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.

Differentiated Thyroid Cancer after Thyroidectomy.

The widespread use of neck US and other imaging modalities has contributed to a phenomenon of increased detection of differentiated thyroid cancer (DTC). Most of these cancers remain indolent, without requiring surgical intervention. Nonetheless, a subset of patients who require surgical treatment experience subsequent disease recurrence. This most commonly occurs in the cervical lymph nodes and thyroid bed, followed by distant metastasis to the lungs and bones. Because imaging is an integral part of postoperative surveillance, radiologists play a central role in the detection of recurrent tumors and in guiding treatment in these patients. US is the primary imaging modality used for postoperative evaluation. Other modalities such as CT, MRI, radioactive iodine imaging, and PET/CT aid in the accurate diagnosis and characterization of recurrent disease. Therefore, radiologists must have a thorough understanding of the utility of these imaging techniques and the imaging characteristics of recurrent DTC when interpreting these multimodality studies. The interpretation of imaging findings should also be correlated with the clinical status of patients and their biochemical markers to minimize interpretative errors. The authors present a broad overview of the postoperative evaluation of DTC, including its initial primary management, staging, and prognostication; clinical risk stratification for recurrent disease; postoperative surveillance with imaging and evaluation of biochemical markers; and management of recurrent DTC. Published under a CC BY 4.0 license. Supplemental material is available for this article.

Frequent neck US in papillary thyroid cancer likely detects non-actionable findings.

BACKGROUND: American Thyroid Association (ATA) low-intermediate-risk papillary thyroid cancer (PTC) patients without structural and biochemical evidence of disease on initial post-treatment evaluation have a low risk of recurrence. Studies have shown that with current ultrasound scans (US) and thyroglobulin assays, recurrences mostly occurred 2-8 years after initial therapy. The ATA recommends that neck US be done 6-12 months after surgery to establish patient's response to therapy, then periodically depending on risk of recurrence. The lack of clarity in recommendations on timing of follow-up US and fear of recurrence leads to frequent tests. OBJECTIVES: To evaluate the utility of routine neck US in ATA low-intermediate-risk PTC patients with no structural disease on neck US and non-stimulated thyroglobulin <1.0 ng/mL after initial therapy. METHODS: A retrospective study of 93 patients from Singapore, Saudi Arabia and Argentina with ATA low (n = 49) to intermediate (n = 44) risk PTC was conducted between 1998 and 2017. The outcome was to measure the frequency of identifying structural disease recurrence and non-actionable US abnormalities. RESULTS: Over a median follow-up of 5 years, five of the 93 patients (5.4%) developed structural neck recurrence on US at a median of 2.5 years after initial treatment. Indeterminate US abnormalities were detected in 19 of the 93 patients (20.4%) leading to additional tests, which did not detect significant disease. CONCLUSION: In ATA low-intermediate-risk PTC with no suspicious findings on neck US and a non-stimulated thyroglobulin of <1.0 ng/mL after initial therapy, frequent US is more likely to identify non-actionable abnormalities than clinically significant disease.

Radiation exposure to allied health personnel handling blood specimens from patients receiving radioactive iodine-131 and recombinant human TSH (thyrogen®) stimulation.

With increasing use of recombinant human TSH (rhTSH) stimulation protocol in radioactive iodine-131 treatment of thyroidectomised differentiated thyroid carcinoma (DTC), there is increasing concern regarding radiation safety during collection and processing of radioactive blood samples. Our study aims to quantify this radiation exposure in the context of current radiation guidelines to provide a practical safety framework. We analysed 45 patients prospectively referred to a tertiary centre in Singapore, who had histologically proven DTC, and who were thyroidectomised and planned for I-131 with rhTSH stimulation. Each patient received rhTSH for two consecutive days, with I-131 administered 24 h after, and a stimulated Thyroglobulin blood sample collected and processed 72 h after the last rhTSH dose. We measured radiation exposures with dosimeters. Based on the average and maximum exposure rates calculated, we extrapolated and derived the number of radioactive blood samples that could be safely collected and processed. Mean hand and body radiation exposures during venepuncture and blood processing were generally significantly higher than background radiation. Based on average exposure rates, the permissible number of blood samples that can be collected and processed is 9.09 × 103per year (24 per day) and 8.70 × 104per year (238 per day), respectively. This is the first study to date to extrapolate permissible thresholds that can serve as a practical guideline to the number of radioactive blood samples which can be safely collected and processed, following radioactive iodine therapy, within the limits of current radiation guidelines. Once validated, generalisations to other radioactive therapies may be considered.

Facing a disruptive threat: how can a nuclear medicine service be prepared for the coronavirus outbreak 2020?

PURPOSE: The aim of this short communication is to outline our experience in policies and processes of a nuclear medicine service during the COVID-19 outbreak in Singapore. METHODS: We describe the key considerations of policies and processes that have been implemented in our nuclear medicine service since the first case of COVID-19 was confirmed in Singapore General Hospital on 23 January 2020, up to the present time. RESULTS: Infection control, screening of patients and visitors, segregation of risk groups, segregation of staff and service continuity plans, communication and staff welfare, using electronic platforms for multi-disciplinary meetings and tele-reporting are discussed. CONCLUSION: Since our hospital received the first patient with COVID-19 in Singapore, our centre has managed 16 COVID-19 cases to date. There has not been any healthcare worker in our institution who has contracted COVID-19 through patient contact. We have highlighted for discussion some of the policies and processes to prepare a nuclear medicine service for the COVID-19 threat.

