Triple negative breast cancer (TNBC) is an aggressive subtype, still with limited therapeutic options. [18F]FDG PET/CT is widely used in TNBC, but evidence regarding its prognostic value remains limited. The TRINE PET study, promoted by the Italian Association of Nuclear Medicine, aimed to evaluate the prognostic relevance and clinical impact of [18F]FDG PET/CT in a large real world TNBC cohort. This retrospective multicenter study included 389 TNBC patients who underwent 707 [18F]FDG PET/CT scans across 23 Italian Nuclear Medicine Units. Clinical settings were baseline staging (n = 257 patients), post neoadjuvant chemotherapy (n = 111 patients), suspected recurrence (n = 144 patients), and advanced metastatic disease (n = 195 patients). Progression free survival (PFS) and overall survival (OS) were assessed using Kaplan–Meier and Cox regression analyses. The influence of [18F]FDG PET/CT on clinical management was evaluated across all settings. During a median follow up of 34 months (1–124), disease progression and death occurred in 39.3

BACKGROUND AND PURPOSE:Whether the performance in detecting local recurrent lesions is similar between multiparametric MRI (mpMRI) and PSMA PET/CT at biochemical failure after radical prostatectomy is controversial and the present study was done to elucidate this point within a prospective phase II on extreme hypofractionation for prostate cancer. MATERIALS AND METHODS:Patients referred for salvage radiotherapy after surgery for pT2-3pN0-x prostate cancer at a single Institution were considered. PSA at biochemical failure had to be higher than 0.2 ng/ml but lower than 2 ng/ml. Patients underwent both mpMRI of the pelvis and PSMA PET/CT. The detection of a discrete lesion within the prostatic fossa was considered the endpoint of the present study. The proportion of patients with positive findings in the two paired groups was compared with the McNemar test, while agreement with Cohen's k test. RESULTS:107 consecutive patients were accrued from September 2022 to September 2024. The mean PSA value at restaging was 0.53 ng/ml. Overall, 68 patients (63.5 %, 95 %CI: 54.1-72.1 %) were found to harbor at least one lesion in the prostatic fossa; 24 (35.3 %), 4 (5.9 %) and 40 (58.8 %) were detected only by mpMRI, only by PSMA PET/CT and by both tests, respectively. The percentage of discordant pairs was higher than expected (28/68, 41.2 %) and significantly different (p < 0.001). The Cohen's agreement between the two imaging modalities was 0.49, p < 0.001. CONCLUSION:mpMRI and PSMA PET/CT show inadequate agreement with the former detecting a significantly higher number of local lesions than the latter with both prognostic and therapeutic implications.

Background/Objectives: To evaluate the efficacy of balloon occlusion trans-arterial hepatic radioembolization with Yttrium-90 (b-TARE) in optimizing dose activity in patients with large or multifocal Hepatocellular Carcinoma (HCC) lesions with heterogeneous macroaggregate distribution by retrospectively comparing outcomes with a similar cohort treated with standard TARE. Methods: This single-center restrospective study included sixty-three consecutive patients with unresectable HCC treated with TARE, of whom 24/63 had balloon-occluded TARE and 39/63 had standard TARE. Both cohorts included large or multifocal HCC lesions characterized by heterogeneous macroaggregate distribution, also in relation to the angiosome framework. The impact of b-TARE was analyzed using 2D and 3D dosimetry with dedicated software on post-procedural SPECT-CT. Dosimetric b-TARE results were retrospectively compared with standard TARE. Results: Both 2D and 3D SPECT-CT analyses demonstrated a better dosimetry profile in the b-TARE group. Concerning 2D evaluation, the activity intensity peak was significantly higher in the b-TARE group compared to the TARE group (998.6 ± 394.9 vs. 578.8 ± 313.3, p = 0.004). Regarding 3D dose analysis, the mean intra-lesion dose administered was significantly higher in the b-TARE group (162.7 ± 54.3 Gy vs. 111.2 ± 44.5 Gy, p = 0.01). There was no increase in significant complications or in the mean dose delivered to the normal liver in the b-TARE group. Conclusions: The employment of balloon occlusion in TARE was associated with a higher activity intensity peak and lesion absorbed dose on voxel-based dosimetry, compared to standard TARE, in patients with heterogeneous HCC and uneven macroaggregate distribution, without increasing mean non-tumoral liver dose.

