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

Primary lumbar hydatid cyst: a case report

A five-year-old male patient presented with swelling in the lumbar region that had persisted for two weeks. Ultrasonography and magnetic resonance imaging revealed a cystic lesion inside his right back muscles. Intra-abdominal organs within the site of inspection were normal. The lumbar region was explored, and a 3x4x5 cm hydatid cyst was detected inside the latissimus dorsi muscles. The cyst was incised and the germinative membrane was removed. Albendazole was used for three months after surgery to prevent recurrences. No problem was detected in a five-year follow-up period. Primary hydatid cyst in the lumbar area is very rare. In hydatid cyst treatment, it is necessary to remove the cyst without contaminating adjacent organs. Medical treatment as an adjunct to surgery increases the chance of full recovery

Are endothelial microparticles early markers of pulmonary hypertension?

Objective: To find out the relation between endothelial microparticles (EMPs), pulmonary arterial stiffness and thickness of pulmonary artery intima media to determine the prognosis of Eisenmenger syndrome and their correlation with echocardiographic and hemodynamic parameters

Cheatham platinum stent implantation in children with coarctation of the aorta: single-centre short-term, intermediate-term, and long-term results from Turkey

Objectives: Our aim was to evaluate patients who were treated by percutaneous stent implantation. Methods: Patients with aortic coarctation (n=35) who had been treated with 38 stents - 12 bare and 26 covered - were evaluated. The demographics and procedural and follow-up data were recorded from hospital registers and compared according to patient specifications, for example, weight and coarctation nature. Results: The procedure was successful in all patients. There was a statistically significant difference between the patients with native coarctation (n=17) and those with recurrent coarctation (n=18) in terms of pre-procedural blood pressures, systolic gradients, coarctation diameters, and the ratio of the coarctation site diameter to the descending aorta diameter. Although all patients received antihypertensive drugs before the procedure, the drug was discontinued in 26 patients during follow-up (p<0.001). Stent migration was observed in four patients with recurrent coarctation (11.4%), and peripheral arterial injury was seen in three patients (8.5%). The mean follow-up time was 34 +/- 16 months. On average, 21 (6-42) months after the procedure, six patients underwent cardiac catheterisation. At least 2 years after the procedure, tomography was performed in 20 patients (57.2%). Patients who were evaluated by multi-slice computerised tomography revealed no pathologies. There was no statistically significant difference between the five patients weighing less than 20 kg and the other 30 patients in terms of demographic and procedural characteristics, procedure success and complication rates, and follow-up data. Conclusion: Stent implantation for aortic coarctation is a method yielding satisfactory results in reducing coarctation gradients, efficient enlargement of the lesion area, and resolution of hypertension for children, including those weighing less than 20 kg

The Role of N-Terminal proBNP in the Clinic Scoring of Heart Failure due to Dilated Cardiomyopathy in Children

Background: We aimed to show sensitivity and specificity of NT-ProBNP in demonstrating the degree of cardiac failure caused by dilated cardiomyopathy (DCMP)

Comparison of response and survival of first-line crizotinib therapy according to EML-4 ALK fusion variants in advanced non-small cell lung cancer patients: A Turkish Oncology Group study

Purpose: In the literature there are conflicting data about the treatment efficacy of anaplastic lymphoma kinase (ALK) translocation positive non-small cell lung cancer (NSCLC) patients according to ALK fusion variants. We aimed to study the impact of ALK fusion variants on the survival of first-line crizotinib-treated NSCLC patients. Methods: 101 locally advanced or metastatic ALK positive NSCLC patients treated with first-line crizotinib between January 2013 and December 2019 were retrospectively evaluated. We studied ALK fusion variants in 38 of those patients with adequate tumor tissue with reverse transcription polymerase chain reaction (RT PCR). Patients having ALK fusion variant 1 (v1) and non-variant 1 (non-v1) were compared for survival and response to crizotinib. Results: Median age was 52.5 years (range 35-74), and 22 of 38 patients were male (57.9%). EML-4 ALK v1 was seen in 26 patients (68.4%) and 12 were non-v1 (variant 3a/b in 6, and non-EML-4 ALK variants in 6 patients). Objective response rate was 60.5% in all patients, whereas it was 61.5% in v1 and 58.3% in non-v1 group. Median progression-free survival (PFS) and overall survival (OS) were similar. Median PFS was 13.1 months in v1, and 12.4 months in non-v1 (p=0.232). Median OS was 23.2 months in v1, and 19.4 months non-v1 (p=0.493). Conclusion: ALK v1 and non-v1 patients had the same OS and PFS after first-line crizotinib treatment, however there was a trend for v1 group for better OS.Turkish Oncology Grou

