Treatment and Long-Term Safety Outcomes of Peptide Receptor Radionuclide Therapy for Metastatic Neuroendocrine Tumours: An Asian Experience.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) is a targeted molecular therapy used to treat neuroendocrine tumours (NETs). It has been shown to be effective and well tolerated in patients with metastatic NETs in several centres in the USA, Europe, and Australia. Tolerability and efficacy data emerging from Asian centres remain few. Epidemiological evidence suggests that there are differences in neuroendocrine neoplasms between the population groups. We aim to describe the treatment and safety outcomes of PRRT in the Asian population. METHODS: One hundred and seven (107) patients with metastatic NETs who had undergone PRRT treatment from January 2012 to March 2019 were included in this retrospective study. The response rates using RECIST 1.1 and qualitative analysis were examined. The overall and progression-free survival curves were also evaluated. RESULTS: The median progression-free survival was 49 months. Response assessment after completion of treatment showed that 33 (37.9%) of 87 patients had partial or complete response. Subgroup analysis comparing high- and low-grade NET showed that there was a significant difference in the time to progression curves. Comparison of the number of cycles and progression-free and overall survival also showed a significant difference. Ten patients (9%) had grade 3 or more haematological toxicities. Four patients (4%) had grade 3/4 hepatobiliary toxicities, although the presence of extensive liver metastases was a confounding factor. None of the patients had grade 3/4 acute kidney injury. CONCLUSION: Our results show that PRRT is safe and effective in the treatment of metastatic NET in the Asian population. There was a significant difference in the progression-free survival curves between low-grade and high-grade NET and in the progression-free and overall survival comparing the number of cycles received.

Safety and efficacy of peptide receptor radionuclide therapy in patients with advanced pheochromocytoma and paraganglioma: A single-institution experience and review of the literature.

INTRODUCTION: Despite advances in diagnosis and management, patients with advanced pheochromocytomas and paragangliomas (PPGL) face limited treatment options. This study aims to evaluate the safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with advanced PPGL, based on a single-institution experience and provide a comprehensive review of the literature. METHODS: A retrospective analysis was conducted on patients with advanced pheochromocytoma and paraganglioma who received PRRT at a single institution from April 2012 to March 2022. Clinical characteristics, treatment response, adverse events, and survival outcomes were assessed. A systematic literature review was also performed. RESULTS: A total of 15 patients with advanced PPGL were included, the majority of whom had both metastatic and functional disease. Most patients received four infusions of 177Lu-DOTATATE (73%). The median therapeutic 177Lu-DOTATATE radioactivity for each infusion was 7.4 GBq. Only one patient was treated with one infusion of 90Y-DOTATATE (4.2 GBq) in addition to three infusions of Lu-177 DOTATATE. Overall, PRRT suggests a promising efficacy with disease control rate of 63.6% by RECIST v1.1. The median overall survival (OS) was not reached and the median progression free survival (PFS) was 25.9 months. In terms of safety, PRRT was well tolerated. Review of the literature revealed consistent findings, supporting the efficacy and safety of PRRT in PPGL. CONCLUSION: This study suggests that PRRT is a safe and effective therapeutic option for patients with PPGL. Our findings align with the existing literature, providing additional evidence to support the use of PRRT in this challenging patient population.

Optimization of Bayesian penalized likelihood reconstruction for 68 Ga-prostate-specific membrane antigen-11 PET/computed tomography.

OBJECTIVE: The objective of this study is to determine the optimal ß value for clinical use in digital 68 Ga-prostate-specific membrane antigen (PSMA-11) PET/computed tomography (CT) imaging. METHODS: 68 Ga PSMA PET/CT of 21 patients with prostate cancer were reconstructed using block-sequential regularized expectation maximization ( ß value of 400-1600) and ordered subsets expectation maximization. Nine independent blinded readers evaluated each reconstruction for overall image quality, noise level and lesion detectability. Maximum standardized uptake value (SUVmax) of the most intense lesion, liver SUVmean and liver SUV SD were recorded. Lesions were then subdivided according to uptake and size; the SUVmax of these lesions were analyzed. RESULTS: There is a statistically significant correlation between improvement in image quality and ß value, with the best being ß 1400. This trend was also seen in image noise ( P  < 0.001), with the least image noise reported with ß 1400. Lesion detectability was not significantly different between the different ß values ( P  =  0.6452). There was no statistically significant difference in SUVmax of the most intense lesion ( P  = 0.9966) and SUVmean of liver background between the different ß values ( P  = 0.9999); however, the SUV SD of the liver background showed a clear trend, with the lowest with ß 1400 ( P  = 0.0008). There was a decreasing trend observed in SUVmax when ß values increased from 800 to 1400 for all four subgroups, and this decrease was greatest in small and low uptake lesions. CONCLUSION: Bayesian penalized likelihood reconstruction algorithms improve image quality without affecting lesion detectability. A ß value of 1400 is optimal.

