title: Prognostic value of positron emission tomography-assessed tumor heterogeneity in patients with thyroid cancer undergoing treatment with radiopeptide therapy.
abstract: BACKGROUND
  Peptide receptor radionuclide therapy (PRRT) is a treatment option for both iodine-refractory differentiated and advanced medullary thyroid cancer (TC). It requires over-expression of somatostatin receptor subtype II (SSTR) that can be non-invasively assessed by positron emission tomography (PET). Assessment of tumor heterogeneity is increasingly used as a tool for prognostication prediction. We investigated the potential of SSTR-PET to assess intraindividual tumor heterogeneity and thereby treatment response prior to PRRT.
  
  
  METHODS
  12 patients with progressive radioiodine-refractory differentiated (1 papillary, 1 oxyphilic, 2 oncocytic, 4 follicular) or medullary (n=4) TC were enrolled. SSTR-PET was performed at baseline. Conventional PET parameters and heterogeneity parameters were analyzed regarding their potential to predict progression-free (PFS, mean, 221 days) and overall survival (OS, mean, 450 days). Parameters of a subgroup of lesions (n=23) were also correlated with morphological response according to modified RECIST criteria.
  
  
  RESULTS
  In patient-based analysis, all conventional parameters failed to predict PFS. Several textural parameters showed a significant capability to assess PFS. Thereby, "Grey level non uniformity" had the highest area under the curve (AUC, 0.93) in Receiver operating characteristics analysis followed by "Contrast" (AUC, 0.89). In lesion-based analysis, only "Entropy" revealed potential to evaluate disease progression. OS could not be assessed by any parameter investigated.
  
  
  CONCLUSIONS
  Tumor heterogeneity seems to be a predictor of response to PRRT in patients with iodine-refractory differentiated/advanced medullary thyroid cancer and outperforms conventional PET parameters like standardized uptake value. In a "theranostic" approach, assessment of textural parameters may help in selecting patients who might benefit from PRRT.
authors.affiliation: Department of Nuclear Medicine, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany. Electronic address: Lapa_c@ukw.de.
authors.forename: Constantin
authors.initials: C
authors.lastname: Lapa
authors.affiliation: Department of Nuclear Medicine, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany. Electronic address: werner_r1@ukw.de.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Werner
authors.affiliation: Department of Nuclear Medicine, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany. Electronic address: Schmid_J1@ukw.de.
authors.forename: Jan-Stefan
authors.initials: JS
authors.lastname: Schmid
authors.affiliation: Mediso Medical Imaging Systems Ltd., Budapest, Hungary. Electronic address: laszlo.papp@mediso.com.
authors.forename: Laszló
authors.initials: L
authors.lastname: Papp
authors.affiliation: Mediso Medical Imaging Systems Ltd., Budapest, Hungary. Electronic address: norbert.zsoter@mediso.hu.
authors.forename: Norbert
authors.initials: N
authors.lastname: Zsótér
authors.affiliation: Department of Nuclear Medicine, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany. Electronic address: biko_j@ukw.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Biko
authors.affiliation: Department of Nuclear Medicine, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany. Electronic address: reiners_c@ukw.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Reiners
authors.affiliation: Department of Nuclear Medicine, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany. Electronic address: herrmann_k1@ukw.de.
authors.forename: Ken
authors.initials: K
authors.lastname: Herrmann
authors.affiliation: Department of Nuclear Medicine, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany. Electronic address: buck_a@ukw.de.
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Buck
authors.affiliation: Department of Nuclear Medicine, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany; Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Bonn, Bonn, Germany. Electronic address: ralph.bundschuh@ukb.uni-bonn.de.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Bundschuh
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D017481:Receptors, Somatostatin / Q000378:metabolism; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D014057:Tomography, X-Ray Computed
chemical_list: D007457:Iodine Radioisotopes; D010455:Peptides; D017481:Receptors, Somatostatin
keywords: Iodine-refractory; Positron emission tomography; Somatostatin receptor; Theranostic; Thyroid cancer; Tumor heterogeneity