CNS Metastasis


By Primary Cancer Type

Cancer type 5-CIBM
all cancers 8.5%
lung cancer 16%
renal cell cancer 10%
melanoma 7%
breast cancer 5%
colorectal cancer 1%
  • 5-CIBM: 5-year cumulative incidence of brain metastases[7]

Hodgkins and Brain Metastasis


  • Brain metastasis of Hodgkin's lymphoma is exceptional, found in only 0.22% of cases all CNS neoplasms.[8]

Treatment of brain metastasis includes:

  • Corticosteroids are typically the first line symptomatic treatment
  • definitive treatment options include craniotomy and resection; WBRT alone or after resection; or SRS.

Breast Cancer and CNS metastasis. [5] [6]

  • Lung cancer is most common cause of brain metastases in women.
  • Breast cancer is the second leading cause of CNS metastasis in women.
  • Risk factors include:
    • HER-2/neu gene overexpression
    • number of metastatic sites
    • ER-negative tumors are more likely to metastasize to the brain than are ER-positive tumors.
  • primary tumor size, # LN+ are not risk factors for CNS metastasis
  • 14.8% of patients with breast cancer and are screened for enrollment in clinical trials of systemic therapy had clinically occult CNS metastases



  • median interval from diagosis of cancer to brain metastases is 12 months.


  • Headache 24% to 53%
  • Focalweakness 16% to 40%
  • Altered mental status 24% to 31%
  • Seizures 15% to 16%
  • ataxia 9% to 20%

Leptomeningeal disease


  • Spinal symptoms are the most common presentation of leptomeningeal disease.
    • Limb weakness with paresthesias and pain occur in the affected limb.
  • Headaches are the most common symptom of cerebral disease.
    • Diplopia is the most common cranial nerve symptom.


  • Gadolinium-enhanced MRI is the modality of choice for both cranial and spinal sites.
  • CT is less sensitive and is not useful for spinal imaging unless a contrast agent is used in the subarachnoid space.


  • Radiation therapy should be given to symptomatic areas and to sites of bulky disease.
  • Radiation is the best treatment for focal leptomeningeal nodules.
  • Focal radiation can help restore normal CNS flow and facilitate effectiveness of intrathecal therapies.

Systemic Therapy

  • Motexafin Gadolinium improved neurocogn progression but OS in Lung Cancer patients (Meyers et al. JCO 22:157-165,2004)

RTOG recursive partitioning for brain metastses

Class KPS Charateristics Median Survival
I KPS ≥ 70 1º controlled
age <65 y.o.
& metastases limited to brain
7.1 mo
II KPS ≥ 70 and one or more unfavorable factors above 4.9 mo.
III KPS < 70 N/A 2.3 mo


  • Alopecia
  • Transient worsening of neurologic symptoms
  • otitis

Late sequel of WBRT

  1. discrete microfoci of white matter necrosis (lacuni) with calcification by 26 weeks
  2. white matter (periventricular) signal intensity on T2 and FLAIR images (? due to edema?)
  3. cortical atrophy (enlarged sulci)
  • Necrosis in patients who receive less than 60 Gy has generally been associated with fractions of greater than 2.5 Gy.
  • Sheline et al. estimated cerebral necrosis of 0.04% to 0.4% for a total radiation dose of 50 to 54 Gy given in 2 Gy QD. (Optic chiasm can tolerate up to 45-50 Gy at 2 Gy per fraction).
  • Intellectual impairment in adults has been noted primarily after intensive chemotherapy and irradiation for the prevention of metastasis from SCLC and tx of CNS lymphomas.

Surgical Resection

  • 2 randomized trials have shown the importance of surgery in addition to RT
  • The American and the Dutch study have included mainly patients with controlled or limited systemic disease and both have reported 9-10 month survival with surgery vs 3-6 months with WBRT alone.(Patchell 1990;Vecht 1993).
  • By contrast the Canadian study which included a higher proportion of patients with an active systemic disease and lower performance scores, failed to show any advantage of surgery plus radiotherapy over radiotherapy alone.(Mintz 1996).
  • Surgical resection + WBRT results in significantly longer survival than WBRT alone for single brain metastasis.

