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Introduction: Neuroendocrine neoplasms (NENs) represent a complex group of tumors arising from neuroendocrine cells, characterized by heterogeneous behavior and challenging diagnostics. Despite advancements in medical technology, NENs present a major challenge in early detection, often leading to delayed diagnosis and variable outcomes. This review aims to provide an in-depth analysis of current diagnostic methods as well as the evolving and future directions of diagnostic strategies for NENs. Area covered: The review extensively covers the evolution of diagnostic tools for NENs, from traditional imaging and biochemical tests to advanced genomic profiling and next-generation sequencing. The emerging role of technologies such as artificial intelligence, machine learning, and liquid biopsies could improve diagnostic precision, as could the integration of imaging modalities such as positron emission tomography (PET)/magnetic resonance imaging (MRI) hybrids and innovative radiotracers. Expert opinion: Despite progress, there is still a significant gap in the early diagnosis of NENs. Bridging this diagnostic gap and integrating advanced technologies and precision medicine are crucial to improving patient outcomes. However, challenges such as low clinical awareness, limited possibility of noninvasive diagnostic tools and funding limitations for rare diseases like NENs are acknowledged.

Intrahepatic cholangiocarcinoma (iCCA) is recognized as the second most frequently diagnosed liver malignancy, following closely after hepatocellular carcinoma. Its incidence has seen a global upsurge in the past several years. Unfortunately, due to the lack of well-defined risk factors and limited diagnostic tools, iCCA is often diagnosed at an advanced stage, resulting in a poor prognosis. While surgery is the only potentially curative option, it is rarely feasible. Currently, there are ongoing investigations into various treatment approaches for unresectable iCCA, including conventional chemotherapies, targeted therapies, immunotherapies, and locoregional treatments. This study aims to explore the role of transarterial radioembolization (TARE) in the treatment of unresectable iCCA and provide a comprehensive review. The findings suggest that TARE is a safe and effective treatment option for unresectable iCCA, with a median overall survival (OS) of 14.9 months in the study cohort. Studies on TARE for unresectable iCCA, both as a first-line treatment (as a neo-adjuvant down-staging strategy) and as adjuvant therapy, have reported varying median response rates (ranging from 34% to 86%) and median OS (12-16 mo). These differences can be attributed to the heterogeneity of the patient population and the limited number of participants in the studies. Most studies have identified tumor burden, portal vein involvement, and the patient’s performance status as key prognostic factors. Furthermore, a phase 2 trial evaluated the combination of TARE and chemotherapy (cisplatin-gemcitabine) as a first-line therapy for locally advanced unresectable iCCA. The results showed promising outcomes, including a median OS of 22 mo and a 22% achievement in down-staging the tumor. In conclusion, TARE represents a viable treatment option for unresectable iCCA, and its combination with systemic chemotherapy has shown promising results. However, it is important to consider treatment-independe

Aims: The aim of this retrospective study was to investigate SUVs variability with respect to lesion size, administered dose, and reconstruction algorithm. Background: SUVmax and SUVpeak are influenced by technical factors as count statistics and reconstruction algorithms. Objective: To fulfill the aim, we evaluated the SUVs variability with respect to lesion size, administered dose, and reconstruction algorithm (ordered - subset expectation maximization plus point spread function option - OSEM+PSF, regularized Bayesian Penalized Likelihood - BPL) in a 5 - rings BGO PET/CT scanner. Method: Discovery IQ scanner (GE Healthcare, Milwaukee, Wisconsin, US) was used for list mode acquisition of 25 FDG patients, 12 injected with 3.7 MBq/kg (Standard Dose protocol - SD) and 13 injected with 1.8 MBq/kg (Low Dose protocol - LD). Each acquisition was reconstructed at different time/FOV with both OSEM+PSF algorithm and BPL using seven different beta factors. SUVs were calculated in 70 lesions and analysed in function of time/FOV and Beta. Image quality was evaluated as a coefficient of variation of the liver (CV - liver). Result: SUVs were not considerably affected by time/FOV. However, SUVs were influenced by beta: differences were higher in small lesions (37% for SUVmax, 15% for SUVpeak) compared to larger ones (14% and 6%). CV - liver ranged from 6% with Beta-500 (LD and SD) to 13% with Beta-200 (LD). CV - liver of BPL with Beta-350 (optimized for clinical practice in our institution) in LD was lower than CV - liver of OSEM+PSF in SD. Conclusion: When a high sensitivity 5 - rings BGO PET/CT scanner is used with the same reconstruction algorithm, quantification by means of SUVmax and SUVpeak is a robust standard compared to the activity and scan duration. However, both SUVs and image quality are influenced by reconstruction algorithms and the related parameters should be considered to obtain the best compromise between detectability, quantification, and noise.

