Prevalence and distribution of vascular calcifications at CT scan in patients with and without large vessel vasculitis: a matched cross-sectional study.

OBJECTIVES: The aim of this study was to compare the prevalence, entity and local distribution of arterial wall calcifications evaluated on CT scans in patients with large vessel vasculitis (LVV) and patients with lymphoma as reference for the population without LVV. METHODS: All consecutive patients diagnosed with LVVs with available baseline positron emission tomography-CT (PET-CT) scan performed between 2007 and 2019 were included; non-LVV patients were lymphoma patients matched by age (±5 years), sex and year of baseline PET-CT (≤2013; >2013). CT images derived from baseline PET-CT scans of both patient groups were retrospectively reviewed by a single radiologist who, after setting a threshold of minimum 130 Hounsfield units, semiautomatically computed vascular calcifications in three separate locations (coronaries, thoracic and abdominal arteries), quantified as Agatston and volume scores. RESULTS: A total of 266 patients were included. Abdominal artery calcifications were equally distributed (mean volume 3220 in LVVs and 2712 in lymphomas). Being in the LVVs group was associated with the presence of thoracic calcifications after adjusting by age and year of diagnosis (OR 4.13, 95% CI 1.35 to 12.66; p=0.013). Similarly, LVVs group was significantly associated with the volume score in the thoracic arteries (p=0.048). In patients >50 years old, calcifications in the coronaries were more extended in non-LVV patients (p=0.027 for volume). CONCLUSION: When compared with patients without LVVs, LVVs patients have higher calcifications in the thoracic arteries, but not in coronary and abdominal arteries.

The diagnostic and prognostic role of combined [18F]FDG and [68Ga]-DOTA-peptides PET/CT in primary pulmonary carcinoids: a multicentric experience.

OBJECTIVES: In the present retrospective multicentric study, we combined [68Ga]-DOTA-peptides and [18F]FDG-PET/CT findings aiming to investigate their capability to differentiate typical (TC) and atypical pulmonary carcinoids (AC) and their prognostic role. METHODS: From three centers, 61 patients were retrospectively included. Based on a dual tracer combination we classified PET scans as score 1, [18F]FDG- and [68Ga]-DOTA-peptides negative; score 2, [68Ga]-DOTA-peptides positive and [18F]FDG-negative; score 3, [68Ga]-DOTA-peptides negative and [18F]FDG-positive; score 4, both tracers positive. Moreover, for each patient, the ratios of SUVmax on [68Ga]-DOTA-PET to that on [18F]FDG-PET were calculated (SUVr). RESULTS: Thirty-five patients had a final diagnosis of TC. Twenty-two TC (57%) had positive [68Ga]-DOTA-peptides PET; instead, 21/26 (81%) AC had positive [18F]FDG-PET/CT. On dual-tracer analysis, scores 1, 2, 3 and 4 were 13%, 20%, 43% and 24% for all populations; 17%, 26%, 20% and 37% for TC; 8%, 11%, 73% and 8% for AC. Median SUVr was significantly higher in TC than AC (6.4 vs. 0.4, p = 0.011). The best value of SUVr to predict the final diagnosis was 1.05 (AUC 0.889). Relapse or progression of disease happened in 17 patients (11 affected by AC) and death in 10 cases (7 AC). AC diagnosis, positive [18F]FDG-PET, negative DOTA-PET and dual tracer score were significantly correlated with PFS (p = 0.013, p = 0.033, p = 0.029 and p = 0.019), while only AC diagnosis with OS (p = 0.022). CONCLUSION: PET/CT findings had also a prognostic role in predicting PFS. Dual-tracer PET behavior may be used to predict the nature of pulmonary carcinoids and select the most appropriate management. KEY POINTS: • Combination of [18F]FDG and [68Ga]-DOTA-peptides PET/CT results may help to differentiate between atypical and typical lung carcinoids. • The SUVmax ratio between [18F]FDG and [68Ga]-DOTA-peptides PET may help to differentiate between atypical and typical lung carcinoids. • Histotype and PET/CT features have a prognostic impact on PFS.

Prognostic value of lesion dissemination in doxorubicin, bleomycin, vinblastine, and dacarbazine-treated, interimPET-negative classical Hodgkin Lymphoma patients: A radio-genomic study.