166Ho-poly-L-lactic acid microspheres (166Ho-PLLA) offer the advantage of using the same microspheres for both Scout and Therapeutic Administrations (SA and TA) in radioembolization compared to 90Y. This study aimed to quantify and correct dead time (DT) effects in dose estimation and assess the predictive power of SA on TA. A 1.9 GBq 166Ho-PLLA activity source was placed in a CIRS phantom and imaged over a week until activity reached 83 MBq, assessing DT effects. Fifteen patients with a single hepatic lesion underwent SA and TA two weeks apart with following SPECT/CT imaging. The mean absorbed dose (AD) and distribution were calculated using the Local Energy Deposition (LED) method for liver, healthy liver (HL) and tumor contours. Three methods were compared for TA AD estimation: no DT correction (M1), whole-image DT correction (M2), and DT correction only for tumor ROI counts (M3). Linear correlation and percentage differences (ΔD

PurposeHolmium-166 has emerged as a promising option for selective internal radiotherapy (SIRT) for hepatic malignancies, but data on routine clinical use are lacking. The purpose of this study was to describe the safety and effectiveness of Holmium-166 SIRT in real-world practice through retrospective analysis of a multicenter registry.MethodsRetrospective analysis was conducted on Holmium-166 SIRT procedures performed between July 15, 2019, and July 15, 2021, across seven European centers. Treatment planning, treatment realization and post-treatment follow-up were conducted according to routine local practice. Safety and effectiveness data were extracted from the patients’ health records. Primary endpoint analysis was assessed for the entire study population with separate analysis for subgroups with hepatocellular carcinoma, metastatic colorectal cancer and intrahepatic cholangiocarcinoma.ResultsA total of 167 SIRT procedures in 146 patients (mean age 66 ± 11 years, 68% male) were retrospectively evaluated. Most common tumor entities were hepatocellular carcinoma (n=55), metastatic colorectal cancer (n=35), intrahepatic cholangiocarcinoma (n=19) and metastatic neuroendocrine tumors (n=10). Nine adverse events grade ≥ 3 according to Common Terminology Criteria for Adverse Events were recorded, including one fatal case of radioembolization-induced liver disease. Response rates and median overall survival for the above mentioned subgroups were comparable to results from previous Holmium-166 trials as well as to results from Yttrium-90 registries.ConclusionThis study confirms that the safety and effectiveness of Holmium-166 SIRT derived from prospective trials also applies in routine clinical practice, reinforcing its potential as a viable treatment option for primary and secondary liver cancer.

Background This study aimed to evaluate the changes in 2-[18F]-FDG PET/CT parameters of lymphoid organs and their association with clinical outcomes in melanoma patients undergoing immunotherapy. Materials and methods Ninety-two consecutive patients with malignant melanoma were enrolled in the study. Patients underwent serial 2-[18F]-FDG PET/CT scans at baseline (PET0), 6 months (PET1), 18 months (PET2), and 36 months after starting immunotherapy. Visual and semiquantitative analyses were performed by two experienced nuclear medicine specialists. Bone marrow uptake was visually quantified using a scale system ranging from 1 to 5, mean standardized uptake values (SUVmean) of the liver and spleen were measured, and the Spleen Liver Ratio (SLR) was calculated. Clinical assessments and disease outcomes were recorded based on physical examinations, routine blood work, serum chemistry studies, and conventional imaging. Progression-free survival (PFS) and overall survival (OS) were also determined. Results Most patients received anti-PD1 therapy, and radiotherapy was combined with systemic treatment in some cases ( n = 12 patients). After 6, and 18 months, clinical disease control was achieved in 74% and 74%, respectively. Patients without clinical disease control exhibited higher bone marrow FDG uptake and an increase in the sites of metabolic lesions. Median SLR values were slightly higher in patients without disease control after 6 and 18 months, but lower after 36 months. At PET0, the median SLR was higher in alive patients than those who died, while it was similar in the following scans. Patients with signs of inflammation on PET1 had a higher baseline SLR, which decreased in the subsequent PET2 scan. Conclusions Changes in bone marrow FDG uptake may serve as potential indicators of treatment response and disease outcomes. SLR would be considered an interesting predictive and prognostic indicator. This study provides insights into the dynamic changes of metabolic parameters during immunotherapy and their clinical implications in malignant melanoma patients.

