3253 - The impact of tumour absorbed dosimetry with survival outcomes after peptide receptor radionuclide therapy in metastatic neuroendocrine tumours.

Background

Peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lutetium (¹⁷⁷Lu) -DOTATATE is effective treatment for neuroendocrine tumors (NETs). Dosimetry assessment can be used to maximize the tumour dose, while keeping the dose delivered to critical organs to acceptable levels. The association between tumour absorbed dosimetry (TAD) and progression-free (PFS) and overall survival (OS) is not well understood.

Methods

Single institution retrospective analysis of patients with metastatic NET whom underwent up to 4 cycles of 7.45GBq ¹⁷⁷Lu octreotate PRRT. Intra-therapeutic tumour dosimetry was performed with non-gated single photon emission computed tomography (SPECT) to quantify activity at 5 time points after administration of ¹⁷⁷ Lu during cycle 1. TAD per injected activity (A₀) and estimated total TAD (multiplied by total administered activity of ¹⁷⁷Lu) was correlated with OS and PFS using the Kaplan–Meier method and Cox proportional-hazards model.

Results

79 patients were included, primary site: gastroenteric (48%), pancreatic (39%), bronchial (9%), other (4%), ECOG Performance status (PS) 0/1 (94%), Grade: G1 (47%), G2 (42%), G3 (11%), Ki-67≤20% (89%), concurrent chemotherapy use (29%). Mean TAD/A₀ was 9(7-11) Gy/GBq. Progressive disease (54%) and death (29%) was seen. Median follow-up of 35 months. Median PFS was 32 [26-38] months. PFS was shorter with increasing ECOG PS (P = 0.02), tumour grade (P < 0.01), Ki-67 (P = 0.01), concurrent chemo-radionuclide therapy (P = 0.02) and reduced TAD (P = 0.036) but not primary site of origin (P = 0.66). A higher TAD led to an improved median PFS in pancreatic (P < 0.01) versus gastroenteric (P = 0.56) NETs. In a multivariate model incorporating ECOG PS, Ki-67 and chemotherapy use, total TAD remained significantly associated with PFS. The mean OS was 40 [36-44] months. OS was shorter with increasing tumour grade (P = 0.05), Ki-67 (P = 0.036) and reduced TAD (P = 0.039).

Conclusions

TAD was independently associated with OS and PFS validating dosimetry assessment in NET patients undergoing PRRT. Prospective refinement of the association on larger, more homogenous cohorts of NET patients is needed.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.