We evaluated the prognostic role of the largest distance between two lesions (Dmax), defined by positron emission tomography (PET) in a retrospective cohort of newly diagnosed classical Hodgkin Lymphoma (cHL) patients. We also explored the molecular bases underlying Dmax through a gene expression analysis of diagnostic biopsies. We included patients diagnosed with cHL from 2007 to 2020, initially treated with ABVD, with available baseline PET for review, and with at least two FDG avid lesions. Patients with available RNA from diagnostic biopsy were eligible for gene expression analysis. Dmax was deduced from the three-dimensional coordinates of the baseline metabolic tumor volume (MTV) and its effect on progression free survival (PFS) was evaluated. Gene expression profiles were correlated with Dmax and analyzed using CIBERSORTx algorithm to perform deconvolution. The study was conducted on 155 eligible cHL patients. Using its median value of 20 cm, Dmax was the only variable independently associated with PFS (HR = 2.70, 95% CI 1.1-6.63, pValue = 0.03) in multivariate analysis of PFS for all patients and for those with early complete metabolic response (iPET-). Among patients with iPET-low Dmax was associated with a 4-year PFS of 90% (95% CI 82.0-98.9) significantly better compared to high Dmax (4-year PFS 72.4%, 95% CI 61.9-84.6). From the analysis of gene expression profiles differences in Dmax were mostly associated with variations in the expression of microenvironmental components. In conclusion our results support tumor dissemination measured through Dmax as novel prognostic factor for cHL patients treated with ABVD.

Predictive and Prognostic Role of Pre-Therapy and Interim 68Ga-DOTATOC PET/CT Parameters in Metastatic Advanced Neuroendocrine Tumor Patients Treated with PRRT.

Peptide receptor radionuclide therapy (PRRT) is an effective therapeutic option in patients with metastatic neuroendocrine tumor (NET). However, PRRT fails in about 15-30% of cases. Identification of biomarkers predicting the response to PRRT is essential for treatment tailoring. We aimed to evaluate the predictive and prognostic role of semiquantitative and volumetric parameters obtained from the 68Ga-DOTATOC PET/CT before therapy (bPET) and after two cycles of PRRT (iPET). A total of 46 patients were included in this retrospective analysis. The primary tumor was 78% gastroenteropancreatic (GEP), 13% broncho-pulmonary and 9% of unknown origin. 35 patients (76.1%) with stable disease or partial response after PRRT were classified as responders and 11 (23.9%) as non-responders. Logistic regression analysis identified that baseline total volume (bTV) was associated with therapy outcome (OR 1.17; 95%CI 1.02-1.32; p = 0.02). No significant association with PRRT response was observed for other variables. High bTV was confirmed as the only variable independently associated with OS (HR 12.76, 95%CI 1.53-107, p = 0.01). In conclusion, high bTV is a negative predictor for PRRT response and is associated with worse OS rates. Early iPET during PRRT apparently does not provide information useful to change the management of NET patients.

The prognostic power of 18F-FDG PET/CT extends to estimating systemic treatment response duration in metastatic castration-resistant prostate cancer (mCRPC) patients.

BACKGROUND: We aimed to test whether the prognostic value of 18 F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) in metastatic castration-resistant prostate cancer (mCRPC) extends to the estimation of systemic treatment response duration. METHODS: mCRPC patients submitted to FDG-PET/CT in four Italian centers from 2005 to 2020 were retrospectively enrolled. Clinical and biochemical data at the time of imaging were collected, and SUV max of the hottest lesion, total metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. The correlation between PET- and biochemical-derived parameters with Overall Survival (OS) was analysed. The prediction of treatment response duration was assessed in the subgroup submitted to FDG-PET/CT in the six months preceding Chemotherapy (namely Docetaxel or Cabazitaxel, 24 patients) or Androgen-Receptor Targeted Agents (ARTA, namely Abiraterone or Enzalutamide, 20 patients) administration. RESULTS: We enrolled 114 mCRPC patients followed-up for a median interval lasting 15 months. While at univariate analysis, prostate-specific antigen (PSA), Alkaline Phosphatase (ALP), MTV, and TLG were associated with OS, at the multivariate Cox regression analysis, the sole MTV could independently predict OS (p < 0.0001). In the subgroup submitted to FDG-PET/CT before the systemic treatment initiation, PSA and TLG could also predict treatment response duration independently (p < 0.05). Of note, while PSA could not indicate the best treatment choice, lower TLG was associated with higher success rates for ARTA but had no impact on chemotherapy efficacy. CONCLUSIONS: FDG-PET/CT's prognostic value extends to predicting treatment response duration in mCRPC, thus potentially guiding the systemic treatment selection.

