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Beer consumers are becoming increasingly discerning about the products they buy, and the value they attach to sustainable brewing is growing. The aim of this research was to analyse how consumers' attitudes towards sustainability influence their preferences for out-of-home beer. Different beer attributes were consider including price, beer packaging, type of brewing (industrial, craft) and the alcohol content of beer. The research also sought to identify consumer segments that exhibit more positive attitudes towards more sustainable beer production. By using data from surveys of Spanish beer consumers, the results show that beer consumers that are more committed to sustainability are those that attach the least importance to price and are more interested in craft beers. The perception of craft beer as a more local or handcrafted is the proposed reason for this preference. In terms of beer packaging, this segment of more environmentally committed consumers value glass bottles over cans; however, they do not show a clear preference for keg beer, which would be a more sustainable form of consumption.

Chemophobia refers to the fear of chemicals and the belief they are harmful or toxic. This phobia can influence people's attitudes and behaviours towards the use of chemicals in food products and other consumer goods. Focusing on the wine sector, there is a growing interest in understanding how consumer perceptions of wine-related health issues affect wine purchasing. In this regard, the presence of sulphites in wine production has become a key topic in the wine industry, as their use is crucial in traditional wine production. The aim of this research was to assess the relationship between the degree of neophobia (wine neophobia and food technology neophobia) and chemophobia in wine consumers and to determine how the presence of sulphites in wine affects their purchasing preferences. The research also aimed to identify consumer segments that exhibit greater acceptance of wines without added sulphites. By using data of 562 surveys to Spanish wine consumers, the results obtained suggest that wine consumers have a relatively high level of chemophobia and show a strong preference for wines without added sulphites. The results of the consumer segmentation showed that higher levels of education and income were generally associated with lower levels of chemophobia. Our results reveal the real perceptions of consumer risk towards the presence of sulphites in wine and show how education and information play a key role in the perception of chemical-related risks in foods.

Objective: Lung cancer exhibits unpredictable recurrence in low-stage tumors and variable responses to different therapeutic interventions. Predicting relapse in early-stage lung cancer can facilitate precision medicine and improve patient survivability. While existing machine learning models rely on clinical data, incorporating genomic information could enhance their efficiency. This study aims to impute and integrate specific types of genomic data with clinical data to improve the accuracy of machine learning models for predicting relapse in early-stage, non-small cell lung cancer patients., Methods: The study utilized a publicly available TCGA lung cancer cohort and imputed genetic pathway scores into the Spanish Lung Cancer Group (SLCG) data, specifically in 1348 early-stage patients. Initially, tumor recurrence was predicted without imputed pathway scores. Subsequently, the SLCG data were augmented with pathway scores imputed from TCGA. The integrative approach aimed to enhance relapse risk prediction performance., Results: The integrative approach achieved improved relapse risk prediction with the following evaluation metrics: an area under the precision-recall curve (PR-AUC) score of 0.75, an area under the ROC (ROC-AUC) score of 0.80, an F1 score of 0.61, and a Precision of 0.80. The prediction explanation model SHAP (SHapley Additive exPlanations) was employed to explain the machine learning model's predictions., Conclusion: We conclude that our explainable predictive model is a promising tool for oncologists that addresses an unmet clinical need of post-treatment patient stratification based on the relapse risk while also improving the predictive power by incorporating proxy genomic data not available for specific patients., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Second-line treatment options are limited for patients with small-cell lung cancer (SCLC). We conducted a PRISMA-standard systematic literature review to evaluate the treatment landscape for patients with relapsed SCLC (PROSPERO number: CRD42022299759). Systematic searches of MEDLINE, Embase, and Cochrane Library were performed (October 2022) to identify publications (prior 5 years) from prospective studies of therapies for relapsed SCLC. Publications were screened against predetermined eligibility criteria; data were extracted to standardized fields. Publication quality was assessed using GRADE. The data were analyzed descriptively, grouped by drug class. Overall, 77 publications involving 6349 patients were included. Studies of tyrosine kinase inhibitors (TKIs) with established cancer indications accounted for 24 publications; topoisomerase I inhibitors for 15; checkpoint inhibitors (CPIs) for 11, and alkylating agents for 9 publications. The remaining 18 publications featured chemotherapies, small-molecule inhibitors, investigational TKIs and monoclonal antibodies, and a cancer vaccine. According to GRADE assessment, 69% of the publications reported low-/very-low-quality evidence; quality limitations included lack of randomization and small sample sizes. Only 6 publications/6 trials reported phase 3 data; 5 publications/2 trials reported phase 2/3 results. Overall, the clinical potential of alkylating agents and CPIs remained unclear; investigations of combination approaches and biomarker-directed usage are warranted. Phase 2 data from TKI trials were consistently promising; no phase 3 data were available. Phase 2 data for a liposomal formulation of irinotecan were promising. We confirmed an absence of promising investigational drug/regimens in late-stage development; thus, relapsed SCLC remains an area of high unmet need., (Copyright © 2023. Published by Elsevier Inc.)

