Lutetium [177Lu]-DOTA-TATE in gastroenteropancreatic-neuroendocrine tumours: rationale, design and baseline characteristics of the Italian prospective observational (REAL-LU) study.

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.

Role of Transhepatic Arterial Radioembolization in Metastatic Colorectal Cancer.

The liver represents the most frequent location of metastatic disease in colorectal cancer (CRC). In oligometastatic disease, while surgery remains the mainstay of treatment, loco-regional therapies allow to locally control tumor progression and prolong survival. There is consensus in the use of transhepatic arterial radioembolization (TARE) in metastatic CRC chemorefractory patients, with liver-only or liver-dominant disease. Beyond this indication, TARE may be considered in other clinical scenarios, such as in the second-line combined with chemotherapy, as a bridge in between different lines of systemic therapies, and as ablative technique under specific circumstances. This paper outlines the current evidence for TARE in mCRC and presents possible future indications and directions.

Yttrium-90 transarterial radioembolization for liver metastases from medullary thyroid cancer.

Objectives: Liver metastases occur in 45% of patients with advanced metastatic medullary thyroid cancer (MTC). Transarterial radioembolization (TARE) has been proposed to treat liver metastases (LM), especially in neuroendocrine tumors. The aim of this study was to investigate the biochemical (calcitonin and carcino-embryonic antigen) and objective response of liver metastases from MTC to TARE. Methods: TARE is an internal radiotherapy in which microspheres loaded with ß-emitting yttrium-90 (90Y) are delivered into the hepatic arteries that supply blood to LM. Eight patients with progressive multiple LM underwent TARE and were followed prospectively. They were clinically, biochemically and radiologically evaluated at 1, 4, 12 and 18 months after TARE. Results: Two patients were excluded from the analysis due to severe liver injury and death due to extrahepatic disease progression, respectively. One month after TARE, a statistically significant (P = 0.02) reduction of calcitonin was observed in all patients and remained clinically relevant during follow-up; reduction of CEA, although not significant, was found in all patients. Significant reduction of liver tumor mass was observed 1, 4 and 12 months after TARE (P = 0.007, P = 0.004, P = 0.002, respectively). After 1 month, three of six patients showed partial response (PR) and three of six stable disease (SD) according to RECIST 1.1, while five of six patients had a PR and one of six a SD according to mRECIST. The clinical response remained relevant 18 months after TARE. Excluding one patient, all others showed only a slight and transient increase in liver enzymes. Conclusions: TARE is effective in LM treatment of MTC. The absence of severe complications and the good tolerability make TARE a valid therapeutic strategy when liver LM are multiple and progressive.

Management of Liver Tumors during the COVID-19 Pandemic: The Added Value of Selective Internal Radiation Therapy (SIRT).

BACKGROUND: In the context of the coronavirus disease 2019 (COVID-19) pandemic, liver-directed therapies (LDTs) may offer minimally invasive integrative tools for tumor control. Among them, selective internal radiation therapy (SIRT) represents a safe, flexible and effective treatment. Purpose of this study is to present our experience with SIRT during the first wave of COVID-19 pandemic and provide an overview of the indications and challenges of SIRT in this scenario. METHODS: We retrospectively analyzed the number of patients evaluated by Multidisciplinary Liver Tumor Board (MLTB) and who were undergoing LDTs between March and July 2020 and compared it with 2019. For patients treated with SIRT, clinical data, treatment details and the best radiological response were collected. RESULTS: Compared to 2019, we observed a 27.5% reduction in the number of patients referred to MLTB and a 28.3% decrease in percutaneous ablations; transarterial chemoembolizations were stable, while SIRT increased by 64%. The majority of SIRT patients (75%) had primary tumors, mostly HCC. The best objective response and disease control rates were 56.7% and 72.2%, respectively. CONCLUSION: The first wave of the COVID-19 pandemic was characterized by an increased demand for SIRT, which represents a safe, flexible and effective treatment, whose manageability will further improve by simplifying the treatment workflow, developing user-friendly and reliable tools for personalized dosimetry and improving interdisciplinary communication.

Assessment of radiation sensitivity of unresectable intrahepatic cholangiocarcinoma in a series of patients submitted to radioembolization with yttrium-90 resin microspheres.