Radiochemical Feasibility of Mixing of 99mTc-MAA and 90Y-Microspheres with Omnipaque Contrast.

Yttrium-90 (90Y) microspheres are widely used for the treatment of liver-dominant malignant tumors. They are infused via catheter into the hepatic artery branches supplying the tumor under fluoroscopic guidance based on pre-therapy angiography and Technetium-99m macroaggregated albumin (99mTc-MAA) planning. However, at present, these microspheres are suspended in radiolucent media such as dextrose 5% (D5) solution. In order to monitor the real-time implantation of the microspheres into the tumor, the 90Y microspheres could be suspended in omnipaque contrast for allowing visualization of the correct distribution of the microspheres into the tumor. The radiochemical purity of mixing 90Y-microspheres in various concentrations of omnipaque was investigated. The radiochemical purity and feasibility of mixing 99mTc-MAA with various concentrations of a standard contrast agent were also investigated. Results showed the radiochemical feasibility of mixing 90Y-microspheres with omnipaque is radiochemically acceptable for allowing real-time visualization of radioembolization under fluoroscopy.

Radioembolisation with Y90-resin microspheres followed by nivolumab for advanced hepatocellular carcinoma (CA 209-678): a single arm, single centre, phase 2 trial.

BACKGROUND: Therapeutic synergism between radiotherapy and immune checkpoint blockade has been observed in preclinical models of hepatocellular carcinoma. We aimed to study the safety and efficacy of sequential radioembolisation with yttrium-90-resin microspheres (Y90-radioembolisation) followed by nivolumab in patients with advanced hepatocellular carcinoma. METHODS: Patients with Child-Pugh A cirrhosis and advanced hepatocellular carcinoma not suitable for curative surgery were treated with Y90-radioembolisation followed by intravenous nivolumab 240 mg 21 days after Y90-radioembolisation and every 2 weeks thereafter. The primary endpoint, assessed in the per-protocol population, was the objective response rate, determined by RECIST version 1.1, defined as the proportion of patients with a confirmed complete or partial response observed for lesions both within and outside the Y90-radioembolisation field. This study is registered with ClinicalTrials.gov, NCT03033446 and has been completed. FINDINGS: 40 patients were enrolled, of whom 36 received Y90-radioembolisation followed by nivolumab. One (3%) patient had a complete response and ten (28%) had a partial response; the objective response rate was 30·6% (95% CI 16·4-48·1). The most common treatment-related adverse events of any grade were pruritus (18 [50%] of 36 patients) and maculopapular rash (13 [36%]). Two (6%) patients experienced grade 3-4 treatment-related adverse events: one patient had a grade 3 increase in alanine aminotransferase levels, grade 3 bilirubin increase, and grade 4 increase in aspartate aminotransferase levels, while the other had a grade 3 maculopapular rash. Five (14%) patients had a treatment-related serious adverse event (Steven-Johnson syndrome, hepatitis E infection, fever, liver abscesses, and ascites). INTERPRETATION: Y90-radioembolisation followed by nivolumab resulted in an encouraging objective response rate in patients with advanced hepatocellular carcinoma, although the activity observed was not as high as the study was powered for. This strategy should be further evaluated in patients with Barcelona Clinic Liver Clinic (BCLC) stage B hepatocellular carcinoma that is ineligible or refractory to transarterial chemoembolisation and patients with BCLC C disease without extrahepatic spread. FUNDING: National Medical Research Council Singapore, Bristol-Myers Squibb, Sirtex.

The exact Deauville score, NABS score and high SUVmax predicts outcome in extranodal natural killer/T-cell lymphoma.

OBJECTIVE: Natural killer T-cell lymphoma (NKTCL) is an aggressive type of non-Hodgkin's lymphoma. While FDG-PET/CT imaging has been increasingly utilized for disease assessment, its prognostic value and potential utility in NKTCL patient stratification remain controversial. We aim to investigate the prognostic utility of FDG-PET/CT and its role in complementing clinical indices. METHODS: We conducted a retrospective review of 72 patients from a tertiary National Cancer Centre with biopsy-proven NKTCL and available FDG-PET/CT data (either baseline, end of treatment or both). Survival analysis was performed using the Kaplan-Meier method and multivariable Cox proportional regression. RESULTS: High initial SUVmax was significantly associated with advanced Ann-Arbor stage (p = 0.0352), elevated LDH levels (p = 0.0059) and plasma EBV DNA detection (p = 0.0278). SUVmax correlated with worse progression-free survival (PFS) (HR 3.68, 95% CI 1.56-8.69, p = 0.0030) and a trend toward worse overall survival (OS) (HR 2.06, 95% CI 0.95-4.45, p = 0.0676). End of treatment Deauville scores of 4-5, as compared to scores of 1-3, was associated with worse PFS (HR 2.72, 95% CI 1.04-7.12, p = 0.0419). Notably, while all patients with scores of 5 developed progressive disease, only 2 of 5 patients with scores of 4 eventually relapsed. Clinical indices (NABS score) were still able to stratify survival outcomes regardless of end-of-treatment Deauville scores. CONCLUSIONS: A Deauville score of 5 is more diagnostic of true disease progression than a score of 4, and NABS score may be used in patients who achieve Deauville scores of 1-3 for further risk stratification. A higher SUVmax at baseline portends a worse prognosis in NKTCL.

