Search

Individualism and collectivism are dimensions of cultural variation thought to shape differences in emotion regulation tendencies, yet research to date has examined these cultural dimensions as country-level features, emphasizing variability across nations. The present study takes the approach of examining cultural differences within nations as predictors of emotion regulation strategies, shifting the perspective instead to individual differences. This present study aimed to address how individual endorsement of individualism-collectivism (i.e. prioritizing individual versus group goals) and vertical-horizontal attitudes (preference for hierarchy versus equality) are associated with use of emotion regulation strategies (i.e., reappraisal and suppression) among college students from seven countries (n = 5,900; female = 70.80%). Overall, we found that individual differences in individualism-collectivism and vertical-horizontal attitudes had strong connections with young adults' emotion regulation styles. Results of our multivariate (i.e., all variables were simultaneously examined) regression model revealed: a) higher endorsement of horizontal individualism and horizontal collectivism were associated with higher use of reappraisal strategies; b) higher endorsement of horizontal individualism and vertical collectivism were associated with higher use of suppression strategies; while higher endorsement of horizontal collectivism was associated with lower use of suppression strategies. A multi-group model supported the generalizability of these associations across countries. These findings demonstrate the value of approaching cultural differences in emotion regulation from an individual differences framework, and not assuming country-level differences are representative of individuals' affective experiences. Further work is needed examining models within-country to examine cultural variation in individualism vs collectivism compared to country-level norms. [ABSTRACT FROM AUTHOR]

The 15-item Distress Tolerance Scale (DTS) is a widely used psychometric measure with evidence generally supporting its reliability and validity. However, limitations related to its ordinal response format and lack of cross-cultural comparisons have yet to be investigated using appropriate methods. The Partial Credit Rasch model was used to evaluate and enhance the psychometric properties of the DTS using responses from 2550 adult participants from the United States of America (USA), England, Canada, South Africa, Spain, and Argentina. The initial poor fit of the DTS to the Rasch model was improved by removing one item and combining locally dependent items into three testlets. These modifications resulted in the best fit of the 14-item DTS to the Rasch model for all the countries in our study, providing evidence of unidimensionality, high reliability and invariance across countries, meditation practice, and gender. Meeting the expectations of the Rasch model permitted the development of ordinal-to-interval conversion algorithms derived from person estimates of the Rasch model. Using the ordinal-to-interval conversion algorithms published in this article, ordinal DTS scores can be transformed into interval-level data, enhancing the precision of this scale for future research and clinical use across people from the six countries in this study and across the English and Spanish versions of the 14-item DTS. [ABSTRACT FROM AUTHOR]

Liquid biopsy, a minimally invasive approach for detecting tumor biomarkers in blood, has emerged as a leading-edge technique in cancer precision medicine. New evidence has shown that liquid biopsies can incidentally detect pathogenic germline variants (PGVs) associated with cancer predisposition, including in patients with a cancer for which genetic testing is not recommended. The ability to detect these incidental PGV in cancer patients through liquid biopsy raises important questions regarding the management of this information and its clinical implications. This incidental identification of PGVs raises concerns about cancer predisposition and the potential impact on patient management, not only in terms of providing access to treatment based on the tumor molecular profiling, but also the management of revealing genetic predisposition in patients and families. Understanding how to interpret this information is essential to ensure proper decision-making and to optimize cancer treatment and prevention strategies. In this review we provide a comprehensive summary of current evidence of incidental PGVs in cancer predisposition genes identified by liquid biopsy in patients with cancer. We critically review the methodological considerations of liquid biopsy as a tool for germline diagnosis, clinical utility and potential implications for cancer prevention, treatment, and research. [ABSTRACT FROM AUTHOR]

Background: Resistance mechanisms to combination therapy with dabrafenib plus trametinib remain poorly understood in patients with BRAFV600E-mutant advanced non-small-cell lung cancer (NSCLC). We examined resistance to BRAF inhibition by single CTC sequencing in BRAFV600E-mutant NSCLC. Methods: CTCs and cfDNA were examined in seven BRAFV600E-mutant NSCLC patients at failure to treatment. Matched tumour tissue was available for four patients. Single CTCs were isolated by fluorescence-activated cell sorting following enrichment and immunofluorescence (Hoechst 33342/CD45/pan-cytokeratins) and sequenced for mutation and copy number-alteration (CNA) analyses. Results: BRAFV600E was found in 4/4 tumour biopsies and 5/7 cfDNA samples. CTC mutations were mostly found in MAPK-independent pathways and only 1/26 CTCs were BRAFV600E mutated. CTC profiles encompassed the majority of matched tumour biopsy CNAs but 72.5% to 84.5% of CTC CNAs were exclusive to CTCs. Extensive diversity, involving MAPK, MAPK-related, cell cycle, DNA repair and immune response pathways, was observed in CTCs and missed by analyses on tumour biopsies and cfDNA. Driver alterations in clinically relevant genes were recurrent in CTCs. Conclusions: Resistance was not driven by BRAFV600E-mutant CTCs. Extensive tumour genomic heterogeneity was found in CTCs compared to tumour biopsies and cfDNA at failure to BRAF inhibition, in BRAFV600E-mutant NSCLC, including relevant alterations that may represent potential treatment opportunities. [ABSTRACT FROM AUTHOR]

Lung cancer poses a global health challenge and stands as the leading cause of cancer-related deaths worldwide. However, its incidence, mortality, and characteristics are not uniform across all regions worldwide. Understanding the factors contributing to this diversity is crucial in a prevalent disease where most cases are diagnosed in advanced stages. Hence, prevention and early diagnosis emerge as the most efficient strategies to enhance outcomes. In Western societies, tobacco consumption constitutes the primary risk factor for lung cancer, accounting for up to 90% of cases. In other geographic locations, different significant factors play a fundamental role in disease development, such as individual genetic predisposition, or exposure to other carcinogens such as radon gas, environmental pollution, occupational exposures, or specific infectious diseases. Comprehensive clinical and molecular characterization of lung cancer in recent decades has enabled us to distinguish different subtypes of lung cancer with distinct phenotypes, genotypes, immunogenicity, treatment responses, and survival rates. The ultimate goal is to prevent and individualize lung cancer management in each community and improve patient outcomes. [ABSTRACT FROM AUTHOR]

The incidence and mortality of lung cancer in women are rising, with both increasing by 124% between 2003 and 2019. The main risk factor for lung cancer is tobacco use, but indoor radon gas exposure is one of the leading causes in nonsmokers. The most recent evidence demonstrates that multiple factors can make women more susceptible to harm from these risk factors or carcinogens. For this consensus statement, the Association for Lung Cancer Research in Women (ICAPEM) invited a group of lung cancer experts to perform a detailed gender-based analysis of lung cancer. Clinically, female patients have different lung cancer profiles, and most actionable driver alterations are more prevalent in women, particularly in never-smokers. Additionally, the impact of certain therapies seems to be different. In the future, it will be necessary to carry out specific studies to improve the understanding of the role of certain biomarkers and gender in the prognosis and evolution of lung cancer. [ABSTRACT FROM AUTHOR]

