Radiation Oncology for Pediatric Cns Tumors

Description

This book reviews the principles and applications of radiotherapy in the management of pediatric brain tumors to allow the reader to gain a full appreciation of the major aspects involved in caring for these patients. Individual sections are devoted to basic principles, specific management for the full range of tumor entities, radiotherapy techniques, and potential toxicities and their management. The book is written and edited by world leaders in pediatric radiotherapy, and care has been taken to cover the latest advances in diagnosis and radiotherapy techniques. Pediatric brain tumors represent a diverse group of neoplasms that require carefully planned management for successful definitive treatment. Radiotherapy is one of the fundamental components in treatment for the majority of these vulnerable patients. The optimal radiation therapy approach will depend on multiple factors, including tumor type and location, extent of disease, age of the patient, and other therapies. A thorough understanding of the natural history of the disease, communication with the multidisciplinary team, full knowledge of available radiotherapy techniques, and consideration of potential acute and late toxicities are therefore essential for each patient.

Table of Contents

1. Part I: Basic Principles
2. Epidemiology of Childhood Brain Tumors
3. Introduction
4. Descriptive Epidemiology
5. Glioma
6. Pilocytic Astrocytoma
7. High-Grade Glioma
8. Brain Stem Gliomas
9. Embryonal Tumors
10. Medulloblastoma
11. Primitive Neuroectodermal Tumor (PNET)
12. Atypical Teratoid/Rhabdoid Tumor (AT/RT)
13. Other Brain Tumors
14. Choroid Plexus Carcinoma
15. Ependymoma
16. Craniopharyngioma
17. Germ Cell Tumors
18. Analytic Epidemiology
19. Environmental Risk Factors
20. Radiation Exposure
21. Ionizing Radiation
22. Nonionizing Radiation
23. Other Environmental Risk Factors
24. Genetic Factors
25. Hereditary Cancer Predisposition Syndromes
26. Neurocutaneous Disorders
27. Turcot Syndrome
28. Conditions Exclusively Having Oncologic Features
29. Hereditary Cancer Predisposition Syndromes Summary
30. References
31. Histopathology of Primary Tumors of the Central Nervous System
32. Meningeal Tumors
33. Meningioma
34. Atypical Meningioma (WHO Grade II)
35. Anaplastic (Malignant) Meningioma
36. Mesenchymal, Non-meningothelial Tumors
37. Solitary Fibrous Tumor/Hemangiopericytoma
38. Capillary Hemangioblastoma
39. Meningeal Sarcomatosis
40. Mesenchymal Chondrosarcoma
41. Melanocytic Lesions
42. Astrocytic Tumors
43. Anaplastic (Malignant) Astrocytoma
44. Glioblastoma
45. Ependymal Tumors
46. Oligodendroglioma
47. Mixed Glioma
48. Choroid Plexus Tumors
49. Embryonal Tumors
50. Neuronal and Mixed Neuronal-Glial Tumors
51. Central Neurocytoma
52. Miscellaneous Tumors
53. Schwannoma (Neurilemmoma)
54. Germ Cell Tumors
55. Suggested Reading
56. Meningiomas
57. Capillary Hemagioblastoma
58. Gliomas
59. Embryonal Tumors: Medulloblastoma
60. ATRT
61. PNET
62. Glioneuronal Tumors/DNET/Lymphoma/Germ Cell Tumors
63. Craniopharyngiomas
64. Imaging of Pediatric Central Nervous System Tumors
65. Imaging Tools
66. Computerized Tomography
67. Magnetic Resonance Imaging
68. Advanced MRI Applications
69. -Weighted Imaging (DWI), Diffusion-Tensor Imaging (DTI) and Tractography
70. MR Perfusion Imaging
71. Magnetic Resonance Spectroscopy (MRS)
72. Functional MRI (fMRI)
73. Vascular Imaging
74. Positron Emission Tomography (PET)
75. Protocol Optimization
76. Supratentorial Tumors
77. Infratentorial Tumors
78. Orbital Tumors
79. Sellar and Suprasellar Tumors
