Br J Radiol 2018 Mar 20
Retreatment with peptide receptor radionuclide therapy in patients with progressing neuroendocrine tumours: efficacy and prognostic factors for response.   
To evaluate the efficacy and toxicity of a repeat peptide receptor radionuclide therapy (PRRT) course in neuroendocrine tumour patients who have progressed following previous PRRT and to identify factors contributing to retreatment outcomes.
This was a retrospective analysis of 47 consecutive patients who had been treated with PRRT (PRRT1) and following disease progression were retreated with a second course of PRRT (PRRT2). We reviewed patient, tumour and treatment characteristics, time to progression after PRRT1 and PRRT2, overall survival and toxicity. We evaluated Kaplan-Meier survival plots, multiple regression analysis on factors predictive of time to progression and toxicity.
PRRT1: 45/47 patients were initially were treated with Y-DOTATATE, with two patients treated with Lu-DOTATATE. The median progression free survival (PFS) following PRRT1 was 30 months [95% confidence interval (CI) (26.9-36.6 months)]. Two patients developed Grade 1 renal toxicity. 3/47 patients had bone marrow toxicity, with 1 of these patients having Grade 3 toxicity. PRRT2: At the second course of treatment, 29 patients were treated with Y-DOTATATE and 18 patients with Lu-DOTATATE. Of the 44 patients with evaluable survival data, 41 patients developed disease progression. The median PFS after PRRT2 was 17.5 months [95% CI (11-23.8 months)]. There was no statistically significant difference in median PFS dependent on the choice of radiopharmaceutical: median PFS for Lu-DOTATATE = 17.2 months, median PFS for Y-DOTATATE = 17.3 months. Male sex and high burden of liver metastases were associated with shorter PFS following a PRRT retreatment course. 17/41 (41%) patients had bone marrow toxicity (2/17 had Grade 3 toxicity; no Grade 4 toxicity was seen). One patient developed myelodysplastic syndrome. 6/41 (14.6%) developed Grade 1 renal toxicity and 1/41 (2.4%) had Grade 4 renal toxicity. The median overall survival from commencement of first PRRT cycle was 71 months.
PRRT retreatment is safe and offers patients, who had progressed following initial PRRT course, a reasonably good PFS. Extra consideration is needed in patients with multiple comorbidities, as they may be at greater risk of renal and haematological toxicity. Male sex and high burden of liver metastases seem to be associated with shorter PFS following PRRT retreatment.
The majority of studies on PRRT have shown that it is effective as an initial treatment. This study with long-term follow-up demonstrates that PRRT is safe and effective retreatment option in patients that have progressed following initial PRRT course.

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