Background: It is important to identify students who would benefit from early interventions to reduce harmful drinking patterns and associated consequences. the Brief Young Adult Alcohol Consequences Questionnaire (B-YAACQ) could be particularly useful as a screening tool in university settings. Objectives. The present study examined the utility of the B-YAACQ to distinguish among students at-risk for problematic alcohol use as measured by the AUDIT. Objectives: The present study examined the utility of the B-YAACQ to distinguish among students at-risk for problematic alcohol use as measured by the AUDIT. Methods: A sample of 6382 students (mean age=20.28, SD=3.75, 72.2% females) from seven countries (i.e., U.S., Canada, South-Africa, Spain, Argentina, Uruguay, England) completed the B-YAACQ, the AUDIT and different measures of alcohol use. Results: ROC analyses suggested that a cutoff score of 5 maximized the YAACQ's discrimination utility to differentiate between students at low versus moderate/high risk in the total sample and across countries (except in Canada, where the cutoff was 4). In addition, a cutoff of 7 differentiated between students at low/moderate versus high risk in the total sample, while cutoffs of 10, 9, 8 and 7 differentiate between students at low/moderate versus high risk in Uruguay, U.S and Spain (10), Argentina (9), England (8), and Canada and South-Africa (7), respectively. Students classified at the three risk levels (i.e., low, moderate and high) differed in age (i.e., a younger age was associated with higher risk) and drinking patters (i.e., higher drinking frequency, quantity, binge drinking and AUDIT and B-YAACQ scores in the higher risk groups). Conclusions: This study suggest that the B-YAACQ is a useful tool to identify college students at-risk for experiencing problematic patterns of alcohol use. [ABSTRACT FROM AUTHOR]

Past research has examined the association of cultural orientation with drinking motives, alcohol use, and alcohol-related problems, mainly, at the country level or in participants from a single region. This study examined the indirect associations of features of cultural orientation (i.e., vertical individualism, vertical collectivism, horizontal individualism, horizontal collectivism; VI, VC, HI, and HC, respectively) with alcohol use and alcohol-related negative consequences, via drinking motives in college students from seven countries. A total of 4093 participants (72.8% female, 27.2% male) across seven countries (USA, Canada, Spain, England, South Africa, Argentina, and Uruguay) completed an online survey that assessed alcohol use and experienced alcohol-related negative consequences, drinking motives, and cultural orientation. A path analysis (Mplus 8.3 software) examined the associations of the proposed model. VI was significantly indirectly associated with alcohol use and alcohol-related negative consequences, mainly via positive reinforcement motives. VC and HC were indirectly associated with alcohol use and alcohol-related negative consequences via conformity motives, although the association was negative for HC and positive for VC. Most of the associations between variables were invariant across countries with the exception of five paths (alcohol use → alcohol-related negative consequences; enhancement motives → alcohol-related negative consequences; enhancement motives → alcohol use; VI → conformity motives; HC → conformity motives). Overall, our findings suggest that the vertical component of individualism and the horizontal component of collectivism might operate as risk or protective factors, respectively. The small effect sizes of some paths suggest that other variables could mediate the association of cultural orientation with alcohol use and/or alcohol-related problems. [ABSTRACT FROM AUTHOR]

The present work aimed to extend the evidence of the structure validity of the Ruminative Thought Style Questionnaire (RTSQ) 15-item version testing: (1) the structure of two competing models (i.e., four-factor correlated model vs a second-order factor model); (2) the measurement invariance of the final model across four countries (U.S., Spain, Argentina, and the Netherlands) and gender groups (male and female); and (3) the invariance across three assessment waves in a subsample of Spanish youths. Participants were college students (mean age = 20.87, SD = 4.47) from the U.S. (n = 1875; 67.1% of females), Spain (T1, n = 732, 63.9% females; T2, n = 370, 71.6% females: T3, n = 307, 60.6% females), Argentina (n = 368, 65.6% females) and the Netherlands (n = 295, 74.8% females). Confirmatory Factor Analyses supported both correlated factors and second-order factor structure in the whole sample. Due to similar fit indices being observed for both models, and considering the theoretical and practical advantages, we kept the second-order model to examine its invariance across groups and time. Measurement invariance analyses showed that the second-order model was invariant across countries, gender, and over time. Comparisons of the total mean score and the subfacet mean scores (i.e., Repetitive Thoughts, Counterfactual Thoughts, Problem-focused Thoughts, and Anticipatory Thoughts) reveled only small differences across country and gender groups. The present work extends the structural validity evidence of the RTSQ, and provides the first evidence concerning its longitudinal stability across time. [ABSTRACT FROM AUTHOR]

While there is evidence that histories of adverse childhood experiences (ACEs) are common in university students and are associated with an increased risk of mental health difficulties, current research has limited geographic and cross-cultural representation. Comparing ACEs across diverse contexts using a standardized measure can illuminate geographic and sociocultural similarities or differences in exposure. The present study aimed to assess ACE exposure and its relationship with mental health symptoms in university students from seven countries. We sampled 5945 university students from the United States, Canada, England, South Africa, Spain, Argentina, and Uruguay. Participants completed the Adverse Childhood Experiences International Questionnaire (ACE-IQ) and the Inventory of Depression and Anxiety Symptoms (IDAS). Most participants (94.8%) reported exposure to at least one type of ACE and 61% reported exposure to four or more types. Repeated exposure to at least one ACE was reported by 70.2% and repeated exposure to at least four ACEs was reported by 21.2%. Spanish students had significantly lower ACE exposure than other students. Cumulative ACE exposure was significantly higher among students in lower income countries, but when repeated exposure was considered these differences fell away. For the total sample, cumulative ACE exposure was significantly associated with severity of depression symptoms, anxiety symptoms, and suicidality. Findings indicate that universities globally should be guided by a trauma-informed approach that recognizes students as a psychologically vulnerable group carrying a long-standing burden of childhood adversity. [ABSTRACT FROM AUTHOR]

Objectives: Mindfulness has been conceptualized as intentionally paying attention to the present moment without judgment. The Five Facet Mindfulness Questionnaire (FFMQ) is one of the most popular measures to assess trait mindfulness. The accurate assessment of mindfulness dispositions is essential for both clinical and research purposes. However, there is limited evidence regarding the psychometric properties of the FFMQ in Argentinian samples. The present study aimed to examine reliability and structural and concurrent validity of the Spanish version of the FFMQ in a sample of Argentinian college students. Methods: A sample of 632 students (69% women; Mage = 24.47, SD = 5.76) enrolled at five public universities in Argentina completed an online survey that assessed mindfulness-related traits (Observing, Describing, Acting with Awareness, Nonjudging of Inner Experience, and Nonreactivity to Inner Experience), emotion-regulation strategies, facets of anxiety sensibility, and symptoms of depression, anxiety, and stress. Results: FFMQ subscales exhibited adequate internal consistency values (α between 0.77 and 0.89; ω between 0.79 and 0.89). An intercorrelated 5-factor model structure showed acceptable fit to the data. The findings also supported configural, metric and scalar invariance across sex and levels of mindfulness experience. The FFMQ demonstrated sensitivity to discriminate participants with vs. without mindfulness experience. We also observed significant correlations between mindfulness dimensions and theoretically-related variables. Conclusions: The present findings support the reliability and validity of FFMQ scores among Argentinian college students. This evidence supports the use of the FFMQ as an appropriate instrument for assessing dispositional mindfulness in Argentinian college students. [ABSTRACT FROM AUTHOR]

