Онкопедиатрия. 2019; 6: 106-112
Режим высокодозной химиотерапии в сочетании с радиотерапией MIBG I131 в лечении пациентов с нейробластомой группы высокого риска: когортное исследование
https://doi.org/10.15690/onco.v6i2.2022Аннотация
Обоснование. Лечение пациентов с нейробластомой высокого риска является проблемой ввиду высокой частоты рецидивов заболевания. Радиотерапия MIBG I131 в сочетании со стандартными режимами высокодозной химиотерапии (ВДХТ) является относительно новым подходом к терапии консолидации в рамках программного лечения некоторых форм нейробластомы. Цель исследования — изучение эффективности и безопасности подобной комбинированной консолидации у пациентов с нейробластомой высокой группы риска в рамках пилотного исследования. Методы. В когортном исследовании оценивали токсичность, а также 2- и 4-летнюю выживаемость в группе из 12 пациентов, получивших консолидацию на основе треосульфана и мелфалана (Treo/Mel) в сочетании с MIBG I131 в рамках программного лечения нейробластомы высокого риска в период с 2014 по 2018 г. Исследование проводили на базе Научно-исследовательского института детской онкологии и гематологии НМИЦ онкологии имени Н.Н. Блохина (Москва). Терапию MIBG I131 осуществляли в условиях изолированного бокса в Российском научном центре рентгенологии и радиологии. Результаты. Максимальная токсичность не превысила 2-й степени у 92% пациентов. Случаев летальной токсичности не отмечено. По итогам, 2- и 4-летняя общая выживаемость пациентов составила 87,5±11,7% (для обоих временных промежутков), 2- и 4-летняя бессобытийная выживаемость — 61,4±15,3 и 49,1± 16,4% соответственно. Заключение. Сочетание радиотерапии MIBG I131 с высокодозной химиотерапией Treo/Mel в режиме консолидации не сопровождается тяжелой токсичностью. В рамках программного лечения четырехлетнюю бессобытийную выживаемость демонстрирует порядка половины пациентов с нейробластомой высокой группы риска и остаточной биологически активной опухолью к моменту консолидации.
Список литературы
1. Yal in B, Kremer LC, van Dalen EC. High-dose chemotherapy and autologous haematopoietic stem cell rescue for children with high-risk neuroblastoma. Cochrane Database Syst Rev. 2015;(10):CD006301. doi: 10.1002/14651858.CD006301.pub4.
2. Treuner J, Klingebiel T, Feine U, et al. Clinical experiences in the treatment of neuroblastoma with 131I-metaiodobenzylguanidine. Pediatr Hematol Oncol. 1986;3(3):205–216. doi: 10.3109/08880018609031220.
3. French S, DuBois SG, Horn B, et al. 131I-MIBG followed by consolidation with busulfan, melphalan and autologous stem cell transplantation for refractory neuroblastoma. Pediatr Blood Cancer. 2013;60(5):879– 884. doi: 10.1002/pbc.24351.
4. Yanik GA, Levine JE, Matthay KK, et al. Pilot study of iodine-131-metaiodobenzylguanidine in combination with myeloablative chemotherapy and autologous stem-cell support for the treatment of neuroblastoma. J Clin Oncol. 2002 20(8):2142–2149. doi: 10.1200/JCO.2002.08.124.
5. Matthay KK, Tan JC, Villablanca JG, et al. Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a new approaches to Neuroblastoma Therapy Consortium Study. J Clin Oncol. 2006;24(3):500– 506. doi: 10.1200/JCO.2005.03.6400.
6. Common Terminology Criteria for Adverse Events. CTCAE 4.03. NCI; 2010. [cited 2018 March 1] Available from: https://ctep.cancer.gov/protocolD-evelopment/electronic_applications/ctc.htm.
7. Lee JW, Lee S, Cho HW, et al. Incorporation of highdose 131I-metaiodobenzylguanidine treatment into tandem high-dose chemotherapy and autologous stem cell transplantation for high-risk neuroblastoma: results of the SMC NB-2009 study. J Hematol Oncol. 2017;10(1):108. doi: 10.1186/s13045-017-0477-0.
8. Kushner BH, Ostrovnaya I, Cheung IY, et al. Lack of survival advantage with autologous stem-cell transplantation in high-risk neuroblastoma consolidated by anti-GD2 immunotherapy and isotretinoin. Oncotarget. 2016;7(4):4155–4166. doi: 10.18632/oncotarget.6393.
9. Talleur AC, Triplett BM, Federico S, et al. Consolidation Therapy for newly diagnosed pediatric patients with high-risk neuroblastoma using busulfan/melphalan, autologous hematopoietic cell transplantation, anti-GD2 antibody, granulocyte-macrophage colonystimulating factor, interleukin-2, and haploidentical natural killer cells. Biol Blood Marrow Transplant. 2017;23(11):1910–1917. doi: 10.1016/j.bbmt.2017.07.011.
