Prognostic models integrating quantitative parameters from baseline and interim positron emission computed tomography in patients with diffuse large B-cell lymphoma: post-hoc analysis from the SAKK38/07 clinical trial.

Positron emission computed tomography (PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL) enrolled in a prospective clinical trial were reviewed to test the impact of quantitative parameters from interim PET/CT scans on overall (OS) and progression-free (PFS) survival. We centrally reviewed baseline and interim PET/CT scans of 138 patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone given every 14 days (R-CHOP14) in the SAKK38/07 trial (ClinicalTrial.gov identifier: NCT00544219). Cutoff values for maximum standardized uptake value (SUVmax ), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and metabolic heterogeneity (MH) were defined by receiver operating characteristic analysis. Responses were scored using the Deauville scale (DS). Patients with DS 5 at interim PET/CT (defined by uptake >2 times higher than in normal liver) had worse PFS (P = 0.014) and OS (P < 0.0001). A SUVmax reduction (Δ) greater than 66% was associated with longer PFS (P = 0.0027) and OS (P < 0.0001). Elevated SUVmax , MTV, TLG, and MH at interim PET/CT also identified patients with poorer outcome. At multivariable analysis, ΔSUVmax and baseline MTV appeared independent outcome predictors. A prognostic model integrating ΔSUVmax and baseline MTV discriminated three risk groups with significantly (log-rank test for trend, P < 0.0001) different PFS and OS. Moreover, the integration of MH and clinical prognostic indices could further refine the prediction of OS. PET metrics-derived prognostic models perform better than the international indices alone. Integration of baseline and interim PET metrics identified poor-risk DLBCL patients who might benefit from alternative treatments.

Comparison of high intensity focused ultrasound and radioiodine for treating toxic thyroid nodules.

PURPOSE: We compared the effectiveness of high intensity focused ultrasound (HIFU) and radioiodine (RAI) to treat patients carrying toxic thyroid nodule (TTN). Normalization of serum thyrotropin (TSH) 1 year after treatment was the primary end-point; concurrent changes in nodules' volume and scintigraphic pattern were also evaluated as secondary end-points. MATERIALS AND METHODS: Among patients ≥18 years old with TTN observed at our centre between January 1st, 2016 and December 31th, 2016 we prospectively enrolled 17 and 15 age and sex-matched patients treated with RAI and HIFU, respectively. Biochemical thyroid tests and nodules' volume were assessed before and 3, 6 and 12 months after treatments. A thyroid scintigraphy was performed before and 1 year after treatment, respectively. RESULTS: The final series included 17 patients treated with RAI and 15 patients treated with HIFU, respectively. Neither demographic nor clinical differences were found at baseline. One year after treatment 14 of 17 RAI-treated and 4 of 15 HIFU-treated patients fulfilled criteria for response to treatment (P = .0008). Indeed, the median TSH value was 1.5 IU/mL and 0.2 IU/mL in HIFU and RAI groups, respectively (P < .0001). Finally, despite a similar decrease in nodules' volume in both groups, a scintigraphic response was achieved in 16 of 17 (94%) RAI-treated compared to 8 of 15 (53%) HIFU-treated patients (P = .024), respectively. CONCLUSIONS: In our series, RAI clearly outperforms HIFU in treating patients carrying TTN and remains the first-line noninvasive treatment in such cases.

Fine-needle aspiration in all thyroid incidentalomas at 18 F-FDG PET/CT: Can EU-TIRADS revise the dogma?

