We performed an external validation of a predictive model for persistent/metastatic disease in patients with differentiated thyroid cancer (DTC) at post-treatment 131I whole-body scintigraphy (WBS). Our study population included 836 patients (median age 44 years, 78

Background: Patients with differentiated thyroid cancer (DTC) are referred to radioactive 131I (RAI) therapy and post-therapy 131I whole-body scintigraphy (WBS) to identify local and/or remote metastases. Positron emission tomography (PET)/computed tomography (CT) imaging with 18F-fluoro-D-glucose (FDG) or 18F-sodium fluoride (NaF) may also be used with these patients for the evaluation of bone metastases. We compared the role of 18F-NaF PET/CT and 18F-FDG-PET/CT in patients with DTC and documented bone metastases at post-therapy WBS. Methods: Ten consecutive DTC patients with iodine avid bone metastasis at post-therapy WBS referred to 18F-NaF PET/CT and 18F-FDG PET/CT were studied. The findings of the three imaging procedures were compared for abnormal detection rates and concordance. Results: At post-therapy 131I WBS, all patients had skeletal involvement with a total of 21 bone iodine avid lesions. At 18F-FDG PET/TC, 19 bone lesions demonstrated increased tracer uptake and CT pathological alterations, while 2 lesions did not show any pathological finding. At 18F-NaF PET/CT, the 19 bone lesions detected at 18F-FDG PET/TC also demonstrated abnormal tracer uptake, and the other 2 bone iodine avid foci did not show any pathological finding. Conclusions: In patients with DTC, 18F-NaF PET/CT did not obtain more information on the metastatic skeletal involvement than post-therapy 131I WBS and 18F-FDG PET/CT.

Second primary malignancies (SPM) are described as any primary, not synchronous, malignancy arising in a different anatomical district, with confirmed histological diagnosis. Age at diagnosis, previous non-thyroidal primary malignancy, and radioactive iodine (RAI) therapy have been proposed as independent risk factors for SPM. RAI therapy is a standard treatment for moderate-high risk differentiated thyroid cancer (DTC), and its effect on the development of SPM has become a critical topic in DTC treatment. The purpose of this retrospective single-center study was to investigate the occurrence and the possible association of non-thyroidal SPM diagnosed after DTC and RAI therapy in a cohort of 1326 consecutive DTC patients referred at our Institution for RAI treatment from 1993 to 2009. Eighty-nine patients with ages ≤ 18 years at the time of DTC diagnosis or with a follow-up of ≤12 months were excluded from the final analysis. All patients underwent a complete clinical and hematological follow-up every 6 months for a minimum of 12 months. During follow-up (mean 89 ± 73 months), 25 patients (2%) had an SPM diagnosis (mean 133 ± 73 months). The most common site of the second malignancy was the breast, accounting for 32% of all SPM, followed by colon-rectal cancer (16%), leukemia, and gynecological and kidney cancer (4%). At Cox univariable regression analysis, age at DTC diagnosis (p < 0.001), age ≥55 years (p < 0.001) and follow-up duration (p < 0.004) were associated with SPM onset, while no significant association was observed with the administered activity of radioiodine. In conclusion, our data suggest that the older a person gets, the more sharply the likelihood of developing additional diseases, such as PMS, increases. Similarly, for follow-up, the more a patient is followed up clinically over time, the higher the risk of new diagnoses increases.

PURPOSE:In pediatric patients with differentiated thyroid cancer (DTC) we assessed the prognostic value of the 12-month response to therapy after initial treatment with surgery and radioactive iodine (RAI). METHODS:We retrospectively evaluated 94 pediatric patients with DTC, treated with surgery and RAI who were initially classified as low, intermediate or high risk of relapse of disease according to the American Thyroid Association (ATA) guidelines. Twelve months after RAI administration the response to therapy was assessed by serum thyroglobulin (Tg) measurement and neck ultrasound and patients were classified as having excellent response (ER) or no-ER. RESULTS:At the 12 months evaluation, 62 (66%) patients had ER and 32 (34%) no-ER. During a mean follow-up time of 86 months (range 9-517), 19 events occurred (20% cumulative event rate). Events occurred more frequently in younger patients (p < 0.05), in those at ATA intermediate/high risk (p < 0.01) and with a pre-RAI therapy Tg level > 10 ng/mL (p < 0.001), and in those with no-ER (p < 0.001). At multivariate analysis, the evidence of no-ER was the only independent predictor of events. CONCLUSION:In pediatric patients with DTC, the response to therapy evaluated 12 months after initial treatment has an independent prognostic impact and is able to predict mid-term outcome. Patients with no-ER at 12 months after RAI therapy should be closely followed-up.

