2022, Number 1
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Rev Cubana Pediatr 2022; 94 (1)
Nimotuzumab combined with radiation therapy in the treatment of infiltrating and diffuse brain stem tumors in children and adolescents
Alert SJ, Chon RI, Ropero TR, Pérez TM, García SD, Forteza SM, Infante PM, Valdés MJ, Ávila PJ
Language: Spanish
References: 33
Page: 1-16
PDF size: 478.83 Kb.
ABSTRACT
Introduction:
Infiltrating and diffuse gliomas of the brain stem in children and adolescents lead to a poor prognosis and a short survival time.
Objective:
Present the results obtained with the combination of nimotuzumab and radiotherapy in brain stem tumors in children and adolescents.
Methods:
The monoclonal antibody called nimotuzumab combined with radiotherapy was applied in a series of 69 patients aged between 2 and 18 years, from 2008 to 2020, and followed until August 2021. They were irradiated at the National Institute of Oncology and Radiobiology in Havana, with a dose in a range of 54 to 59 Gy. Nimotuzumab was applied at the dose of 150 mg/m2 of body surface area, once a week while the radiation treatment was active, then every 2 weeks with the same dose, and finally once a month for 1, 2 or more years.
Results:
At the end of the combined treatment of radiotherapy and nimotuzumab, there was a response in 89.9% of the patients. The median overall survival time was 18.8 months and series survival rates were 76.4; 45.4; 38.9; 32.8; and 31.5% at one, two, three, four, five and more years, respectively, and it was stabilized from this time to 10 years and more. Three relapsed patients were re-radiated.
Conclusions:
The combination of radiotherapy and nimotuzumab was well tolerated and is an option for the treatment in brain stem tumors in children and adolescents.
REFERENCES
Ministerio de Salud Pública. Anuario Estadístico de Salud 2020. La Habana: División de Registros Médicos y Estadísticos de la Salud; 2021 [acceso 22/12/2021]:103-4. Disponible en: Disponible en: https://temas.sld.cu/estadisticasslducl /
Warren E. Diffuse intrinsic pontine glioma: poised for progress. Front Oncol. 2012;2:205. DOI: http://doi.org/3389/fonc.2012.00205
Massimino M, Biassoni V, Miceli R, Schiavells E, Warmuth-Metz M, Modena P, et al. Results of Nimotuzumab and Vinorelbine, radiation and re-irradiation for diffuse pontine glioma in childhood. J Neuro-oncol 2014;118:305-312. DOI: http://doi.org/10.1007/s.11060-014-1428-z
El-Khouly F, Vendhuijezen van Zanten S, Santa-Maria V, Heymans M, Hendrikse N, Kaspers G, Loizos B, et al. Diagnostic and treatment of diffuse intrinsic pontine glioma: ¿where do we stand? J Neuro-oncol. 2019;145:177-84. DOI: http://doi.org/10.1007/s.11060-019-03287-g
Fleischhack G, Massimino M, Marmuth-Metz M, Khuhlaeva E, Janssen G, Graf N, et al. Nimotuzumab and radiotherapy for treatment of newly diagnosed diffuse intrinsic pontine glioma (DIPG): a phase III clinical study. J Neuro-oncol. 2019;143:107-13. DOI: http://doi.org/10.007/s.11060-019-03140-z
Carciller F. Long-term survivors of diffuse intrinsic pontine glioma (DIPG): Trzen Cancer Res. 2019;8:343-345. DOI: http://doi.org/10.21037/tcr.2019.03.12