OBJECTIVE: Focal thyroid incidentalomas (TIs) are observed in 2% of 18 F-FDG PET/CT representing malignancy in one-third of cases. Currently, due to the lack of evidence on their optimal management, guidelines suggest fine-needle aspiration cytology (FNAC). The study aim was to evaluate the role of ultrasound evaluation according to EU-TIRADS to assess the risk of TIs and inform FNAC prescriptions. DESIGN: We retrospectively reviewed 18 F-FDG PET/CT TIs recorded during the period 2014-2017. Enrolled were TIs with histological outcome and autonomous nodules. Cases with uncertain matching between 18 F-FDG PET/CT, ultrasound and histology were excluded. RESULTS: According to the selection criteria, 75 TIs, being 13 (17.3%) malignant and 62 (82.7%) benign, were included. Cancers had significantly higher SUVmax and SUVmax ratio (Mann-Whitney P < 0.01) than benign, and the most accurate cut-offs were >7.1 and >3.65, respectively. At ultrasound, the cancer rate was 0% in EU-TIRADS 2, 2.9% in EU-TIRADS 3, 4.2% in EU-TIRADS 4% and 78.6% in EU-TIRADS 5 (chi-squared P < 0.001). Sensitivity, specificity, PPV, NPV and accuracy for malignancy were 92%, 64%, 35%, 98% and 69% for SUVmax; 85%, 68%, 36%, 96% and 71% for SUVmax ratio; and 85%, 95%, 79%, 97% and 93% for EU-TIRADS, respectively. The absence of all these three features reached a specificity of 97.1%. CONCLUSIONS: EU-TIRADS, within a clinical careful approach, can discriminate with significant accuracy lesions at high risk of malignancy from those at low risk among TIs at 18 F-FDG PET/CT. Additionally, a centre-based threshold for SUV parameters should be useful for the initial assessment of these lesions during PET/CT reading and reporting.

Persistent 18F-FDG Brain PET Fronto-Temporal Hypometabolism and Cognitive Symptoms Two Years after SARS-CoV-2 Infection: A Case Report.

At least 10% of patients experience persistent symptoms after SARS-CoV-2 infection, a condition referred to as post-acute COVID-19, post-acute sequelae of SARS-CoV-2 infection (PASC), long COVID, long-haul COVID, long-term effects of COVID, post-COVID-19 and chronic COVID. In this report, we describe a case of persistent cognitive deficits developed after SARS-CoV-2 infection in a 40-year-old woman with a family history of early-onset Alzheimer's disease (EOAD) since her father was diagnosed with EOAD at the age of 50. We describe the clinical picture and workup, with special emphasis on the alterations of brain glucose metabolism evidenced by 18-fluoro-deoxy-glucose positron emission tomography (FDG-PET), which could be considered a useful marker of the presence and persistence of cognitive deficits.

Integration of Baseline Metabolic Parameters and Mutational Profiles Predicts Long-Term Response to First-Line Therapy in DLBCL Patients: A Post Hoc Analysis of the SAKK38/07 Study.

Accurate estimation of the progression risk after first-line therapy represents an unmet clinical need in diffuse large B-cell lymphoma (DLBCL). Baseline (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) parameters, together with genetic analysis of lymphoma cells, could refine the prediction of treatment failure. We evaluated the combined impact of mutation profiling and baseline PET/CT functional parameters on the outcome of DLBCL patients treated with the R-CHOP14 regimen in the SAKK38/07 clinical trial (NCT00544219). The concomitant presence of mutated SOCS1 with wild-type CREBBP and EP300 defined a group of patients with a favorable prognosis and 2-year progression-free survival (PFS) of 100%. Using an unsupervised recursive partitioning approach, we generated a classification-tree algorithm that predicts treatment outcomes. Patients with elevated metabolic tumor volume (MTV) and high metabolic heterogeneity (MH) (15%) had the highest risk of relapse. Patients with low MTV and favorable mutational profile (9%) had the lowest risk, while the remaining patients constituted the intermediate-risk group (76%). The resulting model stratified patients among three groups with 2-year PFS of 100%, 82%, and 42%, respectively (p < 0.001).

SAKK38/07 study: integration of baseline metabolic heterogeneity and metabolic tumor volume in DLBCL prognostic model.

Several functional parameters from baseline (18)F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography have been proposed as promising biomarkers of treatment efficacy in diffuse large B-cell lymphoma (DLBCL). We tested their ability to predict outcome in 2 cohorts of DLBCL patients receiving conventional immunochemotherapy (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone [R-CHOP] regimen), either every 14 (R-CHOP14) or 21 days (R-CHOP21). Baseline PET analysis was performed in 141 patients with DLBCL treated with R-CHOP14 in the prospective SAKK38/07 study (NCT00544219) of the Swiss Group for Clinical Cancer Research (testing set). Reproducibility was examined in a validation set of 113 patients treated with R-CHOP21. In the SAKK38/07 cohort, progression-free survival (PFS) at 5 years was 83% for patients with low metabolic tumor volume (MTV) and 59% for those with high MTV (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.6-7.0; P = .0005), whereas overall survival (OS) was 91% and 64%, respectively (HR, 4.4; 95% CI, 1.9-10; P = .0001). MTV was the most powerful predictor of outcome also in the validation set. Elevated metabolic heterogeneity (MH) significantly predicted poorer outcomes in the subgroups of patients with elevated MTV. A model integrating MTV and MH identified high-risk patients with shorter PFS (testing set: HR, 5.6; 95% CI, 1.8-17; P < .0001; validation set: HR, 5.6; 95% CI, 1.7-18; P = .0002) and shorter OS (testing set: HR, 9.5; 95% CI, 1.7-52; P < .0001; validation set: HR, 7.6; 95% CI, 2.0-28; P = .0003). This finding was confirmed by an unsupervised regression tree analysis indicating that prognostic models based on MTV and MH may allow early identification of refractory patients who might benefit from treatment intensification. This trial was registered at www.clinicaltrials.gov as #NCT00544219.

