Real-Life Experience with Entrectinib in Neurotrophic Tyrosine Receptor Kinase Fusion-Positive Solid Tumors: A Multicenter Retrospective Trial

Background: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions represent rare somatic mutations in many types of cancer and have enabled the use of promising targeted therapies. In clinical studies, increased response rates to tropomyosin receptor kinase inhibitors have been demonstrated in NTRK fusion-positive cancer types; however, real-world experiences on these targeted agents are scarce. Objective: We evaluated the clinical characteristics and treatment responses of NTRK fusion-positive patients who received entrectinib treatment within the scope of an early access program in Turkey. Patients and methods: This multicenter, retrospective analysis involved 17 patients with solid tumors harboring NTRK fusions or rearrangements from 14 oncology centers between June 2019 and 31 March 2024. Demographic and clinical data were obtained via retrospective review of medical records with a cutoff date of 31 March 2024. Results: The median age at diagnosis of the patients in our study was 42 [interquartile range (IQR) 33–60] years. Nine different types of solid tumors were diagnosed in these patients. The most common NTRK gene rearrangements involved NTRK1 (n = 8), followed by NTRK3 (n = 7). The median duration of entrectinib usage was 6.9 (IQR 3.1–16.1) months. Dose reductions due to side effects were performed in four patients: two due to leukopenia, one due to visual disturbance, and one due to troponin elevation. Leukopenia was the most commonly observed side effect. The objective response rate (ORR) was 35.3% (95% confidence interval (CI) 14.2–62.7), with complete response (CR) achieved in four patients. The duration of response (DOR) in patients who responded after initiating entrectinib was 9.8 (95% CI 0–30.7) months, the median overall survival (mOS) in all patients was 20.8 (95% CI 0–48.5) months, and the time-to-treatment failure (TTF) was 6.4 (95% CI 0–13.5) months. Conclusions: In this retrospective study, we aimed to obtain real-world data concerning the use of entrectinib in patients with solid tumors harboring NTRK fusion genes. Although our findings are partially similar to the results of clinical studies, prospective studies in larger patient groups with more diverse tumor types and different demographic characteristics are needed to confirm the findings. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024

The negative prognostic impact of bone metastasis with a tumor mass

OBJECTIVE:Typically, bone metastasis causes osteolytic and osteoblastic lesions resulting from the interactions of tumor cells with osteoclasts and osteoblasts. In addition to these interactions, tumor tissues may grow inside bones and cause mass lesions. In the present study, we aimed to demonstrate the negative impact of a tumor mass in a large cohort of patients with bone metastatic cancer.METHODS:Data from 335 patients with bone metastases were retrospectively reviewed. For the analysis, all patients were divided into three subgroups with respect to the type of bone metastasis: osteolytic, osteoblastic, or mixed. The patients were subsequently categorized as having bone metastasis with or without a tumor mass, and statistically significant differences in median survival and 2-year overall survival were observed between these patients (the median survival and 2-year overall survival were respectively 3 months and 16% in patients with a tumor mass and 11 months and 26% in patients without a tumor mass; p<0.001).RESULTS:According to multivariate analysis, the presence of bone metastasis with a tumor mass was found to be an independent prognostic factor (p=0.011, hazard ratio: 1.62, 95% confidence interval: 1.11–1.76). Bone metastasis with a tumor mass was more strongly associated with osteolytic lesions, other primary diseases (except for primary breast and prostate cancers), and spinal cord compression.CONCLUSION:Bone metastasis with a tumor mass is a strong and independent negative prognostic factor for survival in cancer patients

The relationship between self and other in aggressive driving and driver behaviors across countries

