than in patients with EH-CCa. Further studies are needed to evaluate the accuracy of 18F-FDG-PET or PET/CT in patients with H-CCa.

Diagnostic Performance of Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in the Postchemotherapy Management of Patients with Seminoma: Systematic Review and Meta-Analysis

Objective. To meta-analyze published data about the diagnostic performance of fluorine-18-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the postchemotherapy management of patients with seminoma. Methods. A comprehensive literature search of studies published through January 2014 on this topic was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity and specificity, positive and negative predictive values (PPV and NPV), accuracy, and area under the summary ROC curve (AUC) of 18F-FDG-PET or PET/CT on a per examination-based analysis were calculated. Subgroup analyses considering the size of residual/recurrent lesions were carried out. Results. Nine studies including 375 scans were selected. The pooled analysis provided the following results: sensitivity 78% (95% confidence interval (95% CI): 67–87%), specificity 86% (95% CI: 81–89%), PPV 58% (95% CI: 48–68%), NPV 94% (95% CI: 90–96%), and accuracy 84% (95% CI: 80–88%). The AUC was 0.90. A better diagnostic accuracy of 18F-FDG-PET or PET/CT in evaluating residual/recurrent lesions >3 cm compared to those <3 cm was found. Conclusions. 18F-FDG-PET and PET/CT were demonstrated to be accurate imaging methods in the postchemotherapy management of patients with seminoma; nevertheless possible sources of false-negative and false-positive results should be considered. The literature focusing on this setting still remains limited and cost-effectiveness analyses are warranted.

The Role of 18F-FDG-PET and PET/CT in Patients with Colorectal Liver Metastases Undergoing Selective Internal Radiation Therapy with Yttrium-90: A First Evidence-Based Review

Purpose. To provide a first evidence-based review of the literature on the role of fluorine-18-fluorodeoxyglucose positron emission tomography and positron emission tomography/computed tomography (FDG-PET and PET/CT) in patients with colorectal liver metastases (CRLM) undergoing selective internal radiation therapy (SIRT) with yttrium-90 (90Y) microspheres. Methods. A comprehensive computer literature search was conducted to find relevant published articles on whole-body FDG-PET or PET/CT in patients with CRLM undergoing SIRT. Results. We identified 19 studies including 833 patients with CRLM undergoing SIRT. The role of FDG-PET or PET/CT was analysed in treatment planning, treatment response evaluation, and as prognostic tool. Conclusion. FDG-PET and PET/CT provide additional information in treatment evaluation of CRLM patients treated with SIRT and may have a role in treatment planning and patient selection. FDG-PET/CT is emerging as good prognostic tool in these patients.

Diagnostic performance of Fluorine-18-Fluorodeoxyglucose positron emission tomography in the assessment of pleural abnormalities in cancer patients: A systematic review and a meta-analysis

OBJECTIVE To systematically review and meta-analyze published data about the diagnostic performance of Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the assessment of pleural abnormalities in cancer patients. METHODS A comprehensive literature search of studies published through June 2013 regarding the role of (18)F-FDG-PET and PET/CT in evaluating pleural abnormalities in cancer patients was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odd ratio (DOR) of (18)F-FDG-PET or PET/CT on a per patient-based analysis were calculated. The area under the summary ROC curve (AUC) was calculated to measure the accuracy of these methods in the assessment of pleural abnormalities. Sub-analyses considering (18)F-FDG-PET/CT and patients with lung cancer only were carried out. RESULTS Eight studies comprising 360 cancer patients (323 with lung cancer) were included. The meta-analysis of these selected studies provided the following results: sensitivity 86% [95% confidence interval (95%CI): 80-91%], specificity 80% [95%CI: 73-85%], LR+ 3.7 [95%CI: 2.8-4.9], LR- 0.18 [95%CI: 0.09-0.34], DOR 27 [95%CI: 13-56]. The AUC was 0.907. No significant improvement considering PET/CT studies only and patients with lung cancer was found. CONCLUSIONS (18)F-FDG-PET and PET/CT demonstrated to be useful diagnostic imaging methods in the assessment of pleural abnormalities in cancer patients, nevertheless possible sources of false-negative and false-positive results should be kept in mind. The literature focusing on the use of (18)F-FDG-PET and PET/CT in this setting remains still limited and prospective studies are needed.

