Ömer GÖRGÜN, Başak KOÇ, Rejin KEBUDİ, Johannes E WOLFF, Abut KEBUDİ, Emin DARENDELİLER

Clinical characteristics, late effects and outcomes in pineoblastomas in children: a single center experience

Background. Pineoblastomas (PB) are rare tumors of the central nervous system and are more common in children. There is no consensus about standard of care. The objective of this study is to analyze the outcome of children with PB. Methods. Six patients with PB who were diagnosed between 1990-2012 were evaluated retrospectively. Demographics, age of diagnosis, first complaint, tumor region, diagnosis type, seeding metastasis to the spinal axis or cerebrospinal fluid (CSF), treatment and survival of these patients were recorded. Results. Three patients had subtotal resection and all patients received chemotherapy and craniospinal irradiation (CSI) after diagnosis. Median follow-up after treatment was 5.5 (range:1-19) years. Two patients are alive with no evidence of disease for 7.5 and 10 years, one of whom was diagnosed with papillary thyroid carcinoma 9.5 years after treatment. One of the patients who died had lived for 19 years after diagnosis. Conclusions. Pineoblastomas are rare but very aggressive tumors; more effective treatment strategies are needed. Survivors should be followed up for late effects such as second malignancies and endocrine deficiencies.

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1. Meredith DM. Advances in diagnostic immunohistochemistry for primary tumors of the central nervous system. Adv Anat Pathol 2020; 27: 206-219. https://doi.org/10.1097/ PAP.0000000000000225

2. Kleihues P, Cavenee WK (eds). Pathology and Genetics of Tumours of the nervous system. World Health Organisation Classification of Tumours Vol 2. Lyon: International Agency for Research on Cancer (IARC) Press, 2000.

3. Kleihues P, Louis DN, Scheithauer BW, et al. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 2002; 61: 215-225. https:// doi.org/10.1093/jnen/61.3.215

4. Tate M, Sughrue ME, Rutkowski MJ, et al. The long-term postsurgical prognosis of patients with pineoblastoma. Cancer 2012; 118: 173-179. https:// doi.org/10.1002/cncr.26300

5. Alexiou GA, Varela M, Prodromou N. Management of pineal region tumors in children. J Solid Tumors 2012; 2: 15-21. https://doi.org/10.5430/jst.v2n2p15

6. Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 1990; 8: 1277-1280. https://doi.org/10.1200/ JCO.1990.8.7.1277

7. Hinkes BG, von Hoff K, Deinlein F, et al. Childhood pineoblastoma: experiences from the prospective multicenter trials HIT-SKK87, HIT-SKK92 and HIT-91. J Neurooncol 2007; 81: 217-223. https://doi. org/10.1007/s11060-006-9221-2

8. Li MH, Bouffet E, Hawkins CE, Squire JA, Huang A. Molecular genetics of supratentorial primitive neuroectodermal tumors and pineoblastoma. Neurosurg Focus 2005; 19: E5. https://doi. org/10.3171/foc.2005.19.5.4

9. Jakacki R, Zeltzer PM, Boyett JM, et al. Survival and prognostic factor following radiation and/ or chemotherapy for primitive neuroectodermal tumors of the pineal region in infants and children: a reports of Childrens Cancer Group. J Clin Oncol 1995; 13: 1377-1383. https://doi.org/10.1200/ JCO.1995.13.6.1377

10. Jakacki RI. Pineal and nonpineal supratentorial primitive neuroectodermal tumors. Child Nerv Syst 1999; 15: 586-591. https://doi.org/10.1007/ s003810050547

11. Reddy AT, Janss AJ, Phillips PC, Weiss HL, Packer RJ. Outcome for children with supratentorial primitive neuroectodermal tumors treated with surgery, radiation and chemotherapy. Cancer 2000; 88: 2189-2193. https://doi.org/10.1002/(SICI)1097- 0142(20000501)88:9<2189::AID-CNCR27>3.0.CO;2-G

12. de Kock L, Sabbaghian N, Druker H, et al. Germ-line and somatic DICER1 mutations in pineoblastoma. Acta Neuropathol 2014; 128: 583-595. https://doi. org/10.1007/s00401-014-1318-7

13. Liu AP, Gudenas B, Lin T, et al. Risk-adapted therapy and biological heterogeneity in pineoblastoma: integrated clinico-pathological analysis from the prospective, multi-center SJMB03 and SJYC07 trials. Acta Neuropathol 2020; 139: 259-271. https://doi. org/10.1007/s00401-019-02106-9

14. Liu AP, Li BK, Pfaff E, et al. Clinical and molecular heterogeneity of pineal parenchymal tumors: a consensus study. Acta Neuropathol 2021; 141: 771- 785. https://doi.org/10.1007/s00401-021-02284-

15. Tomita T. Neurosurgical perspectives in pediatric neurooncology. Childs Nerv Syst 1998; 14: 94-96. https://doi.org/10.1007/s003810050185

16. Cohen BH, Zeltzer PM, Boyett JM, et al. Prognostic factors and treatment results for supratentorial primitive neuroectodermal tumors in children using radiation and chemotherapy: a Childrens Cancer Group randomized trial. J Clin Oncol 1995; 13: 1687- 1696. https://doi.org/10.1200/JCO.1995.13.7.1687

