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

Outcomes of high-risk breast lesions diagnosed using image-guided core needle biopsy: results from a multicenter retrospective study

PURPOSEThe clinical management of high-risk lesions using image-guided biopsy is challenging. This study aimed to evaluate the rates at which such lesions were upgraded to malignancy and identify possible predictive factors for upgrading high-risk lesions.METHODSThis retrospective multicenter analysis included 1.343 patients diagnosed with high-risk lesions using an image-guided core needle or vacuum-assisted biopsy (VAB). Only patients managed using an excisional biopsy or with at least one year of documented radiological follow-up were included. For each, the Breast Imaging Reporting and Data System (BI-RADS) category, number of samples, needle thickness, and lesion size were correlated with malignancy upgrade rates in different histologic subtypes. Pearson’s chi-squared test, the Fisher–Freeman–Halton test, and Fisher’s exact test were used for the statistical analyses.RESULTSThe overall upgrade rate was 20.6%, with the highest rates in the subtypes of intraductal papilloma (IP) with atypia (44.7%; 55/123), followed by atypical ductal hyperplasia (ADH) (38.4%; 144/375), lobular neoplasia (LN) (12.7%; 7/55), papilloma without atypia (9.4%; 58/611), flat epithelial atypia (FEA) (8.7%; 10/114), and radial scars (RSs) (4.6%; 3/65). There was a significant relationship between the upgrade rate and BI-RADS category, number of samples, and lesion size Lesion size was the most predictive factor for an upgrade in all subtypes.CONCLUSIONADH and atypical IP showed considerable upgrade rates to malignancy, requiring surgical excision. The LN, IP without atypia, pure FEA, and RS subtypes showed lower malignancy rates when the BI-RADS category was lower and in smaller lesions that had been adequately sampled using VAB. After being discussed in a multidisciplinary meeting, these cases could be managed with follow-up instead of excision

Nitrik Oksit Sentaz NOS İnhibitörlerinin Sıçanlarda Çok Düşük Frekanslı Manyetik Alanın İndüklediği Analjezi Üzerine Etkileri

Amaç: Elektromanyetik alanın EMA farklı ağrı türlerini azalttığı bilinmektedir. Bununla birlikte, manyetik alanın analjezik etki mekanizması tam olarak anlaşılamamıştır. Bu çalışmanın amacı, nitrik oksit sentaz NOS inhibitörlerinin sıçanlarda çok düşük frekanslı EMA maruziyeti ile oluşan analjezi üzerine etkilerini araştırmaktır.Gereç ve Yöntem: Bu çalışmada 72 yetişkin erkek Wistar albino sıçan yaklaşık 230 ± 12 g ağırlığında kullanıldı. Sıçanlar, 22 ± 2 °C oda sıcaklığında, 12 saat aydınlık/karanlık siklusun sağlandığı ve ses yalıtımı olan ortamda tutuldu. Elektromanyetik alan 50 Hz , her gün dört defa 30 dakika süre ve 15 dakika aralıklar ile 15 gün boyunca uygulandı. Analjezik etki ölçümü tail-flick ve hot-plate testleri ile gerçekleştirildi. Analjezi testinden önce sıçanlara nitrik oksit donörü SNAP 30 mg/kg ve NOS inhibitörleri L-NAME 40 mg/kg ve 7-NI 25 mg/kg intraperitoneal olarak enjekte edildi. Verilerin istatistiksel analizinde varyans analizi iki yönlü ANOVA kullanılmış ve çoklu karşılaştırma Tukey testleri ile yapıldı. İstatistiksel olarak anlamlılık düzeyi

Prognostic significance of blood group antigen expression of tumor tissue in lung cancer patients

WOS: 000179685900009PubMed: 12487558Aims and background: Many prognostic factors have been evaluated both for SCLC and NSCLC. The prognostic significance of blood group antigen expression of tumor tissues has been studied particularly in NSCLC, yielding divergent results. The aim of the present study was to investigate the prognostic value of the tumoral expression of blood group antigens ABH in lung cancer. Methods: The presence of blood group antigens was assessed immunohistochemically in paraffin-embedded tumor samples from 92 patients diagnosed between 1996 and 1997. Monoclonal antibodies were used to detect blood group antigens. Results: The median survival was longer in NSCLC patients whose tumors were positive for blood group antigen A (P = 0.009). Since the expression of blood group antigen A in tumor cells was limited to patients with type A or AB blood, survival analysis of these patients showed survival to be longer in non-small cell lung cancer patients with blood group antigen A-positive tumors (P = 0.0019). Conclusions: Expression of blood group antigen A in tumor cells is an important, favorable prognostic factor in patients with non-small cell lung cancer, which could be useful to stratify patients with blood group A or AB according to possible outcome, and to guide therapeutic decision-making. The expression of blood group antigens ABH should be evaluated in larger series of lung cancer patients (including small and non-small cell lung cancer) with all blood types

Thyroid follicular carcinoma complicating with skin metastasis

Introduction: Thyroid cancer is the most common endocrine malignancy. Lung is the most metastatic site of the disease. Distant metastasis to skin has been rarely reported in the literature. Case report: Here we report a follicular thyroid cancer patient complicating with skin metastasis. Conclusion: Our case reminds us the rare possibility of skin metastasis during the follow up of disseminated TC and importance of cutenaous lesions in differential diagnosis of unexplained symptoms

Is there any prognostic significance in pleural involvement and/or effusion (Ple-I/E) in patients with ALK-positive NSCLC?

