Nebenwirkungen von Krebstherapien auf das zentrale Nervensystem von Kindern und Jugendlichen: aktuelle neuroradiologische Befunde^[1]

Zusammenfassung

Es ist zunehmend wichtig, Komplikationen im ZNS (zentrales Nervensystem), die während und nach pädiatrischen Krebstherapien auftreten, frühzeitig und korrekt zu diagnostizieren, denn die Gesamtüberlebensraten werden dank innovativer und aggressiver onkologischer Therapien immer besser. Höchste Wachsamkeit ist erforderlich, um die radiologischen Merkmale dieser ZNS-Komplikationen zu identifizieren. Der Radiologe muss hierzu mit den früh und spät auftretenden ZNS-Nebenwirkungen von Krebstherapien im Kindes- und Jugendalter vertraut sein (z. B. toxische Effekte, Infektionen, endokrine oder sensorische Dysfunktionen, neuropsychologische Störungen, 2. maligne Erkrankungen), um die bildgestützte Diagnosestellung zu beschleunigen und die assoziierte Morbidität möglichst gering zu halten. Der Ausbau der Kenntnisse über diese Komplikationen wird es ermöglichen, besser zugeschnittene therapeutische Studien zu entwickeln sowie die Patienten effektiver zu überwachen, und so zu einer Steigerung der Lebensqualität durch Verringerung der Folgeschäden bei Überlebenden führen.

Abstract

The need for early, accurate diagnosis of central nervous system (CNS) complications occurring during and after pediatric cancer treatment is growing because of the improvement in overall survival rates related to innovative and aggressive oncologic therapies. An elevated degree of suspicion is needed to recognize the radiologic features of these CNS complications. Radiologists need familiarity with the early and late side effects of cancer therapy in the pediatric CNS (e. g., toxic effects, infection, endocrine or sensory dysfunction, neuropsychologic impairment, second malignancies), in order to accelerate the imaging diagnosis and minimize as much as possible the associated morbidity. Acquisition of knowledge about these complications will enable the development of more appropriate therapeutic trials and more effective patient surveillance and will lead to an improved quality of life by decreasing the long-term sequelae in survivors.

¹ © 2011 The Radiological Society of North America. All rights reserved. Originally puplished in English in RadioGraphics 2011; 31: 1123 – 1139. Online puplished in 10.1148 /rg.314105180. Translated and reprinted with permission of RSNA. RSNA is not responsible for any inaccuracy or error arising from the translation from English to German.