Diagnostic Performance of Positron Emission Tomography/Computed Tomography Using Fluorine-18 Fluorodeoxyglucose in Detecting Locoregional Nodal Involvement in Patients with Anal Canal Cancer: A Systematic Review and Meta-Analysis

Purpose. The diagnostic performance of positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) in detecting nodal involvement in patients with anal canal cancer (ACC) has been investigated by several studies with conflicting results. The aim of our study is to systematically review and meta-analyze published data about this topic. Methods. A comprehensive computer literature search of PubMed/MEDLINE, Scopus, and Embase databases was carried out on July 10 to find relevant articles concerning the diagnostic performance of FDG-PET in detecting locoregional nodal involvement in patients with ACC. No language restriction was used. Pooled diagnostic performance on a lesion-based analysis was calculated. Results. Seven retrospective and five prospective studies have been reviewed. Six studies allowed assessing pooled sensitivity; five studies allowed assessing pooled specificity. Sensitivity and specificity values of FDG-PET/CT on a lesion-based analysis ranged from 31 to 100% and from 53 to 98%, with pooled estimates of 56% (95% CI: 45–67%) and 90% (95% CI: 86–93%), respectively. Conclusions. Our meta-analysis demonstrates that FDG-PET is a specific diagnostic tool in detecting locoregional lymph node involvement in patients with ACC. Low sensitivity is a major concern; however, higher sensitivity could be reached combining FDG-PET with MR scan.

Circulating tumor DNA reveals genetics, clonal evolution and residual disease in classical Hodgkin lymphoma

The rarity of neoplastic cells in the biopsy imposes major technical hurdles that have so far limited genomic studies in classical Hodgkin lymphoma (cHL). By using a highly sensitive and robust deep next-generation sequencing approach for circulating tumor DNA (ctDNA), we aimed to identify the genetics of cHL in different clinical phases, as well as its modifications on treatment. The analysis was based on specimens collected from 80 newly diagnosed and 32 refractory patients with cHL, including longitudinal samples collected under ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy and longitudinal samples from relapsing patients treated with chemotherapy and immunotherapy. ctDNA mirrored Hodgkin and Reed-Sternberg cell genetics, thus establishing ctDNA as an easily accessible source of tumor DNA for cHL genotyping. By identifying STAT6 as the most frequently mutated gene in ∼40% of cases, we refined the current knowledge of cHL genetics. Longitudinal ctDNA profiling identified treatment-dependent patterns of clonal evolution in patients relapsing after chemotherapy and patients maintained in partial remission under immunotherapy. By measuring ctDNA changes during therapy, we propose ctDNA as a radiation-free tool to track residual disease that may integrate positron emission tomography imaging for the early identification of chemorefractory patients with cHL. Collectively, our results provide the proof of concept that ctDNA may serve as a novel precision medicine biomarker in cHL.

CD68+ cell count, early evaluation with PET and plasma TARC levels predict response in Hodgkin lymphoma

Early response evaluation with [18F]fluordeoxyglucose (FDG) positron emission tomography after 2 cycles of chemotherapy (interim PET) has been indicated as the strongest predictor for outcome in classical Hodgkin lymphoma (HL). We studied the prognostic role of the number of tumor‐infiltrating CD68+ cells and of the plasma levels of TARC (thymus and activation‐regulated chemokine) in the context of interim PET in 102 patients with classical HL treated with Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD). After 2 ABVD cycles, interim PET according to Deauville criteria was negative (score 0–3) in 85 patients and positive (score 4–5) in 15 patients (2 patients technically not evaluable). TARC levels were elevated in 89% of patients at diagnosis, and decreased after 2 cycles in 82% of patients. Persistently elevated TARC levels in 18% of patients were significantly associated with a positive PET result (P = 0.007). Strong predictors for progression‐free survival (PFS) were a negative interim PET (85% vs. 28%, P < 0.0001) and CD68+ cell counts <5% (89% vs. 67%, P = 0.006), while TARC levels at diagnosis and at interim evaluation had no prognostic role. In multivariate analysis, interim PET, CD68+ cell counts and presence of B‐symptoms were independently associated with PFS. We conclude that although TARC levels are a biomarker for early response evaluation, they cannot substitute for interim PET as outcome predictor in HL. The evaluation of CD68 counts and B‐symptoms at diagnosis may help to identify low‐risk patients regardless positive interim PET.