International Survey on Management of Paediatric Ependymomas Preliminary

International Survey on Management of Paediatric Ependymomas: Preliminary Results Guirish Solanki¥, G Narenthiran§ Department of Neurosurgery ¥ Birmingham Children’s Hospital & § Wessex Neurological Centre, Southampton, UK

Introduction • Improved survival in most paediatric brain tumours • • developments in diagnostic imaging Improved operative micro-neurosurgical techniques improved delivery of chemotherapy and radiotherapy provision of supportive care. • Some tumours remainly "surgical" lesions • role of adjuvant chemotherapy remains controversial in some situations.

Ependymomas in the UK • Make up about 10% of brain tumours • Majority found in the posterior fossa • Over 50% are below the age of 5 years. • The use of radiotherapy is limited in a significant proportion of children under 3 years of age – Gross Total Resection or – Subtotal Resection for those.

Ependymomas in the UK • In England • Number of new cases per year is small = 35 cases • Large studies of significance take time. • Infants and children under 3 years of age • Tendency to use chemotherapy in the UK • This is not universally accepted. 30 -

The International Survey: Aims • To understand current practice – Extent of resection – Use of chemotherapy – Timing of radiotherapy • Anonymity of individual or unit optional • Report the findings to the International Neurosurgical Online Conference members

The International Survey: Definitions • Gross Total Resection: • Radical curative resection with no visible residual tumour • Sometimes unclear if there is a residue or surgical change • < less than 15 mm 2 on post-op MRI scan accepted • Subtotal Resection: • Resection with residual tumour visible at end of surgery • more than 1. 5 cm square on post-op MRI scan • Second look Surgery: • When initial surgery was incomplete, a second elective surgical procedure to allow a more complete tumour clearance.

The International Survey: Caveats • The questions apply to – supratentorial (ST) and infratentorial(PF) ependymomas – did not include primary spinal tumours. • The presence of spinal metastasis – Not an exclusion for reporting treatment strategy – Management of PF or ST lesions was allowed within this survey and details entered in additional comments for each section.

The International Survey: Methods • An online survey was made available to members of the neurosurgery academic mailing list • International Paediatric Units were also sent the survey by email to increase yield. – Not an exhaustive global list • Data was collected analysed using a standard spreadsheet and analysis package

The International Survey: Respondent and Practice status • Name • Position – (Trainee; Consultant; Senior Lecturer; Professor; Clinical Lead; Head of Department) • Practice details – Mainly adult neurosurgeon (75% adult practice) – Mainly paediatric neurosurgeon(75% paediatric practice) – Combined practice(50 -50) • Institution & Type – Public/Private ± Academic • Address – City/Country/Email /Tel

Case Load & Location • How many paediatric ependymoma cases do you treat per year in your unit? – Between 1 -5 new cases per year – Between 6 -10 new cases per year – More than 10 new cases per year • How many are in the posterior fossa? – <50% – 50 -75% – >75%

Surgical Strategy • Aggressive Radical Curative Resection attempting curative resection – (GTR accepting cranial nerve deficits, hemiparesis, cerebellar/brainstem dysfunction as collateral damage in return for a better chance of cure) • Resection attempting curative resection – (GTR only if possible without significant neurological deficits, accepting residual lesion with better quality of life)

Extent of Resection: GRT/STR • With regards to extent of primary resection: – Achieved GTR in >95% ; – Achieved GTR in 76%-95%; – Achieved GTR in 61%-75%; – Achieved GTR in 50 -60%; – Achieved GTR in < 50% of cases

Adjuvant Therapy following Primary Resection • Posterior fossa under and over 3 years of age (GTR or with STR) – – no adjuvant therapy Chemotherapy Conformal radiotherapy; Craniospinal radiotherapy • Any age In Supratentorial Ependymoma – Resection + no adjuvant therapy – Resection + Chemotherapy followed by radiotherapy over 3 years of age – Resection + radiotherapy over 3 years of age

