Choline PET/CT features to predict survival outcome in high-risk prostate cancer restaging: a preliminary machine-learning radiomics study.

BACKGROUND: Radiomic features are increasingly utilized to evaluate tumor heterogeneity in PET imaging but to date its role has not been investigated for Cho-PET in prostate cancer. The potential application of radiomics features analysis using a machine-learning radiomics algorithm was evaluated to select 18F-Cho PET/CT imaging features to predict disease progression in PCa. METHODS: We retrospectively analyzed high-risk PCa patients who underwent restaging 18F-Cho PET/CT from November 2013 to May 2018. 18F-Cho PET/CT studies and related structures containing volumetric segmentations were imported in the "CGITA" toolbox to extract imaging features from each lesion. A Machine-learning model has been adapted using NCA for feature selection, while DA was used as a method for feature classification and performance analysis. RESULTS: One hundred and six imaging features were extracted for 46 lesions for a total of 4876 features analyzed. No significant differences between the training and validating sets in terms of age, sex, PSA values, lesion location and size (P>0.05) were demonstrated by the machine-learning model. Thirteen features were able to discriminate FU disease status after NCA selection. Best performance in DA classification was obtained using the combination of the 13 selected features (sensitivity 74%, specificity 58% and accuracy 66%) compared to the use of all features (sensitivity 40%, specificity 52%, and accuracy 51%). Per-site performance of the 13 selected features in DA classification were as follows: T = sensitivity 63%, specificity 83%, accuracy 71%; N = sensitivity 87%, specificity 91% of and accuracy 90%; bone-M = sensitivity 33%, specificity 77% and accuracy 66%. CONCLUSIONS: An artificial intelligence model demonstrated to be feasible and able to select a panel of 18F-Cho PET/CT features with valuable association with PCa patients' outcome.

Prevalence of interstitial pneumonia suggestive of COVID-19 at 18F-FDG PET/CT in oncological asymptomatic patients in a high prevalence country during pandemic period: a national multi-centric retrospective study.

PURPOSE: To assess the presence and pattern of incidental interstitial lung alterations suspicious of COVID-19 on fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) ([18F]FDG PET/CT) in asymptomatic oncological patients during the period of active COVID-19 in a country with high prevalence of the virus. METHODS: This is a multi-center retrospective observational study involving 59 Italian centers. We retrospectively reviewed the prevalence of interstitial pneumonia detected during the COVID period (between March 16 and 27, 2020) and compared to a pre-COVID period (January-February 2020) and a control time (in 2019). The diagnosis of interstitial pneumonia was done considering lung alterations of CT of PET. RESULTS: Overall, [18F]FDG PET/CT was performed on 4008 patients in the COVID period, 19,267 in the pre-COVID period, and 5513 in the control period. The rate of interstitial pneumonia suspicious for COVID-19 was significantly higher during the COVID period (7.1%) compared with that found in the pre-COVID (5.35%) and control periods (5.15%) (p < 0.001). Instead, no significant difference among pre-COVID and control periods was present. The prevalence of interstitial pneumonia detected at PET/CT was directly associated with geographic virus diffusion, with the higher rate in Northern Italy. Among 284 interstitial pneumonia detected during COVID period, 169 (59%) were FDG-avid (average SUVmax of 4.1). CONCLUSIONS: A significant increase of interstitial pneumonia incidentally detected with [18F]FDG PET/CT has been demonstrated during the COVID-19 pandemic. A majority of interstitial pneumonia were FDG-avid. Our results underlined the importance of paying attention to incidental CT findings of pneumonia detected at PET/CT, and these reports might help to recognize early COVID-19 cases guiding the subsequent management.

Radiomics analysis of 18F-Choline PET/CT in the prediction of disease outcome in high-risk prostate cancer: an explorative study on machine learning feature classification in 94 patients.