Radioembolization is a valuable therapeutic option in patients with unresectable intrahepatic cholangiocarcinoma. The essential implementation of the absorbed dose calculation methods should take into account also the specific tumor radiosensitivity, expressed by the α parameter. Purpose of this study was to retrospectively calculate it in a series of patients with unresectable intrahepatic cholangiocarcinoma submitted to radioembolization. Twenty-one therapeutic procedures in 15 patients were analysed. Tumor absorbed doses were calculated processing the post-therapeutic 90Y-PET/CT images and the pre-treatment contrast-enhanced CT scans. Tumor absorbed dose and pre- and post-treatment tumor volumes were used to calculate α and α3D parameters (dividing targeted liver in n voxels of the same volume with specific voxel absorbed dose). A tumor volume reduction was observed after treatment. The median of tumor average absorbed dose was 93 Gy (95% CI 81-119) and its correlation with the residual tumor mass was statistically significant. The median of α and α3D parameters was 0.005 Gy-1 (95% CI 0.004-0.008) and 0.007 Gy-1 (95% CI 0.005-0.015), respectively. Multivariate analysis showed tumor volume and tumor absorbed dose as significant predictors of the time to tumor progression. The knowledge of radiobiological parameters gives the possibility to decide the administered activity in order to improve the outcome of the treatment.

[18F]-FDG-PET/CT Correlates With the Response of Radiorefractory Thyroid Cancer to Lenvatinib and Patient Survival.

CONTEXT: 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography ([18F]-FDG-PET/CT)-positive metastatic lesions in radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) have a poor prognosis and lenvatinib represents the best therapy. OBJECTIVE: We investigated the role of [18F]-FDG-PET/CT in the evaluation of metabolic response and prediction of the outcome of RAI-R DTC patients treated with lenvatinib. METHODS: Patients (n = 33) with progressive metastatic RAI-R DTC who were treated with lenvatinib were investigated at baseline and during follow-up with biochemical (thyroglobulin and thyroglobulin antibodies), morphological (whole-body CT scan) and metabolic ([18F]-FDG-PET/CT) evaluation. RESULTS: Nineteen (57.6%) patients showed the greatest metabolic response at the first [18F]-FDG-PET/CT scan, performed after 4 weeks of lenvatinib, while 5/33 (15.1%) patients had this response later. Moreover, 66.7% of patients had both a metabolic response at the first [18F]-FDG-PET/CT scan and a morphological response at the first CT scan. We observed a correlation between the metabolic response at [18F]-FDG-PET/CT scan performed after 4 weeks of treatment and the biochemical response at the same time in 60.6% of patients. The median overall survival (OS) was significantly longer in patients with either a metabolic response at last [18F]-FDG-PET/CT (40.00 vs 8.98 months) or a morphological response at last CT scan (37.22 vs 9.53 months) than in those without response. Moreover, the OS was longer in patients with a metabolic response at [18F]-FDG-PET/CT performed after 4 weeks of treatment (36.53 vs 11.28 months). CONCLUSIONS: Our data show that [18F]-FDG-PET/CT can early predict the response to lenvatinib and correlates with the OS of RAI-R DTC patients treated with this drug.

Yttrium-90 Radioembolization for Hepatocellular Carcinoma with Portal Vein Invasion: Validation of the Milan Prognostic Score.

The aim of the present study was to retrospectively analyze clinical outcomes of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) treated with yttrium-90 radioembolization stratified by Milan PVTT score according to PVTT extension, tumor burden, and bilirubin levels. Seventy patients were included and classified into good (n = 15; 21.4%), intermediate (n = 33; 47.1%), and dismal (n = 22; 31.4%) prognostic groups. Median overall survival durations were 24.6 mo, 13 mo (hazard ratio = 3.2; 95% confidence interval [CI], 1.2-9.7; P = .016), and 5.9 mo (hazard ratio = 4.1; 95% CI, 1.4-13.4; P = .0096), respectively. The Milan score represents an easy tool to select patients with HCC with PVTT who may benefit from radioembolization.

Yttrium-90 Radioembolization in Unresectable Intrahepatic Cholangiocarcinoma: Results of a Multicenter Retrospective Study.

