Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2020; 19: 46-56
Эпидуральная компрессия при нейробластоме у детей первых 6 месяцев жизни: опыт НМИЦ ДГОИ им. Дмитрия Рогачева
https://doi.org/10.24287/1726-1708-2020-19-4-46-56Аннотация
Проявлением нейробластомы (НБ) может быть неврологическая симптоматика, обусловленная распространением опухоли в канал спинного мозга с развитием эпидуральной компрессии (ЭК). Клинические проявления и тактика ведения пациентов при ЭК зависят от ее длительности, уровня и степени воздействия на спинной мозг, возраста пациента и других факторов. Особую сложность в диагностическом и лечебном плане представляет развитие ЭК у детей первых месяцев жизни. В ретроспективный анализ были включены 13 пациентов с НБ, осложненной ЭК спинного мозга, получавших лечение в НМИЦ ДГОИ им. Дмитрия Рогачева за период с 01.01.2012 по 01.12.2018 (82 мес), у которых диагноз был установлен в возрасте от 0 до 6 месяцев. Данное исследование одобрено независимым этическим комитетом и утверждено решением ученого совета ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России. Диагноз НБ устанавливался в соответствии с международными критериями. Стадирование проводилось согласно классификации INSS, стратификация пациентов на группы риска и терапия осуществлялись по модифицированному протоколу немецкой онкологической группы NB-2004. Всем пациентам проводилось диагностическое обследование в рамках алгоритма для нейрогенных опухолей, дополнительно выполнялась магнитно-резонансная томография спинного мозга с контрастным усилением с оценкой уровня распространения и степени компрессии спинного мозга образованием. Все дети были осмотрены неврологом при поступлении и на этапах динамического наблюдения. Медиана возраста на момент постановки диагноза НБ составила 3,9 (0,5-6) месяца. В дебюте заболевания неврологическая симптоматика наблюдалась у 53,8% пациентов, преобладали явления моторного дефицита. Медиана времени от момента появления первых неврологических симптомов до постановки диагноза НБ в этой группе больных составила 1,56 мес. У 46,2% младенцев неврологическая симптоматика в дебюте заболевания отсутствовала или не была констатирована в региональном центре. Первичная опухоль была локализована забрюшинно внеорганно у 61,6%, в заднем средостении – у 30,7% и в области малого таза – у 7,7% пациентов. У всех больных отсутствовала амплификация гена MYCN, в 1 случае статус гена MYCN оценен как Gain; ни в одном случае не было выявлено делеции 1р или 11q. Распределение по стадиям INSS выглядело следующим образом: 2-я – у 15,3%, 3-я – у 46,1%, 4-я – у 23,3% и 4S – у 15,3% больных. Бóльшая часть пациентов (77,7%) была стратифицирована в группу наблюдения, 23,3% – в группу промежуточного риска по протоколу NВ-2004. Уровень инвазии опухоли в спинномозговой канал был различным: шейно-грудной отдел – 15,4% пациентов, грудной – 15,4%, грудопоясничный – 46,2%, поясничный – 15,4% и крестцовый – 7,7%. Нейрохирургическое вмешательство (ламинотомия) выполнено в 4 (30,7%) случаях. У 1 больного ламинотомия была единственной терапевтической опцией (химиотерапия не проводилась). И у 2 пациентов нейрохирургическое вмешательство было выполнено из-за ухудшения неврологической симптоматики на фоне начала первого курса полихимиотерапии (ПХТ). Химиотерапевтическое лечение проводилось 92,3% больных. Пациенты из группы наблюдения получили от 1 до 3 блоков ПХТ (медиана составила 2 курса). Только 1 пациент из группы наблюдения не получал ПХТ, ему было выполнено 2 оперативных вмешательства. В настоящее время живы 10/13 (77%) больных, 3/13 (33%) погибли (2/3 – от инфекционных осложнений терапии, 1/3 – от острой сердечно-сосудистой недостаточности в раннем постоперационном периоде). Медиана наблюдения составила 37,3 мес. Оценка отдаленных эффектов продемонстрировала наличие неврологических нарушений у всех проанализированных пациентов (n = 9), ортопедических нарушений – у 66,6% (6/9) больных. Представленные данные подчеркивают трудность диагностики и ведения больных с ЭК при НБ, необходимость выработки общих стандартов обследования и терапии с определением тактики наблюдения и реабилитации данной группы пациентов.
Список литературы
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2. Martik M., Bronner M. Regulatory Logic Underlying Diversification of the Neural Crest. Trends Genet 2017; 33 (10): 715– 27. DOI: 10.1016/j.tig.2017.07.015
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24. Baysson H., Etard C., Brisse H.J., Bernier M.O. Diagnostic radiation exposure in children and cancer risk: current knowledge and perspectives. Arch Pediatr 2012; 19 (1): 64–7.
