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Radiation Necrosis in the Upper Cervical Spinal Cord in a Patient Treated with Proton Therapy after Radical Resection of the Fourth Ventricle Ependymoma


Authors: J. Mraček 1;  J. Mork 1;  T. Svoboda 2;  J. Ferda 3;  V. Přibáň 1
Authors‘ workplace: Neurochirurgická klinika LF UK a FN Plzeň 1;  Onkologická a radioterapeutická klinika LF UK a FN Plzeň 3 Klinika zobrazovacích metod LF UK a FN Plzeň 2
Published in: Klin Onkol 2017; 30(4): 264-272
Category: Review
doi: https://doi.org/10.14735/amko2017264

Overview

Background:
Radiation necrosis in eloquent areas of the central nervous system (CNS) is one of the most serious forms of toxicity from radiation therapy. The occurrence of radiation necrosis in the CNS is described in a wide range of 3 months to 13 years after radiation therapy. The incidence of this complication covers a wide range of 3–47%. The potential advantage of proton therapy is the ability to reduce dose to normal tissue and escalate tumor dose. Proton beams enter and pass through the tissue with minimal dose deposition until they reach the end of their paths, where the peak of dose, known as the Bragg peak, occurs. Thereafter, a steep dose fall-off is evident. Such a precisely-distributed dose should reduce the toxicity of the treatment.

Patient:
A 23 year-old female patient underwent radical microsurgical resection of anaplastic ependymoma that originated from the floor of the fourth ventricle. The tumor was growing into the foramen magnum dorsally from the medulla oblongata. Taking into account the age of the patient, the localization of the tumor and the required dose of 60 Gy, proton therapy was chosen due to the lower risk of damage to the brain stem. Radiation therapy was performed using pencil beam scanning and one dorsal field. Following this course of treatment, radiation necrosis of the medulla oblongata and the upper cervical spinal cord occurred with fatal clinical impact on the patient. The article analyses possible causes of this complication and a review of the current literature is given.

Conclusion:
Despite the theoretical advantages of proton therapy, no clinical benefit in CNS tumors has yet been proven in comparison with modern methods of photon therapy. Proton therapy is accompanied by many uncertainties which can cause unpredictable complications, such as radiation necrosis at the edges of the target volume. Following proton therapy, there is not only a higher incidence of radiation necrosis but it occurs both sooner and to a higher degree. In cases of high anatomical complexity, the neurosurgeon should cooperate in the creation of the radiation treatment planning to ensure its optimization.

Key words:
brain tumors – ependymoma – radiation therapy – proton therapy – necrosis – radiation necrosis

This work was partially supported by research project MH CZ – DRO (Faculty Hospital in Pilsen – FNPl, 00669806).

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
29. 6. 2017

Accepted:
25. 7. 2017


Sources

1. Cage TA, Clark AJ, Aranda D et al. A systematic review of treatment outcomes in pediatric patients with intracranial ependymomas. J Neurosurg Pediatr 2013; 11 (6): 673–681. doi: 10.3171/2013.2.PEDS12345.

2. Wright KD, Gajjar A. Current treatment options for pediatric and adult patients with ependymoma. Curr Treat Options Oncol 2012; 13 (4): 465–477. doi: 10.1007/s11864-012-0205-5.

3. Plimpton SR, Stence N, Hemenway M et al. Cerebral radiation necrosis in pediatric patients. Pediatr Hematol Oncol 2015; 32 (1): 78–83. doi: 10.3109/08880018.2013.791738.

4. Merchant TE, Farr JB. Proton beam therapy: a fad or a new standard of care. Curr Opin Pediatr 2014; 26 (1): 3–8. doi: 10.1097/MOP.0000000000000048.

5. Combs SE. Does Proton Therapy Have a Future in CNS Tumors? Curr Treat Options Neurol 2017; 19 (3): 12. doi: 10.1007/s11940-017-0447-4.

6. Mohan R, Grosshans D. Proton therapy – present and future. Adv Drug Deliv Rev 2017; 109: 26–44. doi: 10.1016/j.addr.2016.11.006.