BACKGROUND: Y90 transarterial radioembolization (Y90-RE) may improve clinical outcomes of unresectable intrahepatic cholangiocarcinoma (ICC); however, the optimal timing for Y90-RE is still debated. The purpose of this multicenter study was to retrospectively evaluate clinical outcomes of RE in patients with unresectable ICC, comparing three different settings: chemotherapy naïve patients (group A), patients with disease control after first-line chemotherapy (group B) and patients with progression after first-line chemotherapy (group C). MATERIALS AND METHODS: The study included 81 consecutive patients (49 male, mean age 62.4 ± 11.8 years): 35 (43.2%) patients were in group A, 19 (23.5%) in group B, and 27 (33.3%) in group C. Preprocedural clinical variables, tumour response according to RECIST 1.1 and overall survival (OS) were analysed and compared. RESULTS: Baseline demographic and clinical features did not differ significantly among groups, with the exception of prior surgical procedures that were significantly higher in group C patients, and macrovascular invasion that was more frequent in group B. Radiological response was available in 79 patients; objective response and disease control rates were 41.8% and 83.6%, respectively, without significant differences among groups. Median OS was 14.5 months (95% CI: 11.1-16.9) and was not significantly different among treatment groups. At multivariate analysis, tumour burden > 50%, neutrophil-to-lymphocyte (N/L) ratio ≥ 3 and radiological progression as best response resulted to be significant (P < 0.05) independent factors, negatively associated with OS. CONCLUSION: Y90-RE is a valuable treatment option in unresectable ICC, irrespectively from the timing of treatment. Tumour extension, N/L ratio and radiological response affect post-treatment survival.

The sentinel lymph node biopsy technique in papillary thyroid carcinoma: The issue of false-negative findings.

BACKGROUND: The management of papillary thyroid carcinoma (PTC) is changed after introduction of sentinel lymph node biopsy (SNB) technique for nodal staging. Some debate still surrounds the accuracy of this procedure in terms of wide heterogeneity of sentinel lymph node detection and false-negative findings. AIM: to identify the key issues which make it difficult the usefulness of SNB in PTC. METHODS: A comprehensive computer literature search of meta-analyses published in PubMed/MEDLINE and Cochrane library database until June 30, 2019 was conducted. We used a search algorithm based on this combination of terms: (i) "thyroid neoplasm" or "thyroid cancer" or "thyroid carcinoma" or "thyroid malignancy" or "meta-analysis" or "systematic review") AND (ii) "sentinel lymph node biopsy". RESULTS: Comparing 4 written meta-analyses published in the literature, the diagnostic performance of SNB technique in PTC has been summarized. Relatively high false-negative rates (FNR) were reported for each SNB methods: vital-dye (VD: 12.7%; 7%; 0-38%), 99mTc-nanocolloid planar lymphoscintigraphy with the use of intraoperative hand-held gamma probes (LS: 11.3%; 16%; 0-40%), combined LS with VD (LS+VD: 0%; 0-17%), LS with the additional contribution of preoperative SPECT/CT (7-8%). CONCLUSION: Evidence-based data about the diagnostic performance of SNB in PTC are increasing. The nuclear medicine community should reach a consensus on the operational definition of the SLN to better guide the surgeon in identifying the lymph nodes most likely contain metastatic cells. Standardization of SLN identification, removal and analysis are required.

Effect of Sentinel Node Biopsy in Clinically N0, BRAF V600E-Mutated, Small Papillary Thyroid Carcinoma: A Pilot Study.

PURPOSE: BRAF V600E mutation papillary thyroid cancer (PTC) is more aggressive with a higher risk of lymph node involvement and a poorer prognosis. Prior studies failed to demonstrate the superiority of prophylactic lymphadenectomy. We investigated the utility of additional radio-guided sentinel node biopsy (SNB). METHODS: We analyzed 15 patients with N0 PTC by ultrasound and BRAF mutation on preoperative biopsy treated with total thyroidectomy (TT) or TT + prophylactic central neck dissection (PCND) alone or with SNB. Conventional surgery was performed before SNB. We recorded primary tumor diameter, multifocality, extrathyroid infiltration, neoplastic emboli, and tall cell variant. At follow-up, we evaluated basal and stimulated thyroglobulin and ultrasound or radioiodine scintigraphy. RESULTS: Of 15 consecutive patients, 5 received conventional surgery alone, and 10 had SNB. For the first group, 4 underwent TT, and 1 had TT + PCND. Among the SNB group, 1 had no sentinel node detected and underwent a simple TT, 2 had TT + PCND+ SNB in the lateral compartment, and 7 had TT + SNB in 1 to 3 neck compartments. Micrometastases were found in 1 of 3 PCND specimens. Sentinel node biopsy revealed metastasis in 3 of 6 central compartment biopsies, in 2 of 6 biopsies in the ipsilateral lateral compartment, and in none of 2 biopsies in the contralateral compartment. Sentinel node biopsy allowed the removal of micrometastases in 4 of 10 patients. At 53 months' (mean) follow-up, no relapse was documented. CONCLUSIONS: Radio-guided SNB correctly and efficiently stages cN0 BRAF-mutated PTC patients. Sentinel node biopsy could limit time-consuming, risk-exposing compartmental prophylactic dissections.