Background. Transarterial radioembolization (TARE) is an effective treatment to control tumor growth and improve survival in hepatocellular carcinoma (HCC). The role of TARE in downstaging patients to liver transplantation (LT) is unclear. The aim of this study was to investigate the downstaging efficacy of TARE for intermediate and advanced HCC. Methods. Intention-to-treat analysis with multistate modeling was performed. Patients moved through 5 health states: (1) from TARE to listing, (2) from TARE to death without listing, (3) from listing to LT, (4) from listing to death without LT, and (5) from transplant to death. Factors affecting the chance of death after TARE were considered to stratify outcomes. Results. Two hundred fourteen patients underwent TARE. Of those, 43.9% had radiological response, 29.9% were listed, and 22.8% were transplanted. The probability of being alive without LT was 40.5% 1 y after TARE and 11.5% at 5 y. The chance of being listed was 9.4% at 1 y and 0.9% at 5 y. The probability of dying after TARE without LT was 38% at 1 y and 73% at 5 y. The overall survival of patients receiving LT was 61% at 5 y after transplant. Tumor beyond up-to-seven criteria, alfafetoprotein >400 ng/mL, and albumin-bilirubin ≥2 were associated with death. Three risk groups were associated with different response, chances of being listed, and receiving LT. Median survival was 3 y for low-risk, 1.9 y for intermediate-risk, and 9 mo for high-risk patients (P < 0.001). Conclusions. In intermediate and advanced HCC, TARE allows for a 44% chance of response, 30% downstaging, and 23% probability of permitting LT. Patient’s and tumor’s characteristics allow for risk stratification and predict survival from TARE.

Background: Undifferentiated soft-tissue sarcomas (USTS) are one of the most common sarcoma histotypes in adults. The standard of care is surgical excision plus adjuvant radiotherapy, while the use of perioperative chemotherapy is still controversial. The aim of this study was to investigate the value of pre-treatment [18F]FDG PET/CT conventional metrics and textural features in predicting disease-free survival (DFS) and overall survival (OS) in patients with USTS of the limbs and trunk. Methods: [18F]FDG PET/CT scans of 51 consecutive patients with locally advanced USTS were retrospectively evaluated. Conventional and textural PET parameters were analysed and tested as predictive factors for DFS and OS. Results: During a median follow up of 50.7 months, 23 (45.1%) and 29 (56.9%) patients had death or disease progression, respectively. Univariate analysis revealed a significant association for perioperative treatment, PET volumetric parameters and the textural feature GLCM_correlation with DFS and OS. In multivariate analysis, perioperative treatment and GLCM_correlation were the only independent factors, allowing stratification of the population into three different prognostic classes. Conclusion: GLCM_correlation can identify USTS at high risk of relapse and death, thus helping to optimize the perioperative treatment of patients.

