PSMA PET/CT Versus mpMRI for the Detection of Clinically Significant Prostate Cancer: An Updated Overview.

In the last years, PSMA-PET imaging and multiparametric MRI (mpMRI) have improved the clinical management of prostate cancer (PCa) patients. Currently, mpMRI is recommended by the EAU (European Association of Urology) guidelines for the primary diagnosis of PCa, whereas PSMA-PET is reserved for disease staging, particularly in high risk localized or locally advanced disease, as well as for biochemical recurrence after surgery. Nevertheless, several studies have explored the added value of PSMA-PET in other clinical scenarios, including primary diagnosis and especially for the detection of clinically significant PCa (csPCa). In the present contribution, we will provide an overview and an update on the current literature on imaging detection of csPCa, with a particular focus on mpMRI, PSMA-PET and their comparison.

[18F]FDG PET-TC radiomics and machine learning in the evaluation of prostate incidental uptake.

AIM: To evaluate the relevance of incidental prostate [18F]FDG uptake (IPU) and to explore the potential of radiomics and machine learning (ML) to predict prostate cancer (PCa). METHODS: We retrieved [18F]FDG PET/CT scans with evidence of IPU performed in two institutions between 2015 and 2021. Patients were divided into PCa and non-PCa, according to the biopsy. Clinical and PET/CT-derived information (comprehensive of radiomic analysis) were acquired. Five ML models were developed and their performance in discriminating PCa vs non-PCa IPU was evaluated. Radiomic analysis was investigated to predict ISUP Grade. RESULTS: Overall, 56 IPU were identified and 31 patients performed prostate biopsy. Eighteen of those were diagnosed as PCa. Only PSA and radiomic features (eight from CT and nine from PET images, respectively) showed statistically significant difference between PCa and non-PCa patients. Eight features were found to be robust between the two institutions. CT-based ML models showed good performance, especially in terms of negative predictive value (NPV 0.733-0.867). PET-derived ML models results were less accurate except the Random Forest model (NPV = 0.933). Radiomics could not accurately predict ISUP grade. CONCLUSIONS: Paired with PSA, radiomic analysis seems to be promising to discriminate PCa/non-PCa IPU. ML could be a useful tool to identify non-PCa IPU, avoiding further investigations.

Comparison of MRI vs. [18F]FDG PET/CT for Treatment Response Evaluation of Primary Breast Cancer after Neoadjuvant Chemotherapy: Literature Review and Future Perspectives.

The purpose of this systematic review was to investigate the diagnostic accuracy of [18F]FDG PET/CT and breast MRI for primary breast cancer (BC) response assessment after neoadjuvant chemotherapy (NAC) and to evaluate future perspectives in this setting. We performed a critical review using three bibliographic databases (i.e., PubMed, Scopus, and Web of Science) for articles published up to the 6 June 2023, starting from 2012. The Quality Assessment of Diagnosis Accuracy Study (QUADAS-2) tool was adopted to evaluate the risk of bias. A total of 76 studies were identified and screened, while 14 articles were included in our systematic review after a full-text assessment. The total number of patients included was 842. Eight out of fourteen studies (57.1%) were prospective, while all except one study were conducted in a single center. In the majority of the included studies (71.4%), 3.0 Tesla (T) MRI scans were adopted. Three out of fourteen studies (21.4%) used both 1.5 and 3.0 T MRI and only two used 1.5 T. [18F]FDG was the radiotracer used in every study included. All patients accepted surgical treatment after NAC and each study used pathological complete response (pCR) as the reference standard. Some of the studies have demonstrated the superiority of [18F]FDG PET/CT, while others proved that MRI was superior to PET/CT. Recent studies indicate that PET/CT has a better specificity, while MRI has a superior sensitivity for assessing pCR in BC patients after NAC. The complementary value of the combined use of these modalities represents probably the most important tool to improve diagnostic performance in this setting. Overall, larger prospective studies, possibly randomized, are needed, hopefully evaluating PET/MR and allowing for new tools, such as radiomic parameters, to find a proper place in the setting of BC patients undergoing NAC.

Misinterpretation of an inflammatory FDG uptake in a patient treated for Hodgkin lymphoma: a case report.

