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The present work deals with surface modification and gamma (γ) irradiation treatment to improve the performance of polyester/bitumen emulsion polymer-coated jute woven textiles for geotextile applications. There are different formulations of jute used such as raw (untreated) jute textile fabrics (J0) were modified by HEMA (2-hydroxyethyl methacrylate) monomer (J1), raw jute was only coated with the blend of polyester resin/bitumen emulsion (10 %/30 %) (J2), and the HEMA-treated jute was coated with polymer blends (J3). It was revealed that the HEMA treatment increased the tensile breaking force of the polymer-coated jute textiles (J3) by 13.2 %, and moisture properties decreased by 18–24 %. Further, γ-irradiation of 2.5 and 5.0 kGy was exposed to the processed jute fabrics for the yield of improved performance. In this case, a 5.0 kGy dose of γ-irradiation demonstrated maximum improvement compared to their non-irradiated ones, which is 6.1 % and 3.7 % increase of tensile breaking force for J2 (γ) and J3 (γ), respectively, than their non-irradiated jute samples (J2 and J3), whilst the enhancement of the values were 15.4 % and 17.4 %, respectively, compared to the raw jute (J0) sample. The moisture properties were reduced by up to 60 % as a function of γ-irradiation. Further characterization of the jute fabric samples was assessed by FTIR (Fourier Transform Infrared) Spectroscopy, XRD (X-ray diffraction), TGA (Thermogravimetric Analysis), and SEM (Scanning Electron Microscopy) testing.

Abstract Cocaine/crack abstinence periods have higher risk of relapse. Abstinence as initial part of the recovery process is affected by learning and memory changes that could preserve the addictive cycle. To further understand how the interruption of cocaine/crack consumption affects neurotrophin level we performed the present systematic review and meta-analysis following the PRISMA statement (number CRD42019121643). The search formula was conducted in PubMed, Web of Science, Embase, ScienceDirect, and Google Scholar databases. The inclusion criterion was cocaine use disorder in 18 to 60-year-old people, measuring at least one neurotrophin in blood before and after a controlled abstinence period. Studies without pre-post design were excluded. Five investigations had nine different reports, four of them were subjected to a meta-analysis (n = 146). GRADE risk of bias method was followed. Individual studies reported increased peripheral brain derived neurotrophic factor (BDNF) after abstinence, evidence pooled by Hedge’s g showed no significant change in BDNF after abstinence. Relevant heterogeneity in the length of the abstinence period (12–32 days), last cocaine/crack consumption monitoring and blood processing were detected that could help to explain non-significant results. Further improved methods are suggested, and a potential BDNF augmentation hypothesis is proposed that, if true, would help to understand initial abstinence as a re-adaptation period influenced by neurotrophins such as the BDNF.

Background: Species identification in commercially processed food and feed products is one of the important issues. This study was conducted to develop a genetic method for the detection of pig and cattle species in processed food and feed products using newly designed species-specific primers targeting mitochondrial 12S rRNA gene fragments. Methods: Two sets of specific primers were designed based on the 12S rRNA gene sequences of pig and cattle species from GenBank. The primers were validated by using the DNA extracted from nine different chordates, including pig, cattle, chicken, bata fish, bat, toad, African parrot, rat, and human origin. Annealing temperature ranging from 46-54 °C for 30 seconds and template DNA 1:10 serial dilutions ranging from 10 to 0.00001 ng/µl were employed for primer annealing and sensitivity analysis. Samples were analyzed using optimized Polymerase Chain Reaction (PCR) conditions. Results: The most intense expected DNA bands of pig and cattle were produced at 50 °C. Under that optimized annealing temperature pig and cattle-specific primers did not anneal with the DNA of other chordates. Total extracted DNA 0.001 ng and 0.01 ng of pig and cattle respectively containing the mitochondrial DNA (mtDNA) was successfully detected. Conclusion: These findings indicate that the newly designed primer pairs can be used to detect pig and cattle derivatives in various processed food and feed products. DOI: 10.18502/jfqhc.8.4.8256

The purpose of the study is to examine the role of entrepreneur education in the relationship between entrepreneur career and entrepreneurial self-efficacy. The study serves as substantiation for the previous entrepreneurial career studies and promotes better understanding of factors prompting the antecedents to entrepreneurial behavior. There is a need for more empirical research in this aspect because reviewed literature highlighted a number of problems associated with entrepreneurial education and entrepreneurial career in many nations’ world over and particular the developing countries. The study used survey-based method and SEM-PLS is employed to achieve the research objectives of the study. The data is collected from the manufacturing firms in Pakistan.The empirical evidence on the association between entrepreneurial education, entrepreneurial self-efficacy, and entrepreneurial career with moderating effect of SEN will strengthened previously established models such as the entrepreneurial intention model, which is modification in the theory of planned behavior and entrepreneurial event theory, both of which are linked to the theory of reasoned action. It is assumed that human actions are reasoned, controlled and planned. Thus, action is possible for the consequences of the reflected behavior. The findings are in line with the proposed hypothesized results.The study could offer valuable insights into the stage of entrepreneurial education for a range of stakeholders in Pakistan at particular and the world at large. Perhaps it is among the earliest studies of this kind in Pakistan that examined the effects of entrepreneurial education on students’ attitude toward entrepreneurial career. The outcomes from this study would be of beneficial for variety of interested parties including academicians, policymakers, learning institutions, supervisory bodies and the public in general.

