Colon cancer with brain metastasis

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  • 1. JOURNAL READINGVS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 Study2010/10/20 CT 2010/11/01 MR
  • 4. Clinical Courses/p whole brain R/T with 2011/4/30 CT3600cGy/12fractionsduring 2010/11/3-11/18s/p xeloda (2010/10/30)s/p Xeliri x3,2010/11/26-2011/01/07s/p cetuximab with xelirix5, 2011/1/21-2011/3/30 , with lung,liver metastasisprogression
  • 5. Clinical course 2011/8/11 CTs/p Xeliri x4, 2011/4/13-2011/5/25s/p Xeliri x5, 2011/6/16s/p Xeliri x6, 2011/7/1+Avastin with brainmetastasis in regressionbut liver and lung metsmets in progression 2011/8/12 CT 2011/10/5 CTs/p Avastin + DTIC +XELIRI, C1 on2011/10/06
  • 6. Clinical Course UGI bleeding, pneumonia, and ARDS developed She was transferred to Hospice and was expired on 2011/11/13
  • 7. COLON CANCER WITHBRAIN 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 BrainMolecular 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 BrainMetastasis 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 cancerwith Brain metastasis RPA class Size and number of metastasis Treatment
  • 13. RTOG Recursive PartitioningAnalysis(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 PERFORMANCESTATUS SCALE DEFINITIONSRATING (%) CRITERIA
  • 16. Survival by RPA class from theRTOG 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 inpatients with brain metastasesfrom colorectal cancer J Neurooncol (2011) 101:49–5
  • 19. Treatment of brain metastasis incolon cancer
  • 20. 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
  • 21. 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
  • 22. 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
  • 23. 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)
  • 24. 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)
  • 25. WBRT after surgery orradiosurgery 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
  • 26. 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
  • 27. 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
  • 28. 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
  • 29. THANKS FOR YOURATTENTION!