Background: The ETOP 10-16 BOOSTER trial failed to demonstrate a progression-free survival (PFS) benefit for adding bevacizumab to osimertinib in second line. An exploratory subgroup analysis, however, suggested a PFS benefit of the combination in patients with a smoking history and prompted us to do this study., Methods: A systematic review and meta-analysis to evaluate the differential effect of smoking status on the benefit of adding an angiogenesis inhibitor to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor therapy was carried out. All relevant randomized controlled trials appearing in main oncology congresses or in PubMed as of 1 November 2021 were used according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Primarily PFS according to smoking status, and secondarily overall survival (OS) were of interest. Pooled and interaction hazard ratios (HRs) were estimated by fixed or random effects models, depending on the detected degree of heterogeneity. Bias was assessed using the revised Cochrane tool for randomized controlled trials (RoB 2)., Results: Information by smoking was available for 1291 patients for PFS (seven studies) and 678 patients for OS (four studies). The risk of bias was low for all studies. Combination treatment significantly prolonged PFS for smokers [n = 502, HR = 0.55, 95% confidence interval (CI): 0.44-0.69] but not for nonsmokers (n = 789, HR = 0.92, 95% CI: 0.66-1.27; treatment-by-smoking interaction P = 0.02). Similarly, a significant OS benefit was found for smokers (n = 271, HR = 0.66, 95% CI: 0.47-0.93) but not for nonsmokers (n = 407, HR = 1.07, 95% CI: 0.82-1.42; treatment-by-smoking interaction P = 0.03)., Conclusion: In advanced EGFR-non-small-cell lung cancer patients, the addition of an angiogenesis inhibitor to EGFR-tyrosine kinase inhibitor therapy provides a statistically significant PFS and OS benefit in smokers, but not in non-smokers. The biological basis for this observation should be pursued and could determine whether this might be due to a specific co-mutational pattern produced by tobacco exposure., Competing Interests: Disclosure UD reports honorarium as Member of the Tumor Agnostic Evidence Generation working Group of Roche, outside the submitted work. RASo reports advisory role for Amgen, AstraZeneca, Bayer, Bristol Myers Squibb (BMS), Boehringer Ingelheim, Lily, Merck, Novartis, Pfizer, Roche, Taiho, Takeda, and Yuhan and grants from AstraZeneca, Boehringer Ingelheim, outside the submitted work. SP reports grants from Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Clovis, F. Hoffman-La Roche, Illumina, Novartis, Pfizer, Merck Sharp & Dohme (MSD), personal fees from Amgen, AbbVie, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, BMS, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffman-La Roche, Foundations Medicine, Illumina, Janssen, Novartis, PharmaMar, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, MSD, Merck Serono, Merrimack, Medscape, Phosphoplatin Therapeutics, Beigene, Imedex, outside the submitted work. JDC reports grants and personal fees from AstraZeneca, BMS, MSD, and Hoffmann-La Roche, personal fees from Bayer, Boehringer Ingelheim, GlaxoSmithKline (GSK), Jansen-Cilag, Lilly, Novartis, Pfizer, and Takeda, outside the submitted work. LC reports advisory role for AstraZeneca, Roche, and Daichi, outside the submitted work. MF reports grants from AstraZeneca and BMS and other support AstraZeneca, BMS, Boehringer Ingelheim, Janssen, MSD, Pfizer, Roche, and Takeda, outside the submitted work. EN reports grants, personal fees, and non-financial support from Roche, personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from BMS, personal fees and non-financial support from MSD, grants and personal fees from Merck Serono, personal fees from Takeda, grants, personal fees, and non-financial support from Pfizer, personal fees from Lilly, personal fees from Bayer, personal fees from Amgen, personal fees from Boehringer Ingelheim, outside the submitted work. EC reports personal fees from AstraZeneca, Amgen, BMS, MSD, and Roche, outside the submitted work. MAS reports advisory role for Roche and Boehringer Ingelheim, speaker role for Pierre