1. Brain Metastases
Dr Saiqa Spensley

2. Incidence of Brain Metastases
20-40% (Jain et al 2014)
Most common primary tumours- lung, breast, renal and melanoma
CUP accounts for 10-15% of patients with brain metastases
Swedish observational study (Smedby et al 2009):
No. pts admitted to hospital because of brain mets doubled over a 20yr period
Improvements in SACT
Improvements in imaging techniques

3. Driving Legal obligation to inform DVLA
Failure to inform is a criminal offence
Can be fined £1000
Can have QOL implications for patients
Always document you have informed patient and put in correspondence to GP

4. Treatment options Whole Brain Radiotherapy Surgical Resection
Stereotactic Radiotherapy
Best Supportive Care

5. WBRT

7. SRS

8. Median survival poor (2-8- 4.5mths)
WBRT
SRS
Median survival poor ( mths)
Priestman et al 1996
12gy/2# vs 30gy/10#
Headache control better in longer fractionation
Significant adverse effects
Alopecia, fatigue, nausea, vomiting, pain flare, constipation, reduced social functioning
Effort of attending for treatment
Median Survival up to 8 mths
Precise
Single fraction
Higher doses to sharply defined targets
Surrounding tissue spared
Outcomes comparable to neuro-surgery
Rare AEs
Treatment can be repeated
Maximum tumour volume 20cc
“Cost effective and safe but inequitable and variable access is a limiting factor” (NHS England 2015)

9. What do the RCTs tell us?
SRS + WBRT or observation vs neurosurgery + observation or WBRT N=
(Patchell et al 1998, Sahgal et al 2015, Kocher et al 2011)
No survival advantage with WBRT
Sahgal’s data- + survival advantage for pts<50 treated with SRS alone
Andrews et al (2004): WBRT + SRS boost vs WBRT alone for single brain met- survival advantage with SRS boost

10. What about QoL? N=58 1-3 brain mets RCT: SRS vs SRS + WBRT
Chang et al (2009)
Sofietti et al (2013)
N=58
1-3 brain mets
RCT: SRS vs SRS + WBRT
QoL- primary outcome measure
Neuro-cognition assessed at 4 months post treatment
Considerable decline in learning and memory sustained at 6 months- WBRT arm
Trial stopped
Data from the Kocher study
Validated QoL questionnaire + brain cancer module used
Assessed at baseline, 8 weeks and every 3 months
Improved QoL scores: global health status + improved physical and cognitive functioning and less fatigue in SRS and neuro-surgery groups

11. Prognostic Index Models -recognition of need to tailor therapy to appropriate subgroups
Recursive partitioning analysis (RPA)
Validated tool but limitations
GPA (Graded Prognostic Assessment)
Multi-institutional
3940 patients
Analysis of prognostic factors
Site specific-
Diagnosis specific GPA score (4.0 best and 0.0 worst prognosis)
Accurate tool to estimate survival and select appropriate treatment
If GPA survival is 3 months irrespective of diagnosis and conservative management recommended (Sperduto et al 2012)

12. GPA Overall Median survival 7.16 months
However varied from 2.79 to months dependent on diagnosis and GPA
NSCLC 7 months (3-14)
SCLC 4.9 months ( )
Breast 13.8 months ( )
GI cancers 5.36 months ( )

13. Lung Cancer Prognostic Factor 0.5 1.0 Age >60 50-60 <50 KPS
0.5
1.0
Age
>60
50-60
<50
KPS
<70
70-80
>80
ECM
Present -
Absent
No. BM
>3
2-3 1
GPA Score
0-1 MS
3.0
5.5
9.4
14.8

14. Breast Cancer Prognostic Factor 0.5 1.0 1.5 2.0 Age >60 <60 KPS
0.5
1.0
1.5
2.0
Age
>60
<60
KPS
<50 60
70-80
90-100 -
Subtype
Triple negative
ER+, Her2-
ER-, Her2+
ER+, Her2+
GPA Score
0-1 MS
3.4
7.7
15.1
25.3

15. Renal Cell Cancer Prognostic Factor 1.0 2.0 KPS <70 70-80 90-100
1.0
2.0
KPS
<70
70-80
90-100
No. BM
>3
2-3 1
GPA Score
0-1.0 MS
3.3
7.3
11.3
14.8

16. GI Cancers Prognostic Factor 1 2 3 4 KPS <70 70 80 90 100 MS 3.11 2 3 4
KPS
<70 70 80 90
100 MS
3.1
4.4
6.9
13.5

17. CUP Numbers too small to get big dataset for prognostic factors
?extrapolate from lung data set
In fit patient with limited disease refer to neuro-onc MDT
In patients with poor PS or extensive extracranial disease, BSC may be more appropriate

18. CUP Limited data Retrospective study (Bartelt et al 2003 Germany)
916 patients with brain mets treated with WBRT (total dose up to 50Gy)
CUP n=47
16 had solitary met and31 multiple brain mets
RPA class applied 0 in Class I, 23 Class II, 24 Class III
Median OS for CUP 4.8 months
MS for solitary met 7.3 mths vs 3.9 mths for multiple
MS for KPS> months vs 3.2 mths for KPS <70

19. NCCN Guidelines
1-3 mets
Disseminated disease with poor systemic options – consider WBRT or BSC
Limited systemic disease with available systemic options - consider resection or SRS
4 or more mets
Consider WBRT or SRS

20. NICE Guidelines Multiple metastases including brain involvement
Refer patients presenting with apparent brain metastases as the only sign of malignant disease after initial and special investigations to a neuro-oncology MDT for evaluation and treatment.
Do not offer chemotherapy to patients with brain metastases of unknown primary origin except as part of a controlled clinical trial.
Inform patients with brain metastases of unknown primary origin and their carers that there is no evidence that any treatment offers improved survival and there is limited evidence of improvement in neurological symptoms with surgery and/or whole brain radiotherapy

21. Management
Symptoms suggestive of brain mets (headaches/seizures/confusion/nausea and vomiting)
Contrast CT Brain
Refer to Acute Oncology Bleep 3606
Dexamethasone 8mg bd with PPI cover
If seizures prescribe antiepileptic
If brain mets confirmed calculate GPA and chase inform Acute Oncology
Advise NOT TO DRIVE

22. Management If GPA 0-1.0 probable best supportive care
Get Oncology review
Consider discharge planning with CHCFT
Referral to palliative care team
Titrate dexamethasone

23. Management
If GPA >1.0 refer to Bristol Neuro Oncology MDT (referral by 12 on Monday for discussion Wednesday)
MRI Brain with contrast and staging CT CAP
Titration of dexamethasone
Ensure patient has key worker for communication of MDT outcome

24. Any Questions?