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Purpose of Review: There is a critical need for timely and accurate decisions in breast cancer management. This narrative review aims to clarify the potential role of novel PET tracers in optimizing treatment strategies for different breast cancer subtypes., Recent Findings: 2-deoxy-2-[18F]-fluoro-D-glucose PET/computed tomography (FDG PET/CT) has a pivotal role in response assessment in metastatic breast cancer, despite its limitations in certain histological and molecular subtypes. Further PET radiopharmaceuticals have been proposed to address these clinical needing., Summary: FES PET/CT demonstrates its usefulness in assessing ER expression and predicting response to therapy in luminal breast cancer, with implications for treatment optimization and monitoring. In HER2-positive and HER2-low breast cancer, HER2-targeted PET tracers show potential in assessing HER2 status, while their accuracy in predicting response to targeted therapies is still debated. PARP-targeted PET imaging holds potential for selecting patients for PARP inhibitors treatments, particularly in triple-negative breast cancer (TNBC), where imaging tools are crucial due to the absence of specific targets. Immunotherapy and antibody-drug conjugates (ADCs) are emerging treatment options for TNBC, and PET imaging targeting immune checkpoints could aid in treatment selection and response monitoring. The dynamic role of PET/CT imaging in tailoring breast cancer treatments requires further multidisciplinary research to validate the clinical utility of targeted tracers., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To test the ability of high-performance machine learning (ML) models employing clinical, radiological, and radiomic variables to improve non-invasive prediction of the pathological status of prostate cancer (PCa) in a large, single-institution cohort., Methods: Patients who underwent multiparametric MRI and prostatectomy in our institution in 2015-2018 were considered; a total of 949 patients were included. Gradient-boosted decision tree models were separately trained using clinical features alone and in combination with radiological reporting and/or prostate radiomic features to predict pathological T, pathological N, ISUP score, and their change from preclinical assessment. Model behavior was analyzed in terms of performance, feature importance, Shapley additive explanation (SHAP) values, and mean absolute error (MAE). The best model was compared against a naïve model mimicking clinical workflow., Results: The model including all variables was the best performing (AUC values ranging from 0.73 to 0.96 for the six endpoints). Radiomic features brought a small yet measurable boost in performance, with the SHAP values indicating that their contribution can be critical to successful prediction of endpoints for individual patients. MAEs were lower for low-risk patients, suggesting that the models find them easier to classify. The best model outperformed (p ≤ 0.0001) clinical baseline, resulting in significantly fewer false negative predictions and overall was less prone to under-staging., Conclusions: Our results highlight the potential benefit of integrative ML models for pathological status prediction in PCa. Additional studies regarding clinical integration of such models can provide valuable information for personalizing therapy offering a tool to improve non-invasive prediction of pathological status., Clinical Relevance Statement: The best machine learning model was less prone to under-staging of the disease. The improved accuracy of our pathological prediction models could constitute an asset to the clinical workflow by providing clinicians with accurate pathological predictions prior to treatment., Key Points: • Currently, the most common strategies for pre-surgical stratification of prostate cancer (PCa) patients have shown to have suboptimal performances. • The addition of radiological features to the clinical features gave a considerable boost in model performance. Our best model outperforms the naïve model, avoiding under-staging and resulting in a critical advantage in the clinic. •Machine learning models incorporating clinical, radiological, and radiomics features significantly improved accuracy of pathological prediction in prostate cancer, possibly constituting an asset to the clinical workflow., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Salvage radiation therapy (sRT) is often the sole curative option in patients with biochemical recurrence after radical prostatectomy. After sRT, we developed and validated a nomogram to predict freedom from biochemical failure., Objective: This study aims to evaluate prostate-specific membrane antigen-positron emission tomography (PSMA-PET)-based sRT efficacy for postprostatectomy prostate-specific antigen (PSA) persistence or recurrence. Objectives include developing a random survival forest (RSF) model for predicting biochemical failure, comparing it with a Cox model, and assessing predictive accuracy over time. Multinational cohort data will validate the model's performance, aiming to improve clinical management of recurrent prostate cancer., Methods: This multicenter retrospective study collected data from 13 medical facilities across 5 countries: Germany, Cyprus, Australia, Italy, and Switzerland. A total of 1029 patients who underwent sRT following PSMA-PET-based assessment for PSA persistence or recurrence were included. Patients were treated between July 2013 and June 2020, with clinical decisions guided by PSMA-PET results and contemporary standards. The primary end point was freedom from biochemical failure, defined as 2 consecutive PSA rises >0.2 ng/mL after treatment. Data were divided into training (708 patients), testing (271 patients), and external validation (50 patients) sets for machine learning algorithm development and validation. RSF models were used, with 1000 trees per model, optimizing predictive performance using the Harrell concordance index and Brier score. Statistical analysis used R Statistical Software (R Foundation for Statistical Computing), and ethical approval was obtained from participating institutions., Results: Baseline characteristics of 1029 patients undergoing sRT PSMA-PET-based assessment were analyzed. The median age at sRT was 70 (IQR 64-74) years. PSMA-PET scans revealed local recurrences in 43.9% (430/979) and nodal recurrences in 27.2% (266/979) of patients. Treatment included dose-escalated sRT to pelvic lymphatics in 35.6% (349/979) of cases. The external outlier validation set showed distinct features, including higher rates of positive lymph nodes (47/50, 94% vs 266/979, 27.2% in the learning cohort) and lower delivered sRT doses (<66 Gy in 57/979, 5.8% vs 46/50, 92% of patients; P<.001). The RSF model, validated internally and externally, demonstrated robust predictive performance (Harrell C-index range: 0.54-0.91) across training and validation datasets, outperforming a previously published nomogram., Conclusions: The developed RSF model demonstrates enhanced predictive accuracy, potentially improving patient outcomes and assisting clinicians in making treatment decisions., (©Ali Janbain, Andrea Farolfi, Armelle Guenegou-Arnoux, Louis Romengas, Sophia Scharl, Stefano Fanti, Francesca Serani, Jan C Peeken, Sandrine Katsahian, Iosif Strouthos, Konstantinos Ferentinos, Stefan A Koerber, Marco E Vogel, Stephanie E Combs, Alexis Vrachimis, Alessio Giuseppe Morganti, Simon KB Spohn, Anca-Ligia Grosu, Francesco Ceci, Christoph Henkenberens, Stephanie GC Kroeze, Matthias Guckenberger, Claus Belka, Peter Bartenstein, George Hruby, Louise Emmett, Ali Afshar Omerieh, Nina-Sophie Schmidt-Hegemann, Lucas Mose, Daniel M Aebersold, Constantinos Zamboglou, Thomas Wiegel, Mohamed Shelan. Originally published in JMIR Cancer (https://cancer.jmir.org), 20.09.2024.)

Purpose: In radioguided surgery (RGS), radiopharmaceuticals are used to generate preoperative roadmaps (e.g., PET/CT) and to facilitate intraoperative tracing of tracer avid lesions. Within RGS, there is a push toward the use of receptor-targeted radiopharmaceuticals, a trend that also has to align with the surgical move toward minimal invasive robotic surgery. Building on our initial ex vivo evaluation, this study investigates the clinical translation of a DROP-IN β probe in robotic PSMA-guided prostate cancer surgery., Methods: A clinical-grade DROP-IN β probe was developed to support the detection of PET radioisotopes (e.g., 68  Ga). The prototype was evaluated in 7 primary prostate cancer patients, having at least 1 lymph node metastases visible on PSMA-PET. Patients were scheduled for radical prostatectomy combined with extended pelvic lymph node dissection. At the beginning of surgery, patients were injected with 1.1 MBq/kg of [ 68 Ga]Ga-PSMA. The β probe was used to trace PSMA-expressing lymph nodes in vivo. To support intraoperative decision-making, a statistical software algorithm was defined and optimized on this dataset to help the surgeon discriminate between probe signals coming from tumors and healthy tissue., Results: The DROP-IN β probe helped provide the surgeon with autonomous and highly maneuverable tracer detection. A total of 66 samples (i.e., lymph node specimens) were analyzed in vivo, of which 31 (47%) were found to be malignant. After optimization of the signal cutoff algorithm, we found a probe detection rate of 78% of the PSMA-PET-positive samples, a sensitivity of 76%, and a specificity of 93%, as compared to pathologic evaluation., Conclusion: This study shows the first-in-human use of a DROP-IN β probe, supporting the integration of β radio guidance and robotic surgery. The achieved competitive sensitivity and specificity help open the world of robotic RGS to a whole new range of radiopharmaceuticals., (© 2024. The Author(s).)

