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Brain Metastasis

‘First thing we need to do is to eliminate the nihilism while managing patients
with brain metastases’.
‘Give patients with brain metastasis a fair chance – treat them appropriately’

Brain metastasis is a common clinical presentation in advanced carcinoma lung, breast cancer and others diseases.  As the systemic treatment (chemotherapy) is improving (increase in survival), there are many more patients presenting with brain metastasis. Brain metastasis is considered ‘not curative’ and only a small proportion of patient survives more than 2 years after diagnosis. However, with advent of modern neurosurgical technologies, radiation therapy techniques and systemic therapy with higher penetration to brain tissue (blood brain barrier) the prognosis is looking slightly brighter. The main emphasis in last few years is on preservation quality of life and neurological functions.

Incidence:

In clinical practice, brain metastasis in almost 8 to 10 times more common than primary brain tumors. Hence, burden of patients with brain metastasis is huge.

Prognosis in brain metastasis depends upon:

  1. age of presentation (above 60 years have poor prognosis)
  2. Performance status (patient with good general condition do well with treatment)
  3. Systemic disease control (Patients with only disease in brain with controlled primary disease do well)
  4. Also depends upon other factors such as number of brain metastasis, type of primary tumor (breast cancer patients do better than lung cancer) and treatment received.

There is recursive portioning analysis (RPA) classes to define prognosis in brain metastasis:

RPA class

Features

Median Survival (months)

1

KPS>70; Age<65; controlled primary;
no extracranial disease

7.1

2

KPS>70; Age>65; Uncontrolled primary; extracranial metastasis

4.2

3

KPS<70

2.3

Management principles:

Solitary (single) brain metastasis

Single brain metastasis with controlled primary has relatively better prognosis and should be treated aggressively. Usual treatment is surgery if tumour is in assessable non-eloquent area of brain. Surgery will immediately relief the pressure effect and has improvement in symptoms.
However, in a high proportion of patient surgery is not possible because of the location of the tumour and risk of neurological deficit (paralysis). Radiosurgery is indicated in these situations. After surgery or radiosurgery whole brain radiation therapy is given in majority of situation.
However, only a small of patients with brain metastasis receive radiation therapy or surgical management especially in developing countries.

Main advantages of radiosurgery in brain metastasis are:

  • Non-invasive procedure (no opening of skull bone)
  • Minimal side effects
  • Out-patient procedure (usually only one day procedure)

Surgery

Radiosurgery

Lesion

Larger (>4 cm), Non-eloquent area

Small, deep lesions, eloquent area

Effect

Rapid resolution of mass effect

Minimally invasive

Tumour removed

Sterilized

Histopathology

Confirmed

Not

Anesthesia

Required

No

Steroid

Tapped faster

longer

Follow up

Less intensive

More

There are randomized evidences that surgery or radiosurgery improves survival significantly compared with radiation therapy alone. In patients with 1 to 3 brain metastasis with controlled primary radiosurgery / surgery improves survival.
Evidences:                                 

Median Survival (months)

p-value

Patchel

WBRT+ Sx

9.2

0.01

WBRT only

3.4

Vecht

WBRT+ Sx

10

0.04

WBRT only

6

Mintz

WBRT+ Sx

5.6

0.24

WBRT only

6.3

Andrews

WBRT+ Sx

6.5

0.13

WBRT only

5.7

Kondriolka

WBRT+ Sx

11

0.22

WBRT only

7.5

Prospective studies in larger/ multiple tumours treated with radiosurgery (CyberKnife):

Study

Median Voume (cm3)

KPS

Multiple lesions

Median Survival
(months)

Alexender (1995)

3

80

31%

9.4

Aucher (1996)

0%

13

Breneman (1997)

<4 cm

90

57%

10

Shiou (1997)

1.3

90

46%

11

Shirato (1997)

>2 cm:36%

60

0%

9

Pirzhall (1998)

80

26%

5.5

Kim (2000)

2.1

90

15%

11

Nishizaki (2006)

7.2

80

45%

13

Multiple brain metastases

  1. Main treatment in multiple brain metastases is whole brain radiotherapy.
  2. Usually treatment given in 10 days (usually 30 Gy in 10 days or 20 Gy in 5 days).
  3. Conventional radiation therapy is used. No significant role for IMRT or IGRT.
  4. Prognosis in multiple brain metastasis is poor (median survival is less than 6 months).
  5. Surgery or radiosurgery is usually not indicated. Patients are mainly treated with supportive care and steroids.

Summary: Brain metastasis

  • All solitary or less than 3 brain metastasis with controlled primary SHOULD receive whole brain radiation therapy with surgery or RADIOSURGERY (eg. CyberKnife).  
  • There is significant improvement in survival in this cohort of patient with surgery or radiosurgery.
  • All multiple brain metastasis should be treated with whole brain radiation therapy.