A survey of anxiety and burnout in the radiology workforce of a tertiary hospital during the COVID-19 pandemic.

INTRODUCTION: We aimed to study anxiety and burnout among Division of Radiological Sciences (RADSC) staff during the COVID-19 pandemic and identify potential risk and protective factors. These outcomes were compared with non-RADSC staff. METHODS: A cross-sectional online study was conducted between 12 March and 20 July 2020 in the largest public tertiary hospital receiving COVID-19 cases. Burnout and anxiety were assessed with the Physician Work-Life Scale and the Generalized Anxiety Disorder-7 Scale, respectively. Workplace factors were examined as potential risk and protective factors using multivariable ordinary least squares regression analyses, adjusting for pertinent demographic characteristics. RESULTS: RADSC staff (n = 180) and non-RADSC staff (n = 1458) demonstrated moderate-to-severe anxiety rates of 6.7 and 13.2 % and burnout rates of 17.8 and 23.9 %, respectively. RADSC staff reported significantly lower anxiety (mean ± SD: 4.0 ± 3.7 vs 4.9 ± 4.5; P-value < 0.05), burnout (mean ± SD: 1.9 ± 0.7 vs 2.1 ± 0.8; P-value < 0.01), increased teamwork (82.2% vs 74.1%; P-value < 0.05) and fewer night shifts (36.7% vs 41.1%; P-value < 0.01). Among RADSC staff, higher job dedication was associated with lower anxiety (b (95% CI) = -0.28 (-0.45, -0.11)) and burnout (b (95% CI) = -0.07 (-0.11,-0.04)), while longer than usual working hours was associated with increased anxiety (b (95% CI) = 1.42 (0.36, 2.45)) and burnout (b (95% CI) = 0.28 (0.09, 0.48)). CONCLUSIONS: A proportion of RADSC staff reported significant burnout and anxiety, although less compared to the larger hospital cohort. Measures to prevent longer than usual work hours and increase feelings of enthusiasm and pride in one's job may further reduce the prevalence of anxiety problems and burnout in radiology departments.

FDG-PET in suspected dementia with Lewy bodies: a case report.

BACKGROUND: Dementia with Lewy bodies (DLB) is still underdiagnosed or mistaken for other types of neurodegenerative diseases. Biomarkers such as 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) can be helpful. CASE PRESENTATION: A 72-year-old gentleman presented with postural hypotension, hallucination, Parkinsonism and recurrent falls. He also had rapidly progressing cognitive impairment. CT and MRI brain showed atrophy of the frontal lobes with preservation of the hippocampi. FDG-PET was suggestive of DLB. He was subsequently treated with Rivastigmine, with significant improvement of his symptoms. CONCLUSION: This case highlights the challenges in diagnosis of an elderly patient with DLB, the use of neuro-imaging as a diagnostic biomarker, the avoidance of the use of antipsychotic and the response to pharmacological treatment with Rivastigmine after a probable diagnosis of DLB.

Current Status and Growth of Nuclear Theranostics in Singapore.

The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of 'personalised' medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore. We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy. We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.

Multiple Myeloma of Testes and Spermatic Cord on 18F-FDG PET/CT.

Extramedullary multiple myeloma (EM) has negative prognostic implications on the overall survival as well as progression-free survival. Testis is a rare site of EM, which can be a part of diffuse involvement in multiple myeloma or a site of recurrence in patients with remission. We present a case of EM of testes and left spermatic cord in an 80-year-old man who presented with painless progressive enlargement of the scrotum. F-FDG PET/CT revealed tracer avidity of both testes and left spermatic cord. Bilateral radical orchidectomy was subsequently performed, and the diagnosis of multiple myeloma was confirmed on histopathology.

Imaging and Treatment of Post-90Y Radioembolization Radiation Dermatitis.

Y microspheres have been widely used for treatment of liver-dominant malignancies. There have been a few case reports of radiation dermatitis post-inadvertent falciform artery Y radioembolization and a few retrospective studies with prophylactic coiling or use of ice packs prior to radioembolization. Our patient had inadvertent falciform artery radioembolization, which was not predicted on pretherapy angiography or Tc-macroaggregated albumin SPECT/CT but was localized on posttherapy Y PET/CT and treated with topical betamethasone valerate 0.1% BD and ice packing immediately postprocedure. He subsequently developed a small area of periumbilical radiation dermatitis, which resolved after 4 weeks.

