SRS versus Surgery plus WBRT +/- SRS

1. Debate; Counter-point??Debate; Counter-point??
Yes!! SRS is the “in” thing butYes!! SRS is the “in” thing but
don’t count out Surgery + RTdon’t count out Surgery + RT
Dr. Ashutosh Mukherji
Additional Professor,
Department of Radiotherapy,
Regional Cancer Centre, JIPMER

2. Surgery + RTSurgery + RT
SRS
Surgical
excision /
neurosurgery SRS Boost
WBRT

3. • WBRT delivers an even dose of radiation to the entire
brain
• Can treat small, undetectable tumors that may be
developing in different areas of the brain
• Often used to reduce risk of tumor recurrence post
surgery
• Advantages:
• Treat large and small tumors
• Multiple tumors at the same time
• Deep seated that are inaccessible to surgery
Whole Brain Radiation Treatment (WBRT)

4. Stereotactic Radiosurgery
• Advantages:
• Precise - less likely to hurt healthy tissue
• Delivers a higher dose of radiation to a small tumor in a
single treatment session
• When is it used?
• To treat people with up to 3 brain tumors that is not
surgically accessible
• Only treats tumors that can be detected on MRI or CT
scans
• Rare side effects include:
• Swelling
• Neurological problems and Necrosis

5. ISSUES WITH WBRT
ARGUMENTS FOR
• Negative impact of CNS
progression on neurologic
and neurocognitive function
when
• Uncertainty of the value of
salvage treatments in
reversing neurologic
symptoms when omitting
initial WBRT
ARGUMENTS AGAINST
• Risk of long-term
neurotoxicity
• Availability of effective
salvage treatments
5

6. ISSUES WITH WBRT
• Two RCTs and a meta-analysis have reported
that omission of WBRT in patients with newly
diagnosed brain metastases after either
surgery or stereotactic radiosurgery results in
a significantly worse local and distant control.
6
Patchell RA et al. JAMA 280:1485-1489, 1998
Aoyama H et al. JAMA 295:2483-2491, 2006

7. Analysis 1.2. Comparison 1 Whole-Brain Radiotherapy versus Observation, Outcome 2 Progression Free
Survival.
Review: Surgery or radiosurgery plus whole brain radiotherapy versus surgery or radiosurgery alone for brain metastases
Comparison: 1 Whole-Brain Radiotherapy versus Observation
Outcome: 2 Progression Free Survival
Study or subgroup
Whole-Brain
Radiotherapy Observation log [Hazard Ratio] Hazard Ratio Weight Hazard Ratio
N N (SE) IV,Random,95% CI IV,Random,95% CI
Kocher 2011 180 179 -0.34 (0.11) 88.4 % 0.71 [ 0.57, 0.88 ]
Roos 2006 10 9 0.24 (0.52) 11.6 % 1.27 [ 0.46, 3.52 ]
Total (95% CI) 190 188 100.0 % 0.76 [ 0.53, 1.10 ]
Heterogeneity: Tau2 = 0.03; Chi2 = 1.19, df = 1 (P = 0.28); I2 =16%
Test for overall effect: Z = 1.47 (P = 0.14)
Test for subgroup differences: Not applicable
0.5 0.7 1 1.5 2
Favours WBRT Favours Observation
Soon et al, Cochrene metaanalysis, 2014
Brain metastasis: Cochrane meta-analysis 2014
Surgery/SRS+ WBRT Vs SRS/Surgery alone: Progression free Survival
WBRT: Definite reduction in local failure
p-value=0..14

8. 8
WBRT reduced 2-year relapse rate both at initial sites
(surgery: 59% to 27%, P .001; radiosurgery: 31% to 19%, P .
040) and at new sites (surgery: 42% to 23%, P.008;
radiosurgery: 48% to 33%, P.023).
Salvage therapies were used more frequently after OBS than
after WBRT. Intracranial progression caused death in 78 (44%)
of 179 patients in the OBS arm and in 50 (28%) of 180 patients
in the WBRT arm

9. 9

10. • Study by Patchel et al randomly assigned 95 patients with a
single brain metastasis to receive surgery plus adjuvant WBRT
or surgery alone.
• Relapses at the resection site were reduced by WBRT from
46% to 10%, and new intracranial metastases developed in
only 14% of patients compared with 37% of patients without
postoperative WBRT.
• A significant reduction in neurologic death by WBRT was also
observed.
• Median survival was approximately 10 months, with no
difference between the two arms.
10
Patchell RA et al. JAMA 280:1485-1489, 1998

11. • Phase III trial from Japan that randomly assigned 132 patients
with one to four metastases to radiosurgery alone (18 to 25
Gy) or to radiosurgery plus WBRT (30 Gy in 3-Gy fractions).
• At 2 years, adjuvant WBRT resulted in an increased control
rate at the radiosurgical sites of 80%, versus 50% for
radiosurgery alone, and a decreased risk for new brain
metastases of 50%, versus 75% for radiosurgery alone.
• No significant reduction in neurologic deaths was observed.
11
Aoyama H et al. JAMA 295:2483-2491, 2006

12. 12

13. 13

14. Can we treat initially with SRS
instead?
Aoyama (JAMA 2006) SRS +/- WBRT
No difference in overall survival or initial MMSE.
Chang (Lancet Oncology 2009) SRS +/- WBRT
Inferior neurocognitive outcome and lower OS with
WBRT.
Soffietti (JCO 2013) SRS (or surgery) +/- WBRT
Inferior HRQoL with WBRT. No difference in OS.