Hodgkin Lymphoma (HL) is a malignancy involving lymph nodes and lymphatic system. [18F]F-FDG PET/CT (FDG-PET) imaging is routinely used for staging, to assess early chemotherapy response (interim FDG-PET), at the end of treatment (EoT FDG-PET) and for the identification of disease recurrence. We present a case of a 39-year-old man treated for HL. FDG-PET scans performed after first line therapy (both Interim PET and at the end of therapy) demonstrated a persistent and significant mediastinal FDG uptake. The patient was treated with a second line therapy but the FDG-PET uptake did not change. After board discussion a new surgical, thoracoscopy-guided biopsy was performed. Histopathology demonstrated a dense fibrous tissue with occasional chronic inflammatory infiltrates. Persistent FDG-PET positivity may suggest refractory or relapsed disease. However, occasionally, non-malignant conditions are responsible for a persistent FDG uptake, not related to primary disease. An accurate evaluation of clinical history and previous imaging exams is mandatory for clinicians and others experts to avoid misinterpretations of FDG-PET results. Nevertheless, in some cases, only a more invasive procedure, such as a biopsy, may finally lead to a definitive diagnosis.

Role of 18F-FDG PET/CT in evaluating lymph node status in patients with head and neck squamous cell carcinoma.

Objective: The presence of cervical lymph node metastases (CLNM) at diagnosis is one of the most relevant negative prognostic factors in patients with head and neck squamous cell carcinoma (HNSCC). The aim of this study was to analyse 2-deoxy-2[18F]fluoro-D-glucose (FDG) PET/CT findings for the identification of primary tumours and CLNM in a sample of patients affected by HNSCC. Moreover, a maximum standardised uptake value (SUVmax) threshold for the detection of CLNM was estimated. Clinical variables (i.e. smoking and alcohol habits), and tumour features (i.e. EBV and HPV positivity) were also evaluated in relation to FDG PET/CT findings. Methods: We retrospectively analysed patients who underwent FDG PET/CT for HNSCC staging between 2015-2020 at the University Hospital of Ferrara. All patients had cytological or histological confirmation of suspected cervical lymph nodes. Results: In total, 65 patients were enrolled (53 males, 12 females, median age 65.7 years). CLNM of patients with smoking habit had significantly higher SUVmax values than those of patients with previous smoking habit and non-smokers (p = 0.04). p16 positive HNSCC demonstrated a trend for higher SUVmax values on CLNM, in comparison to p16 negative tumours (p = 0.089). ROC curve analysis identified 5.8 as the best cut-off value of SUVmax for the detection of CLNM (AUC = 0.62, sensitivity 71.4% and specificity 72.7%). Conclusions: FDG PET/CT is a useful tool to evaluate CLNM in patients with HNSCC, particularly in those with smoking habit and p16 positive disease. A SUVmax cut-off of 5.8, combined with the use of conventional radiological investigations, may represent a useful tool in the identification of CLNM.

PET Criteria by Cancer Type from Imaging Interpretation to Treatment Response Assessment: Beyond FDG PET Score.

BACKGROUND: in recent years, the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) has emerged as a reliable diagnostic tool in a wide variety of pathological conditions. This review aims to collect and review PET criteria developed for interpretation and treatment response assessment in cases of non-[18F]fluorodeoxyglucose ([18F]FDG) imaging in oncology. METHODS: A wide literature search of the PubMed/MEDLINE, Scopus and Google Scholar databases was made to find relevant published articles about non-[18F]FDG PET response criteria. RESULTS: The comprehensive computer literature search revealed 183 articles. On reviewing the titles and abstracts, 149 articles were excluded because the reported data were not within the field of interest. Finally, 34 articles were selected and retrieved in full-text versions. CONCLUSIONS: available criteria are a promising tool for the interpretation of non-FDG PET scans, but also to assess the response to therapy and therefore to predict the prognosis. However, oriented clinical trials are needed to clearly evaluate their impact on patient management.

Relevance of Volumetric Parameters Applied to [68Ga]Ga-DOTATOC PET/CT in NET Patients Treated with PRRT.

