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Neuroendocrine Tumor Therapy
Tristan R. Lawson, MD; Paige Bennett, MD
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KEY FACTS

  • Terminology

    • Preprocedure

      • Procedure

        • Post Procedure

          TERMINOLOGY

          • Definitions

            • Neuroendocrine tumors (NETs)
              • Arise from neuroendocrine cells in any organ or tissue in body; gastroenteropancreatic is most common
              • Can secrete biologically active peptides or amines; however, most are inactive and can present late with locally advanced or metastatic disease
              • Historically, survival rate for gastroenteropancreatic NETs (GEP-NETs) was 68.1%, but this varies based on primary location
              • Somatostatin subtype 2 (SST2) receptors are overexpressed by GEP-NETs
            • NET therapy with Lu-177 dotatate
              • Radiolabeled somatostatin analog that binds to tumors
                • Administered as series of 4 IV infusions every 8 weeks
                • Each infusion delivers ~ 200 mCi (7.4 Gbq) Lu-177 dotatate
                • Lu-177 decays by beta emission > > > gamma emission; t1/2: 6.73 days
                  • Beta particles penetrate ~ 2.2 mm and are locally destructive to tumor cells
                • Lu-177 dotatate biodistributes after infusion to tumor but also to kidneys, liver, spleen, pituitary, and thyroid
                • Primary elimination of Lu-177 dotatate is by renal excretion
                • FDA approved for SSTR-positive GEP-NETs, though used off-label for other NETs
            • NETTER-1 randomized clinical trial
              • Patients with advanced midgut NETs
              • Increased progression-free survival and response rate for patients receiving Lu-177 dotatate over high-dose somatostatin analog (octreotide)
              • Showed 82% risk reduction for patient on Lu-177 radiotherapy to die or have disease progression compared to long-acting octreotide

          PREPROCEDURE

          • Indications

            • Contraindications

              • Preprocedure Imaging

                • Getting Started

                  PROCEDURE

                  • Patient Position/Location

                    • Procedure Steps

                      • Findings and Reporting

                        • Alternative Procedures/Therapies

                          POST PROCEDURE

                          • Expected Outcome

                            • Things To Do

                              • Things To Avoid

                                OUTCOMES

                                • Complications

                                  Selected References

                                  1. Hennrich U et al: Lutathera®: The first FDA- and EMA-approved radiopharmaceutical for peptide receptor radionuclide therapy. Pharmaceuticals (Basel). 12(3), 2019
                                  2. Cherk MH et al: Changes in biodistribution on 68Ga-DOTA-octreotate PET/CT after long acting somatostatin analogue therapy in neuroendocrine tumour patients may result in pseudoprogression. Cancer Imaging. 18(1):3, 2018
                                  3. Hirmas N et al: Peptide receptor radionuclide therapy and the treatment of gastroentero-pancreatic neuroendocrine tumors: Current findings and future perspectives. Nucl Med Mol Imaging. 52(3):190-9, 2018
                                  4. Kim K et al: Lu-177-Based Peptide Receptor Radionuclide Therapy for Advanced Neuroendocrine Tumors. Nucl Med Mol Imaging. 52(3):208-215, 2018
                                  5. Brabander T et al: Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors. Clin Cancer Res. 23(16):4617-4624, 2017
                                  6. Strosberg J et al: Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med. 376(2):125-135, 2017
                                  7. Deppen SA et al: 68Ga-DOTATATE Compared with 111In-DTPA-Octreotide and Conventional Imaging for Pulmonary and Gastroenteropancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis. J Nucl Med. 57(6):872-8, 2016
                                  8. Hofman MS et al: Somatostatin receptor imaging with 68Ga DOTATATE PET/CT: clinical utility, normal patterns, pearls, and pitfalls in interpretation. Radiographics. 35(2):500-6, 2015
                                  9. Bodei L et al: The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 40(5):800-16, 2013
                                  10. Lutathera Prescribing Information
                                  Related Anatomy
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                                  Related Differential Diagnoses
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                                  References
                                  Tables

