Jonathan Kjær Grønbæk1, Morten Wibroe2, Sebastian Toescu3, Radek Frič4, Birthe Lykke Thomsen5, Lisbeth Nørgaard Møller2, Pernilla Grillner6, Bengt Gustavsson7, Conor Mallucci8, Kristian Aquilina9, Greg Adam Fellows10, Emanuela Molinari11, Magnus Aasved Hjort12, Mia Westerholm-Ormio13, Rosita Kiudeliene14, Katalin Mudra15, Peter Hauser16, Kirsten van Baarsen17, Eelco Hoving17, Julian Zipfel18, Karsten Nysom2, Kjeld Schmiegelow19, Astrid Sehested2, Marianne Juhler20, René Mathiasen21. 1. Department of Neurosurgery, The University Hospital Rigshospitalet, Copenhagen, Denmark; Department of Paediatrics and Adolescent Medicine, The University Hospital Rigshospitalet, Copenhagen, Denmark. 2. Department of Paediatrics and Adolescent Medicine, The University Hospital Rigshospitalet, Copenhagen, Denmark. 3. Department of Neurosurgery, Great Ormond Street Hospital for Children, London, UK; Developmental Imaging and Biophysics Section, University College London Great Ormond Street Institute of Child Health, London, UK. 4. Department of Neurosurgery, Oslo University Hospital, Oslo, Norway. 5. Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark. 6. Pediatric Oncology Unit, Astrid Lindgrens Childrens Hospital, Karolinska University Hospital, Stockholm, Sweden. 7. Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden. 8. Department of Paediatric Neurosurgery, Alder Hey Children's NHS Foundation Trust, Liverpool, UK. 9. Department of Neurosurgery, Great Ormond Street Hospital for Children, London, UK. 10. Department of Paediatric Neurosurgery, Bristol Royal Hospital for Children, Bristol, UK. 11. Department of Neurology, The Queen Elizabeth University Hospital, University of Glasgow, Glasgow, UK. 12. Department of Pediatric Hematology and Oncology, St Olavs Hospital, Trondheim, Norway. 13. Hospital for Children and Adolescents, Helsinki University Hospital, Finland. 14. Center of Pediatric Oncology and Hematology at Pediatric Department and Hospital of Kauno Klinikos, Lithuanian University of Health Sciences, Kaunas, Lithuania. 15. 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary. 16. 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary; Pediatric Oncology and Transplantation Unit, Velkey László Child's Health Center, Borsod-Abaúj-Zemplén County University Teaching Hospital, Miskolc, Hungary. 17. Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands. 18. Division of Pediatric Neurosurgery, Department of Neurosurgery, University Hospital Tübingen, Tübingen, Germany. 19. Department of Paediatrics and Adolescent Medicine, The University Hospital Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark. 20. Department of Neurosurgery, The University Hospital Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Neurosurgery, Aarhus University Hospital, Aarhus, Denmark. 21. Department of Paediatrics and Adolescent Medicine, The University Hospital Rigshospitalet, Copenhagen, Denmark. Electronic address: rene.mathiasen@regionh.dk.
Abstract
BACKGROUND: Brain tumours are the most common solid tumours in childhood. Half of these tumours occur in the posterior fossa, where surgical removal is complicated by the risk of cerebellar mutism syndrome, of which postoperative speech impairment (POSI) is a cardinal symptom, in up to 25% of patients. The surgical approach to midline tumours, mostly undertaken by transvermian or telovelar routes, has been proposed to influence the risk of POSI. We aimed to investigate the risk of developing POSI, the time course of its resolution, and its association with surgical approach and other clinical factors. METHODS: In this observational prospective multicentre cohort study, we included children (aged <18 years) undergoing primary surgery for a posterior fossa tumour at 26 centres in nine European countries. Within 72 h of surgery, the operating neurosurgeon reported details on the tumour location, surgical approach used, duration of surgery, use of traction, and other predetermined factors, using a standardised surgical report form. At 2 weeks, 2 months, and 1 year after surgery, a follow-up questionnaire was filled out by a paediatrician or neurosurgeon, including neurological examination and assessment of speech. Speech was classified as mutism, reduced speech, or habitual speech. POSI was defined as either mutism or severely reduced speech. Ordinal logistic regression was used to analyse the risk of POSI. FINDINGS: Between Aug 11, 2014, and Aug 24, 2020, we recruited 500 children. 426 (85%) patients underwent primary tumour surgery and had data available for further analysis. 192 (45%) patients were female, 234 (55%) patients were male, 81 (19%) patients were aged 0-2 years, 129 (30%) were aged 3-6 years, and 216 (51%) were aged 7-17 years. 0f 376 with known postoperative speech status, 112 (30%) developed POSI, 53 (14%) developed mutism (median 1 day [IQR 0-2]; range 0-10 days), and 59 (16%) developed reduced speech after surgery (0 days [0-1]; 0-4 days). Mutually adjusted analyses indicated that the independent risk factors for development of POSI were younger age (linear spline, p=0·0087), tumour location (four levels, p=0·0010), and tumour histology (five levels, p=0·0030); surgical approach (six levels) was not a significant risk factor (p=0·091). Tumour location outside the fourth ventricle and brainstem had a lower risk of POSI (with fourth ventricle as reference, odds ratio (OR) for cerebellar vermis 0·34 [95% CI 0·14-0·77] and OR for cerebellar hemispheres 0·23 [0·07-0·70]). Compared with pilocytic or pilomyxoid astrocytoma, a higher risk of POSI was seen for medulloblastoma (OR 2·85 [1·47-5·60]) and atypical teratoid rhabdoid tumour (10·30 [2·10-54·45]). We did not find an increased risk of POSI for transvermian surgical approach compared with telovelar (0·89 [0·46-1·73]). Probability of speech improvement from mutism reached 50% around 16 days after mutism onset. INTERPRETATION: Our data suggest that a midline tumour location, younger age, and high-grade tumour histology all increase the risk of speech impairment after posterior fossa tumour surgery. We found no evidence to recommend a preference for telovelar over transvermian surgical approach in the management of posterior fossa tumours in children in relation to the risk of developing POSI. FUNDING: The Danish Childhood Cancer Foundation, the Swedish Childhood Cancer Foundation, the UK Brain Tumour Charity, the Danish Cancer Society, Det Kgl Kjøbenhavnske Skydeselskab og Danske Broderskab, the Danish Capitol Regions Research Fund, Dagmar Marshall Foundation, Rigshospitalet's Research Fund, and Brainstrust.
