A Prospective Randomized Multicenter Study on the Impact of [18F]F-Choline PET/CT Versus Conventional Imaging for Staging Intermediate- to High-Risk Prostate Cancer.

This study aimed to compare the efficacy of [18F]F-choline PET/CT with conventional imaging for staging and managing intermediate- to high-risk prostate cancer (PCa). The primary objective was to assess the ability of PET/CT with [18F]F-choline to identify lymph node and systemic involvement during initial staging. Secondary objectives included evaluating the impact of [18F]F-choline PET/CT on unnecessary local treatments and assessing the safety of [18F]F-choline agents. Additionally, the study aimed to analyze recurrence-free survival and overall survival 5 y after randomization. Methods: A prospective controlled, open, randomized multicenter phase III trial involving 7 Italian centers was conducted. Eligible patients with intermediate- to high-risk PCa were randomized in a 1:1 ratio. Two groups were formed: one undergoing conventional imaging (abdominopelvic contrast-enhanced CT and bone scanning) and the other receiving conventional imaging plus [18F]F-choline PET/CT. The study was terminated prematurely; however, all the endpoints were thoroughly analyzed and enriched. Results: Between February 2016 and December 2020, 256 patients were randomly assigned. In total, 236 patients (117 in the control arm and 119 in the experimental arm) were considered for the final assessment. In the experimental arm, the sensitivity for lymph node metastases, determined by final pathology and serial prostate-specific antigen evaluations, was higher than in the control arm (77.78% vs. 28.57% and 65.62% vs. 17.65%, respectively). The [18F]F-choline was tolerated well. The use of [18F]F-choline PET/CT resulted in an approximately 8% reduction in unnecessary extended lymphadenectomy compared with contrast-enhanced CT. Additionally, [18F]F-choline PET/CT had a marginal impact on 5-y overall survival, contributing to a 4% increase in survival rates. Conclusion: In the initial staging of PCa, [18F]F-choline PET/CT exhibited diagnostic performance superior to that of conventional imaging for detecting metastases. [18F]F-choline PET/CT reduced the rate of unnecessary extensive lymphadenectomy by up to 8%. These findings support the consideration of discontinuing conventional imaging for staging PCa.

Detection rate of 18F-Choline positron emission tomography/computed tomography in patients with non-metastatic hormone sensitive and castrate resistant prostate cancer.

BACKGROUND: To assess the detection rate of 18F-choline PET/CT in non-metastatic hormone-sensitive prostate cancer (hsPCa) and non-metastatic castrate resistant prostate cancer (CRPCa), based on the criteria proposed in the phase III SPARTAN trial and with high Gleason Score (GS). METHODS: Between October 2008 and September 2019, data from a retrospective multicenter study (N.=4 centers), involving patients undergoing 18F-choline PET/CT scans for a biochemical recurrence of PCa, were collected. The following inclusion criteria were used: 1) histologically proven PCa; 2) a non-metastatic disease in accordance with conventional imaging findings; 3) a PSA doubling time (PSAdt) <10 months; 4) a GS>8; and 5) no pelvic node>2 cm. The group of hsPCa and CRPCa patients, were compared by using a non-parametric statistical analysis. Moreover, a logistic regression analysis and ROC curves were used. RESULTS: One hundred forty patients were included. Of these, 82 patients were affected by hsPCa, and 58 had a CRPCa. Overall, 18F-Choline PET/CT was positive in 99/140 (70.7%). It was positive in 55/82 (67.1%) hsPCa patients and in 44/58 (75.9%) CRPCa subjects, respectively. The site of recurrence at 18F-Choline PET/CT were: 16 (27.6%) and 20 (24.4%) in prostatic bed, 25 (43.1%) and 24 (29.3%) in loco-regional lymph nodes and in 27 (46.6%) and 28 (34.1%) in distant organs, respectively for CRPCa and hsPCa patients. The optimal cut-off values for PSA at the time of PET/CT for the prediction or recurrence were 0.5 vs. 2.5 ng/mL for all site of recurrence (AUC: 0.70 vs. 0.72), 0.48 vs. 3.4 ng/mL for prostatic bed (AUC: 0.60 vs. 0.59), 0.5 vs. 1.5 for loco-regional lymph nodes (AUC: 0.62 vs. 0.57) and 2.2 vs. 2.8 ng/mL for distant metastasis (AUC: 0.74 vs. 0.71), respectively in CRPCa and hsPCa (all P=NS). Sensitivities and specificities of 18F-Choline PET/CT for the identification of recurrence disease in all patient population, in hsPCa and CRPCa were 83.7% and 87.5%, 78.9% and 88.9%, 91.4% and 85.7%, respectively. CONCLUSIONS: The rate of positive 18F-Choline PET/CT is similar in patients with a hsPCa and CRPCa, in case of low PSAdt and high GS. Therefore, non-metastatic PCa patients should be assessed by molecular imaging, in order to adapt the most appropriate therapeutic approach.

Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives.

Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have always been considered rare tumors, their incidence has risen over the past few decades. They represent a highly heterogeneous group of neoplasms with several prognostic factors, including disease stage, proliferative index (Ki67), and tumor differentiation. Most of these neoplasms express somatostatin receptors on the cell surface, a feature that has important implications in terms of prognosis, diagnosis, and therapy. Although International Guidelines propose algorithms aimed at guiding therapeutic strategies, GEP-NEN patients are still very different from one another, and the need for personalized treatment continues to increase. Radical surgery is always the best option when feasible; however, up to 80% of cases are metastatic upon diagnosis. Regarding medical treatments, as GEP-NENs are characterized by relatively long overall survival, multiple therapy lines are adopted during the lifetime of these patients, but the optimum sequence to be followed has never been clearly defined. Furthermore, although new molecular markers aimed at predicting the response to therapy, as well as prognostic scores, are currently being studied, their application is still far from being part of daily clinical practice. As they represent a complex disease, with therapeutic protocols that are not completely standardized, GEP-NENs require a multidisciplinary approach. This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.

Neuropsychological and Pet Study of Depersonalization and Derealization: A Single Case Report.

The present work depicts the case of a young man suffering from a depersonalization and derealization (DD) disorder, which mainly affects his own body. When the symptoms concern something else, they almost exclusively affect living beings. Neuropsychological and neuropsychiatric studies, as well as functional neuroanatomy studies, have led to hypothesize possible relationships among cognitive-neurofunctional alterations and symptoms of depersonalization and derealization. The present study suggests that a malfunction of the left frontal and prefrontal cortex causes deficits of working memory, producing some of the symptoms of DD.

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.

Usefulness of 18f-FDG PET-CT in Staging, Restaging, and Response Assessment in Pediatric Rhabdomyosarcoma.

Rhabdomyosarcoma is the most common soft-tissue sarcoma of childhood. Despite clinical advances, subsets of these patients continue to suffer high morbidity and mortality rates associated with their disease. Following the European guidelines for 18F-FDG PET and PET-CT imaging in pediatric oncology, the routine use of 18F-FDG PET-CT may be useful for patients affected by rhabdomyosarcoma, in staging, in the evaluation of response to therapy, and for restaging/detection of relapse. The European Pediatric Protocols are very old, and for staging and restaging, they recommend only radionuclide bone scan. The 18F-FDG PET-CT exam is listed as an optional investigation prescribed according to local availability and local protocols in the investigations panel required at the end of the treatment. We present two cases highlighting the usefulness of 18F-FDG PET-CT in managing pediatric patients affected by rhabdomyosarcoma, providing some bibliographic references.

10-Year Clinical Experience With 18F-Choline PET/CT: An Italian Multicenter Retrospective Assessment of 3343 Patients.

PURPOSE: The primary aim of this multicenter retrospective analysis is to examine the role of F-choline PET/CT as a diagnostic tool for staging and restaging prostate cancer (PCa) in a large population in the light of 10 years of clinical experience. A secondary aim of the study is to produce data on the predictors of a positive F-choline PET/CT result in the setting of PCa primaries and biochemical recurrences. MATERIALS AND METHODS: This multicenter retrospective cohort study is based on data collected by 9 Italian nuclear medicine departments. Between October 2008 and September 2019, 3343 men underwent F-choline PET/CT scans before receiving definitive treatments for a primary PCa or biochemical recurrence. Inclusion criteria were (1) histologically proven PCa (on surgical specimens or prostate biopsies from patients not treated surgically) and (2) availability of clinical and pathological data, including serum prostate specific antigen (PSA) level at the time of PET/CT scanning. RESULTS: F-choline PET/CT was performed in 545 cases (16.4%) for cancer staging and in 2798 (83.6%) for restaging purposes, and the result was positive in 540 (99.1%) for the former and 1993 (71.2%) for the latter. A positive PET/CT result was always associated with a high Gleason score (>7) and high PSA levels (P < 0.01). The percentage of patients with a PSA threshold less than 1.0 ng/mL for performing PET/CT was higher in the years 2014 to 2019 (n = 341, 25% of cases) than during the previous period (n = 148, 16%; in 2008-2013). When used for staging purposes, receiver operating characteristic analysis showed that PSA levels of 9.2, 16.4, and 16.6 ng/mL were the optimal cutoffs for distinguishing between positive and negative PET/CT findings for local disease, lymph node involvement, and metastasis, respectively. In the restaging setting, a PSA level of 1.27 ng/mL was the optimal cutoff for distinguishing between a positive and negative PET/CT scan. CONCLUSIONS: F-choline PET/CT can help identify early recurrences, even in the case of low PSA levels (<1 ng/mL). Our data suggest that important improvements have been made in the interpretation of F-choline images and in patient selection in the last 5 years.

