Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group

Crizotinib is a multikinase inhibitor, effective in non-small cell lung cancer (NSCLC) harboring mesenchymal-epidermal transition (MET) alterations. Although small prospective studies showed efficacy and safety of crizotinib in NSCLC with MET alterations, there is limited real-life data. Aim of this study is to investigate real-life efficacy and safety of crizotinib in patients with advanced NSCLC harboring MET alterations. This was a retrospective, multicenter (17 centers) study of Turkish Oncology Group. Patients' demographic, histological data, treatment, response rates, survival outcomes, and toxicity data were collected. Outcomes were presented for the study population and compared between MET alteration types. Total of 62 patients were included with a median age of 58.5 (range, 26-78). Major histological type was adenocarcinoma, and 3 patients (4.8%) had sarcomatoid component. The most common MET analyzing method was next generation sequencing (90.3%). MET amplification and mutation frequencies were 53.2% (n = 33) and 46.8% (n = 29), respectively. Overall response rate and disease control rate were 56.5% and 74.2% in whole study population, respectively. Median progression free survival (PFS) was 7.2 months (95% confidence interval [CI]: 3.8-10.5), and median overall survival (OS) was 18.7 months (95% CI: 13.7-23.7), regardless of treatment line. Median PFS was 6.1 months (95% CI: 5.6-6.4) for patients with MET amplification, whereas 14.3 months (95% CI: 6.7-21.7) for patients with MET mutation (P = .217). Median PFS was significantly longer in patients who have never smoked (P = .040), have good performance score (P < .001), and responded to the treatment (P < .001). OS was significantly longer in patients with MET mutation (25.6 months, 95% CI: 15.9-35.3) compared to the patients with MET amplification (11.0 months; 95% CI: 5.2-16.8) (P = .049). In never-smokers, median OS was longer than smoker patients (25.6 months [95% CI: 11.8-39.3] vs 16.5 months [95% CI: 9.3-23.6]; P = .049). The most common adverse effects were fatigue (50%), peripheral edema (21%), nausea (29%) and diarrhea (19.4%). Grade 3 or 4 adverse effects were observed in 6.5% of the patients. This real-life data confirms efficacy and safety of crizotinib in the treatment of advanced NSCLC harboring MET alteration

Determination of Levels cytokeratin 18 in chronic pancreatitis

Giriş ve Amaç: Kronik pankreatit (KP), endokrin ve ekzokrin fonksiyonel bozukluk ile giden, pankreasta morfolojik değişikliklerin gözlendiği, kalıcı yıkım, fibrozis, fonksiyon bozukluğu oluşturan inflamatuvar bir hastalıktır. Patogenezinde inflamasyon , fibrozis , apoptozis rol oynar .Sitokeratinler epitelyal hücre iskeletini yapan ara flamentlerdir.Hücrenin şeklini koruma,motilite ve hücreler arası etkileşim gibi birçok işlevleri vardır. .Sitokeratin 18 mesane epiteli, kolon mukozası, hepatosit, pankreas asiner hücresi gibi çeşitli dokulardan sentezlenir ve apoptozisin belirlenmesinde bir marker olarak rol oynayabildiği çeşitli çalışmalarda gösterilmiştir. Bu çalışmanın amacı kronik pankreatitin sitokeratin 18 düzeyi ile ilişkisi olup olmadığını saptamaktır. Gereç ve Yöntem: Kronik pankreatit tanısı ile izlenen 35 hasta ve sağlıklı 35 kontrol grubu çalışmaya dahil edildi. Hastaların 12 saat açlık sonrası açlık serum sitokeratin 18 düzeyleri ölçüldü. Kronik pankreatit ve sitokeratin 18 düzeyleri arasındaki ilişki değerlendirildi. Bulgular: Kronik pankreatli hastaların serum sitokeratin 18 düzeyleri 0,45 ±1,40 g/ml, sağlıklı erişkinlerin değerlendirildiği kontrol grubunda ise sitokeratin düzeyi 0,16 ± 0,16 ng/mL saptandı. Çalışma grubunda ve kontrol grubunda sitokeratin 18 düzeyleri arasında istatiksel olarak anlamlı ilişki saptanmadı. (p:0,23) Tartışma ve Sonuç: Kronik pankreatit patogenezinde apoptozisin rolü bilinmesine karşın biz yaptığımız çalışmada apoptozis belirteci olan sitokeratin 18 düzeyi ile kronik pankreatit arasında ilişki saptayamadık. Sitokeratin 18 in kronik pankreatit tanı ve takibinde kullanılmak için uygun bir marker olmadığını gösterdik. Kronik pankreatit tanı ve progresyonu gösterecek yeni markerların bulunması amacıyla ek çalışmalara ihtiyaç vardırIntroduction and aims: Chronic pancreatitis (CP) is a inflammatory disease that leading to morphological changes, , permanent destruction, fibrosis in pancreas with endocrine and exocrine functional impairment. İnflammation, fibrosis and apoptosis plays role in the pathogenesis of the disease. Cytokeratins compose the intermediate filament cytoskeleton of epithelial cells. Cytokeratin functions are maintain cell shape, motility, and cell-cell interactions. Cytokeratin 18 is synthesized bladder epithelium, colonic mucosa, hepatocytes, pancreatic acinar cells of various tissues. Several studies showed that cytokeratin 18 have a role in apoptosis and can be use as a marker of apoptosis. The aim of this study is to determine relationship between chronic pancreatitsn and cytokeratin 18 . Materials and Methods: 35 chronic pancreatitis patients and 35 healthy volunteers were enrolled for the study. Blood samples for cytokeratin 18 tests were taken after 12 h fasting. Relationship between chronic pancreatin and cytokeratin 18 were evaluated. Results: The mean levels of cytokeratin 18 were 0.45 ± 1.40 ng / ml in patients with chronic pankreatits and the mean levels of cytokeratin 18 were 0.16 ± 0.16 ng / ml in the control group. There was no statistically association between chronic pancreatits and cytokeratin 18 . Discussion and Conclution:. The role of apoptosis in the pathogenesis of chronic pankreatitis well known situation but in this study there was no statistically association between chronic pancreatitis and cytokeratin 18 which is the marker of apoptosis. We showed that cytokeratin is not a reliable marker for the diagnosis and fallow up of chronic pancreatitis and additional studies are needed to show new markers for diagnosis and fallow up of chronic pancreatiti