Purpose: To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading., Methods: PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUV max , PSMA volume , and total PSMA accumulation (PSMA total ) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4., Results: A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUV max , PSMA volume and PSMA total were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p < 0.05). Addition of all three parameters significantly improved the discrimination of clinical models in predicting GG ≥ 4 from 68% (95%CI 63 - 74) to 74% (95%CI 69 - 79) for SUV max , 72% (95%CI 67 - 76) for PSMA volume , 74% (70 - 79) for PSMA total and 75% (95%CI 71 - 80) when all parameters were included (all p < 0.05). Decision-tree analysis resulted in thresholds that discriminate between GG (SUV max 0-6.5, 6.5-15, 15-28, > 28, PSMA vol 0-2, 2-9, 9-20 and > 20 and PSMA total 0-12, 12-98 and > 98). PSMA volume was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 - 1.05). In patients with biopsy GG1-3, PSMA volume  ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMA volume  < 2 (OR 6.36, 95%CI 1.47 - 27.6)., Conclusion: Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice., (© 2024. The Author(s).)

Background: De novo oligometastatic prostate cancer (omPCa) on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is a new disease entity and its optimal management remains unknown., Objective: To analyze the outcomes of patients treated with cytoreductive radical prostatectomy (cRP) for omPCa on PSMA-PET., Design, Setting, and Participants: Overall, 116 patients treated with cRP at 13 European centers were identified. Oligometastatic PCa was defined as miM1a and/or miM1b with five or fewer osseous metastases and/or miM1c with three or fewer lung lesions on PSMA-PET., Intervention: Cytoreductive radical prostatectomy., Outcome Measurements and Statistical Analysis: Thirty-day complications according to Clavien-Dindo, continence rates, time to castration-resistant PCa (CRPC), and overall survival (OS) were analyzed., Results and Limitations: Overall, 95 (82%) patients had miM1b, 18 (16%) miM1a, and three (2.6%) miM1c omPCa. The median prebiopsy prostate-specific antigen was 14 ng/ml, and 102 (88%) men had biopsy grade group ≥3 PCa. The median number of metastases on PSMA-PET was 2; 38 (33%), 29 (25%), and 49 (42%) patients had one, two, and three or more distant positive lesions. A total of 70 (60%) men received neoadjuvant systemic therapy, and 37 (32%) underwent metastasis-directed therapy. Any and Clavien-Dindo grade ≥3 complications occurred in 36 (31%) and six (5%) patients, respectively. At a median follow-up of 27 mo, 19 (16%) patients developed CRPC and eight (7%) patients died. The 1-yr urinary continence rate was 82%. The 2-yr CRPC-free survival and OS were 85.8% (95% confidence interval [CI] 78.5-93.7%) and 98.9% (95% CI 96.8-100%), respectively. The limitations include retrospective design and short-term follow-up., Conclusions: Cytoreductive radical prostatectomy is a safe and feasible treatment option in patients with de novo omPCa on PSMA-PET. Despite overall favorable oncologic outcomes, some of these patients have a non-negligible risk of early progression and thus should be considered for multimodal therapy., Patient Summary: We found that patients treated at expert centers with surgery for prostate cancer, with a limited number of metastases detected using novel molecular imaging, have favorable short-term survival, functional results, and acceptable rates of complications., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose or Objective-The aim of the study is to evaluate the efficacy and safety of SBRT on detectable prostate bed recurrence in RT-naïve prostate cancer patients., Materials and Methods: Eighty-six patients who underwent SBRT for macroscopic bed recurrence after prostatectomy were retrospectively included. Patients were treated based on mpMRI or choline/PSMA PET., Results: The median time to biochemical relapse (BCR) after RP was 46 months, with a median PSA at restaging of 1.04 ng/mL. Forty-six patients were staged with mpMRI and choline/PSMA PET, while ten and thirty were treated based on PET and MRI only, respectively. Only one late G ≥ 2 GI toxicity was observed. With a median BCR follow-up of 14 months, twenty-nine patients experienced a BCR with a median PSA at recurrence of 1.66 ng/mL and a median survival free from the event of 40.1 months. The median time to BCR was 17.9 months. Twenty-seven patients had clinical relapse (CR), with a median CR follow-up of 16.27 months and a median time to CR of 23.0 months. Biochemical recurrence-free survival at one and two years was 88% and 66%, respectively, while clinical recurrence-free survival at one and two years was 92% and 82%, respectively. Regarding local relapses, seven were in the field of treatment, while eight of them were outside the field of treatment., Conclusions: Data showed that SBRT targeting only the macroscopic bed recurrence instead of the whole prostate bed is safe and effective. Additional data and longer follow-ups will provide a clearer indication of the appropriate treatment and staging methodology for these patients.

Background: Radio-guided surgery (RGS) holds promise for improving surgical outcomes in neuroendocrine tumors (NETs). Previous studies showed low specificity (SP) using γ-probes to detect radiation emitted by radio-labeled somatostatin analogs., Objective: We aimed to assess the sensitivity (SE) and SP of the intraoperative RGS approach using a β-probe with a per-lesion analysis, while assessing safety and feasibility as secondary objectives., Methods: This prospective, single-arm, single-center, phase II trial (NCT05448157) enrolled 20 patients diagnosed with small intestine NETs (SI-NETs) with positive lesions detected at 68 Ga-DOTA-TOC positron emission tomography/computed tomography (PET/CT). Patients received an intravenous injection of 1.1 MBq/Kg of 68Ga-DOTA-TOC 10 min prior to surgery. In vivo measurements were conducted using a β-probe. Receiver operating characteristic (ROC) analysis was performed, with the tumor-to-background ratio (TBR) as the independent variable and pathology result (cancer vs. non-cancer) as the dependent variable. The area under the curve (AUC), optimal TBR, and absorbed dose for the surgery staff were reported., Results: The intraoperative RGS approach was feasible in all cases without adverse effects. Of 134 specimens, the AUC was 0.928, with a TBR cut-off of 1.35 yielding 89.3% SE and 86.4% SP. The median absorbed dose for the surgery staff was 30 µSv (range 12-41 µSv)., Conclusion: This study reports optimal accuracy in detecting lesions of SI-NETs using the intraoperative RGS approach with a novel β-probe. The method was found to be safe, feasible, and easily reproducible in daily clinical practice, with minimal radiation exposure for the staff. RGS might potentially improve radical resection rates in SI-NETs., Clinical Trials Registration: 68 Ga-DOTATOC Radio-Guided Surgery with β-Probe in GEP-NET (RGS GEP-NET) [NCT0544815; https://classic., Clinicaltrials: gov/ct2/show/NCT05448157 ]., (© 2024. Society of Surgical Oncology.)