Conference Conference: 44th Congress of the European-Society-for-Medical-Oncology (ESMO) Location: Barcelona, SPAIN Date: SEP 27-OCT 01, 2019 Sponsor(s):European Soc Med Oncol; Japanese Soc Med OncolBackground: ALK mutation occurs in approximately 3-5% of patients with NSCLC. At the baseline, Ple-I/E are more frequent in ALKþ patients with NSCLC. In the study, we aimed to evaluate characteristics of ALKþpatients who have Ple-I/E. Methods: In this multicenter study, patients with ALKþ NSCLC who have Ple-I/E were retrospectively analyzed. Clinical and demographic characteristics of the disease, response rates, median PFS and OS were evaluated in 362 ALKþpatients with NSCLC. Results: Of the patients, 198 (54.7%) were male. The median age at the time of diagnosis was 54 (21-85) years. The median age was higher in male (57 vs 52 years; p¼0.011). The most common histology was adenocarcinoma (100%). At the baseline, 57 (15.7%) patients had Ple-I/E. The median age of patients with Ple-I/E was similar to patients without Ple-I/E (53 vs 55 years; p¼0.541). The rate of smokers was 43.4% (n¼157) in the patients. There was no association between Ple-I/E and gender, lung metastasis and distant LAP metastasis. Pleural involvement was higher in non-smokers than smokers (19.4% vs 13.4%; p¼0.077), but not statistically significant. The frequencies of liver, brain and bone metastasis were a significant higher in ALKþpatients with Ple-I/E compared to those with non-metastatasis (respectively 18.2% vs 4.8%, p¼0.008; 19.1% vs 4.8%, p¼0.002; 20.6% vs 8.9%, p¼0.003). The median PFS was longer in ALKþ patients who have Ple-I/E 18.7 vs 10.6 months, p¼0.017). The 1-, 2- and 3-year PFS were 59%, 36%, and 24% in patients with Ple-I/E and 47%, 24%, and 8% in patients with non-involvement. Similarly, the median OS was longer in ALKþpatients who have pleural involvement/infusion 44.6 vs 22.6 months, p¼0.051). The 1-, 2- and 3- year OS were 78%, 67%, and 57% in patients with Ple-I/E and 66%, 48%, and 34% in patients with non-involvement. Conclusions: Brain, liver and bone metastases are lower in ALKþpatients with Ple-I/E. Presentation with Ple-I/E in patients with ALKþ NSCLC is associated with longer overall and progression-free survival. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.European Society for Medical OncologyJapanese Society of Medical Oncolog

The real-life efficacy and safety of osimertinib in pretreated advanced non-small cell lung cancer patients with T790M mutation: A Turkish Oncology Group Study

Introduction Osimertinib, an irreversible third-generation EGFR-TKI, is the standard of care for second-line treatment of T790M-mutant advanced NSCLC patients whose disease progressed after first-line EGFR-TKI therapy. In this multicenter study, we aimed to determine the real-life efficacy and safety of Osimertinib in pretreated advanced NSCLC patients with T790M mutation. Materials and methods This retrospective trial included advanced T790M-mutant pretreated NSCLC patients who received Osimertinib from 24 different centers in Turkey. Primary endpoint was time-to-treatment discontinuation (TTD). Secondary endpoints were objective response rate (ORR), overall survival (OS), and safety. Results Of 163 patients, 68.7% had EGFR exon 19 deletion and 22.7% had exon 21 L858R mutation. Osimertinib was given as second-line treatment in 96 patients (58.9%) and third-line in 48 patients (29.4%). After median of 13-month follow-up, median TTD was 21.6 months with an 82.2% ORR. Estimated median OS was 32.1 months. Grade 3-4 adverse events were seen in 11.7% of the patients. Conclusion Osimertinib is a highly effective option in second- or third-line treatment of NSCLC patients with T790M mutation, with a favorable safety profile

Lorlatinib in ALK- or ROS1-positive non-small cell lung cancer patients: Experience from an early access program in Turkey

Background: Lorlatinib, a third generation ALK and ROS1 inhibitor, is indicated for the treatment of patients with ALK+ metastatic NSCLC whose disease has progressed on crizotinib and at least one second-generation ALK inhibitor. The aim of this study is to evaluate the efficacy and safety of lorlatinib in an Expanded Access Program (EAP) in Turkey. Method: The EAP was open-label, multicenter, and single-arm. Patients were eligible to receive lorlatinib (100 mg po/day) if they had advanced stage ALK-or ROS1-positive NSCLC and had progressed on crizotinib and/or second generation ALK inhibitors such as ceritinib or alectinib. The primary endpoint was PFS with lorlatinib. Secondary endpoints were objective response rate, overall survival, and safety