© 2019 Elsevier Ltd The main aim of the present study was to investigate the moderating role of aggressive driving of others on the relationship between self-reported aggressive driving behaviors committed by driver himself/herself and drivers’ aberrant and positive driver behaviors (i.e. errors, violations, and positive driver behaviors) among drivers from Estonia, Greece, Kosovo, Russia, and Turkey as the total sample in order to understand the grand pattern. The other aim was to examine the same moderating role of aggressive driving for each country separately. It was hypothesized that the combination of self-reported of aggressive driving behaviors committed by the driver himself/herself and perceiving aggressive acts of other drivers against them associates with more errors and violations for each country and the total sample. On the other hand, this combination was expected to associate with less positive driver behaviors. Surveys were completed by 743 participants from five countries (i.e., Estonia, Greece, Kosovo, Russia, and Turkey). The Driver Anger Indicators Scale (DAIS) and the short version of the Driver Behavior Questionnaire (DBQ) with items of Positive Driver Behavior Scale were used as measurement tools. Moderation analyses were conducted for the total sample and each country separately. The results of the moderation analyses indicated that there was a moderating role of perceiving other drivers as engaging in aggressive behaviors on the relationship between aggressive behaviors of the driver himself/herself and their errors or violations in the total sample and every country except for Russia. However, the significant interaction between aggressive behaviors committed by the driver himself/herself and other drivers' aggressive acts in traffic was related to more positive driver behaviors for Kosovar drivers and less positive driver behaviors for Russian drivers and the total sample. It could be discussed that the way of understanding aggressive behaviors for self and other related to aberrant and positive driver behaviors in traffic may be important to manage aggression for individual level and country level

Road users’ evaluations and perceptions of road infrastructure, trip characteristics, and daily trip experiences across countries

Governments in every country have made attempts to encourage road safety, and road users’ perceptions of these attempts are crucial to understanding community needs and the effectiveness of road safety initiatives. However, while many studies compare countries with respect to fatality rates or possible causative factors related to these fatalities, little is known about how road users in different countries evaluate and perceive their tangible road environments from their own points of view. Therefore, the purpose of this study is to statistically explore drivers’-motorcyclists’, pedestrians’, cyclists’ and public transport users’ evaluations and perceptions of road infrastructure, trip characteristics and daily trip experiences in Estonia, Greece, Kosovo, Russia, and Turkey. In total, 1221 participants completed a questionnaire battery that included different sets of questions for different types of road users. Chi-Square analysis was used to examine the similarities and differences in the evaluations and perceptions of different road users across five countries. The main findings suggest that all road users across the five countries evaluated environmental characteristics significantly differently from each other. No similar trend could be observed within and between road users and countries. This is a quantitative study that provides descriptive information about road users’ perceptions and evaluations across countries, which can be used for both conceptual and practical purposes. In future studies, this study finding can be used for system-based interventions and may inform government regulation on human or human-environmental interactive factors in order to improve regional and overall road safety

Cross-cultural differences in pedestrian behaviors in relation to values: A comparison of five countries

© 2020 Elsevier Ltd This study compared pedestrian behaviors in five countries (Estonia, Greece, Kosovo, Russia, and Turkey) and investigated the relationships between these behaviors and values in each country. The study participants were 131 pedestrians for Estonia, 249 for Greece, 112 for Kosovo, 176 for Russia, and 145 for Turkey. The principal component analyses revealed that the four-factor structure of the Pedestrian Behavior Scale (PBS) was highly consistent across the five countries. ANCOVA results revealed significant differences between countries on the PBS items and scale scores. Specifically, Greek and Turkish participants reported transgressive pedestrian behaviors more frequently than Estonian, Kosovar, and Russian pedestrians while Kosovar participants reported transgressive pedestrian behaviors less frequently than Estonian pedestrians. In addition, Turkish and Russian pedestrians reported lapses and aggressive behaviors more frequently than Estonian, Greek, and Kosovar pedestrians. Finally, Turkish and Estonian pedestrians reported positive behaviors more frequently than Kosovar pedestrians. Unexpectedly, the regression analyses showed that values have varying effects on pedestrian behavior in the five countries. That is, context or country may determine the effect of values on pedestrian behaviors. The results are discussed in relation to the previous literature

Cross-cultural differences in driver aggression, aberrant, and positive driver behaviors