OBJECTIVE: The aim of this study was (1) to investigate the application of texture analysis of choline PET/CT images in prostate cancer (PCa) patients and (2) to propose a machine-learning radiomics model able to select PET features predictive of disease progression in PCa patients with a same high-risk class at restaging. MATERIAL AND METHODS: Ninety-four high-risk PCa patients who underwent restaging Cho-PET/CT were analyzed. Follow-up data were recorded for a minimum of 13 months after the PET/CT scan. PET images were imported in LIFEx toolbox to extract 51 features from each lesion. A statistical system based on correlation matrix and point-biserial-correlation coefficient has been implemented for features reduction and selection, while Discriminant analysis (DA) was used as a method for features classification in a whole sample and sub-groups for primary tumor or local relapse (T), nodal disease (N), and metastatic disease (M). RESULTS: In the whole group, 2 feature (HISTO_Entropy_log10; HISTO_Energy_Uniformity) results were able to discriminate the occurrence of disease progression at follow-up, obtaining the best performance in DA classification (sensitivity 47.1%, specificity 76.5%, positive predictive value (PPV) 46.7%, and accuracy 67.6%). In the sub-group analysis, the best performance in DA classification for T was obtained by selecting 3 features (SUVmin; SHAPE_Sphericity; GLCM_Correlation) with a sensitivity of 91.6%, specificity 84.1%, PPV 79.1%, and accuracy 87%; for N by selecting 2 features (HISTO = _Energy Uniformity; GLZLM_SZLGE) with a sensitivity of 68.1%, specificity 91.4%, PPV 83%, and accuracy 82.6%; and for M by selecting 2 features (HISTO_Entropy_log10 - HISTO_Entropy_log2) with a sensitivity 64.4%, specificity 74.6%, PPV 40.6%, and accuracy 72.5%. CONCLUSION: This machine learning model demonstrated to be feasible and useful to select Cho-PET features for T, N, and M with valuable association with high-risk PCa patients' outcomes. KEY POINTS: • Artificial intelligence applications are feasible and useful to select Cho-PET features. • Our model demonstrated the presence of specific features for T, N, and M with valuable association with high-risk PCa patients' outcomes. • Further prospective studies are necessary to confirm our results and to develop the application of artificial intelligence in PET imaging of PCa.

Sequencing radium 223 and other life-prolonging agents in castration-resistant prostate cancer patients.

Background: Radium 223 (RA223) is currently administered as part of a therapeutic sequence with the other life-prolonging agents (LPAs) for metastatic castration-resistant prostate cancer (mCRPC). Patients & methods: We retrospectively reviewed the clinical records of patients who had received at least three LPAs including RA223. Results: Median overall survival (OS) from the start of first-line treatment was 39.8 months, with the patients who completed all six planned courses of RA223 having a longer OS than those who did not (53.2 vs 29.5 months; p < 0.0001). Conclusions: Our study confirms the activity of RA223 regardless of the treatment line in which it is administered and suggests that patient selection plays a central role in maximizing this activity.

Fracture risk and survival outcomes in metastatic castration-resistant prostate cancer patients sequentially treated with abiraterone acetate and RADIUM-223.

PURPOSE: To evaluate the fracture risk and survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) who received sequentially abiraterone acetate (AA) and radium 223 [223Ra]RaCl2 in the daily clinical practice. MATERIALS: We retrospectively reviewed the records of mCRPC patients who received [223Ra]RaCl2 immediately after progressing during an AA treatment line in everyday clinical practice. RESULTS: We reviewed data of a consecutive series of 94 mCRPC patients. Most of the patients (85.1%) received [223Ra]RaCl2 as second- or third-line treatment. [223Ra]RaCl2 treatment was well-tolerated; there were only four cases of grade 3 anaemia, two cases of grade 3 leukopenia and one case of grade 3 neutropenia. The overall fracture rate is 2.1%; one fracture was recorded during the course of [223Ra]RaCl2 treatment, and one was recorded 1 month after its end. The fractures both occurred at metastatic sites. Median OS from [223Ra]RaCl2 start was more than 14 months regardless of the treatment line when [223Ra]RaCl2 was administered. CONCLUSION: The findings of this study show that the treatment with [223Ra]RaCl2 immediately after AA was active and safe with a very low risk of a fracture. Thus, the present observational report makes a valuable contribution to the current debate concerning the risks and benefits of including [223Ra]RaCl2 in the therapeutic algorithm.

Diagnostic accuracy of cerebrospinal fluid biomarkers measured by chemiluminescent enzyme immunoassay for Alzheimer disease diagnosis.