We assessed the outcome of administration of empiric radioactive iodine (RAI) therapy to patients with differentiated thyroid cancer (DTC), in a propensity-score-matched cohort of patients with biochemical incomplete response (BIR) and without evidence of structural disease. We retrospectively evaluated 820 DTC patients without distant metastases, who underwent total thyroidectomy followed by RAI therapy, with available BIR at 12 months and follow-up evaluations. The patients were categorized according to the administration of empiric therapy (ET). To account for differences between patients with (n = 119) and without (n = 701) ET, a propensity-score-matched cohort of 119 ET and 119 no-ET patients was created. The need for additional therapy and the occurrence of structural disease were considered as end-points. During a median follow-up of 53 months (range 3-285), 57 events occurred (24% cumulative event rate). The rate of events was significantly higher in the no-ET compared to the ET patients (30% vs. 18% p < 0.001). The multivariate Cox analysis identified age (p < 0.01), pre-therapy Tg (p < 0.05) and empiric RAI therapy (p < 0.01) as predictors of outcome. The Kaplan-Meier analysis found that progression-free survival was lower in no-ET patients compared to the ET group (p < 0.01). In patients with DTC treated with surgery and RAI, and with biochemical incomplete response at the 12-month evaluation, their prognosis seemed to be affected by Tg values and the empiric treatment. The identification of candidates for this approach may improve prognosis.

Radiomics is rapidly advancing in precision diagnostics and cancer treatment. However, there are several challenges that need to be addressed before translation to clinical use. This study presents an ad-hoc weighted statistical framework to explore radiomic biomarkers for a better characterization of the radiogenomic phenotypes in breast cancer. Thirty-six female patients with breast cancer were enrolled in this study. Radiomic features were extracted from MRI and PET imaging techniques for malignant and healthy lesions in each patient. To reduce within-subject bias, the ratio of radiomic features extracted from both lesions was calculated for each patient. Radiomic features were further normalized, comparing the z-score, quantile, and whitening normalization methods to reduce between-subjects bias. After feature reduction by Spearman’s correlation, a methodological approach based on a principal component analysis (PCA) was applied. The results were compared and validated on twenty-seven patients to investigate the tumor grade, Ki-67 index, and molecular cancer subtypes using classification methods (LogitBoost, random forest, and linear discriminant analysis). The classification techniques achieved high area-under-the-curve values with one PC that was calculated by normalizing the radiomic features via the quantile method. This pilot study helped us to establish a robust framework of analysis to generate a combined radiomic signature, which may lead to more precise breast cancer prognosis.

BACKGROUND:Prostate cancer is the second most commonly diagnosed cancer in men. The diagnostic accuracy in prostate cancer can be increased by employing a preliminary multiparametric MRI followed by a fusion-targeted biopsy.METHODS:To compare the diagnostic accuracy of fusion-targeted biopsy with the standard systematic biopsy in prostate cancer patients, we enrolled 139 patients on which we performed 139 prostate biopsies consisting of three targeted samples followed by 12 regular systematic samples. Based on histology, we analyzed the diagnostic performance of the two methods.RESULTS:Both methods were equally good at detecting clinically significant cancer (83.3%, 50/60), while systematic biopsy detected more clinically insignificant cancers. However, the best diagnostic performance is obtained by combining the two methods.CONCLUSION:The two methods are best seen as synergistic, and the addition of fusion biopsy can be used to detect more clinically significant prostate cancers than systematic biopsy alone.

