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Practical Guidance on Peptide Receptor Radionuclide Therapy (PRRNT) for Neuroendocrine Tumours

This book “Practical Guidance on Peptide Receptor Radionuclide Therapy (PRRNT) for Neuroendocrine Tumours” is a milestone providing a comprehensive multi-disciplinary guidance to  promote the standardized, effective and safe implementation of best practices for the treating of Neuroendocrine and Gastro-Entero-Pancreatic (GEP) tumours applying PRRNT either alone or in combination with other treatment options while taking into consideration most recent International classification of Neuroendocrine tumours.

This book embarks on providing comprehensive protocols for employing either Yttrium-90 or Lutetium-177 tagged somatostatin receptor-targeting peptides and clinically verified protocols for renal protection. It comprises a comprehensive compilation of medical evidence on top of clinical experience of renowned professionals. Furthermore, it contains clinical presentations, eligibility criteria and means of assessing effectiveness of therapy utilizing molecular and morphological medical imaging techniques. NET is a unique sub-class of cancer in which good percentage of affected patients may be treated successfully by PRRNT while improving their symptoms and their quality of life in the majority of cases. This book is a practical reference for specialists in Clinical Oncology and ion Nuclear Medicine embarking on deploying and executing a comprehensive programme for treating patients with neuroendocrine tumours. The Scientific secretary, Mr. J Zaknun, is indebted to the contribution of the experts whose names are listed in an alphabetic order at the end of this book.

It is currently under review so it should be considered as a draft version of the final publication which is not available yet on the IAEA publications site.

This is a non-editable and non-printable version but it can be freely downloaded.

In the near future the free complete PDF version of the publication will be available.

Contents

• 1. INTRODUCTION
  • 1.1. Background
  • 1.2. Objective
  • 1.3. Scope
  • 1.4. Structure
• 2. NEUROENDOCRINE TUMOURS AND PRRNT
  • 2.1. Rationale
  • 2.2. Epidemiology
  • 2.3. Introduction to classification systems
  • 2.4. Clinical presentation
    • 2.4.1. Introduction
    • 2.4.2. Clinical syndromes
  • 2.5. Clinical course and prognosis
  • 2.6. Confirmation of diagnosis and staging
    • 2.6.1. Revision of histopathology specimens
    • 2.6.2. Biochemical assays in functional tumours
    • 2.6.3. General tumour markers
• 3. SPECIAL CONSIDERATION OF PRRNT IN CHILDREN AND ADOLESCENTS
  • 3.1. Introduction
  • 3.2. Epidemiology
  • 3.3. Tumours in children eligible for PRRNT
    • 3.3.1. Carcinoid (neuroendocrine tumour)
    • 3.3.2. Medullary carcinoma
    • 3.3.3. Multiple endocrine neoplasia
    • 3.3.4. Munchausen’s syndrome by proxy
    • 3.3.5. Neuroblastoma
    • 3.3.6. Pheochromocytoma and paraganglioma
    • 3.3.7. Small cell carcinoma
  • 3.4. Administration of PRRNT in children and young adults
  • 3.5. Teaching points
• 4. ANATOMIC IMAGING
  • 4.1. Introduction
  • 4.2. Endoscopy, ultrasound, and endoscopic ultrasound
  • 4.3. Computed tomography and MRI
• 5. MOLECULAR IMAGING
  • 5.1. Introduction
    • 5.1.1. Somatostatin analogues withdrawal
  • 5.2. SPECT imaging of NET
    • 5.2.1. 111In-OctreoScan®
    • 5.2.2. 99mTc-HYNIC-TOC
  • 5.3. PET-CT imaging of NET
    • 5.3.1. 68Ga-PET/CT for somatostatin receptor imaging
    • 5.3.2. 18F-FDG
    • 5.3.3. 18F-DOPA
  • 5.4. Other molecular targets 38
• 6. OPTIONS OF CARE FOR NET
  • 6.1. Role of surgery in neuroendocrine tumours
  • 6.2. Role of somatostatin analogues
  • 6.3. Molecular basis for somatostatin analogues action
  • 6.4. Antisecretory treatment
    • 6.4.1. Carcinoid syndrome
    • 6.4.2. Prevention and therapy of carcinoid crisis
    • 6.4.3. Antiproliferative treatment
    • 6.4.4. Pharmacokinetics and application of somatostatin analogs
  • 6.5. Side effects
  • 6.6. Interferon
  • 6.7. Concluding remarks on the use of SSA
  • 6.8. Chemotherapy
  • 6.9. Molecular targeted therapies
    • 6.9.1. Introduction
    • 6.9.2. Anti-angiogenic pharmaceuticals
    • 6.9.3. mTOR pathway targeting molecules
  • 6.10. Loco-regional approaches
  • 6.11. Supportive and palliative care
    • 6.11.1. Nutrition
    • 6.11.2. Pain control
    • 6.11.3. Evaluation and treatment of bone metastases
    • 6.11.4. Family counselling and patient’s support
• 7. PEPTIDE RECEPTOR RADIONUCLIDE THERAPY (PRRNT)
  • 7.1. Introduction
    • 7.1.1. Historical development
    • 7.1.2. Rationale
    • 7.1.3. Peptide affinity and pharmacokinetics
    • 7.1.4. Tumours suitable for PRRNT
    • 7.1.5. Outcome: response, survival and toxicity
  • 7.2. Multidisciplinary approach to PRRNT
  • 7.3. Radiopharmaceuticals used for therapy
  • 7.4. Patient eligibility for PRRNT
    • 7.4.1. Inclusion criteria
    • 7.4.2. Aggravating conditions (caveats)
    • 7.4.3. Exclusion criteria
  • 7.5. Implementing PRRNT
    • 7.5.1. Somatostatin analogues withdrawal
    • 7.5.2. Pre-medications for PRRNT
    • 7.5.3. Treatment regimens using 90Y-DOTATATE / 90Y-DOTATOC
    • 7.5.4. Treatment regimens using 177Lu-DOTATATE / 177Lu-DOTATOC
    • 7.5.5. Combination 177Lu/90Y-peptides therapy regimens
    • 7.5.6. Additional measures in the compromised patients
    • 7.5.7. Special considerations for PRRNT in children
    • 7.5.8. Retreatment options
• 8. EVALUATION OF RESPONSE
• 9. PRACTICAL ASPECTS OF PRRNT
  • 9.1. Facility
  • 9.2. Administration of therapeutic radiopharmaceuticals
  • 9.3. Renal protection
    • 9.3.1. Physiology of renal irradiation by PRRNT
    • 9.3.2. Amino acids protection protocols
    • 9.3.3. Gelofusin renal protection protocol
    • 9.3.4. Precautions in special clinical conditions
  • 9.4. Post-therapy imaging
    • 9.4.1. 177Lu-DOTATATE
    • 9.4.2. 90Y-DOTATOC
  • 9.5. Post-therapeutic monitoring and management
    • 9.5.1. In between cycles
    • 9.5.2. Intermediate and long-term follow-up
• 10. DOSIMETRY
  • 10.1. Introduction
  • 10.2. Biological Effective Dose (BED) concept
• ANNEX I. DOSIMETRIC METHODS
• ANNEX II. STRUCTURED CLINICAL HISTORY FORM FOR NET PATIENTS (EXAMPLE)
• ANNEX III. KARNOFSKY INDEX AND LANDSKY PLAY SCALE
• ANNEX IV. THE INFORMED CONSENT
• CONTRIBUTORS TO DRAFTING AND REVIEW