Which factors are associated with cannabis use among adolescents in Andalusia? An application of the I-Change model.

BACKGROUND: Cannabis use is increasing among Andalusian adolescents, causing health, social and financial problems. School nurses visit schools and provide health promotion to adolescents in Andalusia. In order to better tailor health promotion programs, it is important to understand the sociodemographic and motivational factors related to cannabis use in Andalusian adolescents. DESIGN/METHODS: In this cross-sectional study, 369 students (aged 15-18 years) from secondary schools in Andalusia were involved. An anonymous questionnaire based on the I-Change Model was self-administered during school hours. Cannabis users were compared with non-cannabis users regarding sociodemographic and motivational factors. Contingency tables, mean comparison tests, and logistic regression analyses were conducted. RESULTS: The prevalence of cannabis use in the last year was 21.6%. Non-cannabis users had a few positive beliefs toward cannabis use (e.g. the ability to relax or medical benefits), as well as users. Users recognized some disadvantages of cannabis use but played down their importance and mentioned more advantages. Moreover, social influence, especially from peers, plays a critical role in cannabis use. Specific social situations and moods seemed to be special risk factors for cannabis use, such as being at a celebration or feeling good. Results of regression analysis showed that cannabis use is mainly associated with age, low family function, low family affluence, high pocket money, perceiving few disadvantages of cannabis use, much social modeling of cannabis use, social norm and pressure favoring cannabis, low self-efficacy to resist using cannabis and positive intentions to use cannabis. CONCLUSIONS: Based on our results, prevention programmes lead by nurses can be tailored to the factors important to prevent cannabis use, focusing on outlining the disadvantages of cannabis use, alternatives for using cannabis when feeling good, increasing salience of healthy social influences and reinforcing self-efficacy to resist temptations to use cannabis are recommended. CLINICAL RELEVANCE: Nurses need to know the sociodemographic factors and motivations associated with the use of cannabis in adolescents in order to establish effective preventive interventions at school.

Adolescents and youths' opinions about the factors associated with cannabis use: a qualitative study based on the I-Change model.

BACKGROUND: To learn about the experiences and opinions of adolescent non-consumers and regular cannabis users about cannabis use and the factors that determine its use, using the I-Change explanatory model as a basis. METHODS: Qualitative methodology with a content analysis was used. Focus groups were conducted with adolescents who were non-regular cannabis users (those who had not tried cannabis or had only experimented with it before) and semi-structured interviews were conducted with adolescent and young adult in recovery who were in a detoxification program. A deductive analysis of the audio-recorded and transcribed interviews was performed, using the domains of the I-Change Model as a reference. RESULTS: Personal problems, social problems or family problems can lead to cannabis use. There was a lack of knowledge and low risk perception about consumption of this drug. There are other factors that influence consumption, the perception of advantages, such as the feeling of freedom and the influence of the peer group. The consumption of this substance in girls is changing, becoming more and more equal to that of boys. The family has an important role to play in preventing drug use. CONCLUSION: Knowledge of these factors is of vital importance as a prior step to the development of efficient intervention measures adjusted to the needs identified and the characteristics of the population.

Determination of essential biomarkers in lung cancer: a real-world data study in Spain with demographic, clinical, epidemiological and pathological characteristics.