17. Dirks PB, Harris L, Hoffman HJ, Humphreys RP, Drake JM, Rutka JT. Supratentorial primitive neuroectodermal tumors in children. J Neurooncol 1996; 29: 75-84. https://doi.org/10.1007/BF00165520

18. Johnston DL, Keene DL, Lafay-Cousin L, et al. Supratentorial primitive neuroectodermal tumors: a Canadian pediatric brain tumor consortium report. J Neurooncol 2007; 86: 101-108. https://doi. org/10.1007/s11060-007-9440-1

19. McBride SM, Daganzo SM, Banerjee A, et al. Radiation is an important component of multimodality therapy for pediatric non-pineal supratentorial primitive neuroectodermal tumors. Int J Radiat Oncol Biol Phys 2008; 72: 1319-1323. https://doi.org/10.1016/j.ijrobp.2008.03.033

20. Parikh KA, Venable GT, Orr BA, et al. Pineoblastoma- The Experience at St. Jude Children’s Research Hospital. Neurosurgery 2017; 81: 120-128. https:// doi.org/10.1093/neuros/nyx005

21. Huo XL, Wang B, Zhang GJ, et al. Adverse factors of treatment response and overall survival in pediatric and adult patients with pineoblastoma. Cancer Manag Res 2020; 12: 7343-7351. https://doi. org/10.2147/CMAR.S258476

22. Paulino AC, Cha DT, Barker JL Jr, Lo S, Manera RB. Patterns of failure in relation to radiotherapy fields in supratentorial primitive neuroectodermal tumor. Int J Radiat Oncol Biol Phys 2004; 58: 1171-1176. https://doi.org/10.1016/j.ijrobp.2003.08.022

23. Abdelbaki MS, Abu-Arja MH, Davidson TB, et al. Pineoblastoma in children less than six years of age: The Head Start I, II, and III experience. Pediatr Blood Cancer 2020; 67: e28252. https://doi.org/10.1002/ pbc.28252

24. Biswas A, Mallick S, Purkait S, et al. Treatment outcome and patterns of failure in patients of pinealoblastoma: review of literature and clinical experience from a regional cancer centre in North India. Childs Nerv Syst 2015; 31: 1291-1304. https:// doi.org/10.1007/s00381-015-2751-1

25. Jazmati D, Steinmeier T, Khalil DA, et al. Feasibility of proton beam therapy for infants with brain tumours: experiences from the Prospective KiProReg Registry Study. Clin Oncol (R Coll Radiol) 2021; 33: e295-e304. https://doi.org/10.1016/j.clon.2021.03.006

26. Selvanathan SK, Hammouche S, Smethurstv W, Salminen HJ, Jenkinson MD. Outcome and prognostic features in adult pineoblastomas: analysis of cases from the SEER database. Acta Neurochir (Wien) 2012; 154: 863-869. https://doi. org/10.1007/s00701-012-1330-4

27. Pizer BL, Weston CL, Robinson KJ, et al. Analysis of patients with supratentorial primitive neuro- ectodermal tumours entered into the SIOP/UKCCSG PNET 3 study. Eur J Cancer 2006; 42: 1120-1128. https://doi.org/10.1016/j.ejca.2006.01.039

28. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. World Health Organization Histological Classifcation of Tumours of the Central Nervous System. France: International Agency for Research on Cancer, 2016.

29. Mynarek M, Pizer B, Dufour C, et al. Evaluation of age-dependent treatment strategies for children and young adults with pineoblastoma: analysis of pooled European Society for Paediatric Oncology (SIOP-E) and US Head Start data. Neuro Oncol 2017; 19: 576-585. https://doi.org/10.1093/neuonc/now234

30. Friedrich C, von Bueren AO, von Hoff K, et al. Treatment of young children with CNS-primitive neuroectodemal tumors/pineoblastomas in the prospective multicenter trial HIT 2000 using different chemotherapy regimes and radiotherapy. Neuro Oncol 2013; 15: 224-234. https://doi.org/10.1093/ neuonc/nos292

31. Gerber NU, von Hoff K, Resch A, et al. Treatment of children with central nervous system primitive neuroectodermal tumors/pinealoblastomas in the prospective multicentric trial HIT 2000 using hyperfractionated radiation therapy followed by maintenance chemotherapy. Int J Radiat Oncol Biol Phys 2014; 89: 863-871. https://doi.org/10.1016/j. ijrobp.2014.04.017

32. Gorsi HS, Malicki DM, Barsan V, et al. Nivolumab in the treatment of recurrent or refractory pediatric brain tumors: a single institutional experience. J Pediatr Hematol Oncol 2019; 41: e235-e241. https:// doi.org/10.1097/MPH.0000000000001339

33. Choi JY, Kang HJ, Hong KT, et al. Tandem high-dose chemotherapy with topotecan-thiotepa-carboplatin and melphalan-etoposide-carboplatin regimens for pediatric high-risk brain tumors. Int J Clin Oncol 2019; 24: 1515-1525. https://doi.org/10.1007/s10147- 019-01517-8

34. Tian Y, Liu R, Qin J, et al. Retrospective analysis of the clinical characteristics, therapeutic aspects, and prognosis factors of 18 cases of childhood pineoblastoma. World Neurosurg 2018; 116: e162-e168. https://doi.org/10.1016/j. wneu.2018.04.135