Substance Use Motives as Mediators of the Associations between Self-Control Constructs and Negative Substance Use Consequences: A Cross-Cultural Examination.

The present study sought to examine three distinct research questions: a) are self-control constructs (i.e., negative/positive urgency, self-regulation, and emotion-regulation) indirectly related to negative alcohol/marijuana consequences via substance use motives, b) to what extent are these indirect effects consistent across differing drugs (i.e., alcohol and marijuana), and c) are these models invariant across gender and countries. Participants were 2,230 college students (mean age=20.28, SD=0.40; 71.1% females) across 7 countries (USA, Canada, Spain, England, Argentina, Uruguay, and South Africa) who consumed alcohol and marijuana in the last month. Two (one for alcohol and one for marijuana) fully saturated path models were conducted, such that indirect paths were examined for each self-control construct and substance use motive on negative consequences (e.g., negative urgency → coping motives → negative consequences) within the same model. Within the comprehensive alcohol model, we found that lower self-regulation and higher negative urgency/suppression were related to more alcohol consequences via higher coping and conformity motives. For marijuana, we found that lower self-regulation and higher negative urgency/suppression were related to more marijuana consequences via higher coping motives (not significant for conformity motives). Unique to marijuana, we did find support for higher expansion motives indirectly linking positive urgency to more negative consequences. These results were invariant across gender groups and only minor differences across countries emerged. Prevention and intervention programs of alcohol and marijuana around university campuses may benefit from targeting self-control related skills in addition to motives to drug use to prevent and reduce negative drug-related consequences.

Big five personality traits, gaming motives, and regular and disordered gaming: A cross-national examination among college student gamers in seven countries.

INTRODUCTION: Previous research has shown that personality traits and gaming motives are important predictors for explaining regular and disordered gaming. However, the mediating role of gaming motives in the relation between personality traits and video game outcomes (e.g., time spent gaming or disordered gaming) has been scarcely studied and limited cross-national studies have addressed this issue. The present study aimed to examine the direct and indirect effects of the Big Five personality traits on weekly gaming and disordered gaming via gaming motives across seven countries. METHOD: 3540 college student gamers (59.5% women) from the U.S., Canada, Spain, Argentina, Uruguay, South Africa and England completed the online survey. Structural equation modeling was conducted to test models. Multigroup models were employed to test model invariance across countries. RESULTS: Significant, albeit weak, relations were found between personality traits and gaming outcomes, and were mediated mostly by coping motives in predicting disordered gaming, and by social interaction and recreation (to a lesser extent) motives in predicting weekly gaming. Some minor, yet significant, differences across countries appeared and are discussed in detail. DISCUSSION: The present findings indicate that the differential interrelations between personality traits, gaming motives, and video gaming outcomes may be generalized in college students across countries.

Tackling Non-Small Cell Lung Cancer in Young Adults: From Risk Factors and Genetic Susceptibility to Lung Cancer Profile and Outcomes.

Lung cancer has traditionally been associated with advanced age; however, its increasing incidence among young adults raises concerning questions regarding its etiology and unique considerations for this population. In contrast to the older population, the onset of lung cancer at younger age may be attributed to a complex interplay of incompletely understood individual susceptibility and prevalent environmental risk factors beyond tobacco smoke exposure, such as radon gas and air pollution, which are widespread globally. Consequently, this leads to distinct clinical and molecular profiles, requiring a tailored approach. Furthermore, a diagnosis of cancer represents a threatening event during the prime years of a young person's life, prompting concern about career development, social aspects, fertility aspirations, and physical independence. This poses significant additional challenges for health care professionals in a field that remains underexplored. This comprehensive review recognizes lung cancer in young adults as a distinct entity, exploring its clinical and molecular characteristics, diverse predisposing factors, and priorities in terms of quality of life, with the aim of providing practical support to oncologists and enhancing our understanding of this under-researched population.

Rethinking strategies in SCLC: Lessons learned from tiragolumab in the SKYSCRAPER-02 study.

The addition of tiragolumab, an anti-TIGIT inhibitor, to chemotherapy plus atezolizumab demonstrated promising early results for lung cancer. Unfortunately, the phase 3 study SKYSCRAPER-02 did not confirm the anticipated benefit of tiragolumab combination in recalcitrant small-cell lung cancer,1 reiterating the need for a more accurate population selection in clinical trials.

The Spanish Short Dark Tetrad (SD4): Association With Personality and Psychological Problems.