Prognostic factors for survival in patients with mucosal and ocular melanoma treated with ipilimumab: Turkish Oncology Group study

Objectiv

Prognostic factors for survival in patients with metastatic malign melanoma treated with ipilimumab: Turkish Oncology Group study

Purpose Studies in the last decade show survival improvement with checkpoint blocker therapy in patients with metastatic malign melanoma. Our purpose was to define the efficacy of ipilimumab according to the patient's baseline characteristics including absolute lymphocytes count. Methods We collected the data of 97 patients with advanced malign melanoma treated with ipilimumab (3 mg/kg, q3w) retrospectively. Log-rank test was used to analyze the univariate effects of patient's characteristics (age, gender, metastatic sites, ECOG PS, type of melanoma, lactic dehydrogenase levels, anemia, lymphocytes (L), neutrophils (N), N/L ratio), c-kit and BRAF status. Survival analyses were estimated with Kaplan-Meier method. Cox regression analysis was used to assess the possible factors identified with log-rank test. Results The median age was 58, and 58% were male and 90% of patients had at least one prior systemic therapy. The median survival was 9.7 months for all patients; and the 12- and 24-month survival rates were 43% and 19%, respectively. Absolute lymphocytes count, lactic dehydrogenase level, bone metastasis, the number of metastatic sites, and RECIST response were significantly related to survival. After Cox regression analysis, RECIST response (complete or partial response), absolute lymphocytes count (more than 1500/mm(3)) and the number of metastatic sites (less than three sites) remained as significant independent prognostic factors for longer survival. Conclusion Ipilimumab improved survival of patients with metastatic malign melanoma. However, patients with fewer metastatic sites and higher absolute lymphocytes count have a significantly better benefit. To determine if these markers could be used to direct patient therapy, further validation analysis is needed

The efficacy of immunotherapy and chemoimmunotherapy in patients with advanced rare tumors: A Turkish oncology group (TOG) study

Abstract Introduction The advances in immune checkpoint inhibitors (ICIs) were relatively slow in rare tumors. Therefore, we conducted a multi‐center study evaluating the efficacy of ICI monotherapy and the combination of ICIs with chemotherapy (CT) in patients with advanced rare tumors. Methods In this retrospective cohort study, we included 93 patients treated with ICIs for NCI‐defined rare tumors from the 12 cancer centers in Turkey. The primary endpoints were the overall response (ORR) and disease control rate (DCR). Results The cohort's median age was 56, and 53.8% of the patients were male. The most frequent diagnosis was sarcoma (29%), and 81.7% of the patients were previously treated with at least one line of systemic therapy in the advanced stage. The ORR and DCR were 36.8% and 63.2%, respectively. The germ cell tumors had the lowest ORR (0%), while the Merkel cell carcinoma had the highest ORR to ICIs (57.1%). Patients treated with ICI + ICI or ICI plus chemotherapy combinations had higher ORR (55.2% vs. 27.6%, p = 0.012) and DCR (82.8% vs. 53.4%, p = 0.008). The median OS was 13.47 (95% CI: 7.79–19.15) months, and the six and 12‐month survival rates were 71% and 52%. The median duration of response was 16.59 months, and the 12‐month progression‐free survival rate was 66% in responders. The median time‐to‐treatment failure was 5.06 months (95% CI: 3.42–6.71). Three patients had high‐grade irAEs with ICIs (grade 3 colitis, grade 3 gastritis, and grade 3 encephalitis in one patient each). Conclusion We observed over 30% ORR and a 13‐month median OS in patients with rare cancers treated with ICI monotherapy or ICI plus CT combinations. The response rates to ICIs or ICIs plus CT significantly varied across different tumor types. Responding patients had over 2 years of survival, highlighting a need for further trials with ICIs for patients with rare tumors