Purpose: The present pilot study investigates the putative role of radiomics from [18F]FDG PET/CT scans to predict PD-L1 expression status in non-small cell lung cancer (NSCLC) patients. Methods: In a retrospective cohort of 265 patients with biopsy-proven NSCLC, 86 with available PD-L1 immunohistochemical (IHC) assessment and [18F]FDG PET/CT scans have been selected to find putative metabolic markers that predict PD-L1 status (< 1%, 1–49%, and ≥ 50% as per tumor proportion score, clone 22C3). Metabolic parameters have been extracted from three different PET/CT scanners (Discovery 600, Discovery IQ, and Discovery MI) and radiomics features were computed with IBSI compliant algorithms on the original image and on images filtered with LLL and HHH coif1 wavelet, obtaining 527 features per tumor. Univariate and multivariate analysis have been performed to compare PD-L1 expression status and selected radiomic features. Results: Of the 86 analyzed cases, 46 (53%) were negative for PD-L1 IHC, 13 (15%) showed low PD-L1 expression (1–49%), and 27 (31%) were strong expressors (≥ 50%). Maximum standardized uptake value (SUVmax) demonstrated a significant ability to discriminate strong expressor cases at univariate analysis (p = 0.032), but failed to discriminate PD-L1 positive patients (PD-L1 ≥ 1%). Three radiomics features appeared the ablest to discriminate strong expressors: (1) a feature representing the average high frequency lesion content in a spherical VOI (p = 0.009); (2) a feature assessing the correlation between adjacent voxels on the high frequency lesion content (p = 0.004); (3) a feature that emphasizes the presence of small zones with similar grey levels inside the lesion (p = 0.003). The tri-variate linear discriminant model combining the three features achieved a sensitivity of 81% and a specificity of 82% in the test. The ability of radiomics to predict PD-L1 positive patients was instead scarce. Conclusions: Our data indicate a possible role of the [18F]

A 56-year-old woman, previously treated for breast cancer, presented to gynecologists with a lump of the left labium major of the vulva. The FDG pattern resembled as a cIV stage vulvar cancer, whereas biopsy indicated metastases from breast cancer. Metastatic disease to the vulva is particularly uncommon, representing 5% to 8% of all vulvar cancer lesions. However, gynecological uptakes, including vulvar site, have to be kept in mind as a possible site of metastatic lesions from breast cancer.

Background and Objective: Motion due to patient’s breathing can introduce heavy bias in PET/CT, both in image quality and quantitation. This paper is a review of the main technical solutions available to manage movement in PET/CT studies: a) Respiratory Gated (RG), b) Motion Free (MF), c) End Expiration (EE), d) Banana Artefact Management (BAM) and e) Data Driven Gating (DDG). Methods: The most diffused solutions (RG, MF and EE) are based on LIST mode acquisition of a PET Field of View (4D FOV), centered on the anatomical region of interest; to link PET data not only to time and to spatial position but also to the corresponding breathing phase, the synchronized acquisition of the patient’s breathing curve is performed by an external tracking device. Different commercial tools to track and to record patient breathing cycle are available to associate the internal organ motion with a measurable external parameter; for example these systems can measure the pressure on a chest elastic belt, the air flow trough patient nose, the breath-in and breath-out air temperature or the markers movement on the thorax/ abdominal region. Recently DDG techniques are developed to correct respiratory motion without the help of external motion tracking devices and to obtain a comparable result to that based on standard RG protocols. Results: The final result of an RG or DDG protocol is a sequence of 3D images showing organs and lesions movement; using the other motion management options a single 3D motion-free image is obtained without motion artefacts and degradation. Compared to the previously described options the BAM solution is not a real motion management protocol but just a Banana Artefact correction technique obtained using an Attenuation Correction Map calculated merging the Whole Body Helical CT with a Cine CT on the diaphragm area. Conclusion: The motion management in PET/CT imaging shows benefits in terms of image quality, quantification and lesion detectability and it is usef

