Single-centre experience with peptide receptor radionuclide therapy for neuroendocrine tumours (NETs): results using a theranostic molecular imaging-guided approach

Abstract

Aim: To summarise our centre's experience managing patients with neuroendocrine tumours (NETs) in the first 5 years after the introduction of peptide receptor radionuclide therapy (PRRT) with [¹⁷⁷Lu]Lu-DOTA-octreotate (LUTATE). The report emphasises aspects of the patient management related to functional imaging and use of radionuclide therapy.

Methods: We describe the criteria for treatment with LUTATE at our centre, the methodology for patient selection, and the results of an audit of clinical measures, imaging results and patient-reported outcomes. Subjects are treated initially with four cycles of ~ 8 GBq of LUTATE administered as an outpatient every 8 weeks.

Results: In the first 5 years offering LUTATE, we treated 143 individuals with a variety of NETs of which approx. 70% were gastroentero-pancreatic in origin (small bowel: 42%, pancreas: 28%). Males and females were equally represented. Mean age at first treatment with LUTATE was 61 ± 13 years with range 28-87 years. The radiation dose to the organs considered most at risk, the kidneys, averaged 10.6 ± 4.0 Gy in total. Median overall survival (OS) from first receiving LUTATE was 72.5 months with a median progression-free survival (PFS) of 32.3 months. No evidence of renal toxicity was seen. The major long-term complication seen was myelodysplastic syndrome (MDS) with a 5% incidence.

Conclusions: LUTATE treatment for NETs is a safe and effective treatment. Our approach relies heavily on functional and morphological imaging informing the multidisciplinary team of NET specialists to guide appropriate therapy, which we suggest has contributed to the favourable outcomes seen.

Keywords: Multidisciplinary Team (MDT); NETs; Neuroendocrine; PET; Peptide Receptor Radionuclide Therapy (PRRT).

Fig. 1

Kaplan–Meier curves of a progression-free survival (PFS) and b overall survival (OS) from the NETTER-1 trial and our NET centre at RNS. The NETTER-1 trial started to count from randomisation onto the trial, while our starting point was the decision to offer LUTATE treatment

Fig. 2

The average of the pooled subjects’ blood results prior to each cycle of LUTATE are shown plus a follow-up time point after the last cycle. The p values are calculated from a repeated measures ANOVA comparing each measurement to the pre-Cycle 1 baseline value. Error bars represent ± 1σ. NS—not significant (p > 0.05). There are 86 complete datasets in this analysis from the cohort of 142 subjects treated in the period under review

Fig. 3

In case 1 (left), the a PET DOTATATE scan shows multiple hepatic SSTRI-positive lesions which have no uptake on the corresponding b PET FDG scan. The patient went on to successful treatment with LUTATE. In Case 2 (right), however, the c PET DOTATATE scan is essentially negative in the liver, while in d the PET FDG scan demonstrates significant uptake in both the lung lesion and the liver. This patient was deemed not suitable for treatment with LUTATE and was offered systemic medical therapy instead