Giovanni Argiroffi

Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms with increasing incidence, particularly within the gastroenteropancreatic (GEP) system. The liver represents the most common site of metastasis, and neuroendocrine liver metastases (NELMs) significantly impact prognosis, symptom burden, and therapeutic decision-making. Surgical management remains a cornerstone in the treatment of NELMs and encompasses a spectrum of strategies, including curative liver resection, cytoreductive surgery, and, in selected cases, liver transplantation (LT). Hepatic resection, although potentially curative when technically feasible, is applicable only to a highly selected subset of patients, and its benefits in terms of long-term survival and symptom control remain limited by recurrence rates and patient-related factors. Cytoreductive surgery has emerged as a valuable alternative in patients with unresectable disease, with increasing evidence supporting a ≥70% debulking threshold as sufficient to achieve meaningful clinical benefit. This approach may improve survival and quality of life, notably in symptomatic patients, and can be combined with parenchymal-sparing techniques and locoregional therapies. Liver transplantation represents a radical but potentially curative strategy for highly selected patients with liver-only disease, favorable tumor biology, and stable disease. Outcomes are strongly dependent on strict selection criteria, and appropriate patient selection remains critical. The incorporation of systemic treatments, such as somatostatin analogues, targeted therapies, and peptide receptor radionuclide therapy (PRRT), has broadened the available therapeutic options and contributed to redefining current treatment strategies. Overall, the management of NELMs requires a multidisciplinary, individualized approach guided by tumor biology, disease distribution, and patient-specific factors, with the goal of optimizing survival outcomes and preserving quality of life.

Background: Autologous anti‐CD19 chimeric antigen receptor (CAR) T‐cell therapy is an effective treatment for approximately 40% of relapsed/refractory large B cell lymphomas (LBCL), and early identification of patients at risk for relapse or progression after CAR T‐cell therapy represents a clinical need.Methods: The authors conducted a single‐center prospective study on 47 relapsed/refractory LBCL receiving CAR T‐cell therapy to evaluate the prognostic value of baseline and after infusion ¹⁸F‐fluorodeoxyglucose positron emission tomography (PET)‐computed tomography. Qualitative and quantitative metabolic parameters were evaluated before lymphodepletion, at day 30 and 90 post‐infusion.Results: Deep variation of standardized uptake value (SUV)_mean between baseline and day 30 correlated with response at day 90 (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.01–2.2); p = .04) and better progression‐free survival (PFS) (HR, 0.63; 95% CI, 0.41–0.97); p = .04). In the overall population, 1‐year PFS was 63% for Deauville score (DS)1–3 and 39% for DS4–5 patients, respectively (p = .02), however, the prognostic role of DS was lost when survivals are analyzed by considering 38 patients not progressing at 30 days. In these patients, in partial response or stable disease, the combination of DS and variation of SUV_mean allowed identification of three groups with different prognosis: patients with DS1–3 and those with DS4–5 and decreased SUV_mean had similar 1‐year PFS of 62% and 61%, whereas patients with DS4–5 and increased SUV_mean had a poorer 1‐year PFS of 33% (p = .04).Conclusions: PET parameters and association of DS and variation of SUV_mean at 30 days could help in identify patients at high risk of CAR T‐cell failure.Lay summary: This is a single‐center prospective study on 47 lymphoma patients receiving commercial chimeric antigen receptor T‐cell therapy aimed to evaluate the prognostic value of baseline and after infusion ¹⁸F‐fluorodeoxyglucose positron emission tomography. Among patients in partial remission or stable disease at day 30, the authors observed two subgroups with significantly different prognosis; patients with Deauville score (DS)4–5 and a concomitant reduction of standardized uptake value (SUV)_mean had higher probability of long‐lasting response than those with DS4–5 and an increase of SUV_mean.

In this confirmatory study, we tested if a calculation that included the non-uniformity of dose deposition through a voxel-based dosimetric variable Ψ was able to improve the dose–response agreement with respect to the mean absorbed dose D. We performed dosimetry with ^99mTc-MAA SPECT/CT and ⁹⁰Y-PET/CT in 86 patients treated 8 instead of 4 days after the reference date with 2.8 times more ⁹⁰Y glass microspheres/GBq than in our previous study. The lesion-by-lesion response was assessed with the mRECIST method and with an experimental densitometric criterion. A total of 106 lesions were studied. Considering Ψ as a prognostic response marker, having no Ψ provided a significantly higher AUC than D. The correlation, t-test, and AUC values were statistically significant only with the densitometric method and only with post-therapy dosimetry. In comparison with our previous study, the dose–response correlation and AUC values were poorer (maximum r = 0.43, R² = 0.14, maximal AUC = 0.71), and the efficacy at a high dose did not reach 100%. The expected advantages of voxel dosimetry were nullified by the correlation between any Ψ and D due to the limited image spatial resolution. The lower AUC and efficacy may be explained by the mega-clustering effect triggered by the higher number of microspheres/GBq injected on day 8.