• Literatur

• 1 Yeh JM, Nekhlyudov L, Goldie SJ et al. A model-based estimate of cumulative excess mortality in survivors of childhood cancer. Ann Intern Med 2010; 152 : 409-417 W131-W138
• 2 Parisi MT, Fahmy JL, Kaminsky CK et al. Complications of cancer therapy in children: a radiologist’s guide. RadioGraphics 1999; 19: 283-297
• 3 Ullrich NJ. Inherited disorders as a risk factor and predictor of neurodevelopmental outcome in pediatric cancer. Dev Disabil Res Rev 2008; 14: 229-237
• 4 Laningham FH, Kun LE, Reddick WE et al. Childhood central nervous system leukemia: historical perspectives, current therapy, and acute neurological sequelae. Neuroradiology 2007; 49: 873-888
• 5 Neglia JP, Robison LL, Stovall M et al. New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 2006; 98: 1528-1537
• 6 Kalifa C, Grill J. The therapy of infantile malignant brain tumors: current status?. J Neurooncol 2005; 75: 279-285
• 7 Meadows AT, Friedman DL, Neglia JP et al. Second neoplasms in survivors of childhood cancer: findings from the Childhood Cancer Survivor Study cohort. J Clin Oncol 2009; 27: 2356-2362
• 8 Panigrahy A, Blüml S. Neuroimaging of pediatric brain tumors: from basic to advanced magnetic resonance imaging (MRI). J Child Neurol 2009; 24: 1343-1365
• 9 Pollack IF. Diagnosis and treatment of childhood brain tumors: current perspectives. J Child Neurol 2009; 24: 1464-1465
• 10 Kaste SC, Rodriguez-Galindo C, Furman WL et al. Imaging aspects of neurologic emergencies in children treated for non-CNS malignancies. Pediatr Radiol 2000; 30 (08) 558-565
• 11 Turner CD, Rey-Casserly C, Liptak CC et al. Late effects of therapy for pediatric brain tumor survivors. J Child Neurol 2009; 24: 1455-1463
• 12 Broniscer A, Ke W, Fuller CE et al. Second neoplasms in pediatric patients with primary central nervous system tumors: the St. Jude Children’s Research Hospital experience. Cancer 2004; 100: 2246-2252
• 13 Ullrich NJ. Neurologic sequelae of brain tumors in children. J Child Neurol 2009; 24: 1446-1454
• 14 Dubey A, Sung WS, Shaya M et al. Complications of posterior cranial fossa surgery: an institutional experience of 500 patients. Surg Neurol 2009; 72: 369-375
• 15 Rekate HL, Grubb RL, Aram DM et al. Muteness of cerebellar origin. Arch Neurol 1985; 42: 697-698
• 16 Doxey D, Bruce D, Sklar F et al. Posterior fossa syndrome: identifiable risk factors and irreversible complications. Pediatr Neurosurg 1999; 31: 131-136
• 17 McMillan HJ, Keene DL, Matzinger MA et al. Brainstem compression: a predictor of postoperative cerebellar mutism. Childs Nerv Syst 2009; 25: 677-681
• 18 Steinbok P, Cochrane DD, Perrin R et al. Mutism after posterior fossa tumour resection in children: incomplete recovery on long-term follow-up. Pediatr Neurosurg 2003; 39: 179-183
• 19 Rønning C, Sundet K, Due-Tønnessen B et al. Persistent cognitive dysfunction secondary to cerebellar injury in patients treated for posterior fossa tumors in childhood. Pediatr Neurosurg 2005; 41: 15-21
• 20 Puget S, Boddaert N, Viguier D et al. Injuries to inferior vermis and dentate nuclei predict poor neurological and neuropsychological outcome in children with malignant posterior fossa tumors. Cancer 2009; 115: 1338-1347
• 21 El-Bahy K. Telovelar approach to the fourth ventricle: operative findings and results in 16 cases. Acta Neurochir (Wien) 2005; 147: 137-142
• 22 Bhatia R, Tahir M, Chandler CL. The management of hydrocephalus in children with posterior fossa tumours: the role of pre-resectional endoscopic third ventriculostomy. Pediatr Neurosurg 2009; 45: 186-191
• 23 Yamini B, Refai D, Rubin CM et al. Initial endoscopic management of pineal region tumors and associated hydrocephalus: clinical series and literature review. J Neurosurg 2004; 100: 437-441
• 24 Won SC, Kwon SY, Han JW et al. Posterior reversible encephalopathy syndrome in childhood with hematologic/oncologic diseases. J Pediatr Hematol Oncol 2009; 31: 505-508
• 25 Lucchini G, Grioni D, Colombini A et al. Encephalopathy syndrome in children with hemato-oncological disorders is not always posterior and reversible. Pediatr Blood Cancer 2008; 51: 629-633
• 26 Patel AJ, Fox BD, Fulkerson DH et al. Posterior reversible encephalopathy syndrome during posterior fossa tumor resection in a child. J Neurosurg Pediatr 2010; 6: 377-380
• 27 McKinney AM, Short J, Truwit CL et al. Posterior reversible encephalopathy syndrome: incidence of atypical regions of involvement and imaging findings. AJR Am J Roentgenol 2007; 189: 904-912
• 28 Yağmurlu B, Akyürek S, Fitoz S et al. MRI of non-neoplastic cranial complications of malignant disorders. Diagn Interv Radiol 2008; 14: 61-68
