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OLGU SUNUMLARI

N. H72 yas Bayan ?ift?iIki yildir karin agrisi olan hasta ?arpinti, nefes darligi nedeniyle aralik 2009 da basvurdu. NDS: 136/ dk, TA: 90/60 mmHg, Hemoglobin: 4 gr/ dlNe yapmali ? Hangi tetkikler istenmeli ? MCV ? Periferik yayma ? Retik?losit - Feritin. . OLGU 1. OLGU1. Iki g?nd?r siyah ren

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OLGU SUNUMLARI

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    1. OLGU SUNUMLARI Iç Hastaliklari AD Dr. Ozan Balakan

    2. N. H 72 yas Bayan Çiftçi Iki yildir karin agrisi olan hasta çarpinti, nefes darligi nedeniyle aralik 2009 da basvurdu. NDS: 136/ dk, TA: 90/60 mmHg, Hemoglobin: 4 gr/ dl Ne yapmali ? Hangi tetkikler istenmeli ? MCV – Periferik yayma – Retikülosit - Feritin

    3. OLGU1 Iki gündür siyah renkli civik diskilamasi mevcut GIS kanamasi düsünülerek yatirildi. Kan transfüzyonu yapildi Endoskopide korpus ön duvarda ülserovejetan kitle görüldü PATOLOJI: Az diferansiye adenokarsinom

    4.

    5. Tedavi planiniz ? Subat-mayis 2010 arasi neoadjuvan 3 x docetaxel + cisplatin + 5 FU sonrasi batindaki LAP lar kayboldu. Midedeki kitle 2,5 cm ye geriledi (PARSIYEL CEVAP) Mayis 2010 da laparotomi yapildi Damar invazyonu nedeniyle unrezektable kabul edilip palyatif cerrahi (gastrojejunostomi) yapildi

    7. In situ hibridizasyon yöntemi ile cerb-B2 ve kromozom 17 için hazirlanan lamlarda skorlama kriterlerine uygun alanlarda toplam 40 hücrenin çekirdegindeki sinyaller 100X immersiyon ile sayildi. Cerb- B2 için ortalama sinyal sayisi: 9.2 kromozom 17 için 2 olarak saptandi. SONUÇ: SISH pozitif OLGU 1

    8. Trastuzumab için saglik bakanligina basvuru yapildi ancak kabul edilmedi Temmuz - eylül 2010 da 3 x cisplatin 30 mg + 5 FU 1500 mg 7 günde infüzerle 2 haftada bir + trastuzumab 300 mg üç haftada bir. Trastuzumab bulunamayinca kemoterapiyi 2 kür de lapatinib 1250 mg/gün her gün + 100 mg bevacizumab ile birlikte aldi (Parsiyel cevap) Aralik 2010 da tekrar trastuzumab için basvuru yapildi. Kabul edildi OLGU 1

    9. 3 x cisplatin ( 80 mg’ den 50 mg a düsürüldü ) + trastuzumab 300 mg + capecitabin 1000 mg/gün 1-14. gün üç haftada bir (Stable hastalik) Ikinci basvuru sonuçlanincaya kadar ( nisan-mayis 2011) tekrar capecitabine + lapatinib aldi (Stable hastalik) Haziran 2011 de tekrar onay alindi. Cisplatin + capecitabine + trastuzumab tekrar baslandi. Dört kür daha aldi ( Stable hastalik) (sonuncusu 28 eylül 2011) Grade 2 anemi, grade 1 kusma oldu. Grade 2 trombositopeni nedeniyle zaman zaman doz ertelenmesi oldu OLGU 1

    10. I. K 56 yasinda Erkek Mayis 2011 de gögüs agrisi nedeniyle doktora basvurmus. 40 paket-yil sigara öyküsü var. LAD de % 100 darlik saptanmis ve anjioplasti yapilmis Beraberinde anemi de ( hgb: 4 g/dl ) saptaninca tetkik edilmis OLGU 2

    11. Endoskopide özefagus 39. cm den baslayip kardiaya uzanan lümenin % 70 ini dolduran ülserovejetan kitle Patoloji: Intestinal tip adenokarsinom CEA: 114, CA 19-9 > 1200 Yutma güçlügü nedeniyle özefagusa plastik stent yerlestirildi OLGU 2

    12. BT de mediastinal ve sag hiler patolojik çok sayida lenf nodlari. Karacigerde büyügü 3.2 cm çok sayida lezyon, mide korpusunda perigastrik yapilara invaze kitle – duvar kalinlasmasi (en kalin yerinde 3.6 cm). Perigastrik, paraaortik konglomere , çölyak, perikaval, mezenterik çok sayida büyümüs lenf bezi OLGU 2

    13. Hasta LOGIC çalismasi için tarandi. Cerb B2 IHC +3, FISH amplifikasyon pozitif. FISH orani: 25.5/2.2= 11.59 Bu sirada hastanin GIS kanamasi devam ediyordu. Sik sik transfüzyon yapildi Hastanin derin anemik oldugu dönemlerde efor anjinasi oldugundan çalismaya alinmasi medikal monitörce reddedildi OLGU 2

    14. Anti erb B2 tedavi almaya istekli olan hastaya cisplatin 75 mg / m² üç haftada bir + capecitabine 2000 mg/m² 1-14. günler + trastuzumab 4 mg/ kg yükleme dozunu takiben 2mg/ kg haftada bir baslandi Ikinci kür sonrasi ara degerlendirmede tüm lezyonlarda belirgin gerileme oldugu görüldü ( Parsiyel cevap) OLGU 2

