title: Survival prediction in patients undergoing radionuclide therapy based on intratumoral somatostatin-receptor heterogeneity.
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.
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Werner
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: Lapa
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Harun
authors.initials: H
authors.lastname: Ilhan
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Higuchi
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Buck
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Lehner
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.affiliation: Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Bengel
authors.affiliation: Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Imke
authors.initials: I
authors.lastname: Schatka
authors.affiliation: University of Applied Sciences, Hamburg, Germany.
authors.forename: Dirk O
authors.initials: DO
authors.lastname: Muegge
authors.affiliation: Department of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: László
authors.initials: L
authors.lastname: Papp
authors.affiliation: Mediso Medical Imaging Systems Ltd., Budapest, Hungary.
authors.forename: Norbert
authors.initials: N
authors.lastname: Zsótér
authors.affiliation: Department of Nuclear Medicine, University Medical Center Bonn, Bonn, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Große-Ophoff
authors.affiliation: Department of Nuclear Medicine, University Medical Center Bonn, Bonn, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Essler
authors.affiliation: Department of Nuclear Medicine, University Medical Center Bonn, Bonn, Germany.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Bundschuh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy*; D015282:Octreotide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D011379:Prognosis; D012372:ROC Curve; D017481:Receptors, Somatostatin / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D009942:Organometallic Compounds; D017481:Receptors, Somatostatin; C447941:lutetium Lu 177 dotatate; D015282:Octreotide
keywords: SSTR-PET/CT; neuroendocrine tumor; radiopeptide therapy; textural parameters; tumor heterogeneity