Fabre, and travel grants from Roche and PharmaMar, outside the submitted work. RB reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche, AstraZeneca, BMS, Amgen, and MSD, participation on Data Safety Monitoring Board or Advisory Board for AstraZeneca, BMS, and Roche, outside the submitted work. MP reports grants, personal fees, and non-financial support from AstraZeneca, BMS, and Roche, personal fees from MSD and Takeda, outside the submitted work. SC reports non-financial support from Pfizer, Roche, MSD, BMS, outside the submitted work. RASt reports consultant or advisory role for AstraZeneca, BMS, Boehringer Ingelheim, GSK, MSD, Pfizer, Roche, Sandoz, Seattle Genetics, Takeda, speaker honoraria from Amgen, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, GSK, MSD, Novartis, Roche, Data Monitoring Committee (DMC) role from Genentech/Roche and Takeda, and financial support for ETOP and IBCSG trials (where he is president), from AstraZeneca, BMS, Daiichi Sankyo, Celgene, Ipsen, Janssen, Mirati, MSD, Novartis, Pfizer, Pierre Fabre, Roche. All other authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Thymic epithelial tumors are rare neoplastic proliferations of thymic epithelial cells. The aggressiveness of these malignancies increases as higher is the histologic subtype, being thymic carcinoma the most aggressive subtype, with a greater tendency to metastatic spread. In metastatic setting, there is no standard treatment after progression on platinum-based chemotherapy. In this scenario, monotherapy treatment either with lenvatinib, a multi-tyrosine kinase inhibitor with antiangiogenic properties, or pembrolizumab, an immune-checkpoint inhibitor, has reported clinical activity. Potential combination of both agents may have synergistic activity as reported in other cancer types. PECATI trial is a single-arm, investigator-initiated phase II study aiming to assess the activity and safety of the combination of lenvatinib and pembrolizumab in 43 patients with advanced B3-thymoma or thymic carcinoma who progressed on or after at least one previous line of platinum-based chemotherapy. The primary endpoint of the trial is 5-month progression-free survival rate and the secondary endpoints include overall response rate, duration of response, and overall survival., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)

Background: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance., Patients and Methods: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs)., Results: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively., Conclusions: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination., Competing Interests: Disclosure RAS reports advisory role for Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Lily, Merck, Novartis, Pfizer, Roche, Taiho, Takeda and Yuhan and grants from AstraZeneca, Boehringer Ingelheim, outside the submitted work. UD reports honorarium as Member of the Tumor Agnostic Evidence Generation working Group of Roche, outside the submitted work. BCC reports grants from Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, Abbvie, Medpacto, GI Innovation, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp, personal fees from Novartis, AstraZeneca, Champions Oncology, Janssen, Yuhan, Ono, MSD, Medpacto, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp, Boehringer Ingelheim, Roche, BMS, Pfizer, Takeda, KANAPH Therapeutic Inc., Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Joseah BIO, Gencurix Inc., and other from Interpark Bio Convergence Corp, KANAPH Therapeutic Inc., Bridgebio therapeutics, Cyrus therapeutics, Gencurix Inc, DAAN, TheraCanVac Inc., outside the submitted work. EN reports grants, personal fees and non-financial support from Roche, personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from Bristol-Myers-Squibb, personal fees and non-financial support from Merck Sharp Dohme, grants and personal fees from Merck Serono, personal fees from Takeda, grants, personal fees and non-financial support from Pfizer, personal fees from Lilly, personal fees from Bayer, personal fees from Amgen, personal fees from Boehringer Ingelheim, outside the submitted work. EC reports personal