Managing Residual/Recurrent Tumours • Under and over 3 years of age – second look surgery alone – Chemotherapy + second look surgery or – second look surgery + chemotherapy – Second look surgery and conformal / local radiotherapy – second look surgery and craniospinal radiotherapy – Some otherapeutic option (please specify)

Results: Workload • Incidence in most units is between 1 -5 new cases per year. • Few centres do >10 new cases/year. 18 Total >10 cases/year 40 16 35 14 1 -5 new cases/year 30 12 Total 6 -10 new cases/year 25 10 20 8 6 15 4 10 2 5 Sa ud A zu el a US UK ico 6 -10 new cases/year ne M ex ly l Ita Isr ae a di y In an Ge rm an da Fr na il Ca az Br 1 -5 new cases/year Ve i. A ra bi a [S Be A] lg iu m >10 cases/year ce 0 0

Results: Surgical Strategy Curative 30 Radical 25 20 15 10 5 0 >10 cases/year 1 -5 new cases/year 6 -10 new cases/year

Results: Extent of Resection 18 16 GTR in 61 -75% 14 GTR in 76 -95% 12 GTR>95% 10 8 6 4 2 0 >10 cases/year 1 -5 new cases/year 6 -10 new cases/year

Results: Surgical Strategy & Extent of Resection GTR in 61 -75% 18 GTR in 76 -95% 16 GTR>95% 14 12 10 8 6 4 2 0 Curative Radical

Results: Surgical Strategy & Extent of Resection • A surgical strategy of curative resection attempting to preserve function is preferred. • More units perform radical resection now. • Surgical strategy is not uniform and varies geographycally • Most units report GTR in 60 -95% of cases but some units have GTR in >95%.

Adjuvant therapy under age of 3 12 Chemo CSDXT No Adj Rx 10 8 6 4 2 0 GTR in 61 -75% GTR in 76 -95% GTR>95%

Adjuvant Therapy under 3 years 9 Chemo 8 CSDXT 7 DXT 6 No Adj Rx 5 4 3 2 1 0 Brazil Canada France Germany Italy UK USA

Results: Chemotherapy • In children under 3 years adjuvant chemotherapy is given. • An increasing number of units use chemotherapy prior to second look surgery following recurrence or surgery for residual disease. • Adjuvant therapy mode of delivery varies between units. This variation is greater geographically.

Results: Radiotherapy • Radiotherapy is generally accepted as adjuvant therapy for children above 3 years.

Discussion: Extent of surgical resection • The most consistent prognostic factor for cure is extent of resection • Recent reports suggest improved outcomes with a more radical resection strategy and that radiotherapy is given in children under 18 months aiming at improving survival and cure. • Is there an ethical compulsion to treat all costs to save a life? • • • Radical surgical resection Multiple surgical resections. How much is enough? Radiotherapy below 3 years of age

Discussion: Radiotherapy • Radiation therapy – the standard adjuvant treatment, – Need data comparing surgery alone to surgery and postoperative radiotherapy • Craniospinal irradiation – – – used in the past to treat these tumors most common pattern of failure is isolated local relapse. prophylactic spinal irradiation does not prevent spinal dissemination. Conformal radiotherapy is preferred. Hyperfractionated radiotherapy doses of greater than 65 Gy may improve progression-free survival for subtotal resections.

Discussion: Chemotherapy • Role of chemotherapy • • Tumour control until safe to give Radiotherapy under 3 yrs Prelude to further resection any age Adjuvant to radiotherapy (any age) Role in older children needs further clarification

Conclusion • This is only Preliminary data. 48 units so far. • Most units surveyed in Europe do 1 -5 cases/year. The US respondents report greater numbers/unit (> 6 cases /year) • Greater caseload related to more radical surgery. • More radical surgery related to greater extent of resection • Radiotherapy under the age of 3 years more prevalent in the US • Chemotherapy under the age of 3 more prevalent in Europe • A consensus is required on optimal therapy for childhood ependymomas.

Acknowledgements • The Academic Neurosurgery Online Group for hosting the survey. • Respondents for taking the time to contribute.

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