The association of intra-therapeutic heterogeneity of somatostatin receptor expression with morphological treatment response in patients undergoing PRRT with [177Lu]-DOTATATE

PLoS One. 2019 May 15;14(5):e0216781. doi: 10.1371/journal.pone.0216781. eCollection 2019.

Abstract

Aim: Purpose of this study was to evaluate the association of the spatial heterogeneity (asphericity, ASP) in intra-therapeutic SPECT/ CT imaging of somatostatin receptor (SSR) positive metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) for morphological treatment response to peptide receptor radionuclide therapy (PRRT). Secondly, we correlated ASP derived form a pre-therapeutic OctreoScan (ASP[In]) and an intra-therapeutic [177Lu]-SPECT/CT (ASP[Lu]).

Materials and methods: Data from first therapy cycle [177Lu-DOTA0-Tyr3]octreotate ([177Lu]-DOTATATE)-PRRT was retrospectively analyzed in 33 patients (m = 20; w = 13; median age, 72 [46-88] years). The evaluation of response to PRRT was performed according to RECIST 1.1 in responding lesions [RL (SD, PR, CR), n = 104] and non-responding lesions [NRL (PD), n = 27]. The association of SSR tumor heterogeneity with morphological response was evaluated by Kruskal-Wallis test and receiver operating characteristic curve (ROC). The optimal threshold for separation (RL vs. NRL) was calculated using the Youden-index. Relationship between pre- and intra-therapeutic ASP was determined with Spearman's rank correlation coefficient (ρ) and Bland-Altman plots.

Results: A total of 131 lesions (liver: n = 59, lymph nodes: n = 48, bone: n = 19, pancreas: n = 5) were analyzed. Lesions with higher ASP values showed a significantly poorer response to PRRT (PD, median: 11.3, IQR: 8.5-15.5; SD, median: 3.4, IQR: 2.1-4.5; PR, median 1.7, IQR: 0.9-2.8; CR, median: 0.5, IQR: 0.0-1.3); Kruskal-Wallis, p<0.001). ROC analyses revealed a significant separation between RL and NRL for ASP after 4 months (AUC 0.85, p<0.001) and after 12 months (AUC 0.94, p<0.001). The optimal threshold for ASP was >5.45% (sensitivity 96% and specificity 82%). The correlation coefficient of pre- and intra-therapeutic ASP revealed ρ = 0.72 (p <0.01). The mean absolute difference between ASP[In] and ASP[Lu] was -0.04 (95% Limits of Agreement, -6.1-6.0).

Conclusion: Pre- and intra-therapeutic ASP shows a strong correlation and might be an useful tool for therapy monitoring.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / mortality
  • Disease-Free Survival
  • Female
  • Gastrointestinal Neoplasms* / diagnostic imaging
  • Gastrointestinal Neoplasms* / metabolism
  • Gastrointestinal Neoplasms* / mortality
  • Humans
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / mortality
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Neuroendocrine Tumors* / diagnostic imaging
  • Neuroendocrine Tumors* / metabolism
  • Neuroendocrine Tumors* / mortality
  • Octreotide / administration & dosage
  • Octreotide / analogs & derivatives*
  • Pancreatic Neoplasms / diagnostic imaging
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / mortality
  • Receptors, Somatostatin / metabolism*
  • Retrospective Studies
  • Single Photon Emission Computed Tomography Computed Tomography*
  • Survival Rate

Substances

  • 177Lu-octreotide, DOTA(0)-Tyr(3)-
  • Neoplasm Proteins
  • Receptors, Somatostatin
  • Octreotide

Grants and funding

The authors received no specific funding for this work.