Radiation Therapy and Nimotuzumab in Children and Adolescents with Brainstem
DOI:
https://doi.org/10.17140/NOJ-2-111Keywords:
Radiotherapy; Nimotuzumab; Brainstem tumors children adolescents.Abstract
Background: Brainstem gliomas (BSG) are Central Nervous System (CNS) tumors with a median survival time of approximately 9 months. Up to now chemotherapy has not shown to improve survival in these patients. The outcome of Radiation Therapy (RT) in combination with
Nimotuzumab is shown in the present report.
Material and Methods: 28 children and adolescents were included between Jan/2009 and
Dec/2012 with the diagnosis of BSG and follow-up till January 2015. All patients had Diffuse
infiltrative Pontine Gliomas (DIPG) and were irradiated with a dose ranging from 54 to 59.6
Gy at the National Oncology and Radiobiology Institute in Havana, Cuba. Three patients were
planned with IMRT and 25 with 3D Conformal RT. Nimotuzumab was indicated at the dose of
150 mg/m2
weekly during the time of RT treatment, then every 15 days during 8 weeks and finally monthly for 1 year. Univariate and multivariate Cox regression models and Kaplan Meier
survival were analyzed to evaluate the survival.
Results: Median age at diagnosis was 7 years (range 3-18 years old), median overall survival
was 17.3 months (95% CI 14.0-20.5 ) since the beginning of the treatment and the accumulated
survival at 5 years of treatment was 42,9%. There was balance in sex, age and dosage of RT in
the population. Addition of Nimotuzumab to RT was safe.
Conclusions: The combination of Radiotherapy and Nimotuzumab were well tolerated in this
brainstem tumours patient’s series.
References
Bailey S, Howman A, Whealtey K, et al. Diffuse intrinsic pontineglioma treated with prolonged Temozolomide and Ra-diotherapy. Results of a United Kingdom phase II trial (CNS 2007 04). Eur. J. Cancer. 2013; 49: 3856-3862. doi: 10.1016/j. ejca.2013.08.006
Blaney S, Kun L, Hunter J, et al. Tumor of the Central Ner-vous System. In: Pizzo P, Poplack, ed. Principles and Practice of Pediatric Oncology. 5th. Ed. Lippincott Williams & Wilkins, Philadelphia, USA, 2006; 786-864.
Wolff JE, Rytling M, Vats T, et al. Induction treatment for diffuse intrinsic pontineglioma. Experience of M.D. Anderson Cancer Center. Anticancer Res. 2011; 31: 2265-2270.
Marcus K, Dutton SH, Barnes P, et al. A phase I trial of Etani-dazole and hyperfractionated radiotherapy in children with dif-fuse brainstem gliomas. Int J Radiat Oncol Biol Phys. 2013; 55: 1182-1185. doi: 10.1016/S0360-3016(02)04391-2
Fried I, Hawkins C, Scheinemann K, et al. Favorable out-come with conservative treatment for children with low-grade braistem tumors. Pediatr Blood & Cancer. 2012; 58: 556-560. doi: 10.1002/pbc.23200
Hargrave D, Bartels V, Bouffet E. Diffuse brainstem gliomas in children: critical review of clinical trial. Lancet Oncol. 2006; 7: 241-248. doi: 10.1016/S1470-2045(06)70615-5
Jansen MH, van Vuurden DG, Vandertop WP, et al. Diffuse intrinsic pontinegliomas: a systematic update on clinical trials and biology. Cancer Treat Rev. 2012; 38: 27-35. doi: 10.1016/j. ctrv.2011.06.007
Frazier JL, Lee J, Thomale UW, et al. Treatment of diffuse intrinsic brainstem gliomas. Failed approaches and future strat-egies. J Neurosurg. 2009; 3: 259-269. doi: 10.3171/2008.11. PEDS08281
Minturn JE, Fisher MJ. Gliomas in children. Current Treat Options Neurol. 2013; 15: 316-327.