Objective To evaluate the combination of positron emission tomography/computed tomography (PET/CT) and sentinel lymph node (SLN) biopsy in women with apparent early-stage endometrial carcinoma. The correlation between radiomics features extracted from PET images of the primary tumor and the presence of nodal metastases was also analyzed. Methods From November 2006 to March 2019, 167 patients with endometrial cancer were included. All women underwent PET/CT and surgical staging: 60/167 underwent systematic lymphadenectomy (Group 1) while, more recently, 107/167 underwent SLN biopsy (Group 2) with technetium-99m +blue dye or indocyanine green. Histology was used as standard reference. PET endometrial lesions were segmented (n=98); 167 radiomics features were computed inside tumor contours using standard Image Biomarker Standardization Initiative (IBSI) methods. Radiomics features associated with lymph node metastases were identified (Mann-Whitney test) in the training group (A); receiver operating characteristic (ROC) curves, area under the curve (AUC) values were computed and optimal cut-off (Youden index) were assessed in the test group (B). Results In Group 1, eight patients had nodal metastases (13%): Seven correctly ridentified by PET/CT true-positive with one false-negative case. In Group 2, 27 patients (25%) had nodal metastases: 13 true-positive and 14 false-negative. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for pelvic nodal metastases were 87%, 94%, 93%, 70%, and 98% in Group 1 and 48%, 97%, 85%, 87%, and 85% in Group 2, respectively. On radiomics analysis a significant association was found between the presence of lymph node metastases and 64 features. Volume-density, a measurement of shape irregularity, was the most predictive feature (p=0001, AUC=0,77, cut-off 0.35). When t esting cut-off in Group B to discriminate metastatic tumors, PET false-negative findings were reduced from 14 to 8 (-43%).

Introduction 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is a diagnostic tool widely used in oncology, but to date there are no established recommendations for its use in malignant ovarian germ cell tumors. The aim of this study was to evaluate the role of 18F-FDG PET/CT in the clinical management of patients with malignant ovarian germ cell tumors. Methods This was a retrospective review of 18F-FDG PET/CT scans performed in patients diagnosed with malignant ovarian germ cell tumors treated at the gynecology department of San Gerardo Hospital (Monza, Italy) from June 2006 to December 2016. Data collected included clinical history, radiological, biochemical and pathological evaluation, treatment, follow-up, outcome, and clinical indication for the PET/CT scan. PET/CT findings were categorized as negative/normal (no abnormal FDG uptake or physiological uptake), positive/abnormal (FDG uptake considered to indicate active germ cell malignancy), or equivocal (FDG uptake of uncertain significance, not clearly correlated to neoplastic disease). Results A total of 69 PET/CT scans in 37 patients were evaluated. The mean age at diagnosis was 25 years (range 20–48). The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage I (22/37) disease and had a diagnosis of dysgerminomas (18/37). Imaging indications were initial staging before treatment (4/69, 6%), staging after inadequate staging surgery (24/69, 35%), restaging after adjuvant chemotherapy (17/69, 25%), relapse suspect (9/69, 13%), and follow-up (15/69, 21%). Pathology confirmation of PET/CT results was available in 28/69 (40.5%) studies. All negative PET/CT (15/28) cases were confirmed with laparoscopy as true negative; among 13/28 positive PET cases, histopathology confirmed 7 (54%) as true positive and 6 (46%) as false positive (5 inflammatory and 1 mature teratoma implants). Patient-based analysis showed 100% sensitivity, 71% specif

