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

PURPOSE: Gastroenteropancreatic -neuroendocrine tumours (GEP-NETs) are commonly treated with surgical resection or long-term therapies for tumour growth control. Lutetium [177Lu]-DOTA-TATE was approved for the treatment of GEP-NETs after the phase III NETTER 1trial demonstrated improved progression free survival, objective response rates and health-related quality of life (HRQoL) compared to high-dose somatostatin analogues. No real-world data exist on prescribing habits and clinically significant endpoints for [177Lu]Lu-DOTA-TATE treatment in Italy. REAL-LU is a multicentre, long-term observational study in patients with unresectable/metastatic GEP-NETs progressing on standard therapies in Italian clinical practice. A pre-specified interim analysis was performed at the end of the enrolment period, data from which are described herein. METHODS: Overall duration of REAL-LU will be approximately 48 months, with 12- and 36-month recruitment and follow-up periods, respectively. The primary objective is to evaluate [177Lu]Lu-DOTA-TATE effectiveness in terms of progression-free survival. Secondary objectives include safety, impact on HRQoL, and identification of prognostic factors. This pre-specified interim analysis describes patient profiles, at the end of enrollment, of those prescribed [177Lu]Lu-DOTA-TATE for GEP-NETs in Italy. RESULTS: Among 161 evaluable patients, mean age was 64.7 ± 10.3 years at study entry, 83.8% presented with no clinical signs of disease at physical examination, and most had minor disease symptoms. All patients had metastatic disease, most commonly in the liver (83.9%) with a median of two metastatic sites. In 90.7% of patients, the disease was stage IV, and 68.3% had ≥ 1 target lesion. [177Lu]Lu-DOTA-TATE was prescribed mainly as second-line therapy (61.6%) and following surgery (58.4%). HRQoL assessments revealed high levels of functioning and low levels of symptoms at baseline; 50.0% of patients were symptom-free at study entry. CONCLUSION: The characteristics of patients who received [177Lu]Lu-DOTA-TATE in Italy are similar to those of the GEP-NET population of NETTER 1 with trial but with a higher proportion of patients with a grade 2 (71%). With regard to the tumor grade profile, our study cohort appears to be closer to that of NETTER-2 study population which included patients with G2 or G3 advanced GEP-NETs (i.e. Ki-67 ≥ 10% and ≤ 55%). Further analysis of effectiveness and safety can be anticipated as REAL-LU data mature. STUDY REGISTRATION: ClinicalTrials.gov, NCT04727723; Study Registration Date: 25 January, 2021; https://clinicaltrials.gov/study/NCT04727723?cond=NCT04727723&rank=1.

Management of a Patient With Metastatic Gastrointestinal Neuroendocrine Tumor and Meningioma Submitted to Peptide Receptor Radionuclide Therapy With 177 Lu-DOTATATE.

ABSTRACT: A 76-year-old woman affected by pancreatic neuroendocrine tumor previously subjected to surgery with progressive liver disease and a concomitant mild symptomatic meningioma of the left pontocerebellar angle underwent 4 cycles of peptide receptor radionuclide therapy with 177 Lu-DOTATATE. A prophylactic therapy with corticosteroids was carried out before each treatment cycle, and the neurosurgery unit was alerted in case of cerebral edema and related neurologic symptoms. A 68 Ga-DOTATOC PET/CT scan performed after the completion of the 4 cycles' treatment documented a hepatic partial response and a substantial stability of the brain mass. No neurological complications occurred during treatment and follow-up.

Decrease in total lesion glycolysis and survival after yttrium-90-radioembolization in poorly differentiated hepatocellular carcinoma with portal vein tumour thrombosis.