BACKGROUND: The Short Dark Tetrad (SD4) is a recently developed instrument for assessing the "dark" personality traits of psychopathy, narcissism, Machiavellianism, and sadism. We aimed to examine the SD4's psychometric properties, adapting it into Spanish and exploring its structure, gender invariance, reliability, concurrent validity, and nomological network. METHOD: A sample of 668 adults (Mage = 26.36, SD = 10.64, 69.2% females) completed the SD4 and other self-report questionnaires. RESULTS: The results demonstrated sound indices of reliability and concurrent validity, an adequate four-factor structure, and support for gender invariance. Furthermore, most of the findings about the nomological network were in line with prior hypotheses: All four SD4 scales were associated with low levels of agreeableness and antagonism; psychopathy was also related to low conscientiousness, disinhibition and impulse-control problems; narcissism was positively associated with extraversion and negatively associated with internalizing symptoms; Machiavellianism was uncorrelated with impulsivity-related problems, which made it distinct from the psychopathy profile; finally, sadism showed a similar pattern of associations to psychopathy, albeit less strongly linked to impulsivity problems and externalizing behavior. CONCLUSIONS: Overall, the SD4 presents sound psychometric properties, although the overlap between psychopathy and sadism warrants some caution.

Correction: Machine Learning Model for Predicting Mortality Risk in Patients With Complex Chronic Conditions: Retrospective Analysis.

[This corrects the article DOI: 10.2196/52782.].

Incidental pathogenic germline alterations detected through liquid biopsy in patients with solid tumors: prevalence, clinical utility and implications.

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.

Geographic differences in lung cancer: focus on carcinogens, genetic predisposition, and molecular epidemiology.

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.

Resistance to BRAF inhibition explored through single circulating tumour cell molecular profiling in BRAF-mutant non-small-cell lung cancer.

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.

The role of sex and gender in the diagnosis and treatment of lung cancer: the 6th ICAPEM Annual Symposium.

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.

Association Between Lung Immune Prognostic Index and Durvalumab Consolidation Outcomes in Patients With Locally Advanced Non-Small-Cell Lung Cancer.

INTRODUCTION: The LIPI, based on pretreatment derived neutrophils/[leukocytes-neutrophils] ratio (dNLR) and LDH, is associated with immune checkpoint inhibitors (ICI) outcomes in advanced non-small-cell lung cancer (NSCLC). We aimed to assess baseline LIPI correlation with durvalumab consolidation outcomes in the locally advanced setting. MATERIAL AND METHODS: Multicentre retrospective study (330 patients) with stage III unresectable NSCLC treated with durvalumab after chemo-radiotherapy between April 2015 and December 2020; 65 patients treated with chemo-radiotherapy only. Baseline LIPI characterized 3 groups: good (dNLR≤3+LDH≤ULN), intermediate (dNLR>3/LDH>ULN) and poor (dNLR>3+LDH>ULN). Primary endpoint was overall survival (OS). RESULTS: In the durvalumab cohort, median age was 67 years, 95% smokers, 98% with a performance status of 0-1; 60% had nonsquamous histology and 16% a PD-L1 expression <1%. Radiotherapy was delivered concurrently in 81%. LIPI was evaluable in 216 patients: 66% good, 31% intermediate, 3% poor. LIPI significantly correlated with median OS (median follow-up: 19 months): 18.1 months vs. 47.0 months vs. not reached in poor, intermediate and good LIPI groups, respectively (P = .03). A trend between objective response rate and LIPI groups was observed: 0% vs. 41% vs. 45%, respectively (P = .05). The pooled intermediate/poor LIPI group was associated with shorter OS (HR 1.97; P = .03) and higher risk of progressive disease (OR 2.68; P = .047). Survivals and response were not influenced in the control cohort. CONCLUSION: Baseline LIPI correlated with outcomes in patients with locally advanced NSCLC treated with durvalumab consolidation, but not in those who only received chemo-radiotherapy, providing further evidence of its prognostic and potential predictive role of ICI benefit in NSCLC.

IPSOS trial: A "game changer" redefining first-line immunotherapy in platinum-ineligible NSCLC.

First-line therapy for advanced non-small cell lung cancer (NSCLC) involves immunotherapy with or without platinum-based chemotherapy; however, not all patients are fit enough. In the IPSOS trial, atezolizumab monotherapy demonstrated a clinical benefit in platinum-ineligible patients with advanced NSCLC, redefining first-line immunotherapy, and breaking barriers for unfit population in NSCLC.