99mTc-Pertechnetate Scintigraphy Predicts Successful Postoperative Ablation in Differentiated Thyroid Carcinoma Patients Treated with Low Radioiodine Activities.

BACKGROUND: Postoperative routine radioiodine (RAI) treatment is currently debated for patients with low-risk differentiated thyroid carcinoma (DTC) patients. If performed, a low ¹³¹I activity (i.e., 1 to 2 GBq) is recommended with the aim to ablate thyroid remnant and facilitate subsequent follow-up by thyroglobulin measurement. The purpose of this study was to evaluate the relationship between postsurgical technetium-99m (99mTc)-pertechnetate scintigraphy and the rate of successful remnant ablation after low activity radioiodine ablation in patients with DTC. METHODS: Enrolled were 193 patients with low risk DTC who underwent total thyroidectomy and RAI ablation with a fixed 1.1 GBq activity of ¹³¹I. 99mTc-pertechnetate scans were done and thyrotropin stimulated thyroglobulin (sTg) levels measured just before ablation. Ablation effectiveness was assessed 6 to 12 months later by sTg measurement, neck ultrasound and diagnostic whole body scan. RESULTS: A negative 99mTc-perthecnetate scans was the best predictor of successful ablation (P<0.001) followed by preablative sTg levels <0.8 ng/mL (P=0.008) and 99mTc-pertechnetate uptake rate values <0.9% (P=0.065). Neither sex nor age of the patient at the time of ablation or tumor histology and size showed a significant association with the rate of successful ablation. CONCLUSION: The 99mTc-pertechnetate scintigraphy is a simple and feasible tool to predict effectiveness of low activity ¹³¹I thyroid to ablate thyroid remnants in patients with DTC.

18F-FDG uptake changes in liver and mediastinum during chemotherapy in patients with diffuse large B-cell lymphoma.

PURPOSE: The main objective of this study was to assess the intrasubject and intersubjects variability of 18F-FDG uptake in liver (LIV) and mediastinum (MBP) among patients with diffuse large B-cell lymphoma (DLBCL), treated with different chemotherapy regimens. PATIENTS AND METHODS: Fifty patients with DLBCL who underwent 18F-FDG PET/CT scan at baseline, after a few cycles of therapy (interim PET) and on completion of therapy (final PET), were enrolled retrospectively. SUVmean and SUVmax values for LIV and MBP, their differences (LIV - MBP SUVmean and LIV - MBP SUVmax), and their changes were calculated, respectively. RESULTS: Liver uptake significantly increased in the interim in comparison with baseline and final PET, respectively, whereas MBP activity remained stable during chemotherapy. The intersubject variability of 18F-FDG uptake in LIV and MBP ranged from 20.2% to 25.4%. CONCLUSIONS: The variability of the LIV uptake during chemotherapy should be taken into account when this parameter is used to score the interim PET scan and to make decisions in defining response-adapted therapeutic strategies. Vice versa, the stability of MBP activity during therapy provides a more reliable benchmark for the response assessment.Finally, the intersubjects variability of both parameters should be considered when the visual evaluation of the interim PET is performed by point score models.

Could different hydration protocols affect the quality of 18F-FDG PET/CT images?

