Diagnostic yield of FAP-guided positron emission tomography in thyroid cancer: a systematic review.

Background: Several recent studies have proposed the possible application of positron emission tomography/computed tomography (PET/CT) administering radiolabelled fibroblast-activation protein (FAP) inhibitors for various forms of thyroid cancer (TC), including differentiated TC (DTC), and medullary TC (MTC). Methods: The authors conducted an extensive literature search of original studies examining the effectiveness of FAP-guided PET/CT in patients with TC. The papers included were original publications exploring the use of FAP-targeted molecular imaging in restaging metastatic DTC and MTC patients. Results: A total of 6 studies concerning the diagnostic yield of FAP-targeted PET/CT in TC (274 patients, of which 247 DTC and 27 MTC) were included in this systematic review. The included articles reported high values of FAP-targeted PET/CT detection rates in TC, ranging from 81 to 100% in different anatomical sites and overall superior to the comparative imaging method. Conclusion: Although there are promising results, the existing literature on the diagnostic accuracy of FAP-guided PET in this context is still quite limited. To thoroughly evaluate its potential significance in TC patients, it is needed to conduct prospective randomized multicentric trials.

The Role of PSMA PET Imaging in the Classification of the Risk of Prostate Cancer Patients: A Systematic Review on the Insights to Guide an Active Surveillance Approach.

BACKGROUND: active surveillance (AS) is a suitable strategy for patients with prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging is an established tool used to assess PCa. The aim of this review was to evaluate the role of PSMA imaging to guide correct risk-based classification and the AS approach in PCa patients. METHODS: The Scopus, Embase, Web of Science, Cochrane Library, and PubMed/MEDLINE databases were screened to find relevant published articles. RESULTS: 1774 articles were revealed with the literature search. A total of 1764 articles were excluded after applying exclusion criteria (data not within the field of interest, preclinical papers, conference proceedings, reviews, or editorials). Ten studies were finally included in the review, revealing that PSMA PET could have the ability to guide risk-based classification of PCa and the choice of AS, and to guide the execution of biopsies for the research of high-grade PCa, therefore precluding AS. CONCLUSION: this systematic review underlined a possible role of PSMA PET imaging in patients with PCa by correctly re-classifying them on the basis of their risk and guiding AS.

The role of baseline 2-[18 F]-FDG-PET/CT metrics and radiomics features in predicting primary gastric lymphoma diagnosis.

Diffuse Large B-Cell Lymphomas (DLCBL) and mucosa-associated lymphoid tissue (MALT) are the two most common primary gastric lymphomas (PGLs), but have strongly different features. DLBCL is more aggressive, is frequently diagnosed at an advanced stage and has a poorer prognosis. The aim of this retrospective study was to explore the role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (2-[18 F]-FDG-PET/CT) and radiomics features (RFs) in predicting the final diagnosis of patients with PGLs. Ninety-one patients with newly diagnosed PGLs who underwent pre-treatment 2-[18 F]-FDG-PET/CT were included. PET images were qualitatively and semi-quantitatively analyzed by deriving maximum standardized uptake value body weight (SUVbw), maximum standardized uptake value lean body mass (SUVlbm), maximum standardized uptake value body surface area (SUVbsa), lesion to liver SUVmax ratio (L-L SUV R), lesion to blood-pool SUVmax ratio (L-BP SUV R), metabolic tumor volume (gMTV) and total lesion glycolysis of gastric lesion (gTLG), total MTV (tMTV), TLG, and first-order RFs (histogram-related and shape related). Receiver-operating characteristic (ROC) curve analyses were performed to determine the differential diagnostic values of PET parameters. The final diagnosis was DLBCL in 54 (59%) cases and MALT in 37 cases (41%). PGLs showed FDG avidity in 83 cases (90%), 54/54 of DLBCL and 29/37 of MALT. All PET/CT metabolic features, such as stage of disease and tumor size, were significantly higher in DLBCL than MALT; while the presence of H. Pylori infection was more common in MALT. At univariate analysis, all PET/CT metrics were significantly higher in DLBCL than MALT lymphomas, while among RFs only Shape volume_vx and Shape sphericity showed a significant difference between the two groups. In conclusion we demonstrated that 2-[18 F]-FDG-PET/CT parameters can potentially discriminate between DLBCL and MALT lymphomas with high accuracy. Among first-order RFs, only Shape volume_vx and Shape sphericity helped in the differential diagnosis.