Comparison between radioiodine therapy and single-session radiofrequency ablation of autonomously functioning thyroid nodules: A retrospective study.

OBJECTIVE: To compare the efficacy of Radioiodine (RI) and Radiofrequency ablation (RFA) in the treatment of autonomously functioning thyroid nodules (AFTNs). End-points: nodule volume reduction (NVR) and thyroid function normalization. DESIGN, PATIENTS AND MEASUREMENTS: Twenty-two patients (2:20 M:F; 51.9 ± 13.9 years) affected by 25 AFTNs, treated by RFA were retrospectively compared with 25 patients (8:17 M:F; 57.2 ± 12.8 years) affected by a single AFTN treated by RI. Both group showed analogous characteristics as to age, gender, toxic/pretoxic phase and pretreatment nodule volume (calculated by the ellipsoid formula). Thyroid hormone levels and autoimmune thyroid profile were assessed before treatment. A fixed RI activity of 555 MBq (15 mCi) was administered. RFA was performed with an 18G, single-tipped electrode, by the "modified moving shot technique." Thyroid hormones were assessed and the nodule post-treatment volume calculated 12 months after treatment. RESULTS: No statistical difference was found between the post-treatment NVR by comparing RI and RFA (P = 0.69). The volume reduction rates were 68.4 ± 28.9% and 76.4 ± 16.9% after RI and RFA, respectively. As to the thyroid function, 5/25 patients developed clinical hypothyroidism after RI. After RFA, all the 22 patients silenced their AFTN and normalized the thyroid hormones. Subclinical hypothyroidism was recorded in two patients after both RI and RFA. Thus, the functional therapeutic success, defined as the restoration of euthyroidism, was achieved in 18/25 (72%) patients treated by RI and in 20/22 (90.9%) treated by RFA. CONCLUSIONS: No statistical difference in NVR was found between RI and RFA. All patients responded to RI but 5/25 were "over-treated" developing hypothyroidism. RFA was effective in all patients with no case of post-treatment clinical hypothyroidism. No radiation exposure and lower risk of post-treatment hypothyroidism might make RFA the favourite option especially for young patients.

Sentinel Lymph Node Biopsy in Small Papillary Thyroid Cancer: A Meta-analysis.

PURPOSE: The aim of this study was to compare reported results on available techniques for sentinel lymph node detection rate (SDR) in papillary thyroid cancer (PTC). METHODS: The MEDLINE database was searched via a PubMed interface to identify original articles regarding sentinel lymph node biopsy (SNB) in thyroid cancer. Studies were stratified according to the sentinel lymph node (SLN) detection technique: vital-dye (VD), Tc-nanocolloid planar lymphoscintigraphy with the use of intraoperative hand-held gamma probes (LS), both Tc-nanocolloid planar lymphoscintigraphy with intraoperative use of hand-held gamma probe and VD (LS + VD), Tc-nanocolloid planar lymphoscintigraphy with the additional contribution of preoperative SPECT/CT, and intraoperative use of hand-held gamma probe (LS-SPECT/CT). Pooled SDR values were presented with a 95% confidence interval (CI) for each SLN detection techniques. A Z-test was used to compare pooled SDR estimates. False-negative rates were summarized for each method. RESULTS: Forty-five studies were included. Overall SDRs for the VD, LS, LS + VD, and LS-SPECT/CT techniques were 83% (95% CI, 77%-88%; I = 78%), 96% (95% CI, 90%-98%; I = 68%), 87% (95% CI, 65%-96%; I = 75%), and 93% (95% CI, 86%-97%; I = 0%), respectively. False-negative rates were 0% to 38%, 0% to 40%, 0% to 17%, and 7% to 8%, respectively. CONCLUSIONS: In patients with PTC, Tc-nanocolloids offer a higher SDR than that of the VD technique. The addition of SPECT/CT improved identification of metastatic SLNs outside the central neck compartment.

