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.

1. JOURNAL READING
VS鄧豪偉醫師/R4洪逸平

2. 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

3. Image Study
2010/10/20 CT 2010/11/01 MR

4. Clinical Course
s/p whole brain R/T with 2011/4/30 CT
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

5. Clinical course
2011/8/11 CT
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 2011/8/12 CT 2011/10/5 CT
s/p Avastin + DTIC +
XELIRI, C1 on
2011/10/06

6. Clinical Course
 UGI bleeding, pneumonia, and ARDS
developed
 She was transferred to Hospice and was
expired on 2011/11/13

7. COLON CANCER WITH
BRAIN METASTASIS
鄧豪偉醫師/R4洪逸平

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

11. Prognostic factors

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

15. KARNOFSKY PERFORMANCE
STATUS SCALE DEFINITIONS
RATING (%) CRITERIA

16. Survival by RPA class from the
RTOG database
Class I median survival 7.1month
Class II median survival 4.2 month

17. Tumor Biol. (2011) 32:1249–1256

18. Multivariate predictors of survival in
patients with brain metastases
from colorectal cancer
J Neurooncol (2011) 101:49–5

19. Treatment of brain metastasis in
colon cancer

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

31. THANKS FOR YOUR
ATTENTION!