Immune-checkpoint inhibitors (ICI) have revolutionized the therapeutic landscape of cancer. However, optimal patient selection is still an unmet need. One-hundred-forty-six patients with metastatic cancer candidates to ICI at the Hospital Clinic of Barcelona Clinical Trials Unit were prospectively recruited in this observational study. Blood samples were collected at different timepoints, baseline LIPI score calculated and pre-ICI archived tissues retrieved to evaluate PD-L1, tumor-infiltrating lymphocytes (TILs) and PD1 mRNA levels. Tumor assessments were centrally reviewed by RECIST 1.1 criteria. Associations with overall response rates (ORR), durable clinical benefit (DCB), progression-free survival (PFS) and overall survival (OS) were performed with univariable/multivariable logistic and Cox regressions, where appropriate. At a median follow-up of 26.9 months, median PFS and OS were 2.7 and 12.9 months. Response rates were 17.8% with duration of response (DOR) of 4.4 months. LIPI score was independently associated with PFS (p = 0.025) and OS (p < 0.001). Immunotherapy-naïve status was independently associated with better PFS (p = 0.005). Time-to-best response (TTBR) and ORR (p < 0.001 both) were associated with better OS at univariate analysis. PFS and DOR were moderately correlated with OS (p < 0.001 both). A PD-L1 10% cut-off detected worse/best responders in terms of ORR (univariate p = 0.011, multivariate p = 0.028) and DCB (univariate p = 0.043). PD1 mRNA levels were strikingly associated to complete responses (p = 0.021). To resume, in our prospective observational pan-cancer study, baseline LIPI score, immunotherapy-naïve status, cancer type and RT before starting ICI were the most relevant clinical factors independently correlated with immunotherapy outcomes. Longer TTBR seemed to associate with better survival, while PD1 mRNA and PD-L1 protein levels might be tumor-agnostic predictive factors of response to ICI and should be furtherly explored. [ABSTRACT FROM AUTHOR]

Background: Prior research has established that Adverse Childhood Experiences (ACEs) predict harmful alcohol use outcomes. However, underlying mechanisms that could explain these associations are less clear. The present study examined if ACEs are indirectly related to alcohol negative consequences through their associations with distress tolerance and drinking to cope. Method: A sample of 3,763 (71.9% female) college students who drink alcohol from seven countries (U.S., Argentina, Canada, Uruguay, Spain, South Africa, and England) completed online surveys. Path analysis was performed within the whole sample testing the serial unique associations between ACEs→distress tolerance→drinking to cope→negative alcohol-related consequences. Multi-group analysis was performed to determine if the proposed pathways were invariant across gender and countries. Results: Both distress tolerance and drinking to cope uniquely accounted for the relationship between ACEs and negative alcohol-related consequences. Additionally, a significant double-mediation effect was found illustrating that a higher endorsement of ACEs was associated with lower distress tolerance, which in turn was associated with higher drinking to cope, which in turn was associated with more negative alcohol-related consequences. These effects were invariant across countries and gender groups. Conclusions: These findings provide support for the relevance of distress tolerance and coping motives as potential factors in linking ACEs to problematic alcohol use across nations. Our data are consistent with the idea that intervening on distress tolerance and drinking motives could mitigate downstream alcohol-related consequences related to ACEs in college student populations around the world. [ABSTRACT FROM AUTHOR]

PURPOSE: The aim of this study was to assess the cost-effectiveness of using next-generation sequencing (NGS) versus single-gene testing (SgT) for the detection of genetic molecular subtypes and oncogenic markers in patients with advanced non–small-cell lung cancer (NSCLC) in the setting of Spanish reference centers. METHODS: A joint model combining decision tree with partitioned survival models was developed. A two-round consensus panel was performed to describe clinical practice of Spanish reference centers, providing data on testing rate, prevalence of alterations, turnaround times, and treatment pathways. Treatment efficacy data and utility values were obtained from the literature. Only direct costs (euros, 2022), obtained from Spanish databases, were included. A lifetime horizon was considered, so a 3% discount rate for future costs and outcomes was considered. Both deterministic and probabilistic sensitivity analyses were performed to assess uncertainty. RESULTS: A target population of 9,734 patients with advanced NSCLC was estimated. If NGS was used instead of SgT, 1,873 more alterations would be detected and 82 more patients could potentially be enrolled in clinical trials. In the long term, using NGS would provide 1,188 additional quality-adjusted life-years (QALYs) in the target population compared with SgT. On the other hand, the incremental cost of NGS versus SgT in the target population was €21,048,580 euros for a lifetime horizon (€1,333,288 for diagnosis phase only). The obtained incremental cost-utility ratios were €25,895 per QALY gained, below the standard cost-effectiveness thresholds. CONCLUSION: Using NGS in Spanish reference centers for the molecular diagnosis of patients with metastatic NSCLC would be a cost-effective strategy over SgT. Cost-effectiveness analysis of NGS vs SgT for mNSCLC diagnosis in Spanish reference centers [ABSTRACT FROM AUTHOR]

Simple Summary: In this report, we studied the role of the LIPI score, a biological score based on 2 factors, derived neutrophils/(leukocytes minus neutrophils) ratio and lactate dehydrogenase, in population with unresectable urothelial cancer treated with immune checkpoint inhibitor (ICI). This score was associated with clinical outcomes for ICI in several tumor types. In total, 137 and 541 patients were respectively enrolled in a retrospective ICI cohort and a validation cohort. LIPI classified the population of these cohorts in good (52–56%), intermediate (35–36%) and poor (9–12%) prognosis groups. Poor LIPI was associated with a poorer OS for the 2 cohorts. In patients with good prognosis according to the Bellmunt score, LIPI identifies a subset of patients with poorer outcomes. To conclude the LIPI score was associated with survival in unresectable urothelial cancer patients treated by ICI. Future prospective studies will be required to test the combination of Bellmunt score and LIPI score as a more accurate prognosis tool. Few prognostic factors have been identified in patients with metastatic urothelial carcinoma (mUC) treated with immune checkpoint inhibitors (ICIs). The Lung Immune Prognostic Index (LIPI) was associated with clinical outcomes for ICIs in several tumor types. We aim to assess the value of the LIPI in patients with mUC treated with ICIs. A retrospective ICI cohort and a validation cohort (SAUL cohort) included, respectively, patients with mUC treated with ICI in 8 European centers (any line) and patients treated with atezolizumab in a second or further line. A chemotherapy-only cohort was also analyzed. The LIPI score was based on 2 factors, derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) > 3 and lactate dehydrogenase > upper limit of normal, and defined 3 prognostic groups. The association of LIPI with progression-free survival (PFS) and overall survival (OS) was assessed. In the ICI and SAUL cohorts, 137 and 541 patients were respectively analyzed. In the ICI cohort, mPFS and mOS were 3.6 mo (95% CI; 2.6–6.0) and 13.8 mo (95% CI; 11.5–23.2) whereas in the SAUL cohort the mPFS and mOS were 2.2 mo (95% CI; 2.1–2.3) and 8.7 mo (95% CI; 7.8–9.9) respectively. The LIPI classified the population of these cohorts in good (56%; 52%), intermediate (35%; 36%) and poor (9%; 12%) prognostic groups (values for the ICI and SAUL cohorts respectively). Poor LIPI was associated with a poorer OS in both cohorts: hazard ratio (HR) for the ICI cohort = 2.69 (95% CI; 1.24–5.84, p = 0.035); HR = 2. 89 for the SAUL cohort (CI 95%: 1.93–4.32, p < 0.0001). Similar results were found in the chemo cohort. The LIPI score allows to identify different subgroups in patients with good prognostis according to the Bellmunt score criteria, with a subset of patients with poorer outcomes having an mOS of 3.7 mo compared to the good and intermediate LIPI subgroups with mOS of 17.9 and 7.4 mo, respectively. The LIPI score was associated with survival in mUC patients treated by ICIs. Future prospective studies will be required to test the combination of Bellmunt score and the LIPI score as a more accurate prognosis tool. [ABSTRACT FROM AUTHOR]

Purpose of review: To describe the biological rationale of peripheral blood cells (PBC)–derived inflammatory indexes and assess the related prognostic scores for patients with advanced non-small cell lung cancer (aNSCLC) treated with immune-checkpoint inhibitors (ICI). Recent findings: Inflammatory indexes based on PBC may indicate a pro-inflammatory condition affecting the immune response to cancer. The lung immune prognostic index (LIPI), consisting of derived neutrophils-to-lymphocyte ratio (NLR) and lactate dehydrogenase, is a validated prognostic tool, especially for pretreated aNSCLC patients, where the combination of NLR and PD-L1 tumour expression might also be predictive of immunotherapy benefit. In untreated high-PD-L1 aNSCLC patients, the Lung-Immune-Prognostic score (LIPS), including NLR, ECOG PS and concomitant steroids, is prognostic, and its modified version might indicate patients with favourable outcomes despite an ECOG PS of 2. NLR times platelets (i.e., SII), included in the NHS-Lung score, might improve the prognostication for combined chemoimmunotherapy. Summary: PBC-derived inflammatory indexes and related scores represent accurate, reproducible and non-expensive prognostic tools with clinical and research utility. [ABSTRACT FROM AUTHOR]