© 2020 Elsevier Ltd The present study investigated differences in driver aggression for self and others within countries and cultural differences between driver aggression, aberrant, and positive driver behaviors across five countries (Estonia, Greece, Kosovo, Russia, and Turkey). It was predicted that drivers from these five countries differ significantly in terms of driver aggression for self and others, aberrant, and positive driver behaviors. In the study, 743 participants completed the questionnaire package, including the Driver Aggression Indicators Scale (DAIS), the short version of the Driver Behavior Questionnaire (DBQ) with items from the Positive Driver Behavior Scale, and the Demographic Information Form. Paired samples T-tests were conducted to examine the differences in driving aggression between self and others in the five countries. The results indicated that, except for Russian drivers, drivers reported that other drivers had higher driver aggression than themselves. To examine the cross-cultural differences, analysis of covariance (ANCOVA) tests were conducted for the two dimensions of the DAIS (hostile aggression and revenge, and aggressive warnings) and the three dimensions of the DBQ with items from the Positive Driver Behavior Scale (errors, violations, and positive driver behaviors). Cross-country item-based comparisons were then made for the DAIS and the DBQ. The ANCOVA results showed significant differences in both item-based and subscale comparisons. Russian drivers were significantly different from other drivers in terms of hostile aggression and the revenge subscales of the DAIS and positive driver behaviors. Turkish drivers were significantly different from other drivers in several items of the DBQ, including errors and violations. The findings suggest that culture-specific strategies might be conducted for traffic-related anger management. Furthermore, differences in errors and violations among the five countries may be due to cultural differences. Positive driver behaviors might be better promoted in countries by drawing on their distinct cultural road safety strategies

Driver profiles based on values and traffic safety climate and their relationships with driver behaviors

© 2019 Elsevier Ltd Drivers have an important place in the traffic system when the human factor is taken into consideration. Drivers from different cultures are exposed to different values, norms, and traffic systems, and these differences may form various driver behaviors. Thus, traffic climate and individual values can impact driver behaviors. In this study, the relationships between Schwartz's individual values and traffic climate dimensions were examined. Clusters were then created from the traffic climate dimensions and individual values, and the differences in driver behavior within these clusters were investigated. In order to examine similarities and differences between countries, the results from 5 countries (Estonia, Greece, Kosovo, Russia, and Turkey)are presented. Correlational analyses indicated that, while internal requirements and self-transcendence are positively related in all countries, external affective demands and conservation are positively related in Estonia, Kosovo, Russia, and Turkey. Additionally, external affective demands and self-transcendence are positively related in Greece, Kosovo, Russia, and Turkey. A three-cluster structure fitted the data well in all of the five countries. Within-country differences were observed in clusters of Russian and Turkish data in terms of driver behaviors. The detailed results are presented and discussed in relation to the literature

A comparison of the relationship between individual values and aggressive driving in five countries

© 2020, © 2020 Taylor & Francis Group, LLC and The University of Tennessee. Values are supposed to transcend specific situations and contexts. A country-independent relationship is expected between individual values and aggressive driving. The purpose of this novel study was to investigate the relationship between individual values and aggressive driving. The data were collected from five countries, namely, Estonia, Greece, Kosovo, Russia, and Turkey. The number of participants was 124 in Estonian, 272 in Greek, 107 in Kosovar, 132 in Russian, and 87 in Turkish samples. Participants filled out a demographic information form, Driver Anger Indicators Scale, and Short-Schwartz’s Value Survey. Results of hierarchical regression analyses showed that values are related to aggressive driving (i.e., aggressive warnings, hostile aggression and revenge) of self and not to perceived aggressive behaviours of others. Value types were not related to aggressive driving, whereas higher-order values were. Conservation was negatively associated with aggressive warnings of self in the Greek sample, and self-transcendence was negatively associated with hostile aggression and revenge of self in Turkish as well as Greek samples. Social focus was negatively and personal focus was positively associated with both types of aggressive driving in the Greek sample. Social focus was also negatively associated with hostile aggression and revenge in the Russian sample. Growth anxiety-free was negatively associated with hostile aggression and revenge of self in Russian and Turkish samples. The relationships between values and aggressive driving (of self) were not country-independent for the five countries, even though the lack of significant relationships between values and aggressive driving (of others) were country-independent