PracticeUpdate: Haematology & Oncology

Postoperative stereotactic radiosurgery has become a standard of care

for patients with resected brainmetastases

A multi-institutional trial has

found comparable survival,

less cognitive decline, and

better quality of life follow-

ing stereotactic versus whole

brain radiotherapy after re-

section of brain metastases.

aul D. Brown, MD, of the

Mayo Clinic, Rochester, Min-

nesota, explained that surgical

resection of large symptomatic brain

metastases is often indicated to con-

firm diagnosis, remove lesion(s), or

reduce pressure in the brain. Tu-

mour recurrence after surgery alone,

however, is frequent.

Though postoperative whole brain

radiotherapy reduces tumour recur-

rence in the brain significantly and is

the standard of care for patients fol-

lowing resection, the treatment can

negatively impact cognitive function

and quality of life.

Stereotactic radiosurgery targets

escalated doses of radiation with

extreme precision and can eliminate

malignant cells in a single or small

number of sessions while limiting

the impact on surrounding tissue.

Dr Brown remarked, “Stereotactic

radiosurgery to the surgical cavity is

widely used despite a lack of clini-

cal trials to substantiate its effec-

tiveness. Our randomised trial was

the first to clearly demonstrate the

efficacy of stereotactic radiosurgery

vs whole brain radiotherapy in a

postoperative setting.”

From 2011 to 2015, 194 patients,

each with one to four brain metas-

tases, were randomised to stereo-

tactic radiosurgery or whole brain

radiotherapy after surgical resection

of one lesion. Seventy-seven percent

of patients had a single brain and

lung tumours were the primary site

in 59%. Average patient age was 61

years, and study arms were balanced

in baseline patient and tumour

characteristics.

Primary outcomes included over-

all survival and cognitive deteriora-

tion – free survival, defined as a

decline greater than one standard

deviation from baseline on any of six

cognitive tests. Secondary endpoints

included local control of the surgical

bed, time to intracranial failure, and

quality of life.

After a median of 15.6 months, no

statistically significant difference in

overall survival rates was observed

between groups (median overall sur-

vival 11.5 months following stereo-

tactic radiosurgery and 11.8 months

following whole brain radiotherapy).

Moreover, patients who received

stereotactic radiosurgery experi-

enced significantly longer survival

without cognitive decline (median

cognitive deterioration – free sur-

vival 3.2 months for stereotactic ra-

diosurgery and 2.8 months for whole

brain radiotherapy [hazard ratio 2.0;

P < 0.0001]).

The cognitive impact of whole

brain radiotherapy persisted at

6 months following treatment. At

6 months, cognitive deterioration

had occurred in 85.7% of patients

who received whole brain radio-

therapy, versus 53.8% of those who

underwent stereotactic radiosurgery

(P = 0.0006). A higher percentage

of patients who underwent whole

brain radiotherapy experienced

worse immediate recall, memory,

and attention than those treated

with stereotactic radiosurgery.

Whole brain radiotherapy provided

higher overall intracranial tumour

control rates at 6 and 12 months

were 90.0 and 78.6% with whole

brain radiotherapy vs 74.0 and 54.7%

with stereotactic radiosurgery (P <

0.0001). No clinically meaningful

difference was observed in median

surgical bed relapse-free survival

between treatment arms, though

long-term follow-up showed better

control with whole brain radiotherapy

(7.7 vs 7.5 months, P = 0.04).

Patients treated with stereotactic

radiosurgery experienced better

quality of life than those who re-

ceived whole brain radiotherapy.

Three months following treat-

ment, declines in quality of life

and physical wellbeing were sig-

nificantly smaller after stereotactic

radiosurgery than whole brain radio-

therapy (mean change in quality of

life from baseline –1.5 vs –7.0, P

= 0.03; mean change in wellbeing

change from baseline –6.4 vs –20.2,

P = 0.002). At 6 months, physical

wellbeing (decline of –3.2 vs –15.1,

P = 0.016) remained significantly

better in patients who received ste-

reotactic radiosurgery

Dr Brown said, “Our results con-

firm that radiosurgery to the surgical

cavity is a viable treatment option

to improve local control, with less

impact on cognitive function and

quality of life than whole brain

radiotherapy in resected metastatic

brain disease. No significant dif-

ference in survival was observed

between postoperative radiosurgery

and whole brain radiotherapy.”

He added, “Radiosurgery avoids

the well-known toxicities of whole

brain radiotherapy. Furthermore,

due to a smaller time commitment

and quicker recovery after stereotac-

tic radiosurgery, patients can restart

systemic therapies sooner. Radio-

surgery to the surgical cavity after

resection of brain metastases should

be considered a standard of care and

a less toxic alternative to the historic

standard of care.”

Read more from ASTRO 2016 on

PracticeUpdate.com

References: 1.

Pharmaceutical Benefits Scheme. Available from

www.pbs.gov.au,

accessed July 2016.

Dummer R

et al. Ann Oncol

2015;

26 (Suppl 5): 126–32.

Kakavand H

et al. Pathology

2016;48(2):194–202. Novartis Pharmaceuticals Australia Pty Ltd, ABN 18 004 244 160, 54

Waterloo Road, Macquarie Park, NSW 2113. Phone (02) 9805 3555. Item No.: MEL0168. Date of preparation: September 2016.

PATIENTS WHO TEST POSITIVE

FOR THE BRAF MUTATION MAY

BE ELIGIBLE FOR TARGETED

MELANOMA THERAPIES

1,2

BRAF mutation tests are recommended for the following patients:

MANDATORY

• Unresectable stage III or IV

HIGHLY RECOMMENDED

• High-risk resected stage IIc or stage IIIb–IIIc

~40%

OF PATIENTS

WITH MELANOMA

HARBOUR THE

BRAF MUTATION

REQUES

T THE

BRAF TEST

FOR YOUR PATIENTS WITH MELAN

OMA.

CONFIRM BRAF MUTATION STATUS EARLY

HELP EXPEDITE ACCESS TO TARGETED

THERAPIES FOR ADVANCED MELANOMA

ASTRO 2016

VOL. 1 • No. 4 • 2016