Aim: To assess the role of baseline 18F-fluorodeoxyglucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) in predicting response to immunotherapy after 6 months and overall survival (OS) in patients with lung cancer (LC) or malignant melanoma (MM). Methods: Data from a multicenter, retrospective study conducted between March and November 2021 were analyzed. Patients >18 years old with a confirmed diagnosis of LC or MM, who underwent a baseline [18F]FDG-PET/CT within 1-2 months before starting immunotherapy and had a follow-up of at least 12 months were included. PET scans were examined visually and semiquantitatively by physicians at peripheral centers. The metabolic tumor burden (number of lesions with [18F]FDG-uptake) and other parameters were recorded. Clinical response was assessed at 3 and 6 months after starting immunotherapy, and OS was calculated as the time elapsing between the PET scan and death or latest follow-up. Results: The study concerned 177 patients with LC and 101 with MM. Baseline PET/CT was positive in primary or local recurrent lesions in 78.5% and 9.9% of cases, in local/distant lymph nodes in 71.8% and 36.6%, in distant metastases in 58.8% and 84%, respectively, in LC and in MM patients. Among patients with LC, [18F]FDG-uptake in primary/recurrent lung lesions was more often associated with no clinical response to immunotherapy after 6 months than in cases without any tracer uptake. After a mean 21 months, 46.5% of patients with LC and 37.1% with MM had died. A significant correlation emerged between the site/number of [18F]FDG foci and death among patients with LC, but not among those with MM. Conclusions: In patients with LC who are candidates for immunotherapy, baseline [18F]FDG-PET/CT can help to predict response to this therapy after 6 months, and to identify those with a poor prognosis based on their metabolic parameters. For patients with MM, there was only a weak correlation between baseline PET/CT parameters, response to therapy, and survival.

A system for internal and voluntary reporting of abnormal events in a Nuclear Medicine Therapy Unit is described. This system is based on the Internet of Things and is composed of an application for mobile devices and a wireless network of detectors. The application is addressed to healthcare professionals and is intended to be a user-friendly tool to make the reporting procedure little laborious. The network of detectors allows for a real-time measurement of the dose distribution in the patient's room. The staff was involved in all stages, from the design of the dosimetry system and mobile application up to their final testing. Face-to-face interviews were carried out with 24 operators in different roles in the Unit (radiation protection experts, physicians, physicists, nuclear medicine technicians and nurses). The preliminary results of the interviews and the current state of development of the application and the detection network will be described.

Objective:The addition of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) to endocrine therapy impressively improved the outcome of patients with hormone receptor-positive metastatic breast cancer. Despite their great efficacy, not all patients respond to treatment and many of them develop acquired resistance. The aim of this retrospective study was to assess the role of [18F]-FDG PET/CT in predicting PFS and OS in breast cancer patients treated with CDK4/6i.Methods:114 patients who performed an [18F]-FDG PET/CT scan before (PET1) and 2-6 months (PET2) after starting treatment were retrospectively enrolled. Metabolic response was evaluated by EORTC, PERCIST and Deauville Score and correlated to PFS and OS.Results:In patients who did not progress at PET2 (n = 90), PFS rates were not significantly different between classes of response by EORTC and PERCIST. Conversely, patients showing a Deauville score ≤3 had a longer PFS (median PFS 42 vs 21.0 months; p = 0.008). A higher total metabolic tumor volume at PET1 (TMTV1) was also associated with a shorter PFS (median 18 vs 42 months; p = 0.0026). TMTV1 and Deauville score were the only independent prognostic factors for PFS at multivariate analysis and their combination stratified the population in four definite classes of relapse risk. Conversely, the above parameters did not affect OS which was only influenced by a progressive metabolic disease at PET2 (3-years survival rate 29.8 vs 84.9%; p<0.0001).Conclusion:TMTV and metabolic response by Deauville score were significant prognostic factors for PFS in patients with breast cancer treated with CDK4/6i. Their determination could help physicians to select patients who may need a closer follow up.

Background High dose unilobar radioembolization (also termed ‘radiation lobectomy’)—the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy—has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant. Methods The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m 2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose–response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank. Discussion This will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice. Trial registration Netherlands Trial Register NL8902 , registered on 2020–09-15.