Metabolic alterations in cancers can be exploited for diagnostic, prognostic, and therapeutic purposes. This is exemplified by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (FDG-PET), an imaging tool that relies on enhanced glucose uptake by tumors for diagnosis and staging. By performing transcriptomic analysis of breast cancer (BC) samples from patients stratified by FDG-PET, a 54-gene signature (PETsign) is identified that recapitulates FDG uptake. PETsign is independently prognostic of clinical outcome in luminal BCs, the most common and heterogeneous BC molecular subtype, which requires improved stratification criteria to guide therapeutic decision-making. The prognostic power of PETsign is stable across independent BC cohorts and disease stages including the earliest BC stage, arguing that PETsign is an ab initio metabolic signature. Transcriptomic and metabolomic analysis of BC cells reveals that PETsign predicts enhanced glycolytic dependence and reduced reliance on fatty acid oxidation. Moreover, coamplification of PETsign genes occurs frequently in BC arguing for their causal role in pathogenesis. CXCL8 and EGFR signaling pathways feature strongly in PETsign, and their activation in BC cells causes a shift toward a glycolytic phenotype. Thus, PETsign serves as a molecular surrogate for FDG-PET that could inform clinical management strategies for BC patients., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Introduction: The aim of this article was to offer a comprehensive non-systematic review of the literature about the use of Nuclear Medicine imaging exams for the evaluation of prostate cancer (PCa) in the recurrent setting, with a particular regard to positron emission tomography/computed tomography (PET/CT) imaging., Evidence Acquisition: A comprehensive nonsystematic literature review was performed in March 2024. Literature search was updated until March 2024. The most relevant studies have been summarized, giving priority to registered clinical trials and multicenter collaborations., Evidence Synthesis: Restaging BCR with advanced Nuclear Medicine Imaging, such as prostate-specific membrane antigen-PET/CT could lead to stage migration and pave the way for additional management strategies, such as stereotactic ablative radiotherapy in patients with low-burden or oligometastatic disease, potentially delaying the need of systemic therapies. While OS benefits of targeting PET/CT positive disease are still lacking, data on progression- and metastasis-free-survival are emerging. Improvements in quality-of-life assessments are already evident., Conclusions: PCa is one of the most common malignancy in men. In the last 10 years PCa imaging has become significantly more accurate and is now essential for the definition of the extent of the disease in different phases of its natural history. This opened the road to novel management strategies, especially in the recurrent setting, in which the oligometastatic state is now being explored in several trials regarding the prognostic significance of metastasis directed therapies aimed at personalizing the treatment for every single patient.

Prostate cancer (PCa) remains a significant global health challenge, particularly in its advanced stages. Despite progress in early detection and treatment, PCa is the second most common cancer diagnosis among men. This review aims to provide an overview of current therapeutic approaches and innovations in PCa management, focusing on the latest advancements and ongoing challenges. We conducted a narrative review of clinical trials and research studies, focusing on PARP inhibitors (PARPis), phosphoinositide 3 kinase-protein kinase B inhibitors, immunotherapy, and radioligand therapies (RLTs). Data was sourced from major clinical trial databases and peer-reviewed journals. Androgen deprivation therapy and androgen-receptor pathway inhibitors remain foundational in managing castration-sensitive and early-stage castration-resistant PCa (CRPC). PARPi's, such as olaparib and rucaparib, have emerged as vital treatments for metastatic CRPC with homologous recombination repair gene mutations, highlighting the importance of personalized medicine. Immune checkpoint inhibitors (ICIs) have shown clinical benefit limited to specific subgroups of PCa, demonstrating significant improvement in efficacy in patients with microsatellite instability/mismatch repair or cyclin-dependent kinase 12 alteration, highlighting the importance of focusing ongoing research on identifying and characterizing these subgroups to maximize the clinical benefits of ICIs. RLTs have shown effectiveness in treating mCRPC. Different alpha emitters (like [ 225 Ac]PSMA) and beta emitters compounds (like [ 177 Lu]PSMA) impact treatment differently due to their energy transfer characteristics. Clinical trials like VISION and TheraP have demonstrated positive outcomes with RLT, particularly [ 177 Lu]PSMA-617, leading to FDA approval. Ongoing trials and future perspectives explore the potential of [ 225 Ac]PSMA, aiming to improve outcomes for patients with mCRPC. The landscape of PCa treatment is evolving, with significant advancements in both established and novel therapies. The combination of hormonal therapies, chemotherapy, PARPis, immunotherapy, and RLTs, guided by genetic and molecular insights, opens new possibilities for personalized treatment.

Background: High-level evidence on hypofractionated proton therapy (PT) for localized and locally advanced prostate cancer (PCa) patients is currently missing. The aim of this study is to provide a systematic literature review to compare the toxicity and effectiveness of curative radiotherapy with photon therapy (XRT) or PT in PCa., Methods: PubMed, Embase, and the Cochrane Library databases were systematically searched up to April 2022. Men with a diagnosis of PCa who underwent curative hypofractionated RT treatment (PT or XRT) were included. Risk of grade (G) ≥ 2 acute and late genitourinary (GU) OR gastrointestinal (GI) toxicity were the primary outcomes of interest. Secondary outcomes were five-year biochemical relapse-free survival (b-RFS), clinical relapse-free, distant metastasis-free, and prostate cancer-specific survival. Heterogeneity between study-specific estimates was assessed using Chi-square statistics and measured with the I2 index (heterogeneity measure across studies)., Results: A total of 230 studies matched inclusion criteria and, due to overlapped populations, 160 were included in the present analysis. Significant lower rates of G ≥ 2 acute GI incidence (2 % vs 7 %) and improved 5-year biochemical relapse-free survival (95 % vs 91 %) were observed in the PT arm compared to XRT. PT benefits in 5-year biochemical relapse-free survival were maintained for the moderate hypofractionated arm (p-value 0.0122) and among patients in intermediate and low-risk classes (p-values < 0.0001 and 0.0368, respectively). No statistically relevant differences were found for the other considered outcomes., Conclusion: The present study supports that PT is safe and effective for localized PCa treatment, however, more data from RCTs are needed to draw solid evidence in this setting and further effort must be made to identify the patient subgroups that could benefit the most from PT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Malignant pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare tumors and available systemic therapies are limited., Aim: To explore the role of peptide receptor radionuclide therapy (PRRT) with Yttrium-90 ( 90 Y) and Lutetium-177 ( 177 Lu) peptides in pheochromocytomas (PCCs) and paragangliomas (PGLs)., Methods: We retrospectively analyzed more than 1500 patients with histologically proven neuroendocrine tumors treated with 177 Lu- or 90 Y-DOTA-TATE or -TOC between 1999 to 2017 at our Institute. Overall, 30 patients with confirmed malignant PCCs and PGLs matched inclusion/exclusion criteria and were considered eligible for this analysis., Results: Thirty (n = 30) patients were treated: 22 with PGLs and 8 with PCCs (12 M and 18 F, median age 47 [IQR: 35-60 years]). Eighteen patients (n = 18) had head and neck PGLs, 3 patients thoracic PGLs and 1 patient abdominal PGL. Sixteen patients (53%) had locally advanced and fourteen (47%) had metastatic disease. Twenty-seven (90%) patients had disease progression at baseline. Four (13%) patients were treated with 90 Y, sixteen (53%) with 177 Lu and ten (33%) with 90 Y +  177 Lu respectively. The median total cumulative activity from treatment with 90 Y- alone was 9.45 GBq (range 5.11-14.02 GBq), from 177 Lu- alone was 21.9 GBq (7.55-32.12 GBq) and from the combination treatment was 4.94 GBq from 90 Y- and 6.83 GBq from 177 Lu- (ranges 1.04-10.1 and 2.66-20.13 GBq, respectively). Seven out of 30 (23%) patients had partial response and 19 (63%) stable disease. Median follow up was 8.9 years (IQR: 2.9-12). The 5-y and 10-y PFS was 68% (95% CI: 48-82) and 53% (95% CI: 33-69), respectively, whereas 5-y and 10-y OS was 75% (95% CI: 54-87) and 59% (95% CI: 38-75), respectively. Grade 3 or 4 acute hematological toxicity occurred in three patients, two with leucopenia and one with thrombocytopenia, respectively., Conclusion: PRRT with 177 Lu- or 90 Y-DOTA-TATE or -TOC is feasible and well tolerated in advanced PGLs and PCCs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the last decades, the development of PET/CT radiopharmaceuticals, targeting the Prostate-Specific Membrane Antigen (PSMA), changed the management of prostate cancer (PCa) patients thanks to its higher diagnostic accuracy in comparison with conventional imaging both in staging and in recurrence. Alongside molecular imaging, PSMA was studied as a therapeutic agent targeted with various isotopes. In 2021, results from the VISION trial led to the Food and Drug Administration (FDA) approval of [ 177 Lu]Lu-PSMA-617 as a novel therapy for metastatic castration-resistant prostate cancer (mCRPC) and set the basis for a radical change in the future perspectives of PCa treatment and the history of Nuclear Medicine. Despite these promising results, primary resistance in patients treated with single-agent [ 177 Lu]Lu-PSMA-617 remains a real issue. Emerging trials are investigating the use of [ 177 Lu]Lu-PSMA-617 in combination with other PCa therapies in order to cover the multiple oncologic resistance pathways and to overcome tumor heterogeneity. In this review, our aim is to retrace the history of PSMA-targeted therapy from the first preclinical studies to its future applications in PCa.

