Silvia Taralli

Background: Spread through air spaces (STAS) is a prognostic factor for survival in non-small cell lung cancer (NSCLC), but the chance to identify it before surgery remains challenging. In this study, we consider clinical, pathological and metabolic factors, with the aim to identify possible STAS predictors in NSCLC. Methods: Clinical and pathological characteristics of patients who underwent anatomical lung resection from 1 January 2018 to 31 December 2023 were retrospectively reviewed and analyzed. Patients with GGO, AIS, or MIA tumors, metastases, or undergoing neoadjuvant therapy were excluded. The parameters assessed by ¹⁸F-FDG PET/CT were: SUVmax, SUVmean, SUVpeak, TLG and MTV. The primary endpoint was the association between clinical, metabolic, and pathologic characteristics with the presence of STAS. A univariate and multivariate logistic regression model was developed to identify independent predictors of STAS. Results: The final analysis was conducted on 224 patients. Non-lepidic-acinar adenocarcinomas showed a statistically significant higher risk of STAS than the lepidic-acinar histotype: 20.8% vs. 4.3%, p = 0.003, OR 5.87, 95%CI 1.83–18.78. Furthermore, tumor grade was significantly associated with STAS: 4.6% in G1–G2 tumors vs. 23.5% in G3 tumors (p = 0.001, OR 5.79, 95%CI 2.12–15.78); as well as lymph vascular invasion (p = 0.034) and tumor size >2 cm (p = 0.017). Multivariate analysis confirmed high tumor grade as an independent risk factor (OR 4.73, 95%CI 1.16–19.23, p = 0.030). Conclusions: In our study, risk of STAS is not correlated with metabolic parameters, while adenocarcinoma subtypes and tumors grading seem to stratify the risk of STAS occurrence. These results may be consolidated in an external validation analysis to possibly better plan the extent of lung resection.

Background/Objectives: Small-cell prostate cancer (SCPC) is a rare, aggressive variant of prostate cancer with poor prognosis, arising “de novo” or through lineage plasticity from conventional adenocarcinoma under androgen receptor-targeted therapies. Characterized by low PSA levels despite high tumor burden and visceral metastases, SCPC poses diagnostic challenges with conventional and PSMA-targeted imaging due to variable tracer uptake. This narrative review aims to evaluate the role of PET/CT tracers in clinical and preclinical settings for SCPC diagnosis, staging, and management. Methods: A systematic literature search was conducted on PubMed and Scopus up to December 2025 using terms “PET OR positron emission tomography AND prostate OR prostatic AND small-cell NOT non-small-cell”. Eight studies (five clinical, three preclinical) on the role of PET/CT imaging in SCPC were included and analyzed for study design, population, tracers, and findings, with comparative evaluation of diagnostic performance across PET tracers. Results: Clinical studies showed that ¹¹C-choline detects progression at low PSA but misses SCPC; ¹⁸F-FDG exhibited a high SUVmax value for distinguishing SCPC from adenocarcinomas with neuroendocrine differentiation, predicting poor survival; ⁶⁸Ga-DOTATATE identified NEPC/SCPC with promising prognostic/therapeutic value for selected cases. Preclinical models evaluated ⁸⁹Zr-tracers targeting DLL3 or CDCP1 (an antigen expressed in aggressive neuroendocrine tumours) and ¹⁸F-BnTP (a target of mitochondrial activity) in SCPC subtypes, focusing on translational imaging. Conclusions: From this review, although still based on limited literature evidence and mostly derived from retrospective and small SCPC sub-cohorts,¹⁸F-FDG PET/CT currently appears as the most reliable tracer for SCPC, aiding tumor detection and prognostication when PSMA/choline imaging fails. In the preclinical setting, DLL3/CDCP1-targeted agents emerge as promising theranostics tools. Multimodal imaging approach and prospective trials are needed for standardization and patient-based SCPC management.

Background/Objectives: Early progression (EP) occurs in a subset of patients with locally advanced pancreatic cancer (LAPC), limiting the clinical benefit of treatment, and it remains difficult to predict. Methods: We developed a multiparametric predictive model integrating baseline ¹⁸F-FDG PET/CT radiomic features with clinical and biological data. A total of 242 radiomic features were extracted from each imaging modality (CT and PET), including first-order, gray-level co-occurrence matrix (GLCM), and local binary pattern (LBP-TOP) features, and combined with PET-derived metrics and clinical variables. Model development included cross-validation procedures and rigorous feature selection, followed by the training of a two-level decision tree classifier. Results: The model achieved an accuracy of 80.7% and an area under the curve (AUC) of 0.83. Integrated analysis of CT and PET texture enabled the identification of patients at high risk of EP prior to treatment initiation. Conclusions: PET/CT-based radiomic biomarkers, combined with clinical data, can non-invasively capture tumor heterogeneity and improve risk stratification in LAPC, supporting more personalized therapeutic decision-making.