Prognostic value of PET/CT in patients with lymphoma treated with autologous stem cell transplantation for relapsed/refractory or high risk disease.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT scan) has increasingly been used for management of lymphoma, however few and conflicting data have been provided in the setting of high dose therapy with autologous stem cell transplantation (ASCT) so far. METHODS: We retrospectively evaluated the outcome of 47 NHL patients who underwent ASCT for relapsed/refractory disease or high risk disease or partial response after first line treatment, with the aim of testing sensitivity, specificity, positive and negative prognostic value of PET/CT performed before and after ASCT. RESULTS: In our experience pre ASCT-PET/CT predicts outcome of non-Hodgkin's lymphoma patients with chemosensitive relapse, whereas post ASCT-PET showed a better prognostic value for relapsed disease. CONCLUSIONS: Results of our study, if confirmed by studies on a larger scale, could significantly contribute to design future trials and optimize the management of lymphoma patients.

Treatment with combined dabrafenib and trametinib in BRAFV600E-mutated metastatic malignant melanoma: a case of long-term complete response after treatment cessation.

Here, we report the case of a patient, diagnosed with BRAFV600E-mutated metastatic malignant melanoma M1a, who achieved a complete metabolic response after 7 months of treatment with the combination of dabrafenib and trametinib. After 31 months, the treatment was interrupted for patient's decision. To date October 2017, 18 months after the interruption of the treatment with the combination of dabrafenib and trametinib, follow-up Positron Emission Tomography (PET) scans are still documenting complete metabolic response.

Early impact of robot-assisted partial nephrectomy on renal function as assessed by renal scintigraphy.

To measure the early impact of robot-assisted partial nephrectomy (RAPN) on renal function as assessed by renal scan (Tc 99m-DTPA), addressing the issue of risk factors for ischemic damage to the kidney. All patients undergoing RAPN for cT1 renal masses between June 2013 and May 2014 were included in this prospective study. Renal function as expressed by glomerular filtration rate (GFR) was assessed by Technetium 99m-diethylenetriaminepentaacetic acid (Tc 99m-DTPA) renal scan preoperatively and postoperatively at 1 month in every patient. A multivariable analysis was used for the determination of independent factors predictive of GFR decrease of the operated kidney. Overall, 32 patients underwent RAPN in the time interval. Median tumor size, blood loss, and ischemia time were 4 cm, 200 mL, and 24 min, respectively. Two grade III complications occurred (postoperative bleeding in the renal fossa, urinoma). The GFR of the operated kidney decreased significantly from 51.7 ± 15.1 mL/min per 1.73 m(2) preoperatively to 40, 12 ± 12.4 mL/min per 1.73 m(2) 1 month postoperatively (p = 0.001) with a decrease of 22.4 %. On multivariable analysis, only tumor size (p = 0.05) was a predictor of GFR decrease of the operated kidney. Robotic-assisted partial nephrectomy had a detectable impact on early renal function in a series of relatively large tumors and prevailing intermediate nephrometric risk. A mean decrease of 22 % of GFR as assessed by renal scan in the operated kidney was found at 1 month postoperatively. In multivariable analysis, tumor size only was a significant predictor of renal function loss.

Serial 18F-choline-PET imaging in patients receiving enzalutamide for metastatic castration-resistant prostate cancer: response assessment and imaging biomarkers.

AIM: High rate of non-target lesions in metastatic castration-resistant prostate cancer usually limits applicability of Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and this has led to a growing interest in using PET/computed tomography (CT). We prospectively investigated the role of (18)F-choline (FCH)-PET/CT in patients receiving enzalutamide after docetaxel. PATIENTS & METHODS: 30 patients were monitored by means of FCH-PET/CT before and during the treatment. A Cox proportional hazards regression model was used to assess the associations between metabolic parameters and clinical outcomes. RESULTS: Univariate analysis showed no significant correlation between biochemical and FCH-PET responses. Multivariate analysis showed that only baseline maximum standardized uptake value (SUVmax) significantly correlated with biochemical progression-free survival, radiological progression-free survival and overall survival. CONCLUSION: Our findings suggest that FCH-PET/CT may play a role in defining prognosis of patients receiving enzalutamide because baseline SUVmax proved to be an independent prognostic factor.