Aim: The present work reports updated oncological results and patients-reported outcomes at 5 years of phase II trial "Short-term high precision RT for early prostate cancer with SIB to the dominant intraprostatic lesion (DIL) for patients with early-stage PCa"., Methods: Data from patients enrolled within AIRC IG-13218 (NCT01913717) trial were analyzed. Clinical and GU/GI toxicity assessment and PSA measurements were performed every 3 months for at least 2 years after RT end. QoL of enrolled patients was assessed by IPSS, EORTC QLQ-C30, EORTC QLQ-PR25, and IIEF-5. Patients' score changes were calculated at the end of RT and at 1, 12, and 60 months after RT., Results: A total of 65 patients were included. At a median follow-up of 5 years, OS resulted 86%. Biochemical and clinical progression-free survival at 5 years were 95%. The median PSA at baseline was 6.07 ng/ml, while at last follow-up resulted 0.25 ng/ml. IPSS showed a statistically significant variation in urinary function from baseline (p = 0.002), with the most relevant deterioration 1 month after RT, with a recovery toward baseline at 12 months (p ≤ 0.0001). A numerical improvement in QoL according to the EORTC QLQ-C30 has been reported although not statistically significant. No change in sexual activity was recorded after RT., Conclusions: The study confirms that extreme hypofractionation with a DIL boost is safe and effective, with no severe effects on the QoL. The increasing dose to the DIL does not worsen the RT toxicity, thus opening the possibility of an even more escalated treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Pre-operative diagnosis and staging of small intestine neuroendocrine tumors (SI-NETs) remain sub-optimal, with open palpation during surgery still considered the gold standard. This limits a standardized implementation of minimally invasive surgery (MIS). The aim of this single-center retrospective study was to assess a tailored diagnostic work-up to identify candidates at low risk of undetected disease who may benefit from MIS., Methods: Patients diagnosed with SI-NETs between 2013 and 2022 who underwent contrast-enhanced computed tomography enterography (CTE) and Ga68-DOTATOC-positron emission tomography-CT (68 Ga DOTATATE PET/CT) preoperatively and subsequently underwent open surgical resection were included. Imaging studies were reassessed by two radiologists. Combined use of CTE and 68 Ga DOTATATE PET/CT in determining primary lesion disease burden (number of lesions) and LN disease stage (distal and proximal relative to superior mesenteric vessels) was assessed, using surgical reports and pathology as gold standard., Results: Overall, 56 patients were included. Sensitivity of CTE and 68 Ga DOTATATE PET/CT for at least one primary SI-NET was 100% and 94%, respectively. In the presence of concordance between studies, combined use of CTE and 68 Ga DOTATATE PET/CT for detection of single primary tumors improved specificity to 89% (n = 25/28) with a positive predictive value of 87.5% (n = 21/24). Distal LN disease was identified in 89.2% of cases (n = 33/37). The association of single lesion and distal LN disease was found pre-operatively in 32% of patients (n = 18)., Conclusion: Combined use of CTE and 68 Ga DOTATATE PET/CT enables identifying low-risk surgical candidates (single SI-NET lesions with distal LN disease)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Natural Cannabis (NC) and Synthetic Cannabinoids (SCs) use can increase the risk and exacerbate the course of psychotic disorders. These could be influenced by the Aberrant Salience (AS) construct. It refers to an excess of attribution of meaning to stimuli that are otherwise regarded as neutral, thereby transform them into adverse, dangerous, or mysterious entities. This leads the patient to engage in aberrant and consequently incorrect interpretative efforts concerning the normal perception of reality and its relationship with our analytical abilities. AS appears to play a significant role in the onset and perpetuation of psychotic disorders. The internal conflict arising from aberrant attributions of significance leads to delusional thoughts, ultimately culminating in the establishment of a self-sustaining psychosis., Aims: To examine the differences between psychoses course not associated with cannabis use and those associated with NC-use and SCs-use, in terms of psychotic and dissociative symptoms, AS, global functioning and suicidal ideation., Methods: A sample of 62 patients with First Episode Psychosis (FEP) was divided into 3 groups: non cannabis users (non-users, N  = 20); NC-users or rather Delta-9-tetrahydrocannabinol (THC) users (THC-users, N  = 21); SCs-users, commonly referred to as SPICE-users (SPICE-users, N  = 20). Each group underwent assessments at the onset of psychotic symptoms, as well as at the 3 months and 6 months marks, utilizing a range of psychopathological scales. These included the Positive and Negative Syndrome Scale (PANSS) for investigating psychotic symptoms, the Global Assessment of Functioning (GAF) scale for assessing overall functioning, the Dissociative Experiences Scale (DES-II) for measuring dissociative symptoms, the Scale for Suicide Ideation (SSI) for evaluating suicidal ideation and the Aberrant Salience Inventory (ASI) scale for gauging AS., Results: SPICE-users showed more severe and persistent positive symptoms, while negative symptoms were mostly represented among non-users. Non-users showed better recovery than SPICE-users in global functioning. All groups showed a decrease in both ASI scores and subscale scores. SPICE-users exhibited higher global AS scores and less improvement in this aspect compared to other groups., Conclusion: This study may help understanding the role of AS in both non-substance-related and substance-induced psychosis. This knowledge may lead clinician to a better diagnosis and identify patient-tailored psychopharmacological treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ricci, Di Muzio, Ceci, Di Carlo, Mancusi, Piro, Paggi, Pettorruso, Vellante, De Berardis, Martinotti and Maina.)

Prostate cancer (PCa) is the most common cancer diagnosed in men in most developed countries and a leading cause of cancer-related morbidity and mortality. Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has become a valuable tool in the staging and assessment of disease recurrence in PCa, and more recently for assessment for treatment eligibility to PSMA radioligand therapy (RLT). Harmonization of PSMA-PET interpretation and synoptic reports are needed to communicate concisely and reproducibly PSMA-PET/CT to referring physicians and to support clinician therapeutic management decisions in various stages of the disease. Uniform image interpretation is also important to provide comparable data between clinical trials and to translate such data from research to daily practice. This review provides an overview of the value of PSMA-PET across the different clinical stages of PCa, discusses published reporting criteria for PSMA-PET, identifies pitfalls in reporting PSMA, and provides recommendations for synoptic reports., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Currently, main treatment strategies for early-stage non-small cell lung cancer (ES-NSCLC) disease are surgery or stereotactic body radiation therapy (SBRT), with successful local control rates for both approaches. However, regional and distant failure remain critical in SBRT, and it is paramount to identify predictive factors of response to identify high-risk patients who may benefit from more aggressive approaches. The main endpoint of the MONDRIAN trial is to identify multi-omic biomarkers of SBRT response integrating information from the individual fields of radiomics, genomics and proteomics., Methods: MONDRIAN is a prospective observational explorative cohort clinical study, with a data-driven, bottom-up approach. It is expected to enroll 100 ES-NSCLC SBRT candidates treated at an Italian tertiary cancer center with well-recognized expertise in SBRT and thoracic surgery. To identify predictors specific to SBRT, MONDRIAN will include data from 200 patients treated with surgery, in a 1:2 ratio, with comparable clinical characteristics. The project will have an overall expected duration of 60 months, and will be structured into five main tasks: (i) Clinical Study; (ii) Imaging/ Radiomic Study, (iii) Gene Expression Study, (iv) Proteomic Study, (v) Integrative Model Building., Discussion: Thanks to its multi-disciplinary nature, MONDRIAN is expected to provide the opportunity to characterize ES-NSCLC from a multi-omic perspective, with a Radiation Oncology-oriented focus. Other than contributing to a mechanistic understanding of the disease, the study will assist the identification of high-risk patients in a largely unexplored clinical setting. Ultimately, this would orient further clinical research efforts on the combination of SBRT and systemic treatments, such as immunotherapy, with the perspective of improving oncological outcomes in this subset of patients., Trial Registration: The study was prospectively registered at clinicaltrials.gov (NCT05974475)., (© 2023. The Author(s).)