                                  Tables

                                  KEY FACTS

                                  • Terminology

                                    • Preprocedure

                                      • Procedure

                                        • Post Procedure

                                          TERMINOLOGY

                                          • Definitions

                                            • Neuroendocrine tumors (NETs)
                                              • Arise from neuroendocrine cells in any organ or tissue in body; gastroenteropancreatic is most common
                                              • Can secrete biologically active peptides or amines; however, most are inactive and can present late with locally advanced or metastatic disease
                                              • Historically, survival rate for gastroenteropancreatic NETs (GEP-NETs) was 68.1%, but this varies based on primary location
                                              • Somatostatin subtype 2 (SST2) receptors are overexpressed by GEP-NETs
                                            • NET therapy with Lu-177 dotatate
                                              • Radiolabeled somatostatin analog that binds to tumors
                                                • Administered as series of 4 IV infusions every 8 weeks
                                                • Each infusion delivers ~ 200 mCi (7.4 Gbq) Lu-177 dotatate
                                                • Lu-177 decays by beta emission > > > gamma emission; t1/2: 6.73 days
                                                  • Beta particles penetrate ~ 2.2 mm and are locally destructive to tumor cells
                                                • Lu-177 dotatate biodistributes after infusion to tumor but also to kidneys, liver, spleen, pituitary, and thyroid
                                                • Primary elimination of Lu-177 dotatate is by renal excretion
                                                • FDA approved for SSTR-positive GEP-NETs, though used off-label for other NETs
                                            • NETTER-1 randomized clinical trial
                                              • Patients with advanced midgut NETs
                                              • Increased progression-free survival and response rate for patients receiving Lu-177 dotatate over high-dose somatostatin analog (octreotide)
                                              • Showed 82% risk reduction for patient on Lu-177 radiotherapy to die or have disease progression compared to long-acting octreotide

                                          PREPROCEDURE

                                          • Indications

                                            • Contraindications

                                              • Preprocedure Imaging

                                                • Getting Started

                                                  PROCEDURE

                                                  • Patient Position/Location

                                                    • Procedure Steps

                                                      • Findings and Reporting

                                                        • Alternative Procedures/Therapies

                                                          POST PROCEDURE

                                                          • Expected Outcome

                                                            • Things To Do

                                                              • Things To Avoid

                                                                OUTCOMES

                                                                • Complications

                                                                  Selected References

                                                                  1. Hennrich U et al: Lutathera®: The first FDA- and EMA-approved radiopharmaceutical for peptide receptor radionuclide therapy. Pharmaceuticals (Basel). 12(3), 2019
                                                                  2. Cherk MH et al: Changes in biodistribution on 68Ga-DOTA-octreotate PET/CT after long acting somatostatin analogue therapy in neuroendocrine tumour patients may result in pseudoprogression. Cancer Imaging. 18(1):3, 2018
                                                                  3. Hirmas N et al: Peptide receptor radionuclide therapy and the treatment of gastroentero-pancreatic neuroendocrine tumors: Current findings and future perspectives. Nucl Med Mol Imaging. 52(3):190-9, 2018
                                                                  4. Kim K et al: Lu-177-Based Peptide Receptor Radionuclide Therapy for Advanced Neuroendocrine Tumors. Nucl Med Mol Imaging. 52(3):208-215, 2018
                                                                  5. Brabander T et al: Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors. Clin Cancer Res. 23(16):4617-4624, 2017
                                                                  6. Strosberg J et al: Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med. 376(2):125-135, 2017
                                                                  7. Deppen SA et al: 68Ga-DOTATATE Compared with 111In-DTPA-Octreotide and Conventional Imaging for Pulmonary and Gastroenteropancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis. J Nucl Med. 57(6):872-8, 2016
                                                                  8. Hofman MS et al: Somatostatin receptor imaging with 68Ga DOTATATE PET/CT: clinical utility, normal patterns, pearls, and pitfalls in interpretation. Radiographics. 35(2):500-6, 2015
                                                                  9. Bodei L et al: The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 40(5):800-16, 2013
                                                                  10. Lutathera Prescribing Information