Objective: To describe the experience of a Mexican cancer centre in vulvar cancer and the opportunity to incorporate palliative care (PC) during treatment., Patients and Methods: A retrospective study of clinical and sociodemographic characteristics of women with vulvar cancer referred to the PC service (PCS) between 2010 and 2021 is reported. Frequencies were estimated, as well as medians and IQRs, accordingly. Referral time and overall survival were estimated using the Kaplan-Meier method., Results: 125 women with vulvar cancer were seen between 2010 and 2021, but only 42% were seen at PCS, mostly polysymptomatic, after several visits to the emergency room. 89% of the patients seen at PCS died at home., Conclusions: Vulvar cancer is a rare type of cancer, while squamous cell carcinoma is the most frequent type. At the time of referral, almost half of the patients had severe pain, bleeding, malodor, infection and urinary incontinence. Most of these patients lived in poverty, were poorly educated and had multiple surgeries. PC may play an important role in the care of patients with advanced vulvar cancer, relieving the physical and psychological symptoms, avoiding unnecessary hospitalisation and favouring death at home without pain and other symptoms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: While targeted therapies have transformed the treatment landscape of oncogene-addicted non-small cell lung cancer (NSCLC), the influence of sex on treatment outcomes remains insufficiently understood., Objectives: This systematic review aimed to investigate the impact of sex on clinical outcomes in patients with NSCLC harboring driver fusions treated with targeted therapies enrolled in clinical trials., Data Sources and Methods: A comprehensive literature search was conducted using PubMed, Embase, and relevant conference abstracts to identify phase III randomized and early clinical trials that reported sex-specific data, including progression-free survival (PFS), overall survival (OS), overall response rate, and adverse events (AEs), in patients with fusion-positive NSCLC treated with tyrosine kinase inhibitors (TKIs)., Results: This review involved 10 studies reporting PFS data and 3 studies with OS data, focusing on first-line treatments for ALK fusion (9 studies) and RET fusion-positive (1 study) NSCLC. Pooled analysis of hazard ratios (HRs) for PFS and OS in ALK inhibitors trials revealed no significant differences in survival outcomes based on sex. Additionally, none of the studies provided data on sex-based differences in response rates or toxicities, highlighting a significant knowledge gap regarding the impact of sex on secondary outcomes in targeted therapy., Conclusion: This review found no significant sex-related differences in survival outcomes among patients treated with ALK inhibitors. However, the lack of data on sex-specific response and toxicity emphasizes the need for future research to better understand the role of sex in modulating treatment outcomes and treatment decisions with TKIs., Competing Interests: E.A.—Lectures and educational activities: MSD, Janssen; Consulting, Advisory role: from Amgen and Sanofi; Travel, Accommodations: Amgen, Ipsen. D.M.: Lectures and educational activities: Astellas Pharma, PharmaMar, Roche; Travel, Accommodations: Novartis, Lilly, Bristol-Myers Squibb, Merck. D.I.—Lectures and educational activities: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, F. Hoffmann-La Roche, Johnson & Johnson, Lilly, MSD, Pfizer, Pharmamar, Takeda; Consulting, advisory role: AbbVie, Amgen, AstraZeneca, Bayer, BMS, Beigene, Boehringer Ingelheim, F. Hoffmann-La Roche, Johnson & Johnson, Lilly, Merck, MSD, Pfizer, Pharmamar, Sanofi, Takeda; Clinical Trials: AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, F. Hoffmann-La Roche, GSK, Johnson & Johnson, Lilly, Merck, Mirati, MSD, Novartis, Pfizer, Pharmamar, Sanofi; Research Grants: AstraZeneca, BMS, F. Hoffmann-La Roche, GSK. G.L.R.—Consulting, advisory role: Merck Sharp and Dohme, Takeda, Amgen, Eli Lilly, BMS, F. Hoffmann-La Roche, Italfarmaco, Novartis, Sanofi, Pfizer, AstraZeneca. L.M.—Lectures and educational activities: Bristol-Myers Squibb, AstraZeneca, Roche, Takeda, Janssen, Pfizer, MSD, Radonova; Consulting, advisory role: Roche, Takeda, Janssen, MSD; Research Grants: Inivata, AstraZeneca, Gilead; Travel, Accommodations, Expenses: Bristol-Myers Squibb, Roche, Takeda, AstraZeneca, Janssen. All other authors declare no conflicts of interest., (© The Author(s), 2024.)

