This book reviews the current clinical practice of leptomeningeal metastasis (LM) diagnosis and treatment, which is predominately by intrathecal chemotherapy and/or in combination with external beam radiotherapy. LM is a refractory lethal complication of many human malignancies when neoplastic cells grow in the meninges. The use of penetrating emissions from radionuclides has the advantages of visualizing cerebrospinal fluid (CSF) flow and ablating meninges at shallow depths and has been used to diagnose CSF flow anomalies and to treat LM. The scientific bases of using radionuclides inside human CSF and ablating LM will be discussed within the text, with results from established and completed clinical trials to explore optimal use of radionuclides to diagnose and treat LM. Many limitations of current practices of treating LM are also discussed, as well as potential avenues of overcoming these limitations. This book is an ideal guide for clinical researchers in the practice of treating leptomeningeal metastasis including radiologists, neurologists, oncologists and radiotherapists as well as their associates.
Author(s): Franklin C.L. Wong
Publisher: Springer
Year: 2022
Language: English
Pages: 235
City: Cham
Preface
Acknowledgments
Contents
Contributors
Chapter 1: Human Leptomeningeal Metastasis (LM): Epidemiology and Challenges
Leptomeningeal Metastasis Frequency of Occurrence/Incidence
Challenges of LM Treatment
Limited Knowledge of Meningeal Anatomy, Physiology, and Pathophysiology
Limited LM Diagnosis: Cytology, MRI Abnormalities, PET-CT, RANO-LM
Limited Efficacy of LM Therapy
Advantages of Radiopharmaceuticals for Intrathecal Diagnostics and Therapeutics
References
Chapter 2: State of Art of LM Radiographic Diagnosis: Anatomic and Functional Imaging
Introduction
Diagnosis
MR Imaging
CSF Flow Studies
PET/CT
Response Assessment in Neuro-Oncology (RANO) Proposal for Response Criteria
References
Chapter 3: Radionuclides in the Diagnosis and Therapy in Neuro-Oncology
Introduction
Conventional Nuclear Medicine Studies
SPECT and PET Radiopharmaceuticals in Neuro-Oncology
SPECT Radiopharmaceuticals
PET Radiopharmaceuticals
Glucose Metabolism PET Tracers: FDG
Amino Acid PET Tracers
PET Tracers for Assessment of Tumor Hypoxia
PET Tracers for Assessment of Cellular Proliferation
PET Tracers for Assessment of Tumor Perfusion
PET Tracers for Assessment of Tumor Angiogenesis
PET Imaging for Theranostics in Neuro-Oncology
Newer or Potential Tracers for Emerging Cell Targets in Neuro-Oncology PET
Radionuclide Therapy
Introduction
Neurokinin Type-1 Receptor
Tenascin C
Fibronectin
Epidermal Growth Factor Receptor
DNA–Histone H1 Complex
Somatostatin Receptors
Prostate Membrane Antigen
Amino Acid Metabolism
Matrix Metalloproteinase
Radiopharmaceuticals Used in Preclinical Studies
Conclusions
References
Chapter 4: Scintigraphy of Human CSF Flow in Patients with Leptomeningeal Metastasis
Introduction: Imaging of Human CSF Flow
Intrathecal Radiopharmaceuticals Used in Humans (Table 4.1)
Imaging: Multiple Planar Scans of Multiple Time Points
CSF Flow Abnormalities in LM
Intrathecal In-111 DTPA and Pharmacokinetics in LM
Whole-Body Scan Can Derive Effective Half-Life (Te) in CSF
Clearance of Tracer in Human CSF Space (Fig. 4.2a, b)
CSF Clearance of In-111 DTPA in LM (Figs. 4.3 and 4.4)
Slow CSF Clearance with CSF Blockage (Fig. 4.5a, b)
Fast CSF Clearance with CSF Leakage (Fig. 4.6)
Whole-Body CSF Imaging with Tc99m DTPA (Figs. 4.5b and 4.7)
Whole-Body Ga-67 Scan Showed CSF Patency (Fig. 4.8)
Intraparenchymal Injection (Fig. 4.9a–c)
Malfunction of Ommaya Reservoir (Fig. 4.10a, b)
Ventriculoperitoneal Shunt (Figs. 4.11a–c and 4.12)
SPECT-CT of Cisternograms
Discussion
Intrathecal Radiopharmaceuticals
Effective Half-Life (Te) of Radiopharmaceuticals in CSF
Whole-Body Scans and Radiation Dosimetry
References
Chapter 5: State of Art of LM Therapies: Intrathecal and Systemic Approaches
Introduction
Intrathecal (IT) Chemotherapy
Route of Administration of IT Chemotherapy
Commonly Used IT Chemotherapies
Experimental IT Treatments for LM
Temozolomide
Topotecan
Mafosfamide
Diaziquone
ACNU
Immunotherapy
Immunotoxins
Checkpoint Inhibitors
Radiolabeled Monoclonal Antibodies