Impact of enzalutamide administration on primary prostate cancer volume: a metabolic evaluation by choline positron emission tomography in castration-resistant prostate cancer patients.

BACKGROUND: Enzalutamide is active in advanced castration-resistant prostate cancer (CRPC) patients, in whom it has shown to be able to increase survival. We report the enzalutamide effect on primary prostate tumors, assessed by changes of metabolic tumor activity detected by (18)F-fluorocholine-positron emission tomography/computerized tomography ((18)F-FCH PET/CT). PATIENTS AND METHODS: We treated 31 patients with pretreated metastatic CRPC in an enzalutamide named-patient program. All patients were initially evaluated and then followed up by means of repeated (18)F-FCH PET/CT examinations. We identified most radiotracer-avid lesions, which were defined as specific regions of interest (ROIs): for each ROI we defined the maximum radiotracer standardized uptake value (SUVmax) and the threshold-based volume of interest (VOI) with a cutoff SUV value ≥ 2.5. In the 12 patients who did not receive a radical treatment for localized disease, the prostate was also considered an ROI. RESULTS: The baseline prostate median SUVmax of 7.25 showed reductions of 25% (P = .012) and 43% (P = .009) after 3 and 7 months of enzalutamide treatment, respectively. The baseline median prostate VOI of 12.73 cm(3) showed a reduction of 73% (P = .002) at 3 months and a reduction of 90% (P = .005) at 7 months. CONCLUSION: In addition to the metabolic changes of metastatic lesions observed with enzalutamide in CRPC patients, our data have shown significant volume reductions of the primary tumors according to (18)F-FCH PET/CT evaluation. These results could suggest the potential of enzalutamide therapy for localized prostate cancer.

Biochemical and objective response to abiraterone acetate withdrawal: incidence and clinical relevance of a new scenario for castration-resistant prostate cancer.

OBJECTIVE: To describe the incidence and clinical relevance of biochemical and objective responses to abiraterone acetate (AA) withdrawal (AAWD) in patients with castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS: Twenty-six patients with progressive CRPC treated with first-line docetaxel-based chemotherapy were administered with AA at the standard dose of 1000 mg/day in combination with prednisone until progression. The patients were regularly followed up during treatment and after AAWD. RESULTS: Nineteen of the 26 patients discontinued AA because of progression. Three of the patients undergoing AAWD experienced a biochemical response, which was accompanied by a metabolic and radiological response as revealed by choline positron emission tomography in 2 cases. CONCLUSION: Regardless of the underlying molecular bases, AAWD response does not occur rarely. It is sometimes long-lasting and accompanied by a metabolic and radiographic improvement. AAWD response should be taken into account when further therapeutic strategies are planned in patients with CRPC with progressive disease during abiraterone therapy.

Comparison of International Consensus Guidelines versus 18-FDG PET in detecting malignancy of intraductal papillary mucinous neoplasms of the pancreas.

OBJECTIVE: To assess the reliability of the International Consensus Guidelines (ICG) and 18-fluorodeoxyglucose positron emission tomography (PET) in distinguishing benign from malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. BACKGROUND: Since 2006 the ICG have been used to choose immediate surgery or surveillance for IPMN patients, but their low specificity increases the number of benign IPMNs that undergo resective surgery. PET has proved highly sensitive and specific in detecting malignancy in cystic neoplasms of the pancreas, including IPMNs. METHODS: Patients suspected with IPMNs of the pancreas seen at our Department from January 1989 to July 2010 were identified and classified as cases of main duct, mixed type and branch type IPMN. The indication for resection or surveillance was verified a posteriori for all patients according to the ICG. PET was considered positive for a Standardized Uptake Value ≥2.5. Surveillance included clinical examination, laboratory tests, CA 19-9 serum levels, and computed tomography and/or magnetic resonance and magnetic resonance cholangiopancreatography every 6 months for 2 years and yearly thereafter. Endoscopic ultrasound was rarely performed. PET was repeated in clinically or radiologically suspect cases, or if tumor markers increased. RESULTS: Sixty-one main duct or mixed type and 101-branch type IPMNs were included in the study. A histological diagnosis was available for 81 of 162 patients, missing for 1 locally advanced IPMN, whereas 62 patients are under surveillance and it proved impossible to contact 18. Conservative surgery was performed in 16 of 68 patients with benign IPMNs. The sensitivity, specificity, positive and negative predictive value, and accuracy of the ICG in detecting malignancy were 93.2, 22.2, 59.4, 72.7, and 61.2, whereas for PET they were 83.3, 100, 100, 84.6, and 91.3. CONCLUSIONS: PET is more accurate than the ICG in distinguishing benign from malignant (invasive and noninvasive) IPMNs. Prophylactic IPMN resection in young patients fit for surgery should be guided by the ICG, whereas PET should be performed in older patients, cases at increased surgical risk, or when the feasibility of parenchyma-sparing surgery demands a reliable preoperative exclusion of malignancy.

