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 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 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 Brain Molecular Risk Factors 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 Expression of the integrin αvβ3 Increase metastatic potential Promote angiogenesis 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 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 7.1month 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 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 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 removed J. Neurosurg. 79(2), 210–216 (1993) 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) 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), (1998). and The following study showed no 1485–1489 overt benefit may increase neurotoxicity Only recommend in more than one metastasis 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 N. Engl. J. Med. 350(23), 2335–2342 (2004). Digestive and Liver Disease 43 (2011) 286–294 Be aware of intracranial hemorrhage Prophylaxis of Brain Metastasis 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 VEGF-A inhibition(Experimental) Bevacizumab THANKS FOR YOUR ATTENTION!