15. 15
• There is no head-to-head comparison of radiosurgery with
neurosurgery in resectable single metastasis.
• Study by Autcher analyzed 122 patients with resectable
single brain metastasis treated by SRS and WBRT. The
local tumor control was 86% and median OS 56 weeks,
which was comparable to the surgery and WBRT arm of
Patchel’s study.
• Study by O’Neill showed no significant differences in the 1-
year survival between the two SRS and NS (56% and 52%,
respectively).

16. WBRT versus SRS
• Disease free interval
• Number of new metastases
• Extra-cranial disease control
• Patient performance status
• SRS is preferred for lesions in eloquent or surgically
inaccessible areas, is non-invasive, less risk of seeding.
• Surgery is chosen for lesions too large for SRS (>4cm) or in
patients lacking a pathological diagnosis.
• Surgery offers immediate relief of mass effect, reduced
steroid use, and a pathological diagnosis.
Surgery versus SRS

17. Shifting paradigm
Controlled primary with brain oligometases
Original
diagnosis
disease-free
interval
Brain
metastases
WBRT
Traditional paradigm
Original
diagnosis
disease-free
interval
Brain
metastases
SRS
/ Surgery
Emerging paradigm
disease-free
interval
If new brain
metastasis
SRS
/ Surgey
disease-free
interval
If more brain
metastases
SRS or WBRT

18. Multidisciplinary decision-making:
Brain metastases management
Medical oncologist
Neurosurgeon
Radiation oncologist
Customized
patient plan
Patient
SRS
WBRT
Surgery
Supportive
care

19. JROG 99-01
RTOG 95-08
MDACC
Limited Brain metastasis: Concerned over cognitive function
1-3 brain mets
Controlled primary disease
Breast/Lung Ca
ECOG 0
Age<65
Post surgery limited field RTHippocampal sparing RT
Mehta M et al
Gondi V et al
Randomized study
Meta-analysis
Cognitive function benefit
Ph-II Study
Small number
Ongoing Ph III study
ONLY SRS
Ph II studies

20. Evolving standard of care in brain metastasis
Till 1990s:
• Whole brain RT is standard of care
• Studies were focused on dosage schedule
• 30Gy/10# equivalent to 40Gy/16#
• Median survival 6-12 months
Since 1990s:
• Limited brain mets- WBRT+ SRS is standard of care (Level 1
evidence, Rec A)
• Randomized studies showed 2 mo survival benefit on addition of
SRS
• 30Gy/10# + 12 Gy Boost
• Median survival 2 months benefit

21. Evolving standard of care in brain metastasis
• Gondi et al Hippocampal sparing RT randomized study is
onging
• Ph III study (N107c study): Sur +WBRT Vs Sur+ SRS boost
Since
2012:
• Limited brain metastasis- SRS alone (Level 1A evidence, Rec A)
• Randomized studies showed no OS benefit with WBRT
• Meta-analysis confirmed: No OS benefit with WBRT, only LC benefit
• Randomized studies confirmed Cognitive function decline with WBRT
• WBRT only on recurrence / leptomeningial disease
• SRS boost after surgery: reduce local recurrence (Level II, Rec B)
• Preservation of cognitive function
• Hippocampal sparing RT is new & exciting (Level II, Rec B)
• Need randomized study for confirmation of it’s effectiveness
Future:

22. Conclusions
- Limited brain metastasis: SRS alone is the standard of care (Level 1A
evidence, Rec A)
- Multiple brain mets with poor prognosis: WBRT is standard of care
- In limited metastasis, role of WBRT arguable
- There is no overall survival benefit with addition of WBRT vis a vis
SRS ONLY
- Declines in cognitive function & QOL
- Hippocampal sparing RT in limited brain disease is new & exciting
(Level II, Rec B)
- Need randomized evidence with adequate end-point for confirmation of
it’s effectiveness
- SRS boost after surgery: reduce local recurrence (Level II, Rec B)
- Preservation of cognitive function

23. • Thus benefits of RT lies in:
 ensuring protection of
normal tissues and…….
 achieving dose escalation
to tumor volume.
WHEN USED CORRECTLY!!
• Technology has given us
new tools to hit
targets………. BUT LET US
NOT BECOME LIKE
MASLOW ……….

24. Thank youThank you