Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2021; 20: 56-68
Ортопедические нарушения у детей с нейробластомой при интраканальном распространении: опыт НМИЦ ДГОИ им. Дмитрия Рогачева
https://doi.org/10.24287/1726-1708-2021-20-4-56-68Аннотация
Нейробластома (НБ) является самой частой экстракраниальной опухолью у детей. В 5–15% случаев отмечается ее распространение в позвоночный канал с возможностью развития неврологического дефицита и ортопедической патологии как в дебюте заболевания, так и в отдаленном периоде. В анализ включены пациенты с НБ и интраканальным распространением (n = 61), получавшие лечение в НМИЦ ДГОИ им. Дмитрия Рогачева с 01.2012 по 12.2018. Данное исследование одобрено независимым этическим комитетом и утверждено решением ученого совета НМИЦ ДГОИ им. Дмитрия Рогачева. Лечение проводилось по протоколу NB-2004. Всем детям выполнялась магнитно-резонансная томография/компьютерная томография спинного мозга для оценки распространения опухоли в позвоночный канал и степени компрессии спинного мозга. Наличие сколиоза и степень его выраженности оценивались инициально и через 2 года от момента постановки диагноза по данным визуализации с использованием измерения угла Кобба. Степень сколиоза определялась как легкая при 10–25° угла Кобба, средняя при 25–40°, тяжелая при более 40°. В нашем исследовании инициально сколиоз был выявлен у 7/61 (12%) пациентов. Медиана возраста на момент постановки диагноза для этой группы составила 8 (2,3–11,8) месяцев. Соотношение по полу мальчики:девочки – 2,5:1. Первичная опухоль располагалась забрюшинно внеорганно у 4/7 (57%) больных и в заднем средостении у 3/7 (43%). Преобладали пациенты со 2-й и 3-й стадиями по INSS – 4/7 (57%), с 4-й стадией было 2/7 (29%) пациента и с 4S стадией – 1/7 (14%). Наибольшая часть больных была стратифицирована в группу наблюдения – 5/7 (71%). У 6/7 (86%) пациентов опухоль при распространении в позвоночный канал захватывала грудной отдел позвоночника. В 6/7 (86%) случаях отмечено тотальное заполнение позвоночного канала. Нейрохирургическое лечение проведено у 4/7 (57%) пациентов. Анализ ортопедического статуса инициально выявил легкую степень сколиоза у всех больных. Среди пациентов без инициального сколиоза через 2 года от постановки диагноза визуализация для оценки была доступна у 38/54 (70%). В 9/38 (24%) случаях выявлен сколиоз. Медиана возраста на момент постановки НБ составила 8,2 (0,8–42,3) месяца, соотношение по полу мальчики:девочки составило 2:1. Первичная опухоль у 7/9 (78%) больных была локализована в заднем средостении. Преобладали пациенты группы наблюдения 7/9 (78%). У 8/9 (89%) пациентов опухоль распространялась в позвоночный канал на уровнях с захватом грудных позвонков. Большинство составили пациенты с заполнением опухолью от 33 до 66% поперечника позвоночного канала – 4/9 (44%). Нейрохирургическое лечение проведено в 6/9 (67%) случаях. В этой группе отмечен сколиоз легкой степени у 7/9 (78%) пациентов и умеренной степени у 2/9 (22%). Ортопедические проблемы при НБ с интраканальным распространением опухоли могут быть представлены сколиозом и выявляются как в дебюте заболевания, так и в отдаленном периоде, что требует мультидисциплинарного подхода с привлечением к данной проблеме ортопедов.
Список литературы
1. Cheung N.K., Dyer M.A. Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nat Rev Cancer 2013; 13 (6): 397– 411. DOI: 10.1038/nrc3526
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. 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. DOI: 10.1200/JCO.2001.19.1.183
4. Simon T., Niemann C.A., Hero B., Henze G., Suttorp M., Schilling F., et al. Short- and long-term outcome of patients with symptoms of spinal cord compression by neuroblastoma. Dev Med Child Neurol 2012; 54 (4): 347–52 DOI: 10.1111/j.1469-8749.2012.04219.x
5. 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. DOI: 10.1200/JCO.1993.11.8.1466
6. NB2004 protocol. Berthold F (principal investigator). [Электронный ресурс] URL: http://www.kinderkrebsinfo.de/dlja_specialistov/protokoly_gpoh/pohkinderkrebsinfotherapiestudien/nb2004/index_rus.html [cited 2016 March 15].