Background: In the initial staging of patients with high-risk prostate cancer (PCa), prostate-specific membrane antigen positron emission tomography (PSMA-PET) has been established as a front-line imaging modality. The increasing number of PSMA-PET scans performed in the primary staging setting might be associated with decreases in biochemical recurrence (BCR)-free survival (BCR-FS)., Objective: To assess the added prognostic value of presurgical PSMA-PET for BCR-FS compared with the presurgical Cancer of the Prostate Risk Assessment (CAPRA) and postsurgical CAPRA-Surgery (CAPRA-S) scores in patients with intermediate- to high-risk PCa treated with radical prostatectomy (RP) and pelvic lymph node dissection., Design, Setting, and Participants: This is a follow-up study of the surgical cohort evaluated in the multicenter prospective phase 3 imaging trial (n = 277; NCT03368547, NCT02611882, and NCT02919111)., Outcome Measurements and Statistical Analysis: Each 68 Ga-PSMA-11-PET scan was read by three blinded independent readers. PSMA-PET prostate uptake (low vs high), PSMA-PET extraprostatic disease (N1/M1), and CAPRA and CAPRA-S scores were used to assess the risk of BCR. Patients were followed after RP by local investigators using electronic medical records. BCR was defined by a prostate-specific antigen (PSA) level increasing to ≥0.2 ng/ml after RP or initiation of PCa-specific secondary treatment (>6 mo after surgery). Univariate and multivariable Cox models, and c-statistic index were performed to assess the prognostic value of PSMA-PET and for a comparison with the CAPRA and CAPRA-S scores., Results and Limitations: From December 2015 to December 2019, 277 patients underwent surgery after PSMA-PET. Clinical follow-up was obtained in 240/277 (87%) patients. The median follow-up after surgery was 32.4 (interquartile range 23.3-42.9) mo. Of 240 BCR events, 91 (38%) were observed. PSMA-PET N1/M1 was found in 41/240 (17%) patients. PSMA-PET prostate uptake, PSMA-PET N1/M1, and CAPRA and CAPRA-S scores were significant univariate predictors of BCR. The addition of PSMA-PET N1/M1 status to the presurgical CAPRA score improved the risk assessment for BCR significantly in comparison with the presurgical CAPRA score alone (c-statistic 0.70 [0.64-0.75] vs 0.63 [0.57-0.69]; p < 0.001). The C-index of the postsurgical model utilizing the postsurgical CAPRA-S score alone was not significantly different from the presurgical model combining the presurgical CAPRA score and PSMA-PET N1/M1 status (p = 0.19)., Conclusions: Presurgical PSMA-PET was a strong prognostic biomarker improving BCR-FS risk assessment. Its implementation in the presurgical risk assessment with the CAPRA score improved the performance and reduced the difference with the reference standard (postsurgical CAPRA-S score)., Patient Summary: The use prostate-specific membrane antigen positron emission tomography improved the assessment of biochemical recurrence risk in patients with intermediate- and high-risk prostate cancer who were treated with radical prostatectomy and pelvic lymph node dissection., (Copyright © 2023. Published by Elsevier B.V.)

Background: ANGPTL3 (angiopoietin-like 3) is a therapeutic target for reducing plasma levels of triglycerides and low-density lipoprotein cholesterol. A recent trial with vupanorsen, an antisense oligonucleotide targeting hepatic production of ANGPTL3, reported a dose-dependent increase in hepatic fat. It is unclear whether this adverse effect is due to an on-target effect of inhibiting hepatic ANGPTL3., Methods: We recruited participants with ANGPTL3 deficiency related to ANGPTL3 loss-of-function (LoF) mutations, along with wild-type (WT) participants from 2 previously characterized cohorts located in Campodimele, Italy, and St. Louis, MO. Magnetic resonance spectroscopy and magnetic resonance proton density fat fraction were performed to measure hepatic fat fraction and the distribution of extrahepatic fat. To estimate the causal relationship between ANGPTL3 and hepatic fat, we generated a genetic instrument of plasma ANGPTL3 levels as a surrogate for hepatic protein synthesis and performed Mendelian randomization analyses with hepatic fat in the UK Biobank study., Results: We recruited participants with complete (n=6) or partial (n=32) ANGPTL3 deficiency related to ANGPTL3 LoF mutations, as well as WT participants (n=92) without LoF mutations. Participants with ANGPTL3 deficiency exhibited significantly lower total cholesterol (complete deficiency, 78.5 mg/dL; partial deficiency, 172 mg/dL; WT, 188 mg/dL; P <0.05 for both deficiency groups compared with WT), along with plasma triglycerides (complete deficiency, 26 mg/dL; partial deficiency, 79 mg/dL; WT, 88 mg/dL; P <0.05 for both deficiency groups compared with WT) without any significant difference in hepatic fat (complete deficiency, 9.8%; partial deficiency, 10.1%; WT, 9.9%; P >0.05 for both deficiency groups compared with WT) or severity of hepatic steatosis as assessed by magnetic resonance imaging. In addition, ANGPTL3 deficiency did not alter the distribution of extrahepatic fat. Results from Mendelian randomization analyses in 36 703 participants from the UK Biobank demonstrated that genetically determined ANGPTL3 plasma protein levels were causally associated with low-density lipoprotein cholesterol ( P =1.7×10 -17 ) and triglycerides ( P =3.2×10 -18 ) but not with hepatic fat ( P =0.22)., Conclusions: ANGPTL3 deficiency related to LoF mutations in ANGPTL3 , as well as genetically determined reduction of plasma ANGPTL3 levels, is not associated with hepatic steatosis. Therapeutic approaches to inhibit ANGPTL3 production in hepatocytes are not necessarily expected to result in the increased risk for hepatic steatosis that was observed with vupanorsen., Competing Interests: Disclosures Dr Stitziel has received investigator-initiated research funding from Regeneron Pharmaceuticals related to ANGPTL3 (angiopoietin-like 3). Dr Arca has received research grant support from Amryt Pharmaceutical, Amgen, IONIS, Akcea Therapeutics, Daichi-Sankio, Novartis, Pfizer, and Sanofi; has served as a consultant for Amgen, Akcea Therapeutics, Daichi-Sankio, Novartis, Pfizer, Sanofi, and Alfasigma, and has received lecturing fees from Amgen, Amryth Pharmaceutical, Daichi-Sankio, Regeneron, Sanofi, and AlfaSigma. Dr D’Erasmo has received personal fees for public speaking or consultancy or grant support from Amryt Pharmaceuticals, Akcea Therapeutics, Pfizer, SOBI, Amgen, and Sanofi.

