Dose response of pancreatic neuroendocrine tumours treated with peptide receptor radionuclide therapy using ¹⁷⁷Lu-DOTATATE

Abstract

Peptide receptor radionuclide therapy (PRRT) is a promising treatment for patients with neuroendocrine tumors, giving rise to improved survival. Dosimetric calculations in relation to PRRT have been concentrated to normal organ dosimetry in order to limit side effects. However, the relation between the absorbed dose to the tumor and treatment response has so far not been established. Better knowledge in this respect may improve the understanding of treatment effects, allow for improved selection of those patients that are expected to benefit from PRRT and avoid unnecessary treatments. The aim of the present work was to evaluate the dose-response relationship for pancreatic neuroendocrine tumors (PNETs) treated with PRRT using ¹⁷⁷Lu-DOTATATE. Methods: Tumor absorbed dose calculations were performed for 24 lesions in 24 patients with metastasized PNETs treated with repeated cycles of ¹⁷⁷Lu-DOTATATE at 8 weeks intervals. The absorbed dose calculations relied on sequential SPECT/CT imaging at 24, 96 and 168 h after infusion of ¹⁷⁷Lu-DOTATATE. The unit density sphere model from Organ Level Internal Dose Assessment (OLINDA) was used for absorbed dose calculations. The absorbed doses were corrected for partial volume effect (PVE) based on phantom measurements. Based on these results, only tumors larger than 2.2 cm diameter at any time during the treatment were included for analysis. To further decrease the effect of PVE, a subgroup of tumors (larger than 4 cm) were analysed separately. Tumor response was evaluated by CT using Response Evaluation Criteria In Solid Tumors (RECIST). Results: Tumor absorbed doses until best response ranged approximately from 10 to 340 Gy. A two parameter sigmoid fit was fitted to the data and a significant correlation between the absorbed dose and tumor reduction was found, with Pearson correlation coefficient (R²) of 0.64 for tumors larger than 2.2 cm and 0.91 for the subgroup of tumors larger than 4 cm. The largest tumor reduction was 57% after a total absorbed dose of 170 Gy. Conclusion: The results imply a significant correlation between absorbed dose and tumor reduction. However, further studies are necessary to address the large variations in response for similar absorbed doses.