brief description about brain metastsis and management

1. BRAIN
METASTASIS
KIRON G

2. Introduction
• rising incidence
 Increasing survival from recent advances in systemic therapy and
 A greater availability and use of magnetic resonance imaging (MRI).
• The most common primary site is the lung followed by breast.
• Metastatic brain tumors outnumber primary brain tumors by a factor of 10 to 1
• most common neuroanatomical sites are the
 cerebral hemispheres (80%),
 the cerebellum (15%), and
 the brainstem (5%)

3. Pathophysiology
Tumor cells
Penetrate basement
membrane
Cross subendothelial
membrane
Gain access to
circulation
Survive while
circulating (avoid
immune surveillance
by coating themselves
with fibrin and
platelets)
Pass through
microvasculature of
adopted organs
Extravasate into the
organ parenchyma
Reestablish at
secondary site

4. Clinical Presentation
• majority of patients present with neurologic signs and symptoms
• new-onset neurologic symptoms in a known cancer patient should always be
presumed to be from brain metastasis until proven otherwise
• Symptoms
 Hemiparesis
 Cognitive deficits
 Headache
 Mental problems
 Focal weakness
 Ataxia
 Sensory deficitis
 Papilledema
 Seizures
 Speech problems

5. Causes of Neurocognitive Decline
in Brain Tumor Patients
• Radiation induced dementia risk is 2%
• WBRT may actually improve neurocognition
• brain recurrence or progression is associated with a decrease in
neurocognitive function.
• brain tumor (presence, recurrence, and progression) has the greatest effect
on neurocognitive decline
• anticonvulsants, benzodiazepines, opioids, chemotherapy, craniotomy, and,
most importantly, the brain tumor contribute significantly to the
neurocognitive decline of patients with brain tumor

6. Anticonvulsants
• Patients frequently present to the radiation oncologist already started on
prophylactic anticonvulsants.
• This represents one of the most preventable causes of neurocognitive decline
in brain tumor patients
• American Academy of Neurology recommends that prophylactic
anticonvulsants not be initiated in newly diagnosed brain tumor patients
who have not experienced a seizure

7. Diagnosis
• MRI has become the standard of care for imaging of the central nervous
system (CNS) in cancer patients
 solid or ring-enhancing lesions,
 Pseudospherical in shape,
 multiple in number;
 occur in the gray–white junction
• Full systemic workup should be promptly initiated if brain metastasis is the
presenting event.

8. CT
• Often the first line of imaging
• On precontrast imaging,
 the mass may be isodense, hypodense or hyperdense
(classically melanoma) compared to normal brain
parenchyma
 with variable amounts of surrounding vasogenic
edema.
• Following administration of contrast,
 enhancement is also variable and
 can be intense, punctate, nodular or ring-enhancing if
the tumor has out grown its blood supply.

9. MRI - T1
• typically iso- to hypointense
• if hemorrhagic may have intrinsic high
signal
• non-hemorrhagic melanoma metastases
can also have intrinsic high signal due to
the paramagnetic properties of melanin

10. MRI - T1C+
• enhancement pattern can be uniform,
punctate, or ring enhancing, but it is
usually intense
• delayed sequences may show
additional lesions,
• therefore contrast-enhanced MR is the
current standard for small metastases
detection

11. MRI - T2
• typically hyperintense
• hemorrhage may alter this

12. MRI – FLAIR
• typically hyperintense
• hyperintense peri-tumoral edema of variable
amounts

13. MRI - DWI/ADC
• edema is out of proportion with tumor size and appears dark
on DWI
• apparent diffusion coefficient ADC demonstrates facilitated
diffusion in edema

14. MR spectroscopy
• intratumoral choline peak with
• no choline elevation in the peritumoural edema
• any tumor necrosis results in a lipid peak
• NAA depleted

