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

J Cancer Res Clin Oncol. 2022 Jan;148(1):225-236. doi: 10.1007/s00432-021-03672-w. Epub 2021 Jun 10.

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.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiemetics / therapeutic use
  • Ascites / mortality
  • Ascites / pathology
  • Biomarkers, Tumor / analysis
  • Bone Neoplasms / mortality
  • Bone Neoplasms / secondary*
  • Chromogranin A / analysis
  • Endoderm / pathology
  • Female
  • Humans
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary*
  • Male
  • Middle Aged
  • Neural Crest / pathology
  • Neuroendocrine Tumors / mortality*
  • Neuroendocrine Tumors / pathology
  • Neuroendocrine Tumors / radiotherapy*
  • Octreotide / adverse effects
  • Octreotide / analogs & derivatives*
  • Octreotide / therapeutic use
  • Organometallic Compounds / adverse effects
  • Organometallic Compounds / therapeutic use*
  • Progression-Free Survival
  • Radiopharmaceuticals / adverse effects
  • Radiopharmaceuticals / therapeutic use
  • Retrospective Studies

Substances

  • Antiemetics
  • Biomarkers, Tumor
  • Chromogranin A
  • Organometallic Compounds
  • Radiopharmaceuticals
  • lutetium Lu 177 dotatate
  • Octreotide

Associated data

  • ClinicalTrials.gov/NCT02236910