80. Imaging Applications for Patient Management
81. Surgery
82. Radiotherapy Planning and Management
83. Treatment Complications
84. Summary
85. References
86. Surgical Principles in the Treatment of Pediatric Brain Tumors
87. Introduction
88. Surgical Approaches to Brain Tumors
89. Neuro-Navigation
90. Intraoperative Imaging
91. Intraoperative Monitoring
92. Hydrocephalus Management
93. Posterior Fossa Syndrome
94. Interruption of the Dentatothalamocortical Pathway as a Possible Cause of PFS
95. Cerebellar Swelling as a Possible Cause of PFS
96. Mass Effect/Intracranial Pressure Management
97. Steroids
98. Seizure Management
99. References
100. Chemotherapeutic Strategies in Brain Tumors
101. Introduction
102. Chemotherapeutic Drugs
103. Nitrosoureas
104. Ifosfamide/Cyclophosphamide
105. Temozolomide
106. Platinums
107. Vinca Alkaloids
108. Etoposide
109. Chemotherapy in Infantile Brain Tumors
110. Resistance to Chemotherapeutic Drugs
111. Blood Brain Barrier and Mechanisms to Overcome Its Resistance
112. Targeted Chemotherapy
113. References
114. Part II: Embryonal Brain Tumors
115. Medulloblastoma
116. Epidemiology
117. Predisposing Factors
118. Presenting Symptoms
119. Radiographic and Pathologic Findings
120. Radiology
121. Pathology
122. Workup
123. Acute Management
124. Treatment
125. Surgery
126. Radiotherapy
127. Radiotherapy Volume
128. Radiotherapy Dose
129. Chemotherapy
130. Infant Medulloblastoma
131. Target Delineation and Technique
132. Follow-Up and Outcomes
133. Follow-Up Guidelines
134. Future Directions
135. References
136. Supratentorial Primitive Neuroectodermal Tumor
137. Epidemiology
138. Predisposing Factors
139. Etiology
140. Genetic Issues
141. Presenting Symptoms
142. Radiographic Findings
143. Workup
144. Acute Management
145. Treatment
146. Evolution to Current Practice
147. Role of Surgery
148. Role of Chemotherapy
149. Standard Chemotherapy
150. Chemotherapy for Very Young Patients
151. Intensified Chemotherapy
152. Post-RT Chemotherapy
153. Chemotherapy for Pineal SPNET
154. Role of RT
155. Standard Fractionated RT
156. Altered Fractionation RT
157. RT for Very Young Patients
158. Target Delineation
159. RT Volumes
160. Dose
161. For Patients 3 Years of Age or Older
162. For Patients <3 Years of Age
163. Techniques
164. Outcomes
165. Follow-Up Guidelines
166. EFS, PFS, OS
167. Toxicities
168. Future Directions
169. References
170. Atypical Teratoid Rhabdoid Tumors (AT/RT) and ETMR
171. Epidemiology
172. Predisposing Factors
173. Presenting Symptoms
174. Radiographic Findings
175. Workup
176. Treatment
177. Surgery
178. Chemotherapy
179. Radiation Therapy
180. Radiation Fields and Doses
181. Outcomes
182. Toxicities
183. Future Directions
184. References
185. Part III: Glial Tumors
186. Ependymoma
187. Introduction
188. Prognostic Factors
189. Age at Presentation
190. Extent of Surgical Resection
191. Site of Primary Tumor
192. Histopathologic Grade
193. Molecular Prognostic Factors
194. Radiation Therapy
195. Radiation Dose
196. Irradiation Volume
197. Imaging and Treatment Planning
198. Very Young Children
199. Spinal Ependymoma
200. New Radiotherapy Modalities
201. Intensity-Modulated Radiation Therapy
202. Proton Therapy
203. Neurologic, Endocrine, and Cognitive Effects
204. Necrosis, Vasculopathy, and Secondary Brain Tumors
205. Chemotherapy
206. Tumor Recurrence
207. Re-irradiation
208. References
209. Low-Grade Glioma
210. Epidemiology/Predisposing Factors
211. Histology
212. Molecular Genetic Profiles
213. Presenting Symptoms
214. Low-Grade Midline, Supratentorial Tumours
215. Cerebellar Tumours
216. Radiographic Findings