Three years' clinical practice of Radium-223 therapy in patients with symptomatic bone metastases from metastatic castrate-resistant prostate cancer: a single-centre experience.

BACKGROUND: Radium-223 was a treatment approved for patients with metastatic castrate-resistant prostate cancer, symptomatic bone metastases and no-visceral metastases, in progression after at least two prior lines of systemic therapy, or ineligible for any available systemic treatment. The aim of this study was to provide further characterization and sub-selection of patients who would benefit most with Radium-223 treatment. METHODS: We retrospectively analysed 38 patients treated with Radium-223 between 2015 and 2018. All patients underwent a baseline visit and a bone scintigraphy. Bone scan, ALP and PSA levels were repeated after third and after the end of therapy. All patients were re-evaluated after 2 months from the end of therapy. Survival curves were plotted according to the Kaplan-Meier method and differences between groups were analysed by using a two-tailed log-rank test. RESULTS: The response to the treatment in term of change in pain was reduction in 16 patients; no change in 14 and increased in eight. We arbitrarily established a cut-off 10 bone lesions to evaluate the response: patients with less than 10 metastasis had significant differences in PFS (P < 0.001) compared to patients with more than 10, no statistical significance was found considering the OS (P = 0.23) between the two groups. The same results were founded in patients with baseline ALP <220 U/L with a PFS (P < 0.001) and OS (P = 0.027). CONCLUSION: The most important finding was the correlation between the number of bone metastasis and ALP with outcome survival and efficacy of Radium-223 treatment.

18F-FDG PET/CT or PET Role in MALT Lymphoma: An Open Issue not Yet Solved-A Critical Review.

Mucosa-associated lymphoid tissue (MALT) lymphoma involves the mucosa-associated lymphoid tissue potentially arising from any mucosal site, with the stomach as the most common site of involvement. MALT lymphoma is not usually an aggressive disease with a good prognosis except for selected cases. Fluorine-18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is a noninvasive imaging tool used for staging, restaging, and evaluation of the treatment response in non-Hodgkin and Hodgkin lymphoma. However, its effective role in MALT lymphoma is not yet clear. The open question is whether these lymphomas are 18F-FDG avid or not, with conflicting results reported in the literature. Consequently, the possible clinical role of 18F-FDG PET/CT for staging and restaging purposes is under debate. The aim of the present review was to analyze the reported data about the role of 18F-FDG PET or PET/CT in patients with MALT lymphoma. We performed a comprehensive computer literature search of the Scopus, Cochrane, PubMed/MEDLINE, and Embase databases, including articles reported up to August 2019. We included 32 studies that had analyzed 18F-FDG PET or PET/CT for patients with MALT lymphoma. We analyzed the metabolic behavior of MALT lymphoma using 18F-FDG PET and the effect of the PET findings in the staging, treatment response evaluation, and prognosis.

Efficacy of low radioiodine activity versus intermediate-high activity in the ablation of low-risk differentiated thyroid cancer.

PURPOSE: The aim of our study was to compare the efficacy of thyroid remnant ablation using low (1.1 GBq) and intermediate-high radioiodine (RAI) activity (1.85-3.7 GBq) in low-risk differentiated thyroid carcinoma (DTC) and to evaluate the staging role of the whole body scan (WBS) in detection extrathyroidal disease. MATERIALS AND METHODS: We retrospectively included 277 patients who underwent total thyroidectomy and RAI for low-risk DTC and divided them in two groups according to RAI activity at ablation: group 1 (n = 174) treated with low activity (1.1 GBq), and group 2 (n = 103) with intermediate-high activity (1.85-3.7 GBq). To evaluate the successful ablation rate, the WBS 1 year after RAI was visually interpreted using a three-point scale: score 0 in case of absence of visible RAI uptake in thyroid bed; score 1 in presence of faint uptake in the thyroid bed; and score 2 in case of significant RAI uptake in thyroid bed. RESULTS: The success ablation rate was significantly higher in group 2 than group 1 (p < 0.001) with the presence of a positive WBS (score 1-2) in 65% low-activity group and 33% in intermediate-high group. Considering response to therapy categories, excellent response rate was significantly higher in group 2 (p = 0.020), while indeterminate response was higher in group 1 (p value = 0.005). Post RAI imaging revealed extrathyroidal uptake in 27 cases: 17 laterocervical nodal and 10 distant metastases. In both groups similar detection rate of nodal and distant metastases were recognized without any statistical difference. CONCLUSIONS: The ablation rate with intermediate-high RAI activity (1.85-3.7 GBq) was better than with a low activity (1.1 GBq). First WBS may help to recognize nodal and distant metastases in about 10% of cases changing clinical stage and subsequent management.