15. Prognosis
• Performance status and extracranial
disease status have consistently been
shown to impact prognosis.
• Recursive partitioning analysis RPA
Classes
RPA Features Median survival
I KPS ≥ 70
Controlled
primary
Age < 65 years
Brain mets only
7.1 months
II Not meeting the
requirements of I
or III
4.2 months
III KPS < 70
Age > 65 years
Uncontrolled
primary
2.3 months

16. Treatment
• Medical Management
 Medical management of metastatic diseases has mainly focused on the treatment of
cerebral edema, headache, and seizure
• Surgical Management
• Radiation therapy

17. Medical management
• promptly start with corticosteroids
 e.g., dexamethasone or methylprednisolone
 improve edema and neurologic deficits in approximately two-thirds of patients
• 10 mg intravenous (IV) or oral bolus, followed by
• 4 to 6 mg every 6 to 8 hours of dexamethasone equivalent dose (with a
concurrent proton-pump inhibitor [PPI]),
• this is tapered in a clinically cautious manner
• In asymptomatic patients with little peritumoral edema or mass effect,
initial corticosteroids may be reserved until the first sign of neurologic
symptoms.

18. Corticosteroids
Acute side effects may include
• insomnia,
• increased appetite,
• gastritis,
• fluid retention,
• mood swings,
• acne, and
• elevation of blood sugars.
Long-term side effects may include
• weight gain,
• facial plethora,
• pedal edema,
• immunosuppression,
• proximal muscle myopathy,
• cataract formation,
• aseptic necrosis of the femoral head,
and
• osteoporosis

19. Corticosteroids - withdrawal symptoms
• headaches,
• lethargy,
• weakness,
• dizziness,
• anorexia,
• diffuse arthralgias, and
• myalgias.

20. Osmotherapy
• Osmotherapy with mannitol, glycerol, or hypertonic saline is often used in
patients with severe brain edema
• A typical dose of mannitol is 1 g/kg (250 mL of a 20% solution in an average
adult),
 reduction in intracranial pressure of 30 to 60% for 2 to 4 hours.
• Osmotherapy results in massive osmotic diuresis, so fluid and electrolyte
balance should be monitored carefully
• Interestingly, osmotherapy may even enhance disturbance of the blood–
brain barrier:

21. Venous Thromboembolism
• patients with brain tumors and thromboembolism are believed to be at
higher risk for intracranial hemorrhage with anticoagulation
• For patients with brain tumors and venous thromboembolism,
anticoagulation is indicated unless the patient has had an intracerebral
bleed or other contraindication for anticoagulation.

22. Surgical Resection
• provide immediate relief of the tumor mass effect
• should be reserved for
 lesions causing life-threatening complications (herniation) or
 patients with good performance status (i.e., KPS ≥70).

23. Whole-Brain Radiotherapy
• standard of care in patients with brain metastasis.
• given soon after the diagnosis of brain metastasis
• goal of WBRT
 limit tumor progression,
 Sterilize microscopic disease preventing future brain metastasisand
 limit corticosteroid dependency

24. Whole-Brain Radiotherapy
• Complications of treatment include
 alopecia,
 transient worsening of neurologic symptoms, and
 otitis.
• Continuing use of corticosteroids during WBRT may limit the incidence of
most side effects.
• Long-term side effects are possible in survivors but are not expected to
materialize in the majority of poor prognosis patients
 memory loss,
 dementia, and
 decreased concentration

25. Technique of WBRT
• should be conscious and cooperative
• Simulation is done in a supine position with a head rest,
• immobilization is achieved with a custom skull mask
• head is positioned straight and is aligned so that the sagittal laser line
follows the patient's midline
• beam arrangement is lateral opposing fields with collimation to shape the
beam.
• Sheilding may be used to exclude the lens and extra-cranial contents from
direct irradiation
• Megavoltage energy of 4 MV to 6 MV is used.

26. Whole-Brain Radiotherapy
• still no agreement on the dose and fractionation schedule for WBRT
• A total of 30 Gy in 10 fractions continues to be the standard for a vast
majority of patients.
 Not adequate to achieve long-term tumor control.
• In chemotherapy refractory RPA class III patients, a shorter fractionation
scheme (e.g., 20 Gy in 5 fractions) should be considered.
• takes several days to work.
• Radiographic and clinical response rates range from 50% to 75%.

27. Radiosurgery Boost
• noninvasive alternative
• similar local control rates (in the order of 80% to 90% only when combined
with WBRT)
• RTOG-95-08,
 overall survival was not statistically different between the WBRT plus SRS and
WBRT alone arms (6.5 months and 5.7 months, respectively; P = .1356),
 SRS boost Improved the survival in the subgroup of patients with single metastasis.
 local control and performance measures, were higher in the SRS boost arm,
 but this did not translate into a lower death rate from neurologic progression.
 SRS is associated with lower edema and corticosteroid use
• difficult to justify its routine use in patients with multiple metastases in
light of the equivocal phase III SRS boost trials.

28. Surgery and SRS - Advantages
Surgery
• Treatment of larger lesions (>4cm)
• Immediate removal of mass effect and edema
• Histologic confirmation
• Rapid taper of steroids
• Removal of cancer
• Minimal risk of radiation necrosis
• Less intensive follow up
• Less long term dependency on steroids
SRS
• Treatment of small deep lesions or eloquent
areas
• Minimally invasive
• No general anestheia use
• OP procedure
• Treatment of multiple lesions at same session
• Short recovery time
• Potentially avoid WBRT
• Rapid initiation of systemic therapies
• Fewer immediate complications

29. Postoperative or Postradiosurgery
Whole-Brain Radiotherapy
• treated with SRS alone without WBRT experienced worse freedom from new
brain metastasis and overall brain freedom from progression
• importance of postoperative WBRT lies in preventing brain failure and
death from neurologic causes.
• Adjuvant WBRT, therefore, should be considered the standard of care after
local therapy with surgical resection or SRS.

30. Repeat Whole-Brain Radiotherapy
• Repeat WBRT is relatively safe because a vast majority of patients have
limited survival with recurrent or progressive brain metastases after initial
WBRT.
• A minimum of 20 Gy in 1.8 to 2 Gy fractions should be given

31. Concurrent Radiosensitizers
• Concurrent temozolomide with WBRT should be considered in a patient with
bulky brain metastases burden who is unlikely to become a SRS candidate

32. Summary

33. Leptomeningeal metastases
• Aka neoplastic meningitis
• Serious complication
• Often underdiagnosed -> early management can be challenging -> treatment
is mostly palliative
• Very poor prognosis
• Median survival : 2-3 months
• Better outcomes in patients with leukemic and lymphomatous meningitis

34. Clinical Presentation
• Greater than 50% of patients have spinal cord
dysfunction as the primary presenting symptom, followed by
• cranial neuropathies,
• hemispheric defects, and
• nonfocal presentations

35. Diagnosis
• thorough neurologic history and physical examination,
• Contrast enhanced MRI of the brain, and
• examination of the CSF
 opening pressure,
appearance,
 glucose, protein, white and red blood cell counts with differential, and
 the presence of any abnormal cells by cytology or flow cytometry.

36. Radiation therapy
• provides effective palliation in many cases of LMD, such as symptomatic
sites and regions, cranial neuropathies, and cauda equina syndrome
• Craniospinal irradiation is generally not recommended given
the potential toxicity and amount of bone marrow irradiated, which may
preclude the use of chemotherapy

37. Intra–Cerebrospinal Fluid Chemotherapy
• Commonly used intrathecal chemotherapy agents include methotrexate,
cytarabine, liposomal form of cytarabine, and thiotepa
• radiation therapy is delivered prior to intra-CSF therapy

38. Systemic Chemotherapy
• intravenous methotrexate administration is active even when there is
obstruction of CSF flow, which sometimes compromises the subarachnoid
administration of drugs

39. Thank you
Case courtesy of A.Prof Frank Gaillard, Radiopaedia.org, rID: 3972