Background Clinical markers of cognitive decline in Parkinson's disease (PD) encompass several mental non-motor symptoms such as hallucinations, apathy, anxiety, and depression. Furthermore, freezing of gait (FOG) and specific gait alterations have been associated with cognitive dysfunction in PD. Finally, although low cerebrospinal fluid levels of amyloid-β42 have been found to predict cognitive decline in PD, hitherto PET imaging of amyloid-β (Aβ) failed to consistently demonstrate the association between Aβ plaques deposition and mild cognitive impairment in PD (PD-MCI). Aim Finding significant features associated with PD-MCI through a machine learning approach. Patients and methods Patients were assessed with an extensive clinical and neuropsychological examination. Clinical evaluation included the assessment of mental non-motor symptoms and FOG using the specific items of the MDS-UPDRS I and II. Based on the neuropsychological examination, patients were classified as subjects without and with MCI (noPD-MCI, PD-MCI). All patients were evaluated using a motion analysis system. A subgroup of PD patients also underwent amyloid PET imaging. PD-MCI and noPD-MCI subjects were compared with a univariate statistical analysis on demographic data, clinical features, gait analysis variables, and amyloid PET data. Then, machine learning analysis was performed two times: Model 1 was implemented with age, clinical variables (hallucinations/psychosis, depression, anxiety, apathy, sleep problems, FOG), and gait features, while Model 2, including only the subgroup performing PET, was implemented with PET variables combined with the top five features of the former model. Results Seventy-five PD patients were enrolled (33 PD-MCI and 42 noPD-MCI). PD-MCI vs. noPD-MCI resulted in older and showed worse gait patterns, mainly characterized by increased dynamic instability and reduced step length; when comparing amyloid PET data, the two groups did not differ. Regarding the machine learning analyses, evaluation metrics were satisfactory for Model 1 overcoming 80% for accuracy and specificity, whereas they were disappointing for Model 2. Conclusions This study demonstrates that machine learning implemented with specific clinical features and gait variables exhibits high accuracy in predicting PD-MCI, whereas amyloid PET imaging is not able to increase prediction. Additionally, our results prompt that a data mining approach on certain gait parameters might represent a reliable surrogate biomarker of PD-MCI.

The aim of this study was to evaluate the prognostic value of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) parameters provided by simultaneous 18F-fluorodeoxyglucose (FDG) PET/MRI in patients with locally advanced oropharyngeal and hypopharyngeal squamous cell carcinomas (OHSCC). Forty-five patients with locally advanced OHSCC who underwent simultaneous FDG PET/MRI before (chemo)radiotherapy were retrospectively enrolled. Peak standardized uptake value (SULpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary lesion were obtained on PET data. On MRI scans, primary tumor size, diffusion and perfusion parameters were assessed using pre-contrast and high-resolution post-contrast images. Ratios between metabolic/metabolo-volumetric parameters and ADC were calculated. Comparisons between groups were performed by Student’s t test. Survival analysis was performed by univariate Cox proportional hazard regression analysis. Overall survival curves were obtained by the Kaplan–Meier method and compared with the log-rank test. Survivors were censored at the time of the last clinical control. p < 0.05 was considered statistically significant During follow-up (mean 31.4 ± 21 months), there were 15 deaths. Univariate analysis shows that SULpeak and SULpeak/ADCmean were significant predictors of overall survival (OS). At multivariate analysis, only SULpeak remained a significant predictor of OS. Kaplan–Meier survival analyses showed that patients with higher SULpeak had poorer outcome compared to those with lower values (HR: 3.7, p = 0.007). Pre-therapy SULpeak of the primary site was predictive of overall survival in patients with oropharyngeal or hypopharyngeal cancer treated with (chemo)radiotherapy.

Objective The identification of deep myometrial invasion (DMI) represents a fundamental aspect in patients with endometrial cancer (EC) for accurate disease staging. It can be detected on MRI using T2-weighted (T2-w), diffusion weighted (DWI) and dynamic contrast enhanced sequences (DCE). Aim of the study was to perform a multi-reader evaluation of such sequences to identify the most accurate and its reliability for the best protocol. Methods In this multicenter retrospective study, MRI were independently evaluated by 4 radiologists (2 senior and 2 novice) with a sequence-based approach to identify DMI. The performance of the entire protocol was also evaluated. A comparison between the different sequences assessed by the same reader was performed using receiver operating curve and post-hoc analysis. Intraclass Correlation Coefficient (ICC) was used to assess inter- and intra-observer variability. Results A total of 92 patients were included. The performance of the readers did not show significant differences among DWI, DCE and the entire protocol. For only one senior radiologist, who reached the highest diagnostic accuracy with the entire protocol (82,6 %), both DWI (p = 0,0197) and entire protocol (p = 0,0039) were found significantly superior to T2-w. The highest inter-observer agreement was obtained with the entire protocol by expert readers (ICC = 0,77). Conclusions For the detection of DMI, the performances of DWI and DCE alone and that of a complete protocol do not significantly differ, even though the latter ensures the highest reliability particularly for expert readers. In cases in which T2-w and DWI are consistent, an unenhanced protocol could be proposed.