BACKGROUND: The survival of patients with lung cancer has substantially increased in the last decade by about 15%. This increase is, basically, due to targeted therapies available for advanced stages and the emergence of immunotherapy itself. This work aims to study the situation of biomarker testing in Spain. PATIENTS AND METHODS: The Thoracic Tumours Registry (TTR) is an observational, prospective, registry-based study that included patients diagnosed with lung cancer and other thoracic tumours, from September 2016 to 2020. This TTR study was sponsored by the Spanish Lung Cancer Group (GECP) Foundation, an independent, scientific, multidisciplinary oncology society that coordinates more than 550 experts and 182 hospitals across the Spanish territory. RESULTS: Nine thousand two hundred thirty-nine patients diagnosed with stage IV non-small cell lung cancer (NSCLC) between 2106 and 2020 were analysed. 7,467 (80.8%) were non-squamous and 1,772 (19.2%) were squamous. Tumour marker testing was performed in 85.0% of patients with non-squamous tumours vs 56.3% in those with squamous tumours (p-value < 0.001). The global testing of EGFR, ALK, and ROS1 was 78.9, 64.7, 35.6% respectively, in non-squamous histology. PDL1 was determined globally in the same period (46.9%), although if we focus on the last 3 years it exceeds 85%. There has been a significant increase in the last few years of all determinations and there are even close to 10% of molecular determinations that do not yet have targeted drug approval but will have it in the near future. 4,115 cases had a positive result (44.5%) for either EGFR, ALK, KRAS, BRAF, ROS1, or high PDL1. CONCLUSIONS: Despite the lack of a national project and standard protocol in Spain that regulates the determination of biomarkers, the situation is similar to other European countries. Given the growing number of different determinations and their high positivity, national strategies are urgently needed to implement next-generation sequencing (NGS) in an integrated and cost-effective way in lung cancer.

Prognostic model of long-term advanced stage (IIIB-IV) EGFR mutated non-small cell lung cancer (NSCLC) survivors using real-life data.

BACKGROUND: There is a lack of useful diagnostic tools to identify EGFR mutated NSCLC patients with long-term survival. This study develops a prognostic model using real world data to assist clinicians to predict survival beyond 24 months. METHODS: EGFR mutated stage IIIB and IV NSCLC patients diagnosed between January 2009 and December 2017 included in the Spanish Lung Cancer Group (SLCG) thoracic tumor registry. Long-term survival was defined as being alive 24 months after diagnosis. A multivariable prognostic model was carried out using binary logistic regression and internal validation through bootstrapping. A nomogram was developed to facilitate the interpretation and applicability of the model. RESULTS: 505 of the 961 EGFR mutated patients identified in the registry were included, with a median survival of 27.73 months. Factors associated with overall survival longer than 24 months were: being a woman (OR 1.78); absence of the exon 20 insertion mutation (OR 2.77); functional status (ECOG 0-1) (OR 4.92); absence of central nervous system metastases (OR 2.22), absence of liver metastases (OR 1.90) or adrenal involvement (OR 2.35) and low number of metastatic sites (OR 1.22). The model had a good internal validation with a calibration slope equal to 0.781 and discrimination (optimism corrected C-index 0.680). CONCLUSIONS: Survival greater than 24 months can be predicted from six pre-treatment clinicopathological variables. The model has a good discrimination ability. We hypothesized that this model could help the selection of the best treatment sequence in EGFR mutation NSCLC patients.

Bioremediation of petroleum hydrocarbons polluted soil by spent mushroom substrates: Microbiological structure and functionality.

Spent mushroom substrate (SMS) holds valuable microbiota that can be useful in remediating polluted soils with hydrocarbons. However, the microorganisms behind the bioremediation process remain uncertain. In this work, a bioremediation assay of total petroleum hydrocarbons (TPHs) polluted soil by SMS application was performed to elucidate the microorganisms and consortia involved in biodegradation by a metabarcoding analysis. Untreated polluted soil was compared to seven bioremediation treatments by adding SMS of Agaricus bisporus, Pleurotus eryngii, Pleurotus ostreatus, and combinations. Soil microbial activity, TPH biodegradation, taxonomic classification, and predictive functional analysis were evaluated in the microbiopiles at 60 days. Different metagenomics approaches were performed to understand the impact of each SMS on native soil microbiota and TPHs biodegradation. All SMSs enhanced the degradation of aliphatic and aromatic hydrocarbons, being A. bisporus the most effective, promoting an efficient consortium constituted by the bacterial families Alcanivoraceae, Alcaligenaceae, and Dietziaceae along with the fungal genera Scedosporium and Aspergillus. The predictive 16 S rRNA gene study partially explained the decontamination efficacy by observing changes in the taxonomic structure of bacteria and fungi, and changes in the potential profiles of estimated degradative genes across the different treatments. This work provides new insights into TPHs bioremediation.