In the last decades, an important role of cerebrospinal fluid (CSF) biomarkers for Alzheimer disease (AD) diagnosis has emerged. The evaluation of the triad consisting of 42 aminoacid-long amyloid-beta peptide (Aß42), total Tau (tTau) and Tau phosphorylated at threonine 181 (pTau) have been recently integrated into the research diagnostic criteria of AD. For a long time, the enzyme-linked immunosorbent assay (ELISA) has represented the most commonly used method for the measurement of CSF biomarkers levels. This study aimed to assess the diagnostic accuracy of CSF biomarkers, namely Aß42, tTau and pTau and their ratio, measured by fully automated CLEIA assay (Lumipulse). We included 96 patients clinically diagnosed as AD (48) and non-AD (48). All CSF biomarkers levels were measured on Lumipulse G1200 fully automated platform (Fujirebio Inc. Europe, Gent, Belgium). Aß42 levels, 42/40 ratio, 42/tTau ratio, 42/PTau ratio were significantly reduced, and tTau and PTau levels were significantly increased in AD patients in comparison with non-AD patients. The receiving operator curve (ROC) analysis showed good diagnostic accuracy of all CSF biomarkers and their ratios for discriminating AD patients from non-AD patients, with 42/40 ratio having the best AUC (0.724, 95%CI 0.619-0.828; p < 0.001). Our findings support the use of CSF biomarkers measured by CLEIA method on a fully automated platform for AD diagnosis.

Diagnostic and prognostic value of 18F-FDG PET/CT in recurrent germinal tumor carcinoma.

AIM: The aim of this bicentric retrospective study was to assess the diagnostic performance, the prognostic value, the incremental prognostic value and the impact on therapeutic management of 18F-FDG PET/CT in patients with suspected recurrent germinal cell testicular carcinoma (GCT). MATERIALS AND METHODS: From the databases of two centers including 31,500 18F-FDG PET/CT oncological studies, 114 patients affected by GCT were evaluated in a retrospective study. All 114 patients underwent 18F-FDG PET/CT for suspected recurrent disease. Diagnostic performance of visually interpreted 18F-FDG PET/CT and potential impact on the treatment decision were assessed using histology (17 patients), other diagnostic imaging modalities (i.e., contrast enhanced CT in 89 patients and MRI in 15) and clinical follow-up (114 patients) as reference. Progression-free survival (PFS) and overall survival (OS) rates were computed by means of Kaplan-Meier survival analysis. The progression rate (Hazard Ratio-HR) was determined using univariate Cox regression analysis by considering various clinical variables. RESULTS: Recurrent GCT was confirmed in 47 of 52 patients with pathological 18F-FDG PET/CT findings, by means of histology in 18 patients and by other diagnostic imaging modalities/follow-up in 29. Sensitivity, specificity, accuracy, positive and negative likelihood ratio (LR+ and LR-, respectively), pre-test Odds-ratio and post-test Odds-ratio of 18FDG PET/CT were 86.8%, 90.2%, 88.4%, 8.85, 0.14, 0.85, 8.85, respectively.18F-FDG PET/CT impacted significantly on therapeutic management in 26/114 (23%) cases (from palliative to curative in 12 patients, from "wait and watch" to new chemotherapy in six patients and the "wait-and-watch" approach in eight patients with unremarkable findings). At 2 and 5-year follow-up, PFS was significantly longer in patients with a negative than a pathological 18F-FDG PET/CT scan (98% and 95% vs 48% and 38%, respectively; p = 0.02). An unremarkable scan was associated also with a longer OS (98% after 2 years and 95% after 5 years, p = 0.02). At univariate Cox regression analysis, a pathological 18F-FDG PET/CT scan was associated with an increased risk of disease progression (HR = 24.3, CI 95% 14.1-40.6; p = 0.03) and lower OS (HR = 17.3 CI 95% 4,9-77; p < 0.001). Its prognostic value was confirmed also if tested against advanced disease at diagnosis and rising Human Chorionic Gonadotropin Beta (HCGB) or Alpha-Fetoprotein (AFP) (HR = 7.3 for STAGE III-PET+, p = 0.03; HR = 14.3 elevated HCGB-PET+, p = 0.02; HR 10.7 elevated AFP-PET+, p = 0.01) At multivariate analysis, only a pathological 18F-FDG PET/CT scan and advanced disease in terms of TNM staging were predictors of disease progression and OS. 18F-FDG PET/CT showed incremental value over other variables both in predicting PFS (chi-square from 24 to 40, p < 0.001) and OS (chi-square from 32 to 38, p = 0.003). CONCLUSION: 18F-FDG PET/CT has a very good diagnostic performance in patients with suspected recurrent GCT and has an important prognostic value in assessing the rate of PFS and OS. Furthermore, 18F-FDG PET/CT impacted the therapeutic regimen in 23% of patients, thus providing a significant impact in the restaging process.

Whole body magnetic resonance in indolent lymphomas under watchful waiting: The time is now.

