Lokal ileri larinks kanserli olgularda neoadjuvan tedaviye yanıtı belirleyen faktörler
Predictive factors of response to neoadjuvant chemotherapy in local advanced larynx cancer patients
Yazar: MURAT DİNÇER
Danışman: DOÇ. DR. MUSTAFA KADRİ ALTUNDAĞ
Hacettepe Üniversitesi / Tıp Fakültesi / Tıbbi Onkoloji Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2007
Konu: Onkoloji = Oncology

Özet:
Hacettepe Üniversitesi T p Fakültesi Medikal Onkoloji Bölümü'nde Nisan-1999 ile May s-2006 y llar aras nda lokal ileri evre (evre III-IV) larinks kanseri tan s alm ) 84 hastadaindüksiyon kemoterapisine yan t belirleyen klinik, patolojik ve moleküler faktörler ile bufaktörlerin hastal ks z ve genel sa3kal ma etkileri incelendi. Çal )maya 73 erkek, 11 kad nhasta olmak üzere toplam 84 hasta dahil edildi..Ortalama ya) 59 olup, 33 ya) ile 75 ya)aras nda de3i)iyordu. TNM evrelemesine göre 42 olgu evre 3, 39 olgu evre 4a, 1 olgu evre 4bidi. Kemoterapi sonras yan etki geli)me s kl 3 incelendi3inde,56 hastada birinci yada ikinciderecede bulant kusma geli)ti3i gözlendi. 5 Olguda herhangi bir kemik ili3i toksisitesibulgusuna rastlanmad . 24 olguda 1. derece nötropeni 16 olguda ikinci derece nötropeni ,16olguda 3. derece nötropeni,13 olguda 4.derecede nötropeni saptand . Otuzdört olguda1.derecede trombositopeni, 9 olguda ikinci derecede trombositopeni, 15 olguda 3 yada 4.derecede trombositopeni geli)ti3i saptand . 31 Olgu son kontrol tarihinde hastal ks z olaraksaptand .13 olgunun lokal nüksü oldu3u, 2 olgunun metastaz geli)tirdi3i lokal hastal 3 n nkontrolde oldu3u, 16 olguda lokal nüksle birlikte metastaz bulgusunun mevcut oldu3unutespit edildi. EvreIII hastalarda evre IV hastalara göre daha yüksek oranda tam yada k smi yan t gözlendi3isaptand (P=0.006). Kemoterapi sonras nötropeni, trombositopeni (p=0.001) ve anemisigeli)en olgularda (P=0.007) istatistiksel olarak anlaml olacak )ekilde yüksek oranda tamyan t ve k smi yan t gözlendi3i saptand . Olgular n patoloji preparatlar lenfo-vasküler veperi-nöral invazyon varl 3 ile heparanaz ekspresyonu aç s ndan de3erlendirildi. Lenfo-vasküler ve peri-nöral invazyonu olmayan (p=0.01) ve heparanaz ekspresyonu gösterengrupta (P=0.04) istatistiksel olarak anlaml derecede yüksek tam ve k smi yan t oranlarsaptand . Heparanaz pozitifli3i ile genel sa3kal m ili)kisi ara)t r ld 3 nda genel sa3kal maç s ndan anlaml bir farkl l k saptanmad . Olgular n ortanca takip süresi 23.8 ay, ortancagenel sa3kal m 38.2Â±9.53 ay olarak saptand .Anahtar kelimeler: Larinks kanseri, Neoadjuvan, Kemoterapi, Heparanaz

Abstract:
The effects of clinical,pathological and molecular factors as predictors of response to induction chemotherapy on thedisease-free interval and overall survival of 84 patients diagnosed with advanced stage locallarynx cancer (stage III-IV) between April 1999 and May 2006 in the Department of MedicalOncology at Hacettepe University Faculty of Medicine were investigated. Seventy-three menand 11 women were included in the study. Mean age was 59 years, ranging from 33 to 75years. Based on the TNM staging system, 42 patients had Stage III, 39 patients had Stage IVa,and 1 patient had Stage IVb disease. On evaluation of the frequency of the side effects ofchemotherapy, it was observed that 56 patients developed mild or moderate nausea andvomiting. Five patients did not have any signs of bone marrow toxicity. Grade I and IVneutropenia occured in 24 and 13 patients, respectively, while 16 patients each developedgrade II and III neutropenia. While 15 patients did not develop any thrombocytopenia, 34patients developed grade I, 9 patients grade II, and the remaining 15 patients developed grade3 and 4 thrombocytopenia. Twenty-six patients became anemic, while 38 patients remainedunaffected. Thirty-one patients were found to be disease-free on the last date of contact.Thirteen patients had local recurrence, 2 patients had metastasis despite local disease beingunder control, and 16 patients had signs of both local recurrence and metastasis. A completeor partial response occured at a higher rate in patients with stage III disease than those withstage 4 disease. Statistically, patients who developed neutropenia, thrombocytopenia andanemia had a significantly higher rate of complete or partial response to treatment, whencompared to those who did not. The pathology specimens showing lymphovascular andperineural invasion were investigated for heparanase expression. Patients withoutlymphovascular and perineural invasion and those who showed heparanase expression hadsignificantly higher complete and partial response rates. No assocation between heparanasepositivity and overall survival could be ascertained.Key words: Larynx cancer, Neoadjuvant, Chemotherapy, Heparanase