In this case report, we described the pitfalls in the differential diagnosis of a pituitary stalk lesion in a patient affected by Klinefelter Syndrome (KS) that was initially suspected of infundibulo-neuro-hypophysitis (INH). According to the atypical radiological picture for INH, the not-conclusive pathology findings, and the partial response to glucocorticoid treatment, a [18F] fluorocholine ([18F] FCH) positron emission computed tomography (PET-CT) scan was performed and identified a pituitary stalk proliferative lesion that was suggestive for neoplasia. This clinical case emphasizes the prospective and potential diagnostic role of the [18F] FCH PET-CT in pituitary stalk lesions and in the diagnosis of pituitary germinoma. Our article also includes a brief review of the literature, focusing on the differential diagnosis of lesions involving the pituitary stalk, the oncological risk associated with KS, and the role of nuclear imaging in the evaluation of such cases.

Purpose: To prospectively investigate dynamic ¹³N-ammonia PET-CT for evaluating early treatment response and predicting prognosis in advanced hepatocellular carcinoma (HCC) patients who have undergone antiangiogenic therapy. Methods: Dynamic ¹³N-ammonia PET-CT was performed in 23 advanced HCC patients before antiangiogenic therapy (baseline) and in 18/23 patients after 8-10 weeks of treatment (post-therapy). At kinetic PET-CT analysis, mean, maximum, and peak values of K₁ (mL/cm³/min) and k₂ (min⁻¹) were estimated in HCC lesions and non-neoplastic liver using cardiologic ¹³N-ammonia PET-CT in 15 patients without any liver diseases as normal controls. Outcome endpoints were treatment response after 8–10 weeks assessed by contrast-enhanced CT, progression-free survival (PFS), and overall survival (OS). Results: At both baseline and post-therapy PET-CT, all kinetic PET parameters were significantly higher (p < 0.05) in HCC lesions than in non-neoplastic and healthy liver of HCC patients and controls. According to mRECIST criteria, 13/18 patients (72.2%) were responders (1 CR, 1 PR, and 11 SD), and 5/18 patients (27.8%) were non-responders (PD), with no significant differences in baseline and post-therapy PET parameters between the two groups. At follow-up (median: 14.2 months), 15/18 patients (83.3%) experienced radiological progression, and 14/18 (77.8%) died (7/14 within 12 months from treatment). The nine earlier-progression patients (within 6 months from treatment) showed significantly lower baseline K_1mean in HCC lesions than all nine patients with later or no-progression (p = 0.03). Patients still alive 12 months after treatment (n = 11) showed significantly lower post-therapy K_1mean (p = 0.05), K_1max (p = 0.05), and K_1peak (p = 0.03) in non-neoplastic liver than patients with shorter OS (n = 7). Conclusions: In advanced HCC patients treated with antiangiogenic agents, kinetic parameters from baseline and post-therapy ¹³N-ammonia PET-CT may predict early disease progression and survival. PET-CT seems not able to discriminate responders and non-responders after 8-10 weeks of treatment, suggesting the need for future and larger studies after a longer treatment period.

Purpose To investigate metabolic parameters from baseline ¹⁸F-FDG PET/CT as predictors of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) and disease recurrence in locally advanced breast cancer (LABC) patients. Materials and methods From 142 LABC in 137 patients (bilateral-synchronous BC: 5/137), the following parameters from baseline (pre-treatment) ¹⁸F-FDG PET/CT were retrospectively analyzed, along with clinic-histological data: primary tumor activity (SUVmax, SUVmean, SUVpeak, tumor-to-liver ratio—TLR-, MTV, TLG); lymphoid organs activity (spleen and bone marrow SUVmax and SUVmean, spleen-to-liver ratio—SLR-, bone marrow-to-liver ratio—BLR); and PET-positive lymph-nodes’ number. Predictors of pCR and recurrence-free survival (RFS) were assessed by univariable logistic regression and Cox regression (significant or suggestive association: p < 0.05; p < 0.10). Results 74/142 tumors were “Luminal A/B HER2−”, 44/142 “Luminal B HER2+/HER2+”, 24/142 TNBC; pCR after NAC occurred in 26/142 tumors (18.3%) and disease recurrence at follow-up (45 ± 18.1 months) in 25/127 assessable patients (19.7%). Significant or suggestive predictors of NAC response, in Luminal A/B HER2−: lower spleen SUVmax and patients’ age (OR 0.06; 0.93) for pCR; lower TLRmax, TLRmean and BLRmax (OR 1.33; 1.22; and 26.42) for residual disease. Significant negative RFS predictors: higher SUVmax, SUVmean, SUVpeak (HR 1.10; 1.15; 1.11), TLRmax and TLRmean (HR 1.02; 1.00), MTV and TLG (HR 1.32; 1.26) in Luminal A/B HER2−; higher spleen SUVmax, PET-positive nodes’ number and patients’ age (HR 6.24; 1.20; 1.08) in Luminal B HER2+/HER2+. Conclusion Primary tumor and lymphoid organs parameters at baseline ¹⁸F-FDG PET/CT resulted as predictors of NAC response and prognosis in LABC patients, respectively, reflecting the BC cells’ proliferative activity and metabolic burden, and the role of tumor-induced immune-system activation on tumors’ behavior and treatment responsiveness. In LABC candidates to NAC, baseline PET information could improve treatment planning and prognostic stratification.