2-[18F]-FDG PET/CT Semiquantitative and Radiomics Predictive Parameters of Richter's Transformation in CLL Patients.

Background and Objectives: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in developed countries, which can evolve into aggressive lymphoma variants, a process called Richter transformation (RT). The aim of this retrospective study was to analyze the role of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]-FDG PET/CT) and its semiquantitative and radiomics features in detecting RT and evaluate the impact on overall survival (OS). Materials and Methods: One hundred and thirty-seven patients with histologically proven CLL were retrospectively recruited. PET/CT images were qualitatively and semiquantitatively examined by estimating the main metabolic parameters (the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), lesion-to-blood-pool SUV ratio (L-BP SUV R), lesion-to-liver SUV ratio (L-L SUV R), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) and radiomics first- and second- order variables of the lesion with highest uptake. The role of these parameters in predicting RT and OS was analyzed. Results: One hundred and thirty (95%) PET/CT scans were positive, showing an increased tracer uptake at the site of disease, whereas the remaining 7 (5%) scans were negative. SUVbw, SUVlbm, SUVbsa, L-L SUV ratio, and L-BP SUV ratio were significantly higher in the RT group (p < 0.001 in all cases). Radiomics first- and second-order features were not significantly associated with RT. After a median follow-up of 44 months, 56 patients died; OS was significantly shorter in patients with RT than patients without RT (28 vs. 34 months; p = 0.002). Binet-stage, RT, and L-BP SUV R were shown to be independent prognostic features. Conclusions: Semiquantitative PET/CT parameters such as SUVbw, SUVlbm, SUVbsa, L-L SUV ratio and L-BP SUV ratio may be useful in discriminating patients with a high risk of developing RT, whereas Binet-stage, RT, and L-BP SUV R are also significant in predicting OS.

2-[18]F FDG PET/CT dissemination features in adult burkitt lymphoma Are predictive of outcome.

This retrospective study investigated the prognostic role of disease dissemination features (Dmax and Dmaxbsa) measured by 2-[18F]FDG PET/CT in newly diagnosed Burkitt Lymphoma (BL) patients, comparing their performance with other metabolic parameters. We included 78 patients diagnosed with BL between 2010 and 2022 with an available baseline PET, interim PET/CT (iPET) and end of treatment PET/CT (eotPET) and with a minimum of two 2-[18F]FDG avid lesions present at the baseline scan. Dmax was calculated from the three-dimensional coordinates of the baseline metabolic tumor volume (MTV) by using LIFEx software; Dmaxbsa was calculated as Dmax normalized for body surface area according to the Du Bois method. We evaluated their effect on metabolic treatment response evaluated by PET, on progression free survival (PFS) and on overall survival (OS). Dmaxbsa was significantly associated with tumor stage, bulky and extranodal disease, MTV and TLG. At a median follow-up of 49 months, the median PFS and OS were 45 and 48 months. Dmax and Dmaxbsa were significantly higher in not complete metabolic response than complete metabolic response group at iPET and eotPET.As far as PFS, parameters including iPET/CT, eotPET/CT outcomes, MTV and TLG showed to be independent prognostic factors while Dmax and Dmaxbsa were not significantly associated with the outcome. Dissemination features, together with eotPET/CT results, MTV and TLG, demonstrated to be significantly correlated with OS. In conclusion, in this study we demonstrated that dissemination features derived by 2[18F]-FDG PET/CT were significantly correlated with response to treatment and long-term outcome, independently from other PET features.

Application of radiomics and machine learning to thyroid diseases in nuclear medicine: a systematic review.