Introduction: Pembrolizumab stands as a first-line option for patients with advanced non-small cell lung cancer (NSCLC) and high programmed death-ligand 1 (PD-L1) expression (PD-L1 ≥50%). Several factors such as antibiotic exposure, low body mass index (BMI), certain metastatic location or poor performance status may influence outcomes., Methods: We conducted a multicenter retrospective analysis in a cohort of patients with advanced high PD-L1 expression NSCLC treated with first-line pembrolizumab in clinical practice. We sought to evaluate clinical outcomes according to several factors., Results: Among the 494 included patients, median age was 67.29 years, 77% were male, 54% and 38% were former or current smokers, respectively; 84% had an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1, and 48% had a BMI of <25. 32% of patients had bone metastases, 32% brain metastases and 16% liver metastases. 35% of patients had exposure to antibiotics (AB), 44% to corticosteroids and 62% to proton pump inhibitors (PPi). With a median follow-up of 14.3 months, the median overall survival (OS) and progression-free survival (PFS) were 15.9m (95% CI 13.1 to 18.8) and 9.9m (95% CI 7.7 to 12.1), and the overall response rate (ORR) was 43%. After univariate analysis, median OS in patients with ECOG-PS 0 vs. 1 vs. 2 was 36.7m vs. 14.8m vs. 2.7m (p<0.001). Median OS in patients who received treatment with corticosteroids vs. patients without exposure was 11.4m vs. 22.3m (p<0.001). After multivariate analysis, corticosteroid exposure (HR 1.41) and ECOG-PS (HR 2.40) maintained a prognostic impact., Discussion: First-line pembrolizumab outcomes in advanced high PD-L1 expression NSCLC patients could be negatively influenced by corticosteroid exposure or poor ECOG-PS., Competing Interests: The following authors declare potential conflicts of interest outside the submitted work: DI: Consultation Honoraria: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, F. Hoffmann-La Roche, Johnson & Johnson, Lilly, Merck, MSD, Pfizer, Sanofi, Takeda. Speaker Honoraria: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, F. Hoffmann-La Roche, Johnson & Johnson, MSD, Novartis, Pfizer, Takeda. Clinical Trials: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, F. Hoffmann-La Roche, GSK, Janssen, Lilly, Merck, Mirati Therapeutics, MSD, Novartis, Pfizer, Sanofi. Research grant: AstraZeneca, BMS, F. Hoffmann-La Roche, GSK. AC 12th author: AstraZeneca, Advisory Board, Personal. Bayer, Other, Personal, Speaker honoraria. Boehringer Ingelheim, Advisory Board, Personal. Bristol-Myers Squibb, Advisory Board, Personal. Janssen, Advisory Board, Personal. Lilly, Advisory Board, Personal. Merck Sharp & Dohme, Advisory Board, Personal. Novartis, Advisory Board, Personal. Pfizer, Advisory Board, Personal. PharmaMar, Invited Speaker, Personal. Regeneron, Advisory Board, Personal. Roche, Advisory Board, Personal. Sanofi, Advisory Board, Personal. Takeda, Advisory Board, Personal. Merck Sharp & Dohme, Research Grant, Institutional, Financial interest, Drug-only for Investigator-initiated trial. PI: Advisory role and/or travel compensation: Bristol‐Myers Squibb, F. Hoffmann, La Roche AG, MSD Oncology, Pfizer, Medscape, Astra Zeneca, Takeda, Amgen. JS-L: Astra Zeneca, Invited Speaker, Personal. Astra Zeneca, Advisory Board, Personal. BMS, Invited Speaker, Personal. BMS, Advisory Board, Personal. MSD, Invited