BACKGROUND: this study aims to explore the prognostic and predictive role of volumetric parameters on [68Ga]Ga-DOTATOC PET/CT in neuroendocrine tumors (NET) patients treated with peptide receptor radionuclide therapy (PRRT). METHODS: We retrospectively evaluated 39 NET patients (21 male, 18 female; mean age 60.7 y) within the FENET-2016 trial (CTiD:NCT04790708). PRRT was proposed with [177Lu]Lu-DOTATOC alone or combined with [90Y]Y-DOTATOC. [68Ga]Ga-DOTATOC PET/CT was performed at baseline and 3 months after PRRT. For each PET/CT, we calculated SUVmax, SUVmean, somatostatin receptor expressing tumor volume (SRETV), and total lesion somatostatin receptor expression (TLSRE), as well as their percentage of changes (Δ), both for liver (_L) and for total tumor burden (_WB). Early clinical response (3 months after PRRT) and PFS were evaluated according to RECIST 1.1 and institutional NET board. RESULTS: Early clinical response identified 9 partial response (PR), 25 stable disease (SD), and 5 progressive disease (PD). Post-SRETV_WB and ΔSRETV_WB were progressively increased among response groups (p = 0.02 and p = 0.03, respectively). Likewise, median post-SRETV_L was significantly higher in PD patients (p = 0.03). SUVmax and TLSRE did not correlate with early clinical response. Median PFS was 31 months. Patients with ΔSRETV_WB lower than -4.17% as well as those with post-SRETV_WB lower than 34.8 cm3 showed a longer PFS (p = 0.006 and p = 0.06, respectively). Finally, multivariate analysis identified ΔSRETV_WB as an independent predictor for PFS. CONCLUSIONS: our results could strengthen the importance of evaluating the burden of disease on [68Ga]Ga-DOTATOC PET/CT in NET patients treated with PRRT.

FDG PET/CT Volume-Based Quantitative Data and Survival Analysis in Breast Cancer Patients: A Systematic Review of the Literature.

PURPOSE: The study aims to assess the role of SUVs, MTV, TLG, and other FDG PET metric data in predicting the prognosis of patients with newly diagnosed BC. MATERIALS AND METHODS: A systematic review was conducted by using three different databases: Pub- Med, Web of Science, and EMBASE, in the period between January 2011 and May 2021. Studies on the use of FDG PET in BC patients concerning the utility of metric PET data and survival were retrieved. The following keywords were used in diverse combinations: "breast cancer", "18F-FDG", "FDG", "PET", "PET/CT", "FDG PET", "volumetric parameters", "metabolic tumor volume", "MTV", "total lesion glycolysis", "TLG", "prognosis", "prognostic". No limits were applied. The quality of selected papers was assessed by using specific criteria. RESULTS: Totally 123 articles were retrieved, but only 14 studies were selected. In the selected papers, overall, the number of patients was 1850. Overall survival (OS) was the main outcome in three studies, while both OS and disease-free survival (DFS) were considered in the remainder of most papers. PET/CT was performed in patients with BC before surgery or neoadjuvant chemotherapy in 6 studies and in metastatic BC in 8. At multivariable analyses, diverse PET metrics, such as SUVmax, MTV, and TLG, were correlated to recurrence or OS. However, a large heterogeneity for the proposal cut-off, able to discriminate between poor and good prognosis, was found. CONCLUSION: PET metrics are helpful for the prognosis stratification in patients with locally advanced or metastatic BC. However, no specific cut-off values for these variables are now available in this setting of patients.

Glucose Metabolism Modification Induced by Radioligand Therapy with [177Lu]Lu/[90Y]Y-DOTATOC in Advanced Neuroendocrine Neoplasms: A Prospective Pilot Study within FENET-2016 Trial.