• 29 Fisher MJ, Khademian ZP, Simon EM et al. Diffusion-weighted MR imaging of early methotrexate-related neurotoxicity in children. AJNR Am J Neuroradiol 2005; 26: 1686-1689
• 30 Rolf N, Boehm H, Kaindl AM et al. Acute ascending motoric paraplegia following intrathecal chemotherapy for treatment of acute lymphoblastic leukemia in children: case reports and review of the literature. Klin Padiatr 2006; 218: 350-354
• 31 Kieslich M, Porto L, Lanfermann H et al. Cerebrovascular complications of L-asparaginase in the therapy of acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2003; 25: 484-487
• 32 Moharir MD, Shroff M, Stephens D et al. Anticoagulants in pediatric cerebral sinovenous thrombosis: a safety and outcome study. Ann Neurol 2010; 67: 590-599
• 33 Sébire G, Tabarki B, Saunders DE et al. Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome. Brain 2005; 128: 477-489
• 34 Vázquez E, Lucaya J, Castellote A et al. Neuroimaging in pediatric leukemia and lymphoma: differential diagnosis. RadioGraphics 2002; 22: 1411-1428
• 35 Gaviani P, Schwartz RB, Hedley-Whyte ET et al. Diffusion-weighted imaging of fungal cerebral infection. AJNR Am J Neuroradiol 2005; 26: 1115-1121
• 36 Peltola V, Ruuskanen O, Svedström E. Magnetic resonance imaging of lung infections in children. Pediatr Radiol 2008; 38: 1225-1231
• 37 Eibel R, Herzog P, Dietrich O et al. Pulmonary abnormalities in immunocompromised patients: comparative detection with parallel acquisition MR imaging and thin-section helical CT. Radiology 2006; 241: 880-891
• 38 Miller GG, Boivin G, Dummer JS et al. Cytomegalovirus ventriculoencephalitis in a peripheral blood stem cell transplant recipient. Clin Infect Dis 2006; 42: e26-e29
• 39 Arribas JR, Storch GA, Clifford DB et al. Cytomegalovirus encephalitis. Ann Intern Med 1996; 125: 577-587
• 40 Seo SK, Regan A, Cihlar T et al. Cytomegalovirus ventriculoencephalitis in a bone marrow transplant recipient receiving antiviral maintenance: clinical and molecular evidence of drug resistance. Clin Infect Dis 2001; 33: e105-e108
• 41 Baskin HJ, Hedlund G. Neuroimaging of herpesvirus infections in children. Pediatr Radiol 2007; 37: 949-963
• 42 Pastore G, Mosso ML, Magnani C et al. Physical impairment and social life goals among adult long-term survivors of childhood cancer: a population-based study from the childhood cancer registry of Piedmont, Italy. Tumori 2001; 87: 372-378
• 43 Gurney JG, Kadan-Lottick NS, Packer RJ et al. Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survivor Study. Cancer 2003; 97: 663-673
• 44 Aziz NM, Oeffinger KC, Brooks S et al. Comprehensive long-term follow-up programs for pediatric cancer survivors. Cancer 2006; 107: 841-848
• 45 Oeffinger KC, Mertens AC, Sklar CA et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 2006; 355: 1572-1582
• 46 Chan MS, Roebuck DJ, Yuen MP et al. MR imaging of the brain in patients cured of acute lymphoblastic leukemia: the value of gradient echo imaging. AJNR Am J Neuroradiol 2006; 27 (03) 548-552
• 47 Löbel U, Sedlacik J, Sabin ND et al. Three-dimensional susceptibility-weighted imaging and two-dimensional T2*-weighted gradient-echo imaging of intratumoral hemorrhages in pediatric diffuse intrinsic pontineglioma. Neuroradiology 2010; 52: 1167-1177
• 48 Rutkowski S, Bode U, Deinlein F et al. Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 2005; 352: 978-986
• 49 Geyer JR, Sposto R, Jennings M et al. Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children’s Cancer Group. J Clin Oncol 2005; 23: 7621-7631
• 50 Lafay-Cousin L, Bouffet E, Hawkins C et al. Impact of radiation avoidance on survival and neurocognitive outcome in infant medulloblastoma. Curr Oncol 2009; 16: 21-28
• 51 Nagel BJ, Palmer SL, Reddick WE et al. Abnormal hippocampal development in children with medulloblastoma treated with risk-adapted irradiation. AJNR Am J Neuroradiol 2004; 25: 1575-1582
• 52 Palmer SL, Reddick WE, Glass JO et al. Decline in corpus callosum volume among pediatric patients with medulloblastoma: longitudinal MR imaging study. AJNR Am J Neuroradiol 2002; 23: 1088-1094
• 53 Mabbott DJ, Noseworthy MD, Bouffet E et al. Diffusion tensor imaging of white matter after cranial radiation in children for medulloblastoma: correlation with IQ. Neuro Oncol 2006; 8: 244-252
• 54 Reddick WE, Glass JO, Helton KJ et al. Prevalence of leukoencephalopathy in children treated for acute lymphoblastic leukemia with high-dose methotrexate. AJNR Am J Neuroradiol 2005; 26: 1263-1269
• 55 Vázquez E, Castellote A, Piqueras J et al. Second malignancies in pediatric patients: imaging findings and differential diagnosis. RadioGraphics 2003; 23: 1155-1172