Retrospective comparison of flot and modified dcf as first-line chemotherapy in metastatic gastric adenocarcinoma

Background: The aim of our study was to compare the efficacy and the safety of the FLOT and the modified DCF (mDCF) regimens in patients with metastatic gastric (GC) and gastroesophageal junction (GEJ) adenocarcinoma as first-line treatment. Methods: The medical records of 72 patients were retrospectively reviewed. Survivals and hematological adverse events of the patients were examined. Factors affecting survivals were analyzed in univariate analysis. A multivariate analysis was performed with the factors contributing to survivals in univariate analysis. Results: The median PFS (mPFS) was 10.1 months (95% CI, 6.8-13.4) in the FLOT arm (n = 33) and 7.4 months (95% CI, 9.1-21.6) in the mDCF arm (n = 39) (p = 0.041). The median OS (mOS) was 12.9 months (95% CI, 9.7-16.1) in the FLOT arm and 15.4 months (95% CI, 9.1-21.6) in the mDCF arm (p = 0.622). It was found that all grade neutropenia was 51.3% vs. 72.7% (p = 0.063), febrile neutropenia was 8.3% vs. 6.3% (p = 0.743), and thrombocytopenia was 48.7% vs. 51.5% (p = 0.813) in the FLOT and mDCF arms, respectively. Anemia was 59% in the FLOT arm and 100% in the mDCF arm (p < 0.001). Grade 3-4 anemia was 7.7% in the FLOT arm and 24.2% in the mDCF arm (p = 0.052). Discussion: It was shown that the mPFS was significantly increased in the FLOT arm compared to the mDCF arm as the first-line treatment in patients with metastatic GC and GEJC. Hematological adverse events were more favorable in the FLOT arm than in the mDCF arm

Risk Tabanlı Deniz Ambulansı Tasarımı

Denizde, emniyeti en üst düzeye çıkarmak için risk faktörlerini modellemek ve risk tabanlı tasarım araçlarını kullanmak önemlidir. Emniyeti arttırmak ve müşteri taleplerini karşılamak için etkin risk modelleme teknikleri ve karar verme araçlarının geliştirilmesi ve uygulanması gerekmektedir. Bu çalışmada, mevcut bir deniz ambulans teknesi operasyon riskleri incelenmiş ve mevcut tekne risk tabanlı bir yaklaşımla yeniden tasarlanmıştır. Risk değerlendirmesi ve model tasarımında, Hata Türü ve Etki Analizi (FMEA) kullanılmış ve risk öncelik sayıları (RPNs) hesaplanmıştır. Bu çalışmadan elde edilen sonuçlar, deniz ambulans teknelerinin emniyetini arttırmaya ve potansiyel risklerin önlenmesine veya azaltılmasına katkıda bulunacaktır