Speaker, Personal. MSD, Advisory Board, Personal. Roche, Invited Speaker, Personal. Roche, Advisory board, Personal. Eisai, Invited Speaker, Personal. La Roche Posay, invited Speaker, Personal. AB: Astrazeneca advisory board and personal and invited speaker, BMS expert testimony and invited speaker, MSD invited speaker, Novartis invited speaker, Pfizer invited speaker, Personal, Piere Fabre invited speaker, Roche invited speaker and advisory board, Sanofy advisory board and invited speakerBMS, Principal Investigator, Clinical Trial CA224-1044. Pfizer, Principal Investigator, Clinical Trial C4221016. EA: Consultant or Advisory Role: MSD, Bristol-Myers, Roche, Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Lilly, Takeda. Speaking: MSD, Bristol-Myers, Roche, Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Lilly, Takeda. Co-founder: Trialing Health S.L. MC: Consultant or Advisory Role: Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Lilly, MSD, Takeda, Phyzer, Kyowa, Sanofi,Jansen. Speaking: Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Lilly, MSD, Takeda, Kyowa, Pierre-fabre, Novocure, Sanofi, Jansen. MF: AstraZeneca, Invited Speaker, Personal. BMS, Invited Speaker, Personal. BMS, Advisory Board, Personal. Janssen, Invited Speaker, Personal. Janssen, Advisory Board, Personal. Pfizer, Invited Speaker, Personal. RG-C: Astra Zeneca, Invited Speaker, Personal; Astra Zeneca, Advisory Board, Personal; BMS, Invited Speaker, Personal; BMS, Advisory Board, Personal; Jansen, Advisory Board, Personal; Jansen, Invited Speaker, Personal; lilly, Invited Speaker, Personal; lilly, Advisory Board, Personal; MSD, Advisory Board, Personal; novartis, Invited Speaker, Personal; novartis, Advisory Board, Personal; pfizer, Invited Speaker, Personal; pfizer, Advisory Board, Personal; roche, Invited Speaker, Personal; roche, Advisory Board, Personal; Sanofi, Advisory Board, Personal; Takeda, Advisory Board, Personal; Takeda, Invited Speaker, Personal; Astra Zeneca, Steering Committee Member, Personal, Financial interest; Jansen, Steering Committee Member, Personal, Financial interest. EF: Personal honoraria for advisory board participation from Abbvie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, BMS, Eli Lilly, F. Hoffmann-La Roche, Genmab, Gilead, GSK, Janssen, Merck Serono, MSD, Novartis, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, Turning Point, Daiichi Sankyo; personal speaker honoraria from Amgen, AstraZeneca, BMS, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, MSD, Peervoice, Pfizer, Sanofi, Takeda, Touch Oncology; Board of Director role: Grifols; financial support for meeting attendance and/or travel from AstraZeneca, Janssen, Roche. MM: Advisory Board,consulting fees or sspeakin honoraria: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Helsinn Therapeutics, Eli Lilly, Immedica, Beigene, MSD, Novartis, Pfizer, F. Hoffmann-La Roche Ltd., Takeda, Sanofi, Janssen, Amgen, Cassen. Research funding institution: Bristol-Myers Squibb, AstraZeneca, F. Hoffmann-La Roche Ltd. Travel and accommodation support: AstraZeneca, F. Hoffmann-La Roche Ltd., Pfizer, MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Piedra, Martínez-Recio, Hernández, Morán, Arriola, Recuero-Borau, Cobo, Cordeiro, Mosquera, Fernández, García-Campelo, Calles, Álvarez, Zapata-García, Isla, Callejo, Iranzo, Serra-López, Barba, Sullivan, Felip and Majem.)