fees from AstraZeneca, Amgen, BMS, MSD and Roche, outside the submitted work. JdC reports grants and personal fees from AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme and Hoffmann-La Roche, personal fees from Bayer, Boehringer Ingelheim, Glaxosmithkline, Jansen-Cilag, Lilly, Novartis, Pfizer and Takeda, outside the submitted work. MAS reports advisory role for Roche and Boehringer Ingelheim, speaker role for Pierre Fabre and travel grants from Roche and PharmaMar, outside the submitted work. RB reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Roche, AstraZeneca, BMS, AMGEN and MSD, participation on Data Safety Monitoring Board or Advisory Board for AstraZeneca, BMS and Roche. LC reports advisory role for AstraZeneca, Roche and Daichi, outside the submitted work. MPP reports grants, personal fees and non-financial support from AstraZeneca, BMS and ROCHE, personal fees from MSD and TAKEDA, outside the submitted work. RGC reports Advisory Board, Consultancy or Speaker honoraria from MSD, Bristol-Myers Squibb, Roche, Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Lilly, Takeda, Janssen and Sanofi. SC reports non-financial support from Pfizer, Roche, MSD and BMS, outside the submitted work. MF reports grants from Astra Zeneca and BMS and other support from AstraZeneca, BMS, Boehringer Ingelheim, Janssen, MSD, Pfizer, Roche and Takeda, outside the submitted work. JGS reports grants for consulting or advisory role from Roche, Boehringer Ingelheim, EUSA Pharma, research funding from Roche and travel, and accommodation expenses from Roche, BMS, Merck Sharp & Dohme and Pfizer, outside the submitted work. MD reports personal fees from AstraZeneca, BMS, Boehringer Ingelheim, MSD, Pfizer, Roche and Takeda, outside the submitted work. MM reports grants and personal fees from Bristol-Myers Squibb, Pierre Fabre, personal fees and non-financial support from AstraZeneca, Boehringer Ingelheim, F. Hoffman – La Roche, Merck Sharp and Dohme, and personal fees from Kyowa Kirin, outside the submitted work. JMST reports personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Roche, Takeda and MSD, outside the submitted work. CB reports consulting or advisory role for AstraZeneca, Pfizer, Roche, Takeda, Janssen-Cilag and Boehringer Ingelheim, as well as travel support from AstraZeneca and Takeda, outside the submitted work. MP reports grants from AstraZeneca, BMS, Boehringer Ingelheim, Roche, Takeda, Vifor, and personal fees from Abbvie, AstraZeneca, BMS, Boehringer Ingelheim, Eisei, MSD, Novartis, Pfizer, Roche, Takeda, Merck and Janssen, outside the submitted work. RAS reports consultant or advisory role for AstraZeneca, BMS, Janssen, MSD, Pfizer, Regeneron, Roche, Seattle Genetics and Takeda, speaker honoraria from Amgen, AstraZeneca, Blueprint, Eli Lilly, GSK, MSD, Novartis, Roche and Sandoz, DMC role from Genentech/Roche and Takeda, and financial support for ETOP and IBCSG trials, where he is president and scientific chair, from AstraZeneca, BMS, Ipsen, MSD, Novartis, Pierre Fabre, Roche and Pfizer. SP reports grants from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffman – La Roche, Illumina, Novartis, Pfizer, Merck Sharp and Dohme, personal fees from Amgen, Abbvie, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffman – La Roche, Foundations Medicine, Illumina, Janssen, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Merck Sharp and Dohme, Merck Serono, Merrimack, Medscape, Phosphoplatin Therapeutics, Beigene and Imedex, outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2021 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Background: To assess the efficacy and safety of a metronomic schedule of oral vinorelbine (mVNR) in advanced non-small-cell lung cancer (NSCLC) in patients unfit for platinum-based combination chemotherapy., Patients and Methods: This was a multicenter, prospective, randomized, open-label phase II study in treatment-naive patients with TNM stage IIIB/IV NSCLC. Patients received mVNR at a fixed dose of 50 mg × 3 or standard schedule 60-80 mg/m 2 weekly until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) without grade 4 toxicity (G4PFS; NCI-CTC v4). Main secondary objectives were