A New Genus of the Microascaceae (Ascomycota) Family from a Hypersaline Lagoon in Spain and the Delimitation of the Genus Wardomyces.

The Saladas de Sástago-Bujaraloz is an endorheic and arheic complex of lagoons located in the Ebro Basin and protected by the Ramsar Convention on Wetlands. Due to the semi-arid climate of the region and the high salinity of their waters, these lagoons constitute an extreme environment. We surveyed the biodiversity of salt-tolerant and halophilic fungi residents of the Laguna de Pito, a lagoon belonging to this complex. Therefore, we collected several samples of water, sediments, and soil of the periphery. Throughout the study, we isolated 21 fungal species, including a strain morphologically related to the family Microascaceae. However, this strain did not morphologically match any of genera within this family. After an in-depth morphological characterization and phylogenetic analysis using a concatenated sequence dataset of four phylogenetically informative molecular markers (the internal transcribed spacer region (ITS) of the nuclear ribosomal DNA (nrDNA); the D1-D2 domains of the 28S gene of the nuclear ribosomal RNA (LSU); and a fragment of the translation elongation factor 1-alpha (EF-1α) and the ß-tubulin (tub2) genes), we established the new genus Dactyliodendromyces, with Dactyliodendromyces holomorphus as its species. Additionally, as a result of our taxonomic study, we reclassified the paraphyletic genus Wardomyces into three different genera: Wardomyces sensu stricto, Parawardomyces gen. nov., and Pseudowardomyces gen. nov., with Parawardomyces ovalis (formerly Wardomyces ovalis) and Pseudowardomyces humicola (formerly Wardomyces humicola) as the type species of their respective genera. Furthermore, we propose new combinations, including Parawardomyces giganteus (formerly Wardomyces giganteus) and Pseudowardomyces pulvinatus (formerly Wardomyces pulvinatus).

Methodological and strategic insights for online survey studies: an analysis based on the CHERRIES checklist.

The use of online surveys has become a valuable and widely employed tool in health research. However, the use of such instruments necessitates methodological rigor and optimization in their design to achieve the best response rates. Drawing upon relevant literature and the international CHERRIES guidelines for the development of online surveys, this article addresses methodological aspects related to ethical considerations and data protection (with reference to the Association of Internet Research's online ethics guide), study design and validation, recruitment, data collection processes, and data management and analysis. In conclusion, given the context of overexposure to online surveys, which can influence recruitment and response rates, strategies for their maximization are provided, encompassing both static and dynamic aspects of survey design.

Beliefs About Cannabis Use Among Male and Female Andalusian Adolescents.

Objectives: This study assessed potential differences between girls and boys in the prevalence rates of cannabis use, sociodemographic factors, and beliefs about cannabis use. Methods: 1,896 Andalusian adolescents aged 14-18 participated in an online survey based on the I-Change model. The survey assessed their beliefs about cannabis use, including attitudes, social influences, self-efficacy, action planning, and intention to use. Multivariate analyses of variance were then conducted to examine potential gender differences in these beliefs, while controlling for last month's cannabis use. Results: Significantly more boys used cannabis in the last month, had boyfriends/girlfriends, and had more pocket money compared to girls. Additionally, girls - in comparison to boys - were more convinced of the disadvantages of cannabis use, but were also more convinced of some of the advantages (such as freedom from boredom, and medicinal use), reported having less favorable social norms for cannabis use, had more female best friends using cannabis, and felt pressure to use cannabis from their female peers. Conclusion: These findings highlight the need for cannabis prevention programs to consider gender differences in beliefs about cannabis use. Programs should not only address general risk factors for cannabis use but also evaluate if their interventions effectively target beliefs that are particularly important for girls and boys.

A genetic profiling guideline to support diagnosis and clinical management of lymphomas.

