財團法人台灣癌症臨床研究發展基金會
JOURNAL READING
VS鄧豪偉醫師/R4洪逸平
Patient Profile
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Age: 58 y/o
Gender: Female
Diagnosis:
Adenocarcinoma of rectum, pT3N2b(12/21)M1,
stage IV, with limited pelvis seeding, liver and lung
metastasis
s/p LAR + BSO + resection of limited pelvis seeding, Port-A
insertion on 2010/6/9
s/p FOLFOX-4 *6 (2010-9-20) with progessive disease
s/p 2 cycle of FOLFIRI on 2010/10/19
Image Study
2010/10/20 CT
2010/11/01 MR
Clinical Course
s/p whole brain R/T with
3600cGy/12fractions
during 2010/11/3-11/18
s/p xeloda (2010/10/30)
s/p Xeliri x3,
2010/11/262011/01/07
s/p cetuximab with xeliri
x5, 2011/1/212011/3/30 , with lung,
liver metastasis
progression
2011/4/30 CT
Clinical course
2011/8/11 CT
s/p Xeliri x4, 2011/4/132011/5/25
s/p Xeliri x5, 2011/6/16
s/p Xeliri x6, 2011/7/1
+Avastin with brain
metastasis in regression
but liver and lung mets
mets in progression
s/p Avastin + DTIC +
XELIRI, C1 on
2011/10/06
2011/8/12 CT
2011/10/5 CT
Clinical Course
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UGI bleeding, pneumonia, and ARDS developed
She was transferred to Hospice and was expired on
2011/11/13
COLON CANCER WITH
BRAIN METASTASIS
鄧豪偉醫師/R4洪逸平
Outline
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Case presentation
Introduction of metastatic brain tumor
Prognostic factor of brain metastasis
Treatment of colon cancer with brain metastasis
Conclusion
Metastatic Cancer in Brain
Molecular Risk Factors
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Mediators of cancer cell to pass BBB:
Nature 459(7249), 1005–1009
(2009).
 COX2
(also known as PTGS2),
 the EGF receptor (EGFR) ligand HBEGF
 α -2,6-sialyltransferase ST6GALNAC5
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Expression of the integrin αvβ3
 Increase
metastatic potential
 Promote angiogenesis
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Proc. Natl Acad. Sci. USA 106(26),
10666–10671 (2009)
CXCL12(stromal cell-derived factor 1a) ligand 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
Possibly risk factors of Brain Metastasis
in Colorectal cancer
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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
Prognostic factors
Prognostic Factor of colon cancer with
Brain metastasis
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RPA class
Size and number of metastasis
Treatment
RTOG Recursive Partitioning
Analysis(RPA)
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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)
RTOG Recursive Tree
Int. J. Radiation Oncology Biol. Phys., Vol. 47,
No. 4, pp. 1001–1006, 2000
KARNOFSKY PERFORMANCE STATUS
SCALE DEFINITIONS RATING (%)
CRITERIA
Survival by RPA class from the RTOG
database
Class I median survival 7.1month
Class II median survival 4.2 months
Tumor Biol. (2011) 32:1249–1256
Multivariate predictors of survival in
patients with brain metastases from
colorectal cancer
J Neurooncol (2011) 101:49–55
Treatment of brain metastasis in
colon cancer
Conventional Treatment
Whole Brain radiation therapy
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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
Conventional Treatment
Whole Brain radiation therapy
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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
Symptomatic treatment
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Anti-convulsant:
 if
symptomatic convulsion. Prophylactic use is not
recommended
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Corticosteroid (Dexamethasone, up to 30mg/day):
 reduction
of brain edema, rapidly Improve of
neurological function and quality of life
Surgery
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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
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No more than 3 tumors should be removed
J. Neurosurg. 79(2), 210–216 (1993)
Stereotactic radiosurgery
gamma knife surgery
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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)
WBRT after surgery or radiosurgery
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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),
(1998). and
The following study showed
no 1485–1489
overt benefit
may increase neurotoxicity
Only recommend in more than one metastasis
Chemotherapy
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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
Target therapy
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Bevacizumab may be
benefit
N. Engl. J. Med. 350(23), 2335–2342 (2004).
Digestive and Liver Disease 43 (2011) 286–294
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Be aware of
intracranial
hemorrhage
Prophylaxis of Brain Metastasis
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prophylactic cranial irradiation: useful in SCLC and
N. Engl. J. Med. 341(7), 476–484 (1999)
NSCLC with brain Mets
N. Engl. J. Med. 357(7), 664–672 (2007)
76(3), responders
220–228 (2009).
Gy in ten fractions to first-lineOncology
treatment
 In other cancers and neurotoxicity need further validation
 25
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VEGF-A inhibition(Experimental)
 Bevacizumab
THANKS FOR YOUR
ATTENTION!