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

Kolon Kanseri ile Tükürük Mikrobiyom İlişkisi

Aim: The aim of this study was to examine the presence and amount of Fusobacterium nucleatum (Fn), Porphyromonas gingivalis (Pg) and Streptococcus gallolyticus subspecies gallolyticus (Sg) in saliva samples of colorectal cancer (CRC) patients in comparison with healthy controls. Material and Method: Patients with newly diagnosed CRC who have not yet received any treatment were included in the study. Control group consisted of individuals over 50 years of age without a prior diagnosis of malignancy. Polymerase chain reaction (PCR) analyzes were performed with 16S rRNA for identification and quantification of Fn, Sg and Pg strains. Bacterial quantities were reported in log10 copies/ml saliva units. Results: A total of 148 subjects including 71 patients and 77 controls were included in the study. The total amount of bacteria in the saliva samples from the patient and control group were similar (7,51±0,50 vs 7,45±0,62 log10 copies/ml, p=0,549). Detection rates of Fn (97,2% vs 96,1% p>0,99), Sg (31% vs 27,3% p=0,619) and Pg (76,1% vs 75,3% p=0,917) were similar in two groups. Mean Fn amount was higher in patient saliva samples compared with controls (6,89±1,07 vs 6,35±0,78 log10 copies/ml, p=0,001). Mean Sg amount was higher in patient saliva samples (4,12±0,99 vs 3,15±0,58 log10 copies/ml, p<0,001). Saliva Pg amount was similar in two groups. The frequency and amount of Fn, Sg, and Pg were similar in the comparison of tumor localization (right vs left colon) and stage (stage 1-2-3 vs stage 4). Fusobacterium nucleatum and Streptococcus gallolyticus subspecies gallolyticus were found to be significantly lower in the microsatellite insability (MSI) (+) group than in the MSI (-) group [6,15 (4,35-7,96) vs 7,03 (5,18-8,97) log10 copies/ml p=0,036 for Fn; 3,44 (3,18-3,92) vs 4,13 (3,48-7,44) log10 copies/ml, p=0,022 for Sg, respectively]. Evaluation of the salivary Sg amount by ROC curve analysis found to have diagnostic value for CRC (AUC: 0,84 %95 GA 0,72-0,96 p<0,001). Quantity of Sg above 3,32 log10 copy/ml was the best predictor cutoff value for CRC with 82% sensitivity and 76% specificity. Conclusion: In this study, the salivary samples of colorectal cancer patients had higher amounts of Fn and Sg than the control group. This finding may be important for etiopathogenesis of CRC, identification of high-risk groups for CRC, screening of CRC and studies of oral and gingival health for CRC prevention.Hacettepe Üniversitesi, Proje No: THD-2017-12288.TEŞEKKÜR iii ÖZET iv ABSTRACT v İÇİNDEKİLER vi SİMGELER VE KISALTMALAR viii ŞEKİLLER x TABLOLAR xi 1. GİRİŞ VE AMAÇ 1 2. GENEL BİLGİLER 2-23 2.1. Epidemiyoloji 2 2.2. Etiyoloji 2 2.3. Kolorektal Kanserden Korunma 9 2.4. Kolorektal Kanser Taramaları 11 2.5. Kolorektal Kanser Tanısı 17 2.6. Kolorektal Kanser Tedavisi 22 3. MATERYAL-METOT 24-28 3.1. Örnekler ve Verilerin Toplanması 24 3.2. Real-time PCR yöntemi 24 3.3. İstatistiksel Analiz 28 3.4. Etik Kurul Onayı 28 4. BULGULAR 29-35 4.1. Demografik Veriler 29 4.2. Tümör özellikleri 29 4.3. Mikrobiyolojik İnceleme Sonuçları 30 5. TARTIŞMA 36-44 6. SONUÇLAR VE ÖNERİLER 45-46 KAYNAKLAR 47-59 EKLER Ek 1. Etik Kurul OnayıAmaç: Bu araştırmada kolorektal kanser (KRK) hastalarının tükürük örneklerinde Fusobacterium nucleatum (Fn), Porphyromonas Gingivalis (Pg) ve Streptococcus gallolyticus subspecies gallolyticus (Sg) varlığı ve miktarının incelenmesi ve sağlıklı kontrollerle karşılaştırılması amaçlandı. Gereç ve Yöntem: Çalışmaya KRK tanısı yeni konmuş olup henüz herhangi bir tedavi almamış hastalar dahil edildi. Elli yaş üzeri, kanser öyküsü olmayan bireyler kontrol grubuna dahil edildi. Fn, Sg ve Pg suşlarının saptanması ve kantifikasyonu için 16S rRNA ile polimeraz zincir reaksiyonu (PCR) analizleri yapıldı ve elde edilen veriler hastalar ve kontrol grubunda karşılaştırıldı. Bakteri miktarları log10 kopya/ml birimi ile raporlandı. Bulgular: Çalışmaya 71 hasta 77 kontrol olmak üzere toplam 148 kişi dahil edilerek tükürük örneği alındı. Hasta ve kontrol grubunun mikrobiyolojik ve klinik verileri analiz edildi. Hasta ve kontrol grubundan elde edilen tükürük örneklerinde total bakteri miktarı benzerdi (7,51±0,50 vs 7,45±0,62 log10 kopya/ml, p=0,549), iki grupta Fn (%97,2 vs %96,1 p>0,99), Sg (%31 vs %27,3 p=0,619) ve Pg (%76,1 vs %75,3 p=0,917) saptanma oranları benzerdi. Kantitatif analizde ise hastaların tükürük örneklerinde Fn ve Sg miktarı kontrol grubundan daha yüksek bulundu. Ortalama Fn miktarı hastaların tükürük örneklerinde 6,89±1,07 log10 kopya/ml, kontrollerde ise 6,35±0,78 log10 kopya/ml idi (p=0,001). Ortalama Sg miktarı hastaların tükürük örneklerinde 4,12±0,99 log10 kopya/ml, kontrollerde ise 3,15±0,58 log10 kopya/ml idi (p<0,001). Tükürük Pg miktarı iki grupta benzerdi. Tümörün yerleşimi (sağ vs sol kolon) ve evresine (Evre 1-2-3 vs evre 4) göre yapılan karşılaştırmalarda Fn, Sg ve Pg saptanma oranları ve miktarı benzerdi. Mikrosatellit instabilite (MSİ) (+) olan grupta Fn ve Sg miktarının MSİ (-) gruba göre anlamlı derecede daha düşük olduğu görüldü [Fn için sırasıyla 6,15 (4,35-7,96) vs 7,03 (5,18-8,97) log10 kopya/ml p=0,036; Sg için sırasıyla 3,44 (3,18-3,92) vs 4,13 (3,48-7,44) log10 kopya/ml, p=0,022]. ROC eğrisi analizi ile yapılan değerlendirmede, tükürük Sg miktarının KRK’yi öngörmede tanısal değeri olduğu görüldü (AUC: 0,84 %95 GA 0,72-0,96 p<0,001). Sınır değer 3,32 log10 kopya/ml olarak belirlendiğinde, bunun üzerinde Sg miktarının KRK için %82 duyarlılık ve %76 özgüllüğü olduğu görüldü Sonuç: Araştırmamızda, kolorektal kanser hastalarının tükürük örneklerinde Fn ve Sg miktarı kontrol grubundan daha yüksek bulundu. Bu bulgu KRK’nin etiyo-patogenezi, KRK açısından yüksek riskli grupların belirlenmesi, tarama çalışmaları ve KRK’yi önlemeye yönelik ağız ve diş eti sağlığına yönelik çalışmalar için önemli olabilir