7. Armoogum KS, Thorp N. Dosimetric Comparison and Potential for Improved Clinical Outcomes of Paediatric CNS Patients Treated with Protons or IMRT. Cancers (Basel) 2015; 7 (2): 706–722. doi: 10.3390/cancers7020706.

8. Fink J, Born D, Chamberlain MC. Radiation necrosis: relevance with respect to treatment of primary and secondary brain tumors. Curr Neurol Neurosci Rep 2012; 12 (3): 276–285. doi: 10.1007/s11910-012-0258-7.

9. Freund D, Zhang R, Sanders M et al. Predictive Risk of Radiation Induced Cerebral Necrosis in Pediatric Brain Cancer Patients after VMAT Versus Proton Therapy. Cancers (Basel) 2015; 7 (2): 617–630. doi: 10.3390/cancers7020617.

10. Parvez K, Parvez A, Zadeh G. The diagnosis and treatment of pseudoprogression, radiation necrosis and brain tumor recurrence. Int J Mol Sci 2014; 15 (7): 11832–11846. doi: 10.3390/ijms150711832.

11. Hygino da Cruz LC Jr, Rodriguez I, Domingues RC et al. Pseudoprogression and pseudoresponse: imaging challenges in the assessment of posttreatment glioma. AJNR Am J Neuroradiol 2011; 32 (11): 1978–1985. doi: 10.3174/ajnr.A2397.

12. Greene-Schloesser D, Robbins ME, Peiffer AM et al. Radiation-induced brain injury: a review. Front Oncol 2012; 2: 73. doi: 10.3389/fonc.2012.00073.

13. Drezner N, Hardy KK, Wells E et al. Treatment of pediatric cerebral radiation necrosis: a systematic review. J Neurooncol 2016; 130 (1): 141–148.

14. MacDonald SM, Laack NN, Terezakis S. Humbling Advances in Technology: Protons, Brainstem Necrosis, and the Self-Driving Car. Int J Radiat Oncol Biol Phys 2017; 97 (2): 216–219. doi: 10.1016/j.ijrobp.2016.08.001.

15. Ruben JD, Dally M, Bailey M et al. Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy. Int J Radiat Oncol Biol Phys 2006; 65 (2): 499–508.

16. Anand AK, Chaudhory AR, Aggarwal HN et al. Survival outcome and neurotoxicity in patients of high-grade gliomas treated with conformal radiation and temozolamide. J Cancer Res Ther 2012; 8 (1): 50–56. doi: 10.4103/0973-1482.95174.

17. Jakacki RI, Burger PC, Zhou T et al. Outcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy: a Children‘s Oncology Group Phase I/II study. J Clin Oncol 2012; 30 (21): 2648–2653. doi: 10.1200/JCO.2011.40.2792.

18. Sabin ND, Merchant TE, Harreld JH et al. Imaging changes in very young children with brain tumors treated with proton therapy and chemotherapy. AJNR Am J Neuroradiol 2013; 34 (2): 446–450. doi: 10.3174/ajnr.A3219.

19. Indelicato DJ, Flampouri S, Rotondo RL et al. Incidence and dosimetric parameters of pediatric brainstem toxicity following proton therapy. Acta Oncol 2014; 53 (10): 1298–1304. doi: 10.3109/0284186X.2014.957414.

20. Gunther JR, Sato M, Chintagumpala M et al. Imaging Changes in Pediatric Intracranial Ependymoma Patients Treated With Proton Beam Radiation Therapy Com-pared to Intensity Modulated Radiation Therapy. Int J Radiat Oncol Biol Phys 2015; 93 (1): 54–63. doi: 10.1016/j.ijrobp.2015.05.018.

21. Giantsoudi D, Sethi RV, Yeap BY et al. Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury. Int J Radiat Oncol Biol Phys 2016; 95 (1): 287–296. doi: 10.1016/j.ijrobp.2015.09.015.

22. Kralik SF, Ho CY, Finke W et al. Radiation Necrosis in Pediatric Patients with Brain Tumors Treated with Proton Radiotherapy. AJNR Am J Neuroradiol 2015; 36 (8): 1572–1578. doi: 10.3174/ajnr.A4333.