BACKGROUND: In the last years growing evidences on the role of radiomics and machine learning (ML) applied to different nuclear medicine imaging modalities for the assessment of thyroid diseases are starting to emerge. The aim of this systematic review was therefore to analyze the diagnostic performances of these technologies in this setting. METHODS: A wide literature search of the PubMed/MEDLINE, Scopus and Web of Science databases was made in order to find relevant published articles about the role of radiomics or ML on nuclear medicine imaging for the evaluation of different thyroid diseases. RESULTS: Seventeen studies were included in the systematic review. Radiomics and ML were applied for assessment of thyroid incidentalomas at 18 F-FDG PET, evaluation of cytologically indeterminate thyroid nodules, assessment of thyroid cancer and classification of thyroid diseases using nuclear medicine techniques. CONCLUSION: Despite some intrinsic limitations of radiomics and ML may have affect the results of this review, these technologies seem to have a promising role in the assessment of thyroid diseases. Validation of preliminary findings in multicentric studies is needed to translate radiomics and ML approaches in the clinical setting.

Does it work in childhood and adolescence? The predictive role of postoperative/preablative stimulated thyroglobulin levels in paediatric thyroid cancer. A systematic review of the literature.

BACKGROUND: Thyroglobulin is a well-established disease marker during follow-up in paediatric differentiated thyroid cancer. However, no conclusive data on the role of endogenously stimulated thyroglobulin after thyroidectomy (ptTg) in predicting disease-specific outcomes are available. This review aims to establish the prognostic value of ptTg in children with DTC. METHODS: Online medical databases were searched for studies evaluating the association between ptTg and disease-specific outcomes in DTC-affected children. Documents not in English, preclinical studies, other review articles, case reports, and small case series were excluded. The risk of bias was assessed with the QUADAS-2 tool. RESULTS: Twelve studies, analysing 1043 children in total, were included in the review. They all had a retrospective design and were published between 2016 and 2022. Of all patients, 1008 (97%) and 849 (81%) had undergone thyroidectomy and RAI, respectively. Eight studies (756 children) evaluated the correlation between ptTg and disease persistence/relapse: six reported a significant association between these parameters; a specific ptTg cut-off (10-14 ng/ml) was identified at the multivariate analysis in three studies. The remaining four studies assessed the link between ptTg levels and disease extension, with three reporting a correlation between ptTg and lung/nodal metastases. DISCUSSION: ptTg is a readily available and inexpensive parameter, bearing a strong prognostic power in identifying disease persistence, relapse, and the presence of metastases in children affected by DTC.

Diagnostic Accuracy of [68Ga]Ga Labeled Fibroblast-Activation Protein Inhibitors in Detecting Head and Neck Cancer Lesions Using Positron Emission Tomography: A Systematic Review and a Meta-Analysis.

Several studies have examined the use of positron emission tomography (PET) using [68Ga]Ga-radiolabeled fibroblast-activation protein inhibitors (FAPi) across multiple subtypes of head and neck cancer (HNC). The purpose of the present study was to evaluate the diagnostic accuracy of a newly developed molecular imaging approach in the context of HNC through a comprehensive review and meta-analysis. A thorough literature review was conducted to identify scholarly articles about the diagnostic effectiveness of FAP-targeted PET imaging. The present study incorporates original publications assessing the efficacy of this innovative molecular imaging test in both newly diagnosed and previously treated HNC patients. This systematic review examined eleven investigations, of which nine were deemed suitable for inclusion in the subsequent meta-analysis. The quantitative synthesis yielded a pooled detection rate of 99% for primary HNC lesions. Additionally, on a per patient-based analysis, the pooled sensitivity and specificity for regional lymph node metastases were found to be 90% and 84%, respectively. The analysis revealed a statistical heterogeneity among the studies for the detection rate of primary HNC lesions. The quantitative findings presented in this study indicate a favorable diagnostic performance of FAP-targeted PET imaging in detecting primary HNC tumors. In contrast, discordant results concerning the diagnostic accuracy of lymph node metastases were found. However, further multicentric trials are required to validate the efficacy of FAP-targeted PET in this specific group of patients.

Thyroid disease and autoimmunity in obese patients: a narrative review.