The standard treatment of differentiated thyroid cancer (DTC) consists of surgery followed by iodine-131 (131I) administration. Although the majority of DTC has a very good prognosis, more aggressive histologic subtypes convey a worse prognosis. Follow-up consists of periodically measurements of serum thyroglobulin, thyroglobulin antibodies and neck ultrasound and 123I/131I whole-body scan. However, undifferentiated thyroid tumors have a lower avidity for radioiodine and the ability of DTC to concentrate 131I may be lost in metastatic disease. Positron emission tomography (PET)/computed tomography (CT) has been introduced in the evaluation of patients with thyroid tumors and the 2-[18F]-fluoro-2-deoxyd-glucose (18F-FDG) has been largely validated as marker of cell's metabolism. According to the 2015 American Thyroid Association guidelines, 18F-FDG PET/CT is recommended in the follow-up of high-risk patients with elevated serum thyroglobulin and negative 131I imaging, in the assessment of metastatic patients, for lesion detection and risk stratification and in predicting the response to therapy. It should be considered that well-differentiated iodine avid lesions could not concentrate 18F-FDG, and a reciprocal pattern of iodine and 18F-FDG uptake has been observed. Beyond 18F-FDG, other tracers are available for PET imaging of thyroid tumors, such as Iodine-124 (124I), 18F-tetrafluoroborate and Gallium-68 prostate-specific membrane antigen. Moreover, the recent introduction of PET/MRI, offers now several opportunities in the field of patients with DTC. This review summarizes the evidences on the role of PET/CT in management of patients with DTC, focusing on potential applications and on elucidating some still debating points.

OBJECTIVE:To investigate the association of mural parameters of MR-enterography (MRE) with one-year therapeutic management of Crohn's disease (CD) patients. METHODS:CD patients, undergone MRE with diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps between January 2017 and June 2018, were retrospectively enrolled. Extramural complications represented an exclusion criterion because of their potential influence on the intrinsic characteristic of the bowel wall. Two groups of patients were defined on the base of the therapeutic management adopted at 1-year follow-up: Medical-group and surgical-group. The following MRE parameters were evaluated: wall-thickening, longitudinal-extension, T2-fat-suppression-mural-signal, ulcers, mural-oedema, wall-enhancement-rate/pattern, DWI-scores, ADC-values, strictures. RESULTS:70 CD patients were enrolled. 57/70 (81.4%) were included in Medical-group and 13/70 (18.6%) in Surgical-group. ADCmean and strictures resulted to be significantly (p < 0.01) different between the two groups. The ADCmean showed to be significantly associated to conservative management [p < 0.01; OR: 0.0003; 95% CI (0.00-0.13)], while the strictures to surgical management [p < 0.01; OR: 29.7; 95% CI (4.9-179.7)]. ROC curves for ADCmean showed that AUC was 0.717 [95% CI (0.607-0.810), p < 0.01] with an optimal cut-off value of 1.081 × 10-3 mm2 s-1. A negative predictive value of 90.2% was observed associating ADCmean values > 1.081 × 10-3 mm2 s-1 to conservative therapy. 13/17 (76%) strictures with an ADCmean > 1.081 × 10-3 mm2 s-1 benefited of conservative therapy. CONCLUSION:ADCmean values calculated on DWI-MRE may be associated to 1-year conservative medical therapy in patients with CD without extramural complications. ADVANCES IN KNOWLEDGE:ADC maps may be proposed to select CD patients with a lower burden of mural active inflammatory cells and/or fibrosis benefiting of 1-year conservative treatment.