Hoffman LM, Veldhuijzen van Zanten S, Colditz N, Baugh J, Chaney B, Hoffman N, et al. Clinical, radiologic, pathologic and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG). A Collaborative report from the International and European Society for Pediatric Oncology DIPG Registries. J Clin Oncol. 2018;36:1963-072. DOI: http://doi.org/10.1200/jco10.1200/jco2017
Parsons DW, Pollack IF, Hans-Kogan D, Poussaint T, Adesina A, Chintagrampala M. Gliomas, ependimomas and other non -embrional tumors of the Central Nervous System. In: Pizzo I, Philip A, editors. Principles and Practice of Pediatric Oncology. Seventh ed. China, Hong-Kong: Wolters Kluery; 2016 [acceso 22/08/2021]:627-58. Disponible en: Disponible en: http://www.solution.lnw.cons/access
Cohen K, Heideman R, Zhou T, Holmes E, Lavey R, Buffet E, et al. Temozolamide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children’s Oncology group. Neuro-oncol 2011;13:410-6. DOI: http://doi.org/10.1093/neuonc/noq205
Crotty E, Leary S, Geyer J, Olson J, Millard N, Sato A, et al. Children wdoiith DIPG and high grade glioma treated with temozolamide, irinotecan and bevazisumab. The Seattle Children’s Hospital experience. J Neuro-oncol. 2020;148:607-17. DOI: http://doi.org/10.1007/s.11060-20-03558w
Jackson S, Patay Z, Howarth R, Panandiker Z, Onar-Thomas A, Broniscer A, et al. Clinicoradiologic characteristies of long-term survivors of diffuse intrinsic pontine gliomas. J Neurooncol 2013;114:339-44. DOI: http://doi.org/10.1007/s11060-013-1189-o
Gallito M, Lazarev S, Wasserman T, Stafford J, Wolden S, Terezakis S, et al. Role of radiation therapy in the management of diffuse intrinsic pontine glioma: a systematic review. Adv Radiat Oncol 2019;4:520-31. DOI: http://doi.org/10.1016/jadro.2019.63.009.i
Izzuddeen Y, Gupta S, Haresh KP, Sharma D, Guridhar P, Rath G. Hypofractionated radiotherapy with temozolamide in diffuse intrinsic pontine glioma: a randomized controlled trial. J Neurooncol. 2020;146:91-95. DOI: http://doi.org/10.1007/s.1160-019-03340-7.14
Cooney T, Lane A, Bartels U. International Diffuse Intrinsic Pontine Gliomas Registry Study. Neuro-oncol 2017;19:1279-80. DOI: http://doi.org/10.1093/neuonc/noc107
Fernández A, Spitze K, Pérez R, Boehmer F-D, Eckert K, Zschiesche W, et al. A new monoclonal antibody for detection of EGF recertors in western blots and paraffin-embebed tissue sections. J Cell Bioch 1992;49:157-65. DOI: http://doi.org/10.1002/jcb.240490208
Crombet-Ramos T, Rack J, Perez R, Viloia-Petit A. Antiproliferative, antiangiogenic and proapoptotic activity of h-R3 a humanizd anti-EGF R antibody. Int J Cancer. 2002;101:567-75. DOI: http://doi.org/10.1002/ije.10647
Cabanas R, Saurez G, Alert J, Reyes A, Valdes J, Gonzalez A, et al. Prolonged use of Nimotuzumab in children with Central Nervous System tumors: safety and feasibility. Cancer Biother Radiopharm 2014;29:173-8. DOI: http://doi.org/10.1089/cbr.2013.159
Boland WK, Bebb G. Expert opinion, Nimotuzumab, a novel anti-EGFR activity while minimizing skin toxicity. Expert Opin Biol Ther. 2009:1199-1206. DOI: http://doi.org/1517/14712590311/0709
Bartels U, Wolff J, Gore L, Dunkel I, Gilheeney S, Allen J, et al. Phase II study of safety an efficacy of Nimotuzumab in pediatric patients with progressive diffuse intrinsic pontine glioma. Neuro-oncology. 2014;16:1554-9. DOI: http://doi.org/10.1093/neuonc/neu091
