Metastatik safra yolu kanseri olan yaşlı hastalarda optimal tedavi yaklaşımları ve prognostik faktörler

Introduction: There is a lack of evidence of the outcomes in elderly patients advanced stage biliary tract cancer due to the patients aged over 65 years are less than 25% in many prospective trials. We designed a retrospective multicenter study to evaluate the factors affecting treatment and survival in elderly patients with advanced-stage biliary tract cancer. Materials and methods: A total of 116 patients with advanced stage biliary tract cancer aged ≥65 years were included, and the treatment responses, survival, and toxicity rates were evaluated with respect to age groups Results: There was no significant difference between age and response to treatment, survival, or toxicity. The median progression-free survival and overall survival were 5.3, and 11.8 months respectively. Multivariate analysis indicated that ECOG PS (p<0.001 CI95% 1.5-3.7) and PNI (p<0.001 CI 95% 0.14-0.41) were significant independent prognostic factors for PFS. The independent prognostic factors for OS were choice of frontline regimen, NLR and PNI (p=0.007 CI 95% 0.71 – 0.94, p=0.006 CI 95% 1.2 – 3.1, p=0.001 CI 95% 0.35 – 0.91, respectively). Discussion: This study confirms the general prognostic relevance of inflammatory parameters and the importance of frontline treatment in elderly patients with advanced-stage biliary tract tumors. Additionally, getting older does not indicate that treatment will be avoided or that they will have a worse prognosis and suffer from more toxicities.Giriş: 65 yaş üzeri hastaların klinik çalışmaların %25’inden daha azını oluşturması nedeniyle biliyer sistem kanseri olan ileri yaş hastaların yönetimi konusunda kanıt eksiği bulunmaktadır. Bu amaçla, metastatik safra yolu kanseri tanılı yaşlı hastalarda tedaviyi ve sağkalımı etkileyen faktörleri değerlendirmek için retrospektif çok merkezli bir çalışma tasarladık. Gereç ve yöntemler: Çalışmaya 65 yaş ve üzeri, ileri evre safra yolu kanseri tanısı almış, 116 hasta dahil edildi ve yaş gruplarına göre tedavi yanıtları, sağkalım ve toksisite oranları değerlendirildi. Bulgular: Median yaşa göre gruplandırılıdğında; yaş ile tedaviye yanıt, sağkalım, toksisite arasında anlamlı bir fark bulunmadı. Tüm populasyonda medyan progresyonsuz sağkalım (PSK) ve genel sağkalım (GSK) sırasıyla 5.3, 11.8 aydı. Multivariate analizde, PSK için bağımsız prognostik faktörler preformans durumu(ECOG PS) (p<0.001 CI95% 1.5-3.7) ve Prognostik nutrisyonel indek (PNI) (p<0.001 CI 95% 0.14-0.41) olarak bulundu. GSK için ise bağımsız prognostik faktörler, birinci sıra tedavi seçimi, Notrofil Lenfosit oranı (p=0,007 CI %95 0,71 – 0,94) ve PNI (p=0,001 CI %95 0,35 – 0,91) olarak bulundu. Tartışma: Metastatik safra yolu kanseri olan yaşlı hastalarda prognozu etkileyen temel faktöreler inflamatuar parametreler ve birinci basamakta seçilen kemoterapi rejimidir. İleri yaş ile sağkalım, toksiste profili ve tedavi toleransı farklılık göstermemektedir

Clinicopathological factors and their effect on prognosis in patients with metastatic colorectal cancer

