The Bristol Gamma Knife Centre & NICE Adult Brain Tumour Guidelines Dr Alison Cameron Consultant Clinical Oncologist

Stereotactic Radiosurgery / Radiotherapy in Bristol Service commenced in 2002- utilised a modified Linac. Initially treated patients with brain metastases, later extended to benign disease Gamma Knife (Perfexion) October 2013, upgraded to Icon July 2015. Market-leading intracranial SRS/SRT machine in terms of conformality and dose drop-off- minimises the dose to normal brain Icon Frame- single fraction treatments where high precision needed- for example- pituitary adenomas close to chiasm, or if a patient can not tolerate a mask (claustrophobia) Mask with intra-fraction monitoring: Single fraction treatments in patients where a frame is higher risk (post craniotomy) Multiple fraction treatment

Stereotactic Radiotherapy (2-30 fractions) Government define SRT (for SRT tariff) as 2-5# 5# SRT for large meningioma with significant oedema who are not suitable for operation 25-30# SRT small (<10cc) benign tumours 0-2mm to optics or within brainstem where SRS is higher risk to normal tissue but want to spare normal brain from long term effects of wider fields from VMAT/IMRT 2-3# Adaptive SRT- for large metastases where tumours have time to shrink between the 2 weekly fractions so reducing the normal brain dose and increasing tolerability

12Gy 22.5Gy 8Gy 4 Gy 12Gy 12Gy 8Gy 4Gy 8Gy FGK 0.5mm PTV VMAT 1 mm PTV

Dosimetric Study: Fractionated Gamma Knife v 7 field RT (v VMAT) GTV mean 3.2cc [1.55-5.3cc] Dose to optic apparatus/ orbit: no difference Homogeneity: D5 higher with FGK v Linac plans: 116% v 102% (p<0.05) All FGK plan hot spots within the tumour- at least 1.5mm away from any part of the optic apparatus FGK 7F 1mm FGK v 7F 1mm 7F 5mm FGK v 7F 5mm Hippocampus median 3.2 Gy 8.5Gy p=0.003 10.6Gy p=0.0001 Factor Difference 1 2.7 3.3 >=50% dose 8.1cc 27.4cc p<0.0001 49.4cc p=0.0002 3.4 6.1

Trigeminal Schwannoma 54Gy in 30# covering PTV by 90% Protons Yellow=5Gy Purple =30Gy Red=50.4Gy FractionatedGamma Knife

#2: 10Gy 4.512cc 31 mins No additional CBCT #1: 10Gy 6.972cc 2 small metastasis (0.1cc) 24Gy each total 1 hour 8 mins No additional CBCT #2: 10Gy 4.512cc 31 mins No additional CBCT #3: 10Gy 2.265cc 39 mins 2 extra CBCT due to movement >1mm

Treatment at The Bristol Gamma Knife Centre:15 Oct 2013-13 Oct 2016 mets (383) AN (134) Meningioma (57) TN (38) Pituitary (14) Other (22) Total=648 pt Mask= 78 pt

Commissioning Process 2015/2016 Tier 1&2- 17 centres around the UK each associated with a neurosurgical centre. Treat adults (>=16yr) brain metastases and benign brain tumours with 1-5# Tier 3&4- Adult Functional (TN) and all ages Vascular (and non- commissioned tumours agreed through IFR). 2 England Centres (London- south; Sheffield- North) Paediatric tumour- 2 England Centres (London- south; Leeds- North) Substantial QA process- testing machine accuracy, contouring and planning. All tomotherapy machines not commissioned after this process, several linac centres required help with planning to achieve adequate plans. Complex cases push limits of linac planning.

South West Area Joint service with Plymouth given geography of region- both centres must treat >100 pt Meeting December 2016 to agree joint protocols Recent sad changes in Plymouth- service may require additional support from Bristol Extensive (but poorly written) outcome data upload required by NHS England

NICE Adult Brain Tumour Guidelines Limited to management of suspected glioma, meningioma and brain metastases, and, for rehabilitation, all patients with brain tumours Scoping workshop (April 2016)- attended by myself and Marcus Bradley representing Bristol. Committee- 3 Neurosurgeons, 3 Clinical Oncologist, 3 Patient/Carer, 2 CNS, 2 AHP (OT and Psychologist), 1 Neurologist, 1 Pathologist, 1 Radiologist, Guideline Alliance team- reasearchers, project managers, health economist. First meeting July 2016. Completion Nov 2017.

1.1 What is the most effective diagnostic imaging in newly diagnosed glioma? 1.2 What is the most effective diagnostic imaging in newly diagnosed meningioma? 1.3 What is the most effective diagnostic imaging in newly diagnosed brain metastases? 1.4 What are the most useful molecular markers to guide treatment for gliomas? 1.5 What are the most useful molecular markers to estimate prognosis for gliomas? 2.1 What is the optimal initial treatment (surgery [including extent of resection], radiotherapy, observation, chemotherapy or combinations of these) for low grade glioma? 2.2 What is the most effective method of resecting high-grade glioma (for example with 5ALA, awake craniotomy, intraoperative ultrasound, intraoperative MRI)? 2.3 What is the optimal management (surgery, radiotherapy, chemotherapy, combinations of these, or other therapies such as metformin or tumour-treating fields) of recurrent high-grade glioma? 3.1 Which adults with previously untreated meningioma should have radiotherapy? 3.2 Which adults with recurrent meningioma should have radiotherapy? 4.1 What is the most effective intracranial treatment (surgery, stereotactic radiotherapy, whole-brain radiotherapy or combinations of these) for a single brain metastasis? 4.2 What is the most effective intracranial treatment (surgery, stereotactic radiotherapy, whole-brain radiotherapy, combinations of these, or no treatment) for multiple brain metastases? 5.1 What is the most effective follow-up protocol (including duration, frequency and tests) to detect recurrence after treatment for glioma? 5.2 What is the most effective follow-up protocol (including duration, frequency and tests) to detect recurrence after treatment for meningioma? 5.3 What is the most effective follow-up protocol (including duration, frequency and tests) to detect intracranial recurrence after treatment for brain metastases? 5.4 What is the most effective surveillance protocol (including no surveillance) for detecting late effects of treatment for glioma, meningioma or brain metastases? 5.5 What are the health and social care support needs of people with brain tumours (primary) and brain metastases and their families and carers? 6.1 Which adults with primary brain tumours or brain metastases should be referred for neurological rehabilitation assessment and when is the optimal time to refer?