Chassot A, Canale S, Varlet P. Radiotherapy with concurrent and adjuvant Temozolamide in children with newly diagnosed intrinsic pontinegliomas. J Neuroncol. 2012; 106: 399-407. doi: 10.1007/s11060-011-0681-7
Cohen KJ, Heideman RL, Zhou T. Temozolamide in the treatment of children with newly diagnosed diffuse intrinsic pontinegliomas: a report from the Children’s Oncology Group. Neuroncol. 2011; 13: 410-416. doi: 10.1093/neuonc/noq205
Janssens G, Jansen M, Launers G, et al. Hypofractionations conventional radiation therapy for newly diagnosed diffuse in-trinsic poutine gliomas: a matched cohort analysis. Int. J Radia-tion Oncol Biol Phys. 2013. doi: 10.1016/j.ijrobp.2012.04.006
Solomon MT, Selva JC, Figueredo J, et al. Radiotherapy plus Nimotuzumab or placebo in the treatment of high grade glioma patients: results from a randomized, double blind trial. BMC Cancer. 2013: 299. doi: 10.1186/1471-2407-13.299
Fernandez A, Spitze E, Perez R, et al. A new monoclonal an-tibody for detection of EGF receptors in western blots and paraf-fin-embebed tissue sections. J Cell Biochm. 1992; 49: 152-165.
Garrido G, Tikhomitov IA, Rabasa A, et al. Bivalent bind-ing by intermediate affinity of Nimotuzumab: a contribution to explain antibody clinical profile. Cancer Biol Ther. 2011; 11: 373-382.
Boland WK, Bebb G. Expert opinion, nimotuzumab, a novel anti-EGFR monoclonal antibody that retains anti-EGFR activity while minimizing skin toxicity. Expert Opin Biol Ther. 2009; 9: 1199-1206. doi: 10.1517/14712590903110709
Lam C, Bouffet F, Bartels U. Nimotuzumab in pediatric glio-ma. Future Oncol. 2009; 5: 1349-1361. doi: 10.2217/fon.09.119
Massimino M, Bode U, Bassani V, et al. Nimotuzumab for pediatric diffuse intrinsic pontinegliomas. Expert Opin Biol Ther. 2011; 11: 247-256. doi: 10.1517/14712598.2011.546341
Rivera F, Vega-Villegas ME, Lopez-Brea MF, et al. Current situation of Pantumumab, Matuzumab, Nimotu-zumab and Zalutumumab. ActaOncol. 2008; 47: 9-19. doi: 10.1080/02841860701704724
Chon I, Chi D, Alert J, et al. Transition from 2D to 3D Con-formal Radiotherapy in high grade gliomas: our experience in Cuba. ICARO, Vienna April 2009. Book of extended synopsis. 38-39, IAEA-CN-170-2009.
Jallo GI, Biser-Rohrbaugh A, Freed D. Brainstem gliomas. Chids Nerv Syst. 2004; 20: 143-153.
Freeman CR, Krischer JP, Sanford RA. Final results of a study of escalating doses of hyperfractionated radiotherapy in brainstem tumors in children: a Pediatric Oncology Group Study. Int J Radiat Oncol Biol Phys. 1993; 27: 197-206. doi: 10.1016/0360-3016(93)90228-N
Fangusard J. Pediatric high-grade gliomas and Difusse In-trinsic Pontine Gliomas (DIPG). J Child Neurol. 2009; 24: 1409- 1417. doi: 10.1177/0883073809338960
Negretti L, Bouchireb K, Levy-Piedbois C, et al. Hypo-fractionated radiotherapy in the treatment of diffuse intrinsic pontinegliomas in children: a single institution’s experience. J Neuro-oncol. 2011; 104:773-777.
Ueoka DL, Nogueira J, Campos JC, et al. Brainstem gli-omas-retrospective analysis of 86 patients. J NeurolSci. 2009; 281: 20-23. doi: 10.1016/j.jns.2009.03.009
Combs SE, Steck I, Schulz-Ertner D, et al. Long-term out-come of high-precision radiotherapy in patients with brainstem gliomas. Results from a difficult-to-treat population using frac-tionated stereotactic radiotherapy. Radiother Oncol. 2009; 91: 60-66. doi: 10.1016/j.radonc.2009.02.012
Freeman CR, Suissa S. Brainstem tumors in children: results of a survey of 62 patients treated with radiotherapy. Int J Ra-diat Oncol Biol Phys. 1986; 12: 1823-1828. doi: 10.1016/0360- 3016(86)90325-1
Kabudi R, Cafir FB, Agauglu FY, et al. Pediatric diffuse in-trinsic pontineglioma patients from a single center. Childs Nerv Syst. 2013; 29: 583-588. doi: 10.1007/s00381-012-1986-3
Kabudi R, Cafir FB. Management of diffuse pontineglioma in children: recent development. Paediatr Drugs. 3013; 5: 351- 362. doi: 10.1007/s40272-013-0033-5
Panoff JE, Koru-Sengul T, Khatib Z. The role of Radiation Therapy technique and dose for pediatric patients with diffuse intrinsic pontineglioma. Int J Radiat Oncol Biol Phys. 2013; 87: S594-S595.