A Case of Well-differentiated Hepatocellular Carcinoma Identified on Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography.

Prostate-specific membrane antigen (PSMA) is a glycosylated type-II transmembrane protein highly expressed in certain tumor cells. To the best of our knowledge, this is the first case reported of an isolated well-differentiated hepatocellular carcinoma (HCC) strongly suspected on gallium-68 (68Ga)-PSMA positron emission tomography/computed tomography (PET/CT), which was not well characterized both on magnetic resonance imaging (MRI) liver with Primovist as well as fluorine-18 (18F)-choline PET/CT. Our patient had previous prostate cancer and previously was imaged using 18F-choline PET/CT. The last scan showed an indeterminate segment VII hypodensity which was not significantly choline-avid. The lesion was initially stable on serial MRI scans but then showed growth from 1.0 to 1.5 cm. 68Ga-PSMA PET/CT was performed. The lesion was intensely tracer-avid. This was surgically excised and histology confirmed the presence of well-differentiated HCC. Well-differentiated HCC can be optimally imaged using 68Ga-PSMA PET/CT and further prospective studies are needed to look into the potential of this imaging modality.

The Utility of FDG PET/CT in IgG4-Related Disease with a Focus on Coronary Artery Involvement.

PURPOSE: Our case series aims to study the growing use of FDG PET/CT in diagnostic evaluation and follow up of IgG4-RD with emphasis on patients presenting with coronary artery involvement. METHODS: We conducted a search on the nuclear medicine and rheumatology service databases and identified patients with histologically proven IgG4-RD with FDG PET/CT performed at the Singapore General Hospital. The radiological, clinical, and laboratory findings of these patients were analyzed retrospectively. RESULTS: The series included ten male and two female patients. The commonest organ involved (five patients) was the pancreas. In three patients, coronary artery involvement manifested as soft tissue masses surrounding the arterial lumens. In these patients, histological diagnosis was established from alternative biopsy sites with abnormal metabolic activity on FDG PET/CT.Correlation between laboratory and metabolic imaging findings was not statistically significant in our series.Four patients had follow-up FDG PET/CT; three showed interval reduction in metabolic activity to baseline. One showed persistent abnormal metabolic activity before a rise in IgG4 levels. The metabolic imaging response was used to guide steroid dose. CONCLUSIONS: FDG PET/CT is a useful tool in evaluation and follow-up of IgG4-RD, particularly in identifying alternative biopsy sites in patients who present with coronary artery involvement. Hypermetabolic coronary artery masses on FDG PET/CT should raise clinical suspicion of IgG4-RD. As the coronary artery masses may not show decrease in size after treatment, FDG PET/CT is also useful for metabolic response assessment.

The epidemiology of hypernatraemia in hospitalised children in Lothian: a 10-year study showing differences between dehydration, osmoregulatory dysfunction and salt poisoning.

INTRODUCTION: The relative frequencies of the causes of hypernatraemia in children after the neonatal period are unknown. Salt poisoning and osmoregulatory dysfunction are extremely rare and potentially fatal. In this retrospective 10-year study, the incidence, causes and differential biochemistry of hypernatraemia in children is examined. METHODS: Children with hypernatraemia (sodium ≥ 150 mmol/litre) aged >2 weeks to 17 years were identified from laboratory data of two paediatric departments serving the Lothian region of Scotland. A review of patient notes established time of onset and cause. Denominator data were available from the Scottish Health Service. RESULTS: On admission to hospital, 1 in 2288 children (1:1535 admitted as an emergency) had hypernatraemia. This is 1 in 30 563 Lothian children <17 years. Overall 0.04% hospital stays had an episode of hypernatraemia. In 45 children admitted with 64 separate episodes (11 from a case of salt poisoning), the commonest cause was dehydration secondary to either gastroenteritis or systemic infection; 31% had an underlying chronic neurological disorder. A total of 177 further cases developed hypernatraemia after admission. The commonest causes were dehydration secondary to severe systemic infection and postoperative cardiac surgery. Urine sodium:creatinine ratio and fractional excretion of sodium were both much higher in the salt poisoning case than in a child with osmoregulatory dysfunction or children with simple dehydration. CONCLUSIONS: Hypernatraemia after 2 weeks of age is uncommon, and on admission is usually associated with dehydration. Salt poisoning and osmoregulatory dysfunction are rare but should be considered in cases of repeated hypernatraemia without obvious cause. Routine measurement of urea, creatinine and electrolytes on paired urine and plasma on admission will differentiate these rare causes.