Exposure to radon progeny results in heterogeneous dose distributions in many different spatial scales. The aim of this review is to provide an overview on the state of the art in epidemiology, clinical observations, cell biology, dosimetry, and modelling related to radon exposure and its association with lung cancer, along with priorities for future research. Particular attention is paid on the effects of spatial variation in dose delivery within the organs, a factor not considered in radiation protection. It is concluded that a multidisciplinary approach is required to improve risk assessment and mechanistic understanding of carcinogenesis related to radon exposure. To achieve these goals, important steps would be to clarify whether radon can cause other diseases than lung cancer, and to investigate radon-related health risks in children or persons at young ages. Also, a better understanding of the combined effects of radon and smoking is needed, which can be achieved by integrating epidemiological, clinical, pathological, and molecular oncology data to obtain a radon-associated signature. While in vitro models derived from primary human bronchial epithelial cells can help to identify new and corroborate existing biomarkers, they also allow to study the effects of heterogeneous dose distributions including the effects of locally high doses. These novel approaches can provide valuable input and validation data for mathematical models for risk assessment. These models can be applied to quantitatively translate the knowledge obtained from radon exposure to other exposures resulting in heterogeneous dose distributions within an organ to support radiation protection in general. [ABSTRACT FROM AUTHOR]

Simple Summary: The Lung Immune Prognostic Index (LIPI) is a score that combines pretreatment dNLR (neutrophils/(leukocytes − neutrophils) and lactate dehydrogenase (LDH) and is correlated with outcomes in patients with non-small-cell lung cancer treated with anti PD-(L)1 but has not been validated in an older cohort of patients. LIPI is associated with poorer overall survival in older patients. LIPI is a simple and accessible worldwide tool that could serve as a prognostic factor and can be useful in identifying patients who will not benefit from such treatment. Immunotherapy with immune checkpoint blockers (ICB) represents a valid therapeutic option in older patients for several solid cancer types. However, most of the data concerning efficacy and adverse events of ICB available are derived from younger and fitter patients. Reliable biomarkers are needed to better select the population that will benefit from ICB especially in older patients who may be at a higher risk of developing immune-related adverse events (irAEs) with a greater impact on their quality of life. The Lung Immune Prognostic Index (LIPI) is a score that combines pretreatment dNLR (neutrophils/[leukocytes − neutrophils]) and lactate dehydrogenase (LDH) and is correlated with outcomes in patients treated with ICB in non-small-cell lung cancer. We aimed to assess the impact of LIPI in ICB outcomes in a dedicated cohort of older patients. The primary objective was to study the prognostic role of LIPI score in patients aged 70 years or above in a real-life population treated with anti-programmed death-(ligand)1 (anti PD-(L)1). dNLR and LDH were collected in a prospective cohort of patients aged 70 years or above treated with PD-(L)1 inhibitors with metastatic disease between June 2014 and October 2017 at Gustave Roussy. LIPI categorizes the population into three different prognostic groups: good (dNLR ≤ 3 and LDH ≤ ULN—upper normal limit), intermediate (dNLR > 3 or LDH > ULN), and poor (dNLR > 3 and LDH > ULN). Anti PD-(L)1 benefit was analyzed according to overall survival (OS), progression free survival (PFS), and overall response rate (ORR) using RECIST v1.1. criteria. In the 191 older patients treated, most of them (95%) were ICB-naïve, and 160 (84%) had an ECOG performance status of 0–1 with a median age at ICB treatment of 77 (range, 70–93). The most common tumor types were melanoma (66%) and non-small-cell lung cancer (15%). The median follow-up duration was 18.8 months (95% CI 14.7–24.2). LIPI classified the population into three different groups: 38 (23%) patients had a good LIPI score, 84 (51%) had an intermediate LIPI score, and 43 (26%) had a poor LIPI score. The median OS was 20.7 months [95% CI, 12.6–not reached] compared to 11.2 months [95% CI, 8.41–22.2] and 4.7 months [95% CI, 2.2–11.3] in patients with a good, intermediate, and poor LIPI score, respectively (p = 0.0003). The median PFS was 9.2 months [95% CI, 6.2–18.1] in the good LIPI group, 7.2 months [95% CI, 5.4–13] in the intermediate LIPI group, and 3.9 months [95% CI, 2.3–8.2] in the poor LIPI group (p = 0.09). The rate of early death (OS < 3 months) was 37% in the poor LIPI group compared to 5% in the good LIPI group (<0.001). Poor LIPI score was associated with a poorer outcome in older patients treated with anti PD-(L)1. LIPI is a simple and accessible worldwide tool that can serve as a prognostic factor and can be useful for stratification benefit from ICB. [ABSTRACT FROM AUTHOR]

Immunotherapy has dramatically changed the therapeutic landscape of oncology, and has become standard of care in multiple cancer types in front or late lines of therapy, with some longstanding responses and outstanding results. Notwithstanding, its use has brought a totally unique spectrum of adverse events, characterized by a myriad of diverse manifestations affecting nearly every organ and system of the body, including the endocrine, nervous, cardiac, respiratory and gastrointestinal systems. Uncommon adverse events, defined as those occurring in less than 1% of patients, comprise an even more heterogeneous group of diseases that are being seen more recurrently as the use of immune check-point inhibitors increases and indications spread in different tumor types and stages. Here, we comprehensively review some uncommon, but exceedingly important, immune-related adverse events, with special emphasis in the clinical approach and diagnostic workup, aiming to reunite the evidence published previously, allowing an increase in awareness and knowledge from all specialists implicated in the diagnosis, treatment, and care of cancer patients treated with immunotherapy. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop a 60-item, abridged form of the Junior Spanish version of the NEO-PI-R (JS NEO-A60), consisting of 12 items per dimension. A sample of 399 high school students completed two personality scales to examine the factor structure (Exploratory Structural Equation Model), reliability and convergent validity of the JS NEO-A60. Our sample also completed several consequential life outcome measures in order to examine criterion validity. The five-factor structure, along with representation of the majority of lower-order facets, was satisfactorily covered by the JS NEO-A60. Sources of reliability (internal consistency and test-retest) and validity (convergent) were adequate. The life outcome variables revealed links to personality traits in the expected direction. Namely, internalizing emotional symptoms (anxiety and depression) were mainly predicted by emotional instability. Symptoms of behavioral problems (aggression and antisocial behavior) were predicted by low scores in both agreeableness and conscientiousness. Life satisfaction was significantly predicted by emotional stability. Last, academic performance via students' grades was predicted by conscientiousness and openness. We conclude that the JS NEO-A60 is a sound inventory to assess the five broad personality domains in Spanish-speaking adolescents. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy has been positioned as frontline therapy for advanced non-small cell lung cancer (NSCLC), alone when PD-L1 tumor expression is high, or combined with chemotherapy otherwise. However, 50% of the patients do not respond to the treatment and the mechanisms of resistance are not well defined. Moreover, it is not clear whether chemo-immunotherapy could be advantageous in high PD-L1 tumor expression. We have found that baseline circulating low-density neutrophils (LDN) identify a subset of patients intrinsically refractory to immunotherapy. Interestingly, responses can be achieved with CT+IT, detecting a progressive depletion of LDN. Besides the potential role as predictive biomarker we observed that resistance was mediated by soluble molecules related with the HGF/c-MET pathway. Our findings establish circulating myeloid cells as one of the main mediators of resistance to immunotherapy in NSCLC, and give a rationale for potential drug combinations that might improve the outcomes. Single-agent immunotherapy has been widely accepted as frontline treatment for advanced non-small cell lung cancer (NSCLC) with high tumor PD-L1 expression, but most patients do not respond and the mechanisms of resistance are not well known. Several works have highlighted the immunosuppressive activities of myeloid subpopulations, including low-density neutrophils (LDNs), although the context in which these cells play their role is not well defined. We prospectively monitored LDNs in peripheral blood from patients with NSCLC treated with anti-PD-1 immune checkpoint inhibitors (ICIs) as frontline therapy, in a cohort of patients treated with anti-PD1 immunotherapy combined with chemotherapy (CT+IT), and correlated values with outcomes. We explored the underlying mechanisms through ex vivo experiments. Elevated baseline LDNs predict primary resistance to ICI monotherapy in patients with NSCLC, and are not associated with response to CT+IT. Circulating LDNs mediate resistance in NSCLC receiving ICI as frontline therapy through humoral immunosuppression. A depletion of this population with CT+IT might overcome resistance, suggesting that patients with high PD-L1 tumor expression and high baseline LDNs might benefit from this combination. The activation of the HGF/c-MET pathway in patients with elevated LDNs revealed by quantitative proteomics supports potential drug combinations targeting this pathway. [ABSTRACT FROM AUTHOR]