INTRODUCTION: The high prevalence of obesity and thyroid diseases worldwide justifies di per se their simultaneous coexistence. In recent decades, there has been a parallel and significant rise in obesity and thyroid diseases in industrialised countries, although the underlying mechanisms are complex and not well known. MATERIAL AND METHODS: The authors accomplished a comprehensive literature search of original articles concerning obesity and thyroid status. Original papers exploring the association between these two morbidities in children and adults were included. RESULTS: A total of 79 articles were included in the present analysis. A total of 12% of obese children (mean age 10.9 ± 1.4 years) showed a thyroid disease, and they were younger than healthy obese children (10.9 ± 1.2 vs. 11.0 ± 0.4 years, p < 0.001). Isolated hyperthyrotropinaemia was the most frequent finding in children (10.1%). Autoimmune thyroid disease was more frequent in puberal age. Thyroid antibodies and subclinical hypothyroidism were more frequent in obese that in non-obese patients (7% vs. 3%, p < 0.001; 10% vs. 6%, p < 0.001). Among obese adults, 62.2% displayed a thyroid disease; those affected were younger (35.3 ± 6.8 vs. 41.0 ± 1.9 years, p < 0.001), heavier [body mass index (BMI): 39.4 ± 6.3 vs. 36.1 ± 2.3 kg/m², p < 0.001], and more frequently female (13% vs. 8%, p < 0.001). The most frequent disease was overt hypothyroidism (29.9%). BMI appears to be correlated with TSH levels in obese adults. Overt hypothyroidism was significantly more frequent in obese patients (7% vs. 3%, p < 0.005), but no difference was found in thyroid antibodies (15% vs. 14%, p = 0.178). CONCLUSIONS: An undeniable relationship between obesity and thyroid impairments exists. Isolated hyperthyrotropinaemia is frequently seen in obese children, often followed by spontaneous resolution. Subclinical hypothyroidism should never be treated in children or adults with the aim of reducing body weight.

PET/CT and Conventional Imaging for the Assessment of Neuroendocrine Prostate Cancer: A Systematic Review.

BACKGROUND: Neuroendocrine prostate cancer (NEPC) is a rare neoplasm, and the role of both conventional imaging (CI) and positron emission tomography/computed tomography (PET/CT) for its assessment has not been clearly evaluated and demonstrated. The aim of this systematic review was to analyze the diagnostic performances of these imaging modalities in this setting. METHODS: A wide literature search of the PubMed/MEDLINE, Scopus, and Web of Science databases was made to find relevant published articles about the role of CI and PET/CT for the evaluation of NEPC. RESULTS: 13 studies were included in the systematic review. PET/CT imaging with different radiopharmaceuticals has been evaluated in many studies (10) compared to CI (3 studies), which has only a limited role in NEPC. Focusing on PET/CT, a study used [18F]FDG, labeled somatostatin analogs were used in 5 cases, a study used [68Ga]Ga-FAPI-04, [68Ga]Ga-PSMA-11 was evaluated in a single case, and two works used different tracers. CONCLUSION: Published data on the role of PET/CT for the assessment of NEPC are limited. At present, it is still uncertain which tracer performs best, and although [18F]FDG has been evaluated and seems to offer some advantages in availability and clinical staging, other tracers may be more useful to understand tumor biology or identify targets for subsequent radioligand therapy. Further research is therefore desirable. In contrast, data are still limited to draw a final conclusion on the role and the specific characteristics of CI in this rare form of neoplasm, and therefore, more studies are needed in this setting.

Prevalence of Incidental Findings Suspicious for Transthyretin Cardiac Amyloidosis among Patients Undergoing Bone Scintigraphy: A Systematic Review and a Meta-Analysis.

BACKGROUND: The myocardial uptake of bone-seeking tracers suspicious for transthyretin cardiac amyloidosis (ATTR-CA) can be incidentally detected in patients undergoing bone scintigraphy for noncardiac reasons. We conducted a systematic review and meta-analysis to assess the prevalence of these scintigraphic findings. METHODS: A comprehensive literature search was performed using two bibliographic databases (PubMed/MEDLINE and Cochrane Library), searching for articles related to the review question. Eligible articles were selected, and relevant data were extracted by two authors. The pooled prevalence of incidental findings suspicious for ATTR-CA among patients undergoing bone scintigraphy was calculated on a per-patient-based analysis using a random-effects model. The pooled measure was provided with 95% confidence interval (95% CI) values. RESULTS: Among 219 records, 11 articles were selected for the systematic review and 10 for the meta-analysis. The pooled prevalence of incidental findings suspicious for ATTR-CA was 1.1% (95% CI: 0.7-1.4%) with heterogeneity due to the characteristics of the included studies, patients, and index tests. These findings are more prevalent in older men. CONCLUSIONS: The prevalence of incidental findings of ATTR-CA among patients undergoing bone scintigraphy is low but not negligible. Nuclear medicine physicians should suggest, in the scintigraphic report, further clinical investigations when these findings are detected. Prospective studies are warranted.