Sentinel lymph node biopsy in small papillary thyroid cancer. A review on novel surgical techniques.

PURPOSE: Sentinel lymph node biopsy (SNB) in patients with papillary thyroid carcinoma (PTC) and negative for clinically neck lymph node metastatic involvement (N0) has emerged as a promising minimally invasive procedure to detect metastatic nodes. METHODS: The MEDLINE database was searched via the PubMed interface on 10 January 2018 for the MeSH headings "sentinel lymph node biopsy" and "thyroid carcinoma". RESULTS: Vital blue dye, radioisotope, and the combination of both techniques are used in PTC patients. These methods and the emerging role of SPECT/CT are discussed in this review. The sentinel lymph node (SLN) identification rates ranged from 0 to 100% for blue dye, 83 to 100% for radioisotopes, and 66 to 100% for the combination of both techniques, respectively. CONCLUSIONS: SNB based on radioisotope technique with the use of intraoperative gamma-probe is an accurate and safe method that allows the highest SLN detection rate. There is sufficient evidence to propagate the increasing use of SNB procedure that has the potential to avoid prophylactic lymph node surgery in patients clinically N0.

223Ra-chloride therapy in men with hormone-refractory prostate cancer and skeletal metastases: Real-world experience.

BACKGROUND: Radium-223 (223Ra) chloride, an alpha emitter, has been shown to improve overall survival (OS) and pain control, and to delay skeletal-related events, in patients with castration-resistant prostate cancer (CRPC) and bone metastases. Our retrospective observational study presents the first Italian experience on the efficacy and safety of 223Ra therapy in routine clinical practice. METHODS: A total of 83 patients with metastatic CRPC were treated with 223Ra at 3 Italian centers between August 2013 and August 2016. 223Ra-chloride (55 kBq/kg) was administered every 4 weeks for a total of 6 cycles. Primary endpoints were OS and progression-free survival (PFS). Secondary endpoints included toxicity, pain evaluation using numeric rating scale (NRS), symptomatic skeletal-related events and biomarkers response. RESULTS: Patients had a median age of 75 (range 53-89) years. The majority of men showed a Gleason score of 7, 8, or 9. Forty-one patients completed 6 treatment cycles; 33 stopped treatment before completing 6 cycles. Nine were still receiving therapy at the time of data collection. At the end of therapy, NRS pain scores significantly improved ( p < .000001). OS was a mean of 10.1 months, while median OS had not been attained. According to Kaplan-Meier estimation, OS and PFS were 17.5 and 7.7 months, respectively. There was a significant correlation between OS and PFS with the number of 223Ra cycles; patients receiving all 6 cycles experienced the major benefit from the therapy. 223Ra was well-tolerated. CONCLUSIONS: 223Ra alpha therapy is an important therapeutic option for men with CRPC and symptomatic skeletal metastases.

Response Assessment by Volumetric Iodine Uptake Measurement: Preliminary Experience in Patients with Intermediate-Advanced Hepatocellular Carcinoma Treated with Yttrium-90 Radioembolization.

