Luca Ceriani

[18F]Fluorodeoxyglucose Positron Emission Tomography Predicts Survival After Chemoimmunotherapy for Primary Mediastinal Large B-Cell Lymphoma: Results of the International Extranodal Lymphoma Study Group IELSG-26 Study

PURPOSE To assess the role of [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) after rituximab and anthracycline-containing chemoimmunotherapy in patients with primary mediastinal large B-cell lymphoma (PMLBCL). PATIENTS AND METHODS Among 125 patients prospectively enrolled, 115 were eligible for central review of PET/CT scans at the completion of standard chemoimmunotherapy, by using a five-point scale. Consolidation radiotherapy (RT) was permitted and given to 102 patients. RESULTS Fifty-four patients (47%) achieved a complete metabolic response (CMR), defined as a completely negative scan or with residual [18F]FDG activity below the mediastinal blood pool (MBP) uptake. In the remaining 61 patients (53%), the residual uptake was higher than MBP uptake but below the liver uptake in 27 (23%), slightly higher than the liver uptake in 24 (21%), and markedly higher in 10 (9%). CMR after chemoimmunotherapy predicted higher 5-year progression-free survival (PFS; 98% v 82%; P=.0044) and overall survival (OS; 100% v 91%; P=.0298). Patients with residual uptake higher than MBP uptake but below liver uptake had equally good outcomes without any recurrence. Using the liver uptake as cutoff for PET positivity (boundary of score, 3 to 4) discriminated most effectively between high or low risk of failure, with 5-year PFS of 99% versus 68% (P<.001) and 5-year OS of 100% versus 83% (P<.001). CONCLUSION More than 90% of patients are projected to be alive and progression-free at 5 years, despite a low CMR rate (47%) after chemoimmunotherapy. This study provides a basis for using PET/CT to define the role of RT in PMLBCL.

Relationship between prostate-specific antigen kinetics and detection rate of radiolabelled choline PET/CT in restaging prostate cancer patients: a meta-analysis.

Abstract Background: The aim of the article was to systematically review published data about the relationship between prostate-specific antigen (PSA) kinetics, including PSA doubling time (PSAdt) and PSA velocity (PSAvel), and detection rate (DR) of positron emission tomography/computed tomography (PET/CT) using radiolabelled choline in restaging prostate cancer (PCa). Methods: A comprehensive literature search of studies published through July 2013 regarding the relationship between PSA kinetics and DR of radiolabelled choline PET/CT was carried out. Furthermore, a meta-analysis was performed in order to establish the DR of radiolabelled choline PET/CT using different cut-off values of PSAdt (≤ or >6 months) and PSAvel [>1 or ≤1 ng/(mL year) and >2 or ≤2 ng/(mL year)]. Moreover, a pooled analysis to establish whether PSAdt and PSAvel (using the abovementioned cut-off values) may predict positive PET/CT results was carried out. Results: Fourteen articles were selected. The pooled DR of radiolabelled choline PET/CT in restaging PCa was 58% [95% confidence interval (CI) 55–60]. Most articles reported a relationship between PSA kinetics and DR of PET/CT. Pooled DR of radiolabelled choline PET/CT increased to 65% (95% CI 58–71) when PSAdt was ≤6 months and to 71% (95% CI 66–76) and 77% (95% CI 71–82) when PSAvel was >1 or >2 ng/(mL year), respectively. PSAdt ≤6 months and PSAvel >1 or >2 ng/(mL year) proved to be relevant factors in predicting the positive result of radiolabelled choline PET/CT. Conclusions: Due to the strong relationship between PSA kinetics and DR of radiolabelled choline PET/CT, beyond PSA values, PSAdt and PSAvel should be taken into account in the selection of PCa patients who should undergo radiolabelled choline PET/CT for restaging.