In recent years, major advances have been achieved in our understanding of non-small-cell lung cancer (NSCLC) with oncogenic driver alterations and in the specific treatment of these with tyrosine kinase inhibitors. Currently, state-of-the-art management of patients with NSCLC (particularly adenocarcinoma or non-adenocarcinoma but with mild tobacco exposure) consists of the determination of EGFR, ALK, ROS1 and BRAF status, as they have US FDA and EMA approved targeted therapies. The increase in molecular knowledge of NSCLC and the development of drugs against other targets has settled new therapeutic indications. In this review we have incorporated the development around MET, KRAS and NTRK in the diagnosis of NSCLC given the therapeutic potential that they represent, as well as the drugs approved for these indications. [ABSTRACT FROM AUTHOR]

Simple Summary: Radon represents the main risk factor of lung cancer in non-smokers and the second one in smoking patients. In Europe, there are several radon-prone areas, but regulatory policies may vary between countries. Radon causes DNA damage and high genomic tumor instability, but its exact carcinogenesis mechanism in lung cancer remains unknown. Molecular drivers in NSCLC are more often described in non-smoker patients and a potential association between radon exposure and oncogenic-driven NSCLC has been postulated. This is an updated review on indoor radon exposure and its role in lung cancer carcinogenesis, especially focusing on its potential relation with NSCLC with driver genomic alterations. We want to contribute to rising knowledge and awareness on this still silent but preventable lung cancer risk factor. Lung cancer is a public health problem and the first cause of cancer death worldwide. Radon is a radioactive gas that tends to accumulate inside homes, and it is the second lung cancer risk factor after smoking, and the first one in non-smokers. In Europe, there are several radon-prone areas, and although the 2013/59 EURATOM directive is aimed to regulate indoor radon exposition, regulating measures can vary between countries. Radon emits alpha-ionizing radiation that has been linked to a wide variety of cytotoxic and genotoxic effects; however, the link between lung cancer and radon from the genomic point of view remains poorly described. Driver molecular alterations have been recently identified in non-small lung cancer (NSCLC), such as somatic mutations (EGFR, BRAF, HER2, MET) or chromosomal rearrangements (ALK, ROS1, RET, NTRK), mainly in the non-smoking population, where no risk factor has been identified yet. An association between radon exposure and oncogenic NSCLC in non-smokers has been hypothesised. This paper provides a practical, concise and updated review on the implications of indoor radon in lung cancer carcinogenesis, and especially of its potential relation with NSCLC with driver genomic alterations. [ABSTRACT FROM AUTHOR]

The Community Reinforcement Approach Happiness Scale (CRA-HS) is widely used for assessing the quality of life in addiction treatment, but the amount of research on the psychometric properties has been scant. The present study sought to (a) test for measurement invariance of the CRA-HS across college students (n = 3388) in five countries (i.e., United States., Spain, Argentina, Uruguay, and the Netherlands); (b) evaluate differences on the CRA-HS (i.e., latent mean differences) as a function of sex and country, and (c) compare criterion-related validity. Using multi-group confirmatory factor analyses, we found a shortened 10-item version of the CRA-HS to be invariant across sex, but only configural and metric invariance was found across countries. Across all countries, criterion-related validity of the CRA-HS scores across different countries emerged. Our findings serve as a foundation for future cross-cultural work testing models in which subjective well-being (i.e., happiness) is an important clinical/routine outcome among college students. [ABSTRACT FROM AUTHOR]

The study of the bifactor structure of psychopathology, which includes a general factor of psychopathology (or p factor) in addition to the internalizing and externalizing factors, has gained attention. However, its associations with the Five-Factor Model (FFM) of personality has been addressed in few studies, and none has examined different plausible etiological models (i.e., continuity, pathoplasty, complication) to explain its relationship, which is the aim of the present research. Additionally, the longitudinal association of the General Factor of Personality (GFP) and the p factor will be also explored. Personality and psychopathological symptoms of high school students were assessed at three time points (once a year) (n = 655; M = 13.79, SD = 1.24; 49.8% girls). Confirmatory Factor Analysis (and measurement invariance across waves) were tested for the traits, the GFP and the bifactor model of psychopathology. While the bifactor model and the one-factor solution for each personality trait displayed good fit to the data and remained invariant over time, the structure of the GFP was adequate and invariant in two of the three waves. The resulting factors were included in cross-lagged panel models and showed that the FFM traits and the psychopathology factors influenced each other reciprocally. Most associations fell in line with the continuity model, but minor pathoplastic and complication effects were also reported. Similar associations were found between the GFP and the p factor. These results suggest that interventions in riskier personality profiles might prevent the development of general and more specific psychopathology spectra. [ABSTRACT FROM AUTHOR]

Immunotherapy using immune checkpoint modulators has revolutionized the oncology field, emerging as a new standard of care for multiple indications, including non-small cell lung cancer (NSCLC). However, prognosis for patients with lung cancer is still poor. Although immunotherapy is highly effective in some cases, not all patients experience significant or durable responses, and further strategies are needed to improve outcomes. Therapeutic cancer vaccines are designed to exploit the body's immune system to activate long-lasting memory against tumor cells that ensure tumor regression, with minimal toxicity. A unique feature of cancer vaccines lies in their complementary approach to boost antitumor immunity that could potentially act synergistically with immune checkpoint inhibitors (ICIs). However, single-line immunization against tumor epitopes with vaccine-based therapeutics has been disappointingly unsuccessful, to date, in lung cancer. The high level of success of several recent vaccines against SARS-CoV-2 has highlighted the evolving advances in science and technology in the vaccines field, raising hope that this strategy can be successfully applied to cancer treatments. In this review, we describe the biology behind the cancer vaccines, and discuss current evidence for the different types of therapeutic cancer vaccines in NSCLC, including their mechanisms of action, current clinical development, and future strategies. [ABSTRACT FROM AUTHOR]