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28. Fawzy M., El-Beltagy M., Shafei M.E., Zaghloul M.S., Kinaai N.A., Refaat A., et al. Intraspinal neuroblastoma: Treatment options and neurological outcome of spinal cord compression. Oncol Lett 2014; 9 (2): 907–11. DOI: 10.3892/ol.2014.2795
Pediatric Hematology/Oncology and Immunopathology. 2020; 19: 46-56
Epidural compression in infants less than 6 months of life with neuroblastoma: experience of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology
https://doi.org/10.24287/1726-1708-2020-19-4-46-56Abstract
Neuroblastoma (NB) can manifest through neurological symptoms caused by tumor extension into the spinal canal and the resulting epidural compression (EC). Clinical symptoms and management in patients with epidural compression depend on its level and duration, the severity of spinal cord compression, the patient's age and other factors. One of the biggest challenges is the diagnosis and treatment of EC in infants in the first months of life. Our retrospective analysis included 13 patients with NB complicated by spinal cord EC who had been diagnosed at the age of 0–6 months and treated at the D. Rogachev NMRCPHOI over the period from 01.01.2012 to 01.12.2018 (82 months). The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI of the Ministry of Healthcare of the Russian Federation. The diagnosis of NB was based on the international diagnostic criteria. The tumors were staged in accordance with the INSS classification. The patients were stratified into risk groups and treated according to the modified NB-2004 protocol of the German Oncology Group. All the patients underwent diagnostic testing for neurogenic tumors as well as contrast-enhanced magnetic resonance imaging of the spinal cord with the assessment of the level of tumor invasion and the degree of spinal cord compression. The children were evaluated by a neurologist at admission and at follow-up visits. The median age at diagnosis of NB was 3.9 (0.5–6) months. At disease onset, 53.8% of patients had neurological symptoms, with motor deficiencies being the most common ones. In this group of patients, the median time from first neurological symptoms to diagnosis of NB was 1.56 months. Neurological symptoms at disease onset were not present or diagnosed at local healthcare facilities in 46.2% of infants. Extra-organic retroperitoneal primary tumors were found in 61.6% of patients; 30.7% of primary tumors were located in the posterior mediastinum, and 7.7% of primary tumors – in the lesser pelvis. No patients had MYCN-amplified tumors; in 1 case the MYCN gene status was evaluated as Gain; neither 1p nor 11q deletions were detected. The distribution of patients by INSS stages was as follows: stage 2 – 15.3%, stage 3 – 46.1%, stage 4 – 23.3% and stage 4S – 15.3%. The majority of patients (77.7%) were stratified into an observation group, the remaining patients (23.3%) were allocated to a medium risk group in accordance with the NB-2004 protocol. The level of tumor invasion into the spinal cord canal varied. Tumor invasion at the level of the cervicothoracic spine was observed in 15.4% of patients, at the level of the thoracic spine – in 15.4%, at the level of the thoracolumbar spine – in 46.2%, at the level of the lumbar spine – in 15.4%, and at the level of the sacral spine – in 7.7%. Neurosurgical intervention (laminotomy) was performed in 4 cases (30.7%). In one patient, laminotomy was the only treatment option (chemotherapy was not given). In two patients, neurosurgery was performed because of the deterioration of neurological symptoms caused by the start of the first polychemotherapy (PCHT) cycle. Chemotherapy was carried out in 92.3% patients. The patients from the observation group received 1–3 PCHT cycles (the median number of cycles was 2). Only one patient from the observation group did not receive PCHT. This patient underwent 2 surgeries. Currently, 10/13 (77%) patients are alive, 3/13 (33%) patients are dead (2/3 patients died of therapy-related infectious complications, and 1/3 – of acute heart failure in the early postoperative period). The median follow-up was 37.3 months. According to the assessment of late effects, neurological disorders were found in all the analyzed patients (n = 9), and orthopedic disorders were found in 66.6% (6/9) patients. The results of our analysis illustrate both the difficulty of diagnosis and management of EC in patients with NB and the need¬ for uniform testing and treatment standards with established follow-up and rehabilitation strategies for this group of patients.
References
1. Cheung N.K., Dyer M.A. Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nat Rev Cancer 2013; 13 (6): 397–411.
2. Martik M., Bronner M. Regulatory Logic Underlying Diversification of the Neural Crest. Trends Genet 2017; 33 (10): 715– 27. DOI: 10.1016/j.tig.2017.07.015
3. Papaioannou G., McHugh K. Neuroblastoma in childhood: review and radiological findings. Cancer Imaging 2005; 5 (1): 116– 27. DOI: 10.1102/1470-7330.2005.0104
4. De Bernardi B., Pianca C., Pistamiglio P., Veneselli E., Viscardi E., Pession A., et al. Neuroblastoma with symptomatic spinal cord compression at diagnosis: treatment and results with 76 cases. J Clin Oncol 2001; 19 (1): 183–90.
5. Simon T., Niemann C.A., Hero B., Henze G., Suttorp M., Schilling F.H., et al. Shortand long-term outcome of patients with symptoms of spinal cord compression by neuroblastoma. Dev Med Child Neurol 2012; 54 (4): 347–52.