safety, disease control rate (DCR) without grade 4 toxicity (G4DCR), DCR, PFS, overall survival (OS) and quality of life (QoL)., Results: A total of 167 patients were included, 83 and 84 patients in the mVNR and standard arms, respectively. The median G4PFS was 4.0 months [95% confidence interval (CI): 2.6-4.3] and 2.2 months (95% CI: 1.5-2.9), hazard ration (HR) = 0.63 (95% CI: 0.45-0.88), P = 0.0068 in favor of metronomic arm; G4DCR was 45.8% and 26.8% in the mVNR and standard arms, respectively. Grade 3-4 treatment-related adverse events were less frequent in the mVNR arm (25.3% versus 54.4%) mainly owing to a reduction in all grades (15.7% versus 51.9%) and grade 3-4 neutropenia (10.8% versus 42%). PFS was 4.3 (95% CI: 3.3-5.1) and 3.9 months (95% CI: 2.8-5.2) in mVNR and standard arms, respectively. No difference in median OS was observed. QoL was comparable between arms., Conclusions: Metronomic oral vinorelbine significantly prolonged median G4PFS in advanced NSCLC patients unfit for platinum combinations as first-line treatment. It was associated with a clear reduction in toxicity and may be considered as an important option in this challenging population., Competing Interests: Disclosure AC has disclosed expert testimony (Pierre Fabre), travel accommodations/expenses (Roche, Pierre Fabre). A Morabito has disclosed speaker's bureau (Pfizer, BMS, Boehringer, MSD, Roche, AstraZeneca). FG has disclosed advisory boards/consultations (Eli Lilly, Roche, Boehringer Ingelheim, AstraZeneca, Pierre Fabre, BMS, MSD, Novartis); honoraria: seminar/talks to industry (Eli Lilly, Roche, Boehringer Ingelheim, AstraZeneca, Pierre Fabre, Amgen, Celgene, BMS, MSD); research funding (AstraZeneca, BMS, MSD). RR has disclosed consulting/advisory (Roche, MSD, Pfizer, Novartis, Boehringer Ingelheim). G-LC has disclosed consulting/advisory (Pfizer, Boehringer Ingelheim, Astellas). JB-B reports grants and personal fees from Roche-Genentech, grants from Pfizer, personal fees from MSD, personal fees from BMS, personal fees from AstraZeneca, personal fees from Novartis and grants from Pierre Fabre outside the submitted work. PL is an employee of Pierre Fabre Médicament. CTTM is an employee of Pierre Fabre Médicament. SG, biostatistician, is an employee of Pierre Fabre Médicament (IRPF). DK has disclosed consultancy and advisory board: Pfizer, AstraZeneca, Roche/Genentech, BMS, MSD. T-EC reports consulting/advisory, personal fees from Astellas Pharma, Janssen, BMS, Merck Serono, Amgen, Roche, Pfizer, Boehringer Ingelheim, Servier, A-D Pharm, Lilly, AstraZeneca and Novartis; non-financial support from Pfizer, Sanofi, Boehringer Ingelheim, Merck, Servier, Ipsen, Amgen, Adpharm, AstraZeneca, Roche, BMS, Lilly, Janssen, Novartis and Astellas Pharma. All other authors declare no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Biological differences between the sexes have a major impact on disease and treatment outcome. In this paper, we evaluate the prognostic value of sex in stage IV non-small-cell lung cancer (NSCLC) in the context of routine clinical data, and compare this information with other external datasets., Methods: Clinical data from stage IV NSCLC patients from Hospital Puerta de Hierro (HPH) were retrieved from electronic health records using big data analytics (N = 397). In addition, data from the Spanish Lung Cancer Group (GECP) Tumor Registry (N = 1382) and from a published study available from the cBioPortal (MSK) (N = 601) were analyzed. Survival curves were estimated using the Kaplan-Meier method. A Cox proportional hazards regression model was used to assess the prognostic value of sex. A meta-analysis to compare the outcome for males and females in terms of overall survival (OS) and progression free survival (PFS) was performed., Results: The median OS time was 12 months for males and 19 months for females (overall HR = 0.77; 95% CI: 0.68-0.87; P < 0.001). Similarly, females with stage IV NSCLC harboring an EGFR-sensitizing mutation lived significantly longer than males (median OS: males, 19 months; females, 32 months) with a lower risk of death compared with males (overall HR = 0.75; 95% CI: 0.67-0.84). In addition, female patients