Unstimulated Highly Sensitive Thyroglobulin in Follow-up of Differentiated Thyroid Cancer Patients: A Meta-Analysis

CONTEXT Serum thyroglobulin (Tg) is an indicator of differentiated thyroid cancer (DTC) relapse. OBJECTIVE Our objective was to conduct a meta-analysis of published data about the diagnostic performance of highly sensitive serum Tg (hsTg) during levothyroxine therapy in DTC follow-up. DATA SOURCES We performed a comprehensive literature search of PubMed/MEDLINE and Scopus for studies published until July 2013. STUDY SELECTION Studies investigating the diagnostic performance of basal hsTg in monitoring DTC were eligible. Exclusion criteria were 1) articles not within the field of interest; 2) reviews, letters, or conference proceedings; 3) articles evaluating serum Tg measurement with a functional sensitivity >0.1 ng/mL; 4) overlap in patient data; and 5) insufficient data to reassess diagnostic performance of basal serum hsTg. DATA EXTRACTION Information was collected concerning basic study data, patient characteristics, and technical aspects. For each study, the number of true-positive, false-positive, true-negative, and false-negative findings for basal hsTg, considering stimulated Tg measurement as a reference standard, were recorded. DATA SYNTHESIS Pooled data demonstrated that the negative predictive value of hsTg was 97% and 99% considering a stimulated Tg measurement >1 ng/mL and >2 ng/mL as cutoffs for positivity, respectively. Despite the high pooled sensitivity of basal hsTg, the pooled specificity, accuracy, and positive predictive value were insufficient to completely substitute for a stimulated Tg measurement. CONCLUSIONS Basal hsTg measurement has a very high negative predictive value but an insufficient positive predictive value for monitoring DTC patients. Therefore, a Tg stimulation test can be avoided in patients with an undetectable basal hsTg, whereas a stimulated Tg measurement should be considered when hsTg levels are detectable.

Utility of baseline 18FDG PET/CT functional parameters in defining prognosis of primary mediastinal (thymic) large B-cell lymphoma

The International Extranodal Lymphoma Study Group (IELSG) 26 study was designed to evaluate the role of (18)F-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) in the management of primary mediastinal (thymic) large B-cell lymphoma (PMBCL). We examined the prognostic impact of functional PET parameters at diagnosis. Metabolic activity defined by the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) was measured on baseline 18FDG PET/CT following a standard protocol in a prospectively enrolled cohort of 103 PMBCL patients. All received combination chemoimmunotherapy with doxorubicin- and rituximab-based regimens; 93 had consolidation radiotherapy. Cutoff values were determined using the receiver-operating characteristic curve. At a median follow-up of 36 months, progression-free survival (PFS) and overall survival (OS) were 87% and 94%, respectively. In univariate analysis, elevated MTV and TLG were significantly associated with worse PFS and OS. Only TLG retained statistical significance for both OS (P = .001) and PFS (P < .001) in multivariate analysis. At 5 years, OS was 100% for patients with low TLG vs 80% for those with high TLG (P = .0001), whereas PFS was 99% vs 64%, respectively (P < .0001). TLG on baseline PET appeared to be a powerful predictor of PMBCL outcomes and warrants further validation as a biomarker. The IELSG 26 study was registered at www.clinicaltrials.gov as #NCT00944567.

Thyroglobulin assay during thyroxine treatment in low-risk differentiated thyroid cancer management : comparison with recombinant human thyrotropin-stimulated assay and imaging procedures

Abstract Background: Circulating human thyroglobulin (TG) measurement has a pivotal role in the management of patients affected by differentiated thyroid cancer (DTC). Undetectable thyrotropin (TSH)-stimulated serum TG after thyroid ablation (i.e., thyroidectomy and radioiodine) implies the absence of residual or relapsing DTC. Recently, high-cost recombinant human TSH (rhTSH) was proposed for TG stimulation to avoid uncomfortable thyroxine (T4) withdrawal. However, only a small fraction of relapsing DTC patients showed undetectable TG under T4 treatment (onT4-TG) by high-sensitivity assays. The present study was undertaken to compare onT4-TG with the rhTSH-stimulated TG assay (rhTSH-TG), 131I scanning and neck ultrasound (US) with fine-needle aspiration biopsy. Methods: We enrolled 117 patients with histologically proven DTC treated by total thyroidectomy and radioiodine. Inclusion criteria were: complete tumour excision, no radioiodine uptake outside of the thyroid bed at post-treatment scan and undetectable onT4-TG 3months after primary treatment. At 1year after radioiodine treatment, all patients underwent onT4-TG assay, rhTSH-stimulated TG assay, 131I scanning and neck US. Based on histology, clinical data and long-term follow-up, persistent/relapsing disease was confirmed in 14 patients. Results: onT4- and rhTSH-TG were positive in 10 and 12 patients, respectively and two patients converted from undetectable to detectable TG after rhTSH administration. Neck US was positive in 10 patients and a combination of US with onT4- and rhTSH-TG assays showed positivity in 13 and 14 out 14 patients, respectively. A radioiodine scan was positive in six patients, all with positive onT4- and rhTSH-TG levels. Globally, the negative predictive value of the onT4- and rhTSH-TG assays was 99% and 100%, respectively, and 104 rhTSH stimulations had to be performed to detect one local recurrence with negative onT4-TG. Conclusions: Our preliminary data need further confirmation on larger groups of patients, but seem to indicate that onT4-TG assay by a high-sensitivity method combined with neck US may avoid rhTSH stimulation in low-risk DTC patients after surgery and radioiodine thyroid ablation.

