Survival prediction in patients undergoing radionuclide therapy based on intratumoral somatostatin-receptor heterogeneity

Rudolf A. Werner, Constantin Lapa, Harun Ilhan, Takahiro Higuchi, Andreas K. Buck, Sebastian Lehner, Peter Bartenstein, Frank Bengel, Imke Schatka, Dirk O. Muegge, László Papp, Norbert Zsótér, Tobias Große-Ophoff, Markus Essler, Ralph A. Bundschuh

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The NETTER-1 trial demonstrated significantly improved progression-free survival (PFS) for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET) emphasizing the high demand for response prediction in appropriate candidates. In this multicenter study, we aimed to elucidate the prognostic value of tumor heterogeneity as assessed by somatostatin receptor (SSTR)-PET/CT. 141 patients with SSTR-expressing tumors were analyzed obtaining SSTR-PET/CT before PRRT (1-6 cycles, 177Lu somatostatin analog). Using the Interview Fusion Workstation (Mediso), a total of 872 metastases were manually segmented. Conventional PET parameters as well as textural features representing intratumoral heterogeneity were computed. The prognostic ability for PFS and overall survival (OS) were examined. After performing Cox regression, independent parameters were determined by ROC analysis to obtain cut-off values to be used for Kaplan-Meier analysis. Within follow-up (median, 43.1 months), 75 patients showed disease progression (median, 22.2 m) and 54 patients died (median, 27.6 m). Cox analysis identified 8 statistically independent heterogeneity parameters for time-to-progression and time-to-death. Among them, the textural feature Entropy predicted both PFS and OS. Conventional PET parameters failed in response prediction. Imaging-based heterogeneity assessment provides prognostic information in PRRT candidates and outperformed conventional PET parameters. Its implementation in clinical practice can pave the way for individualized patient management.

Original languageEnglish
Pages (from-to)7039-7049
Number of pages11
JournalOncotarget
Volume8
Issue number4
DOIs
Publication statusPublished - Jan 1 2017

Keywords

  • Neuroendocrine tumor
  • Radiopeptide therapy
  • SSTR-PET/CT
  • Textural parameters
  • Tumor heterogeneity

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Werner, R. A., Lapa, C., Ilhan, H., Higuchi, T., Buck, A. K., Lehner, S., Bartenstein, P., Bengel, F., Schatka, I., Muegge, D. O., Papp, L., Zsótér, N., Große-Ophoff, T., Essler, M., & Bundschuh, R. A. (2017). Survival prediction in patients undergoing radionuclide therapy based on intratumoral somatostatin-receptor heterogeneity. Oncotarget, 8(4), 7039-7049. https://doi.org/10.18632/oncotarget.12402