Colon cancer with brain metastasis


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Colon cancer with brain metastasis

  1. 1. JOURNAL READINGVS鄧豪偉醫師/R4洪逸平
  2. 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. 3. Image Study2010/10/20 CT 2010/11/01 MR
  4. 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. 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. 6. Clinical Course UGI bleeding, pneumonia, and ARDS developed She was transferred to Hospice and was expired on 2011/11/13
  8. 8. Outline Case presentation Introduction of metastatic brain tumor Prognostic factor of brain metastasis Treatment of colon cancer with brain metastasis Conclusion
  9. 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. 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. 11. Prognostic factors
  12. 12. Prognostic Factor of colon cancerwith Brain metastasis RPA class Size and number of metastasis Treatment
  13. 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. 14. RTOG Recursive Tree Int. J. Radiation Oncology Biol. Phys., Vol. 47, No. 4, pp. 1001–1006, 2000
  16. 16. Survival by RPA class from theRTOG database Class I median survival 7.1month Class II median survival 4.2 month
  17. 17. Tumor Biol. (2011) 32:1249–1256
  18. 18. Multivariate predictors of survival inpatients with brain metastasesfrom colorectal cancer J Neurooncol (2011) 101:49–5
  19. 19. Treatment of brain metastasis incolon cancer
  20. 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. 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. 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. 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. 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. 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. 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. 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. 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