Introduction: Circulating tumor DNA (ctDNA) testing may identify patients at high risk for recurrence following chemoradiation (CRT) for locally advanced non-small cell lung cancer (LA-NSCLC). We evaluated the feasibility of ctDNA testing on a readily available commercial fixed-gene panel to predict outcomes in patients with LA-NSCLC. Methods: Plasma of 43 patients was collected at CRT initiation (pre-CRT), completion (post-CRT1), quarterly follow up for 12 months (post-CRT2, 3, 4, 5 respectively) after CRT, and at disease progression. ctDNA analysis was performed using InVisionFirst®-Lung to detect mutations in 36 cancer-related genes. ctDNA clearance was defined as absence of pre-CRT variants at post-CRT1. Patients without detectable pre-CRT variants or no post-CRT1 samples were excluded. Results: Twenty eight of 43 patients (65%) had detectable variants pre-CRT. Nineteen of 43 patients (44%) had detectable pre-CRT variants and post-CRT1 samples and were included in analysis. Median age at diagnosis was 65 years (43-82), and most patients had stage IIIB disease (10/19, 53%). Two patients died from non-cancer related causes before post-CRT2 and were excluded from further analysis. All three patients who did not clear ctDNA had tumor relapse with a median time to relapse of 74 days (30-238), while 50% (7/14) of those who cleared ctDNA have remained disease free. Progression free survival was longer in patients who cleared ctDNA compared to those who did not (median 567 vs 74 d, p = 0.01). Conclusions: Although it is feasible to use ctDNA testing on a limited gene panel to identify patients with LA-NSCLC who are at high risk for disease recurrence following CRT, further studies will be necessary to optimize these assays before they can be used to inform clinical care in patients with lung cancer. [ABSTRACT FROM AUTHOR]

Background: Problematic cannabis use is common among young adults across the world. However, limited research has examined whether etiological models predicting negative consequences are universal.Objective: The present study examined whether the Five-Factor Model of personality (openness, conscientiousness, extraversion, agreeableness, and neuroticism) relates to cannabis outcomes via use of cannabis protective behavioral strategies (PBS) in a cross-national sample of college student cannabis users (i.e., used cannabis in the last 30 days).Method: Participants were 1175 university students (63.27% female) across five countries (United States, Argentina, Spain, Uruguay, and the Netherlands) recruited to complete an online survey.Results: PBS use mediated the associations between personality traits and cannabis consequences, such that higher conscientiousness (β = .20), agreeableness (β = .11), and lower emotional stability [i.e., higher neuroticism] (β = -.14) were associated with more PBS use. Higher PBS use was, in turn, associated with lower frequency of cannabis use (β = -.32); lower frequency of use was then associated with fewer cannabis consequences (β = .34). This sequential pathway was invariant across sex, but not countries. Notably, there were a number of differences in links between PBS and cannabis outcomes when comparing countries (e.g., negative associations in the US sample, but positive associations in the Argentina sample).Conclusions: Cannabis PBS mediates the relationship between personality traits and cannabis outcomes, but there are nuanced differences across countries (i.e., relationship between PBS and cannabis outcomes). Overall, students that are low in conscientiousness, agreeableness, and neuroticism and/or report low rates of PBS use may benefit from cannabis PBS-focused interventions that promote utilization of PBS. [ABSTRACT FROM AUTHOR]

TGF-β is secreted in the tumour microenvironment in a latent, inactive form bound to latency associated protein and activated by the integrin αV subunit. The activation of latent TGF-β by cancer-cell-expressed αV re-shapes the tumour microenvironment, and this could affect patient responses to PD-1-targeting therapy. Here we show, using multiplex immunofluorescence staining in cohorts of anti-PD-1 and anti-PD-L1-treated lung cancer patients, that decreased expression of cancer cell αV is associated with improved immunotherapy-related, progression-free survival, as well as with an increased density of CD8+CD103+ tumour-infiltrating lymphocytes. Mechanistically, tumour αV regulates CD8 T cell recruitment, induces CD103 expression on activated CD8+ T cells and promotes their differentiation to granzyme B-producing CD103+CD69+ resident memory T cells via autocrine TGF-β signalling. Thus, our work provides the underlying principle of targeting cancer cell αV for more efficient PD-1 checkpoint blockade therapy. Response to PD-1 checkpoint blockade is unpredictable in lung cancer patients. Here authors show in human lung and mouse tumour models that low or absent αV integrin expression leads to better tumour growth control by anti-PD-1 via reduced TGF-β activation and hence increased infiltration of anti-tumour CD8+ T cells. [ABSTRACT FROM AUTHOR]

Gatekeeper mutations are identified in only 50% of the cases at resistance to Anaplastic Lymphoma Kinase (ALK)-tyrosine kinase inhibitors (TKIs). Circulating tumor cells (CTCs) are relevant tools to identify additional resistance mechanisms and can be sequenced at the single-cell level. Here, we provide in-depth investigation of copy number alteration (CNA) heterogeneity in phenotypically characterized CTCs at resistance to ALK-TKIs in ALK-positive non-small cell lung cancer. Single CTC isolation and phenotyping were performed by DEPArray or fluorescence-activated cell sorting following enrichment and immunofluorescence staining (ALK/cytokeratins/CD45/Hoechst). CNA heterogeneity was evaluated in six ALK-rearranged patients harboring ≥ 10 CTCs/20 mL blood at resistance to 1st and 3rd ALK-TKIs and one presented gatekeeper mutations. Out of 82 CTCs isolated by FACS, 30 (37%) were ALK+/cytokeratins-, 46 (56%) ALK-/cytokeratins+ and 4 (5%) ALK+/cytokeratins+. Sequencing of 43 CTCs showed highly altered CNA profiles and high levels of chromosomal instability (CIN). Half of CTCs displayed a ploidy >2n and 32% experienced whole-genome doubling. Hierarchical clustering showed significant intra-patient and wide inter-patient CTC diversity. Classification of 121 oncogenic drivers revealed the predominant activation of cell cycle and DNA repair pathways and of RTK/RAS and PI3K to a lower frequency. CTCs showed wide CNA heterogeneity and elevated CIN at resistance to ALK-TKIs. The emergence of epithelial ALK-negative CTCs may drive resistance through activation of bypass signaling pathways, while ALK-rearranged CTCs showed epithelial-to-mesenchymal transition characteristics potentially contributing to ALK-TKI resistance. Comprehensive analysis of CTCs could be of great help to clinicians for precision medicine and resistance to ALK-targeted therapies. [ABSTRACT FROM AUTHOR]

Copyright of Adicciones is the property of Sociedad Cientifica Espanola de Estudios sobre el Alcohol and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The present research built on the Self-Reported Delinquency interview and the Antisocial Behavior Scale to develop an updated brief instrument to measure antisocial behavior. College students (n = 3188, 67.75% women) from the USA, Argentina, the Netherlands and Spain completed an online survey. Analyses that combined approaches from the Classical Test Theory and Item Response Theory were conducted to select the items for the brief version. Findings suggested that a 13-item Brief Antisocial Behavior Scale (B-ABS) fulfilled the high-quality criteria: salient factor loadings, adequate discrimination, variability in response endorsement, adequate fit based on infit/outfit values, nondifferent item functioning across the four participating countries, and Cronbach's alpha and ordinal omega coefficients higher than.70. The B-ABS scores generally significantly correlated with personality scores, mental health and marijuana outcomes, showing criterion-related validity evidence. Our overall findings suggest that B-ABS adequately assesses antisocial behavior in young adults from different countries/cultures. [ABSTRACT FROM AUTHOR]