The new lymphoma classifications (International Consensus Classification of Mature Lymphoid Neoplasms, and 5th World Health Organization Classification of Lymphoid Neoplasms) include genetics as an integral part of lymphoma diagnosis, allowing better lymphoma subclassification, patient risk stratification, and prediction of treatment response. Lymphomas are characterized by very few recurrent and disease-specific mutations, and most entities have a heterogenous genetic landscape with a long tail of recurrently mutated genes. Most of these occur at low frequencies, reflecting the clinical heterogeneity of lymphomas. Multiple studies have identified genetic markers that improve diagnostics and prognostication, and next-generation sequencing is becoming an essential tool in the clinical laboratory. This review provides a "next-generation sequencing" guide for lymphomas. It discusses the genetic alterations of the most frequent mature lymphoma entities with diagnostic, prognostic, and predictive potential and proposes targeted sequencing panels to detect mutations and copy-number alterations for B- and NK/T-cell lymphomas.

Difficulties on the access to innovative targeted therapies for lung cancer in Spain.

PURPOSE: Spanish Lung Cancer Group (SLCG) conducted a review to analyze the barriers to access to innovative targeted therapies for non-small cell lung cancer (NSCLC) in clinical practice in Spain. METHODS: Review all relevant content published on websites of European Commission, European Medicines Agency, and Spanish Agency of Medicines and Medical Products regarding the authorization and access to oncology treatments. RESULTS: More than 20 targeted therapies are available to treat different molecular alterations in patients with NSCLC. European Commission has approved treatments for genomic alterations involving the following genes: ALK, RET, ROS1, EGFR, BRAF, NTRK, KRAS, MET. However, the availability of these therapies in Spain is not complete, as innovative treatments are not reimbursed or funded late, with only five of these alterations currently covered by National Health System. CONCLUSION: SLCG considers imperative to improve the access in Spain to innovative treatments for NSCLC to reduce inequity across European countries.

Advanced non-squamous NSCLC with no actionable oncogenic driver in Spain: a cross-sectional descriptive analysis of data from the Thoracic Tumor Registry.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for the vast majority of all diagnosed lung cancers. According to their histology, most NSCLCs are considered non-squamous cell carcinoma (NSCC), and up to 85% of the latter may lack either one of the two main actionable oncogenic drivers (i.e., EGFR mutations and ALK rearrangements). OBJECTIVE: Our analysis aimed to describe the clinical and epidemiological characteristics of Spanish patients suffering from NSCC with no actionable oncogenic driver in daily clinical practice. DESIGN: A retrospective, cross-sectional, descriptive analysis. METHODS: We analyzed the records of all Spanish patients with advanced NSCC diagnosed between January 2011 and January 2020 and included in the Spanish Thoracic Tumor Registry database. We evaluated the presence of metastasis and molecular profiling at the time of diagnosis and treatments received. We also assessed overall survival (OS) and progression-free survival (PFS) according to first-line treatment. RESULTS: One thousand seven hundred ninety-seven Spanish patients with NSCC were included. They were mainly men (73.2%), smokers (current [44.4%] and former [44.4%]) and presented adenocarcinoma histology (97.6%). Most patients had at least one comorbidity (80.4%) and one metastatic site (96.8%), and a non-negligible number of those tested were PD-L1 positive (35.2%). Notably, the presence of liver metastasis indicated a shorter median OS and PFS than metastasis in other locations (p < 0.001). Chemotherapy was more often prescribed than immunotherapy as first-, second-, and third-line treatment in that period. In first-line, the OS rates were similar in patients receiving either regimen, but PFS rates significantly better in patients treated with immunotherapy (p = 0.026). Also, a high number of patients did not reach second- and third-line treatment, suggesting the failure of current early diagnostic measures and therapies. CONCLUSIONS: This analysis of the most lethal tumor in Spain could highlight the strengths and the weaknesses of its clinical management and set the ground for further advances and research.

Describing differences among populations of thoracic tumors patients under and over 80 years: Data analysis from the SLCG thoracic tumor registry.

OBJECTIVES: Cancer is a disease of old age; however, most studies usually included minority of patients fit elderly. The purpose is to investigate the clinical characteristics and genetic information of patients with thoracic tumors who are 80 years old or older compared to those under 80 years old. STUDY DESIGN AND METHODS: The Thoracic Tumor Registry (TTR) is a Spanish observational, prospective cohort study that included patients diagnosed with thoracic tumors. Data were collected from medical records related to sociodemographic, epidemiological, clinical, molecular/genetic, and treatment outcome variables. RESULTS: The total number of patients, recruited from August 2016 to April 2023, was 26.193 (93,1 % were younger than 80 years and 6,9 % were 80 years or older). In the group of older patients: the male ratio increased (72,9 % vs. 80 %); the number of elderly people who had never smoked or were ex-smokers increased (9,9 % vs. 21,1 % and 44,8 % vs. 61,3 %, respectively) and the number of current smokers decreased (43,3 % vs. 17,5 %); had higher ECOG performance status at diagnosis (for ECOG ≥ 2, 15 % vs. 32,9 %), and there were more patients with previous cancer (17,3 % vs. 28 %). The proportion of men is higher than that of women (73 % vs. 27 % in <80 years and 80 % vs. 20 % in ≥80 years). For all biomarkers, the proportion of patients who had a molecular determination was lower in older patients. There were no differences in terms of alterations in the biomarkers tested; except for EGFR, for which the positivity rate was higher in patients aged 80 years and older (25 % vs. 15,3 %). CONCLUSION: The proportion of older patients with targeted mutations is higher. So, at least at diagnosis, it should be proceeded in a standard way. Then, when it comes to treatment, comorbidities and patient's baseline situation should be considered. CLINICAL TRIAL REGISTRATION: NCT02941458.

Bevacizumab in advanced breast cancer: a new model for the assessment of activity in non-first-line treatment regimens.

The activity of bevacizumab (BVZ) in advanced lines is not well known. In the treatment of metastatic breast cancer, the response rate and time to treatment failure (TTF) decrease with progression through successive therapeutic lines. The objective of this study was to compare BVZ activity in advanced treatment lines with that achieved in the previous line in routine clinical practice. Ninety-six patients who had received BVZ treatment in second or subsequent treatment lines were selected from five Spanish hospitals. Analysis was carried out of the differences in TTF and response rate in the lines with BVZ and those in earlier lines. Data analysis was carried out in two different ways: (a) by comparing treatment groups according to the treatment line received, using a Cox regression model with random effects, and the McNemar test to analysis the response rate, and (b) by comparing intrapatient data, using the Wilcoxon signed-rank test. In 62 patients, the TTF (adjusted for treatment line) was longer in the BVZ treatment line than that in the previous line. In the BVZ lines, there was a significant reduction in the probability of treatment failure [hazard ratio 0.52; 95% confidence interval (CI) 0.38-0.71]. The median TTF was 4.27 months (95% CI 3.7-5) in the previous line and 6.18 months (95% CI 5.5-7.93) in the BVZ line. The percentage of patients with an objective response was 33.3% in the previous lines and 52.1% (P=0.005) in the BVZ line. Contrary to expectation, more patients showed better results with the BVZ line than with the previous line. BVZ treatment in advanced lines improves the results obtained in previous treatment lines. This suggests that BVZ is active in advanced lines and that it produces favourable changes in the natural history of patients with metastatic breast carcinoma.

The influence of peer's social networks on adolescent's cannabis use: a systematic review of longitudinal studies.

Aim: A systematic review was performed to summarize the key findings of the peer influence on cannabis use through Social Network Analysis (SNA) studies and identify limitations and gaps with the purpose of informing future research and practice. Longitudinal studies were included since they provide robust information about social relationships change over time. Background: Adolescents' cannabis use is a global problem, which has awakened an interest in its determinants such as social influences. Research has shown the importance of these influences on cannabis uptake and use. SNA is an useful relational approach to examine socialization mechanisms related to the onset of cannabis use in adolescents. Method: A search was conducted in PyscINFO, PubMed, Scopus and Web of Science for longitudinal articles published until February 2023, to examine cannabis use and peer's social networks. We focus on peers' influence of peers on cannabis use. Additionally, information about effect of cannabis use for peer selection was collected. Results: The results of the included studies (n = 8) showed that friends' cannabis use was most often/strongly associated with cannabis use. There was also an increase of cannabis use when the adolescent did not feel close to the school's peers, had a higher proportion of friendships relative to the total number of ties in the neighborhood, had a central position, did not belong to any group but had ties to members of two or more groups, had cannabis user friends (especially in early ages), and lived in a neighborhood where cannabis was used. Conclusion: Cannabis use is mainly related to friends' use. Yet, future studies are warranted to control for relevant selection effects to further knowledge on network effects on cannabis use, improving the design, and improving the modeling of the network. This systematic review may inform about the critical aspects of preventing cannabis use among adolescents, taking into consideration their complex social environment.

