Due to its overexpression on the surface of prostate cancer cells, prostate-specific membrane antigen (PSMA) is a relatively novel effective target for molecular imaging and radioligand therapy (RLT) in prostate cancer. Recent studies reported that PSMA is expressed in the neovasculature of various types of cancer and regulates tumour cell invasion as well as tumour angiogenesis. Several authors explored the role of diagnostic and therapeutic PSMA radioligands in various malignancies. In this narrative review, we describe the current status of the literature on PSMA radioligands’ application in solid tumours other than prostate cancer to explore their potential role as diagnostic or therapeutic agents, with particular regard to the relevance of PSMA radioligand uptake as neoangiogenetic biomarker. Hence, a comprehensive review of the literature was performed to find relevant articles on the applications of PSMA radioligands in non-prostate solid tumours. Data on the general, methodological and clinical aspects of all included studies were collected. Forty full-text papers were selected for final review, 8 of which explored PSMA radioligand PET/CT performances in gliomas, 3 in salivary gland malignancies, 6 in thyroid cancer, 2 in breast cancer, 16 in renal cell carcinoma and 5 in hepatocellular carcinoma. In the included studies, PSMA radioligand PET showed promising performance in patients with non-prostate solid tumours. Further studies are needed to better define its potential role in oncological patients management, especially in those undergoing antineoangiogenic therapies, and to assess the efficacy of PSMA-RLT in this clinical context.

Growing studies have recently reported on the promising application of radiolabeled-fibroblast activation protein inhibitors (FAPIs) as diagnostic and therapeutic agents in various oncological populations. To exclusively evaluate the current evidence on the diagnostic and therapeutic role of FAPI radiotracers in patients with breast cancer (BC), a narrative review of the available literature was performed. A search algorithm from PubMed/MEDLINE, based on the combination of “PET” OR “positron emission tomography” and “FAPI” and ”cancer”, with a last update in February 2022, was applied. From 233 identified articles, 33 studies conducted in BC patients and with available data on PET imaging or radiolabeled-FAPI therapy were finally considered, for a total of 191 patients. Despite some clinical and methodological heterogeneity among the reviewed articles, ⁶⁸Ga-FAPI PET/CT emerges as a valuable diagnostic tool in BC patients both at staging and restaging, also demonstrating several technical advantages and an overall better performance than ¹⁸F-FDG, especially in histotypes with well-known low ¹⁸F-FDG avidity. Moreover, although with still limited clinical evidence in BC, radiolabeled FAPIs emerge as promising therapeutic agents in a theranostic perspective, increasing the possibility of more personalized treatments. From these results, future research directions on FAPI radiotracers application in BC patients are suggested.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin tumor. Currently, 18F-fluoro-deoxy-glucose (18F-FDG) PET/CT is the functional imaging modality of choice. Few data are available on the use of 68Ga-somatostatin analogs. The aim of our study was to evaluate and compare the diagnostic performance of 18F-FDG and 68Ga-somatostatin analog PET/CT in MCC patients. Fifteen patients (12 males, 3 females; median age 73 years; range 41–81 years) with histologically proven MCC (4 with unknown primary lesion) who underwent both 18F-FDG and 68Ga-somatostatin analog PET/CT for staging, re-staging, or treatment response assessment were retrospectively evaluated. Results of both studies were qualitatively analyzed and compared on a patient- and lesion-based analysis, using histology or clinical/radiological follow-up as reference standard for final diagnosis. According to final diagnosis, 8/15 patients had at least one MCC lesion and 7/15 had no evidence of disease. On a patient-based analysis, 18F-FDG and 68Ga-somatostatin analogs correctly classified as positive 8/8 (100% sensitivity) patients and as negative 6/7 (85.7% specificity) and 5/7 (71.4% specificity) patients, respectively, with no significant difference. On a lesion-based analysis, 18F-FDG detected 67/75 lesions (89%) and 68Ga-somatostatin analogs 69/75 (92%), with no significant difference. In four patients with unknown primary MCC, both tracers failed to identify the primary MCC site. Our preliminary data suggest that 18F-FDG and 68Ga-somatostatin analog PET/CT provide good and equivalent diagnostic performance, adding interesting insights into the complex MCC biology. However, these results do not suggest that 18F-FDG PET/CT should be replaced by 68Ga-somatostatin receptor imaging, which should be performed in addition, according to clinical indication, to the perspective of “personalized medicine.”