This study assessed the long-term predictive value of the response to therapy, evaluated by serum thyroglobulin (Tg) determination and neck ultrasound, and estimated the potential additional impact of diagnostic whole-body scan (WBS) in patients with differentiated thyroid cancer (DTC) treated with surgery and radioactive iodine (RAI) therapy. We retrospectively evaluated 606 DTC patients treated with surgery and RAI. Response to 131I therapy at 12 months was assessed by serum Tg measurement, neck ultrasound, and diagnostic WBS. According to American Thyroid Association (ATA) guidelines, patients were classified as having a low, intermediate or high risk of recurrence and at 12 months as having an excellent response (ER) or no-ER. Follow-up was then performed every 6–12 months with serum Tg determination and imaging procedures. With a median follow-up of 105 months (range 10–384), 42 (7%) events requiring further treatments occurred. Twenty-five patients had additional RAI therapy, 11 with structural disease in the thyroid bed, eight in both thyroid bed and neck lymph nodes, four had lung metastases and two had bone metastases. The other 17 patients had additional surgery for nodal disease followed by RAI therapy. The ATA intermediate and high risk of recurrence, post-operative and pre-RAI therapy Tg ≥ 10 ng/mL, and the absence of ER at 12 months were independent predictors of events. Diagnostic WBS at 12 months permitted the identification of only five recurrences among the 219 ER patients according to serum Tg levels and ultrasound. In DTC patients, the response to therapy at 12 months after RAI therapy could rely on serum Tg measurement and neck ultrasound, while diagnostic WBS was not routinely indicated in patients considered in ER.

Objectives: Bipolar disorder (BD) has been suggested to be a risk factor for the development of Parkinson's disease (PD). Standard treatment of BD includes drugs that are known to induce drug-induced parkinsonism (DIP). Clinical differentiation between PD and DIP is crucial and might be aided by functional neuroimaging of the dopaminergic nigrostriatal pathway. Methods: Twenty consecutive BD patients with parkinsonism were clinically assessed and underwent 123I-ioflupane dopamine transporter single-photon emission computer tomography (SPECT). Imaging data of BD patients with pathological scans were further compared to a population of 40 de novo PD patients. Results: Four BD patients had abnormal scans, but their clinical features and cumulative exposure to both antipsychotic drugs and lithium were similar to those of BD patients with normal dopamine transporter imaging. BD patients with pathological scans had putaminal binding ratio and putamen-to-caudate ratios higher than those of PD patients despite a similar motor symptom burden. Conclusions: Up to 20% of BD patients with parkinsonism might have an underlying dopaminergic deficit, which would not be due to cumulative exposure to offending drugs and is ostensibly higher than expected in the general population. This supports the evidence that BD represents a risk factor for subsequent development of neurodegenerative parkinsonism, the nature of which needs to be elucidated.

Aim: To assess the value of bone scintigraphy and 18F-fluorocholine PET/computed tomography (CT) in predicting outcome in patients with prostate cancer and bone metastases treated with 223radium. Materials & methods: Retrospective analysis of 48 patients that underwent 223radium therapy. End points were pain relief and overall survival. Results: After therapy, pain relief was observed in 27 patients. Patients without pain relief had more bone lesions at PET/CT than at bone scintigraphy (pretherapy imaging mismatch). In 39 patients who completed treatment protocol, post-therapy alkaline phosphatase and pretherapy imaging mismatch were independent predictors of poor overall survival. Conclusion: Patients with more lesions at 18F-fluorocholine PET/CT than at bone scintigraphy had a poor prognosis. The combined imaging approach could be useful to predict outcome after 223radium therapy.

