Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study.

PURPOSE: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. METHODS: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. RESULTS: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. CONCLUSIONS: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov : NCT01578239, EudraCT: 2011-005049-11.

Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Adults with Inoperable or Metastatic Somatostatin Receptor-Positive Pheochromocytomas/Paragangliomas, Bronchial and Unknown Origin Neuroendocrine Tumors, and Medullary Thyroid Carcinoma: A Systematic Literature Review.

BACKGROUND: We have performed a systematic review to evaluate the efficacy and safety of [177Lu]Lu-DOTA-TATE, a radioligand therapy, in advanced somatostatin receptor-positive pheochromocytoma/paraganglioma (PPGL), thymic neuroendocrine tumor (NET), bronchial NET, unknown primary NET, or medullary thyroid carcinoma (MTC). METHODS: Studies identified in PubMed from inception to 13 May 2021 must have assessed [177Lu]Lu-DOTA-TATE as a single agent and reported outcome data for the specific NET types of interest. RESULTS: Two independent reviewers performed the screening and data extraction, resulting in 16 publications: PPGL (n = 7), bronchial NETs (n = 6; one also included NETs of unknown origin), and MTC (n = 3). Overall, [177Lu]Lu-DOTA-TATE offers encouraging antitumor activity (overall tumor response rates and disease control rates) across NET types. Safety was favorable with most adverse events mild to moderate in severity, transient, and consistent with those seen in patients with gastroenteropancreatic (GEP)-NETs. CONCLUSIONS: [177Lu]Lu-DOTA-TATE has been used effectively in clinical practice to treat NETs of non-GEP origin.

Dual-phase F-18 FDG PET-CT in staging and lymphoscintigraphy for detection of sentinel lymph nodes in oral cavity cancers.

AIM: Our objective was to evaluate the diagnostic role of dual-phase fluor-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography-computed tomography (PET-CT) and planar lymphoscintigraphy in patients with oral cavity cancer (OCC). We also investigated the combined impact of F-18 FDG PET-CT and sentinel lymph node biopsy (SLNB) in decision making for patients with OCC. METHODS: Sixteen patients (4 female, 12 male; age range, 29-81 years) were included in this prospective study. F-18 FDG PET-CT [1 (early) and 2 h (delayed) after injection] and planar lymphoscintigraphy (2h before the surgery) were performed for all the patients before surgery. The sensitivity, specificity, and negative and positive predictive values in F-18 FDG PET-CT for the early and the delayed scans and tumor/liver uptake (T/L) in the lymph nodes were calculated. Receiver operating characteristic curves were obtained for standardized uptake value (SUV)max and T/L. RESULTS: Histopathological evaluations revealed that 5 patients had metastatic lymph nodes (pN+) whereas 11 patients had benign lymph nodes (pN-). Out of 43 lymph nodes visualized as cN(+) in F-18 FDG PET-CT, 14 were pathologically positive for malignancy, whereas 29 were pathologically benign. There was no statistical difference between the N(+) and N(-) patients in terms of age, depth of primary tumor, and the number of mitoses. However, there was a significant difference between the N(+) and N(-) patients (P=.011) in terms of early and delayed F-18 FDG uptake of primary tumors. There was a statistically significant difference in the value of SUVmax between the early and the delayed scans for the malignant lymph nodes (P=.00). CONCLUSION: This study indicates that F-18 FDG PET-CT is a reliable method for the correct evaluation of primary tumor and N staging in OCCs. Delayed phase of F-18 FDG imaging may increase primary lesion detectability due to higher FDG uptake in primary tumors compared to the early phase of imaging. F-18 FDG PET-CT might demonstrate skip metastasis in lymph nodes which can be missed with SLNB. Although SUV values increased in the delayed phase of F-18 PET-CT imaging in detecting lymph node metastases, the specificity and positive predictive value did not increase.