7. Cobb J. Outline for the study of scoliosis. Instr Course Lect 1948; 5: 261–75.
8. Srinivasalu S., Modi H., Smehta S., Suh S., Chen T., Murun T. Cobb angle measurement of scoliosis using computer measurement of digitally acquired radiographs-intraobserver and interobserver variability. Asian Spine J 2008; 2 (2): 90–3. DOI: 10.4184/asj.2008.2.2.90
9. [Электронный ресурс] URL: https://www.physio-pedia.com/Cobb%27s_angle. Дата обращения 16.09.2021.
10. Hoover М., Bowman L., Crawford S., Stack C., Donaldson J., Grayhack J., et al. Long-term outcome of patients with intraspinal neuroblastoma. Med Pediatr Oncol 1999; 32 (5): 353–9 DOI: 10.1002/(sici)1096- 911x(199905)32:5
11. Hell А.K., Kühnle I., Lorenz H.M., Braunschweig L., Lüders K.A., Bock H.C. et al. Spinal Deformities after Childhood Tumors. Cancers 2020; 12 (12): 3555. DOI: 10.3390/cancers12123555
12. Горохова Е.В., Качанов Д.Ю., Меришавян О.Б., Хомякова С.П., Озеров С.С., Щербаков А.П. и др. Эпидуральная компрессия при нейробластоме у детей первых 6 месяцев жизни: опыт НМИЦ ДГОИ им. Дмитрия Рогачева. Вопросы гематологии/онкологии и иммунопатологии в педиатрии 2020; 19 (4): 46–56. DOI: 10.24287/1726-1708-2020-19-4-46-56
13. Katzenstein М., Naranjo A., Tenney S., London W., Handler W., Schmidt M., et al. Neurologic and Orthopedic Manifestations of Spinal Cord Compression in Intermediate risk Neuroblastoma: A report from the Children’s Oncology Group (COG) study ANBL0531. Advances in Neuroblastoma Research (ANR) meeting 2021. 25–27 January 2021.www.anr2021.org
14. Paulino A., Fowler B. 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
15. Sandberg D., Bilsky M., Kushner B., Souweidane M., Kramer K., Laquaglia M., et al. Treatment of Spinal Involvement in Neuroblastoma Patients. Pediatr Neurosurg 2003; 39:291–298. DOI: 10.1159/000075256
16. Katzenstein M., Kent P., London W., Cohn S. Treatment and Outcome of 83 Children With Intraspinal Neuroblastoma: The Pediatric Oncology Group Experience J Clin Oncol 2001; 19 (4): 1047–55. DOI: 10.1200/JCO.2001.19.4.1047
17. Anakwenze О., Auerbach J., Buck D., Garg S., Simon S., Sutton L., et al. The role of concurrent fusion to prevent spinal deformity after intramedullary spinal cord tumor excision in children. J Pediatr Orthop 2011; 31 (5): 475–9 DOI: 10.1097/BPO.0b013e318220bb46
18. Lonstein J.E. Post-laminectomy kyphosis. Clin Orthop 1977; 128: 93–100.
19. Shikata J., Yamamuro T., Shimizu K., Saito T. Combined laminoplasty and posterolateral fusion for spinal canal surgery in children an adolescents. Clin Orthop 1990; 259: 92–9.
20. Deutsch H., Haid R.W., Rodts G.E., Mummaneni P.V. Postlaminectomy cervical deformity. Neurosurg Focus 2003; 15 (3): Е5. DOI: 10.3171/ foc.2003.15.3.5
21. Hayes F.A., Green A.A., O’Connor D.M. Chemotherapeutic management of epidural neuroblastoma. Med Pediatr Oncol 1989; 17: 6–8. DOI: 10.1002/mpo.2950170103
22. Ash S., Haupt R., Kraal K., Plantaz D., Wiecrorek A., Kachanov D., et al. Spinal Canal Invasion in Peripheral Neuroblastic Tumors - A Siopen Prospective Study Registry. PD-018. 49th Congress of the International Society of Paediatric Oncology (SIOP). 12–15 October, 2017. Washington, DC. USA. Pediatr Blood Cancer 2017; 64 Suppl 3 (Suppl 3): S121.
