Intra-arterial peptide-receptor radionuclide therapy for neuro-endocrine tumour liver metastases: an in-patient randomised controlled trial (LUTIA)
Sander C. Ebbers, Maarten W. Barentsz, Daphne M. V. de Vries–Huizing, Michelle W. J. Versleijen, Elisabeth G. Klompenhouwer, Margot Tesselaar, Marcel P. M. Stokkel, Tessa Brabander, Johannes Hofland, Adriaan Moelker, Rachel S. van Leeuwaarde, Maarten L. J. Smits, Arthur J. A. T. Braat, Marnix G. E. H. Lam
Abstract
Abstract Purpose Peptide receptor radionuclide therapy (PRRT) using [ 177 Lu]Lu-DOTATATE has been shown to effectively prolong progression free survival in grade 1–2 gastroenteropancreatic neuroendocrine tumours (GEP-NET), but is less efficacious in patients with extensive liver metastases. The aim was to investigate whether tumour uptake in liver metastases can be enhanced by intra-arterial administration of [ 177 Lu]Lu-DOTATATE into the hepatic artery, in order to improve tumour response without increasing toxicity. Methods Twenty-seven patients with grade 1–2 GEP-NET, and bi-lobar liver metastases were randomized to receive intra-arterial PRRT in the left or right liver lobe for four consecutive cycles. The contralateral liver lobe and extrahepatic disease were treated via a “second-pass” effect and the contralateral lobe was used as the control lobe. Up to three metastases (> 3 cm) per liver lobe were identified as target lesions at baseline on contrast-enhanced CT. The primary endpoint was the tumour-to-non-tumour (T/N) uptake ratio on the 24 h post-treatment [ 177 Lu]Lu-SPECT/CT after the first cycle. This was calculated for each target lesion in both lobes using the mean uptake. T/N ratios in both lobes were compared using paired-samples t -test. Findings After the first cycle, a non-significant difference in T/N uptake ratio was observed: T/N IA = 17·4 vs. T/N control = 16·2 ( p = 0·299). The mean increase in T/N was 17% (1·17; 95% CI [1·00; 1·37]). Of all patients, 67% (18/27) showed any increase in T/N ratio after the first cycle. Conclusion Intra-arterial [ 177 Lu]Lu-DOTATATE is safe, but does not lead to a clinically significant increase in tumour uptake.