PET/CT using radiolabeled fibroblast activation protein inhibitors (FAPIs) is a promising diagnostic tool in oncology, especially when non-increased and/or physiologically high [¹⁸F]FDG uptake (as in liver parenchyma) is observed. We aimed to review the role of PET/CT using radiolabeled FAPIs in primary and/or metastatic liver lesions, and to compare their performances with more “conventional” radiopharmaceuticals. A search algorithm based on the terms “FAPI” AND (“hepatic” OR “liver”) was applied, with the last update on 1st January 2024. Out of 177 articles retrieved, 76 studies reporting on the diagnostic application of radiolabeled FAPI PET/CT in at least one patient harboring primary or metastatic liver lesion(s) were fully analyzed. Although there was some heterogeneity in clinical conditions and/or study methodology, PET/CT with radiolabeled FAPIs showed an excellent performance in common primary liver malignancies (hepatocarcinoma, intrahepatic cholangiocarcinoma) and liver metastases (mostly from the gastrointestinal tract and lungs). A higher tumor-to-background ratio for FAPIs than for [¹⁸F]FDG was found in primary and metastatic liver lesions, due to lower background activity. Despite limited clinical evidence, radiolabeled FAPIs may be used to assess the suitability and effectiveness of FAPI-derived therapeutic agents such as [¹⁷⁷Lu]Lu-FAPI. However, future prospective research on a wider population is needed to confirm the excellent performance.

Background: B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy. Medullary and extramedullary disease relapse is a well-known occurrence in B-ALL pediatric patients treated with standard chemo-immunotherapy and, more recently, with chimeric antigen receptor (CAR)-T cell therapy. ¹⁸F-Fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) emerges as a sensitive imaging tool for detecting disease relapse at extra-medullary sites, with only limited literature evidence in the CAR-T therapy setting. Case Report: In a 12-year-old female treated with CAR-T therapy for B-ALL relapse, ¹⁸F-FDG PET/CT scan performed for surveillance, after disease remission, detected a solitary and clinically occult relapse in the breast parenchyma that was histologically confirmed. Conclusion: At our knowledge, this is the first report about a pediatric B-ALL patient with a solitary and occult breast relapse after CAR-T therapy, early discovered by ¹⁸F-FDG PET/CT during disease monitoring.

Aim: The aim was to investigate the use of comprehensive pretreatment staging with multiple diagnostic modalities, including functional imaging and minimally invasive surgical procedures, in locally advanced pancreatic cancer (LAPC) patients. The primary objective was to detect occult metastatic disease using staging laparoscopy and 18F-FDG-positron emission tomography (PET)/computed tomography (CT) scan. The study also evaluated treatment efficacy and outcomes in LAPC patients treated with combined therapies. Materials and methods: This study was a secondary analysis of three prospective studies of chemoradiotherapy (CRT) with or without induction chemotherapy (IC). The inclusion period was from December 2009 until February 2023. An intensified pretreatment staging was conducted for all LAPC patients. Patients without distant disease at initial staging, with borderline resectable or unresectable LAPC, were enrolled in CRT combination protocols (CRT with or without IC). IC regimens included GemOx or FOLFIRINOX for four cycles, followed by concurrent CRT with gemcitabine. The primary endpoint was the detection of occult metastatic disease, and secondary objectives included resection rate, treatment toxicity, overall survival (OS), progression-free survival (PFS), local control, and metastasis-free survival. Results: Out of the 134 LAPC patients, 33.5% were identified with metastatic disease. Of these, 23.1% had a positive exploratory laparoscopy. Additionally, 13.4% were identified as having distant metastases by 18-FDG PET/CT. The median PFS for all patients who completed CRT was 14.3 months, and the median OS was 17.2 months. Resected patients after the combined therapies demonstrated significantly improved outcomes compared tonon-resected patients (median PFS, 22.5 months vs. 9.5 months, PPPPP=0.05), and this data was confirmed at multivariate analysis (95% CI: 0.09–0.98, P=0.04). Hematological and gastrointestinal toxicities were observed during treatment, with manageable adverse events. Conclusions: The use of comprehensive pretreatment staging, including laparoscopy and 18F-FDG-PET/CT scan, is an effective approach in identifying occult metastatic disease in LAPC patients. Our findings offer valuable insights into accurate staging and treatment efficacy, providing evidence-based support for optimal management strategies in LAPC patients.