217. Work-Up
218. General Management
219. Surgery
220. Chemotherapy
221. Radiation Therapy
222. Response of Tumour to Treatment
223. Radiotherapy Following Chemotherapy
224. Dose Response Effects
225. Proton Therapy
226. Brachytherapy
227. Radiosurgery
228. Radiotherapy in Grade II Astrocytoma
229. Other Rare Histological Subtypes
230. Radiotherapy in Leptomeningeal Dissemination
231. Radiotherapy Treatment Planning
232. Radiotherapy Target Volume Definition
233. Late Effects
234. Follow-Up
235. Future Directions
236. References
237. Optic Pathway Glioma
238. Epidemiology
239. Predisposing Factors
240. Presenting Symptoms
241. Radiographic Findings
242. Workup
243. Acute Management
244. Treatment
245. Target Delineation
246. Outcomes
247. Treatment Toxicity
248. Future Directions
249. References
250. High-Grade Glioma
251. Epidemiology
252. Predisposing Factors
253. Etiology
254. Genetic Issues
255. Presenting Symptoms
256. Radiographic Findings
257. Workup
258. Acute Management
259. CSF
260. Mass Effect
261. Steroid Use
262. Treatment
263. Evolution to Current Treatment
264. Role of Surgery
265. Role of Chemotherapy
266. Role of Radiotherapy
267. Sequencing of Radiotherapy and Chemotherapy
268. Radiotherapy Dose
269. Target Delineation
270. Radiotherapy Tumor Target Volumes
271. Radiotherapy Organs at Risk
272. Outcomes
273. Follow-Up Guidelines
274. EFS, DFS, OS
275. Toxicities
276. Future Directions
277. References
278. Brainstem Tumors
279. Introduction
280. Focal Tumors
281. Treatment
282. Surgery
283. Chemotherapy
284. Radiotherapy
285. Evolution of Practice and Future Directions
286. Diffuse Intrinsic Pontine Gliomas
287. Workup
288. Acute Management
289. Treatment
290. Radiotherapy
291. Chemotherapy
292. Treatment Outcomes
293. Follow-Up After Radiotherapy
294. Treatment at Progression
295. Evolution of Practice and Future Directions
296. References
297. Part IV: Germ Cell Tumors
298. Central Nervous System Germinoma
299. Epidemiology
300. Predisposing Factors
301. Presenting Symptoms
302. Radiographic Findings
303. Workup
304. Acute Management
305. Treatment
306. Surgery
307. Radiotherapy
308. Chemotherapy and Reduced-Dose Radiation
309. Target Delineation
310. Outcomes
311. Future Directions
312. References
313. Central Nervous System Nongerminomatous Germ Cell Tumors
314. Epidemiology
315. Biology of Intracranial Germ Cell Tumors
316. Presenting Symptoms
317. Radiographic Findings
318. Workup
319. Acute Management
320. Treatment
321. Chemotherapy
322. Radiotherapy
323. Radiotherapy Volume and Dose
324. Radiotherapy Technique
325. Surgery
326. Target Delineation
327. Outcomes
328. Toxicities
329. Future Directions
330. References
331. Part V: Miscellaneous Tumors
332. Craniopharyngioma
333. Epidemiology
334. Predisposing Factors: Etiology and Genetics
335. Presenting Symptoms
336. Radiographic Findings
337. Workup
338. Treatment
339. Surgery
340. Radiation Therapy
341. Radiation Details
342. Cystic Considerations for Radiation Planning
343. Intracavitary Therapies
344. Outcomes
345. Outcomes
346. Toxicities
347. References
348. CNS Leukemia
349. Epidemiology
350. Predisposing Factors
351. Etiology
352. Genetic Issues
353. Presenting Symptoms/Findings
354. Workup
355. Cytogenetics
356. Acute Management
357. Treatment
358. General Principles
359. Role of RT: Initial Therapy
360. Role of RT: Relapsed ALL
361. Role of RT: AML
362. Target Delineation
363. RT Volumes
364. Dose
365. Techniques
366. Outcomes
367. Follow-Up Guidelines
368. Cure and Survival
369. Toxicities
370. Secondary Malignancies
371. Hypopituitarism
372. Cognitive Dysfunction