[18F]F-FDG (FDG) PET is emerging as a relevant diagnostic and prognostic tool in neuroendocrine neoplasms (NENs), as a simultaneous decrease in [68Ga]Ga-DOTA peptides and increase in FDG uptake (the "flip-flop" phenomenon) occurs during the natural history of these tumors. The aim of this study was to evaluate the variations on FDG PET in NEN patients treated with two different schemes of radioligand therapy (RLT) and to correlate them with clinical−pathologic variables. A prospective evaluation of 108 lesions in 56 patients (33 males and 23 females; median age, 64.5 years) affected by NENs of various primary origins (28 pancreatic, 13 gastrointestinal, 9 bronchial, 6 unknown primary (CUP-NENs) and 1 pheochromocytoma) and grades (median Ki-67 = 9%) was performed. The patients were treated with RLT within the phase II clinical trial FENET-2016 (CTID: NCT04790708). RLT was offered for 32 patients with the MONO scheme (five cycles of [177Lu]Lu-DOTATOC) and for 24 with the DUO scheme (three cycles of [177Lu]Lu-DOTATOC alternated with two cycles of [90Y]Y-DOTATOC). Variations in terms of the ΔSUVmax of a maximum of three target lesions per patient (58 for MONO and 50 for DUO RLT) were assessed between baseline and 3 months post-RLT FDG PET. In patients with negative baseline FDG PET, the three most relevant lesions on [68Ga]Ga-DOTA-peptide PET were assessed and matched on post-RLT FDG PET, to check for any possible changes in FDG avidity. Thirty-five patients (62.5%) had at least one pathological FDG uptake at the baseline scans, but the number was reduced to 29 (52%) after RLT. In the patients treated with DUO-scheme RLT, 20 out of 50 lesions were FDG positive before therapy, whereas only 14 were confirmed after RLT (p = 0.03). Moreover, none of the 30 FDG-negative lesions showed an increased FDG uptake after RLT. The lesions of patients with pancreatic and CUP-NENs treated with the DUO scheme demonstrated a significant reduction in ΔSUVmax in comparison to those treated with MONO RLT (p = 0.03 and p = 0.04, respectively). Moreover, we found a mild positive correlation between the grading and ΔSUVmax in patients treated with the MONO scheme (r = 0.39, p < 0.02), while no evidence was detected for patients treated with the DUO scheme. Our results suggest that RLT, mostly with the DUO scheme, could be effective in changing NEN lesions' glycometabolism, in particular, in patients affected by pancreatic and CUP-NENs, regardless of their Ki-67 index. Probably, associating [90Y]Y-labelled peptides, which have high energy emission and a crossfire effect, and [177Lu]Lu ones, characterized by a longer half-life and a safer profile for organs at risk, might represent a valid option in FDG-positive NENs addressed to RLT. Further studies are needed to validate our preliminary findings. In our opinion, FDG PET/CT should represent a potent tool for fully assessing a patient's disease characteristics, both before and after RLT.

The Role of [68Ga]PSMA PET/CT for Clinical Suspicion of Prostate Cancer in Patients with or without Previous Negative Biopsy: A Systematic Review.

The purpose of the study is to systematically evaluate the evidence regarding the role of [68Ga]PSMA PET/CT for clinical suspicions of prostate cancer in patients with or without previous negative biopsy. We performed a critical review of PubMed and Web of Science according to the PRISMA statement. Eighteen publications were selected for inclusion in this analysis. QUADAS-2 evaluation was adopted for quality analyses. [68Ga]PSMA-11 was the radiotracer of choice in 15 studies, while [68Ga]PSMA-617 was used in another 3. In 8 articles, there was a direct comparison with mpMRI. The total number of patients included was 1379, ranging from 15 to 291, with a median age of 64 years (range: 42-90). The median baseline PSA value was 12.9 ng/mL, ranging from 0.85 to 4156 ng/mL. Some studies evaluated the PSMA uptake comparing the SUVmax of suspicious lesions with the SUVmax of the normal biodistribution to find out optimal cut-off points. In addition, some studies suggested a significant association between PSA levels, PSA density, and [68Ga]PSMA PET/CT finding. [68Ga]PSMA PET/CT seems to be more accurate in identifying primary prostate cancer with PSA values between 4 and 20 ng/mL than mpMRI. Moreover, in some trials, the combination of PSMA PET/CT and MRI improved the NPV in the detection of clinically significant prostate cancer (csPCa) than MRI alone. Our findings are limited by the small numbers of studies and patient heterogeneity. [68Ga]PSMA PET/CT is a promising technique in patients with clinical suspicion of PCa and precedent negative biopsy or contraindications to MRI. Furthermore, its use combined with MRI improves sensitivity for csPCa detection and can avoid unnecessary biopsies.

Impact on the long-term prognosis of FDG PET/CT in luminal-A and luminal-B breast cancer.