Kebudi R, Betul Cakir F, Gorgum O, Altinok P, Iribas A, et al. Nimotuzumab-containing regimen for pediatric diffuse pontine gliomas: a retrospective multicenter study and review of the literature. Child’s Nervous System 2019;35:83-9. DOI: http://doi.org/10.1007/s00381-018-4001-g
Bode U, Massimino M, Bach F, Zimmermann M, Khuhlaeva E, Westphal M, et al. Nimotuzumab treatment of malignant gliomas. Expert Opin Biol Ther. 2012;12:1649-59. DOI: http://doi.org/110.1517/14712598.2012.7833367
Alert J, Chon I, Cabanas R, Reno Garcia D, Perez M, Ropero R. Radiation therapy and Nimotuzumab in children and adolescents: a 5- years Institutional experience. Neuro Open J. 2015;2:45-50. DOI: http://doi.org/10.17140/noj-2-111
Alert J, Chon I, Cabanas R, Reno J, Garcia D, Perez M, Ropero R. Long-term survival in diffuse infiltrative brainstem gliomas in children and adolescents: treated with radiotherapy and Nimotuzumab. Int J Radiol Radiat Ther. 2018;5:267-70. DOI: http://doi.org/10.1546/ijrrt-2018.05.00176
Bone U, Cabanas R, Saurez G, Crombet T, Lorenzo P, Massimino M, et al. Anti-EGFR Nimotuzumab for DIPG in recurrent or children with hig grade glioma: 10 years. In: Adella Ca, editor. Stem Cell Oncology. London: Taylor Francis Group; 2018. p. 251-7.
Tinkle Ch, Campbell K, Han Y, Li Y, Bianski B, Bronisar A, et al. Radiation dose response of neurologic symptoms during conformal radiotherapy for diffuse intrinsic pontine glioma. J Neurooncol. 2020;147:195-203. DOI: http://doi.org/10.1007/s11060-20-03415-w
Hersh D, Kumar R, Moore K, Smith L, Tinkle C, Chiang J, et al. Safety and efficacy of brainstem biopsy in children and young adults. J Neurosurg: Pediatrics. 2020;5:572-7. DOI: http://doi.org/10.3171/2020.4.PEDS2092
Hamish C, Kickingereder P, Fisher M, Simon T, Ruge M. Update on the diagnostic value and safety of stereotactic biopsy for pediatric brainstem tumors: a systematic review and meta-analysis of 735 cases. J Neurosurg: Pediatrics. 2017;20:261-8. DOI: http://doi.org/10.3171/2017.2 PEDS1665
Jansen MH, Vuurden DG, Vandertop WP, Kaspers GI. Diffuse intrinsic pontine gliomas: a systematic update in clinical trials and biology. Cancer Treat Rev. 2012;38:27-35. DOI: http://doi.org/10.1016/jj.ctr.2011.06.007
Alert J, Chon I, Valdes J, Ropero R, Pérez M, Garcia D, et al. Very long-term survival, 5 years and more in diffuse intrinsic pontine gliomas in children and adolescents treated with Radiotherapy and Nimotuzumab. Int J Radiol Radiat Ther. 2021;8:86-90. DOI: http://doi.org/10.15406/ijrrt.2021.08.00299
Hassan H, Pinches A, Picton Sv, Phillips R. Survival rates and prognostic predictors of high grade braibstem gliomas in children: a systematic review and meta-analysis. J Neurooncol. 2017;135:13-20. DOI: http://doi.org/10.1007/s11060-017-2546-i
Tsang D, Laperriere N. Re-irradiation for pediatric tumors. Clin Oncol. 2019;31:191-8. DOI: http://doi.org/10.1016/clon.2018.10.003
Janssens GO, Gandolla L, Bolle S, Mandeville H, Ramos-Albiac M, van Beck K, et al. Survival benefict for patients with diffuse intrinsic pontine glioma (DIPG) undergoing re-irradiation at first progression: a matched-cohort analysis on behalf of the SIOP-G-HGG/DIPG Working Group. Eur J Cancer 2017;73:38-47. DOI: http://doi.org/10.1016/j.ejca.2016.1207
Lassaletta A, Strother D, Laperriere N. Reirradiation in patients with diffuse intrinsic pontine gliomas: The Canadian experience. Pediatr Blood Cancer. 2018;65:e26988. DOI: http://doi.org/10.11.1002/pbc26988