373. Leukoencephalopathy
374. Somnolence Syndrome
375. Future Directions
376. References
377. Spinal Tumors
378. Epidemiology
379. Predisposing Factors
380. Etiology
381. Genetic Issues
382. Presenting Symptoms
383. Radiographic Findings
384. Workup
385. Acute Management
386. Treatment
387. Role of Surgery
388. Role of Chemotherapy
389. Role of Radiation Therapy
390. Target Delineation
391. Radiotherapy Volume
392. Dose
393. Techniques
394. Outcomes
395. Follow-up Guidelines
396. Future Directions
397. References
398. Choroid Plexus Tumors
399. Epidemiology and Histopathology
400. Predisposing Factors
401. Presenting Symptoms
402. Radiographic Findings
403. Workup
404. Acute Management/Surgical Treatment
405. Postoperative Management
406. Radiation Planning Guidelines
407. Local Radiation and Boost After CSI
408. Craniospinal Irradiation
409. Outcomes
410. Chemotherapy Toxicities
411. Radiation Toxicities
412. Survival
413. Follow-Up
414. Future Directions
415. References
416. Proton Therapy for Skull Base Chordomas in the Pediatric and Adolescent Patient
417. Introduction
418. Presenting Symptoms
419. The Role of Surgery
420. Target Delineation
421. Tumor and Target Volume Prescription Doses
422. Organs at Risk, Special Dose Considerations
423. Normal Tissue Constraints Versus Target Coverage
424. Prognostic Factors
425. Proton Therapy Results
426. Systemic Therapy
427. Summary
428. References
429. Pituitary Tumors: Pituitary Adenomas and Langerhans Cell Histiocytosis Associated Diabetes Insi
430. Introduction
431. Pituitary Adenomas
432. Epidemiology
433. Predisposing Factors
434. Presenting Symptoms
435. Radiographic Findings
436. Workup
437. Treatment
438. Radiation Therapy Techniques
439. Conventionally Fractionated Radiation Therapy
440. Stereotactic Radiosurgery
441. Outcomes
442. Langerhans Cell Histiocytosis Involving the Pituitary Gland
443. Epidemiology and Predisposing Factors
444. Radiographic Findings and Workup
445. Treatment
446. Radiation Techniques
447. Outcomes and Late Effects
448. References
449. Pediatric Brain Metastases
450. Introduction
451. Epidemiology
452. Pathophysiology
453. Clinical Presentation
454. Imaging of Brain Metastases
455. Ewing Sarcoma
456. Rhabdomyosarcoma
457. Osteosarcoma
458. Neuroblastoma
459. Hepatoblastoma
460. Germ Cell Tumors
461. Melanoma
462. Wilms Tumor
463. Clear Cell Sarcoma of the Kidney
464. Rhabdoid Tumor of the Kidney
465. Radiation Techniques
466. References
467. Part VI: Radiotherapy Practice
468. Anesthesia for Immobilization
469. Introduction
470. Manuscript
471. Personnel
472. Treatment Room Set Up
473. Supplies
474. Airway Supplies
475. Vascular Access Devices
476. Medication
477. Monitoring
478. Anesthetic Management
479. Pre-procedural Assessment
480. Fasting Guidelines
481. Delivery of Anesthesia
482. Patient Recovery and Discharge
483. References
484. Image Guidance in Pediatric Brain Radiotherapy
485. Indications
486. IGRT Approaches
487. Planar-Based IGRT
488. CT-Based IGRT
489. MRI-Based IGRT
490. Other IGRT Modalities
491. Image Guidance Procedure
492. Potential Advantages/Disadvantages
493. Advantages of IGRT
494. Disadvantages of IGRT
495. Trials/Clinical Data
496. Radiation Doses and Toxicities Associated with IGRT
497. Use of Lower Dose Pediatric IGRT Protocols
498. References
499. Conformal Radiation Therapy for Pediatric CNS Tumors
500. Introduction
501. Conformal Radiation Therapy for Pediatric CNS Tumors
502. References
503. Proton Therapy for Pediatric Brain Tumors
504. Introduction
505. History
506. Proton Therapy Delivery Systems