ᅟ: The indolent non-Hodgkin lymphomas (i-NHLs) are characterised by 'indolent' clinical behaviour with slow growth and prolonged natural history. The watchful waiting (WW) strategy is a frequently employed treatment option in these patients. This implies a strict monitoring by imaging examinations, including 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) and CT. A major concern is radiation exposure due to regularly monitoring by conventional imaging procedures. Several studies have demonstrated the reliability of whole-body magnetic resonance imaging (WB-MRI) for lymphoma staging. WB-MRI could be useful for active surveillance in i-NHLs providing the suspect of disease progression that can be then confirmed by additional diagnostic procedures, including 18F-FDG-PET/CT. The directive 2013/59 by the European Union claims that if a radiation-free imaging technique allows obtaining the same diagnostic results, it should be invariably used. In this setting, WB-MRI may be considered a reasonable option in i-NHLs under WW, replacing imaging modalities that cause exposure to ionising radiations. This will help to reduce the cancer risk in i-NHL patients for whom chemo-/radiotherapy remain the usual treatment options following the usually long WW phase. The scientific community should raise the awareness of the risk of ionising radiations in i-NHLs and the emphasise the need for establishing the proper place of WB-MRI in lymphoma imaging. KEY POINTS: • Watchful waiting is a reasonable option in patients with indolent non-Hodgkin lymphomas. • Imaging is crucial to monitor patients with indolent non-Hodgkin lymphomas. • CT and 18 F-FDG-PET/CT are commonly used, implying a substantial radiation exposure. • WB-MRI is highly reliable in lymphoma staging. • WB-MRI may be considered to monitor indolent non-Hodgkin lymphomas under watchful waiting.

Could 68-Ga PSMA PET/CT become a new tool in the decision-making strategy of prostate cancer patients with biochemical recurrence of PSA after radical prostatectomy? A preliminary, monocentric series.

AIM: To evaluate the impact of gallium68 PSMA-11 (HBED-CC)-PET/CT on decision-making strategy of patients with relapsing prostate cancer (PC) presenting a second biochemical relapse after radical prostatectomy (RP) and salvage RT or salvage androgen deprivation therapy (ADT). MATERIALS AND METHODS: 40 patients were retrospectively analyzed. All of them had received prostatectomy. Thirteen out of 40 were addressed to gallium68 PSMA-11 (HBED-CC)-PET/CT for a biochemical relapse after RP, 14/40 after a salvage RT and 13/40 after salvage or adjuvant ADT. The PSA level ranged between 0.1 and 1.62 ng/ml (median value: 0.51 ng/ml). We studied the impact on the decision-making process of a multidisciplinary tumor board of additional data obtained from gallium68 PSMA-11 (HBED-CC)-PET/CT. RESULTS: Thirty-one out of 40 evaluated patients showed positive findings at gallium68 PSMA-11 (HBED-CC)-PET/CT (77.5%). Of them, five were positive in the prostatic bed, nine in the pelvic nodes, twelve in nodes outside the pelvis and eight at bone level. Nine patients presented two different sites of relapse (22.5%). Gallium68 PSMA-11 (HBED-CC)-PET/CT data changed the therapeutic approach in 28 patients (70%). CONCLUSIONS: Gallium68 PSMA-11 (HBED-CC)-PET/CT can be a useful tool in the restaging of post-RP, RT or ADT patients presenting biochemical relapse of PC and it could change the decision-making process in up of 70% of these patients. Prospective, larger series are needed to establish the correct role of this very promising tool in the staging and therapeutic approach of PC patients.

Recurrent bladder carcinoma: clinical and prognostic role of 18 F-FDG PET/CT.