Purpose of Review: There has been a growing interest in the use of novel molecular imaging modalities for the management of prostate cancer (PCa), spanning from diagnostic to therapeutic settings. The aim of this review is to provide a comprehensive overview of recently published studies investigating the use of novel nuclear medicine tracers across different stages of PCa management., Recent Findings: Emerging evidence supports the use of molecular imaging for preoperative staging of PCa, where prostate-specific membrane antigen (PSMA) PET has shown superior accuracy compared to conventional imaging for the detection of nodal and distant metastases, which needs to be translated to new risk stratification. A role for PSMA PET has been proposed for PCa diagnosis, with local activity associated with histology. Surgical guidance, using either visual feedback or gamma-ray detectors to identify tissues with accumulated radio-labeled tracers, may improve the ability to resect locoregional diseases and thus maximize oncological control. PSMA targeted therapy (Lu-PSMA) has been mainly investigated in the castration-resistant setting, but might have a role in earlier settings such as neoadjuvant treatment., Summary: Novel molecular imaging using PSMA-based tracers could significantly improve PCa management in the diagnosis, staging, and intraoperative guidance settings, potentially leading to personalized and effective treatment decisions., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Aim of the present analysis was to report results of a systematic review of the literature in the setting of patients treated with hypoF PT for benign lesions of the central nervous system (CNS)., Methods: The methodology complied with the PRISMA recommendations. PubMed, EMBASE and Scopus databases were interrogated in September 2022., Results: Twelve papers have been selected including patients treated for base of the skull meningiomas (6 papers), vestibular schwannoma (3 papers) and pituitary adenomas (3 papers). Clinical outcomes were evaluated with both radiologic images and clinical parameters. Long-term toxicity was reported in all but one series with an incidence ranging from 2 % to 7 % in patients treated for base of skull meningioma and 1-9 % for schwannoma., Conclusions: HypoF PT is a safe and effective treatment in selected benign tumors of the CNS. Further dosimetric and clinical comparisons are required to better refine the patients' selection criteria., Competing Interests: Declaration of Competing Interest BAJF received speakers fees from Roche, Bayer, Janssen, Carl Zeiss, Ipsen, Accuray, Astellas, Elekta, IBA and Astra Zeneca. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

To evaluate the association between radiomic features (RFs) extracted from 18 F-FDG PET/CT ( 18 F-FDG-PET) with progression-free survival (PFS) and overall survival (OS) in diffuse large-B-cell lymphoma (DLBCL) patients eligible to first-line chemotherapy. DLBCL patients who underwent 18 F-FDG-PET prior to first-line chemotherapy were retrospectively analyzed. RFs were extracted from the lesion showing the highest uptake. A radiomic score to predict PFS and OS was obtained by multivariable Elastic Net Cox model. Radiomic univariate model, clinical and combined clinical-radiomic multivariable models to predict PFS and OS were obtained. 112 patients were analyzed. Median follow-up was 34.7 months (Inter-Quartile Range (IQR) 11.3-66.3 months) for PFS and 41.1 (IQR 18.4-68.9) for OS. Radiomic score resulted associated with PFS and OS (p < 0.001), outperforming conventional PET parameters. C-index (95% CI) for PFS prediction were 0.67 (0.58-0.76), 0.81 (0.75-0.88) and 0.84 (0.77-0.91) for clinical, radiomic and combined clinical-radiomic model, respectively. C-index for OS were 0.77 (0.66-0.89), 0.84 (0.76-0.91) and 0.90 (0.81-0.98). In the Kaplan-Meier analysis (low-IPI vs. high-IPI), the radiomic score was significant predictor of PFS (p < 0.001). The radiomic score was an independent prognostic biomarker of survival in DLBCL patients. The extraction of RFs from baseline 18 F-FDG-PET might be proposed in DLBCL to stratify high-risk versus low-risk patients of relapse after first-line therapy, especially in low-IPI patients., (© 2023 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

Proof of correlation between psychotic spectrum disorders and suicide are found in literature, as well as between cannabis use disorder (CUD) and suicide and between CUD and schizophrenia. The study population of the selected papers consists of subjects diagnosed with schizophrenia spectrum or cannabis or SCs induced psychosis. Our objective is to assess how suicide risk (defined as suicidal ideation/attempt or death by suicide) in this population may vary with exposure to cannabis or one of its main active compounds. We searched PubMed, Scopus and Psycinfo database from January 2010 to February 2022. Study designs of the included articles are distributed as follows: 6 cross-sectional studies, 3 cohort studies, 1 case-control studies, 1 randomized double-blind study, 1 case report. Selected cohort studies seem to agree in identifying an increased suicide risk in patients with schizophrenia spectrum disorders when exposed to cannabis use. The case-control study and selected cross-sectionals provide contradictory data. However, qualitative analysis seem to point toward a positive correlation between cannabis use and increased suicidal risk in patients with schizophrenia spectrum disorders. In conclusion, emerging data on the correlation between cannabis use and suicide risk in patients with schizophrenia or other schizophrenic spectrum disorders are insufficient to draw firm conclusions. Nonetheless these studies seem to suggest a positive correlation of cannabis use with increased suicide risk, particularly regarding first episode psychosis (FEP) and male gender. Clinicians should be aware of the possibility of a higher risk of suicidal behavior associated specifically with cannabis use for men and patients during FEP.

This review provides a formal overview of current automatic segmentation studies that use deep learning in radiotherapy. It covers 807 published papers and includes multiple cancer sites, image types (CT/MRI/PET), and segmentation methods. We collect key statistics about the papers to uncover commonalities, trends, and methods, and identify areas where more research might be needed. Moreover, we analyzed the corpus by posing explicit questions aimed at providing high-quality and actionable insights, including: "What should researchers think about when starting a segmentation study?", "How can research practices in medical image segmentation be improved?", "What is missing from the current corpus?", and more. This allowed us to provide practical guidelines on how to conduct a good segmentation study in today's competitive environment that will be useful for future research within the field, regardless of the specific radiotherapeutic subfield. To aid in our analysis, we used the large language model ChatGPT to condense information.

Purpose: The purpose of this retrospective, multicenter study was to assess efficacy of PSMA-PET/CT-guided salvage radiotherapy (sRT) in patients with recurrent or persistent PSA after primary surgery and PSA levels < 0.2 ng/ml., Methods: The study included patients from a pooled cohort (n = 1223) of 11 centers from 6 countries. Patients with PSA levels > 0.2 ng/ml prior to sRT or without sRT to the prostatic fossa were excluded. The primary study endpoint was biochemical recurrence-free survival (BRFS) and BR was defined as PSA nadir after sRT + 0.2 ng/ml. Cox regression analysis was performed to assess the impact of clinical parameters on BRFS. Recurrence patterns after sRT were analyzed., Results: The final cohort consisted of 273 patients; 78/273 (28.6%) and 48/273 (17.6%) patients had local or nodal recurrence on PET/CT. The most frequently applied sRT dose to the prostatic fossa was 66-70 Gy (n = 143/273, 52.4%). SRT to pelvic lymphatics was delivered in 87/273 (31.9%) patients and androgen deprivation therapy was given to 36/273 (13.2%) patients. After a median follow-up time of 31.1 months (IQR: 20-44), 60/273 (22%) patients had biochemical recurrence. The 2- and 3-year BRFS was 90.1% and 79.2%, respectively. The presence of seminal vesicle invasion in surgery (p = 0.019) and local recurrences in PET/CT (p = 0.039) had a significant impact on BR in multivariate analysis. In 16 patients, information on recurrence patterns on PSMA-PET/CT after sRT was available and one had recurrent disease inside the RT field., Conclusion: This multicenter analysis suggests that implementation of PSMA-PET/CT imaging for sRT guidance might be of benefit for patients with very low PSA levels after surgery due to promising BRFS rates and a low number of relapses within the sRT field., (© 2023. The Author(s).)

Background/purpose: The present study aimed to assess whether SRT to the prostatic fossa should be initiated in a timely manner after detecting biochemical recurrence (BR) in patients with prostate cancer, when no correlate was identified with prostate-specific membrane antigen positron emission tomography (PSMA-PET)., Materials and Methods: This retrospective, multicenter analysis included 1222 patients referred for PSMA-PET after a radical prostatectomy due to BR. Exclusion criteria were: pathological lymph node metastases, prostate-specific antigen (PSA) persistence, distant or lymph node metastases, nodal irradiation, and androgen deprivation therapy (ADT). This led to a cohort of 341 patients. Biochemical progression-free survival (BPFS) was the primary study endpoint., Results: The median follow-up was 28.0 months. The 3-year BPFS was 71.6% in PET-negative cases and 80.8% in locally PET-positive cases. This difference was significant in univariate (p = 0.019), but not multivariate analyses (p = 0.366, HR: 1.46, 95%CI: 0.64-3.32). The 3-year BPFS in PET-negative cases was significantly influenced by age (p = 0.005), initial pT3/4 (p < 0.001), pathology scores (ISUP) ≥ 3 (p = 0.026), and doses to fossa > 70 Gy (p = 0.027) in univariate analyses. In multivariate analyses, only age (HR: 1.096, 95%CI: 1.023-1.175, p = 0.009) and PSA-doubling time (HR: 0.339, 95%CI: 0.139-0.826, p = 0.017) remained significant., Conclusion: To our best knowledge, this study provided the largest SRT analysis in patients without ADT that were lymph node-negative on PSMA-PET. A multivariate analysis showed no significant difference in BPFS between locally PET-positive and PET-negative cases. These results supported the current EAU recommendation to initiate SRT in a timely manner after detecting BR in PET negative patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: The urological community's opinion over the management of men being found with pathologically positive nodes (pN+) following radical prostatectomy (RP) performed with curative intent after preoperative negative conventional staging (cN0M0) has never been assessed. This remains crucial, especially considering the advent of novel imaging modalities. Our aim was to investigate the current opinion on management of pN+ cN0M0 prostate cancer (PCa) in the European urological community., Methods: Following validation, a 31-item survey, complying with the Cherries checklist, was distributed using a web link from December 2021 to April 2022 to 10 urological societies mailing list. Social media (Twitter, Facebook) were also used., Results: We received 253 replies. The majority were Urologists (96.8%), younger than 60 (90.5%); 5.2% did not have access to PET-scans; 78.9% believed pN+ is a multifaceted category; 10-years CSS was marked as 71 to 95% by 17.5%. Gold standard management was stated not being ADT by 80.8% and being RT±ADT by 52.3%. Early sRT±ADT was considered an option vs. aRT±ADT by 72.4%. In case of BCR 71% would perform and decide management based on PSMA-PET whilst 3.7% would not perform PSMA-PET. pN+ management is still unclear for 77.1%. On multivariate analysis PSMA-PET availability related to a lower and higher likelihood of considering aRT±ADT as standard and of considering early salvage versus aRT respectively (P < .05)., Conclusions: The Urological community has an acceptable awareness of pN+ disease and management, although it may overestimate disease aggressiveness. The majority consider pN+ PCa as a multifaceted category and rely on a risk-adapted approach. Expectant compared to immediate upfront management and new imaging modalities are increasingly considered., (Copyright © 2022. Published by Elsevier Inc.)

Invasive lobular cancer (ILC) is the second most frequent histological type of breast cancer (BC) and includes a heterogeneous spectrum of diseases with unique characteristics, especially the infiltrative growth pattern and metastatic spread. [ 18 F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) is extensively used in oncology and BC patient evaluation. Its role in ILCs is considered suboptimal due to its low FDG avidity. Therefore, ILCs could benefit from molecular imaging with non-FDG tracers that target other specific pathways, contributing to precision medicine. This narrative review aims to summarize the current literature on the use of FDG-PET/CT in ILC and to discuss future opportunities given by the development of innovative non-FDG radiotracers.

Importance: Prostate-specific antigen membrane positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) after radical prostatectomy for patients with recurrent or persistent prostate cancer., Objective: To develop and validate a nomogram for prediction of freedom from biochemical failure (FFBF) after PSMA-PET-based sRT., Design, Setting, and Participants: This retrospective cohort study included 1029 patients with prostate cancer treated between July 1, 2013, and June 30, 2020, at 11 centers from 5 countries. The initial database consisted of 1221 patients. All patients had a PSMA-PET scan prior to sRT. Data were analyzed in November 2022., Exposures: Patients with a detectable post-radical prostatectomy prostate-specific antigen (PSA) level treated with sRT to the prostatic fossa with or without additional sRT to pelvic lymphatics or concurrent androgen deprivation therapy (ADT) were eligible., Main Outcomes and Measures: The FFBF rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse was defined as a PSA nadir of 0.2 ng/mL after sRT., Results: In the nomogram creation and validation process, 1029 patients (median age at sRT, 70 years [IQR, 64-74 years]) were included and further divided into a training set (n = 708), internal validation set (n = 271), and external outlier validation set (n = 50). The median follow-up was 32 months (IQR, 21-45 months). Based on the PSMA-PET scan prior to sRT, 437 patients (42.5%) had local recurrences and 313 patients (30.4%) had nodal recurrences. Pelvic lymphatics were electively irradiated for 395 patients (38.4%). All patients received sRT to the prostatic fossa: 103 (10.0%) received a dose of less than 66 Gy, 551 (53.5%) received a dose of 66 to 70 Gy, and 375 (36.5%) received a dose of more than 70 Gy. Androgen deprivation therapy was given to 325 (31.6%) patients. On multivariable Cox proportional hazards regression analysis, pre-sRT PSA level (hazard ratio [HR], 1.80 [95% CI, 1.41-2.31]), International Society of Urological Pathology grade in surgery specimen (grade 5 vs 1+2: HR, 2.39 [95% CI, 1.63-3.50], pT stage (pT3b+pT4 vs pT2: HR, 1.91 [95% CI, 1.39-2.67]), surgical margins (R0 vs R1+R2+Rx: HR, 0.60 [95% CI, 0.48-0.78]), ADT use (HR, 0.49 [95% CI, 0.37-0.65]), sRT dose (>70 vs ≤66 Gy: HR, 0.44 [95% CI, 0.29-0.67]), and nodal recurrence detected on PSMA-PET scans (HR, 1.42 [95% CI, 1.09-1.85]) were associated with FFBF. The mean (SD) nomogram concordance index for FFBF was 0.72 (0.06) for the internal validation cohort and 0.67 (0.11) in the external outlier validation cohort., Conclusions and Relevance: This cohort study of patients with prostate cancer presents an internally and externally validated nomogram that estimated individual patient outcomes after PSMA-PET-guided sRT.

Here we aim to provide updated guidance and standards for the indication, acquisition, and interpretation of PSMA PET/CT for prostate cancer imaging. Procedures and characteristics are reported for a variety of available PSMA small radioligands. Different scenarios for the clinical use of PSMA-ligand PET/CT are discussed. This document provides clinicians and technicians with the best available evidence, to support the implementation of PSMA PET/CT imaging in research and routine practice., (© 2023. The Author(s).)

Context: The introduction of prostate-specific membrane antigen positron emission tomography (PSMA-PET) had a substantial impact on the management of prostate cancer (PCa) patients with a stage migration phenomenon and consequent treatment changes., Objective: To summarise the role of PSMA-PET to define the burden of disease through an accurate location of metastatic site(s) in PCa patients, describing the most common locations at PSMA-PET in the primary staging and recurrence setting, and to assess the clinical impact in the decision-making process., Evidence Acquisition: A comprehensive nonsystematic literature review was performed in April 2022. Literature search was updated until March 2022. The most relevant studies have been summarised, giving priority to registered clinical trials and multicentre collaborations., Evidence Synthesis: PSMA-PET showed higher diagnostic accuracy than conventional imaging both in newly diagnosed PCa and in recurrent disease. This greater accuracy led to a migration of a higher proportion of patients identified with metastatic disease. Bone metastases were reported as the most frequent site of metastatic spread in staging (up to 17%) and restaging (up to 18%). In staging, considering the suboptimal sensitivity in lymph node metastasis detection prior to radical surgery, PSMA-PET should be performed in patients with high risk or unfavourable intermediate risk only, and it is not recommended to routinely avoid pelvic lymph node dissection in case of a negative scan. In case of prostate-specific antigen relapse, PSMA-PET had higher diagnostic accuracy than other diagnostic procedures in the early detection of the sites of recurrence, thus influencing the therapy decision-making process., Conclusions: PSMA-PET detects a higher number of lesions than conventional imaging or other PET radiotracers, especially metastatic lesions unseen with other modalities. The high diagnostic accuracy of PSMA-PET leads to a significant patient upstage and thus an impact in clinical management, even if the overall impact on cancer mortality is still to be assessed., Patient Summary: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) identifies metastatic lesions with higher accuracy than conventional imaging, both in primary prostate cancer and during disease recurrence. Skeletal metastasis and extrapelvic lymph nodes are the most common sites of metastatic spread. The high accuracy of PSMA-PET in the detection of metastatic disease led to a significant impact on patient management, even if the overall impact on cancer mortality is still to be assessed., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is used to select recurrent prostate cancer (PCa) patients for metastases-directed therapy (MDT). We aimed to evaluate the oncologic outcomes of second-line PSMA-guided MDT in oligo-recurrent PCa patients., Methods: we performed a retrospective analysis of 113 recurrent PCa after previous radical prostatectomy and salvage therapies with oligorecurrent disease at PSMA-PET (≤3 lesions in N1/M1a-b) in three high-volume European centres. Patients underwent second-line salvage treatments: MDT targeted to PSMA (including surgery and/or radiotherapy), and the conventional approach (observation or Androgen Deprivation Therapy [ADT]). Patients were stratified according to treatments (MDT vs. conventional approach). Patients who underwent MDT were stratified according to stage in PSMA-PET (N1 vs. M1a-b). The primary outcome of the study was Progression-free survival (PFS). Secondary outcomes were Metastases-free survival (MFS) and Castration Resistant PCa free survival (CRPC-FS). Kaplan-Meier analyses assessed PFS, MFS and CRPC-FS. Multivariable Cox regression models identified predictors of progression and metastatic disease., Results: Overall, 91 (80%) and 22 (20%) patients were treated with MDT and the conventional approach, respectively. The median follow-up after PSMA-PET was 31 months. Patients who underwent MDT had a similar PFS compared to the conventional approach ( p = 0.3). Individuals referred to MDT had significantly higher MFS and CRPC-FS compared to those who were treated with the conventional approach (73.5% and 94.7% vs. 30.5% and 79.5%; all p ≤ 0.001). In patients undergoing MDT, no significant differences were found for PFS and MFS according to N1 vs. M1a-b disease, while CRPC-FS estimates were significantly higher in patients with N1 vs. M1a-b (100% vs. 86.1%; p = 0.02). At multivariable analyses, age (HR = 0.96) and ADT during second line salvage treatment (HR = 0.5) were independent predictors of PFS; MDT (HR 0.27) was the only independent predictor of MFS (all p ≤ 0.04) Conclusion: Patients who underwent second-line PSMA-guided MDT experienced higher MFS and CRPC-FS compared to men who received conventional management.

Aims: The Craving Typology Questionnaire (CTQ) is a psychometric instrument used to assess alcohol craving in normal controls and subjects with alcohol use disorder (AUD). It allows a dimensional self-rating assessment of craving according to a three-pathway psychobiological model of craving distinguishing craving into a reward, relief and obsessive component. The aim of the present study is to evaluate psychometric properties of the CTQ-15, a revised version of CTQ with 15 items., Methods: The CTQ-15 was firstly administered to two groups of control subjects, one (414 subjects) used for the exploratory factor analysis and the other one (415 subjects) for the confirmatory factor analysis. A three-factor model was assessed and compared to alternative models., Results: The resulting structure was in line with the original scale CTQ. Obsessive craving accounted for 15.20% of the total variance, relief craving for the 13.99% and reward craving for 13.13% of the total variance. The three-factor model (M1) reached good fit indices (CFI = 0.96, TLI = 0.95, RMSEA = 0.06 and SRMR = 0.05) and was significantly better than other alternative models. Reliability showed good internal consistency for each scale, i.e. obsessive craving (α = 0.92), relief craving (α = 0.82) and reward craving (α = 0.81)., Conclusions: The CTQ-15 proved to be reliable and practical for identifying the three dimensions of craving in clinical practice. Craving plays a crucial role in the mechanisms of dependence and relapse; thus, characterizing the craving can be fundamental to a targeted drug therapy., (© The Author(s) 2022. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background: Combination systemic therapies have become the standard for metastatic hormone-sensitive prostate cancer (mHSPC). However, the effect of age on oncologic outcomes remains unknown. Our aim was to perform a systematic review, meta-analysis, and network meta-analysis (NMA) on the effect of chronological age on overall survival (OS) in patients treated with combination therapies for mHSPC., Methods: We searched the PubMed ® , Web of Science TM , and Scopus ® databases to identify randomized controlled trials (RCTs) that analyzed the efficacy of combination systemic therapies using ADT plus docetaxel and/or androgen receptor signaling inhibitor (ARSI) in patients with mHSPC. We included studies, which provided separate hazard ratios (HRs) for younger vs. older patients. The selected age cut-off was 70 years (±5 years). Our outcome of interest was OS., Results: We included nine RCTs with a total of 9183 patients. Younger and older men constituted 51% and 49% of included patients, respectively. Docetaxel plus ADT significantly improved OS among both older (HR 0.79, 95% CI 0.63-0.99, p = 0.04) and younger patients (HR 0.79, 95% CI 0.69-0.90, p < 0.001) with no differences according to age. ARSI plus ADT improved OS in older (HR 0.72, 95% CI 0.64-0.80, p < 0.001) and younger (HR 0.58, 95% CI 0.51-0.66, p < 0.001) patients; younger patients did benefit more (p = 0.02). On NMA treatment ranking, triplet therapy showed the highest probability of OS benefit irrespective of age group; in older patients, the benefit of triplet therapy compared to doublet was less expressed., Conclusions: Patients with mHSPC benefit from combination systemic therapies irrespective of age; the effect is, however, more evident in younger patients. Chronological age alone seems not to be a selection criteria for the administration of combination systemic therapies., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Emerging evidence indicates that chemoresistance is closely related to altered metabolism in cancer. Here, we hypothesized that distinct metabolic gene expression profiling (GEP) signatures might be correlated with outcome and with specific fluorodeoxyglucose positron emission tomography (FDG-PET) radiomic profiles in diffuse large B-cell lymphoma (DLBCL). We retrospectively analyzed a discovery cohort of 48 consecutive patients with DLBCL treated at our center with standard first-line chemoimmunotherapy by performing targeted GEP (T-GEP)- and FDG-PET radiomic analyses on the same target lesions at baseline. T-GEP-based metabolic profiling identified a 6-gene signature independently associated with outcomes in univariate and multivariate analyses. This signature included genes regulating mitochondrial oxidative metabolism (SCL25A1, PDK4, PDPR) that were upregulated and was inversely associated with genes involved in hypoxia and glycolysis (MAP2K1, HIF1A, GBE1) that were downregulated. These data were validated in 2 large publicly available cohorts. By integrating FDG-PET radiomics and T-GEP, we identified a radiometabolic signature (RadSig) including 4 radiomic features (histo kurtosis, histo energy, shape sphericity, and neighboring gray level dependence matrix contrast), significantly associated with the metabolic GEP-based signature (r = 0.43, P = .0027) and with progression-free survival (P = .028). These results were confirmed using different target lesions, an alternative segmentation method, and were validated in an independent cohort of 64 patients. RadSig retained independent prognostic value in relation to the International Prognostic Index score and metabolic tumor volume (MTV). Integration of RadSig and MTV further refined prognostic stratification. This study provides the proof of principle for the use of FDG-PET radiomics as a tool for noninvasive assessment of cancer metabolism and prognostic stratification in DLBCL., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)