title: Dose response of pancreatic neuroendocrine tumors treated with peptide receptor radionuclide therapy using 177Lu-DOTATATE.
abstract: Peptide receptor radionuclide therapy (PRRT) is a promising treatment for patients with neuroendocrine tumors, giving rise to improved survival. Dosimetric calculations in relation to PRRT have been concentrated to normal organ dosimetry in order to limit side effects. However, the relation between the absorbed dose to the tumor and treatment response has so far not been established. Better knowledge in this respect may improve the understanding of treatment effects, allow for improved selection of those patients who are expected to benefit from PRRT, and avoid unnecessary treatments. The aim of the present work was to evaluate the dose-response relationship for pancreatic neuroendocrine tumors treated with PRRT using (177)Lu-DOTATATE.
  
  
  METHODS
  Tumor-absorbed dose calculations were performed for 24 lesions in 24 patients with metastasized pancreatic neuroendocrine tumors treated with repeated cycles of (177)Lu-DOTATATE at 8-wk intervals. The absorbed dose calculations relied on sequential SPECT/CT imaging at 24, 96, and 168 h after infusion of (177)Lu-DOTATATE. The unit density sphere model from OLINDA was used for absorbed dose calculations. The absorbed doses were corrected for partial-volume effect based on phantom measurements. On the basis of these results, only tumors larger than 2.2 cm in diameter at any time during the treatment were included for analysis. To further decrease the effect of partial-volume effect, a subgroup of tumors (>4.0 cm) was analyzed separately. Tumor response was evaluated by CT using Response Evaluation Criteria In Solid Tumors.
  
  
  RESULTS
  Tumor-absorbed doses until best response ranged approximately from 10 to 340 Gy. A 2-parameter sigmoid fit was fitted to the data, and a significant correlation between the absorbed dose and tumor reduction was found, with a Pearson correlation coefficient (R(2)) of 0.64 for tumors larger than 2.2 cm and 0.91 for the subgroup of tumors larger than 4.0 cm. The largest tumor reduction was 57% after a total absorbed dose of 170 Gy.
  
  
  CONCLUSIONS
  The results imply a significant correlation between absorbed dose and tumor reduction. However, further studies are necessary to address the large variations in response for similar absorbed doses.
authors.affiliation: Nuclear Medicine and PET, Department of Radiology, Oncology, and Radiation Science, Uppsala University, Uppsala, Sweden Medical Physics, Uppsala University Hospital, Uppsala, Sweden ezgi.ilan@akademiska.se.
authors.forename: Ezgi
authors.initials: E
authors.lastname: Ilan
authors.affiliation: Nuclear Medicine and PET, Department of Radiology, Oncology, and Radiation Science, Uppsala University, Uppsala, Sweden Medical Physics, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Sandström
authors.affiliation: Nuclear Medicine and PET, Department of Radiology, Oncology, and Radiation Science, Uppsala University, Uppsala, Sweden Molecular Imaging, Medical Imaging Centre, Uppsala University Hospital, Uppsala, Sweden; and.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Wassberg
authors.affiliation: Nuclear Medicine and PET, Department of Radiology, Oncology, and Radiation Science, Uppsala University, Uppsala, Sweden Molecular Imaging, Medical Imaging Centre, Uppsala University Hospital, Uppsala, Sweden; and.
authors.forename: Anders
authors.initials: A
authors.lastname: Sundin
authors.affiliation: Nuclear Medicine and PET, Department of Radiology, Oncology, and Radiation Science, Uppsala University, Uppsala, Sweden Molecular Imaging, Medical Imaging Centre, Uppsala University Hospital, Uppsala, Sweden; and.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Garske-Román
authors.affiliation: Section of Endocrine Oncology, Department of Medical Science, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Barbro
authors.initials: B
authors.lastname: Eriksson
authors.affiliation: Section of Endocrine Oncology, Department of Medical Science, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Dan
authors.initials: D
authors.lastname: Granberg
authors.affiliation: Nuclear Medicine and PET, Department of Radiology, Oncology, and Radiation Science, Uppsala University, Uppsala, Sweden Medical Physics, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
mesh_terms: D000328:Adult; D000368:Aged; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007668:Kidney / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000532:radiotherapy*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000532:radiotherapy*; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D011868:Radioisotopes / Q000627:therapeutic use; D011874:Radiometry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D018000:Receptors, Peptide / Q000737:chemistry; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: C504257:177Lu-octreotide, DOTA(0)-Tyr(3)-; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D018000:Receptors, Peptide; D015282:Octreotide
keywords: 177Lu-DOTATATE; RECIST; dose-response; dosimetry; neuroendocrine tumors