507. Preliminary Dosimetric Studies in Children
508. Current Status
509. Clinical Outcomes
510. Non-proton Charged Particles
511. Cost-Effectiveness
512. Ethics
513. References
514. Craniospinal Irradiation
515. Introduction
516. CSI Dose
517. CSI Target Volume
518. CSI Technique
519. Three-Dimensional Conformal Photon Therapy
520. Advanced Photon Techniques
521. Electron Therapy
522. Proton Therapy
523. Treatment Setup Verification
524. Treatment Delivery and Toxicity Monitoring
525. References
526. Special Radiation Techniques for Pediatric Brain Tumors: Hypofractionation, Radiosurgery, and
527. Introduction
528. Treatment Types
529. Considerations in Pediatric Patients
530. Individual Applications of Hypofractionation and Stereotactic Radiosurgery
531. Malignant Disease
532. Brainstem Glioma
533. Intrinsic Pontine Glioma
534. Brainstem Glioma
535. Ependymoma
536. Low-Grade Glioma
537. Medulloblastoma
538. Primitive Neuroectodermal Tumor
539. Germ Cell Tumor
540. Benign Disease
541. Arteriovenous Malformation
542. Craniopharyngioma
543. Pituitary Adenoma
544. Vestibular Schwannoma
545. Meningioma
546. Special Cases
547. Infants
548. Brachytherapy
549. Toxicity
550. Follow-Up
551. References
552. Reirradiation
553. Background
554. Biologically Effective Dose (BED)
555. Normal Tissue Tolerance
556. Studies by Tumor Type
557. Ependymoma
558. Medulloblastoma
559. Gliomas
560. Particular Radiation Planning Issues
561. References
562. Part VII: Radiotherapy Toxicity and Management
563. Neuropsychological Late Effects of Radiotherapy for Pediatric Brain Tumors
564. Predisposing Factors
565. Pathophysiology
566. Clinical Presentation and Consequences
567. Neurocognitive Functioning
568. Academic Functioning
569. Adaptive, Emotional/Behavioral, and Psychosocial Functioning
570. Methodological Considerations
571. Therapeutic Interventions
572. Pharmacologic Interventions
573. Cognitive Remediation
574. Educational Interventions
575. Socioemotional Interventions
576. Prevention
577. Summary
578. References
579. Endocrine Sequelae of Central Nervous System Irradiation
580. Introduction
581. Predisposing Factors
582. Pathophysiology
583. Clinical Presentation and Consequences
584. GH Deficiency
585. Central Precocious Puberty and LH/FSH Deficiencies
586. TSH Deficiency
587. ACTH Deficiency
588. Hyperprolactinemia
589. Other Endocrine Consequences of Irradiation Given for CNS Tumors
590. Therapeutic Interventions and Prevention
591. Summary
592. References
593. Ophthalmic Outcomes for Children Treated with CNS Radiation
594. Introduction
595. Predisposing Factors
596. Pathophysiology
597. Clinical Presentation
598. Consequences
599. Lids, Lacrimal Gland and Drainage, Conjunctiva
600. Cornea
601. Iris and Anterior Segment
602. Lens
603. Retina
604. Optic Pathway
605. Non-optic Cranial Nerves
606. Therapeutic Interventions
607. Lids and Lacrimal Gland System
608. Conjunctiva
609. Cornea
610. Iris
611. Lens
612. Retina
613. Optic Pathway and Non-optic Cranial Nerves
614. Prevention
615. References
616. Hearing
617. Introduction
618. Predisposing Factors
619. Cisplatin
620. Pathophysiology
621. Outer Ear
622. Middle Ear
623. Inner Ear
624. Clinical Presentation
625. Consequences
626. Therapeutic Interventions
627. Amifostine
628. Steroids
629. Hearing Aids
630. Cochlear Implants
631. Prevention
632. RT Dose Tolerance Guidelines
633. References
634. Vascular Late Effects of Cranial Radiation
635. Introduction
636. Types of Vascular Pathologies Observed in Survivors After Cranial Radiation
637. Ischemic Stroke
638. Vascular Malformations
639. Veno-Occlusive Disease and Moyamoya
640. Aneurysm