Aim: The aim of this study was to assess whether the use of sentinel lymph node (SLN) in addition to lymphadenectomy was associated with survival benefit in patients with early-stage cervical cancer., Methods: International, multicenter, retrospective study., Inclusion Criteria: cervical cancer treated between 01/2007 and 12/2016 by surgery only; squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, FIGO 2009 stage IB1-IIA2, negative surgical margins, and laparotomy approach. Patients undergoing neo-adjuvant and/or adjuvant treatment and/or with positive para-aortic lymph nodes, were excluded. Women with positive pelvic nodes who refused adjuvant treatment, were included. Lymph node assessment was performed by SLN (with ultrastaging protocol) plus pelvic lymphadenectomy ('SLN' group) or pelvic lymphadenectomy alone ('non-SLN' group)., Results: 1083 patients were included: 300 (27.7 %) in SLN and 783 (72.3 %) in non-SLN group. 77 (7.1 %) patients had recurrence (N = 11, 3.7 % SLN versus N = 66, 8.4 % non-SLN, p = 0.005) and 34 (3.1 %) (N = 4, 1.3 % SLN versus N = 30, 3.8 % non-SLN, p = 0.033) died. SLN group had better 5-year disease-free survival (DFS) (96.0 %,95 %CI:93.5-98.5 versus 92.0 %,95 %CI:90.0-94.0; p = 0.024). No 5-year overall survival (OS) difference was shown (98.4 %,95 %CI:96.8-99.9 versus 96.8 %,95 %CI:95.4-98.2; p = 0.160). SLN biopsy and lower stage were independent factors associated with improved DFS (HR:0.505,95 %CI:0.266-0.959, p = 0.037 and HR:2.703,95 %CI:1.389-5.261, p = 0.003, respectively). Incidence of pelvic central recurrences was higher in the non-SLN group (1.7 % versus 4.5 %, p = 0.039)., Conclusion: Adding SLN biopsy to pelvic lymphadenectomy was associated with lower recurrence and death rate and improved 5-year DFS. This might be explained by the lower rate of missed nodal metastasis thanks to the use of SLN ultrastaging. SLN biopsy should be recommended in patients with early-stage cervical cancer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Abu-Rustum received research funding paid to the institution from GRAIL. Memorial Sloan Kettering Cancer Center also has equity in GRAIL. All remaining authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The aim of this study was to compare overall survival between open and minimally invasive radical hysterectomy with participants followed for 4.5 years. The primary objective was to evaluate whether minimally invasive surgery was noninferior in disease-free survival (DFS) to abdominal radical hysterectomy. Secondary outcomes included overall survival. Sample size was based on DFS of 90% at 4.5 years and 7.2% noninferiority margin for minimally invasive surgery. A total of 631 patients were enrolled: 319 assigned to minimally invasive and 312 to open surgery. Of these, 289 (90.6%) patients underwent minimally invasive surgery and 274 (87.8%) patients open surgery. At 4.5 years, DFS was 85.0% in the minimally invasive group and 96% in the open group (difference of -11.1; 95% CI, -15.8 to -6.3; P = .95 for noninferiority). Minimally invasive surgery was associated with lower rate of DFS compared with open surgery (hazard ratio [HR], 3.91 [95% CI, 2.02 to 7.58]; P < .001). Rate of overall survival at 4.5 years was 90.6% versus 96.2% for the minimally invasive and open surgery groups, respectively (HR for death of any cause = 2.71 [95% CI, 1.32 to 5.59]; P = .007). Given higher recurrence rate and worse overall survival with minimally invasive surgery, an open approach should be standard of care.

The development of immune checkpoint inhibitors (ICIs) has changed the therapeutic paradigm of lung cancer (LC), becoming the standard of treatment for previously untreated advanced non-small cell lung cancer (NSCLC) without actionable mutations. It has allowed the achievement of durable responses and resulted in significant survival benefits. However, not all patients respond; hence, molecular biomarkers are needed to help us predict which patients will respond. With this objective, a prospective observational study was designed, including a cohort of 55 patients with NSCLC who received ICIs. We studied whether biomarkers such as TCRβ and specific cytokines involved in the regulation of T cell activity were related to the immunotherapy response. In the survival analysis, it was found that patients with higher TCRβ clonality, lower TCRβ evenness, higher TCRβ Shannon diversity and lower TCRβ convergence had higher overall survival (OS) and progression-free survival (PFS). However, no statistically significant association was observed. Regarding cytokines, those patients with higher levels of IL-2 and IL-15 presented statistically significantly shorter OS and PFS, respectively. In fact, in the multivariable analysis, the high IL-15 level increased the risk of death by three times. Although the sample size was small and more studies are needed to confirm our results, our study reveals promising markers of responses to ICIs.