10. Sekimizu M, Osumi T, Fukano R, et al. A phase I/II study of crizotinib for recurrent or refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma and a phase i study of crizotinib for recurrent or refractory neuroblastoma : study protocol for a multicenter single-arm open-label trial. Acta Med Okayama. 2018;72(4):431–436. doi: 10.18926/AMO/56184.
Oncopediatrics. 2019; 6: 106-112
High Dose Chemotherapy with MIBG I131 in Treatment of Patients with Neuroblastoma of High-Risk: a Cohort Study
https://doi.org/10.15690/onco.v6i2.2022Abstract
Background. Poor-risk neuroblastoma treatment is still a challenge because of high relapse rate. Combination of high dose chemotherapy (HDCT) with MIBG I131 radiotherapy is a relatively new strategy for consolidation regimens in some patients with neuroblastoma. Objective. The aim of the study was to assess the safety and efficacy of a complex consolidation in a treatment of high-risk neuroblastoma patients in a pilot clinical trial. Methods. In our cohort study we analyzed toxicity along with 2- and 4- years OS and EFS in a cohort of 12 patients who got a consolidation based on Treo/ Mel HDCT in combination with MIBG I131 as a part of high-risk neuroblastoma treatment protocol since 2014 till 2018. The study was conducted in the Pediatric Oncology and Hematology Scientific Research Institute of Blokhin’s National Medical Cancer Research Center (Moscow). The treatment with MIBG I131 was done in settings of isolated ward of Russian Scientific Center of Roentgenology and Radiology. Results. Maximum cumulative organ toxicity of grade 2 or less was seen in 92% of patients. There was no treatment-related mortality. OS for 2 and 4 years was 87,5% ± 11,7% (for both time points). EFS for 2 and 4 years – 61,4 ± 15,3% and 49,1 ± 16,4%, respectively. Conclusion. Consolidation regimen based on Treo/Mel with MIBG I131 is safe. As a part of treatment program, it provides 4-years EFS for about a half of patients with poor-risk neuroblastoma with active residual tumor at the moment of consolidation.
References
1. Yal in B, Kremer LC, van Dalen EC. High-dose chemotherapy and autologous haematopoietic stem cell rescue for children with high-risk neuroblastoma. Cochrane Database Syst Rev. 2015;(10):CD006301. doi: 10.1002/14651858.CD006301.pub4.
2. Treuner J, Klingebiel T, Feine U, et al. Clinical experiences in the treatment of neuroblastoma with 131I-metaiodobenzylguanidine. Pediatr Hematol Oncol. 1986;3(3):205–216. doi: 10.3109/08880018609031220.
3. French S, DuBois SG, Horn B, et al. 131I-MIBG followed by consolidation with busulfan, melphalan and autologous stem cell transplantation for refractory neuroblastoma. Pediatr Blood Cancer. 2013;60(5):879– 884. doi: 10.1002/pbc.24351.
4. Yanik GA, Levine JE, Matthay KK, et al. Pilot study of iodine-131-metaiodobenzylguanidine in combination with myeloablative chemotherapy and autologous stem-cell support for the treatment of neuroblastoma. J Clin Oncol. 2002 20(8):2142–2149. doi: 10.1200/JCO.2002.08.124.
5. Matthay KK, Tan JC, Villablanca JG, et al. Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a new approaches to Neuroblastoma Therapy Consortium Study. J Clin Oncol. 2006;24(3):500– 506. doi: 10.1200/JCO.2005.03.6400.
6. Common Terminology Criteria for Adverse Events. CTCAE 4.03. NCI; 2010. [cited 2018 March 1] Available from: https://ctep.cancer.gov/protocolD-evelopment/electronic_applications/ctc.htm.
7. Lee JW, Lee S, Cho HW, et al. Incorporation of highdose 131I-metaiodobenzylguanidine treatment into tandem high-dose chemotherapy and autologous stem cell transplantation for high-risk neuroblastoma: results of the SMC NB-2009 study. J Hematol Oncol. 2017;10(1):108. doi: 10.1186/s13045-017-0477-0.
8. Kushner BH, Ostrovnaya I, Cheung IY, et al. Lack of survival advantage with autologous stem-cell transplantation in high-risk neuroblastoma consolidated by anti-GD2 immunotherapy and isotretinoin. Oncotarget. 2016;7(4):4155–4166. doi: 10.18632/oncotarget.6393.
9. Talleur AC, Triplett BM, Federico S, et al. Consolidation Therapy for newly diagnosed pediatric patients with high-risk neuroblastoma using busulfan/melphalan, autologous hematopoietic cell transplantation, anti-GD2 antibody, granulocyte-macrophage colonystimulating factor, interleukin-2, and haploidentical natural killer cells. Biol Blood Marrow Transplant. 2017;23(11):1910–1917. doi: 10.1016/j.bbmt.2017.07.011.
10. Sekimizu M, Osumi T, Fukano R, et al. A phase I/II study of crizotinib for recurrent or refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma and a phase i study of crizotinib for recurrent or refractory neuroblastoma : study protocol for a multicenter single-arm open-label trial. Acta Med Okayama. 2018;72(4):431–436. doi: 10.18926/AMO/56184.