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

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.

68Ga-PSMA PET thyroid incidentalomas.

INTRODUCTION: Thyroid incidentaloma is defined as a thyroid lesion incidentally and newly detected by imaging techniques performed for an unrelated purpose and especially for a non-thyroid disease. The aim of this review is to evaluate the prevalence and clinical significance of focal incidental radiolabelled prostate-specific membrane antigen (PSMA) uptake in the thyroid gland [PSMA thyroid incidentaloma (PTI)] revealed by PET/CT or PET/MRI. METHODS: A comprehensive literature search of the PubMed/MEDLINE, Scopus, and Embase databases was conducted to find relevant published articles about the prevalence and clinical significance of PTIs detected by PET/CT or PET/MRI in patients studied for other oncologic purposes. RESULTS: Twelve articles were included in the systematic review. Among 23 PTIs, 6 were malignant (5 primary thyroid tumors and one metastasis from renal cell carcinoma), one was a follicular lesion of undetermined significance, and the rest were benign. CONCLUSION: Despite being very rare, though probably underestimated, PTIs frequently signal the presence of unexpected lesions in the thyroid which differ from the indicated reason for which the patient was initially scanned and concerning which the risk of malignancy is not negligible.

Radioguided lung lesion localization: introducing a fluoroscopy system in a SPECT/CT scan.

PURPOSE: The purpose was to report our experience in the use of radiotracer localization and resection of small, indistinct, or nonpalpable pulmonary lesions. We developed an innovative technique implementing a fluoroscopy system on a single-photon emission computed tomography/computed tomography (SPECT/CT) scan that allowed to perform CT-guided injection of radiotracer directly on SPECT/CT. PATIENTS AND METHODS: Patients were selected for the radiotracer procedure in presence of difficulties in locating nodules with video-assisted thoracoscopic surgery (VATS). Overall, 0.2 ml of technetium-99m macroaggregated albumin and 0.3 ml of nonionic iodinated contrast were injected under CT guidance. During the VATS procedure, an endoscopic gamma detecting probe was introduced to scan the lung surface. The area of major radioactivity, which matched with the area of the nodule, was resected. RESULTS: Between January 2016 and October 2018, 37 patients underwent CT-guided radiotracer injection. The mean nodule size was 11 mm. CT nodule morphology characteristics were as follows: 15 nodules were ground glass, 12 were solid, and 10 were partly solid. No significant adverse events occurred. In one patient, the surgeons decided for an open thoracotomy after unsuccessfully VATS. Overall, lobectomy was performed in two patients, segmentectomy in one, and wedge resection in 33 patients. No mortality occurred. The pathological diagnosis was 15 (42%) primary lung cancer, eight (22%) metastases, and 13 (36%) benign lesions. CONCLUSION: Radioguided pulmonary nodule localization is a reliable procedure with a high rate of success, minimal complications, and lower risk of failures, with no associated mortality or significant morbidity. Our SPECT/CT system is the first to benefit from the technological improvement with successfully implementation and application of fluoroscopy to SPECT/CT.

Clinical and prognostic role of detection timing of distant metastases in patients with differentiated thyroid cancer.