The use of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs), such as lorlatinib, for the treatment of patients with ALK gene rearrangement (or ALK-positive) non-small cell lung cancer (NSCLC) has been shown to improve the overall survival and quality of life of these patients. However, lorlatinib is not exempt from potential adverse events. Adequate monitoring and management of these adverse events are critical for increasing patient adherence to lorlatinib, thereby maximizing the benefits of treatment and minimizing the risks associated with treatment discontinuation. Considering that the adverse events of lorlatinib can affect different organs and systems, the participation of a multidisciplinary team, including cardiologists, neurologists, internal medicine specialists, and oncology pharmacists, is needed. This article presents specific and pragmatic strategies for identifying and treating the most relevant adverse events associated with lorlatinib in patients with advanced ALK-positive NSCLC based on the clinical experience of a multidisciplinary panel of experts., (© 2024. The Author(s).)

Purpose: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC., Experimental Design: We analyzed tumor samples from 58 patients with ES-SCLC enrolled in two multicenter single-arm phase IIIb studies evaluating frontline chemoimmunotherapy in Spain: n = 32 from the IMfirst trial and n = 26 from the CANTABRICO trial. We used the GeoMx Digital Spatial Profiler system to perform multi-region transcriptomic analysis. For subtype classification, we performed hierarchical clustering using the relative expression of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y)., Results: Subtype distribution was found to be similar between bothcohorts, except for SCLC-P, which was not identified in the CANTABRICO&#95;DSP cohort. A total of 44% of the patients in both cohorts had tumors with multiple coexisting transcriptional subtypes. Transcriptional subtypes or subtype heterogeneity was not associated with outcomes. Most potential targets did not show subtype-specific expression. Consistently in both cohorts, tumors from patients with long-term benefit (time to progression ≥12 months) contained an IFNγ-dominated mRNA profile, including enhanced capacity for antigen presentation. Hypoxia and glycolytic pathways were associated with resistance to chemoimmunotherapy., Conclusions: This work suggests that intratumoral heterogeneity, inconsistent association with outcome, and unclear subtype-specific target expression might be significant challenges for subtype-based precision oncology in SCLC. Preexisting IFNγ-driven immunity and mitochondrial metabolism seem to be correlates of long-term efficacy in this study, although the absence of a chemotherapy control arm precludes concluding that these are predictive features specific for immunotherapy., (©2024 American Association for Cancer Research.)

Lung cancer is a leading cause of morbidity and mortality globally, with its high mortality rate attributed mainly to non-small cell lung cancer (NSCLC). Although immunotherapy with immune checkpoint inhibitors (ICI) has revolutionized its treatment, patient response is highly variable and lacking predictive markers. We conducted a prospective study on 55 patients with NSCLC undergoing ICI therapy to identify predictive markers of both response and immune-related adverse events (IrAEs) in the airway microbiota. We also analyzed the clinical evolution and overall survival (OS) with respect to treatments that affect the integrity of the microbiota, such as antibiotics and corticosteroids. Our results demonstrated that respiratory microbiota differ significantly in ICI responders: they have higher alpha diversity values and lower abundance of the Firmicutes phylum and the Streptococcus genus. Employing a logistic regression model, the abundance of Gemella was the major predictor of non-ICI response, whereas Lachnoanaerobaculum was the best predictor of a positive response to ICI. The most relevant results were that antibiotic consumption is linked to a lower ICI response, and the use of corticosteroids correlated with poorer overall survival. Whereas previous studies have focused on gut microbiota, our findings highlight the importance of the respiratory microbiota in predicting the treatment response. Future research should explore microbiota modulation strategies to enhance immunotherapy outcomes. Understanding the impact of antibiotics, corticosteroids, and microbiota on NSCLC immunotherapy will help personalize treatment and improve patient outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP)., Methods: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI)., Results: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients., Conclusions: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)