Kolorektal kanserler dünya genelinde en sık tanı alan kanser türünden biridir. Günümüzde çalışmalarda sağ veya sol kolona lokalize tümörlerin epidemiyolojik, histopatolojik, moleküler ve embriyolojik farklılıklar gösterdiği ve bunun tedavi ve prognozda etkili olabileceği gösterilmiştir. Çalışmamızda, metastatik kolorektal tanısı almış hastalarda klinikopatolojik ve moleküler faktörler arasındaki ilişkisinin gösterilmesi ile bu faktörlerin, özellikle tümör lokalizasyonun genel sağkalım (GSK) ve progresyonsuz sağkalım(PSK) üzerindeki etkilerinin geriye dönük olarak araştırılması amaçlandı. Çalışmaya İstanbul Medipol Üniversitesi Tıp Fakültesi, Tıbbi Onkoloji Kliniğinde takip ve tedavi edilen, yeni tanı konulmuş 201 de novo metastatik kolorektal kanserli hasta dahil edilmiştir. Hastaların klinikopatolojik verileri ve moleküler özelikleri (BRAF/RAS mutasyonları) hasta dosyalarından kaydedildi. Hastaların mevcut parametrelere göre GKS ve PSK'ları analiz edildi. Tümör, hastaların 61'inde sağ kolonda lokalize, 140'ıında sol kolonda lokalizeydi. Moleküler özellikler incelendiğinde hastaların 105'i (%52.2) RAS mutant, 96'sı (%47.8) RAS mutant olmayan (Wild Tip: WT) olarak saptandı. Hastaların önemli çoğunluğu BRAF WT idi (n=154, %76.6). Tümör lokalizasyonuna göre PSK ve GKS için tek değişkenli analiz yapıldığında sağ kolon yerleşimli olan hastaların PSK ve GSK süreleri, sol kolon yerleşimli olanlardan anlamlı olarak daha kötüydü (sırasıyla p=0,003 ve p=0.005). RAS popülasyonu incelendiğinde de RAS WT grupta hem PSK hem de GSK süreleri sağ kolon tümörlerinde anlamlı olarak daha kısaydı. Çalışmamızda tümör lokalizasyonun sıklık dağılımı, sağ kolon tümörlerinde daha kısa sağkalım süreleri ve moleküler farklılıklar ile ilgili veriler literatür ile uyumlu bulundu. Tümör lokasyonunun günümüzde prognostik ve tedavi açısından da prediktif bir faktör olduğu gösterilmiştir. Çalışmamızda tümör lokasyonunun özellikle genetik, prognoz, tedavi faydalanımı açısından farklı özelliklere sahip olabileceği ortaya konulmuştur.Colorectal Cancer is one of the most commonly diagnosed cancer worldwide. Recently, studies revealed differences between right and left-sided colon cancer regarding epidemiology, histopathology, molecular,embriology and their possible effect on treatment plan and prognosis. The aim of present study was retrospectively analyize associations between clinicopathologic and molecular features and their impact , particularly tumor localization, on overall survival(OS) and progression-free survival(PFS) in patients diagnosed with metastatic colorectal cancer. The study included newly diagnosed 201 de novo metastatic colorectal cancer patients who were followed-up and treated in Istanbul Medipol University Medical Faculty, Medical Oncology Clinic. Clinicopathological data and molecular features (BRAF / RAS mutations) were obtained from the patient records. OS and PFSs of patients were analyzed according to current parameters. The tumor was localized in the right colon in 140 patients and in the left colon in 61 patients. When the molecular features were analyzed, 105 (52.2%) of the patients were RAS mutants and 96 (47.8%) were non-RAS mutants (Wild Type: WT). Vast majorty of patients were BRAF WT (n=14, 76,6%). When the univariate analysis for OS and PSK was performed according to tumor localization, the OS and PFS duration of the patients with right colon were significantly worse than those in the left colon (p = 0.003 and p = 0.005, respectively). Additionaly, both OS and PFS rate in the RAS WT group were significantly worse than in right colon tumors based on RAS popülation investigations. In our study, parameters including frequency of tumor localization, shorter survival rates in right colon tumors and molecular differences were consistent with the literature. Tumor location has been shown to be a predictive factor in prognostic and therapeutic aspects. In present study, it has been shown that tumor location may have different characteristics especially in terms of genetic, prognosis and treatment benefit

Real-life analysis of treatment approaches and the role of inflammatory markers on survival in patients with advanced biliary tract cancer

Objectives: Advanced-stage biliary tract cancers (BTC) are rare malignancies with poor prognosis. There are few prospective trials, but several retrospective studies regarding treatment options. In this study, we aimed to investigate the role of systemic inflammatory parameters (SIP) and other possible independent factors that may affect survival and treatment approaches and to determine the benefit of later-line treatments in these patients. Methods: A total of 284 patients, initially diagnosed with advanced stage or progressed after curative treatment of BTC, from different oncology centers in Turkey were included in this retrospective study. The prognostic significance of clinicopathological factors, SIPs and treatment options was analyzed. Results: At a median follow-up of 13 months, the median progression-free survival (PFS) was 6.1 months (95% CI:5.51–6.82), and the median overall survival (OS) time was 16.8 months (95% CI: 13.9–19.6). Treatment choice (p <.001 HR:0.70 CI95% 0.55–0.9), performance status (p <.001 HR:2.74 CI 95% 2.12–3.54) and neutrophil-to-lymphocyte ratio (NLR) (p =.02 HR:1.38 CI 95% 1.03–1.84) were independent prognostic factors for PFS. For OS, the independent prognostic indicators were determined as The Eastern Cooperative Oncology Group Performance Status (ECOG PS) (p <.001 HR:1.78 CI 95% 1.5–2.3), Systemic Immune-inflammation Index (SII) (p <.001 HR:0.51 CI95% 0.36–0.73) and stage at diagnosis (p =.002 HR:1.79 CI 95% 1.24–2.59). Furthermore, second and third line treatments significantly prolonged OS in advanced BTC (p <.001 HR:0.55 CI 95% 0.38–0.79; p =.007 HR:0.51 CI95% 0.31–0.83, respectively). Conclusion: SII and NLR are useful prognostic factors and may be helpful in making treatment decisions. Additionally, second and later-line treatments in advanced BTC have a significant impact on survival under real-life conditions

Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy.

Background There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). Methods A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and >= 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. Results The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. Conclusion Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET