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- 1. Dr. Şeref Kömürcü Meme Kanseri Beyin Metastazında Sistemik Tedavi Ankara , 20 Mart 20 10
- 5. Nam et al. Breast Cancer Research 2008; 10 *Beyin metastazlı hastalar hariç. † Üç grubun karşılaştırılması 47 ( 37.3 ) 138 (24.8) 19 (16.1) Triple-negative (ER-/PR-/HER2-) 37 ( 29.4 ) 91 (16.4) 15 (12.7) HER2+/ER- (ER-/PR-/HER2+) 19 (15.1) 73 (13.1) 16 (13.6) Luminal B (ER or PR+/HER2+) < 0.0001 23 (18.3) 254 (46.7) 68 (57.6) Luminal A (ER or PR+/HER2-) Beyin metastazı ( n = 126) Metastatik ( n = 556) Erken evre ( n = 118) p Değeri† No. (%) IHC Alt tipi Meme Kanseri Alt tiplerinde Beyin Metastazı Riski
- 11. Tanı: o Lomber Ponksiyon pozitif sitoloji: 1 LP: %50 3 LP: %90 o Beyin/Spinal MRI meningeal tutulum(%50) Leptomeningeal Metastaz
- 19. Beyin metastazlı meme kanserinde kemoterapi 56 YD- Mtx Chougule Araştırma Olgu sayısı Kemoterapi OR (%) Median OS (ay) Rosner 100 CA, CFP, MVP 50 10 Cocconi 22 CDDP/VP16 55 14.5 Lange 61 RT+Ifo/BCNU 65 8 Boogerd 20 CMF, CAF 76 6.3 Oberhoff 16 Topo 38 6,25 Kouvaris 33 RT+Tem 57.6 12 Rivera 24 Tem+Cap 18 3 Christodoulo 32 Tem+CDDP 28.1 5.5 Kurt 20 Cap 45 7.3
- 23. Her-2 ve Beyin Metastazı Evre IV hastalıkta Her2 (+)’ liği beyin metastazı riskini artıran bağımsız bir faktördür (%9 vs %1.9) Her2 (+) metastatik meme kanserli hastaların 1/3’ ünde beyin metastazı görülür Bendell et al. Cancer 1997. Weitzen et al. ASCO 2002. Wardley et al. ASCO 2002. Heinrech et al. ASCO 2003.
- 25. Beyin metastazı olanlarda Trastuzumab ’in BOS düzeyleri Stemmler et al 2007 Serum : BOS Trastuzumab oranı 420:1 76:1 49:1 CSF ’te Trastuzumab (ng/mL)
- 26. Beyin Metastazından Sonra Toplam Sağkalım n= 598 Dawood S. Annals of Oncol.2008; 19 Median Lower 95% CI Upper 95% CI P value HER2 Negative 6.3 5.5 7.5 Positive 11.6 10.0 14.3 <0.0001 HER2 / Trastuzumab Positive no trastuz. 6.1 3.5 11.2 Positive + trastuz. 11.6 9.9 14.5 <0.0001 CNS metastases Both 4.1 2.6 7.4 Brain 9.0 7.8 10.5 Leptomeningeal 9.4 0.9 — 0.0001 No. of metastases One 12.2 10.0 17.6 Two 10.0 8.4 20.0 Three 8.9 6.8 30.2 Multiple 6.8 6.2 8.5 0.0003 Treatment Surgery and WBRT 18.7 12.5 30.2 WBRT alone 7.3 6.3 9.0 Surgery alone 15.3 11.1 25.5 None 6.1 5.2 8.7 <0.0001
- 27. Beyin metastazında t rastuzumab Kirsch et al 2005 Sağkalım (%) mSSS hastalığı tanısından sonraki süre ( ay ) 100 80 60 40 20 0 0 10 30 40 20 HER2 po z iti f , Trastuzumab (n=36) HER2 po z iti f , Trastuzumab yok (n=11) HER2 negati f (n=48) p<0.0001
- 28. Lapatinib Küçük bir molekül (<1 kDa) ---- KBB’ ni geçer Preklinik çalışmalarda HER2 hedefli olarak kullanılan ilk ilaç Brunilde Gril. J Natl Cancer Inst 2008;100 241 hasta, Lapatinib Kısmi yanıt : 7 hasta %20-50 küçülme : 19 hasta Lin et al. Meme Kanserinde Beyin Metastazı
- 29. Beyin metastazı—Yanıt oranı ORR (%) Oberhoff et al 2001; Lin et al 2006, 2007; Rivera et al 2006; Tsao et al 2006; Addeo et al 2007; Hedde et al 2007; Ekenel et al 2007 % 7 % 5 % 36-74 % 38 % 18 % 20
- 31. Motexafin ve Efaproxiral Çalışma Metod Sonuç Carde et al JCO 2001 Faz I/II 30 Gy WBRT + Motexafin 39/22 hasta İyi tolere edildi MS 4.7 ay Mehta et al JCO 2003 Faz III 30 Gy WBRT ± Motexafin 401 hasta MS 5.2 vs 4.9 ay Shaw et al JCO 2003 Faz II 30 Gy WBRT + Efaproxiral 69 hasta MS 6.4 ay H i po ks i %10, Baş ağrısı % 10 Anemi % 4 Suh et al Neurooncol 2003 Faz III 30 Gy WBRT + Efaproxiral 538 hasta MS 5.3 vs 4.5 ay
Notas do Editor
- Recent studies have demonstrated the antitumor activity of topotecan against brain metastases, with objective Topotecan response rates ranging from 33%-63% in patients with various solid tumors.
- Reports of tamoxifen and megestrol acetate.
- Stemmler H-J, Schmitt M, Willems A, et al. Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood–brain barrier. Anticancer Drugs 2007; 18: 23-28.
- Kirsch DG, Ledezma CJ, Mathews CS, et al. Survival after brain metastases from breast cancer in the trastuzumab era [letter]. J Clin Oncol 2005; 23: 2114-2116.
- WBRT + methyl-CCNU + tegafur, mCNS disease from primary lung cancer: Tsao MN, Lloyd N, Wong R, et al. Whole brain radiotherapy for the treatment of multiple brain metastases. Cochrane Database Syst Rev 2006; 3: CD003869. Data from page 11. WBRT + topotecan, mCNS disease from primary solid tumours including breast cancer: Hedde JP, Neuhaus T, Schuller H, et al. A phase I/II trial of topotecan and radiation therapy for brain metastases in patients with solid tumors. Int J Radiat Oncol Biol Phys 2007; 68: 839-844. WBRT + methyl-CCNU or ACNU, mCNS disease from primary lung cancer: Tsao MN, Lloyd N, Wong R, et al. Whole brain radiotherapy for the treatment of multiple brain metastases. Cochrane Database Syst Rev 2006; 3: CD003869. Data from page 11. WBRT + temozolomide, mCNS disease from primary solid tumours including breast cancer: Addeo R, Caraglia M, Faiola V, et al. Concomitant treatment of brain metastasis with whole brain radiotherapy [WBRT] and temozolomide [TMZ] is active and improves quality of life. BMC Cancer 2007; 7: 18. Toptecan, mCNS disease from primary breast cancer: Oberhoff C, Kieback DG, Würstlein R, et al. Topotecan chemotherapy in patients with breast cancer and brain metastases: results of a pilot study. Onkologie 2001; 24: 256-260. WBRT , mCNS disease from primary lung cancer: Tsao MN, Lloyd N, Wong R, et al. Whole brain radiotherapy for the treatment of multiple brain metastases. Cochrane Database Syst Rev 2006; 3: CD003869. Data from page 11. Xeloda, mCNS disease from primary breast cancer: Ekenel M, Hormigo AM, Peak S, et al. Capecitabine Therapy of Central Nervous System Metastases from Breast Cancer. J Neurooncol 2007. Epub 5 July. Xeloda + temozolomide, mCNS disease from primary breast cancer: Rivera E, Meyers C, Groves M, et al. Phase I study of capecitabine in combination with temozolomide in the treatment of patients with brain metastases from breast carcinoma. Cancer 2006; 107: 1348-1354. Xeloda + lapatinib (EGF105084 ext), mCNS disease from primary breast cancer: Lin NU, Dieras V, Paul D, et al. EGF105084, a phase II study of lapatinib for brain metastases in patients (pts) with HER2+ breast cancer following trastuzumab (H) based systemic therapy and cranial radiotherapy (RT). Oral presentation (abs 1012) at the 43rd ASCO Annual Meeting, Chicago, Illinois, USA, 1-5 June, 2007. Lapatinib (EGF105084), mCNS disease from primary breast cancer: Lin NU, Dieras V, Paul D, et al. EGF105084, a phase II study of lapatinib for brain metastases in patients (pts) with HER2+ breast cancer following trastuzumab (H) based systemic therapy and cranial radiotherapy (RT). Oral presentation (abs 1012) at the 43rd ASCO Annual Meeting, Chicago, Illinois, USA, 1-5 June, 2007. Lapatinib (NCI-6969), mCNS disease from primary breast cancer: Lin NU, Carey LA, Liu MC, et al. Phase II trial of lapatinib for brain metastases in patients with HER2+ breast cancer. Oral presentation (abs 503) at the 42nd ASCO Annual Meeting, Atlanta, Georgia, USA, 2-6 June, 2006.