UNLABELLED: In a group of oncologic patients undergoing (18)F-FDG PET/CT, we compared 4 different protocols of hydration to investigate their impact on image quality and to choose the best practice. METHODS: One hundred twenty subjects undergoing (18)F-FDG PET/CT were randomized into 4 groups: group A, receiving free oral hydration; group B, receiving an intravenous injection of 10 mg of furosemide and infusion of 500 mL of saline solution starting 5 min after tracer injection; group C, receiving oral hydration with 500 mL of water; and group D, receiving intravenous injection of 10 mg of furosemide and infusion of 250 mL of the saline solution starting 30 min after the (18)F-FDG injection. The maximum standardized uptake value of muscular and adipose tissues, blood pool (aortic and left ventricular cavity), bladder, and renal parenchyma was calculated for each subject. RESULTS: These 4 groups were comparable in age, body mass index, blood glucose level, and serum creatinine level. Group A showed the worst results. The controlled hydration protocols (groups B, C, and D) provided lower background activity in the soft tissues and lower urinary activity in the bladder and kidney without significant differences in blood activity. The administration of furosemide produces lower activity in the urinary tract without significant changes in (18)F-FDG distribution in the muscle, fat, or blood pool. The best results were in group D. CONCLUSION: Controlled hydration, particularly with standardized parenteral protocols, reduces the background activity in the soft tissues with the potential benefit of increasing the tumor-to-background contrast. Furosemide does not change tracer distribution in normal tissues but improves the quality of PET/CT images, reducing activity in the excretory system, particularly if the furosemide is administered late after (18)F-FDG injection.

Multi-field-of-view SPECT is superior to whole-body scanning for assessing metastatic bone disease in patients with prostate cancer.

AIM: The aim of this study was to compare the diagnostic performance of whole-body bone scintigraphy (WBS) and multi-field-of-view single photon emission tomography (multi-FOV SPECT) with 99mTc-oxidronate (99mTc-HDP) in patients with prostate cancer (PCa). METHODS: In a prospective study, WBS and SPECT acquisitions were performed in 194 patients with histologically confirmed PCa and serum prostate-specific antigen (PSA) levels above 10 ng/mL. Scans obtained using the two modalities were interpreted separately. Clinical and biochemical follow-up, radiological studies and biopsies served as benchmarks for the assessments. The impact of PSA level on WBS and SPECT results was also evaluated. RESULTS: The patient-based sensitivity, specificity, accuracy, PPV and NPV values of SPECT examinations were higher than those of WBS, especially in patients with serum PSA levels <40 ng/mL. CONCLUSION: Multi-FOV SPECT proved to be more sensitive and specific than WBS in detecting bone metastases in PCa patients.

Three-dimensional ordered-subset expectation maximization iterative protocol for evaluation of left ventricular volumes and function by quantitative gated SPECT: a dynamic phantom study.

UNLABELLED: The purposes of this study were to characterize the performance of a 3-dimensional (3D) ordered-subset expectation maximization (OSEM) algorithm in the quantification of left ventricular (LV) function with (99m)Tc-labeled agent gated SPECT (G-SPECT), the QGS program, and a beating-heart phantom and to optimize the reconstruction parameters for clinical applications. METHODS: A G-SPECT image of a dynamic heart phantom simulating the beating left ventricle was acquired. The exact volumes of the phantom were known and were as follows: end-diastolic volume (EDV) of 112 mL, end-systolic volume (ESV) of 37 mL, and stroke volume (SV) of 75 mL; these volumes produced an LV ejection fraction (LVEF) of 67%. Tomographic reconstructions were obtained after 10-20 iterations (I) with 4, 8, and 16 subsets (S) at full width at half maximum (FWHM) gaussian postprocessing filter cutoff values of 8-15 mm. The QGS program was used for quantitative measurements. RESULTS: Measured values ranged from 72 to 92 mL for EDV, from 18 to 32 mL for ESV, and from 54 to 63 mL for SV, and the calculated LVEF ranged from 65% to 76%. Overall, the combination of 10 I, 8 S, and a cutoff filter value of 10 mm produced the most accurate results. The plot of the measures with respect to the expectation maximization-equivalent iterations (I x S product) revealed a bell-shaped curve for the LV volumes and a reverse distribution for the LVEF, with the best results in the intermediate range. In particular, FWHM cutoff values exceeding 10 mm affected the estimation of the LV volumes. CONCLUSION: The QGS program is able to correctly calculate the LVEF when used in association with an optimized 3D OSEM algorithm (8 S, 10 I, and FWHM of 10 mm) but underestimates the LV volumes. However, various combinations of technical parameters, including a limited range of I and S (80-160 expectation maximization-equivalent iterations) and low cutoff values (< or =10 mm) for the gaussian postprocessing filter, produced results with similar accuracies and without clinically relevant differences in the LV volumes and the estimated LVEF.