1. GAMMA KNIFE RADIOSURGERY PREDICTORS FOR OVERALL SURVIVAL
FOR BRAIN METASTASES
PREDICTORS FOR OVERALL SURVIVAL
Cornel Tancu, GK Clinical Research Fellow

2. Brief History
2012: partnership between University College London Hospitals NHS Foundation Trust and Medical Equipment Solutions Limited Company
October The first GK procedure
April Official opening of our centre
November th patient treated
June QSRC/UCLH – 7 years contract with NHS England to treat all 4 tiers as a new NHS implementation plan
October 2016 First paediatric patient treated for AVM
March procedures

3. GK INDICATIONS Benign tumours: Vascular: Functional: Metastases
Vestibular Schwannoma
Meningioma
Pituitary adenoma
Other benign (other schwannoma, haemangioblastoma, glomus tumour, etc)
Metastases
Vascular:
Arterio-venous malformations (AVM)
Cavernoma
Paediatric AVM
Functional:
Trigeminal Neuralgia

4. GK procedures 917 procedures until the end of December 2017 27% 19%
25%
13.5%
15%
19% 44 22 69
182
185
167
248
917
20% 21
121
161
150
187
277

5. GK SRS for BRAIN METASTASES - BACKGROUND
GK SRS became a well-established treatment for brain metastases (BM).
Recent studies have demonstrated its non-inferiority for survival in multi- metastatic patients (5-10 comparing with 2-4 BM) .
(Yamamoto et al., Lancet 2014).
Emerging data suggest that total Tumor Intracranial Volume (TIV) of BM is an important predictor of disease burden and outcome.

6. Material and Methods Population:
156 consecutive patients with BMs treated between 29/10/2012 and 31/12/2017
Mean follow-up period: 12.5 months (0.3 –43mths)
Method:
Prospective & retrospective data collection from CDR, PACS and Leksell Gamma Plan Station
Excel table
Kaplan-Meier estimation of survival, Log-Rank test and Cox regression in SPSS 17
OBJECTIVE :
OVERALL SURVIVAL AND PREDICTORS
LOCAL TUMOUR CONTROL
ADVERSE RADIATION EFFECTS (ARE)

7. Procedures: 182 Patients: 156 Metastases: 619
POPULATION
Procedures: Patients: Metastases: 619
Total intracranial volume of BM
Mean BMs/procedure: 4
Range: 1 – 20
Range= 25mm to 25cc
Mean TIV= 3.5cc; Median=2cc

8. Example of good response of a large BM
6 weeks post GK

9. Example of good response of a large BM
6 weeks post GK
6 weeks post GK
6 weeks post GK

10. Fractionated treatment for large BM (N=3)
10Gy x3 #
GK 1st #, TV=24.3cc
2nd #, TV=13.7cc
3rd #, TV=8.5cc
6 weeks after, TV=6cc

11. I. LOCAL TUMOUR CONTROL (n=333 metastases)
OVERALL RATE OF CONTROL FOR EACH TREATED METASTASIS: 94.6%
LCR in old BM series
Institution
BM/pts
Med. Dose
Crude LCR%
UCSF
219/100 18 82
Pittsburgh
229/130 16 89
Karolinska
105/85 27 94

12. Target Volume was the main predictor parameter for ARE (p<0.0001)
III. ADVERSE RADIATION EFFECTS (ARE)
(Tumour swelling, increased perilesional oedema or radionecrosis)
Overall rate of any ARE =8.7% (29/333 lesions)
Target Volume was the main predictor parameter for ARE (p<0.0001)
By example, for lesions with a TV>0.25cc (D≈8mm) ARE=16.7% (22/132)

13. III. OVERALL SURVIVAL (N=152)
Older series:
Kondziolka (1999): SRS+WBRT 11mths
Chidel (2000): SRS alone 10.5mths
Sneed (2002): 11.3 mths
Sneed (39): 14 mths (15.2mths for RPA class1)
Yamamoto - RCT JLGK0901 (2014): 12mths
Median Overall Survival
15.6 mths

14. THE NUMBER OF BRAIN METASTASES AT TREATMENT
p= Log Rank test
Univariate Cox regression:
The groups of 2-4 and >5 metastases did not show a statistically significant difference in overall survival- p=0.230

15. Total Intracranial Volume of BMs
Total volume: Median: 2cc; Mean: 3.5cc; Range: cc
3 categories – equal number of patients
Volume categ (cc) Nb
Estimated Median survival (months)
Small
<0.14cc 49
27.7
Medium 52
15.6
Large
>3.6 51
9.5
Overall
152
p=0.002 Log Rank test

16. II.OVERALL SURVIVAL– Prognostic Factors
VARIABLE
(continuous)
Univariate Cox proportional hazard regression model
 MULTIVARIATE Cox regression
Hazard ratio
(95% Confidence Limits)
p value
Total Intracranial Volume
1.085,
0.001
1.073,
0.008
Primary
(Lung vs Others)
1.59,
0.04
1.518,
0.075
Number of metastases
(continous)
1.024,
0.270
1.023,
0.330
(Single vs Multiple)
0.630,
0.071
0.641,
0.088
Total Intracranial Volume was found to be the only independent intracranial parameter for overall survival.

17. DISCUSSION – Total Intracranial Volume
Gonda, Yamamoto,Chen et al, European Journal of Cancer 2014:
‘The cumulative tumour volume independently associated with overall survival (p < 0.001)’.
Baschnagel A et al, JNS 2017:
‘The total brain metastasis volume was a strong and independent predictor for overall survival, distant brain failure, and local control, even when considering the number of metastases’.

18. ‘On demand’ GK SRS CONCLUSIONS
GOOD OVERALL SURVIVAL (MEDIAN=15.6 MONTHS)
THE TOTAL INTRACRANIAL VOLUME OF METASTASES, BUT NOT THE NUMBER OF METASTASES, WAS A NEGATIVE PREDICTOR OF THE SURVIVAL.
LOCAL TUMOUR CONTROL OF >94%
TARGET VOLUME WAS THE MAIN INDEPENDENT PREDICTOR OF LOCAL CONTROL RATE AND OF SIDE-EFFECTS
‘On demand’ GK SRS

19. Future developments with the GK ICON for BM
Possibility to treat larger metastases/ postoperative cavities, with lower side-effects
Reduced doses for organs at risk by using fractionation, when required
Staged treatments for patients with large number of BM
Mask treatments for repeated GK procedures and/or for anxious patients

20. GK
CyberKnife ?

21. Thank you QSRC Team Consultant Neurosurgeons Therapeutic Radiographers
QSRC Executive Director
Lynne Brooks
Consultant Neurosurgeons
Mr N Kitchen – Medical Director
Mr R Bradford
Miss J Grieve
Miss M Murphy
Mr A McEvoy
Mr L Thorne
Miss H Sethi
Mr J Hyam
Mr G James – paediatric
Mr M Tisdal - paediatric
Physicists –
Medical Physics Limited
Ian Paddick
Alex Dimitriadis
Phil Tapper
Clinical Fellow
C. Tancu
Local Manager Mike Allcock
Therapeutic
Radiographers
Katie Jeanson
A. Polonsky
W. Kinnaird
Elise Arnett
Administrative
Emily Brooks
Consultant Neuroradiologists
Dr K Miszkiel
Dr P Rangi
Dr. P. Cowley
Dr S. Bisdas
Dr F Roberson - paediatric
Dr A Rennie - paediatric
MDT Coordinator
Sam Atrey
Nurse: Glenda Jimenez