CNS Metastasis
Table of Contents
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Incidence
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
Incidnece
- 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
Presentation
Timing
- median interval from diagosis of cancer to brain metastases is 12 months.
Symptoms
- Headache 24% to 53%
- Focalweakness 16% to 40%
- Altered mental status 24% to 31%
- Seizures 15% to 16%
- ataxia 9% to 20%
Leptomeningeal disease
Presentation
- 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.
Imaging
- 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.
Treatment
- 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 |
Complications
- Alopecia
- Transient worsening of neurologic symptoms
- otitis
Late sequel of WBRT
- discrete microfoci of white matter necrosis (lacuni) with calcification by 26 weeks
- white matter (periventricular) signal intensity on T2 and FLAIR images (? due to edema?)
- 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]
SRS
- 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
Retreatment
- 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
Bibliography
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.
page revision: 32, last edited: 27 Jun 2008 15:41