Kabudi R, Cafir FB, Agaoglis D. Diffuse Intrinsic Pontine Gliomas (DIPG) in children: results from a single center. Neu-rooncol. 2012; 14: 29.
Zapotocky M, Churackova M, Malinova B, et al. Chemo-therapy added to Radiotherapy failed to improve dismist out-come of children with DIPG: single institution experience. Neu-ro-oncol. 2012; 14: 30.
Nolre L, Vasconcelos F, Lima F, et al. Pediatric brainstem glioma: experience of one Brazilian Institution. Neuro-oncol. 2012; 14: 16.
Broniscer A, Laningham FH, Sanders RP, et al. Young age may predict a better outcome for diffuse pontineglioma. Cancer. 2008; 113: 566-572. doi: 10.1002/cncr.23584
Osorio M, Cruz T, del Castillo R, et al. Nimotuzumab plus Radiotherapy for unresectable squamous-cell carcinoma of the Head and Neck. Cancer Biol & Ther. 2010; 9: 343-349.
Ramos Suzarte M, Lorenzo Luaces P, Lazo N, et al. Treat-ment of malignant, non-resectable epithelial origen esophageal tumors with the humanized antiepidermal growth factor anti-body Nimotuzumab combined with radiation therapy and che-motherapy. Cancer Biol & Ther. 2012; 13: 1-6.
Liang J, Mingzam E, Gang W, et al. Nimotuzumab combined with radiation therapy on esophageal cáncer. Preliminary study of Phase 2 Clinical Trial. Int J Radiat Oncol Biol Phys. 2013; 87: S292. doi: 10.1016/j.ijrobp.2013.06.765
Cabanas R, Suarez G, Crombet T, et al. Safety and effica-cy results of children and adolescents Central Nervous System Tumor. Nimotuzumab expanded access program. Ped Blood & Cancer. 2011; 57: 705-897.
Crombet T, Cabanas R, Alert J. et al. Nimotuzumab and Ra-diotherapy in children and adolescents with brainstem gliomas: preliminary results from a phase II Study. European J Cancer. 2009; 7: 4974.
Cabanas R, Crombet T, Alert J, et al. Nimotuzumab in chil-dren and adolescents with brainstem tumors: a Phase II study. Ped Blood & Cancer. 2009; 59: 830-831.
Alert J, Reno J, Garcia D, et al. Three dimensional Confor-mal Radiotherapy concurrent with chemotherapy plus Nimotu-zumab in the treatment of Head and Neck cancer in children and adolescents: experience in a single institution. Ped Blood & Cancer. 2012; 59: 94.
Bude U, Buchen S, Warmouth-Metz, et al. Final report of phase II trial of Nimotuzumab in the treatment of refractory and relapsed high grade gliomas in children and adolescents. ASCO Meeting. J ClinOncol. 2007; 25.
Massimino M, Biassoiri V, Gandola I, et al. Nimotuzumab and Vinoralbine concomitantly to radiation and as a maintenance for diffuse pontineglioma in childhood: results from a serie of 12 patients. J Clin Oncol. 2011; 26: 9577.
Cabanas R, Saurez G, Alert J, et al. Prolonged use of nimo-tuzumab in children with central nervous system tumors: safety and feasibility. Biother Radiopharm. 2014; 29: 173-178.
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content published in Neuro (NEURO) is licensed under the Creative Commons Attribution 4.0 International License (CC BY 4.0). This license allows anyone to copy, distribute, transmit, and adapt the work — including for commercial purposes — provided appropriate credit is given to the original author(s) and source.