23. Plantaz D., Rubie H., Michon J., Mechinaud F., Coze C., Chastagner P., et al. The treatment of neuroblastoma with intraspinal extension with chemotherapy followed by surgical removal of residual disease. A prospective study of 42 patients--results of the NBL 90 Study of the French Society of Pediatric Oncology. Cancer 1996; 78: 311–9. DOI: 10.1002/(SICI)1097- 0142(19960715)78:23.0.CO;2-Z
24. De Jonge T., Slullitel H., Dubousset J., Miladi L., Wicart P., Illés T. Late-onset spinal deformities in children treated by laminectomy and radiation therapy for malignant tumours. Eur Spine J 2005; 14 (8): 765–71. DOI: 10.1007/s00586-004- 0778-1
Pediatric Hematology/Oncology and Immunopathology. 2021; 20: 56-68
Orthopedic disorders in children suffering from neuroblastoma with intraspinal extension: the experience of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology
https://doi.org/10.24287/1726-1708-2021-20-4-56-68Abstract
Neuroblastoma (NB) is the most common extracranial tumor in children. In 5–15% of cases, the tumor extends into the spinal canal and can potentially cause neurological deficits and orthopedic problems that can develop both at the onset of the disease and at a later time. We analyzed data of 61 patients with NB and intraspinal extension who had been treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology over the period from Jan 2012 to Dec 2018. The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI. The treatment was delivered in accordance with the NB-2004 protocol. In all the children, magnetic resonance imaging and/or computed tomography of the CNS were performed to evaluate intraspinal extension of the tumor as well as the degree of spinal cord compression. The presence of scoliosis and its severity were determined at the baseline and at 2 years after the diagnosis using imaging data and Cobb angle measurement. Scoliosis was classified as mild if the Cobb angle was 10–25°, moderate if it was 25–40°, and severe if it exceeded 40°. In our study, 7/61 (12%) patients were diagnosed with scoliosis at the baseline assessment. The median age at diagnosis was 8.0 (2.3–11.8) months. The male to female ratio was 2.5:1. In 4/7 (57%) patients, the primary tumor was located in the retroperitoneum (outside the major organs), and in 3/7 (43%) patients – in the posterior mediastinum. In this group, 4/7 (57%) patients had INSS stage 2 or 3 tumors, 2/7 (29%) patients had stage 4 disease, and 1/7 (14%) had INSS stage 4S. The majority of patients (5/7 (71%)) were stratified into an observation group. In 6/7 (86%) patients, the tumor extended into the spinal canal involving the thoracic spine. In 6/7 (86%) cases, there was evidence of complete obstruction of the spinal canal. Neurosurgery was performed in 4/7 (57%) patients. All these patients were diagnosed with mild scoliosis at the baseline. At 2 years after the diagnosis, imaging data were available for 38/54 (70%) patients who had not had scoliosis at the baseline. This time, scoliosis was diagnosed in 9/38 (24%) cases. The median age at NB diagnosis was 8.2 (0.8–42.3) months, the male to female ratio was 2:1. In 7/9 (78%) patients, the primary tumor was located in the posterior mediastinum. The majority of patients were stratified into an observation group (7/9 (78%)). In 8/9 (89%) patients, the tumor extended into the spinal canal involving the thoracic vertebrae. In the majority of patients (4/9(44%)), the tumor filled 33 to 66% of the spinal canal. Neurosurgery was performed in 6/9 (67%) patients. In this group, 7/9 (78%) patients were diagnosed with mild scoliosis and 2/9 (22%) patients – with moderate scoliosis. NB with intraspinal extension can lead to various orthopedic problems including scoliosis that can be revealed both at the onset of the disease and at a later time, meaning that this condition requires a multidisciplinary approach involving orthopedic specialists.
References
1. Cheung N.K., Dyer M.A. Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nat Rev Cancer 2013; 13 (6): 397– 411. DOI: 10.1038/nrc3526
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. 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. DOI: 10.1200/JCO.2001.19.1.183
4. Simon T., Niemann C.A., Hero B., Henze G., Suttorp M., Schilling F., et al. Short- and long-term outcome of patients with symptoms of spinal cord compression by neuroblastoma. Dev Med Child Neurol 2012; 54 (4): 347–52 DOI: 10.1111/j.1469-8749.2012.04219.x
5. 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. DOI: 10.1200/JCO.1993.11.8.1466
6. NB2004 protocol. Berthold F (principal investigator). [Elektronnyi resurs] URL: http://www.kinderkrebsinfo.de/dlja_specialistov/protokoly_gpoh/pohkinderkrebsinfotherapiestudien/nb2004/index_rus.html [cited 2016 March 15].
7. Cobb J. Outline for the study of scoliosis. Instr Course Lect 1948; 5: 261–75.
8. Srinivasalu S., Modi H., Smehta S., Suh S., Chen T., Murun T. Cobb angle measurement of scoliosis using computer measurement of digitally acquired radiographs-intraobserver and interobserver variability. Asian Spine J 2008; 2 (2): 90–3. DOI: 10.4184/asj.2008.2.2.90
9. [Elektronnyi resurs] URL: https://www.physio-pedia.com/Cobb%27s_angle. Data obrashcheniya 16.09.2021.
