This document presents the case of a 58-year-old female patient with stage IV rectal adenocarcinoma that has metastasized to the liver, lungs, and brain. It discusses prognostic factors for colon cancer patients with brain metastases such as RPA class and tumor size/number, and treatments including whole brain radiation, surgery, stereotactic radiosurgery, chemotherapy, and targeted therapies. Overall survival is typically 3-7 months with whole brain radiation and depends on the patient's RPA class, with class I having the best prognosis. Surgical resection or radiosurgery may be considered for a limited number of accessible brain metastases.
8. Outline
Case presentation
Introduction of metastatic brain tumor
Prognostic factor of brain metastasis
Treatment of colon cancer with brain
metastasis
Conclusion
9. Metastatic Cancer in Brain
Molecular Risk Factors
Mediators of cancer cell to pass BBB:
Nature 459(7249), 1005–100
COX2 (also known as PTGS2), (2009).
the EGF receptor (EGFR) ligand HBEGF
α -2,6-sialyltransferase ST6GALNAC5
Expression of the integrin αvβ3
Increasemetastatic potential
Proc. Natl Acad. Sci. USA
Promote angiogenesis
106(26),
CXCL12(stromal cell-derived factor (2009)ligand
10666–10671 1a)
of the CXCR4 chemokine receptor
expressed in the brain
Semin. Cancer Biol. 14(3), 181–185 (2004).
Clinical Colorectal Cancer, Vol. 8, No. 2, 100-105,
2009
10. Possibly risk factors of Brain
Metastasis in Colorectal cancer
The majority of patients with brain metastases
had concomitant systemic metastases,
especially to lung (72.2% with lung metastases)
Extended treatment options resulting in
improved survival for patients with metastatic
CRC was associated with as much as 3%
increased incidence of brain
J Neurooncol (2011) 101:49–55
12. Prognostic Factor of colon cancer
with Brain metastasis
RPA class
Size and number of metastasis
Treatment
13. RTOG Recursive Partitioning
Analysis(RPA)
The Radiation Therapy Oncology Group
(RTOG) randomized 445 patients with brain
metastatic tumor
The patients were subgrouping into 3
classes (RPA class I, RPA class II, RPA
class III)
14. RTOG Recursive Tree
Int. J. Radiation Oncology Biol. Phys., Vol.
47, No. 4, pp. 1001–1006, 2000
21. Conventional Treatment
Whole Brain radiation therapy
WBRT had been standard treatment for brain
metastasis since 1950s, recommended for
multiple metastasis
May extend the median survival from 1-2 to 3-
7 months
22. Conventional Treatment
Whole Brain radiation therapy
The most commonly used WBRT schedule
has been 30 Gy in ten 3 Gy fractions
Response rate: 60%
Tumor shrinkage after RT correlated with
better survival and neurocognitive function
Radiosensitizers(efaproxiral, topotecan or
motexafin gadolinium) may be tried
23. Symptomatic treatment
Anti-convulsant:
ifsymptomatic convulsion. Prophylactic use is not
recommended
Corticosteroid (Dexamethasone, up to
30mg/day):
reduction of brain edema, rapidly Improve of
neurological function and quality of life
24. Surgery
Surgery is recommended to remove single
metastasis if
The primary lesion is under control
The lesion is accessible
The lesion is symptomatic or life-threatening
No more than 3 tumors should be removed
J. Neurosurg. 79(2), 210–216 (1993)
25. Stereotactic radiosurgery
gamma knife surgery
Small, well-collimated beams of ionizing radiation
to ablate cerebral metastases of 3–4 cm or
smaller
Advancements in 3D computer-aided planning
and the high degree of immobilization have
minimized the amount of radiation that passes
through healthy brain tissue
An alternative to surgery and WBRT
Main advantage: for small lesions(2.5-3cm) not
amendable by surgery or for pts not suitable for
surgery
Tumor shrinkage is slow (over weeks to months)
26. WBRT after surgery or
radiosurgery
Approximately 80% of patients of brain
metastasis will eventually have multiple
metastases
A phase III trial showed a relapse rate of 18%
in the WBRT group vs 70% in the surgery-only
group; p < 0.001 JAMA 280(17), 1485–1489 (1998).
The following study showed no overt benefit
and may increase neurotoxicity
Only recommend in more than one metastasis
27. Chemotherapy
No standard paradigm for the use of
chemotherapy for brain metastases
Temozolomide as an alkylating agent shows
good BBB penetration, and has a favorable
side-effect profile
28. Target therapy
Bevacizumab may
be benefit
N. Engl. J. Med. 350(23), 2335–2342
(2004). and Liver Disease 43 (2011) 286–294
Digestive
Be aware of
intracranial
hemorrhage
29. Prophylaxis of Brain Metastasis
prophylactic cranial irradiation: useful in
SCLC and NSCLC with brain Mets 341(7), 664–672 (19
N. Engl. J. Med.
N. Engl. J. Med. 357(7),
476–484
(20
25 Oncology 76(3), 220–228 (2009).
Gy in ten fractions to first-line treatment
responders
In other cancers and neurotoxicity need
further validation
VEGF-A inhibition(Experimental)
Bevacizumab