Introduction Multidisciplinary treatment strategy involving adjuvant radiotherapy for advanced vulvar cancer could be useful in offering the best personalized clinical approach. In 2013, the VULvar CANcer Multi-Disciplinary Team (Vul.Can MDT) was set up in our institution, in order to share knowledge and expertise, high-quality diagnosis, and evidence-based decision making in the context of personalized medicine. The aim of this observational study was to report on our series of vulvar cancer patients managed postoperatively with radiotherapy within the framework of a formal multidisciplinary tumor board. Methods Coupling surgical and oncological international guidelines with “case-by-case” discussions, a multi-specialist consensus was progressively reached and internal recommendations were developed and introduced in the daily routine. Data from vulvar cancer patients who underwent primary surgery and adjuvant radiotherapy throughout a 5-year period were retrospectively collected. Actuarial local control was the primary endpoint, while secondary end-points were acute and late toxicities, disease-free survival, and overall survival. Toxicity was evaluated according to the Common Toxicity Criteria Adverse Event v 4.0 scale. Results The analysis included 35 patients with squamous vulvar cancer treated with adjuvant radiotherapy±chemotherapy, from April 2013 to September 2017. Median age was 70 years (range 18–87), all patients underwent surgery followed by concomitant chemoradiation (45.7%) or radiotherapy alone (54.3%). The median prophylactic dose on lymphatic drainage was 45 Gy, while positive nodes and perineal area received 51.2 Gy and 52.6 Gy, respectively. Chemotherapy involved the cisplatin-based regimen (45.7%)±5-fluorouracil (37.1%). Median follow-up was 32 months (range 6–72): the 24-months local control, disease-free survival, and actuarial overall survival rates were 88.6%, 82.0%, and 91.0%, respectively. Low rates of severe acute (12%) and late (3%) toxicities occurred. Discussion The outcomes of this series support the benefit of a multidisciplinary personalized approach in the management of vulvar cancer.

Purpose: Gastroenteropancreatic -neuroendocrine tumours (GEP-NETs) are commonly treated with surgical resection or long-term therapies for tumour growth control. Lutetium [¹⁷⁷Lu]-DOTA-TATE was approved for the treatment of GEP-NETs after the phase III NETTER 1trial demonstrated improved progression free survival, objective response rates and health-related quality of life (HRQoL) compared to high-dose somatostatin analogues. No real-world data exist on prescribing habits and clinically significant endpoints for [¹⁷⁷Lu]Lu-DOTA-TATE treatment in Italy. REAL-LU is a multicentre, long-term observational study in patients with unresectable/metastatic GEP-NETs progressing on standard therapies in Italian clinical practice. A pre-specified interim analysis was performed at the end of the enrolment period, data from which are described herein. Methods: Overall duration of REAL-LU will be approximately 48 months, with 12- and 36-month recruitment and follow-up periods, respectively. The primary objective is to evaluate [¹⁷⁷Lu]Lu-DOTA-TATE effectiveness in terms of progression-free survival. Secondary objectives include safety, impact on HRQoL, and identification of prognostic factors. This pre-specified interim analysis describes patient profiles, at the end of enrollment, of those prescribed [¹⁷⁷Lu]Lu-DOTA-TATE for GEP-NETs in Italy. Results: Among 161 evaluable patients, mean age was 64.7 ± 10.3 years at study entry, 83.8% presented with no clinical signs of disease at physical examination, and most had minor disease symptoms. All patients had metastatic disease, most commonly in the liver (83.9%) with a median of two metastatic sites. In 90.7% of patients, the disease was stage IV, and 68.3% had ≥ 1 target lesion. [¹⁷⁷Lu]Lu-DOTA-TATE was prescribed mainly as second-line therapy (61.6%) and following surgery (58.4%). HRQoL assessments revealed high levels of functioning and low levels of symptoms at baseline; 50.0% of patients were symptom-free at study entry. Conclusion: The characteristics of patients who received [177Lu]Lu-DOTA-TATE in Italy are similar to those of the GEP-NET population of NETTER 1 with trial but with a higher proportion of patients with a grade 2 (71%). With regard to the tumor grade profile, our study cohort appears to be closer to that of NETTER-2 study population which included patients with G2 or G3 advanced GEP-NETs (i.e. Ki-67 ≥ 10% and ≤ 55%). Further analysis of effectiveness and safety can be anticipated as REAL-LU data mature. Study Registration: ClinicalTrials.gov, NCT04727723; Study Registration Date: 25 January, 2021; https://clinicaltrials.gov/study/NCT04727723?cond=NCT04727723&rank=1