Constantin Lapa1, Rudolf A Werner2, Jan-Stefan Schmid3, Laszló Papp4, Norbert Zsótér5, Johannes Biko6, Christoph Reiners7, Ken Herrmann8, Andreas K Buck9, Ralph A Bundschuh10. 1. Department of Nuclear Medicine, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany. Electronic address: Lapa_c@ukw.de. 2. Department of Nuclear Medicine, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany. Electronic address: werner_r1@ukw.de. 3. Department of Nuclear Medicine, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany. Electronic address: Schmid_J1@ukw.de. 4. Mediso Medical Imaging Systems Ltd., Budapest, Hungary. Electronic address: laszlo.papp@mediso.com. 5. Mediso Medical Imaging Systems Ltd., Budapest, Hungary. Electronic address: norbert.zsoter@mediso.hu. 6. Department of Nuclear Medicine, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany. Electronic address: biko_j@ukw.de. 7. Department of Nuclear Medicine, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany. Electronic address: reiners_c@ukw.de. 8. Department of Nuclear Medicine, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany. Electronic address: herrmann_k1@ukw.de. 9. Department of Nuclear Medicine, Universitätsklinikum Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany. Electronic address: buck_a@ukw.de. 10. 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.
Abstract
INTRODUCTION: 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.
INTRODUCTION: 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: Christoph Wetz; I Apostolova; I G Steffen; F Hofheinz; C Furth; D Kupitz; J Ruf; M Venerito; S Klose; Holger Amthauer Journal: Mol Imaging Biol Date: 2017-06 Impact factor: 3.488
Authors: Rudolf A Werner; Matthias Kroiss; Masatoyo Nakajo; Dirk O Mügge; Stefanie Hahner; Martin Fassnacht; Andreas Schirbel; Christina Bluemel; Takahiro Higuchi; Laszló Papp; Norbert Zsótér; Andreas K Buck; Ralph A Bundschuh; Constantin Lapa Journal: Endocrine Date: 2016-05-02 Impact factor: 3.633
Authors: Kyle Current; Catherine Meyer; Clara E Magyar; Christine E Mona; Joel Almajano; Roger Slavik; Andreea D Stuparu; Chloe Cheng; David W Dawson; Caius G Radu; Johannes Czernin; Katharina Lueckerath Journal: Clin Cancer Res Date: 2020-01-13 Impact factor: 12.531
Authors: Maryam Gul; Kimberley-Jane C Bonjoc; David Gorlin; Chi Wah Wong; Amirah Salem; Vincent La; Aleksandr Filippov; Abbas Chaudhry; Muhammad H Imam; Ammar A Chaudhry Journal: Front Oncol Date: 2021-07-07 Impact factor: 6.244
Authors: Uta Eberlein; Carina Nowak; Christina Bluemel; Andreas Konrad Buck; Rudolf Alexander Werner; Harry Scherthan; Michael Lassmann Journal: Eur J Nucl Med Mol Imaging Date: 2015-06-06 Impact factor: 9.236
Authors: 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 Journal: Oncotarget Date: 2017-01-24
Authors: Rudolf A Werner; Seval Beykan; Takahiro Higuchi; Katharina Lückerath; Alexander Weich; Michael Scheurlen; Christina Bluemel; Ken Herrmann; Andreas K Buck; Michael Lassmann; Constantin Lapa; Heribert Hänscheid Journal: Oncotarget Date: 2016-07-05