Neoadjuvan Kemoterapi ile Tedavi Edilen Lokal İleri Evre Küçük Hücreli Dışı Akciğer Kanseri Hastalarının Sağkalımında Histopatolojik Yanıt ve Prognostik Belirteçlerin Korelasyonu

Year 2019, , 28 - 36, 30.04.2019

Samed Rahatlı , Nadire Küçüköztaş Selim Yalçın , Merih Tepeoğlu Dalokay Kılıç

https://doi.org/10.24938/kutfd.465529

Abstract

Amaç: Neoadjuvan kemoterapi almış olan evre III küçük hücreli dışı akciğer kanserli (KHDAK) hastalarda neoadjuvan tedavi yanıtlarının belirlenmesi ile, prognoza katkısı ile eksizyon   onarım çapraz-tamamlayıcı grup 1 (ERCC1) ve Ribonükleotid Redüktaz alt ünitesi Ml (RRM1) ekspresyonunun tedavi yanıtı ve prognozla ilişkisinin belirlenmesini hedeflendi.

Gereç ve Yöntemler: Bu çalışmaya 2003-2013 yılları arasında Evre III KHDAK tanısıyla neoadjuvan kemoterapi alıp 27 hasta dahil edildi. Neoadjuvan cisplatin alan hastaların akciğer biyopsi dokularında ERCC1 ve gemsitabin alan hastaların biyopsi materyallerinde RRM1 protein ekpresyonu immünohistokimyasal yöntemle değerlendirildi.

Bulgular: Medyan yaş 59 (45-75)’du. Hastaların 19 (%70.4)’u evre IIIA, 8 (%29.6)’i evre IIIB idi. Hastaların hepsi cisplatin bazlı neoadjuvan kemoterapi aldı. Hastaların 15 (%55.6)’inin takiplerinde nüks tespit edildi. Ortanca takip süresi 36 aydı. Tüm olgulara ilişkin ortalama hastalıksız sağ kalım (HSK) 26.6 aydı. Genel sağkalım (GSK) ise 48 ay olarak bulundu. Evre IIIA ve IIIB açısından bakıldığında HSK (p=0.379) ve GSK (p=0.69) açısından anlamlı fark bulunmadı. Hastaların 16 (%59.3)’sında neoadjuvan KT sonrası cerrahi patoloji materyallerinde viabl tümör oranı %10 ve altında, 11 (%40) hastada ise viabl tümör oranı %10’nun üstünde bulundu. Bu açıdan da değerlendirildiğinde HSK (p=0.16) ve GSK (p=0.097) farkı saptanmadı. Düşük ERCC1 ekspresyonu olan hastalarla yüksek ERCC1 ekspresyonu olan hastalar arasında sağkalım farkı saptanmadı. Gemsitabin direncini gösteren RRM1 yüksek ekpresyonu olan hastalar da düşük ekspresyon olan hastalar ile benzer sağ kalım oranlarına sahipti.

Sonuç: Çalışmamızda neoadjuvan kemoterapi alan evre III KHDAK’li hastalarda HSK ve GSK süreleri genel verilere göre daha uzun bulundu. Sisplatin ve gemsitabin tedavisi açısından prediktif markerlar olan ERCC1 ve RRM1 ile tedavi yanıtı ve sağkalım arasında anlamlı ilişki bulunmadı.

Keywords

ERCC1, RRM1, akciğer Kanseri, Evre III, Neoadjuvan Kemoterapi

CORRELATION OF HISTOPATHOLOGIC RESPONSE AND PROGNOSTIC MARKERS WITH THE SURVIVAL IN LOCALLY ADVANCED NON-SMALL CELL LUNG CANCER PATIENTS TREATED WITH NEOADJUVANT CHEMOTHERAPY

Abstract

Objective: We aimed to determine the response and prognosis to neoadjuvant chemotherapy in patients with stage III non-small-cell lung cancer (NSCLC) who had received neoadjuvant therapy and to determine the relationship with prognosis and treatment response of the expression of excision repair cross-complementation group 1 protein (ERCC1) and Ribonucleotide reductase regulatory subunit M1 (RRM1) protein.

Material and Methods: Twenty-seven patients with stage III NSCLC who received neoadjuvant chemotherapy and had been operated between 2003 and 2013 were included in this study. Lung tissue biopsies were evaluated by immunohistochemical methods for ERCC1 protein expression in patients who received cisplatin and RRM1 protein expression who received gemcitabine.

Results: Median age was 59 (45-75). Nineteen patients (70.4%) were at stage IIIA and eight patients (29.6 %) were at stage IIIB. All patients received neoadjuvant cisplatin-based chemotherapy. Fifteen patients (55.6%) relapsed during follow-up. The median follow-up time was 36 months. The median disease-free survival (DFS) was 26.6 months, overall survival (OS) was 48 months. From the perspective of stage IIIA and IIIB DFS (p=0.379) and OS (p=0.69) did not differ significantly. Sixteen patients’ (59.3%) viable tumor ratio was ≤10%, 11 patients’ (40%) viable tumor ratio was >10%. When considered from this point of view DFS (p=0.16) and OS (p=0.097) showed no difference. More patients survived in the low ERCC1 expression group. Patients with low ERCC1 expression and patients with high ERCC1 expression showed no difference in terms of survival.

Conclusion: Patients with high RRM1 expression showing resistance to gemcitabine and with low RRM1 expression had similar survival rates. In patients with stage III NSCLC who received neoadjuvant chemotherapy, OS and DFS durations longer than literature were found.

Keywords

ERCC1, RRM1, Lung Cancer, Stage III, Neoadjuvant Chemotherapy

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