Background: A radiomic approach was applied in 18F-FDG PET endometrial cancer, to investigate if imaging features computed on the primary tumour could improve sensitivity in nodal metastases detection. One hundred fifteen women with histologically proven endometrial cancer who underwent preoperatve 18F-FDG PET/CT were retrospectively considered. SUV, MTV, TLG, geometrical shape, histograms and texture features were computed inside tumour contours. On a first group of 86 patients (DB1), univariate association with LN metastases was computed by Mann-Whitney test and a neural network multivariate model was developed. Univariate and multivariate models were assessed with leave one out on 20 training sessions and on a second group of 29 patients (DB2). A unified framework combining LN metastases visual detection results and radiomic analysis was also assessed.Results: Sensitivity and specificity of LN visual detection were 50% and 99% on DB1 and 33% and 95% on DB2, respectively. A unique heterogeneity feature computed on the primary tumour (the zone percentage of the grey level size zone matrix, GLSZM ZP) was able to predict LN metastases better than any other feature or multivariate model (sensitivity and specificity of 75% and 81% on DB1 and of 89% and 80% on DB2). Tumours with LN metastases are in fact generally characterized by a lower GLSZM ZP value, i.e. by the co-presence of high-uptake and low-uptake areas. The combination of visual detection and GLSZM ZP values in a unified framework obtained sensitivity and specificity of 94% and 67% on DB1 and of 89% and 75% on DB2, respectively.Conclusions: The computation of imaging features on the primary tumour increases nodal staging detection sensitivity in 18F-FDG PET and can be considered for a better patient stratification for treatment selection. Results need a confirmation on larger cohort studies

Purpose: The aim of the present study was to evaluate the added diagnostic value of respiratory-gated 4D18F–FDG PET/CT in liver lesion detection and characterization in a European multicenter retrospective study. Methods: Fifty-six oncological patients (29 males and 27 females, mean age, 61.2 ± 11.2 years) from five European centers, submitted to standard 3D–PET/CT and liver 4D–PET/CT were retrospectively evaluated. Based on visual analysis, liver PET/CT findings were scored as positive, negative, or equivocal both in 3D and 4D PET/CT. The impact of 4D–PET/CT on the confidence in classifying liver lesions was assessed. PET/CT findings were compared to histology and clinical follow-up as standard reference and diagnostic accuracy was calculated for both techniques. At semi-quantitative analysis, SUVmax was calculated for each detected lesion in 3D and 4D–PET/CT. Results: Overall, 72 liver lesions were considered for the analysis. Based on visual analysis in 3D–PET/CT, 32/72 (44.4%) lesions were considered positive, 21/72 (29.2%) negative, and 19/72 (26.4%) equivocal, while in 4D–PET/CT 48/72 (66.7%) lesions were defined positive, 23/72 (31.9%) negative, and 1/72 (1.4%) equivocal. 4D–PET/CT findings increased the confidence in lesion definition in 37/72 lesions (51.4%). Considering 3D equivocal lesions as positive, sensitivity, specificity, and accuracy were 88.9, 70.0, and 83.1%, respectively, while the same figures were 67.7, 90.0, and 73.8% if 3D equivocal findings were included as negative. 4D–PET/CT sensitivity, specificity, and accuracy were 97.8, 90.0, and 95.4%, respectively, considering equivocal lesions as positive and 95.6, 90.0, and 93.8% considering equivocal lesions as negative. The SUVmax of the liver lesions in 4D–PET (mean ± SD, 6.9 ± 3.2) was significantly higher (p < 0.001) than SUVmax in 3D–PET (mean ± SD, 5.2 ± 2.3). Conclusions: Respiratory-gated PET/CT technique is a valuable clinical tool in diagnosing liver lesions, reducing 3D undetermined fi

