Relationship Between Xanthine Oxidoreductase Activity and BRCA1 Levels in Patients with Stage IIIA and IIIB Non-Small Cell Lung Cancer Being Treated with Neoadjuvant Chemotherapy

Objective: Lung cancer is the leading cause of cancer-related death worldwide. Treatment in locally advanced non-small cell lung cancer (NSCLC) is heterogeneous. The cure rates after complete surgical resections are not as good as expected. A better understanding of the biology of NSCLC might allow the selection of appropriate treatment. Only a few studies have been carried out on the prognostic value of xanthine oxidoreductase (XOR) and BRCA1 in lung cancer. Material and Methods: In this study, 35 patients with stage IIIA and stage IIIB of NSCLC were included. They were operated in Baskent Ankara and Adana hospitals and received neoadjuvant chemotherapy. The regular follow-up of all the patients was done in Baskent University Medical Oncology, Thoracic Surgery Department. The clinical and histopathological parameters (age, gender, stage, smoking history, performance status, and neoadjuvant chemotherapy), along with the immunohistochemical study of BRCA1 and XOR staining, were examined, and correlated with survival outcomes. Results: Median overall survival time was reported as 38.5 months, and 5-year survival rate was 33%. The presence of BRCA1 was positively associated with shorter overall survival in stage III lung cancer patients, who were followed up with the neoadjuvant platinum-based chemotherapy regime (p<0.05). There was no relation between XOR activity and overall survival outcomes. Conclusion: BRCA1-positive status might be prognostic in patients with Stage IIIA and IIIB of NSCLC

Hepatosellüler karsinomda tedavi yaklaşımları

Hepatosellüler karsinoma (HCC) özellikle viral hepatit insidansı yüksek olan Asya ve Uzak Doğu'da sık görülen bir tümördür. Viral hepatitlere bağlı kronik karaciğer hastalığı zemininde gelişen HCC da tedavi gerektiren sadece tümörün kendisini değil aynı zamanda altta yatan karaciğer hastalığıdır. Cerrahi rezeksiyon, küratif bir yöntem olmasına rağmen sirozun varlığı hastaların %90'nında rezeksiyona engel olmaktadır. Bununla beraber sıklıkla yaygın ya da çoklu lezyonlara rastlanıldığı için, hastalar küratif rezeksiyona uygun olmamaktadırlar. Karaciğer transplantasyonu hem altta yatan kronik karaciğer hastalığının tedavisinde hem de HCC tedavisinde kür sağlayıcı bir tedavidir, merkezimizde genişletilmiş kriterlerle yapılan karaciğer transplantasyonlarda oldukça başarılı sonuçlar alınmaktadır. Cerrahi girişime uygun olmayan hastalarda lokal ablatif tedaviler gündeme gelmektedir. Transarteriel kemoembolisazyon (TACE), perkütan alkol enjeksiyonu (PAE) ya da radyofrekans ablasyon (RF) sık kullanılan yöntemler olup, küçük solid lezyonlarda etkili olabilmektedir. Ekstrahepatik yayılım varlığında, cerrahi rezeksiyona uygun olmayan hastalarda sistemik kemoterapiler kullanılmaktadır. Sisplatin, doksorubisin, etoposit ve 5-Florourasil gibi pek çok ilaç tek başına yada kombine olarak kullanılmış ancak yanıt oranları %8-18 ile sınırlı kalmıştır. Sisplatin, interferon-alfa-2b, doksorubisin ve 5-florourasil (PIAF) kombinasyonu ile bu grup hastalarda yüksek yanıt oranı elde edilmiş olmasına rağmen doksorubisinle karşılaştırıldığında sağ kalım avantajı sağlamadığı görülmüştür. Ciddi morbiditesi olması nedeniyle bu kombinasyonun henüz standart olarak kabul edilmemektedir. Son yıllarda HCC da etkinliği gösterilen bir ajanda, Raf kinaz inhibitörü olan sorafenibdir. Faz III çalışmada plaseboya karşı anlamlı olarak sağ kalım avantajı sağladığı gösterildiğinden dolayı, sorefenib HCC'un tedavisinde umut verici gibi görünmektedir. Hepatocelluler carcinoma is common especially in Asia and Far East where the incidence of viral hepatitis is very high. Treatment of HCC includes the treatment of underlying chronic liver disease caused by viral hepatitis and the tumor itself. Although, surgical resection is the curative treatment procedure for the disease, presence of cirrhosis hinders the resection at about 90% of patients. Besides, owing to diffuse and multiple lesions, most of the patients are not suitable for the curative resection. Liver transplantation can cure both the underlying chronic liver disease and the HCC. Liver transplantation are performed according to expanded criteria and successful results have been obtained at our center. Local and ablative treatments are put on to the agenda in patients whom are not suitable for surgical intervention. Transarterial chemoembolisation (TACE), percutaneous alcohol injections (PAI) and radiofrequency ablation (RF) are the most common procedures that are effective in small solitary lesions. Systemic chemotherapies are used in the case of extrahepatic dissemination or in patients with unresectable disease. Cisplatin, doxorubicin, etoposite and 5-flourouracil have been used both as a single agent and in combinations but the response rates are limited between 8 to 18%. In this group of patients although the higher response rate was achieved with the combination of cisplatin, interferon-?-2b, doxorubicin and 5-flourouracil (PIAF), no survival advantage was obtained when compared with doxorubicin. This combination has not been accepted as a standard because of its severe morbidity. Recently sorefenib, a Raf kinase intibitor, was shown to be effective in HCC. Owing to survival advantage in a phase III trial when comparing to placebo, sorefenib seems to be proming agent in HCC