Patchell's Randomized Study[1]

End Points biopsy + WBRT Surgery + WBRT p-value
Median survival 4.2 mo. 10 mo. < .01

Patchell's Randomized Study[2]

End Points Surgery Surgery + WBRT p-value
Any CNS recurrence 70% 18% < .01
Local recurrence 46% 10% < .01
Distant Brain 37% 14% < .01
Median survival 12 mo. 10mo. NS
Death from CNS 44% 14% < .01
  • 88% CNS recurrence in surgery group received delayed WBRT
  • randomized trial of single metastases to the brain

Post-operative radiation

  • 3 completed trials 2 including Patchell is positive. One is negative.
  • Phase III study from USA have reported that adjuvant WBRT after complete surgical resection significantly reduces local and distant CNS relapses (18% with surgery + WBRT vs 70% with surgery alone)(Patchell 1998).
  • Post-op WBRT after surgery does NOT have a survival benefit compared to surgery alone

Radiation Dose

  • Optimal dose is unknown
  • 20 Gy in 5 fractions to 40 Gy in 20 fractions have been tried.
  • A minority o fpatients (10-20%), who have been treated with 30 Gy in 10 fractions to the whole brain who survive for longer than 1 year develop radiation-induced dementia.[9]


  • No randomized trials of SRS vs surgical resection

SRS+WBRT vs WBRT for 1-3 Brain metastasis

RTOG 9805 (2004)

Groups # pts Median Survival Stable KPS at 6 months
37.5 Gy in 12 fractions WBRT 164 4.9 mo 27%
37.5 Gy in 12 fractions WBRT + SRS from 15 to 24 Gy 167 6.5 mo 43%
p-value .039*
  • Trial included up to 3 metastases but median survival was improved for single metastasis.
  • Lung primary benefited most from SRS boost + WBRT


  • Some studies suggest that retreatment of pts with brain mets may be feasible.

Wong et al. IJROBP 34(3): 585-90, 1996. (MAYO)

  • 86 pts were re-irradiated for brain mets.
  • Median dose of 1st course was 30 Gy and of the 2nd course 20 Gy.
  • Results: 27% had resolution of symptoms and 43% had partial improvement.
  • The median survival after the 2nd course was 4 months.
  • On multivariate analysis the only significant prognostic factor for survival was the absence of extracranial mets (p=0.05).
  • There was no severe acute toxicity and only 5 pts had radiographic evidence of radiation changes.

Conformality Indexes

  • Extrapolating from the treatment parameters used in the RTOG 9005 trial, the PIV/TV ratio should be <2.0 to minimize complications
  • PIV = volume bound by prescription isodose line
  • TV = tumor volume
1. Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, Markesbery WR, Macdonald JS, Young B. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990 Feb 22;322(8):494-500.
2. Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, Markesbery WR, Foon KA, Young B. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA. 1998 Nov 4;280(17):1485-9. PMID: 9809728
3. Harris, JR. Diseases of the Breast, 3rd edition, Lippincott, Williams and Wilkins, 2004;
4. Miller, K, et al. Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival. Annals of Oncology. 2003;4:1972-1977.
5. Sparrow, GE, et al. Brain metastases from breast cancer: clinical course, prognosis and influence of treatment. Clinical Oncology. 1981;7:291-301.
6. Stewart, JF, et al. Estrogen receptors, sites of metastatic disease and survival in recurrent breast cancer. European Journal of Cancer. 1981;17:449-453.
7. Schouten LJ, Rutten J, Huveneers HA, Twijnstra A. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer. 2002 May 15;94(10):2698-705. PMID: 12173339
8. Zimmerman HM. Malignant lymphomas of the nervous system. Acta Neurophatholigica 1975; 6: 69-74.
9. DeAngelis L. Delattre J. Posner J: Radiation induced dementia in paties cured of brain metastases. Neurology. 1989;39:789.
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