A Prospective Multicenter Study Examining the Relationship Between Thyroid Cancer Treatment Outcomes and the Presence of Autoimmune Thyroiditis.

Background: There is some controversy on the potential relationship between autoimmune processes and clinicopathologic features as well as prognosis of differentiated thyroid cancer (DTC), and the evidence is limited by its largely retrospective nature. We examined the relationship between the presence of autoimmune thyroiditis (AT) and 1-year thyroid cancer treatment outcomes in a large multicenter study using prospectively collected data. Methods: We included data from consecutive DTC patients enrolled in the Italian Thyroid Cancer Observatory (ITCO) database (NCT04031339). We divided the groups according to the presence (AT) or absence (no autoimmune thyroiditis [noAT]) of associated AT. We used propensity score matching to compare the clinical features and outcomes between the two groups at 1-year follow-up. Results: We included data from 4233 DTC patients, including 3172 (75%) females. The American Thyroid Association (ATA) risk levels were as follows: 51% (2160/4233) low risk, 41.3% (1750/4233) intermediate risk, and 7.6% (323/4233) high risk. There were 1552 patients (36.7%) who had AT. Before propensity score matching, AT patients were significantly younger and had a smaller and bilateral tumor (p < 0.0001). Patients with AT more frequently fell into the low- and intermediate-risk categories, while the ATA high risk was more frequent among noAT patients (p = 0.004). After propensity score matching, patients with AT more frequently showed evidence of disease (structural/biochemical incomplete response) versus excellent/indeterminate response, compared with patients without AT (7.3% vs. 4.5%, p = 0.001), with an odds ratio of 1.86 ([confidence interval: 1.3-2.6], p = 0.0001). However, when considering only structural persistence as the outcome, no statistically significant differences were observed between patients with or without AT (3.4% vs. 2.7%, p = 0.35). The elevated risk associated with the ATA intermediate and high risk at diagnosis remained consistently statistically significant. Conclusions: In this large prospective series, biochemical persistence was more frequent, at 1-year follow-up, in AT patients. However, there was no significant association between the presence of AT and structural persistence of disease. These findings may be explained by the presence of a residual thyroid tissue.

Role of splenic and bone marrow uptake at 18 F-FDG PET/CT for the assessment of large vessels vasculitis and the influence of glucocorticoids therapy on their values.

INTRODUCTION: To assess the relationship between splenic and bone marrow (BM) uptake with the presence of large vessel vasculitis (LVV) at 18 F-FDG PET/CT and to evaluate the influence of glucocorticoid (GC) therapy on these uptakes. METHODS: One hundred and one subjects with LVV and 18 F-FDG PET/CT were included in the study. Clinical features, including blood samples and duration of GC therapy, were collected. Standardized uptake value body weight max (SUVmax) of the spleen, BM, liver and arterial walls were extracted; spleen/liver (SL) and BM/liver (BML) ratios were calculated. Chi-square and T-test were used to assess the relationship between PET/CT parameters and clinical features with the presence of LVV. Rank correlation was used to evaluate the correlation between PET/CT parameters and clinical parameters. Receiver operating curve (ROC) analysis was used to find the best parameter able to discriminate between positive and negative PET/CT. All analyses were performed considering the duration of GC therapy. RESULTS: Significant correlation for PET/CT results with spleen uptake (P-value = 0.001), SL (P-value < 0.001) and BML (P-value = 0.005) were reported in patients with no more than 3 days of therapy; the correlation with SL was confirmed in the total cohort of patients. A value of 0.92 for SL had an AUC of 0.959, a sensitivity of 92.6% and a specificity of 96.6% (P-value < 0.001) in predicting PET/CT results. CONCLUSION: Higher splenic and BM uptake in patients with positive PET/CT for LVV were reported. A long duration of GC therapy is able to reduce such uptakes.

Diagnostic Performance of Positron Emission Tomography with Fibroblast-Activating Protein Inhibitors in Gastric Cancer: A Systematic Review and Meta-Analysis.