Tumor relapse after pancreatic cancer resection is detected earlier by 18-FDG PET than by CT.

INTRODUCTION: Pancreatic cancer recurrence is often difficult to detect by conventional imaging. Our aim was to evaluate the impact of fluorodeoxyglucose-positron emission tomography (FDG-PET) in the diagnosis of recurrent pancreatic cancer. METHODS: One-hundred thirty-eight patients were followed after resection for pancreatic cancer. Sixty-six underwent only CT and were excluded. Seventy-two patients also had FDG-PET. Recurrent patients were divided in two groups: group-1, CT positive and group 2, CT non diagnostic, FDG-PET positive. Characteristics and survival curves of the two groups were compared. Significance was set at p < 0.05. RESULTS: Overall, tumors recurred in 63 of 72 (87.5%) patients; two patients had a second cancer resected, thanks to FDG-PET. Tumor relapse was detected by CT in 35 patients and by FDG-PET in 61. Prognostic factors were similar in groups 1 and 2. Five out of 35 group 1 patients underwent surgery (two R0, two bypass, and one exploratory). Ten out of 28 group 2 patients underwent surgery (four R0, two R2, two bypass, and two exploratory). FDG-PET influenced treatment strategies in 32 of 72 patients (44.4%). Group 2 patients survived longer (P = 0.09), but the difference was not significant. Disease-free survival was similar in groups 1 and 2. CONCLUSION: Tumor relapse is detected earlier by FDG-PET than by CT. FDG-PET can help select the best candidates for surgical exploration, although the real benefit is still to be defined. It influences treatment strategies in a significant percentage of patients. An earlier diagnosis did not influence survival due to the lack of effective therapies.

Imaging with non-FDG PET tracers: outlook for current clinical applications.

Apart from the historical and clinical relevance of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG), various other new tracers are gaining a remarkable place in functional imaging. Their contribution to clinical decision-making is irreplaceable in several disciplines. In this brief review we aimed to describe the main non-FDG PET tracers based on their clinical relevance and application for patient care.

Radiotracer imaging studies in hepatic encephalopathy: ISHEN practice guidelines.

There is lack of consensus on radiotracer usage in hepatic encephalopathy (HE). We have focused our attention on three main areas: (i) radiotracer imaging in animal models of HE, (ii) methodological issues of radiotracer imaging in HE and (iii) radiotracer imaging studies on the pathophysiology and (new) therapies in HE. We suggest the following: 1. Positron emission tomography (PET) and single photon emission computed tomography lend themselves to the study of animal models of HE, but the models that are suitable depend on the specific research question. Magnetic resonance imaging (MRI) may be a useful alternative technique. 2. Owing to the cost of the technique, there is a need for multicentre human PET studies to overcome the problem of underpowered small studies being undertaken in individual research centres. There should be a unified PET protocol with central, anonymised data analysis in one centre, using validated methodology, on behalf of all participating centres. Such studies would be useful for the assessment of early intervention in patients with subtle neuropsychiatric symptoms, or for clarification of the effect of liver transplantation on HE. 3. While radiotracer imaging modalities remain useful research tools for the study of pathogenesis and for the assessment of treatment effects, there is no consensus on the use of imaging in routine clinical practice for diagnosis and prognosis. The most promising objective tools appear to be magnetic resonance spectroscopy (MRS) and volumetric MRI, which can be performed in multiple centres without the difficulties that radiotracer imaging entail.

PET imaging with 11C-acetate in prostate cancer: a biochemical, radiochemical and clinical perspective.

PURPOSE: In the present study, the potential clinical role of 11C-acetate PET mainly in the differential diagnosis, in the staging and in the follow-up of prostate cancer patients is reported. METHODS: Each of the above points has been accurately investigated by studying the specific biochemical and radiobiochemical behaviour of this positron emitter compound. RESULTS AND CONCLUSION: The imaging quality of 11C-acetate PET and its unique mechanisms of cellular uptake, make such radiotracer a powerful tool in evaluating all the steps of the prostatic cancer.