    15. TEDAVI ÖNCESI SONRASI

    16. Metastatik mide kanserinde rejimler 1. Murad AM, et al. Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer. 1993 Jul 1;72(1):37-41. 2. Vanhoefer U, et al. Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol. 2000 Jul;18(14):2648-57. 3. Ajani JA, et al. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: The FLAGS trial. J Clin Oncol. 2010 Mar 20;28(9):1547-53. 4. Van Cutsem E, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. 5. Dank M, et al. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. 6. Cunningham D, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. 7. Kang YK, et al. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. ---------------------------- Feb 2010: Update FLAGS ref.1. Murad AM, et al. Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer. 1993 Jul 1;72(1):37-41. 2. Vanhoefer U, et al. Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol. 2000 Jul;18(14):2648-57. 3. Ajani JA, et al. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: The FLAGS trial. J Clin Oncol. 2010 Mar 20;28(9):1547-53. 4. Van Cutsem E, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. 5. Dank M, et al. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. 6. Cunningham D, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. 7. Kang YK, et al. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. ---------------------------- Feb 2010: Update FLAGS ref.

    17. HER-2 Pozitifligi ve prognoz

    18. ToGA çalisma dizayni Eligibility criteria for the ToGA trial include: >18 years of age, HER2-positive histologically confirmed gastric cancer or gastro-oesophageal adenocarcinoma, with inoperable, locally advanced or recurrent and/or metastatic disease. The ToGA trial planned to recruit 584 patients. An additional 10 patients, who had already signed the informed consent form when the screening cut-off was reached, were allowed to enter the trial, resulting in a total of 594 patients recruited. The primary end point is overall survival in the two treatment arms. Secondary end points include progression-free survival, overall response rate, clinical benefit rate, duration of response and safety profile.Eligibility criteria for the ToGA trial include: >18 years of age, HER2-positive histologically confirmed gastric cancer or gastro-oesophageal adenocarcinoma, with inoperable, locally advanced or recurrent and/or metastatic disease. The ToGA trial planned to recruit 584 patients. An additional 10 patients, who had already signed the informed consent form when the screening cut-off was reached, were allowed to enter the trial, resulting in a total of 594 patients recruited. The primary end point is overall survival in the two treatment arms. Secondary end points include progression-free survival, overall response rate, clinical benefit rate, duration of response and safety profile.

    19. ToGA dozlar Capecitabine 1000 mg/m2 bid 1-14. günler 3 haftada bir 6 siklus 5-Fluorouracil 800 mg/m2/gün sürekli iv infüzyon 1-5. günler 3 haftada bir 6 siklus Cisplatin 80 mg/m2 1. gün 3 haftada bir 6 siklus Trastuzumab 8 mg/kg yükleme dozu takiben 6 mg/kg 3 haftada bir progresyona kadar

    21. ToGA subgrup analizleri

    22. ToGA subgrup analizi

    23. ToGA ÇALISMASI

    24. ToGA hematolojik toksisiteler

    25. ToGA toksisiteler

    26. ToGA kardiyak olaylar

    27. Trastuzumab mide çalismalari

    28. Mide kanseri lapatinib

    29. Pertuzumab

    30. Trastuzumab 1. Murad AM, et al. Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer. 1993 Jul 1;72(1):37-41. 2. Vanhoefer U, et al. Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol. 2000 Jul;18(14):2648-57. 3. Ajani JA, et al. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: The FLAGS trial. J Clin Oncol. 2010 Mar 20;28(9):1547-53. 4. Van Cutsem E, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. 5. Dank M, et al. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. Epub 2008 Jun 16. 6. Cunningham D, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. 7. Kang YK, et al. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. 8. Van Cutsem E, et al. Efficacy results from the ToGA trial: A phase III study of trastuzumab added to standard chemotherapy (CT) in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC). J Clin Oncol 27:18s, 2009 (suppl; abstr LBA4509) ----------------------------- Feb 2010: update FLAGS ref.1. Murad AM, et al. Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer. 1993 Jul 1;72(1):37-41. 2. Vanhoefer U, et al. Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol. 2000 Jul;18(14):2648-57. 3. Ajani JA, et al. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: The FLAGS trial. J Clin Oncol. 2010 Mar 20;28(9):1547-53. 4. Van Cutsem E, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. 5. Dank M, et al. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. Epub 2008 Jun 16. 6. Cunningham D, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. 7. Kang YK, et al. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. 8. Van Cutsem E, et al. Efficacy results from the ToGA trial: A phase III study of trastuzumab added to standard chemotherapy (CT) in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC). J Clin Oncol 27:18s, 2009 (suppl; abstr LBA4509) ----------------------------- Feb 2010: update FLAGS ref.

    31. Dünyada mide kanseri tedavsi 1. Okines C, et al. Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 21 (Supplement 5) 2010 2. NCCN Clinical Practice Guidelines in Oncology; Gastric Cancer v.2.2010 3. [Japanese Gastric Cancer Society. Guidelines for Diagnosis and Treatment of Carcinoma of the Stomach. 2004, addendum 2008] (in Japanese) --------------- Updated according to NCCN 2010v21. Okines C, et al. Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 21 (Supplement 5) 2010 2. NCCN Clinical Practice Guidelines in Oncology; Gastric Cancer v.2.2010 3. [Japanese Gastric Cancer Society. Guidelines for Diagnosis and Treatment of Carcinoma of the Stomach. 2004, addendum 2008] (in Japanese) --------------- Updated according to NCCN 2010v2

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