Immune-mediated hearing loss associated with immune checkpoint inhibitors : A Systematic Review

The ICI-related hearing loss was reported in patients treated with ICIs. However, the presentation, accompanying irAEs, management, and hearing outcomes were heterogeneous. Additionally, while the development of irAEs was regarded as a denominator of robust immune activation and improved prognosis, the prognostic impact of ICI-related hearing loss on tumor response and survival is unknown. Therefore, we aimed to evaluate the presentation, management, hearing outcomes, and treatment efficacy in patients who developed ICI-related hearing loss with a systematic review of individual patient data from case reports and case series

The Efficacy of Immune Checkpoint Inhibitors in Microsatellite Stable Colorectal Cancer: A Systematic Review

The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer care, particularly in immune-inflamed tumors with high mutational burdens. However, their effectiveness in microsatellite stable (MSS) colorectal cancer (CRC) is limited. This systematic review aims to evaluate the efficacy of ICIs in MSS CRC and explore promising combination strategies. A comprehensive search identified 52 clinical trials included in the review. Monotherapy with ICIs demonstrated limited clinical activity in MSS CRC, with response rates below 10%. Combination strategies involving tyrosine kinase inhibitors (TKIs), chemotherapy, and other tumor microenvironment modifications were investigated. Combination therapy with anti-VEGF agents yielded varying results, with some studies reporting improved outcomes. The combination of ICIs with chemotherapy showed promise, especially in early treatment settings. Additionally, combinations involving BRAF inhibitors, CAR-T therapy, and TGF beta inhibitors were studied, but further research is needed to optimize these approaches. Ongoing studies are evaluating various combination regimens, including ICI-TKI and ICI-chemotherapy. Patient stratification based on molecular subtypes, such as consensus molecular subtypes (CMS), may facilitate individualized treatment and improve outcomes. In conclusion, while ICI monotherapy has limited efficacy in MSS CRC, combination strategies hold promise for enhancing patient outcomes. Further research is necessary to identify optimal combination approaches and predictive biomarkers for treatment response