PURPOSE: This study aims to evaluate the prognostic role of the decrease in total lesion glycolysis (TLG) assessed by fluorine-18-fluorodeoxyglucose (F-FDG) PET-computed tomography (CT) 1 month after yttrium-90-radioembolization (Y-RE) in patients affected by hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT). PATIENTS AND METHODS: Twenty-one patients with histologically proven poorly differentiated HCC and evidence of PVTT at the enhanced multislice CT underwent Y-RE. All patients underwent an F-FDG PET-CT scan at baseline and 1 month after the loco-regional therapy. The variation in TLG (ΔTLG) between the two studies was calculated. Patients were divided in two groups (group 1: 1 month ΔTLG >50%, group 2: ΔTLG <50%). Statistical analysis was carried out to assess the prognostic role of TLG in overall survival (OS). RESULTS: On the 21 patients enrolled, all presented a decrease in TLG after the administration of Y-microspheres. The OS was 11.5±1.2 months. Nine out of 21 (42.9%) patients showed ΔTLG more than 50% with a mean OS of 16.8±1.3 months, whereas the remaining 12 (57.1%) patients had ΔTLG less than 50% with a mean OS of 7.5±0.5 months. Statistical analysis showed ΔTLG to be a significant (P<0.001) predictor of survival. None of the other examined variables including age, Child-Pugh classification, previously performed therapies, the presence of extrahepatic metastases, α-fetoprotein and bilirubin levels had a significant prognostic impact on patients' outcome. CONCLUSION: Decrease in TLG measured by F-FDG PET-CT is correlated with a trend towards a longer median survival in patients affected by HCC and PVTT who have undergone Y-RE.

A case report of thyroid carcinoma confined to ovary and concurrently occult in the thyroid: is conservative treatment always advised?

INTRODUCTION: Struma ovarii is an ovarian teratoma, represented in more than 50% by thyroid tissue. Five percent of struma ovarii cases have been proven to be malignant and, as in the thyroid gland, papillary thyroid carcinoma is the most common histotype arising in struma ovarii. Because of the unusual occurrence of this tumor, its management and follow-up after pelvic surgery is still controversial. Usually, total thyroidectomy followed by radioiodine treatment is the choice treatment in metastatic malignant struma ovarii, while these procedures are still controversial in non-metastatic thyroid cancer arising in struma ovarii. CASE PRESENTATION: We report a female with follicular variant of papillary thyroid carcinoma arising in struma ovarii. After pelvic surgery, thyroid morphofunctional examinations were performed and a single nodular lesion in the left lobe was discovered. The patient underwent total thyroidectomy and histological examination showed a papillary carcinoma. Radioiodine-ablation of residual thyroid tissue was performed and levothyroxine mildly-suppressive treatment was started. CONCLUSIONS: A more aggressive treatment should not be denied for malignant struma ovarii without any evidence, even when apparently confined into the ovary. However, in selected cases, aggressive treatment may be advisable to decrease the risk of recurrence and to allow an accurate follow-up.

90Y-PET for the assessment of microsphere biodistribution after selective internal radiotherapy.

OBJECTIVES: To demonstrate the feasibility of 90Y-PET imaging for biodistribution assessment after selective internal radiotherapy treatments with 90Y-microspheres, comparing the results with 99mTc-macroaggregated albumin (MAA) images obtained with single-photon emission computed tomography. METHODS: Preliminary studies were performed with the aim of evaluating the imaging system spatial resolution and scanner sensitivity for detecting annihilation photons. Subsequently, microsphere distribution was evaluated in 10 patients who underwent liver selective internal radiotherapy treatment. 99mTc-MAA and 90Y-microsphere were simultaneously injected for immediate monitoring after treatment. For each patient, the metastases detected with 90Y-PET and 99mTc-MAA were assessed and compared with 18F-fluorodeoxyglucose-PET (18F-FDG-PET) obtained before treatment and used as an imaging benchmark procedure. The correlation between these techniques was thus investigated in terms of matching lesions. Lesions were considered true positive in the case of matching with 18F-FDG-PET. The sensitivity of both techniques was evaluated as the true-positive fraction of detected spots in the treated liver sectors. RESULTS: With our experimental setup, a maximum scanner sensitivity of 0.577 and 0.077 cps/MBq was obtained for three-dimensional and two-dimensional acquisitions, respectively. A good correlation was obtained between images obtained before and after treatment, with 90Y-PET being by far the most accurate technique in detecting microsphere distribution and tumor nonhomogeneity areas. A sensitivity as high as 0.91 was obtained with 90Y-PET, whereas 99mTc-MAA imaging showed a SE of 0.75. CONCLUSION: 90Y-PET is a promising and reliable technique for microsphere biodistribution evaluation after liver selective internal radiotherapy treatment. Because of the better resolution and the possibility to perform computed tomography fusion, 90Y-PET images are more accurate than 99mTc-MAA single-photon emission computed tomography, which is now considered the gold standard for biodistribution assessment.