Survival predictors of 177Lu-Dotatate peptide receptor radionuclide therapy (PRRT) in patients with progressive well-differentiated neuroendocrine tumors (NETS)

Abstract

Purpose: 177Lu-Dotatate is an emerging treatment modality for patients with unresectable or metastatic well-differentiated NETs. This study examines survival predictors in patients who received 177Lu-Dotatate.

Methods: A retrospective single-center review was conducted, examining 47 individuals with progressive well-differentiated NETs treated with 177Lu-Dotatate (four induction cycles of 5.5 GBq at 10-week intervals followed by eight maintenance cycles of 3.7 GBq at 6-month intervals).

Results: Median follow-up was 63.1 months with a median progression-free survival (PFS) of 34.1 months. However, median overall survival (OS) was not reached at the time of analysis. The presence of ≥ 5 bone metastases (hazard ratio HR 4.33; p = 0.015), non-gastroenteropancreatic (non-GEP) NETs (HR 3.22; p = 0.025) and development of interim ascites (HR 3.15; p = 0.047) independently predicted a worse OS. Patients with chromogranin A of ≥ 4 × upper limit of normal (ULN) had shorter OS (p < 0.001) and PFS (p = 0.004). Similarly, those with pre-existing ascites demonstrated a worse OS (p = 0.009) and PFS (p = 0.026). Liver metastases involving greater than 50% liver volume and the existence of unusual metastatic locations had a negative impact on OS (p = 0.033) and PFS (p = 0.026), respectively.

Conclusion: High burden of skeletal and hepatic metastases, non-GEP-NETs, chromogranin A of ≥ 4 × ULN, unusual metastatic sites, pre-existing and interim ascites are predictors of poor outcomes in patients treated with 177Lu-Dotatate. These common indicators can be used for the risk stratification and identification of patients most likely to benefit from PRRT.

Trial registration: ClinicalTrials.gov identifier: NCT02236910, Retrospectively registered on September, 2014.

Keywords: Lu-Dotatate; Neuroendocrine; PRRT; Prognostic factors; Survival predictors.

Conflict of interest statement

The authors declare that they have no conflict of interest.

© 2021. The Author(s).

Figures

Fig. 1

Kaplan–Meier curves for OS: a the median OS for the study group had not been reached. b OS by chromogranin A; there was a significant difference in the OS between patients with chromogranin A of ≥ 4 × ULN and those with chromogranin A of < 4 × ULN (p < 0.001). c OS survival by burden of liver metastases; there was a significant difference in the OS between patients with liver metastases of > 50% liver volume compared to those with ≤ 50% liver volume (p = 0.033). d OS by pre-existing ascites; patients with pre-existing ascites prior PRRT initiation had a shorter OS compared to those without pre-existing ascites (p = 0.009)

Fig. 2

Kaplan–Meier curves for OS: a OS by number of bone metastases; there was a significantly shorter OS in patients with (≥ 5) bone deposits compared to patients with (0–4) bone deposits (p = 0.028). b OS by primary tumor site; a longer OS was observed in patients with GEP-NETs vs non-GEP-NETs (p = 0.011). c OS by interim ascites; patients who developed ascites during the period of treatment with 177Lu-Dotatate or after its cessation had a shorter OS (p = 0.026)

Fig. 3

Kaplan–Meier curves for PFS: a the median PFS of the study group was 34.1 months; b PFS by Chromogranin A; there was a significant difference in the PFS between patients with chromogranin A of ≥ 4 × ULN compared to those with chromogranin A of < 4 × ULN (p = 0.004); c PFS by presence of uncommon sites of metastases; patients with uncommon/unusual metastatic sites had a poor PFS (p = 0.026); d PFS by pre-existing ascites; patients with pre-existing ascites prior PRRT initiation had a shorter PFS compared to those without pre-existing ascites (p = 0.026)