Endocrine Abstracts

Background: Peptide Receptor Radionuclide Therapy (PRRT) is an approved second- or third-line treatment for advanced metastatic neuroendocrine tumours (NETs). While generally well tolerated, PRRT can cause toxicities, particularly haematological, including bone marrow suppression and malignancies. The underlying risk factors remain unclear.

Methods: Our study was a single-centre, retrospective observational analysis of patients with histologically confirmed NETs who received PRRT from 2015 to 2024. Patients were reviewed at the South Wales NET Multidisciplinary Team meeting and referred for PRRT at the Royal Free Hospital in London where they received PRRT with ¹⁷⁷Lu-DOTATATE at a dose of 7.477 GBq/cycle, administered every 10 to 12 weeks for up to four to six cycles. Toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, focusing on persistent haematological dysfunction (PHD) and Serious Adverse Events (SAEs) 3 to 5 resulting in hospitalization or death. We analysed haematological changes from baseline to two years post-PRRT (Wilcoxon Rank Test) and identified predictors of PHD through logistic regression, using GraphPad Prism version 10.0.0.

Results: Seventy-four patients received at least one PRRT cycle; 68% had midgut primaries and 55% were grade 1. Four cycles were given to 59 patients (80%), whereas 13 (18%) received 5 or 6 cycles. SAEs occurred in 21 patients (28.4%): gastrointestinal (7; 9.4%), renal (6; 8.1%), and haematological (5; 6.8%) including bone marrow suppression (n = 3) and AML (n = 2). Median time from last PRRT to toxicity was 60 days (gastrointestinal), 37.5 days (renal), and 180 days (haematological). Significant changes occurred in haemoglobin (P < 0.001, n = 36), MCV (P = 0.006, n = 31), lymphocytes (P < 0.001, n = 40) and platelets (P = 0.001, n = 34) at two years post-PRRT. Three patients (4%) developed bone marrow failure leading to discontinuation, and 20 (27%) had PHD. Regression analysis identified tumour grade (P = 0.004) and bone metastases (P = 0.010) as significant predictors of haematological toxicity.

Conclusion: Higher-grade (2&3) NETs and bone metastases are significantly associated with delayed haematological toxicity following PRRT. Previous treatments were not contributory. Vigilant monitoring of high-risk patients is essential to optimise long-term outcomes.

Keywords: Haematological toxicity, Peptide Receptor Radionuclide Therapy (PRRT), Neuroendocrine Tumours (NETs)