Thyroglobulin assay 4 weeks after thyroidectomy predicts outcome in low-risk papillary thyroid carcinoma.

Abstract Background: Thyroidectomy followed by administration of large activities of 131I is the treatment of choice for differentiated thyroid carcinomas. Due to its good prognosis, some authors argue that papillary thyroid cancer with a diameter of up to 10mm can be treated by surgery alone. In the new TNM classification started in 2002, the T1 group now encompasses all tumours with a diameter up to 20mm, which widens the indications for a conservative approach. In this instance, prognostic markers are needed to better select patients before planning non-aggressive treatment. Serum thyroglobulin plays a pivotal role in thyroid carcinoma management after thyroid ablation (i.e., surgery and radioiodine) but is of limited value before these treatments. However, thyroglobulin assay performed after surgery but before radioiodine treatment has been proven to be useful in predicting the presence/absence of distant metastasis. Patients and methods: Our study was undertaken in patients affected by pT1 papillary thyroid carcinoma to evaluate the predictive value of post-surgery thyroglobulin assay on 1) restaging immediately after radioiodine treatment and 2) restaging at 12months. We selected 156 patients affected by pT1 histologically proven papillary thyroid carcinoma, submitted to total thyroidectomy. Serum thyroglobulin was assayed by a specific immunoradiometric method 4weeks after surgery, just before radioiodine administration. Cut-off levels were selected by receiver operating characteristic curve analysis. Thyroglobulin levels were compared to the results of a post-radioiodine treatment scan and 12-month restaging. Results: Globally, 23 out of 156 patients showed persistent/recurrent disease (15%). Post-surgery thyroglobulin levels above 4.50μg/L identified 94% of patients with metastasis at post-dose scan, and a level below 3.20μg/L identified 86% and 93% of relapsed and disease-free patients at 12-month restaging, respectively. Multivariate analysis and Spearman rank correlation showed that the N-status and post-surgery thyroglobulin level are independent prognostic factors. Conclusions: The post-surgery thyroglobulin level could be systematically assayed in patients with pT1-papillary thyroid carcinoma and taken into account in planning treatment.

Thyroglobulin measurement before rhTSH‐aided 131I ablation in detecting metastases from differentiated thyroid carcinoma

Aim  Thyroidectomy followed by administration of large activities of 131‐iodine (131I) is the treatment of choice for differentiated thyroid carcinoma (DTC). The serum thyroglobulin (Tg) measurement during hypothyroidism (offT4‐Tg), just before radioiodine thyroid ablation, has proved to be effective for predicting persistent/recurrent disease. However, the Tg measurement cannot be used as a corresponding value for pre‐ablative offT4‐Tg when recombinant human TSH (rhTSH) is used as stimulus before treatment. The present study was undertaken to evaluate if post‐thyroidectomy Tg values, measured before rhTSH‐stimulated radioiodine ablation is of prognostic value in patients affected by DTC.

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.

Relationship between serum thyroglobulin and 18FDG-PET/CT in 131I-negative differentiated thyroid carcinomas.

The purpose of this study was to assess the relationship between [18F]‐fluorodeoxyglucose (18FDG)‐positron emission tomography/CT (18FDG‐PET/CT) and serum thyroglobulin (Tg) in patients with recurrent differentiated thyroid carcinoma (DTC).

99mTc-sestamibi scanning in thyroid nodules with nondiagnostic cytology

Our aim in this study was to assess the relevance of 99mTc‐sestaMIBI (MIBI) scan in the diagnostic evaluation of thyroid nodules with nondiagnostic cytology.