First-in-human results of terbium-161 [Tb]Tb-PSMA-I&T dual beta-Auger radioligand therapy in patients with metastatic castration-resistant prostate cancer (VIOLET): a single-centre, single-arm, phase 1/2 study.

Background: Terbium-161 (Tb) emits beta-radiation similar to lutetium-177 (Lu), with additional radiation over ultra-short path lengths from Auger electrons. Tb has shown superior in-vitro and in-vivo efficacy compared with Lu. We aimed to evaluate the safety of [Tb]Tb-PSMA-I&T in patients with metastatic castration-resistant prostate cancer (mCRPC).

Peptide receptor radionuclide therapy in malignant insulinoma.

The management of malignant insulinoma (MI) presents dual management challenges of hypoglycaemia and tumour control. This study aims to analyse long-term outcomes of PRRT for the treatment of MI. We retrospectively reviewed consecutive patients with MI treated with [177Lu]Lu-DOTATATE (LuTATE) at two Australian NET centres between 2004 and 2022.

Safety and efficacy of re-treatment with [Lu]Lu-DOTA-Octreotate radionuclide therapy in progressive gastro-entero-pancreatic neuroendocrine tumours - a single centre experience.

Aim: Patients with gastro-entero-pancreatic neuroendocrine tumours (GEP NET) who retain somatostatin receptor (SSTR) expression after initial response to [Lu]Lu-DOTA-Octreotate (LuTate) peptide receptor radionuclide therapy (PRRT) are amenable to re-treatment (R-PRRT) upon progression. We assessed the safety and efficacy of R-PRRT in patients with progressive metastatic GEP NET.

Materials And Methods: A retrospective analysis, approved by institutional ethics board, was performed in patients with GEP NET who received R-PRRT for either symptomatically or radiologically progressive disease.

Therapy-Related Myeloid Neoplasms After [Lu]Lu-PSMA Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: A Case Series.

[Lu]Lu-prostate-specific membrane antigen (PSMA) therapy has a favorable toxicity profile in patients with metastatic castration-resistant prostate cancer (mCRPC). Therapy-related myeloid neoplasm (t-MN) has been described after [Lu]Lu-DOTATATE but has not, to our knowledge, yet been reported after [Lu]Lu-PSMA. This case series describes 5 patients with mCRPC who developed t-MN after [Lu]Lu-PSMA at our institution.

Peptide receptor radionuclide therapy for ectopic Cushing's syndrome caused by metastatic neuroendocrine neoplasms.

Background: Metastatic gastroenteropancreatic neuroendocrine neoplasms (GEPNEN) can cause ectopic Cushing's syndrome (ECS). ECS is highly morbid and medical therapy is complex and can be ineffective. Patients unsuitable for bilateral adrenalectomy (BA) have dismal outcomes.

[Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial.

Background: Enzalutamide and lutetium-177 [Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer.

Prostate-specific Membrane Antigen Positron Emission Tomography-detected Disease Extent and Overall Survival of Patients with High-risk Nonmetastatic Castration-resistant Prostate Cancer: An International Multicenter Retrospective Study.

Previously, we demonstrated that prostate-specific membrane antigen positron emission tomography (PSMA-PET) revealed distant metastases in 109/200 patients (39% distant nodes, 24% bone, and 6% visceral organ) with nonmetastatic castration-resistant prostate cancer (nmCRPC) and high-risk features (International Society of Urological Pathology score ≥4 and/or prostate-specific antigen doubling time ≤10 mo) without metastases by conventional imaging. However, the impact of disease extent determined by PSMA-PET on patient outcomes is unknown. We followed these 200 patients for a median of 43 mo after PSMA-PET and retrospectively assessed the association between patient characteristics, PSMA-PET findings, treatment management, and outcomes using a Kaplan-Meier model and Cox multivariable regressions.

Radiation Dosimetry in Lu-PSMA-617 Therapy.

Radionuclide therapy using the small molecule PSMA bound to the beta-emitting radionuclide, Lutetium-177 (Lu-PSMA) has demonstrated efficacy and survival benefit castrate resistant metastatic disease and represents a novel new line of therapy. Whilst dosimetry was critical for early development, it was not incorporated into either the TheraP or VISION randomized studies, highlighting the difficulty of adopting dosimetry in routine clinical practice. Accumulated clinical experience has also shown that the common (and generally low grade) toxicities such as nausea, xerostomia, and cytopenias are not readily predicted on the basis of dosimetry estimates.

Actinium-225 Prostate-specific Membrane Antigen Theranostics: Will α Beat β?

Optimisation of prostate-specific membrane antigen (PSMA) based radioligand therapy (RLT) requires a focus on prospective trials.

A role of PSMA PET/CT in multimodality imaging approach in adenoid cystic carcinoma.

Adenoid cystic carcinoma is a rare disease and characterised by slow but unrelenting local progression and risk of haematogenous metastases. We present a case of locally unresectable disease where PSMA PET/CT provided complementary staging and early treatment response assessment.

Prostate-specific membrane antigen PET/computed tomography for staging prostate cancer.

Purpose Of Review: Molecular imaging with PET/CT targeting the prostate-specific membrane antigen (PSMA) receptor is increasingly utilized in men with prostate cancer (PCa), with clinical indications now expanding beyond biochemical recurrence. PSMA PET/CT often detects sub-centimetre size pathologic nodes and low-volume bone marrow disease that are occult on conventional imaging when the lesion does not cause sclerosis or osteoblastic reaction in surrounding bone. This review focuses on recent evidence for PSMA PET/CT in initial disease staging.