Readiness for Change in the Implementation of a 3D Printing Initiative in a Catalan Tertiary Hospital Using the Normalization Process Theory: Survey Study.

BACKGROUND: The high failure rate of innovation projects motivates us to understand the perceptions about resistances and barriers of the main stakeholders to improving success rates. OBJECTIVE: This study aims to analyze the readiness for change in the implementation of a 3D printing project in a Catalan tertiary hospital prior to its implementation. METHODS: We used a web-based, voluntary, and anonymous survey using the Normalization Measurement Development questionnaire (NoMAD) to gather views and perceptions from a selected group of health care professionals at Germans Trias i Pujol University Hospital. RESULTS: In this study, 58 professionals, including heads of service (n=30, 51%), doctors (n=18, 31%), nurses (n=7, 12%), and support staff (n=3, 5%), responded to the questionnaire. All groups saw the value of the project and were willing to enroll and support it. Respondents reported the highest scores (out of 5) in cognitive participation (mean 4.45, SD 0.04), coherence (mean 3.72, SD 0.13), and reflective monitoring (mean 3.80, SD 0.25). The weakest score was in collective action (mean 3.52, SD 0.12). There were no statistically significant differences in scores among professions in the survey. CONCLUSIONS: The 3D printing project implementation should pay attention to preparing, defining, sharing, and supporting the operational work involved in its use and implementation. It should also understand, assess, and communicate the ways in which the new set of practices can affect the users and others around them. We suggest that health officers and politicians consider this experience as a solid ground toward the development of a more efficient health innovation system and as a catalyst for transformation.

Utility of the Brief Young Adult Alcohol Consequences Questionnaire to Identify College Students At-Risk for Alcohol Related Problems: Relative Operating Characteristics across Seven Countries.

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.

Association of Circulating Tumor DNA Testing Before Tissue Diagnosis With Time to Treatment Among Patients With Suspected Advanced Lung Cancer: The ACCELERATE Nonrandomized Clinical Trial.

Importance: Liquid biopsy has emerged as a complement to tumor tissue profiling for advanced non-small cell lung cancer (NSCLC). The optimal way to integrate liquid biopsy into the diagnostic algorithm for patients with newly diagnosed advanced NSCLC remains unclear. Objective: To evaluate the use of circulating tumor DNA (ctDNA) genotyping before tissue diagnosis among patients with suspected advanced NSCLC and its association with time to treatment. Design, Setting, and Participants: This single-group nonrandomized clinical trial was conducted among 150 patients at the Princess Margaret Cancer Centre-University Health Network (Toronto, Ontario, Canada) between July 1, 2021, and November 30, 2022. Patients referred for investigation and diagnosis of lung cancer were eligible if they had radiologic evidence of advanced lung cancer prior to a tissue diagnosis. Interventions: Patients underwent plasma ctDNA testing with a next-generation sequencing (NGS) assay before lung cancer diagnosis. Diagnostic biopsy and tissue NGS were performed per standard of care. Main Outcome and Measures: The primary end point was time from referral to treatment initiation among patients with advanced nonsquamous NSCLC using ctDNA testing before diagnosis (ACCELERATE [Accelerating Lung Cancer Diagnosis Through Liquid Biopsy] cohort). This cohort was compared with a reference cohort using standard tissue genotyping after tissue diagnosis. Results: Of the 150 patients (median age at diagnosis, 68 years [range, 33-91 years]; 80 men [53%]) enrolled, 90 (60%) had advanced nonsquamous NSCLC. The median time to treatment was 39 days (IQR, 27-52 days) for the ACCELERATE cohort vs 62 days (IQR, 44-82 days) for the reference cohort (P < .001). Among the ACCELERATE cohort, the median turnaround time from sample collection to genotyping results was 7 days (IQR, 6-9 days) for plasma and 23 days (IQR, 18-28 days) for tissue NGS (P < .001). Of the 90 patients with advanced nonsquamous NSCLC, 21 (23%) started targeted therapy before tissue NGS results were available, and 11 (12%) had actionable alterations identified only through plasma testing. Conclusions and Relevance: This nonrandomized clinical trial found that the use of plasma ctDNA genotyping before tissue diagnosis among patients with suspected advanced NSCLC was associated with accelerated time to treatment compared with a reference cohort undergoing standard tissue testing. Trial Registration: ClinicalTrials.gov Identifier: NCT04863924.