IT Immunotherapy
Gene Therapy
Systemic Chemotherapy
Hormonal Therapy
Targeted Therapies
Breast Cancer
IT Trastuzumab
Lung Cancer
Melanoma
Conclusion
References
Chapter 6: Radiation Therapy for Leptomeningeal Disease
Introduction
Indications for Radiotherapy
Good Risk LMD
Poor Risk LMD
Radiotherapy Details and Techniques
Involved-Field Radiotherapy
Whole Brain Radiotherapy
Craniospinal Irradiation
Special Histologic Considerations
Mixed Histologies
Breast Cancer
Pediatric Central Nervous System Disease
Gastrointestinal Cancer
Adult CNS Gliomas
Non-small Cell Lung Cancer
Melanoma
Leukemia/Lymphoma
Gynecologic Cancer
Esthesioneuroblastoma
Pediatric Rhabdomyosarcoma
Treatment Related Toxicities
Involved-Field Radiation Therapy
Whole Brain Radiation Therapy
Craniospinal Irradiation
Conclusions
References
Chapter 7: Neurophysiology Evaluation in Leptomengeal Metastasis Disease
Introduction
Evoked Potentials (SSEP, BAER, VEP, TMS)
References
Chapter 8: Radionuclide Leptomeningeal Metastasis Therapy Trials
Introduction: Rationale for Intrathecal Radionuclide Therapy Trials (Table 8.1)
P-32 Chromic Phosphate Colloids
Au-198 Gold Colloids
I-125 Iododeoxyuridine (IUDR)
Radiolabeled Monoclonal Antibodies
I-131 MoAb (HMGF1, HMFG2, UJ181.4, F811.13, FD32)
I-131 Mel 14 F (ab′)2
I-131 81C6
I-124 and I-131 3F8
I-124 and I-131 Omburtamab
Lu-177 DTPA-Omburtamab
Intrathecal Radionuclide Therapy Dosing Scheme (Table 8.2)
Efficacy and Toxicity of Intrathecal Radionuclide Therapy (Table 8.3)
Radiation Dosimetry as Potential Guidance (Table 8.4)
Conclusions
References
Chapter 9: Simulated Radiation Dosimetry Models After Intraventricular and Intralumbar Injection of Radiopharmaceuticals
Introduction
Methodology
Radionuclides and Radiopharmaceuticals
Biokinetic Models of CSF and Flow
Radiation Dosimetry from Activity Absorbed into the Systemic Circulation
MCNP Monte Carlo Radiation Transport Simulations
Final Dosimetry Estimates
Results from Intraventricular Injections [19]
CSF and Organ Dosimetry
Absorbed Dose as a Function of Depth Surrounding CSF Spaces
Ventricular Stasis (VS)
Results from Intralumbar Injections
CSF and Organ Dosimetry
Absorbed Dose Vs. Depth
Lumbar Stasis (LS)
Conclusion
Discussion
Limitations of Dosimetric Models
Prediction of Potential Toxicities and Efficacy in LM
Dosing Considerations: An Example with Y-90 DTPA
Additional Dosimetric Considerations: CSF Blockage, Postsurgical Cavity Therapy
Appendix: Dosimetry Methods for Brain Dose as a Function of Depth
References
Chapter 10: Human Radiation Dosimetry from Imaging: Guidance for Therapy
Introduction
Radionuclide and Radiopharmaceutical Properties
Quantitative Imaging of Radionuclides
Data Processing for Dosimetry
Summary
References
Chapter 11: Regulatory Oversight of Radiopharmaceuticals
Introduction
Federal Regulatory Authority of Radiopharmacuticals
Nuclear Regulatory Commission
Food and Drug Administration
Other Pertinent Regulatory Agencies
Occupational Safety and Health Administration (OSHA)
Environmental Protection Agency (EPA)
Department of Transportation (DOT)
State Regulatory Control
NRC/State Health Radiation Control: RAM Inspection
State Boards of Pharmacy (BOP): Pharmacy Inspection
Accreditation Organizations: The Joint Commission Inspection
Internal/Local Regulatory Authority
Radiation Safety Committee/Radiation Safety Office
Radioactive Drug Research Committee
Institutional Review Board
Regulatory Outlook of Radiopharmaceuticals
References
Chapter 12: Radionuclides in the Management of Leptomeningeal Metastasis: Framework and Opportunities
Introduction: Radiopharmaceuticals in LM Management
Intrathecal Radiopharmaceuticals for Assessment of CSF Flow
CSF Radionuclide Imaging and Radiation Dosimetry
Considerations in Intrathecal Radiopharmaceuticals Therapy
Molecular Targeting Versus Geographic Targeting
Novel Intrathecal Use of Radiopharmaceuticals with Therapeutic Potentials
Radioactive Cations
Radioactive Anions (Halides- I-131, I-124 NaI, and Perhaps At-211)
Radiolabeled Monoclonal Antibodies and Proteins
Radio-Labeled Peptides (In-111 Octreotide, Cu-67 Sartate, Lu-177 Lutathera)
Potential Use of Alpha Emitters (Radium-223)
Conclusion
References
Index
