The document discusses treatment options for brain metastases including surgery, whole brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). It notes that while WBRT was traditionally used, studies show SRS alone may be preferred for limited brain metastases to avoid cognitive decline risks from WBRT. For larger or multiple tumors, WBRT provides better local and distant tumor control compared to SRS alone. Ongoing research evaluates hippocampal-sparing WBRT and the role of SRS boost after surgery to improve outcomes while preserving cognition. The optimal approach depends on disease factors and emerging evidence favors SRS for limited metastases to balance survival benefits with quality of life.

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