Colon cancer with brain metastasis
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JOURNAL READING
VS鄧豪偉醫師 /R4洪逸平
Patient Profile
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, 2010/11/26-2011/01/07 s/p cetuximab with xeliri x5, 2011/1/21-2011/3/30 , with lung, liver metastasis progression
2011/4/30 CT
Clinical course
s/p Xeliri x4, 2011/4/13-2011/5/25 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
2011/8/11 CT
2011/8/12 CT 2011/10/5 CT
Clinical Course
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
Case presentation Introduction of metastatic brain tumor Prognostic factor of brain metastasis Treatment of colon cancer with brain
metastasis Conclusion
Metastatic Cancer in BrainMolecular Risk Factors
Mediators of cancer cell to pass BBB: COX2 (also known as PTGS2), the EGF receptor (EGFR) ligand HBEGF α -2,6-sialyltransferase ST6GALNAC5
Expression of the integrin αvβ3 Increase metastatic potential Promote angiogenesis
CXCL12(stromal cell-derived factor 1a) ligand of the CXCR4 chemokine receptor expressed in the brain
Nature 459(7249), 1005–1009 (2009).
Proc. Natl Acad. Sci. USA 106(26),10666–10671 (2009)
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
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
RPA class Size and number of metastasis Treatment
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)
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 7.1monthClass 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 TreatmentWhole 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
Conventional TreatmentWhole 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
Symptomatic treatment
Anti-convulsant: if symptomatic 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
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
removedJ. Neurosurg. 79(2), 210–216 (1993)
Stereotactic radiosurgerygamma 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)
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
The following study showed no overt benefit and may increase neurotoxicity
Only recommend in more than one metastasis
JAMA 280(17), 1485–1489 (1998).
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
Target therapy
Bevacizumab may be benefit
Be aware of intracranial hemorrhage
N. Engl. J. Med. 350(23), 2335–2342 (2004).Digestive and Liver Disease 43 (2011) 286–294
Prophylaxis of Brain Metastasis
prophylactic cranial irradiation: useful in SCLC and NSCLC with brain Mets 25 Gy in ten fractions to first-line treatment
responders In other cancers and neurotoxicity
need further validation VEGF-A inhibition(Experimental)
Bevacizumab
N. Engl. J. Med. 357(7), 664–672 (2007).
N. Engl. J. Med. 341(7), 476–484 (1999).Oncology 76(3), 220–228 (2009).
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