Various papers have introduced the use of positron emission tomography (PET) with [68Ga]Ga-radiolabeled fibroblast-activation protein inhibitor (FAPi) radiopharmaceuticals in different subtypes of gastric cancer (GC). Our aim was to assess the diagnostic performance of this novel molecular imaging technique in GC with a systematic review and meta-analysis. A straightforward literature search of papers concerning the diagnostic performance of FAP-targeted PET imaging was performed. Original articles evaluating this novel molecular imaging examination in both newly diagnosed GC patients and GC patients with disease relapse were included. The systematic review included nine original studies, and eight of them were also eligible for meta-analysis. The quantitative synthesis provided pooled detection rates of 95% and 97% for the assessment of primary tumor and distant metastases, respectively, and a pooled sensitivity and specificity of 74% and 89%, respectively, for regional lymph node metastases. Significant statistical heterogeneity among the included studies was found only in the analysis of the primary tumor detection rate (I2 = 64%). Conclusions: Beyond the limitations of this systematic review and meta-analysis (i.e., all the included studies were conducted in Asia, and using [18F]FDG PET/CT as a comparator of the index test), the quantitative data provided demonstrate the promising diagnostic performance of FAP-targeted PET imaging in GC. Nevertheless, more prospective multicentric studies are needed to confirm the excellent performances of FAP-targeted PET in this cluster of patients.

18F-FDG PET/CT Maximum Tumor Dissemination (Dmax) in Lymphoma: A New Prognostic Factor?

Recently, several studies introduced the potential prognostic usefulness of maximum tumor dissemination (Dmax) measured by 2-deoxy-2-fluorine-18-fluoro-D-glucose positron-emission tomography/computed tomography (18F-FDG PET/CT). Dmax is a simple three-dimensional feature that represents the maximal distance between the two farthest hypermetabolic PET lesions. A comprehensive computer literature search of PubMed/MEDLINE, Embase, and Cochrane libraries was conducted, including articles indexed up to 28 February 2023. Ultimately, 19 studies analyzing the value of 18F-FDG PET/CT Dmax in patients with lymphomas were included. Despite their heterogeneity, most studies showed a significant prognostic role of Dmax in predicting progression-free survival (PFS) and overall survival (OS). Some articles showed that the combination of Dmax with other metabolic features, such as MTV and interim PET response, proved to better stratify the risk of relapse or death. However, some methodological open questions need to be clarified before introducing Dmax into clinical practice.

Can Baseline [18F]FDG PET/CT Predict Response to Immunotherapy After 6 Months and Overall Survival in Patients with Lung Cancer or Malignant Melanoma? A Multicenter Retrospective Study.

Aim: To assess the role of baseline 18F-fluorodeoxyglucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) in predicting response to immunotherapy after 6 months and overall survival (OS) in patients with lung cancer (LC) or malignant melanoma (MM). Materials and Methods: Data from a multicenter, retrospective study conducted between March and November 2021 were analyzed. Patients >18 years old with a confirmed diagnosis of LC or MM, who underwent a baseline [18F]FDG-PET/CT within 1-2 months before starting immunotherapy and had a follow-up of at least 12 months were included. PET scans were examined visually and semiquantitatively by physicians at peripheral centers. The metabolic tumor burden (number of lesions with [18F]FDG-uptake) and other parameters were recorded. Clinical response was assessed at 3 and 6 months after starting immunotherapy, and OS was calculated as the time elapsing between the PET scan and death or latest follow-up. Results: The study concerned 177 patients with LC and 101 with MM. Baseline PET/CT was positive in primary or local recurrent lesions in 78.5% and 9.9% of cases, in local/distant lymph nodes in 71.8% and 36.6%, in distant metastases in 58.8% and 84%, respectively, in LC and in MM patients. Among patients with LC, [18F]FDG-uptake in primary/recurrent lung lesions was more often associated with no clinical response to immunotherapy after 6 months than in cases without any tracer uptake. After a mean 21 months, 46.5% of patients with LC and 37.1% with MM had died. A significant correlation emerged between the site/number of [18F]FDG foci and death among patients with LC, but not among those with MM. Conclusions: In patients with LC who are candidates for immunotherapy, baseline [18F]FDG-PET/CT can help to predict response to this therapy after 6 months, and to identify those with a poor prognosis based on their metabolic parameters. For patients with MM, there was only a weak correlation between baseline PET/CT parameters, response to therapy, and survival.

