Clinical results of radionuclide therapy of neuroendocrine tumours with 90Y-DOTATATE and tandem 90Y/177Lu-DOTATATE: which is a better therapy option?

Abstract

Purpose: Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues is a treatment option for patients with disseminated neuroendocrine tumours (NET). A combination treatment using the high-energy 90Y beta emitter for larger lesions and the lower energy 177Lu for smaller lesions has been postulated in the literature.The aim of the study was to evaluate combined 90Y/177Lu-DOTATATE therapy in comparison to 90Y-DOTATATE alone.

Methods: Fifty patients with disseminated NET were included in the study prospectively and divided into two groups: group A (n=25) was treated with 90Y-DOTATATE, whereas group B (n=25) received the 1:1 90Y/177Lu-DOTATATE. The administered activity was based on 3.7 GBq/m2 body surface area in three to five cycles, with amino acid infusion for nephroprotection.

Results: The median overall survival time in group A was 26.2 months while in group B median survival was not reached. Overall survival was significantly higher in group B (p=0.027). Median event-free survival time in group A was 21.4 months and in group B 29.4 months (p>0.1). At the 12-month follow-up, comparison of group A vs group B showed stable disease (SD) in 13 vs 16 patients, disease regression (RD) in 5 vs 3 patients and disease progression (PD) in 3 vs 4 patients; 4 and 2 patients died, respectively. The 24-month follow-up results were SD in nine vs ten patients, RD in one patient vs none and PD in four patients in both groups; three and four patients died, respectively. Side effects were rare and mild.

Conclusion: The results indicate that therapy with tandem radioisotopes (90Y/177Lu-DOTATATE) provides longer overall survival than with a single radioisotope (90Y-DOTATATE) and the safety of both methods is comparable.

Fig. 1

A 58-year-old man with multiple liver and peritoneum metastases of gastrinoma. a SRS with ^99mTc-HYNIC-TATE before treatment with uptake in metastatic lesions in liver and peritoneum. b 24-h post-therapeutic image after administration of ⁹⁰Y-DOTATATE using bremsstrahlung

Fig. 2

A 42-year-old man with multiple bone metastases of atypical bronchial carcinoid tumour without hormonal activity. a SRS with ^99mTc-HYNIC-TATE before treatment with uptake in metastatic lesions in bone. b 24-h post-therapeutic image after administration of ⁹⁰Y/¹⁷⁷Lu-DOTATATE using ¹⁷⁷Lu photopeak

Fig. 3

Kaplan-Meier estimators of OS

Fig. 4

Kaplan-Meier estimators of EFS

Fig. 5

Comparison of the PRRT results (SD, RD, PD and patients who died): a 12 months, b 24 months, c 36 months follow-up

Fig. 6

Changes on CT in the size of the biggest tumours 3–6 months after completed therapy. The line represents median reduction of tumour size in % for both groups

Fig. 7

Correlation between tumour size and type of therapy before and 3–6 months after therapy

Fig. 8

A 62-year-old woman with multiple bone and liver metastases of pancreas neuroendocrine carcinoma without hormonal activity. a SRS with ^99mTc-HYNIC-TATE before treatment with uptake in metastatic lesions in bone and liver. b 12-month follow-up shows reduced number of metastases, with only a few visible in bone. c 24-month follow-up shows nearly complete response to treatment