6. Plantaz D., Rubie H., Michon J., Mechinaud F., Coze C., Chastagner P., et al. Thetreatment of neuroblastoma with intraspinal extension with chemotherapy followed by surgical removal of residual disease, a prospective study of 42 children. Results of the NBL 90 Study of the French Society of Paediatric Oncology. Cancer 1996; 78: 311–9.
7. Brodeur G., Pritchard J., Berthold F., Carlsen N., Castel V., Castelberry R., et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 1993; 11 (8): 1466–7.
8. NB2004 protocol. Berthold F (principal investigator). [Elektronnyi resurs]. URL: http://www.kinderkrebsinfo.de/dlja_specialistov/protokoly_gpoh/pohkinderkrebsinfotherapiestudien/nb2004/index_rus.html. (Data obrashcheniya 01.12.2020)
9. Aids to the Investigation of Peripheral Nerve Injuries. Medical Research Council: Nerve Injuries Research Committee. His Majesty’s Stationery Office: 1942; pp. 48 (iii) and 74 figures and 7 diagrams; with Aids to the Examination of the Peripheral Nervous System. By Michael O’Brien for the Guarantors of Brain. Saunders Elsevier: 2010; pp. [8] 64 and 94 Figures. Brain 2010: 133; 2838–44.
10. Kraal K., Blom T., van Noesel M., Kremer L., Caron H., Tytgat G., et al. Treatment and outcome of neuroblastoma with intraspinal extension: A systematic review Pediatr Blood Cancer 2017; 64 (8). DOI: 10.1002/pbc.26451
11. Gigliotti A.R., De Ioris M.A., De Grandis E., Podda M., Cellini M., Sorrentino S., et al. Congenital neuroblastoma with symptoms of epidural compression at birth. Pediatr Hematol Oncol 2016; 33 (2): 94–101.
12. De Bernardi B., Gambini C., Haupt R., Granata C., Rizzo A., Conte M. Retrospective study of childhood ganglioneuroma J Clin Oncol 2008; 26 (10): 1710–6. DOI: 10.1200/JCO.2006.08.8799
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17. Harter D., Weiner H. Spine tumors. In Albright A.L., Pollack I., Adelson P. (eds.). Principles and Practice of Pediatric Neurosurgery, ed 3. New York: Thieme; 2014. Rp. 721–773.
18. Kelley S.P., Ashford R.U., Rao A.S., Dickson R.A. Primary bone tumours of the spine: a 42-year survey from the Leeds Regional Bone Tumour Registry. Eur Spine J 2007; 16: 405–9.
19. Ravindra V.M., Eli I.M., Schmidt M.H., Brockmeyer D.L. Primary osseous tumors of the pediatric spinal column: review of pathology and surgical decision making. Neurosurg Focus 2016; 41 (2): E3.
20. Fenart D., Deville A., Donzeau M., Bruneton J. Retroperitoneal neuroblastoma diagnosed in utero. Apropos of 1 case. J Radiol 1983; 64: 359–61.
21. Fisher J.P., Tweddle D.A. Neonatal neuroblastoma. Semin Fetal Neonatal Med 2012; 17 (4): 207.
22. Angelini P., Plantaz D., De Bernardi B., Passagia J.-G., Rubie H., Pastore G. et al. Late sequelae of symptomatic epidural compression in children with localized neuroblastoma. Pediatr Blood Cancer 2011; 57 (3): 473–80.
23. Laur O., Nandu H., Titelbaum D.S., Nunez D.B., Khurana B. Nontraumatic Spinal Cord Compression: MRI Primer for Emergency Department Radiologists. radiographics 2019; 39 (6): 1862–80.
24. Baysson H., Etard C., Brisse H.J., Bernier M.O. Diagnostic radiation exposure in children and cancer risk: current knowledge and perspectives. Arch Pediatr 2012; 19 (1): 64–7.
25. Li S., Zhong N., Xu W., Yang X., Wei H., Xiao J. The impact of surgical timing on neurological outcomes and survival in patients with complete paralysis caused by spinal tumours : evaluation of surgery on patients with complete paralysis due to neoplastic epidural spinal cord compression. Bone Joint J 2019; 101-B (7): 872–9. DOI: 10.1302/0301-620X.101B7.BJJ-2018-1173.R1
26. Pio L., Blanc T., de Saint Denis T., Irtan S., Valteau-Couanet D., Michon J., et al. Multidisciplinary surgical strategy for dumbbell neuroblastoma: A single-center experience of 32 cases. Pediatr Blood Cancer 2019; 66 Suppl 3: e27670.
27. Paulino A.C., Fowler B.Z. Risk factors for scoliosis in children with neuroblastoma. Int J Radiat Oncol Biol Phys 2005; 61 (3): 865–9. DOI: 10.1016/j.ijrobp.2004.07.719
28. Fawzy M., El-Beltagy M., Shafei M.E., Zaghloul M.S., Kinaai N.A., Refaat A., et al. Intraspinal neuroblastoma: Treatment options and neurological outcome of spinal cord compression. Oncol Lett 2014; 9 (2): 907–11. DOI: 10.3892/ol.2014.2795