PURPOSE: The aim of the present study was to explore the prognostic role of 2- deoxy-2-[18F]fluoro-D-glucose PET (FDG PET)/CT in recurrent luminal A and luminal B breast cancer. MATERIALS AND METHODS: From two institutional databases, we retrospectively retrieved data about breast cancer patients undergoing FDG PET/CT between 2011 and 2018 for the assessment of recurrency. Molecular subtypes of breast cancer were defined based on the expression of estrogen, progesterone, human epidermal growth factor receptor 2 (HER2)-b receptors and proliferation index. Overall survival (OS, intended as the time from PET/CT and the time of death) was registered for each patient, by checking the medical charts. Parametric and survival analyses were computed. RESULTS: Data of 179 patients were retrieved. Sixty-three patients had luminal A, 88 luminal B and 28 luminal B/He breast cancer. At the time of PET/CT scan, cancer antigen (CA) 15.3 levels was within the normal range in 119 patients, whereas it was increased in 60 patients. FDG PET/CT results were suggestive for disease recurrence in 114 (63.7%) patients. The median time lapse from the FDG PET/CT scan to the last clinical follow-up visit was 51 months (1-192 months). Patients with evidence of a PET/CT scan suggestive for disease recurrence showed a significantly shorter OS (P < 0.001) compared to patients with no PET/CT evidence of recurrence, in each subset of luminal breast cancer. Moreover, PET/CT was able to stratify the prognosis of patients independently from the level of tumor marker. CONCLUSION: These data suggest that FDG PET/CT may be an attractive prognostic tool in recurrent breast cancer. Our study supports its prognostic role both in luminal A and B-type molecular subtypes, regardless of the CA 15.3 levels.

Incidental Findings of Acute Myeloid Leukemia in Sjögren's Syndrome Detected by Nuclear Medicine Techniques.

A 46-year-old female with Sjögren's syndrome previously treated with corticosteroids was referred to our department for suspicious humeral head osteonecrosis. Dual-phase bone scan showed an increased radiotracer distribution in the head of the left humerus. Nevertheless, whole-body scan revealed multiple sites of heterogeneous skeletal uptake. As lymphoproliferative disorder was hypothesized, also based on laboratory examination, F-18 fluorodeoxyglucose positron-emission tomography/computed tomography was performed and showed increased uptake in several osseous structures and in the subcutaneous nodules. Finally, bone marrow biopsy confirmed the diagnosis of acute myeloid leukemia as well as skin nodule biopsy revealed infiltration by malignant cells.

90Y/177Lu-DOTATOC: From Preclinical Studies to Application in Humans.

The PRRT (Peptide Receptor Radionuclide Therapy) is a promising modality treatment for patients with inoperable or metastatic neuroendocrine tumors (NETs). Progression-free survival (PFS) and overall survival (OS) of these patients are favorably comparable with standard therapies. The protagonist in this type of therapy is a somatostatin-modified peptide fragment ([Tyr3] octreotide), equipped with a specific chelating system (DOTA) capable of creating a stable bond with ß-emitting radionuclides, such as yttrium-90 and lutetium-177. In this review, covering twenty five years of literature, we describe the characteristics and performances of the two most used therapeutic radiopharmaceuticals for the NETs radio-treatment: [90Y]Y-DOTATOC and [177Lu]Lu-DOTATOC taking this opportunity to retrace the most significant results that have determined their success, promoting them from preclinical studies to application in humans.

Clinical-Diagnostic Relevance of Breast "Incidentaloma" Detected During 18F-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography/Computed Tomography: Correlation with Radiological Imaging and Histopathology.

AIM: This study aims to study the clinical-diagnostic relevance of incidental breast uptake ("incidentaloma") on 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan performed for other indications and to correlate it with radiological imaging and histopathology. MATERIALS AND METHODS: We retrospectively evaluated 3675 FDG-PET scans, identifying 43 patients with breast "incidentaloma." Thirty of these findings were further investigated with clinical examination, mammography (MMX), UltraSound (US) and/or magnetic resonance (MR). Cases suspected for malignancy underwent US-guided macro-biopsy (USMB) or MR-guided biopsy. Correlations between FDG-PET, radiology findings, age, and histopathology were evaluated. RESULTS: patients who performed both US and MMX were 19. Ten consequently underwent USMB, one MR-guided biopsy, the remaining 8 were not further investigated. Nine patients had a diagnosis of malignancy. Among 11 patients who performed only US and consequently, USMB 6 had a diagnosis of malignancy. Histopathology of the 22 patients with both morphological and glucometabolic alterations showed different types of benign or malignant neoplasia, with a cumulative 68.2% incidence of malignancy. Seven lesions showed a SUVmax >2.5, while the remaining 15 a SUVmax <2.5. There was no statistically significant correlation between SUVmax and histology, therefore SUVmax parameter should not be used to discriminate between benign and malignant findings. No significant correlation between patient age and tumor characterization was found. CONCLUSIONS: incidental mammary uptake during an FDG-PET scan may represent a clue suggesting to investigate PET findings. In this subset of patients, early diagnosis may lead to a change in clinical management with a favorable impact on prognosis and a significant reduction in healthcare costs.