AIM: A small number of studies evaluated the detection rate of lesions from bladder carcinoma (BC) of 18 F-FDG PET/CT in the restaging process. However, the prognostic role of FDG PET/CT still remains unclear. The aim of the present study was to evaluate the accuracy, the effect upon treatment decision, and the prognostic value of FDG PET/CT in patients with suspected recurrent BC. MATERIALS AND METHODS: Forty-one patients affected by BC underwent FDG PET/CT for restaging purpose. The diagnostic accuracy of visually interpreted FDG PET/CT was assessed compared to histology (n = 8), other diagnostic imaging modalities (contrast-enhanced CT in 38/41 patients and MRI in 15/41) and clinical follow-up (n = 41). Semiquantitative PET values (SUVmax, SUVmean, SUL, MTV, TLG) were calculated using a graph-based method. Progression-free survival (PFS) and overall survival (OS) were assessed by using Kaplan-Meier curves. The risk of progression (hazard ratio, HR) was computed by Cox regression analysis by considering all the available variables. RESULTS: PET was considered positive in 21 of 41 patients. Of these, recurrent BC was confirmed in 20 (95 %). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG PET/CT were 87 %, 94 %, 95 %, 85 %, 90 %. AUC was 0.9 (95 %IC 0.8-1). Bayesian positive and negative likelihood ratios were 14.5 and 0.13, respectively. FDG PET/CT findings modified the therapeutic approach in 16 patients (modified therapy in 10 PET-positive patients, watch-and-wait in six PET-negative patients). PFS was significantly longer in patients with negative scan vs. those with pathological findings (85 % vs. 24 %, p < 0.05; HR = 12.4; p = 0.001). Moreover, an unremarkable study was associated with a longer OS (88 % vs. 47 % after 2 years and 87 % vs. 25 % after 3 years, respectively, p < 0.05). Standardized uptake value (SUV)max > 6 and total lesion glycolysis (TLG) > 8.5 were recognized as the most accurate thresholds to predict PFS (2-year PFS 62 % for SUVmax < 6 vs. 15 % for SUVmax > 6, p = 0.018; 2-year PFS 66 % for TLG < 8.5 vs. 18 % for TLG > 8.5, p = 0.09). CONCLUSION: A very good diagnostic performance for FDG PET/CT was confirmed in patients with suspected recurrent BC. FDG PET/CT allowed for a change in treatment decision in about 40 % of cases and showed an important prognostic value in assessing PFS and OS.

18F-FDG PET reveals unique features of large vessel inflammation in patients with Takayasu's arteritis.

PURPOSE: The object of this study was to assess whether 18F-fluorodeoxyglucose PET/CT (FDG PET/CT) provides novel information in patients with Takayasu's arteritis (TA) in addition to that provided by current activity assessment, to analyse the effects of possible confounders, such as arterial grafts, and to verify whether PET/CT could be informative in lesions <4 mm thick. METHODS: We studied 30 patients with TA, evaluated from October 2010 to April 2014 by both PET/CT and magnetic resonance imaging (MRI). All arterial lesions were evaluated by PET both qualitatively (positive/negative) and semiquantitatively (maximum standardized uptake value, SUVmax), and the thickness of lesions in the MRI field of view was evaluated. In a per-patient analysis, the relationships between the PET data and acute-phase reactants and NIH criteria for active TA were evaluated. In a per-lesion analysis, the relationships between the PET features of each lesion and MRI morphological data were evaluated. The effects of the presence of arterial grafts were also evaluated. RESULTS: Increased FDG uptake was seen in 16 of 30 patients (53%) and in 46 of 177 vascular lesions (26%). Significant periprosthetic FDG uptake was seen in 6 of 7 patients (86%) with previous vascular surgery and in 10 of 11 of grafts (91%). Graft-associated uptake influenced the PET results in three patients (10%) and the SUVmax values in five patients (17%). Of 39 lesions with significant FDG uptake, 15 (38%) were <4 mm thick. Lesion thickness was correlated with lesion SUVmax in FDG-avid lesions only. FDG arterial uptake was not associated with systemic inflammation or NIH criteria. CONCLUSIONS: PET/CT reveals unique and fundamental features of arterial involvement in TA. PET/CT may be useful in the assessment of local inflammatory and vascular remodelling events independent of systemic inflammation during follow-up, even in lesions in which the arterial wall is <4 mm. The presence of arterial grafts is a potential confounder. Prospective studies are required to correlate PET findings with relevant clinical outcomes.

18F-Fluorodeoxyglucose-PET/CT in locally advanced head and neck cancer can influence the stage migration and nodal radiation treatment volumes.

AIM: To analyze the impact of 18F-fluorodeoxyglucose-PET/CT (PET/CT) in the radiotherapy (RT) planning strategy in HNC, correlating CT-scan and PET/CT performances. MATERIALS AND METHODS: Inclusion criteria were: age >18 years old, histologically proven head and neck cancer (HNC), patients candidate to definitive RT ± chemotherapy, stage of disease by means of PET/TC and CT-scan performed at our Cancer Care Center. RESULTS: Sixty patients were analyzed. The following primary tumor sites were investigated: nasopharynx (13%), oropharynx (42%), oral cavity (32%) and larynx non-glottic (13%). Globally, PET/CT findings caused changes on nodal radiation treatment volumes in 10% of all the population of study. Specifically, in 5 cases out of 19 oral cavity tumors (26%), PET/CT detected neck-nodes positive (not detected at CT-scan). These findings have allowed to change the patients management, including PET/CT neck-nodes positive in the high-risk RT volumes. CONCLUSION: In the RT planning strategy, the present findings support the use of PET/CT to improve upfront regional staging of HNC disease, particularly for oral cavity tumors. Further investigations are advocated to evaluate if this strategy could impact on long-term outcomes in terms of local control and overall survival.