Tackling Osimertinib Resistance in EGFR-Mutant Non-Small Cell Lung Cancer.

The current landscape of targeted therapies directed against oncogenic driver alterations in non-small cell lung cancer (NSCLC) is expanding. Patients with EGFR-mutant NSCLC can derive significant benefit from EGFR tyrosine kinase inhibitor (TKI) therapy, including the third-generation EGFR TKI osimertinib. However, invariably, all patients will experience disease progression with this therapy mainly due to the adaptation of cancer cells through primary or secondary molecular mechanisms of resistance. The comprehension and access to tissue and cell-free DNA next-generation sequencing have fueled the development of innovative therapeutic strategies to prevent and overcome resistance to osimertinib in the clinical setting. Herein, we review the biological and clinical implications of molecular mechanisms of osimertinib resistance and the ongoing development of therapeutic strategies to overcome or prevent resistance.

Integrative Pan-Cancer Genomic and Transcriptomic Analyses of Refractory Metastatic Cancer.

Metastatic relapse after treatment is the leading cause of cancer mortality, and known resistance mechanisms are missing for most treatments administered to patients. To bridge this gap, we analyze a pan-cancer cohort (META-PRISM) of 1,031 refractory metastatic tumors profiled via whole-exome and transcriptome sequencing. META-PRISM tumors, particularly prostate, bladder, and pancreatic types, displayed the most transformed genomes compared with primary untreated tumors. Standard-of-care resistance biomarkers were identified only in lung and colon cancers-9.6% of META-PRISM tumors, indicating that too few resistance mechanisms have received clinical validation. In contrast, we verified the enrichment of multiple investigational and hypothetical resistance mechanisms in treated compared with nontreated patients, thereby confirming their putative role in treatment resistance. Additionally, we demonstrated that molecular markers improve 6-month survival prediction, particularly in patients with advanced breast cancer. Our analysis establishes the utility of the META-PRISM cohort for investigating resistance mechanisms and performing predictive analyses in cancer. SIGNIFICANCE: This study highlights the paucity of standard-of-care markers that explain treatment resistance and the promise of investigational and hypothetical markers awaiting further validation. It also demonstrates the utility of molecular profiling in advanced-stage cancers, particularly breast cancer, to improve the survival prediction and assess eligibility to phase I clinical trials. This article is highlighted in the In This Issue feature, p. 1027.

Cost-Effectiveness of Next-Generation Sequencing Versus Single-Gene Testing for the Molecular Diagnosis of Patients With Metastatic Non-Small-Cell Lung Cancer From the Perspective of Spanish Reference Centers.

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.

Childhood Traumatic Experiences and Negative Alcohol-Related Consequences in Adulthood: A Cross-Cultural Examination of Distress Tolerance and Drinking to Cope.

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.

Biomarkers of response to immunotherapy in early stage non-small cell lung cancer.

Immunotherapy with immune-checkpoint inhibitors (ICIs) targeting programmed cell death 1 or programmed death-ligand 1 has revolutionised the treatment of advanced non-small cell lung cancer (NSCLC) and has been investigated in early NSCLC, alone or in combination with chemotherapy, anti-CTLA-4 antibodies and radiotherapy. Although more mature data are needed before setting a change of paradigm in early stages, reports of pathological response rates and disease-free survival are promising, especially with neoadjuvant multimodality approaches. Nevertheless, major pathological response rates for neoadjuvant anti-PD-(L)1 monotherapy rarely exceed 40%, and biomarkers for characterising patients who may benefit the most from ICIs are lacking. These biomarkers have a distinct value from the metastatic setting, with highly different tumour biologies. Among the most investigated so far in this context, programmed death-ligand 1 expression and, to a lesser extent, tumour mutational burden seem to correlate better with higher pathological response rates and survival. Epidermal growth factor receptor, Serine/Threonine Kinase 11and Kelch-like ECH-associated protein 1 mutations rise as essential determinations for the treatment selection in early-stage NSCLC. Emerging and promising approaches comprise evaluation of blood-based ratios, microbiota, and baseline intratumoural TCR clonality. Circulating tumour DNA will be of great help in the near future when selecting best candidates for adjuvant ICIs, monitoring the tumour response to the neoadjuvant treatment in order to improve the rates of complete resections in the early stage.