The role of warm ischemia time on functional outcomes after robotic partial nephrectomy: a radionuclide renal scan study from the clock randomized trial.

PURPOSE: To evaluate the relationship between warm ischemia time (WIT) duration and renal function after robot-assisted partial nephrectomy (RAPN). METHODS: The CLOCK trial is a phase 3 randomized controlled trial comparing on- vs off-clamp RAPN. All patients underwent pre- and postoperative renal scintigraphy. Six-month absolute variation of eGFR (AV-GFR), rate of relative variation in eGFR over 25% (RV-GFR > 25), absolute variation of split renal function (SRF) at scintigraphy (AV-SRF). The relationships WIT/outcomes were assessed by correlation graphs and then modeled by uni- and multivariable regression. RESULTS: 324 patients were included (206 on-clamp, 118 off-clamp RAPN). Correlation graphs showed a threshold on WIT equal to 10 min. The differences in outcome measures between cases with WIT < vs ≥ 10 min were: AV-GFR - 3.7 vs - 7.5 ml/min (p < 0.001); AV-SRF - 1% vs - 3.6% (p < 0.001); RV-GFR > 25 9.3% vs 17.8% (p = 0.008). Multivariable models found that AV-GFR was related to WIT ≥ 10 min (regression coefficient [RC] - 0.52, p = 0.019), age (RC - 0.35, p = 0.001) and baseline eGFR (RC - 0.30, p < 0.001); RV-GFR > 25 to WIT ≥ 10 min (odds ratio [OR] 1.11, p = 0.007) and acute kidney injury defined as > 50% increase in serum creatinine (OR 19.7, p = 0.009); AV-SRF to WIT ≥ 10 min (RC - 0.30, p = 0.018), baseline SRF (RC - 0.76, p < 0.001) and RENAL score (RC - 0.60. p = 0.028). The main limitation was that the CLOCK trial was designed on a different endpoint and therefore the present analysis could be underpowered. CONCLUSIONS: Up to 10 min WIT had no consequences on functional outcomes. Above the 10-min threshold, a statistically significant, but clinically negligible impact was found.

Combined forced diuresis and late acquisition on [68Ga]Ga-PSMA-11 PET/CT for biochemical recurrent prostate cancer: a clinical practice-oriented study.

OBJECTIVES: Increased detection of prostate cancer (PCa) recurrences using [68Ga]Ga-PSMA-11 PET/CT has been reported by adding forced diuresis or late-phase imaging to the standard protocol. However, the combination of these procedures in the clinical setting is still not standardized. METHODS: One hundred prospectively recruited biochemical recurrent PCa patients were restaged with dual-phase [68Ga]Ga-PSMA-11 PET/CT from September 2020 to October 2021. All patients received a standard scan (60 min), followed by diuretics (140 min) and a late-phase abdominopelvic scan (180 min). PET readers with low (n = 2), intermediate (n = 2), or high (n = 2) experience rated (i) standard and (ii) standard + forced diuresis late-phase images in a stepwise fashion according to E-PSMA guidelines, scoring their level of confidence. Study endpoints were (i) accuracy against a composite reference standard, (ii) reader's confidence level, and (iii) interobserver agreement. RESULTS: Forced diuresis late-phase imaging increased the reader's confidence category for local and nodal restaging (both p < 0.0001), and the interobserver agreement in identifying nodal recurrences (from moderate to substantial, p < 0.01). However, it significantly increased diagnostic accuracy exclusively for local uptakes rated by low-experienced readers (from 76.5 to 84%, p = 0.05) and for nodal uptakes rated as uncertain at standard imaging (from 68.1 to 78.5%, p < 0.05). In this framework, SUVmax kinetics resulted in an independent predictor of PCa recurrence compared to standard metrics, potentially guiding the dual-phase PET/CT interpretation. CONCLUSIONS: The present results do not support the systematic combination of forced diuresis and late-phase imaging in the clinical setting, but allow the identification of patients-, lesions-, and reader-based scenarios that might benefit from it. KEY POINTS: • Increased detection of prostate cancer recurrences has been reported by adding diuretics administration or an additional late abdominopelvic scan to the standard [68Ga]Ga-PSMA-11 PET/CT procedure. • We verified the added value of combined forced diuresis and delayed imaging, showing that this protocol only slightly increases the diagnostic accuracy of [68Ga]Ga-PSMA-11 PET/CT, thus not justifying its systematic use in clinics. • However, it can be helpful in specific clinical scenarios, e.g., when PET/CT is reported by low-experienced readers. Moreover, it increased the reader's confidence and the agreement among observers.