The standard treatment of differentiated thyroid cancer (DTC) consists of surgery followed by iodine-131 (I-131) administration. Although the majority of DTC has a very good prognosis, more aggressive histologic subtypes convey a worse prognosis. Follow-up consists of periodically measurements of serum thyroglobulin, thyroglobulin antibodies and neck ultrasound and I-123/I-131 whole-body scan. However, undifferentiated thyroid tumors have a lower avidity for radioiodine and the ability of DTC to concentrate I-131 may be lost in metastatic disease. Positron emission tomography (PET)/computed tomography (CT) has been introduced in the evaluation of patients with thyroid tumors and the 2-[18F]-fluoro-2-deoxyd-glucose (F-18-FDG) has been largely validated as marker of cell's metabolism. According to the 2015 American Thyroid Association guidelines, F-18-FDG PET/CT is recommended in the follow-up of high-risk patients with elevated serum thyroglobulin and negative I-131 imaging, in the assessment of metastatic patients, for lesion detection and risk stratification and in predicting the response to therapy. It should be considered that well-differentiated iodine avid lesions could not concentrate F-18-FDG, and a reciprocal pattern of iodine and F-18-FDG uptake has been observed. Beyond F-18-FDG, other tracers are available for PET imaging of thyroid tumors, such as Iodine-124 (I-124), F-18-tetrafluoroborate and Gallium-68 prostate-specific membrane antigen. Moreover, the recent introduction of PET/MRI, offers now several opportunities in the field of patients with DTC. This review summarizes the evidences on the role of PET/CT in management of patients with DTC, focusing on potential applications and on elucidating some still debating points. (C) 2021 Societe francaise de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Recently brown adipose tissue (BAT) activation has been proposed to have a possible role in breast cancer. The aim of this study was to evaluate BAT activation in patients with breast cancer and its relationship with molecular characteristics of tumor. The study group comprised 79 patients with histologically proven ductal breast carcinoma (51 ± 13 years). Data on distribution, intensity (SUVmax), and total metabolic activity (TMA) of BAT were obtained from [18F] FDG-PET/CT. Clinical and biochemical data were obtained from the database. BAT activation was present in 12 of the 79 patients (15.2 %). Patients with BAT activation were younger and had a lower body mass index (BMI) (p < 0.05 and p < 0.0005, respectively) and showed less frequently metastasis (p < 0.05). No significant differences were found in estrogen receptor (ER), progesterone receptor (PgR), Ki67, grade, and in molecular subtypes. In patients younger than 55 years and with a BMI < 26, no significant differences were observed between patients with and without BAT activation. In the 12 patients with BAT activation, a significant inverse correlation was observed between TMA and BMI (r = − 0.64, p < 0.05). TMA and SUVmax were higher in grade 2 than in grade 3 patients. No significant differences were found in both TMA and SUVmax between patients with and without lymph node metastases. A significant difference in both TMA and SUVmax was observed among different molecular types, with luminal B patients showing higher values. In conclusion, the present study suggests a relation between BAT activation and positive known prognostic factor in breast cancer, such as intermediate tumor grade and luminal B cancer type.

In multiple myeloma (MM) patients, 18F-FDG-PET/CT allows either the detection of disease spread by using visual parameters based on the Italian Myeloma criteria for PET Use (IMPeTUs) or the direct measurement of metabolic tumor burden by volume-based parameters such as metabolic tumor volume (MTV). The purpose is to evaluate the contribution of visual and volumetric parameters in the prediction of progression-free survival (PFS) and overall survival (OS) in MM patients. Forty-seven patients in stage IIIA who had undergone whole-body 18F-FDG-PET/CT were retrospectively evaluated. In each patient, visual parameters were determined and compared with volumetric parameters for PFS and OS prediction after a mean follow-up period of 53 months. Among the visual and volumetric parameters tested, a statistically significant difference was found between maximum standardized uptake value, MTV, total lesion glycolysis, and number of lytic lesions of patients with (n = 26) or without (n = 21) progression (p = 0.0400, p = 0.0065, p = 0.015, and p = 0.0220, respectively) and of dead (n = 24) vs survivors (n = 23) (p = 0.0171, p = 0.0037, p = 0.0060, and p = 0.0270, respectively). At univariate and multivariate analysis, MTV and hemoglobin were predictive of both PFS (p = 0.008) and OS (p = 0.0026). The best MTV discriminative value assessed by receiver operating characteristic curve analysis for predicting both PFS and OS was 39.4 ml. By Kaplan-Meier analysis and log-rank test, PFS and OS were significantly better in patients with MTV ≤ 39.4 ml (p = 0.0004 and p = 0.0001, respectively) as compared with those having an MTV higher than the cutoff. The volume-based parameter MTV determined by 18F-FDG-PET/CT may be used in the prediction of PFS and OS in myeloma patients.