641. Cavernous Malformations and Telangiectasias
642. Hemorrhage
643. Necrosis
644. Other Vascular Effects of Cranial Radiotherapy
645. Risk Factors, Prevention, and Treatment
646. Risk and Prevention
647. Treatment
648. Future Directions
649. References
650. Second Neoplasms After Successful Treatment for Pediatric Central Nervous System Tumors
651. Introduction
652. Genetic and Familial Factors Influencing the Risk of Second Neoplasms
653. The Effects of Cancer Therapies on Neoplasm Development in the Central Nervous System
654. Increased Risk in Healthy Individuals
655. Increased Risk in Individuals with Non-CNS Neoplasms
656. Increased Risk in Individuals with CNS Neoplasms
657. Radiotherapy
658. Cytotoxic Chemotherapy
659. Other Risk Factors
660. Second Neoplasms Following Childhood Central Nervous System Tumors
661. Incidence of Second Neoplasms in Survivors of Childhood Central Nervous System Tumors
662. Increasing Rate of Secondary Neoplasms
663. Time from Initial Diagnosis to Diagnosis of Second Neoplasm
664. Common Second Neoplasm Histologies
665. Within the CNS
666. Outside the CNS
667. Treatment Outcomes Following Secondary Neoplasms of the Central Nervous System
668. Gliomas
669. Meningiomas
670. Risk Reduction Strategies
671. References
672. Afterword
673. Introduction
674. The First Problem: The Logical Problem of Evil
675. Scientific Rationalizations, Evil, and Childhood Cancer
676. Common Responses to the Problem of Evil
677. Believing, Accepting Evil, and Responding to Evil
678. Does Everything Happen for a Reason?
679. An Alternative Approach to the Problem of Evil
680. The Second Problem: The Problem of the Physician’s “License to Heal”
681. The Third Problem: The Problem of Informed Consent and the Slippery Slope
682. References

Editors Biography

Anita Mahajan is a Professor at the Mayo Clinic in Rochester, Minnesota since 2017. She serves as the Clinical Director of Particle Therapy in the Department of Radiation Oncology. In this role, she oversees the day to day operations of the center and is heavily involved in planning future upgrades.
Upon completing her residency training in Montreal, Canada and a fellowship in proton therapy at Massachusetts General Hospital, Dr. Mahajan joined the faculty at Tufts New England Medical Center. Dr. Mahajan worked at MD Anderson Cancer Center for 15 years where she was the Section Chief for the Pediatric and CNS Radiation Oncology service. She had also served as the Proton Therapy Medical Director and the Associate Residency Program Director.
Dr. Mahajan’s clinicalinterests have been in radiation oncology for children, adult CNS tumors, particle therapy and other advanced technologies. During her time in Houston, she developed a robust pediatric proton practice, lead many research initiatives which resulted in over a sixty publication and several ongoing collaborations. Currently she is involved in advanced radiation therapy planning outcomes for proton therapy which will increase planning accuracy, delivery with biologic dose evaluation.

Arnold Paulino is a Professor of Radiation Oncology and Director of Pediatric Radiation Oncology at the MD Anderson Cancer Center. He did his residency in Chicago, Illinois and did a one year pediatric radiation oncology fellowship at St. Jude Children’s Research Hospital. He has been treating childhood cancer for more than 25 years. His main research interest is understanding how radiotherapy can be used while minimizing late effects. He is an author of more than 200 peer-reviewed articles and more than 40 book chapters, mostly on pediatric cancer.