Temporal Evolution and Prognostic Role of Indeterminate Response Sub-Groups in Patients with Differentiated Thyroid Cancer after Initial Therapy with Radioiodine.

The clinical outcome of patients affected by Differentiated Thyroid Carcinoma (DTC) and an indeterminate response (IR) after initial therapy is not yet clear. IR includes three different sub-groups of patients: (1) IRTg+ group: Detectable thyroglobulin (Tg), regardless of antithyroglobulin antibodies (TgAb) presence or imaging studies; (2) IRTgAb+ group: Positive TgAb, regardless of Tg levels and nonspecific imaging findings; (3) IRImaging+ group: Nonspecific findings on neck ultrasonography or faint uptake in the thyroid bed on the whole-body scan, negative TgAb, and undetectable Tg. The main aim of this retrospective study was to investigate the dynamic evolution and prognostic role of these patients. From January 2010 to December 2017, 2176 patients who received radioiodine for DTC after total thyroidectomy were included. Two-hundred-eighty-eight patients had IR one year after therapy (187 TgAb+, 76 Tg+, 25 imaging+). After two years, 110 patients (38%) were reclassified as an excellent response and 5 (2%) as an incomplete response; after five years, 221 (77%) achieved an excellent response and 11 (4%) showed an incomplete response. One-year stimulated Tg and nodal disease at diagnosis may predict the final status of the disease. Progression-free survival was significantly shorter in IRTg+ than in IRTgAb+ and IRimaging+ groups. Considering Tg+ patients, a threshold of 3.3 ng/mL is best to predict prognosis.

ITA-IMMUNO-PET: The Role of [18F]FDG PET/CT for Assessing Response to Immunotherapy in Patients with Some Solid Tumors.

AIM: To examine the role of [18F]FDG PET/CT for assessing response to immunotherapy in patients with some solid tumors. METHODS: Data recorded in a multicenter (n = 17), retrospective database between March and November 2021 were analyzed. The sample included patients with a confirmed diagnosis of a solid tumor who underwent serial [18F]FDG PET/CT (before and after one or more cycles of immunotherapy), who were >18 years of age, and had a follow-up of at least 12 months after their first PET/CT scan. Patients enrolled in clinical trials or without a confirmed diagnosis of cancer were excluded. The authors classified cases as having a complete or partial metabolic response to immunotherapy, or stable or progressive metabolic disease, based on a visual and semiquantitative analysis according to the EORTC criteria. Clinical response to immunotherapy was assessed at much the same time points as the serial PET scans, and both the obtained responses were compared. RESULTS: The study concerned 311 patients (median age: 67; range: 31-89 years) in all. The most common neoplasm was lung cancer (56.9%), followed by malignant melanoma (32.5%). Nivolumab was administered in 46.3%, and pembrolizumab in 40.5% of patients. Baseline PET and a first PET scan performed at a median 3 months after starting immunotherapy were available for all 311 patients, while subsequent PET scans were obtained after a median 6, 12, 16, and 21 months for 199 (64%), 102 (33%), 46 (15%), and 23 (7%) patients, respectively. Clinical response to therapy was recorded at around the same time points after starting immunotherapy for 252 (81%), 173 (56%), 85 (27%), 40 (13%), and 22 (7%) patients, respectively. After a median 18 (1-137) months, 113 (36.3%) patients had died. On Kaplan-Meier analysis, metabolic responders on the first two serial PET scans showed a better prognosis than non-responders, while clinical response became prognostically informative from the second assessment after starting immunotherapy onwards. CONCLUSIONS: [18F]FDG PET/CT could have a role in the assessment of response to immunotherapy in patients with some solid tumors. It can provide prognostic information and thus contribute to a patient's appropriate treatment. Prospective randomized controlled trials are mandatory.