Background. Immunotherapy represents one of the fundamental treatments in the management of some types of cancer, especially malignant melanoma. Toxicity derived from increased immune system activity can manifest in multiple organs and systems. We present a case of hematological toxicity, manifested as hemophagocytic syndrome (HPS), which was successfully treated with an anti-interleukin-6 antibody (tocilizumab). Case Report. This case presents a 75-year-old woman diagnosed with metastatic choroidal melanoma, refractory to several lines of treatment. After the failure of the previous lines, ipilimumab was started. After the third dose, she developed grade 2 thrombocytopenia and anemia accompanied by elevated levels of ferritin, triglycerides, and decreased fibrinogen. Hemophagocytosis was observed in the bone marrow biopsy, and a PET-CT showed splenomegaly with increased metabolism. Treatment was based on high doses of corticosteroids and tocilizumab. Four days after the start of treatment, progressive clinical and analytical improvement was observed, achieving total remission of the condition. Discussion. HPS induced by immunotherapy is due to an immunorelated cytokine storm syndrome (CSS). The administration of the anti-interleukin-6 receptor antibody drug acted on this cytokine cascade, leading to stabilization and subsequent remission. For this reason, the use of tocilizumab should be part of the immunotherapy-induced HPS treatment algorithm. [ABSTRACT FROM AUTHOR]

The impact of violent video game exposure (VVGE) on aggressive behaviors has been extensively explored, but still remains controversial. Although some studies have shown slight detrimental short-term effects of VVGE, other studies have failed to find any consequence. In addition, the existence of long-lasting effects on aggressiveness, or their impact on adolescents, are still not well established. One limitation of most of these studies is that they do not control for other important risk variables for aggressive behaviors, such as personality and deviant peers, nor have they investigated the possible moderation role of these risk factors in the link between VVGE and aggression. Therefore, the main aim was to examine the additive and interactive role of VVGE, personality, and deviant peers in adolescent aggressive behaviors cross-sectionally and longitudinally. Many regression analyses and a cross-lagged autoregressive model were carried out. At both waves, aggressive behavior was predicted by having deviant peers and specific personality traits, especially low agreeableness. VVGE also presented a slight but significant effect at both waves, but it became nonsignificant when controlling for other variables. No long-term effects on the relation between VVGE and aggressive behaviors were found. Some moderation effects were consistently found at both waves: when participants reported having more deviant peers, the effects of VVGE and low agreeableness on aggressive behaviors significantly increased. These findings suggest that multiple biopsychosocial variables and their complex interplay need to be examined to gain a better understanding of the origin and expression of aggressive behavior. [ABSTRACT FROM AUTHOR]

The main aim of the present study was to develop and validate a checklist for adolescents, the Life Events Inventory for Adolescents (LEIA), for screening stressful life events (SLEs) of different nature (major–minor, dependent–independent, and personal–interpersonal). The LEIA was administered together with another SLE checklist (Escala de Acontecimientos Vitales [Life Events Scale], EAV), and with measures of life satisfaction and externalizing and internalizing symptoms. The results showed that the kappa and the percentage agreement reliability indices were adequate. Regarding validity evidences, the correlations found between the LEIA and the EAV ranged from.65 to.69, and between the LEIA and the psychopathological symptoms ranged from.26 to.38. Specifically, major dependent noninterpersonal SLEs were the best predictors of externalizing psychopathology; while major independent noninterpersonal SLEs were the best predictors of internalizing symptoms and low life satisfaction. To conclude, the LEIA could be considered an adequate checklist to screen for SLEs in adolescents. [ABSTRACT FROM AUTHOR]

Gaming motives are important factors for explaining individual differences in videogame-related behaviors. The aim of the present study was to develop a new comprehensive but brief instrument–the Videogaming Motives Questionnaire (VMQ)–which embraces some of the most relevant gaming motives. In a first study, a pilot exploratory factor analysis (EFA) with data from 140 undergraduates was performed on items from twelve potential motives. This identified eight main factors: recreation, social interaction, coping, violent reward, fantasy, cognitive development, customization, and competition. In Studies 2 and 3, an EFA and a confirmatory factor analysis were performed on two independent samples of 407 adolescents and 260 young adults, respectively. The VMQ presented a robust eight-factor structure, with all scales showing adequate reliability indices. In reference to criterion validity, all motives presented specific associations with hours spent playing videogames, disordered gaming, and game genre preferences. More specifically, and in both adolescents and young adults, social interaction was the main motive related to time spent gaming, whereas disordered gaming was related to both coping and social interaction motives. Based on these findings, it is concluded that the VMQ is a brief and psychometrically appropriate tool for assessing the most relevant videogaming motives. [ABSTRACT FROM AUTHOR]

Objectives: The aim of our study was to investigate the association between driver oncogene alterations and metastatic patterns on imaging assessment, in a large cohort of metastatic lung adenocarcinoma patients. Methods: From January 2010 to May 2017, 550 patients with stage IV lung adenocarcinoma with molecular analysis were studied retrospectively including 135 EGFR-mutated, 81 ALK-rearrangement, 47 BRAF-mutated, 141 KRAS-mutated, and 146 negative tumors for these 4 mutations (4N). After review of the complete imaging report by two radiologists (junior and senior) to identify metastatic sites, univariate correlation analyzes were performed. Results: We found differences in metastatic tropism depending on the molecular alteration type when compared with the non-mutated 4N group: in the EGFR group, pleural metastases were more frequent (32% versus 20%; p = 0.021), and adrenal and node metastases less common (6% versus 23%; p < 0.001 and 11% versus 23%; p = 0.011). In the ALK group, there were more brain and lung metastases (respectively 42% versus 29%; p = 0.043 and 37% versus 24%; p = 0.037). In the BRAF group, pleural and pericardial metastases were more common (respectively 47% versus 20%; p < 0.001 and 11% versus 3%; p = 0.04) and bone metastases were rarer (21% versus 42%; p = 0.011). Lymphangitis was more frequent in EGFR, ALK, and BRAF groups (respectively 6%, 7%, and 15% versus 1%); p = 0.016; p = 0.009; and p < 0.001. Conclusion: The application of these correlations between molecular status and metastatic tropism in clinical practice may lead to earlier and more accurate identification of patients for targeted therapy. Key Points: • Bone and brain metastasis are the most common organs involved in lung adenocarcinoma but the relative incidence of each metastatic site depends on the molecular alteration. • EGFR-mutated tumors preferentially spread to the pleura and less commonly to adrenals, ALK-rearrangement tumors usually spread to the brain and the lungs, whereas BRAF-mutated tumors are unlikely to spread to bones and have a serous (pericardial ad pleural) tropism. • These correlations could help in the clinical management of patients with metastatic lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

PURPOSE: Hyperprogressive disease (HPD), fast progression (FP), and early death (ED) have been described in 13.8%, 4.7%, and 5.6% and in 5.1%, 2.8%, and 6.8%, respectively, of patients with non–small-cell lung cancer (NSCLC) treated with single-agent programmed cell death ligand 1 inhibitors (ICI) or chemotherapy, respectively. Whether FP/ED and HPD represent overlapping patterns is unknown. PATIENTS AND METHODS: FP, ED, and HPD were retrospectively assessed in patients with NSCLC treated with single-agent ICI or chemotherapy. Eligibility required 2 computed tomography (CT) scans before and 1 CT scan during treatment. (1) HPD, (2) FP, (3) ED were defined as (1) RECIST version 1.1 progression at first CT scan and tumor growth rate variation per month > 50%, (2) ≥ 50% increase in the sum of the longest diameters of target lesions within 6 weeks from baseline, and (3) death as a result of radiologic progression within 12 weeks from baseline CT scan, respectively. RESULTS: Of 406 ICI-treated NSCLC, 56 patients (13.8%), 9 patients (2.2%), and 36 patients (8.8%) were HPD, FP, and ED, respectively. Eight (14.2%) and 20 (35.7%) of 56 patients with HPD were also FP and ED. ED significantly correlated with baseline Eastern Cooperative Oncology Group performance status ≥ 2 compared with HPD (33% v 13%, P =.02). Overall survival was significantly longer for HPD (3.4 months [95% CI, 2.7 to 4.0 months]) compared with FP (0.7 months [95% CI, 0.6 to 0.8 months]); HR, 0.18 [95% CI, 0.08 to 0.42]; P <.0001) and ED (1.4 months [95% CI, 1.3 to 1.6 months]); HR, 0.19 [95% CI, 0.11 to 0.34]); P <.0001), whereas it did not differ between FP and ED (HR, 1.3 [95% CI, 0.56 to 3.0]; P =.55). Of 59 patients with NSCLC treated with single-agent chemotherapy, the HPD, FP, and ED rates were 5.1%, 1.7%, and 6.7%, respectively. CONCLUSION: FP, ED, and HPD represent distinct progression patterns with limited overlap and different survival outcomes. [ABSTRACT FROM AUTHOR]