Clinicopathologic Characteristics and Survival of Patients with Gastroenteropancreatic Neuroendocrine Neoplasm in a Multi-Ethnic Asian Institution.

BACKGROUND: Epidemiological evidence suggests there are differences in gastroenteropancreatic neuroendocrine neoplasm (GEPNEN) among population groups. We aimed to contribute to the current evidence by evaluating the clinicopathological characteristics of GEPNEN in a multi-ethnic Asian group. MATERIALS AND METHODS: This was a retrospective chart review of patients diagnosed with GEPNEN at a tertiary medical institution at Singhealth Outram Campus, Singapore, between 1995 and 2015. RESULTS: Two hundred ninety-five patients were included in the evaluation, comprising Chinese (74.6%), Malay (4.4%), Indian (9.5%) and other (11.5%) ethnic backgrounds. The median age at diagnosis was 59 years; 52.5% were males. Distribution of disease stage at diagnosis was: localised (42.4%), regional (15.3%) and distant (38.0%). The three most common primary tumour sites were located in the pancreas (38.6%), rectum (19.7%) and stomach (9.5%), which varied significantly with ethnic background and age at diagnosis. Malay patients were younger (median 42 years) at diagnosis than Chinese (60 years). Patients with an appendiceal neuroendocrine neoplasm (NEN) (48 years) were younger compared to oesophageal NEN (66 years). Disease stage correlated with primary tumour site and grade (p < 0.001). Median overall survival (OS) for all GEPNEN was 10.2 years. Age at diagnosis, disease stage and grading were prognostic factors of OS in multivariable analyses. CONCLUSION: Our findings correspond with other studies that focus on GEPNEN incidences in Asian countries, with the pancreas, rectum and stomach being the most common primary tumour sites. Our findings suggest racial differences in primary tumour site and age at diagnosis. Further prospective population-based registries are required to understand these epidemiological differences.

The role of PET/CT in the evaluation of skeletal metastases.

Osseous metastatic disease from malignancy is a common occurrence with significant patient morbidity and mortality as well as increasing health care expenditures. Patient management plans frequently change with the identification of skeletal metastasis and the upstaging of disease status. Bone scintigraphy remains the current mainstay of diagnostic imaging procedures in nuclear medicine for the early detection of skeletal metastasis owing to their high sensitivity. Emerging positron tracers and the increasing use and availability of hybrid single-photon emission computed tomography and positron emission tomography (PET)/computed tomography machines enable physicians to diagnose metastatic disease in bones with superior accuracy. This review introduces the basics of PET and the commonly used positron tracers used to evaluate skeletal metastases.

A case of metastatic lymphoepithelial carcinoma of parotid gland identified on 68gallium DOTA-[Tyr3] octreotate PET CT.

The authors present the case of a 59-year-old lady diagnosed with lymphoepithelial carcinoma (LEC) of the left parotid gland. The primary tumour was identified using contrast-enhanced CT, and diagnosis was confirmed via fine needle aspiration cytology and immunohistochemistry. Staging using fluorine-18 fluorodeoxyglucose PET CT revealed regional nodal metastases, while no distant metastasis was evident. Following radical radiotherapy, a favourable locoregional response was observed on MRI, yet the patient's plasma Epstein-Barr virus load continued to rise. Given her primary tumour's somatostatin receptor type 2 (SSTR2) positivity, gallium-68 DOTA-[Tyr3] octreotate PET CT (68Ga-DOTATATE PET CT) was performed, revealing multiple distant metastases with DOTATATE avidity. Despite attempts at palliative chemotherapy and immunotherapy, disease progression led to the decision for the best supportive care. The unique presentation of metastatic LEC on 68Ga-DOTATATE PET CT suggests a potential role for SSTR2-targeted imaging in diagnosis and management.

Safety and Efficacy of 90Y Selective Internal Radiation Therapy Using Glass Microspheres in Hepatocellular Carcinoma: A Southeast Asian Single-Institution Initial Experience.

Our objective was to demonstrate primarily the safety and secondarily the efficacy of 90Y glass microspheres in selective internal radiation therapy (SIRT) for hepatocellular carcinoma (HCC) in a local Southeast Asian hospital. Methods: Eleven consecutive patients with small, unresectable, nonmetastatic HCC and referred for locoregional therapy with SIRT with a curative intention were followed up for 6 mo after the procedure by way of interviews, blood tests, and anatomic scans. Results: Although 5 patients had deranged liver function tests after the procedure, in only 1 patient did this constitute a grade 1 toxicity (in alkaline phosphatase) by the Common Terminology Criteria for Adverse Events. Half the patients showed a reduction in serum α-fetoprotein measurements, and 6 of 11 patients demonstrated an objective response (complete or partial) on imaging. Conclusion: SIRT with 90Y glass microspheres is a safe and efficacious locoregional therapy for unresectable HCC. There are similar articles published in the West; however, the patient population there comprises far fewer Asians and the underlying cause for HCC is different from that in the Asian population. Despite these differences, SIRT is an equally effective and safe option for such patients.