PURPOSE: Distant metastases (DM) from DTC occur in 5-25% of cases and are correlated to lower survival; the prognostic significance of the temporal onset of DM is unclear. Our aim was to retrospectively analyze the prevalence of DM and to assess the prognostic role of the timing of manifestation of DM regarding the outcome. MATERIALS AND METHODS: We included 174 patients (mean age 64 years). According to the time of manifestation, DM were divided in two groups: synchronous DM (SDM, n = 108) defined as metastases present at initial diagnosis and metachronous DM (MDM, n = 66) as diagnosed during follow-up. SDM were further sub grouped in pre-RAIT when diagnosed during pre-surgery work-up (n = 35) and baseline-RAIT when detected by first whole body scan after RAIT (n = 73). Disease-specific survival (DSS) was analyzed using the Kaplan-Meier method. RESULTS: Total RAI activities and number of treatments were significantly higher in MDM, also loss of RAI avidity was more frequent in MDM. Forty-four patients died during follow-up, of which 41 were DTC-related deaths, 5-year and 10-year DSS were 80% and 56%. On univariate analysis MDM had significantly shorter DSS; also histotype and RAI avidity were significant risk factors of impaired survival. On multivariate analysis, only loss of RAI avidity remained as independent negative predictor (p = 0.043). Considering SDM, DSS was significantly shorter in pre-RAIT group than baseline-RAIT (p = 0.004). Instead there was no significant difference between pre-RAIT-SDM and MDM in survival outcome (p = 0.875). CONCLUSIONS: In DTC with DM, loss of RAI uptake has an important role in survival. No significant difference in survival outcome was discovered between SDM and MDM; but, among SDM, pre-RAIT had significant shorter DSS than baseline-RAIT.

18F-choline PET/CT incidental thyroid uptake in patients studied for prostate cancer.

PURPOSE: Thyroid incidental uptake is defined as a thyroid uptake incidentally detected by imaging examinations performed for non-thyroid disease. The aim of this study was to establish the prevalence and the pathological nature of focal thyroid incidental uptake (FTIU) among patients studied with 18F-choline-PET/CT. MATERIALS AND METHODS: We retrospectively evaluated 368 patients who performed 18F-choline-PET/CT between June 2016 and August 2018. The PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value (SUVmax) and the mean SUV (SUVmean) of the thyroid gland and of the FTIU; every focal thyroid uptake deviating from physiological distribution and background was considered FTIU. Final diagnosis of FTIU was obtained by cytological or histological examination after surgery. RESULTS: The average SUVmax and SUVmean of thyroid gland in population were 3 and 1.8. Among 368 patients, FTIU was identified in nine cases (2.4%) and eight underwent further investigations to determine the nature. Two FTIU were classified as malignant (thyroid carcinoma), whereas five were benign (three nodular hyperplasia, one follicular adenoma, one Hurtle cell adenoma) and one indeterminate at cytological examination. In malignant lesions, average SUVmax was 9.6 and 4.5, respectively, while average SUVmean was 5.3 and 2.9, respectively. Average SUVmax and SUVmean of benign lesions were 4.9 and 3.2 and of the indeterminate lesion 5 and 3, respectively. CONCLUSIONS: 18F-choline-PET/CT FTIU may be a relevant diagnostic reality, which requires further investigations and affects management, especially considering that, despite being mainly benign, also malignancy is possible.

Possible delayed diagnosis and treatment of metastatic differentiated thyroid cancer by adopting the 2015 ATA guidelines.

OBJECTIVE: According to the 2015 American Thyroid Association (ATA) guidelines, thyroid ablation by iodine-131 (I-131) therapy is absolutely recommended only in patients with high-risk differentiated thyroid cancer (DTC). Often distant metastases are not recognized early and they can stay silent for long time. The aim of our study was to retrospectively analyze the prevalence of metastatic disease before and after I-131 and to evaluate the influence of the new ATA guidelines in the management of DTC. METHODS: We retrospectively analyzed 140 patients showing distant metastases. All metastases were detected by whole-body scan after I-131 and confirmed by histology and/or other imaging modalities. RESULTS: In 26/140 patients metastases were detected before I-131, while in 114/140 were discovered after I-131. Comparing patients with metastases detected before and after I-131, no differences were demonstrated considering age, sex, histotype, tumor size, multifocality of cancer and metastatic localization. Metastatic DTC discovered before radioiodine had higher thyroglobulin and received a higher radioiodine total activity and number of treatments. Considering patients with distant metastases, according to the 2015 ATA guidelines, 38 patients would have been categorized as high risk, 22 as low risk and 80 as intermediate risk. Among intermediate-risk patients, only in 25 cases (31%) I-131 treatment would have been appropriate according to 2015 ATA recommendations; in the remaining 56 cases (69%), I-131 would not have been recommended. CONCLUSIONS: According to the 2015 ATA guidelines, most of metastatic patients would not have been treated after surgery, with the risk of late diagnosis and delayed treatment.