Objective: To give an updated overview on clinical aspects and survival effects of lutetium-177–prostate-specific membrane antigen (PSMA) (¹⁷⁷Lu-PSMA) radioligand therapy (RLT), a novel treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: PubMed/MEDLINE database was searched for relevant articles published up to March 2021. The search was restricted to English-language articles. Results: Current evidence from the literature consistently demonstrated the efficacy, safety, and survival benefit of ¹⁷⁷Lu-PSMA RLT in mCRPC. However, current data rely predominantly on retrospective analyses, showing heterogeneity of patient population and treatment protocols. More recently, results from the first randomized phase II study (TheraP) demonstrated that ¹⁷⁷Lu-PMSA therapy significantly improved prostate-specific antigen response rate (66% vs 37%) and had fewer grade 3/4 adverse events when compared to cabazitaxel in patients with docetaxel-pretreated, progressive mCRPC. This review is intended to provide an updated overview of treatment protocols and responses, toxicity profile, and survival effects of ¹⁷⁷Lu-PSMA RLT. Conclusions: ¹⁷⁷Lu-PSMA RLT has emerged as a promising targeted treatment in mCRPC. It is currently applied in compassionate use programs and following exhaustion of approved therapies. Crucial for establishing this treatment in routine clinical management will be the results of the phase III VISION trial, which may confirm the encouraging patient outcomes reported to date.

Meningiomas account for approximately 30% of all new diagnoses of intracranial masses. The 2016 World Health Organization’s (WHO) classification currently represents the clinical standard for meningioma’s grading and prognostic stratification. However, watchful waiting is frequently the chosen treatment option, although this means the absence of a certain histological diagnosis. Consequently, MRI (or less frequently CT) brain imaging currently represents the unique available tool to define diagnosis, grading, and treatment planning in many cases. Nonetheless, these neuroimaging modalities show some limitations, particularly in the evaluation of skull base lesions. The emerging evidence supporting the use of radiolabelled somatostatin receptor analogues (such as dota-peptides) to provide molecular imaging of meningiomas might at least partially overcome these limitations. Moreover, their potential therapeutic usage might enrich the current clinical offering for these patients. Starting from the strengths and weaknesses of structural and functional neuroimaging in meningiomas, in the present article we systematically reviewed the published studies regarding the use of radiolabelled dota-peptides in surgery and radiotherapy planning, in the restaging of treated patients, as well as in peptide-receptor radionuclide therapy of meningioma.

Trans-1-amino-3-¹⁸F-fluorocyclobutanecarboxylic-acid (anti-[¹⁸F]-FACBC) has been approved for the detection of prostate cancer (PCa) in patients with elevated prostate-specific-antigen following prior treatment. This review and meta-analysis aimed to investigate the diagnostic performance of ¹⁸F-FACBC positron emission tomography/computed-tomography (PET/CT) in the detection of primary/recurrent PCa. A bibliographic search was performed including several databases, using the following terms: “FACBC”/“fluciclovine” AND “prostate cancer”/“prostate” AND “PET”/“Positron Emission Tomography”. Fifteen and 9 studies were included in the systematic reviews and meta-analysis, respectively. At patient-based analysis, the pooled sensitivity and specificity of ¹⁸F-FACBC-PET/CT for the assessment of PCa were 86.3% and 75.9%, respectively. The pooled diagnostic odds-ratio value was 16.453, with heterogeneity of 30%. At the regional-based-analysis, the pooled sensitivity of ¹⁸F-FACBC-PET/CT for the evaluation of primary/recurrent disease in the prostatic bed was higher than in the extra-prostatic regions (90.4% vs. 76.5%, respectively); conversely, the pooled specificity was higher for the evaluation of extra-prostatic region than the prostatic bed (89% vs. 45%, respectively). ¹⁸F-FACBC-PET/CT seems to be promising in recurrent PCa, particularly for the evaluation of the prostatic bed. Additional studies to evaluate its utility in clinical routine are mandatory.