Circulating tumor DNA (ctDNA)-based molecular profiling is rapidly gaining traction in clinical practice of advanced cancer patients with multi-gene next-generation sequencing (NGS) panels. However, clinical outcomes remain poorly described and deserve further validation with personalized treatment of patients with genomic alterations detected in plasma ctDNA. Here, we describe the outcomes, disease control rate (DCR) at 3 months and progression-free survival (PFS) in oncogenic-addicted advanced NSCLC patients with actionable alterations identified in plasma by ctDNA liquid biopsy assay, InVisionFirst®-Lung. A pooled retrospective analysis was completed of 81 advanced NSCLC patients with all classes of alterations predicting response to current FDA approved drugs: sensitizing common EGFR mutations (78%, n = 63) with T790M (73%, 46/63), ALK / ROS1 gene fusions (17%, n = 14) and BRAF V600E mutations (5%, n = 4). Actionable driver alterations detected in liquid biopsy were confirmed by prior tissue genomic profiling in all patients, and all patients received personalized treatment. Of 82 patients treated with matched targeted therapies, 10% were at first-line, 41% at second-line, and 49% beyond second-line. Acquired T790M at TKI relapse was detected in 73% (46/63) of patients, and all prospective patients (34/46) initiated osimertinib treatment based on ctDNA results. The 3-month DCR was 86% in 81 evaluable patients. The median PFS was of 14.8 months (12.1–22.9m). Baseline ctDNA allelic fraction of genomic driver did not correlate with the response rate of personalized treatment (p = 0.29). ctDNA molecular profiling is an accurate and reliable tool for the detection of clinically relevant molecular alterations in advanced NSCLC patients. Clinical outcomes with targeted therapies endorse the use of liquid biopsy by amplicon-based NGS ctDNA analysis in first line and relapse testing for advanced NSCLC patients. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to evaluate if imaging biomarkers on FDG PET are associated with clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). Methods: In this retrospective monocentric study, we included 109 patients with advanced NSCLC who underwent baseline FDG PET/CT before ICI initiation between July 2013 and September 2018. Clinical, biological (including dNLR = neutrophils/[leukocytes minus neutrophils]), pathological and PET parameters (tumor SUVmax, total metabolic tumor volume [TMTV]) were evaluated. A multivariate prediction model was developed using Cox models for progression-free survival (PFS) and overall survival (OS). The association between biomarkers on FDG PET/CT and disease clinical benefit (DCB) was tested using logistic regression. Results: Eighty patients were eligible. Median follow-up was 11.6 months (95%CI 7.7–15.5). Sixty-four and 52 patients experienced progression and death, respectively. DCB was 40%. In multivariate analyses, TMTV > 75 cm3 and dNLR > 3 were associated with shorter OS (HR 2.5, 95%CI 1.3–4.7 and HR 3.3, 95%CI 1.6–6.4) and absence of DCB (OR 0.3, 95%CI 0.1–0.9 and OR 0.4, 95%CI 0.2–0.9). Unlike TMTV, dNLR was a significant prognostic factor for PFS (HR 1.9, 95%CI 1.1–3.3) along with anemia (HR 1.9, 95%CI 1.2–3.8). No association was observed between tumor SUVmax and PFS or OS. Conclusion: Baseline tumor burden (TMTV) on FDG PET/CT scans and inflammatory status (dNLR) were associated with poor OS and absence of DCB for ICI treatment in advanced NSCLC patients, unlike tumor SUVmax, and may be used together to improve the selection of appropriate candidates. [ABSTRACT FROM AUTHOR]

PURPOSE: Liquid biopsy specimen genomic profiling is integrated in non–small-cell lung cancer (NSCLC) guidelines; however, data on the clinical relevance for ALK /ROS1 alterations are scarce. We evaluated the clinical utility of a targeted amplicon-based assay in a large prospective cohort of patients with ALK/ROS1 -positive NSCLC and its impact on outcomes. PATIENTS AND METHODS: Patients with advanced ALK/ROS1 -positive NSCLC were prospectively enrolled in the study by researchers at eight French institutions. Plasma samples were analyzed using InVisionFirst-Lung and correlated with clinical outcomes. RESULTS: Of the 128 patients included in the study, 101 were positive for ALK and 27 for ROS1 alterations. Blood samples (N = 405) were collected from 29 patients naïve for treatment with tyrosine kinase inhibitors (TKI) or from 375 patients under treatment, including 105 samples collected at disease progression (PD). Sensitivity was 67% (n = 18 of 27) for ALK/ROS1 fusion detection. Higher detection was observed for ALK fusions at TKI failure (n = 33 of 74; 46%) versus in patients with therapeutic response (n = 12 of 109; 11%). ALK -resistance mutations were detected in 22% patients (n = 16 of 74) overall; 43% of the total ALK -resistance mutations identified occurred after next-generation TKI therapy. ALK G1202R was the most common mutation detected (n = 7 of 16). Heterogeneity of resistance was observed. ROS1 G2032R resistance was detected in 30% (n = 3 of 10). The absence of circulating tumor DNA mutations at TKI failure was associated with prolonged median overall survival (105.7 months). Complex ALK -resistance mutations correlated with poor overall survival (median, 26.9 months v NR for single mutation; P =.003) and progression-free survival to subsequent therapy (median 1.7 v 6.3 months; P =.003). CONCLUSION: Next-generation, targeted, amplicon-based sequencing for liquid biopsy specimen profiling provides clinically relevant detection of ALK/ROS1 fusions in TKI-naïve patients and allows for the identification of resistance mutations in patients treated with TKIs. Liquid biopsy specimens from patients treated with TKIs may affect clinical outcomes and capture heterogeneity of TKI resistance, supporting their role in selecting sequential therapy. [ABSTRACT FROM AUTHOR]

Mindful individuals are able to acknowledge mind wandering and live in the present moment in a nonjudgmental way. Previous studies have found that both mind wandering and mindfulness are associated with subjective well-being. However, the main predictor of happiness is personality; more specifically, happier people are emotionally stable and extraverted. The present study aimed to explore the contribution of the five factors of personality, dispositional mindfulness facets and a mindfulness intervention to happiness. A sample of 372 university students was assessed with the NEO-Five Factor Inventory, and another sample of 217 community adults answered the Big Five Personality Trait Short Questionnaire. Both samples, 589 participants in all, completed the Five Facet Mindfulness Questionnaire and the Subjective Happiness Scale. Furthermore, 55 participants from the general population sample took a 6-week training course in meditation and developing mindfulness. The regression analyses showed that emotional stability and extraversion traits were the strongest predictors of subjective well-being. Nonetheless, the nonjudging facet, which is nonevaluative/acceptance awareness of thoughts and feelings, still remained a significant predictor of happiness when personality was accounted for. Finally, mindfulness training did not increase subjective well-being. Being nonjudgmental of one's inner thoughts, feelings and sensations contributes to happiness even when personality is taken into account. Accordingly, it seems reasonable that mindfulness training that intends to improve subjective well-being should focus on noticing thoughts without judging them. [ABSTRACT FROM AUTHOR]