10. Hoover M., Bowman L., Crawford S., Stack C., Donaldson J., Grayhack J., et al. Long-term outcome of patients with intraspinal neuroblastoma. Med Pediatr Oncol 1999; 32 (5): 353–9 DOI: 10.1002/(sici)1096- 911x(199905)32:5
11. Hell A.K., Kühnle I., Lorenz H.M., Braunschweig L., Lüders K.A., Bock H.C. et al. Spinal Deformities after Childhood Tumors. Cancers 2020; 12 (12): 3555. DOI: 10.3390/cancers12123555
12. Gorokhova E.V., Kachanov D.Yu., Merishavyan O.B., Khomyakova S.P., Ozerov S.S., Shcherbakov A.P. i dr. Epidural'naya kompressiya pri neiroblastome u detei pervykh 6 mesyatsev zhizni: opyt NMITs DGOI im. Dmitriya Rogacheva. Voprosy gematologii/onkologii i immunopatologii v pediatrii 2020; 19 (4): 46–56. DOI: 10.24287/1726-1708-2020-19-4-46-56
13. Katzenstein M., Naranjo A., Tenney S., London W., Handler W., Schmidt M., et al. Neurologic and Orthopedic Manifestations of Spinal Cord Compression in Intermediate risk Neuroblastoma: A report from the Children’s Oncology Group (COG) study ANBL0531. Advances in Neuroblastoma Research (ANR) meeting 2021. 25–27 January 2021.www.anr2021.org
14. Paulino A., Fowler B. 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
15. Sandberg D., Bilsky M., Kushner B., Souweidane M., Kramer K., Laquaglia M., et al. Treatment of Spinal Involvement in Neuroblastoma Patients. Pediatr Neurosurg 2003; 39:291–298. DOI: 10.1159/000075256
16. Katzenstein M., Kent P., London W., Cohn S. Treatment and Outcome of 83 Children With Intraspinal Neuroblastoma: The Pediatric Oncology Group Experience J Clin Oncol 2001; 19 (4): 1047–55. DOI: 10.1200/JCO.2001.19.4.1047
17. Anakwenze O., Auerbach J., Buck D., Garg S., Simon S., Sutton L., et al. The role of concurrent fusion to prevent spinal deformity after intramedullary spinal cord tumor excision in children. J Pediatr Orthop 2011; 31 (5): 475–9 DOI: 10.1097/BPO.0b013e318220bb46
18. Lonstein J.E. Post-laminectomy kyphosis. Clin Orthop 1977; 128: 93–100.
19. Shikata J., Yamamuro T., Shimizu K., Saito T. Combined laminoplasty and posterolateral fusion for spinal canal surgery in children an adolescents. Clin Orthop 1990; 259: 92–9.
20. Deutsch H., Haid R.W., Rodts G.E., Mummaneni P.V. Postlaminectomy cervical deformity. Neurosurg Focus 2003; 15 (3): E5. DOI: 10.3171/ foc.2003.15.3.5
21. Hayes F.A., Green A.A., O’Connor D.M. Chemotherapeutic management of epidural neuroblastoma. Med Pediatr Oncol 1989; 17: 6–8. DOI: 10.1002/mpo.2950170103
22. Ash S., Haupt R., Kraal K., Plantaz D., Wiecrorek A., Kachanov D., et al. Spinal Canal Invasion in Peripheral Neuroblastic Tumors - A Siopen Prospective Study Registry. PD-018. 49th Congress of the International Society of Paediatric Oncology (SIOP). 12–15 October, 2017. Washington, DC. USA. Pediatr Blood Cancer 2017; 64 Suppl 3 (Suppl 3): S121.
23. Plantaz D., Rubie H., Michon J., Mechinaud F., Coze C., Chastagner P., et al. The treatment of neuroblastoma with intraspinal extension with chemotherapy followed by surgical removal of residual disease. A prospective study of 42 patients--results of the NBL 90 Study of the French Society of Pediatric Oncology. Cancer 1996; 78: 311–9. DOI: 10.1002/(SICI)1097- 0142(19960715)78:23.0.CO;2-Z
24. De Jonge T., Slullitel H., Dubousset J., Miladi L., Wicart P., Illés T. Late-onset spinal deformities in children treated by laminectomy and radiation therapy for malignant tumours. Eur Spine J 2005; 14 (8): 765–71. DOI: 10.1007/s00586-004- 0778-1