Phase II Trial of Atezolizumab Combined With Carboplatin and Pemetrexed for Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer With Untreated Brain Metastases (Atezo-Brain, GECP17/05).

PURPOSE: The Atezo-Brain study evaluated atezolizumab combined with chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) with untreated brain metastases, a population traditionally excluded from trials. METHODS: This single-arm phase II clinical trial enrolled patients with advanced nonsquamous NSCLC with untreated brain metastases without neurologic symptoms or asymptomatic with medical treatment. Dexamethasone was allowed up to 4 mg once daily. Atezolizumab plus carboplatin and pemetrexed was given for four to six cycles followed by atezolizumab plus pemetrexed until progression for a maximum of 2 years. The primary end points were to determine the progression-free survival (PFS) rate at 12 weeks and the incidence of grade ≥3 adverse events during the first 9 weeks. Intracranial outcomes were assessed using response assessment in neuro-oncology brain metastases criteria. RESULTS: Forty patients were enrolled and 22 (55%) were receiving corticosteroids at baseline. The overall 12-week PFS rate was 62.2% (95% credibility interval [CrI], 47.1 to 76.2). The rate of grade 3/4 adverse events during the first 9 weeks was 27.5%. Most neurologic events were grade 1 and 2 but five patients (12.5%) experienced grade 3-4 neurologic events. With a median follow-up of 31 months, intracranial median PFS was 6.9 months and response rate was 42.7% (95% CrI, 28.1 to 57.9). Systemic median PFS was 8.9 months and response rate was 45% (95% CrI, 28.1 to 57.9). The median overall survival (OS) was 11.8 months (95% CI, 7.6 to 16.9) and the 2-year OS rate was 27.5% (95% CI, 16.6 to 45.5). CONCLUSION: Atezolizumab plus carboplatin and pemetrexed demonstrates activity in patients with advanced nonsquamous NSCLC with untreated brain metastases with an acceptable safety profile.

Real-world treatment patterns and survival outcomes for patients with stage III non-small cell lung cancer in Spain: a nationwide cohort study.

Background: The burden of non-small cell lung cancer (NSCLC) remains high in Spain, with lung cancer accounting for 20% of cancer-related deaths annually. Programs such as the Spanish Thoracic Tumour Registry (TTR) and the global I-O Optimise initiative have been developed to observe patients in clinical practice with the aim of improving outcomes. This analysis examined treatment patterns and survival in patients with stage III NSCLC from the TTR. These patients represent a heterogenous group with complex treatment pathways. Methods: The TTR is an ongoing, observational, prospective, and retrospective cohort multicentre study (NCT02941458) that follows patients with thoracic cancer in Spain. Adults aged ≥18 years with stage IIIA/IIIB NSCLC enrolled in the TTR between 01 Jan 2010 and 31 Oct 2019 were included in this analysis. Initial treatment received was described by cancer stage and histology (squamous and non-squamous NSCLC). Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were calculated over a 5-year period. Results: A total of 1,838 patients were included in the cohort, including 1,082 with stage IIIA (58.9%) and 756 with stage IIIB (41.1%). Median follow-up was 18.3 months. The median age of patients was 66 years, and most had non-squamous NSCLC (54.0%), were male (81.2%), and were active or former smokers (93.4%). Overall, 26.3% of patients received surgical resection (37.0% for stage IIIA and 11.1% for stage IIIB). The most frequent initial treatment received was concurrent chemoradiotherapy for stage IIIA (30.2%) and stage IIIB (37.0%) patients. Median OS was lower in patients with stage IIIB than stage IIIA (28 vs. 37 months) disease and was lower for patients with squamous than non-squamous histology (19 vs. 26 months). Median PFS and OS varied when patients were stratified by initial treatment. Conclusions: This TTR analysis describes the clinical reality surrounding the initial management and survival outcomes for stage III NSCLC in Spain and presents survival outcomes comparable with other real-world evidence. It provides insights into the diverse approaches used before the availability of immunotherapies and targeted treatments in the non-metastatic NSCLC setting.

