Effects of the growth pattern of medulloblastoma on short-term neurological impairments after surgery: results from the prospective multicenter HIT-SIOP PNET 4 study

Author:

Schepke Elizabeth12,Tisell Magnus34,Kennedy Colin5,Puget Stephanie6,Ferroli Paolo7,Chevignard Mathilde8910,Doz François1112,Pizer Barry13,Rutkowski Stefan14,Massimino Maura15,Navajas Aurora16,Schwalbe Edward1718,Hicks Debbie17,Clifford Steven C.17,Pietsch Torsten19,Lannering Birgitta20

Affiliation:

1. Sahlgrenska Cancer Center, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg;

2. Department of Pediatrics, Sahlgrenska University Hospital, Gothenburg;

3. Department of Neurosurgery, Sahlgrenska University Hospital and

4. Institute of Neuroscience and Physiology, Department of Neuroscience, Sahlgrenska Academy, University of Gothenburg, Sweden;

5. University of Southampton Faculty of Medicine and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom;

6. Département de Neurochirurgie Pédiatrique, Hôpital Necker-Enfants Malades, Université, Paris, France;

7. Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy;

8. Rehabilitation Department for Children with Acquired Neurological Injury, Saint Maurice Hospitals, Saint Maurice;

9. Laboratoire d’Imagerie Biomédicale and

10. GRC 24 HaMCRe, Sorbonne Université, Paris;

11. SIREDO Cancer Center (Care, Innovation & Research, in Childhood, Adolescent and Young-Adult Oncology), Institut Curie Paris;

12. Department of Pediatrics, University Paris Descartes, Paris, France;

13. Department of Oncology, Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom;

14. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

15. Fondazione Istituto di Ricovero e Cura a Carattere Scientifico IRCCS Istituto Nazionale dei Tumori, Milan, Italy;

16. BioCruces Health Research Institute, Bilbao, Spain;

17. Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne;

18. Department of Applied Sciences, Northumbria University, Newcastle-upon-Tyne, United Kingdom;

19. Institute of Neuropathology, DGNN Brain Tumour Reference Center, University of Bonn, Germany; and

20. Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Germany

Abstract

OBJECTIVEExtensive resection of a tumor in the posterior fossa in children is associated with the risk of neurological deficits. The objective of this study was to prospectively evaluate the short-term neurological morbidity in children after medulloblastoma surgery and relate this to the tumor’s growth pattern and to the extent of resection.METHODSIn 160 patients taking part in the HIT-SIOP PNET 4 (Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma) trial, neurosurgeons prospectively responded to questions concerning the growth pattern of the tumor they had resected. The extent of resection (gross, near, or subtotal) was evaluated using MRI. The patients’ neurological status before resection and around 30 days after resection was recorded.RESULTSInvasive tumor growth, defined as local invasion in the brain or meninges, cranial nerve, or major vessel, was reported in 58% of the patients. After surgery almost 70% of all patients were affected by one or several neurological impairments (e.g., impaired vision, impaired extraocular movements, and ataxia). However, this figure was very similar to the preoperative findings. Invasive tumor growth implied a significantly higher number of impairments after surgery (p = 0.03) and greater deterioration regarding extraocular movements (p = 0.012), facial weakness (p = 0.048), and ataxia in the arms (p = 0.014) and trunk (p = 0.025) compared with noninvasive tumor growth. This deterioration was not dependent on the extent of resection performed. Progression-free survival (PFS) at 5 years was 80% ± 4% and 76% ± 5% for patients with invasive and noninvasive tumor growth, respectively, with no difference in the 5-year PFS for extent of resection.CONCLUSIONSPreoperative neurological impairments and invasive tumor growth were strong predictors of deterioration in short-term neurological outcome after medulloblastoma neurosurgery, whereas the extent of resection was not. Neither tumor invasiveness nor extent of resection influenced PFS. These findings support the continuation of maximal safe resection in medulloblastoma surgery where functional risks are not taken in areas with tumor invasion.

Publisher

Journal of Neurosurgery Publishing Group (JNSPG)

Subject

General Medicine

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