benefited more from EGFR inhibitors in terms of PFS and OS (overall HR = 0.45; 95% CI: 0.32-0.64, and HR = 0.62; 95% CI: 0.48-0.80, respectively). Median PFS was 21 months in females and 12 months in males (P < 0.001)., Conclusions: Using routine clinical data we confirmed the previous finding that among stage IV NSCLC patients, females had a significantly better prognosis than males. The effect size of the sex was notable, highlighting the fact that survival rates are usually estimated and patients are generally managed without considering the sexes separately, which may lead to suboptimal results., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Approximately 30% of tumor biopsies from patients with advanced-stage lung adenocarcinomas yield insufficient tissue for successful molecular subtyping. We have analyzed the clinical utility of next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) in patients with inadequate tumor samples for tissue genotyping., Patients and Methods: We conducted the study in a multi-institutional prospective cohort of clinically unselected patients with advanced-stage lung adenocarcinomas with insufficient tissue for EGFR, ALK or ROS1 genotyping across 12 Spanish institutions (n = 93). ctDNA NGS was carried out by Guardant Health (Guardant360, Redwood City, CA), using a hybrid-capture-based 73-gene panel. Variants were deemed actionable if they were part of the OncoKB precision oncology knowledge database and classified in four levels of actionability based on their clinical or preclinical evidence for drug response., Results: Eighty-three out of 93 patients (89%) had detectable levels of ctDNA. Potentially actionable level 1-4 genomic alterations were detected in 53 cases (57%), of which 13 (14%) had level 1-2A alterations (Food and Drug Administration-approved and standard-care biomarkers according to lung cancer guidelines). Frequencies of each genomic alteration in ctDNA were consistent with those observed in unselected pulmonary adenocarcinomas. The majority of the patients (62%), particularly those with actionable alterations (87%), had more than one pathogenic variant in ctDNA. The median turnaround time to genomic results was 13 days. Twelve patients (13%) received genotype-matched therapies based on ctDNA results, deriving the expected clinical benefit. Patients with co-occurring pathogenic alterations had a significantly shorter median overall survival as compared with patients without co-occurring pathogenic alteration (multivariate hazard ratio = 5.35, P = 0.01)., Conclusion: Digital NGS of ctDNA in lung cancers with insufficient tumor samples for tissue sequencing detects actionable variants that frequently co-occur with other potentially clinically relevant genomic alterations, allowing timely initiation of genotype-matched therapies., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients., Patients and Methods: Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial. In both trials, patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin, those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin, and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone. The primary end point was progression-free survival (PFS)., Results: Two hundred and seventy-nine patients in the SLCG trial and 124 in the Chinese trial were assessable for PFS. PFS in the control and experimental arms in the SLCG trial was 5.49 and 4.38 months, respectively [log rank P = 0.07; hazard ratio (HR) 1.28; P = 0.03]. In the Chinese trial, PFS was 4.74 and 3.78 months, respectively (log rank P = 0.82; HR 0.95; P = 0.82)., Conclusion: Accrual was prematurely closed on the SLCG trial due to the absence of clinical benefit in the experimental over the control arm. However, the BREC studies provide proof of concept that an international, nonindustry, biomarker-directed trial is feasible. Thanks to the groundwork laid by these studies, we expect that ongoing further research on alternative biomarkers to elucidate DNA repair mechanisms will help define novel therapeutic approaches., Trial Registration: NCT00617656/GECP-BREC and ChiCTR-TRC-12001860/BREC-CHINA., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)