Atezolizumab Plus Bevacizumab as First-line Treatment for Patients With Metastatic Nonsquamous Non-Small Cell Lung Cancer With High Tumor Mutation Burden: A Nonrandomized Controlled Trial.

Importance: Antiangiogenic drug combinations with anti-programmed cell death 1 protein and anti-programmed cell death 1 ligand 1 (PD-L1) agents are a novel treatment option for lung cancer. However, survival remains limited, and the activity of these combinations for tumors with high tumor mutation burden (TMB) is unknown. Objective: To assess the clinical benefits and safety of atezolizumab plus bevacizumab for patients with high-TMB advanced nonsquamous non-small cell lung cancer (NSCLC). Design, Setting, and Participants: This multicenter, single-arm, open-label, phase 2 nonrandomized controlled trial (Atezolizumab Plus Bevacizumab in First-Line NSCLC Patients [TELMA]) included treatment-naive patients aged 18 years or older with confirmed stage IIIB-IV nonsquamous NSCLC with TMB of 10 or more mutations/megabase and no EGFR, ALK, STK11, MDM2, or ROS1 alterations. From May 2019 through January 2021, patients were assessed at 13 sites in Spain, with follow-up until February 28, 2022. Interventions: Participants were given atezolizumab, 1200 mg, plus bevacizumab, 15 mg/kg, on day 1 of each 21-day cycle. Treatment was continued until documented disease progression, unacceptable toxic effects, patient withdrawal, investigator decision, or death. Main Outcomes and Measures: The primary end point was 12-month progression-free survival (PFS) rate (according to Response Evaluation Criteria in Solid Tumours, version 1.1 criteria); PFS was defined as the time from enrollment to disease progression or death. Adverse events were monitored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: A total of 307 patients were assessed for trial eligibility, of whom 266 were ineligible for enrollment. Of the 41 patients enrolled, 3 did not fulfill all inclusion criteria and were excluded. The remaining 38 patients (28 [73.7%] male; mean [SD] age, 63.7 [8.3] years) constituted the per-protocol population. The 12-month PFS rate was 51.3% (95% CI, 34.2%-66.0%), which met the primary end point. The 12-month overall survival (OS) rate was 72.0% (95% CI, 54.1%-83.9%). The median PFS was 13.0 months (95% CI, 7.9-18.0 months), and the median OS was not reached. Of the 38 patients, 16 (42.1%) achieved an objective response and 30 (78.9%) achieved disease control. The median time to response was 2.8 months (IQR, 2.8-3.58 months), with a median duration of response of 11.7 months (range, 3.57-22.4 months; the response was ongoing at cutoff). Of 16 responses, 8 (50.0%) were ongoing. Most adverse events were grade 1 or 2. For atezolizumab, the most common adverse events were fatigue (6 [15.8%]) and pruritus (6 [15.8%]). For bevacizumab, they were hypertension (10 [26.3%]) and proteinuria (4 [10.5%]). Drug discontinuation occurred in 2 patients receiving atezolizumab (5.3%) and 3 patients receiving bevacizumab (7.9%). PD-L1 levels were not associated with response, PFS, or OS. Conclusions and Relevance: These findings suggest that atezolizumab with bevacizumab is a potential treatment for high-TMB nonsquamous NSCLC. Trial Registration: ClinicalTrials.gov Identifier: NCT03836066.

Immunogenicity of COVID-19 vaccines in lung cancer patients.

OBJECTIVE: Patients with lung cancer are at increased risk of SARS-CoV-2 infection and severe complications from COVID-19, but information on the efficacy of anti-SARS-CoV-2 vaccine in these patients is scarce. We aimed at evaluating the safety and immunogenicity of COVID-19 vaccines in this population. PATIENTS AND METHODS: The prospective, nationwide SOLID substudy, enrolled adults with lung cancer who were fully vaccinated against COVID-19. Serum anti-SARS-CoV-2 IgG antibody levels were quantitatively assessed two weeks and six months after receipt of the last dose using a chemiluminescent microparticle immunoassay. Multivariate odds ratios for the association between demographic and clinical factors and seronegativity after vaccination were estimated. RESULTS: 1973 lung cancer patients were enrolled. Most patients had stage IV disease (66%) and were receiving active cancer treatment (82.7%). No significant differences were found in the probability of being seronegative for anti-SARS-CoV-2 IgG antibodies after full vaccination between patients who were receiving active cancer treatment and those who were not (p = 0.396). The administration of immunotherapy or oral targeted therapy and immunization with mRNA-1273 COVID-19 vaccine were factors independently associated with increased odds of being seropositive after vaccination. From all patients, 1405 received the second dose of vaccine and high levels of antibody titers were observed in 93.6% of patients two weeks after second dose. At six months, multivariate logistic regression analysis showed that performance status ≥ 2 was independently associated with a higher probability of being seronegative after full vaccination with an OR 4.15. On the other hand, received chemotherapy or oral target therapy and vaccination with mRNA-1273 were a factor independently associated with lower odds of being seronegative after full vaccination with an OR 0.52, 0.37 and 0.34, respectively. CONCLUSIONS: Lung cancer patients can safely achieve a strong immune response against SARS-CoV-2 after full vaccination, regardless of the cancer treatment received. TRIAL REGISTRATION: NCT04407143.

Recommendations for the Implementation of the Self-Administration of Alpha-1 Antitrypsin.

Purpose: Administration of exogenous alpha-1 antitrypsin (AAT) is the only specific therapy for the management of pulmonary morbidity in patients with AAT deficiency. It requires weekly or biweekly intravenous infusions, which may impact patient independence and quality of life. Self-administration of AAT therapy is an alternative to reduce the burden for patients who require AAT therapy. We presented herein experts' recommendations for the implementation of a program for the self-administration of AAT. Methods: This project was conducted using a modified nominal group technique and was undertaken in two online meetings involving the participation of 25 experts: specialists in pulmonology (n=17), nurses (n=5) and hospital pharmacists (n=3). Results: The following issues were discussed, and several recommendations were agreed upon on the following topics: a) patient profile and clinical evaluation, establishing selection criteria that should include clinical as well as social criteria; b) role of health care professionals, suggested roles for specialists in pulmonology, nurses, and hospital pharmacists; c) training by the nurse, including recommendations before initiating the training and the content of the training sessions; and d) logistic issues and follow-up, adherence, and patient support. Conclusion: We expect this proposal to increase awareness of this therapeutic alternative and facilitate the implementation of self-administration programs, thus contributing to optimizing the patient experience with AAT therapy. Further research on the outcomes of these programs, especially from the patient perspective, will also help to improve their design and implementation.

Clinical impact of delays in the management of lung cancer patients in the last decade: systematic review.

INTRODUCTION: Due to the importance of lung cancer early treatment because of its severity and extent worldwide a systematic literature review was conducted about the impact of delays in waiting times on the disease prognosis. MATERIALS AND METHODS: We conducted a systematic search of observational studies (2010-2020) including adult patients diagnosed with lung cancer and reporting healthcare timelines and their clinical consequences. RESULTS: We included 38 articles containing data on waiting times and prognosis; only 31 articles linked this forecast to a specific waiting time. We identified 41 healthcare time intervals and found medians of 6-121 days from diagnosis to treatment and 4-19.5 days from primary care to specialist visit: 37.5% of the intervals indicated better prognosis with longer waiting times. CONCLUSIONS: All articles emphasized that waiting times must be reduced to achieve good management and prognosis of lung cancer. Further prospective studies are needed on the relationship between waiting times and prognosis of lung cancer.