Scleroderma After 5-Fluorouracil and Folinic Acid Therapy in a Patient with Colon Carcinoma

Skleroderma cilt altında ve iç organlarda artmış kollajen birikimi ile karakterize bir bağ dokusu hastalığıdır. Etiyolojisi tam aydınlatılamamakla birlikte bazı kimyasal ajanların ve çevresel faktörlerin etyopatogenezde rol oynadığı kabul edilmektedir. Progresif sistemik skleroderma olan olgularda gastrointestinal kanal karsinomlarının arttığına dair sınırlı veri bulunmaktadır. Kolon karsinomu tedavisinde kullanılan 5-florourasil ile skleroderma ilişkisine dair literatürde sadece iki olgu bildirilmiştir. 5-florourasil ve folinik asit tedavisi verilen timik karsinomlu bir olguda ise skleroderma benzeri klinik tablo ve otoantikor pozitifliği bildirilmiştir. Bu yazıda, 51 yaşında kolon karsinomu tanısıyla 3 kür 5-florourasil ve folinik asit tedavisi alan ve daha sonra scleroderma geliştiren bir olgu sunulmuşturSistemic sclerosis is a connective tissue disease which is characterized by the increase amount of collagene in subcutaneous tissue and internal organs. Several chemical agents and environmental factors are accused fort he etiopathogenesis however the etiology is not clear. There is limited data abput the increased frequency of colon carcinoma in the cases with sistemic sclerosis. There are 2 cases in the literature about the association between scleroderma and 5-fluorouracil which is used for the treatment of colon carcinoma. Similar clinical course and autoantibody positivity was also reported in a patient with tymic carcinoma who had been treated with 5-FU and folinic acid. In this article, a 51-year-old woman who developed scleroderma after 5-FU and folinic acid therapy which had been started for colon carcinoma has been reporte

Evre IV Küçük Hücreli Dışı Akciğer Kanserli Olgularda Prognostik Faktörlerin İncelenmesi

Amaç: Çalışmamızda, ileri evre küçük hücreli dışı akciğer karsinomlu hastalarda tedavi öncesi prognostik faktörlerin sağkalım üzerine etkilerini değerlendirmeyi amaçladık. Hastalar ve Yöntem: Şubat 2004 - Aralık 2006 tarihleri arasında kliniğimize baş- vurmuş evre IV küçük hücreli dışı, kemoterapi almış olan 73 hasta retrospektif olarak değerlendirildi. Bulgular: Performansı sıfır, 65 yaşından daha genç hastaların yaşam süreleri di- ğerlerine göre anlamlı olarak uzun bulunurken, histopatolojik alt grup, sigara içimi, kilo kaybı ve cinsiyet farkının yaşam süresi üzerinde anlamlı bir etkisi yoktu (p>0.05). Metastaz varlığı ile sağkalım süresi karşılaştırıldığında, istatistiksel olarak anlamlı bir fark saptanmamıştır. LDH seviyesi yüksek olanların yaşam süresinin daha kısa olduğu görüldü. Sonuç: 65 yaştan genç olmak, performansın iyi olması, normal LDH düzeyi ileri evre küçük hücreli dışı akciğer kanserli olguların uzun yaşam süresinde önemli rol oynar

Glass: Global lorlatinib for ALK(+) and ROS1(+) retrospective study: Real world data of 123 NSCLC patients

Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1( + ) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib.Methods: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria.Results: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. The ALK( + ) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 +/- 1.6 months and median overall survival (mOS) was 89.1 +/- 19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 +/- 2.5 months and mOS of 90.3 +/- 24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters.The most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients.Conclusion: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 +/- 19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 +/- 24 months is unprecedented for ROS1( + ) NSCLC.Pfize

Glass: Global lorlatinib for ALK(+) and ROS1(+) retrospective study: Real world data of 123 NSCLC patients

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