Diagnostic accuracy of FDG PET/CT for clinical evaluation at the end of treatment of HL and NHL: a comparison of the Deauville Criteria (DC) and the International Harmonization Project Criteria (IHPC).

PURPOSE: To evaluate the accuracy and prognostic value of FDG PET/CT for response assessment after treatment in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) when using the Deauville Criteria (DC) and the International Harmonization Project Criteria (IHPC). METHODS: This retrospective study included 101 patients (35 HL, 66 NHL) who underwent early restaging FDG PET/CT after treatment. Scans were evaluated using the IHPC and DC. Two thresholds of positivity for the DC were used: a score of at least 3 (DC3, i.e. scores 3 - 5) and a score of at least 4 (DC4, i.e. a score of 4 or 5). Accuracy was assessed using conventional diagnostic procedures, multidisciplinary team case notes, further PET/CT scans and/or follow-up. Progression-free survival and overall survival were computed using the Kaplan-Meier method. The Cox proportional hazards model was used to identify predictors of outcome. RESULTS: Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of FDG PET/CT for early restaging were, respectively, 92 %, 87 %, 74 %, 92 % and 86 % using DC4, 97 %, 76 %, 64 %, 98 % and 84 % using DC3, and 97 %, 67 %, 57 %, 98 % and 76 % using the IHPC. FDG PET/CT positivity was associated with a worse cumulative survival rate over a 2-year period when using DC4 in comparison with the IHPC (20 % vs. 49 %; p < 0.05) and DC3 (47 %; p < 0.05). Cox regression analysis showed different risks of progression in patients positive on FDG PET/CT using the IHPC, DC3 and DC4 (hazard ratios 1.57, 0.7 and 3.2, respectively). CONCLUSION: FDG PET/CT using DC4 showed higher diagnostic accuracy for HL and NHL than FDG PET/CT using either the IHPC or DC3, indicating its value in predicting clinical outcome after treatment.

Recurrent renal cell carcinoma: clinical and prognostic value of FDG PET/CT.

PURPOSE: The purpose of our study was 1) to evaluate the diagnostic performance of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT), 2) to assess the impact of FDG PET/CT on treatment decision-making, and 3) to estimate the prognostic value of FDG PET/CT in the restaging process among patients with renal cell carcinoma (RCC). METHODS: From the FDG PET/CT databases of San Raffaele Hospital in Milan, Italy, and the Veneto Institute of Oncology in Padua, Italy, we selected 104 patients with a certain diagnosis of RCC after surgery, and for whom at least 24 months of post-surgical FDG PET/CT, clinical, and instrumental follow-up data was available. The sensitivity and specificity of FDG PET/CT were assessed by histology and/or other imaging as standard of reference. Progression-free survival (PFS) and overall survival (OS) were computed using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used to identify predictors of outcome. RESULTS: FDG PET/CT resulted in a positive diagnosis in 58 patients and a negative diagnosis in 46 patients. Sensitivity and specificity were 74% and 80%, respectively. FDG PET/CT findings influenced therapeutic management in 45/104 cases (43%). After a median follow-up period of 37 months (± standard deviation 12.9), 51 (49%) patients had recurrence of disease, and 26 (25%) had died. In analysis of OS, positive versus negative FDG PET/CT was associated with worse cumulative survival rates over a 5-year period (19% vs. 69%, respectively; p <0.05). Similarly, a positive FDG PET/CT correlated with a lower 3-year PFS rate. In addition, univariate and multivariate analysis revealed that a positive scan, alone or in combination with disease stage III-IV or nuclear grading 3-4, was associated with high risk of progression (multivariate analysis = hazard ratios [HRs] of 4.01, 3.7, and 2.8, respectively; all p < 0.05). CONCLUSIONS: FDG PET/CT is a valuable tool both in treatment decision-making and for predicting survival and progression in patients affected by RCC.

Predictive value of (18)F-FDG PET/CT in restaging patients affected by ovarian carcinoma: a multicentre study.

PURPOSE: Ovarian cancer is the eighth most common malignancy among women and has a high mortality rate. Prognostic factors able to drive an effective therapy are essential. (18)F-Fluoro-2-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) has been investigated in patients with epithelial ovarian cancer and showed promise in diagnosing, staging, detecting recurrent lesions and monitoring treatment response. Conversely, its prognostic role remains unclear. We aimed at assessing the prognostic value of (18)F-FDG PET/CT performed in the restaging process in a multicentre study. METHODS: We evaluated 168 patients affected by ovarian carcinoma, who underwent a restaging (18)F-FDG PET/CT. The presence of local recurrences, lymph node involvement and distant metastasis was recorded as well as lesion dimensions, maximum and mean standardized uptake values (SUVmax and SUVmean, respectively). Progression-free survival (PFS) and overall survival (OS) at 3 and 4 years were computed by using Kaplan-Meier curves. Increased odds ratio was assessed using Cox regression analysis testing all lesion parameters measured by PET/CT. RESULTS: PFS was significantly longer in patients with a negative than a positive restaging PET/CT study (3- and 4-year PFS 64 and 53% vs 23 and 12%, respectively; p < 0.001). Similarly, a negative study was associated with a significantly higher OS rate after 4 years of follow-up (67 vs 25% in negative and positive groups, respectively; p < 0.001). Lymph node or distant involvement were also independently associated with an increased risk of disease progression [hazard ratio (HR) 1.6 and 2.2, respectively; p = 0.003]. Moreover, PET/CT showed an incremental prognostic value compared to the International Federation of Gynecology and Obstetrics (FIGO) staging system. In the analysis of patient subsets, individuals with the same FIGO stage I-II but with negative PET had a significantly better 4-year OS than patients with low FIGO stage but positive PET. This implies that patients with the same FIGO stage can be further prognostically stratified using PET (p = 0.01). At receiver-operating characteristic (ROC) analysis, no thresholds for semiquantitative parameters were predictive of a worse outcome. CONCLUSION: (18)F-FDG PET/CT has an important prognostic value in assessing the risk of disease progression and mortality rate. An efficacious therapy planning might therefore effectively rely on (18)F-FDG PET/CT findings. Semiquantitative data were not proven to be an effective tool to predict disease progression.

Neuropsychological and FDG-PET profiles in VGKC autoimmune limbic encephalitis.

BACKGROUND: Limbic encephalitis (LE) is characterized by an acute or subacute onset with memory impairments, confusional state, behavioral disorders, variably associated with seizures and dystonic movements. It is due to inflammatory processes that selectively affect the medial temporal lobe structures. Voltage-gate potassium channel (VGKC) autoantibodies are frequently observed. In this study, we assessed at the individual level FDG-PET brain metabolic dysfunctions and neuropsychological profiles in three autoimmune LE cases seropositive for neuronal VGKC-complex autoantibodies. MATERIALS AND METHODS: LGI1 and CASPR2 potassium channel complex autoantibody subtyping was performed. Cognitive abilities were evaluated with an in-depth neuropsychological battery focused on episodic memory and affective recognition/processing skills. FDG-PET data were analyzed at single-subject level according to a standardized and validated voxel-based Statistical Parametric Mapping (SPM) method. RESULTS: Patients showed severe episodic memory and fear recognition deficits at the neuropsychological assessment. No disorder of mentalizing processing was present. Variable patterns of increases and decreases of brain glucose metabolism emerged in the limbic structures, highlighting the pathology-driven selective vulnerability of this system. Additional involvement of cortical and subcortical regions, particularly in the sensorimotor system and basal ganglia, was found. CONCLUSIONS: Episodic memory and fear recognition deficits characterize the cognitive profile of LE. Commonalities and differences may occur in the brain metabolic patterns. Single-subject voxel-based analysis of FDG-PET imaging could be useful in the early detection of the metabolic correlates of cognitive and non-cognitive deficits characterizing LE condition.

Diagnostic and prognostic value of 18F-FDG PET/CT in comparison with morphological imaging in primary adrenal gland malignancies - a multicenter experience.

