Türkiye’de akciğer kanserinde genetik mutasyonların bölgesel dağılımı (REDIGMA)

Introduction: The results of standard chemotherapy in lung cancer are not very satisfactory, so it is important to identify genetic mutations that provide targeted therapies. Recent reports have suggested influences of racial difference on the frequency of mutation in lung cancer. We aimed to determine the frequency and regional distribution of genetic mutations of non-small cell lung cancer (NSCLC) in Turkey. Materials and Methods: Regional distribution of genetic mutations in lung cancer in Turkey (REDIGMA) study was carried out as a prospective, cross-sectional, observational study in a large number of centers in which lung cancer patients were followed and could perform genetic mutation analysis on patients’ biopsy materials. Results: The 703 patients (77.7% male, mean age 63.3 ± 12.5 years) who were diagnosed as NSCLC from 25 different centers were included in the study. Tumor samples from patients were reported as 87.1% adenocarcinoma, 6.4% squamous cell carcinoma and 6.5% other. Mutation tests were found to be positive in 18.9% of these patients. The mutations were 69.9% EGFR, 26.3% ALK, 1.6% ROS and 2.2% PDL. Mutations were higher in women and non-smokers (p< 0.000, p< 0.001). Again, the frequency of mutations in adenocarcinoma was higher in metastatic disease. There was no difference between the patient’s age, area of residence, comorbidity and clinical stage and mutation frequency. Conclusion: Our study revealed that the EGFR mutation rate in Turkey with NSCLC was similar to East European, African–American and Caucasian patients, and was lower than in East Asia.Giriş: Akciğer kanserinde standart kemoterapinin sonuçları çok tatmin edici değildir, bu nedenle hedefe yönelik tedavileri sağlayan genetik mutasyonları belirlemek önemlidir. Son raporlar, ırksal farklılığın ve bölgesel değişikliğin akciğer kanserinde mutasyon sıklığı üzerindeki etkilerini göstermiştir. Çalışmamızda küçük hücreli dışı akciğer kanseri (KHDAK)'nde genetik mutasyonların Türkiye'deki sıklığını ve bölgesel dağılımını belirlemeyi amaçladık. Materyal ve Metod: Türkiye'de akciğer kanserinde genetik mutasyonların bölgesel dağılımı (REDIGMA) çalışması, akciğer kanseri hastalarının takip edildiği ve hastaların biyopsisinde genetik mutasyon analizi yapılabilecek çok sayıda merkezde prospektif, kesitsel ve gözlemsel bir çalışma olarak gerçekleştirildi. Bulgular: Çalışmaya 25 farklı merkezden KHDAK tanısı konan 703 hasta (%77.7 erkek, ortalama yaş 63.3 ± 12.5 yıl) alındı. Hastalardan alınan tümör örnekleri %87.1 adenokarsinom, %6.4 skuamöz hücreli karsinom ve %6.5 diğer olarak bildirildi. Mutasyon testleri bu hastaların %18.9'unda pozitif bulundu. Mutasyonlar %69.9 EGFR, %26.3 ALK, %1.6 ROS ve %2.2 PDL idi. Mutasyonlar kadınlarda ve sigara içmeyenlerde istatistiksel olarak daha yüksek tespit edildi (p< 0.000, p< 0.001). Yine, adenokarsinomdaki mutasyonların sıklığı metastatik hastalıkta daha yüksekti. Hastanın yaşı, ikamet alanı, komorbiditesi, klinik evresi ve mutasyon sıklığı arasında farklılık saptanmamıştır. Sonuç: Çalışmamızın sonucunda Türkiye geneli mutasyon pozitifliği literatür ile karşılaştırıldığında Türkiye’de KHDAK'lı hastalarda EGFR mutasyon oranının Doğu Avrupa, Afrikalı-Amerikalı ve Kafkasyalı hastalara benzer ve Doğu Asya'dan daha düşük olduğu ortaya koyulmuştu

Diagnostic delay in rare diseases

OBJECTIVE Post-operative radiotherapy (PORT) in non-small cell lung cancer (NSCLC), especially after complete resection, has long been an unresolved dilemma and debated among therapeutic disciplines. We aimed to evaluate the effects of different radiotherapy volumes and techniques on local-regional recurrence patterns and PORT results in patients with NSCLC. METHODS The results of 389 patients who underwent surgery and received PORT at 11 centers were analyzed retrospectively. The surgical margin was positive or closes in 100 (26%) patients. The PORT dose was a median of 50 Gy (36-60 Gy). Intensity-modulated RT methods were used in 68 (17.5%) patients. RESULTS The first recurrence of the patients who developed relapse, local recurrence was found in 77 (19.8%) patients, distant recurrence was found in 95 (24%) patients, and both recurrences was found in 30 (8%) patients. The median time to locoregional relapse was 14 months (1.84-59.7 months). Local-regional recurrence was not significantly higher in patients with positive surgical margins than in negative pa-tients (39% vs. 29%, p=0.1), but the dose administered to these patients was also higher. Mediastinal recurrence occurred in 28 (19%) patients who did not receive radiotherapy to the mediastinum; 25 of these recurrences (89%) were just near or outside the field. Cardiac events became 7% in all groups and did not change according to chosen mediastinal radiotherapy volume. CONCLUSION A clear description of the PORT volumes according to the localization of the primary tumor and the involved lymph nodes would be beneficial in terms of establishing the recurrence/toxicity balance better

Prognostic significance of protein kinase B/Akt pathway in patients with non-small cell lung cancer

WOS: 000334153000023PubMed ID: 24659658Purpose: Akt, also known as protein kinase B (PKB), is an intracellular signal transduction protein activated by growth hormones. PKB/Akt is frequently activated in a variety of cancer types, but its role in the development and progression of lung cancer has not been completely elucidated yet. The aim of the present study was to determine the prognostic value of PKB/Akt in non-small cell lung cancer (NSCLC). Methods: A total of 32 tumor samples from NSCLL patients were examined before treatment. The staining characteristics of the cases were evaluated in terms of age, stage (T and N), response to therapy, histological type, tumor size, and ECOG performance status (PS). Results: No statistical correlation was found between PKB/Akt expression and gender, ECOG PS and stage (T and N), while significant correlation between cytoplasmic PKB/akt expression and age was detected (p < 0.05). In addition, squamous cell carcinoma histology was significantly associated with both nuclear and cytoplasmic staining (p=0.033), and tumor size (< 5 cm) was correlated with nuclear PKB/Akt expression (p =0.03). Both overall survival (OS) and progression-free survival (PFS) were similar in patients with and without both nuclear and cytoplasmic PKB/Akt expression. Conclusion: Our results showed that although PKB/Akt was not associated with survival in NSCLC patients, it may be a potential therapeutic target for NSCLC; more studies with higher numbers of patients are needed to verify this hypothesis