Mechanistic Insights for Optimizing PSMA Radioligand Therapy.

PSMA radioligand therapy is a promising new class of therapy for prostate cancer. Heterogeneity of PSMA expression is an important factor explaining variability in clinical results. The ability to visualize the target with theranostics provides unique mechanistic insights.

Prognostic biomarkers in men with metastatic castration-resistant prostate cancer receiving [177Lu]-PSMA-617.

Purpose: We analysed quantitative biomarkers derived from both baseline whole-body imaging and blood serum to identify prognostic markers in patients treated within the lutetium-177 prostate-specific membrane antigen (LuPSMA) phase 2 trial.

Methods: PET image analysis was carried out using whole-body segmentation quantifying molecular tumour volume (SUV > 3 threshold for PSMA, SUV > liver+2sd for fluorodeoxyglucose (FDG) including SUVmax and SUVmean. For baseline bone scans, EXINI bone scan index (BSI) was used to calculate the percentage of involved bone.

Efficacy of Peptide Receptor Radionuclide Therapy for Esthesioneuroblastoma.

Esthesioneuroblastoma is rare, with limited therapeutic options when unresectable or metastatic; however, expression of somatostatin receptors qualifies it for peptide receptor radionuclide therapy (PRRT). We report outcomes of PRRT in esthesioneuroblastoma from 2 referral centers. Using PRRT databases at 2 European Neuroendocrine Tumor Society Centers of Excellence, cases were sought between 2004 and 2018 of patients who had PRRT with recurrent or metastatic esthesioneuroblastoma deemed unsuitable for further conventional therapies.

Long-Term Follow-up and Outcomes of Retreatment in an Expanded 50-Patient Single-Center Phase II Prospective Trial of Lu-PSMA-617 Theranostics in Metastatic Castration-Resistant Prostate Cancer.

Lu-PSMA-617 is a radioligand with high affinity for prostate-specific membrane antigen (PSMA), enabling targeted β-irradiation of prostate cancer. We have previously reported favorable activity with low toxicity in a prospective phase II trial involving 30 men with metastatic castration-resistant prostate cancer. We now report their longer-term outcomes, including a 20-patient extension cohort and outcomes of subsequent systemic treatments after completion of trial therapy.

Mitogen-Activated Protein Kinase Pathway Inhibition for Redifferentiation of Radioiodine Refractory Differentiated Thyroid Cancer: An Evolving Protocol.

Some patients with metastatic differentiated thyroid cancer (DTC) lack iodine avidity and are therefore unsuitable for radioactive iodine (RAI) therapy. Limited experience suggests that single-agent selective mitogen-activated protein kinase (MAPK) pathway inhibitors can restore expression of the sodium-iodide symporter rendering RAI refractory (RAIR) DTC patients amenable to RAI therapy. The aim of this study was to assess the feasibility of mutation-guided MAPK-pathway blockade combined with thyroid hormone withdrawal (THW) for redifferentiation.

Setting the stage: Contemporary staging of non-melanomatous skin cancer and implementation of the new American Joint Committee on cancer eighth edition staging manual.

Non-melanomatous skin cancer (NMSC) generally refers to basal cell and squamous cell carcinoma of the skin. The majority of patients are curatively treated with simple excision. Only few present with locally advanced disease or have evidence of high-risk features, placing them at an elevated risk of relapse.

Poor Outcomes for Patients with Metastatic Castration-resistant Prostate Cancer with Low Prostate-specific Membrane Antigen (PSMA) Expression Deemed Ineligible for Lu-labelled PSMA Radioligand Therapy.

Background: Prostate-specific membrane antigen (PSMA) is overexpressed in metastatic castration-resistant prostate cancer (mCRPC) and represents a target for imaging and therapy. We undertook a prospective trial of Lu-PSMA-617 radioligand therapy in men with high PSMA expression who progressed after standard therapies.

Objective: To determine outcomes for men screened for the trial but not treated because of low PSMA expression.

The Role of 68Ga-DOTA-Octreotate PET/CT in Follow-Up of SDH-Associated Pheochromocytoma and Paraganglioma.

Purpose: Germline succinate dehydrogenase (SDHx) mutation carriers, especially SDHB, are at increased risk for malignancy and require life-long surveillance. Current guidelines recommend periodic whole-body MRI imaging. We assessed the incremental value of 68Ga-DOTA-octreotate (GaTate) positron emission tomography (PET)/CT compared with conventional imaging in such patients.

Dosimetry of Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer: Correlations Between Pretherapeutic Imaging and Whole-Body Tumor Dosimetry with Treatment Outcomes.

Lu-prostate-specific membrane antigen (PSMA)-617 enables targeted delivery of β-particle radiation to prostate cancer. We determined its radiation dosimetry and relationships to pretherapeutic imaging and outcomes. Thirty patients with prostate cancer receiving Lu-PSMA-617 within a prospective clinical trial (ACTRN12615000912583) were studied.

EBUS-TBNA Cytology Specimens are Predictive of Occupational Dust Exposure in Patients With Bilateral Mediastinal and Hilar Lymphadenopathy.

Objectives: The aim of this study was to describe the cytological features of patients with significant occupational dust exposure presenting with benign bilateral mediastinal and hilar lymphadenopathy (BHL).

Methods: A retrospective cohort study including patients undergoing EBUS-TBNA for investigation of benign BHL. Patient characteristics, dust exposure history, radiology, and cytology samples from EBUS-TBNA were assessed.