Aim: A review was conducted to update the recent published literature on sentinel lymph-node (SLN) procedures in endometrial cancer. Materials and methods: A comprehensive literature search was performed in PubMed and Cochrane library, searching from English language publication of the last 10 years about sentinel lymph node (SLN) in endometrial cancer. Eligible studies had a sample size > 30 patients and reported at least the detection rate. Detection rate, bilateral mapping rate, sensitivity (SN), and negative predictive value (NPV) were evaluated. Different techniques were assessed both for detection rate and for bilateral mapping. A subgroup analysis on studies focused on SPET was performed. Results: Forty studies were considered for the analysis (6162 patients). The overall detection rate of SLN mapping was 87.7% (95% CI 77.6–97.9%, range 62–100%). The pooled bilateral mapping rate was 59.9% (95% CI 43.2–76.6%, range 21–92%). The pooled SN resulted 98.3% (range: 50–100%) and the pooled NPV was 99.5% (range 86–100%). Cervical injection was the most used technique. Indocyanine green (ICG) and the combination of radiotracer/blue dye resulted in the highest SLN detection rates: 95% (95% CI 86–100%) and 90% (95% CI 79–100%) with cervical injection, respectively. ICG demonstrated the highest values of bilateral nodal mapping 75% (95% CI 60–91%) with cervical injection. Studies focused on SPET/CT showed a low/moderate correlation between SPET imaging and intraoperative findings. Conclusion: SLN mapping accurately predicts nodal status in women with endometrial cancer. Future prospective evaluation of prognosis/outcome is needed to define the impact of this technique for personalized therapy

The aim of this study was to assess the role of 18F-FDG PET/CT in preoperative staging of vulvar cancer patients. 29 pts (69 years, range 51-88) with vulvar cancer (clinical apparent stage I-II), underwent preoperative FDG-PET/CT scan followed by radical vulvectomy and bilateral (or monolateral in case of tumor >2 cm from midline) inguinal lymphadenectomy ± sentinel node biopsy. PET/CT images were analyzed in consensus and correlated to histological findings according to a pt-based and a groin-based analyses. SUV max of the nodal uptake of each inguinal area (if present) was calculated and correlated to histological findings. The presence of distant metastases was also considered and confirmed. PET/CT analysis in consensus resulted negative at the inguinal LN level in 17 pts (10 true negative, 7 false negative) and positive in 12 pts (7 true positive, 5 false positive). Incidence of LN metastases resulted 48%. On pt-based analysis, sensitivity, specificity, accuracy, and negative and positive predictive value of PET/CT in detecting LN metastases were 50%, 67%, 59%, 59%, and 58%, respectively. On a groin-based analysis, considering overall 50 LN-sites, sensitivity, specificity, accuracy, and negative and positive predictive value of PET/CT were 53%, 85%, 73%, 67%, and 76%, respectively. The mean value of SUV max was 6.1 (range 0.7-16.2) for metastatic nodes, whereas 1.6 (range 0.7 - 5.4) for negative lymph-nodes (P = .007). PET/CT detected pelvic (n = 1) and both pelvic/paraortic (n = 1) nodal metastases. In clinical early stage vulvar cancer FDG PET/CT showed low sensitivity and moderate specificity for N-staging; therefore, it is not an accurate tool for the nodal status assessment. PET/CT may not be cost-effective in detecting the rare event of distant metastases, but further studies are needed.

Study Objective To compare sentinel lymph node (SLN) mapping in women with cervical cancer stage >IB1 (tumor size >2 cm) using indocyanine green (ICG) versus the standard technique using radioisotope technetium 99m radiocolloid (Tc99m) radiotracer with or without blue dye. Design European multicenter, retrospective observational study (Canadian Task Force classification II-2). Setting Four academic medical centers. Patients Ninety-five women with stage IB1 cervical cancer (>2 cm) who underwent SLN mapping with Tc99m with or without blue dye or ICG and radical hysterectomy. Intervention The detection rate and bilateral mapping rate were compared between ICG and standard Tc99m radiotracer with or without blue dye. Lymphadenectomy was performed, and the false-negative rate was assessed. Measurements and Main Results Forty-seven patients underwent SLN mapping with Tc99m with or without blue dye, and 48 did so with ICG. All patients underwent radical hysterectomy with or without bilateral salpingo-oophorectomy between 2008 and 2016. The overall detection rate of SLN mapping was 91.5% for Tc99m with or without blue dye and 100% for ICG. A 91.7% rate of bilateral migration was achieved for ICG, significantly higher than the 66% obtained with Tc99m with or without blue dye (p =.025). Nine of the 23 SLN-positive patients (39.1%) were diagnosed exclusively as a result of the ultrastaging used to identify micrometastases or isolated tumor cells only. Conclusions In advanced cervical cancer (stage IB1 >2 cm), the detection rate and bilateral migration rate on real-time fluorescent SLN mapping were higher with ICG than with Tc99m radiotracer with or without blue dye. SLN mapping and ultrastaging can provide additional information for nodal staging in advanced cervical cancer. In this setting, ICG is a promising tool for mapping, appearing less affected by higher disease stage compared with traditional methods.