PURPOSE: To retrospectively compare early response to yttrium-90 radioembolization (Y90) according to volumetric iodine uptake (VIU) changes, Response Evaluation Criteria In Solid Tumor 1.1 (RECIST 1.1) and modified RECIST (mRECIST) in patients with intermediate-advanced hepatocellular carcinoma (HCC) and to explore their association with survival. MATERIALS AND METHODS: Twenty-four patients treated with Y90 and evaluated with dual-energy computed tomography before and 6 weeks after treatment were included. VIU was measured on late arterial phase spectral images; 6-week VIU response was defined as: complete response (CR, absence of enhancing tumor), partial response (PR, ≥ 15% VIU reduction), progressive disease (PD, ≥ 10% VIU increase) and stable disease (criteria of CR/PR/PD not met). RECIST 1.1 and mRECIST were evaluated at 6 weeks and 6 months. Responders included CR and PR. Overall survival (OS) was evaluated by Kaplan-Meier analysis and compared by Cox regression analysis. RESULTS: High intraobserver and interobserver agreements were observed in VIU measurements (k > 0.98). VIU identified a higher number of responders (18 patients, 75%), compared to RECIST 1.1 (12.5% at 6 weeks and 23.8% at 6 months) and mRECIST (29.2% at 6 weeks and 61.9% at 6 months). There was no significant correlation between OS and RECIST 1.1 (P = 0.45 at 6 weeks; P = 0.21 at 6 months) or mRECIST (P = 0.38 at 6 weeks; P = 0.79 at 6 months); median OS was significantly higher in VIU responders (17.2 months) compared to non-responders (7.4 months) (P = 0.0022; HR 8.85; 95% CI 1.29-88.1). CONCLUSION: VIU is highly reproducible; as opposite to mRECIST and RECIST 1.1, early VIU response correlates with OS after Y90 in intermediate-advanced HCC patients.

Clinical Impact of Radioguided Localization in the Treatment of Solitary Pulmonary Nodule: A 20-Year Retrospective Analysis.

PURPOSE: Incidental solitary pulmonary nodules (SPNs) have become an increasingly common CT finding worldwide. Although there are currently many imaging strategies for evaluating SPNs, the differential diagnosis and management of SPNs remains complex because of overlap between benign and malignant processes. Moreover, transbronchial or percutaneous CT-guided biopsies do not always allow definitive diagnoses. In such cases, video-assisted thoracic surgery (VATS) has become the preferred surgical procedure for diagnosis and, in selected cases, for treatment of indeterminate SPNs. The difficulties in localizing smaller, deeper, and ground-glass nodules have been approached with different techniques. The aim of this study was to report 20 years of experience with radioguided thoracoscopic resection of SPNs at the Regional Centre of Nuclear Medicine of Pisa. METHODS: Three hundred ninety-five patients with SPNs less than 2 cm and deeper than 5 mm below the visceral pleura underwent CT-guided injection of a suspension composed of 0.1 to 0.2 mL Tc-labeled human albumin macroaggregates (Tc-MAA) and of 0.2 to 0.3 mL of nonionic contrast medium into or adjacent to the SPN. During VATS, the pulmonary area with the highest target/background ratio identified by an 11-mm-diameter collimated thoracoscopic gamma probe was resected. RESULTS: From 1997 to 2016, approximately 395 patients with SPN underwent VATS wedge resection using the radioguided technique. Mean SPN size was 13 mm (range, 5-20 mm) with mean distance of 15 mm (range, 6-39 mm) from the visceral pleura. Mean VATS procedural time was 40 minutes (range, 20-90 minutes), with an average time of 3 minutes (range, 1-5 minutes) to localize the nodule. Neither mortality nor major perioperative complication was reported. The success rate of VATS with radioguidance in our series was 99%. Histological examination revealed 206 benign lesions (52%), 59 primary lung tumors (15%), and 130 metastatic nodules (33%). CONCLUSIONS: This study demonstrates that radioguided SPN localization by VATS is a feasible, safe, and rapid procedure with highly successful rate of SPN resection.

Management of metastatic castration-resistant prostate cancer: A focus on radium-223: Opinions and suggestions from an expert multidisciplinary panel.

Radium-223, a calcium mimetic bone-seeking radionuclide that selectively targets bone metastases with alpha particles, is approved for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases. In patients with mCRPC, treatment with radium-223 has been associated with survival benefit, regardless of prior docetaxel use, and also has a positive impact on symptomatic skeletal events and quality of life. Radium-223 is best suited for patients with symptomatic mCRPC and bone-predominant disease and no visceral metastases, and may lead to better outcomes when given early in the course of the disease. An expert multidisciplinary panel convened in Milan, Italy to review the current best-evidence literature on radium-223 and to convey their personal expertise with the use of radium-223 and identify possible strategies for best practice. This article summarizes the best available evidence for the use of radium-223, discusses the essential role of the multidisciplinary team in delivering effective treatment for mCRPC, clarifies pre- and post-treatment evaluation and monitoring, and outlines future scenarios for radium-223 in the treatment of men with MCRPC.