BACKGROUND: Brain tumours are the most common solid tumours in childhood. Half of these tumours occur in the posterior fossa, where surgical removal is complicated by the risk of cerebellar mutism syndrome, of which postoperative speech impairment (POSI) is a cardinal symptom, in up to 25% of patients. The surgical approach to midline tumours, mostly undertaken by transvermian or telovelar routes, has been proposed to influence the risk of POSI. We aimed to investigate the risk of developing POSI, the time course of its resolution, and its association with surgical approach and other clinical factors. METHODS: In this observational prospective multicentre cohort study, we included children (aged <18 years) undergoing primary surgery for a posterior fossa tumour at 26 centres in nine European countries. Within 72 h of surgery, the operating neurosurgeon reported details on the tumour location, surgical approach used, duration of surgery, use of traction, and other predetermined factors, using a standardised surgical report form. At 2 weeks, 2 months, and 1 year after surgery, a follow-up questionnaire was filled out by a paediatrician or neurosurgeon, including neurological examination and assessment of speech. Speech was classified as mutism, reduced speech, or habitual speech. POSI was defined as either mutism or severely reduced speech. Ordinal logistic regression was used to analyse the risk of POSI. FINDINGS: Between Aug 11, 2014, and Aug 24, 2020, we recruited 500 children. 426 (85%) patients underwent primary tumour surgery and had data available for further analysis. 192 (45%) patients were female, 234 (55%) patients were male, 81 (19%) patients were aged 0-2 years, 129 (30%) were aged 3-6 years, and 216 (51%) were aged 7-17 years. 0f 376 with known postoperative speech status, 112 (30%) developed POSI, 53 (14%) developed mutism (median 1 day [IQR 0-2]; range 0-10 days), and 59 (16%) developed reduced speech after surgery (0 days [0-1]; 0-4 days). Mutually adjusted analyses indicated that the independent risk factors for development of POSI were younger age (linear spline, p=0·0087), tumour location (four levels, p=0·0010), and tumour histology (five levels, p=0·0030); surgical approach (six levels) was not a significant risk factor (p=0·091). Tumour location outside the fourth ventricle and brainstem had a lower risk of POSI (with fourth ventricle as reference, odds ratio (OR) for cerebellar vermis 0·34 [95% CI 0·14-0·77] and OR for cerebellar hemispheres 0·23 [0·07-0·70]). Compared with pilocytic or pilomyxoid astrocytoma, a higher risk of POSI was seen for medulloblastoma (OR 2·85 [1·47-5·60]) and atypical teratoid rhabdoid tumour (10·30 [2·10-54·45]). We did not find an increased risk of POSI for transvermian surgical approach compared with telovelar (0·89 [0·46-1·73]). Probability of speech improvement from mutism reached 50% around 16 days after mutism onset. INTERPRETATION: Our data suggest that a midline tumour location, younger age, and high-grade tumour histology all increase the risk of speech impairment after posterior fossa tumour surgery. We found no evidence to recommend a preference for telovelar over transvermian surgical approach in the management of posterior fossa tumours in children in relation to the risk of developing POSI. FUNDING: The Danish Childhood Cancer Foundation, the Swedish Childhood Cancer Foundation, the UK Brain Tumour Charity, the Danish Cancer Society, Det Kgl Kjøbenhavnske Skydeselskab og Danske Broderskab, the Danish Capitol Regions Research Fund, Dagmar Marshall Foundation, Rigshospitalet's Research Fund, and Brainstrust.
Authors: Jai Sidpra; Adam P Marcus; Ulrike Löbel; Sebastian M Toescu; Derek Yecies; Gerald Grant; Kristen Yeom; David M Mirsky; Hani J Marcus; Kristian Aquilina; Kshitij Mankad Journal: Neurooncol Adv Date: 2022-01-10
Authors: Stefania Picariello; Pietro Spennato; Jonathan Roth; Nir Shimony; Alessandra Marini; Lucia De Martino; Giancarlo Nicosia; Giuseppe Mirone; Maria Serena De Santi; Fabio Savoia; Maria Elena Errico; Lucia Quaglietta; Shlomi Costantini; Giuseppe Cinalli Journal: Diagnostics (Basel) Date: 2022-03-04