OBJECTIVE: To evaluate the diagnostic and prognostic role of fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in comparison to morphological imaging such as computed tomography in primary adrenal malignancies. MATERIALS AND METHODS: In this multicenter retrospective study, 68 patients with adrenal malignancy were included. All patients had histologically proven diagnosis of primary adrenal malignancy (adrenocortical carcinoma, malignant pheochromocytoma, neuroblastoma and lymphoma), one whole body (18)F-FDG PET/CT scan and one whole-body contrast enhancement computed tomography (CECT) scan acquired within one month and were followed clinically and by performing morphological tests for at least 12 months. RESULTS: Overall sensitivity, specificity, accuracy, positive and negative predictive values for CECT and (18)F-FDG PET/CT were respectively, 59%, 100%, 65%, 100%, 27% and 75%, 100%, 82%, 100% and 63%. For adrenocortical carcinomas, (18)F-FDG PET/CT showed a better accuracy (93.4%) than CECT (75%). For neuroblastomas (18)F-FDG PET/CT also showed better accuracy (70.4%) than CECT (66.7%). For malignant pheochromocytomas (18)F-FDG PET/CT and CECT showed the same accuracy (90%). For primary adrenal lymphomas, (18)F-FDG PET/CT showed better accuracy (100%) than CECT (74.41%). Kaplan-Mayer curves showed that "histotypes" and "metastases at the last follow-up" were similarly detected for both disease free survival (DFS) and overall survival (OS), while "global 18F-FDG PET/CT" and "presence of metastases at diagnosis" were significant for DFS. Stratifying the sample by the presence or absence of metastases at diagnosis, standardized uptake value (SUVmax) was a significant prognostic factor for DFS when metastases were absent (Wald test=7.035, P=0.008). CONCLUSION: Our multicenter study demonstrated that (18)F-FDG PET/CT better than CECT diagnosed adrenal malignancies achieving also a good prognostic performance. Therefore management algorithms should include (18)F-FDG PET/CT.

Prostate-specific membrane antigen-PET/CT may result in stage migration in prostate cancer: performances, quantitative analysis, and potential criticism in the clinical practice.

AIM: The early detection of prostate cancer (PCa) metastatic disease with PET imaging leads to stage migration and change of disease management. We aimed to assess the impact on clinical management deriving from prostate-specific membrane antigen (PSMA) imaging with a digital PET/CT during the routine application in the staging and restaging process of PCa. MATERIAL AND METHODS: Eighty consecutive PCa patients underwent 18F-PSMA-1007. Digital PET/CT were retrospectively evaluated and discussed with oncologists to evaluate the impact on clinical management. Performances analysis, correlation among variables also considering semiquantitative parameters have been conducted. RESULTS: In the whole group of 80 patients at staging (N = 31) and restaging (N = 49), the detection rate of PSMA PET was 85% for all lesions. At staging, the performance analysis resulted in sensitivity 77.6%, specificity 89.5%, negative predictive value (NPV) 77.6%, positive predictive value (PPV) 89.5%, accuracy 85.7%, and area under curve (AUC) 0.87%. The performance of restaging PET in the group of patients with PSA values <1 ng/ml resulted in the following values: sensitivity 66.7%, specificity 92.9%, NPV 85.7%, PPV 81.3%, accuracy 82.6%, and AUC 0.79. Semiquantitative analysis revealed a mean value of SUVmax, metabolic tumor volume, and total lesion PSMA expression with differences in patients with high risk compared to low intermediate. At restaging PET, semiquantitative values of patients with total prostate specific antigen (tPSA) ≤ 1 ng/ml were significantly less than those of the tPSA > 1 ng/ml. A significant impact on clinical management was reported in 46/80 patients (57.5%) based on PSMA PET findings at staging and restaging. CONCLUSION: Although PSMA-PET provides optimal performances, its current role in redefining a better staging should be translated in the current clinical scenario about potential improvement in clinical/survival outcomes.

Artificial Intelligence Analysis Using MRI and PET Imaging in Gliomas: A Narrative Review.

The lack of early detection and a high rate of recurrence/progression after surgery are defined as the most common causes of a very poor prognosis of Gliomas. The developments of quantification systems with special regards to artificial intelligence (AI) on medical images (CT, MRI, PET) are under evaluation in the clinical and research context in view of several applications providing different information related to the reconstruction of imaging, the segmentation of tissues acquired, the selection of features, and the proper data analyses. Different approaches of AI have been proposed as the machine and deep learning, which utilize artificial neural networks inspired by neuronal architectures. In addition, new systems have been developed using AI techniques to offer suggestions or make decisions in medical diagnosis, emulating the judgment of radiologist experts. The potential clinical role of AI focuses on the prediction of disease progression in more aggressive forms in gliomas, differential diagnosis (pseudoprogression vs. proper progression), and the follow-up of aggressive gliomas. This narrative Review will focus on the available applications of AI in brain tumor diagnosis, mainly related to malignant gliomas, with particular attention to the postoperative application of MRI and PET imaging, considering the current state of technical approach and the evaluation after treatment (including surgery, radiotherapy/chemotherapy, and prognostic stratification).