Objective: The aim of this study was to compare preoperative SPECT/CT with gamma-probe and methylene blue-dye (MBD) in the identification of sentinel lymph node (SLN) in early stage endometrial cancer. Methods: 40 stage-I EC patients (66.7 ± 9.7 years) underwent preoperative lymphoscintigraphy. After about 3 h from Tc-99m-albumin nanocolloid cervical injection, all patients underwent SPECT/CT study. MBD was injected into the cervix just before surgery under general anesthesia. All patients underwent SLN biopsy, hysterectomy, bilateral salpingo-oophorectomy, and radical regional lymphadenectomy. SPECT/CT findings were compared to those of gamma-probe and MBD techniques. Results: In 2 patients no nodal migration was observed, neither with MBD nor radiotracer. Detection rate of at least one SLN was 90% (36/40 patients) with SPECT/CT, 88% (35/40) intra-operatively with gamma-probe and 80% (32/40) with MBD. Only in 7/40 patients a bilateral migration was obtained with all considered modalities. In particular, bilateral detection was achieved in 26 patients with SPECT/CT, in 24 with gamma-probe and in 10 patients with MBD. The concordance site between SPECT/CT and intraoperative gamma-probe was 73% (29/40 patients: 2 without migration, 21 bilateral and 6 monolateral SLNs); while concordance site with MBD was found in 40% (16/40: 8 bilateral, 6 monolateral SLNs, 2 without SLNs). Overall, 628 LNs were dissected (mean 18 LNs per patient). The median number of SLNs removed was 2 (mean 2.5 per patient). Out of 91 SLNs: 43 were “hot and blue (HB)”, 10 were blue only and 38 were hot only. LN metastases rate was 16%: 9/90 SLNs (7 HB, 2 hot only) were positive for metastases in 6 patients. Four non-SLNs were found positive in 3 patients, and all presented concomitant positive SLNs. False negative rate was 0%. Conclusions: SPECT/CT had the highest detection rate and achieved the highest rate of bilateral mapping, compared to gamma-probe and MDB. SPECT/CT had moderate concordance wi

Objectives: The purpose of this study was to assess the quality of care in patients who underwent sentinel lymph node (SLN) mapping for endometrial and cervical cancer staging, and evaluate the impact of different techniques on patient satisfaction, i.e. radiotracer Tc99m versus indocyanine green (ICG) or methylene blue injection. Method: Women with preoperative stage I endometrial cancer or stage I (1A2–1B1) cervical cancer who underwent surgical staging, including SLN mapping, were considered for this study. Patient satisfaction was assessed using the European Organisation for Research and Treatment of Cancer IN-PATSAT32 questionnaire. Women were classified into two groups according to the different nodal mapping techniques: intracervical preoperative injection of Tc99m nanocolloid + intraoperative blue dye (Group 1) versus intraoperative cervical injection of ICG or blue dye (Group 2). Differences in patient satisfaction scores between the groups were analyzed. Results: Of the 178 eligible women, 143 were included in the study (endometrial cancer n = 106, cervical cancer n = 37): 57 underwent SLN mapping with Tc99m and blue dye (Group 1), and 86 women were mapped intraoperatively with blue dye alone or ICG (Group 2). Analysis of IN-PATSAT32 questionnaire scores showed a higher patient satisfaction score for patients in Group 2 (p = 0.001), which was independent of the physician and surgical outcomes evaluated. The scores were statistically better for Group 2, and also in rating doctors (p = 0.0001), nurses (p = 0.006), and care and services organizations (p = 0.001). Conclusions: Cervical and endometrial cancer patients who underwent SLN mapping by ICG or blue dye perceived a better quality of care when compared with those patients who underwent the combined radiocolloid and blue dye technique.