23. McDonald MW, Linton OR, Calley CS. Dose-volume relationships associated with temporal lobe radiation necrosis after skull base proton beam therapy. Int J Radiat Oncol Biol Phys 2015; 91 (2): 261–267. doi: 10.1016/j.ijrobp.2014.10.011.

24. Murphy ES, Merchant TE, Wu S et al. Necrosis after craniospinal irradiation: results from a prospective series of children with central nervous system embryonal tumors. Int J Radiat Oncol Biol Phys 2012; 83 (5): e655–e660. doi: 10.1016/j.ijrobp.2012.01.061.

25. Merchant TE, Li C, Xiong X et al. Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study. Lancet Oncol 2009; 10 (3): 258–266.

26. Paganetti H, Niemierko A, Ancukiewicz M et al. Relative biological effectiveness (RBE) values for proton beam therapy. Int J Radiat Oncol Biol Phys 2002; 53 (2): 407–421.

27. Paganetti H, van Luijk P. Biological considerations when comparing proton therapy with photon therapy. Semin Radiat Oncol 2013; 23 (2): 77–87. doi: 10.1016/j.semradonc.2012.11.002.

28. Paganetti H. Range uncertainties in proton therapy and the role of Monte Carlo simulations. Phys Med Biol 2012; 57 (11): R99–R117. doi: 10.1088/0031-9155/57/11/R99.

29. Grassberger C, Trofimov A, Lomax A et al. Variations in linear energy transfer within clinical proton therapy fields and the potential for biological treatment planning. Int J Radiat Oncol Biol Phys 2011; 80 (5): 1559–1566. doi: 10.1016/j.ijrobp.2010.10.027.

30. Paganetti H, Athar BS, Moteabbed M et al. Assessment of radiation-induced second cancer risks in proton therapy and IMRT for organs inside the primary radiation field. Phys Med Biol 2012; 57 (19): 6047–6061. doi: 10.1088/0031-9155/57/19/6047.

31. Farr JB, Dessy F, De Wilde O et al. Fundamental radiological and geometric performance of two types of proton beam modulated discrete scanning systems. Med Phys 2013; 40 (7): 072101. doi: 10.1118/1.4807643.

32. Noel G, Gondi V. Proton therapy for tumors of the base of the skull. Chin Clin Oncol 2016; 5 (4): 51. doi: 10.21037/cco.2016.07.05.

33. Barragán AM, Differding S, Janssens G et al. Feasibility and robustness of dose painting by numbers in proton therapy with contour-driven plan optimization. Med Phys 2015; 42 (4): 2006–2017. doi: 10.1118/1.4915082.

34. Leroy R, Benahmed N, Hulstaert F et al. Proton Therapy in Children: A Systematic Review of Clinical Effectiveness in 15 Pediatric Cancers. Int J Radiat Oncol Biol Phys 2016; 95 (1): 267–278. doi: 10.1016/j.ijrobp.2015.10.025.

35. Jones B, Wilson P, Nagano A et al. Dilemmas concerning dose distribution and the influence of relative biological effect in proton beam therapy of medulloblastoma. Br J Radiol 2012; 85 (1018): e912–e918. doi: 10.1259/bjr/24498486.

36. Newhauser WD, Durante M. Assessing the risk of second malignancies after modern radiotherapy. Nat Rev Cancer 2011; 11 (6): 438–448. doi: 10.1038/nrc3069.

37. Laprie A, Hu Y, Alapetite C et al. Paediatric brain tumours: a review of radiotherapy, state of the art and challenges for the future regarding protontherapy and carbontherapy. Cancer Radiother 2015; 19 (8): 775–789. doi: 10.1016/j.canrad.2015.05.028.

38. Pehlivan B, Ares C, Lomax AJ et al. Temporal lobe toxicity analysis after proton radiation therapy for skull base tumors. Int J Radiat Oncol Biol Phys 2012; 83 (5): 1432–1440. doi: 10.1016/j.ijrobp.2011.10.042.

39. Verma V, Mishra MV, Mehta MP. A systematic review of the cost and cost-effectiveness studies of proton radiotherapy. Cancer 2016; 122 (10): 1483–1501. doi: 10.1002/cncr.29882.

Labels
Paediatric clinical oncology Surgery Clinical oncology
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