Lung Cancer最新文献

{"title":"Blood-brain barrier and blood-brain tumor barrier penetrating peptide-drug conjugate as targeted therapy for the treatment of lung cancer brain metastasis","authors":"Meng-Zhu Zheng ,&nbsp;Zhan-Qun Yang ,&nbsp;Sun-Li Cai ,&nbsp;Li-Ting Zheng ,&nbsp;Yuan Xue ,&nbsp;Long Chen ,&nbsp;Jian Lin","doi":"10.1016/j.lungcan.2024.107957","DOIUrl":"10.1016/j.lungcan.2024.107957","url":null,"abstract":"<div><p>Lung cancer is the leading cause of cancer deaths worldwide. Brain metastasis of lung cancer, which counts for nearly 50% of late-stage lung cancer patients, is a sign of a really poor prognosis. However, the presence of blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB) limits the penetration of drugs from the blood into the brain and thus restricts their accumulation in brain tumors. Systematic delivery of drugs into brain and brain tumor lesion using BBB and BBTB penetrating vehicles represents a promising strategy to overcome the BBB and BBTB limitations. Hence, we validated one of our previously identified BBB/BBTB penetrating peptide and its drug conjugate form for the treatment of lung cancer brain metastasis. With in vitro experiment, we first validated that the receptor LRP1, which mediated the peptide penetration of the BBB, was expressed on lung cancer cells and thus can be targeted by the peptide to overcome BBTB. With this delivery peptide, we constructed peptide-paclitaxel conjugate (the PDC) and in vitro validation showed that the PDC can across the BBB and efficiently kill lung cancer cells. We therefore constructed mouse lung cancer brain metastasis xenograft. In vivo anti-tumor validations showed that the PDC efficiently inhibited the proliferation of the brain resident lung cancer cells and significantly expanded the survival of the mouse xenograft, with no visible damages to the organs. Overall, our study provided potential therapeutic drugs for the treatment of lung cancer brain metastasis that may be clinically effective in the near future.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107957"},"PeriodicalIF":4.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung cancer screening – Time for an update?","authors":"Henry M. Marshall,&nbsp;Kwun M. Fong","doi":"10.1016/j.lungcan.2024.107956","DOIUrl":"10.1016/j.lungcan.2024.107956","url":null,"abstract":"<div><div>Lung cancer screening can reduce the mortality of lung cancer, the leading cause of cancer death worldwide. Real world screening experience highlights areas for improvement in a complex and changing world, particularly ethnic disparity, and the potential for new and emerging risk factors, in addition to well known risk of smoking and asbestos exposure. Biomarkers offer the promise of objective risk assessment but are not yet ready for clinical practice. This review discusses some of the major issues faced by lung cancer screening and the potential role for biomarkers.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107956"},"PeriodicalIF":4.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0169500224004902/pdfft?md5=071bc5b4254ab122d6d6b12bb00daade&pid=1-s2.0-S0169500224004902-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142315326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Soluble PD-L1 shows no association to relapse and overall survival in early stage non-small cell lung cancer (NSCLC)","authors":"F.O. Mildner ,&nbsp;M.M. Sykora ,&nbsp;H. Hackl ,&nbsp;A. Amann ,&nbsp;B. Zelger ,&nbsp;S. Sprung ,&nbsp;M.L. Buch ,&nbsp;F. Nocera ,&nbsp;P. Moser ,&nbsp;H. Maier ,&nbsp;F. Augustin ,&nbsp;C. Manzl ,&nbsp;F. Kocher ,&nbsp;A. Pircher ,&nbsp;J. Lindenmann ,&nbsp;I Mykoliuk ,&nbsp;S. Raftopoulou ,&nbsp;J. Kargl ,&nbsp;D. Wolf ,&nbsp;S. Sopper ,&nbsp;G. Gamerith","doi":"10.1016/j.lungcan.2024.107955","DOIUrl":"10.1016/j.lungcan.2024.107955","url":null,"abstract":"<div><h3>Background</h3><p>Cancer immune evasion is critical in non-small cell lung cancer (NSCLC) and has been targeted by immunotherapy. High soluble (s)PD-L1 is associated with reduced survival and treatment failure in advanced stages. Here we evaluated the effects of sPD-L1 on T cells, relapse free survival, and overall survival in early stage NSCLC.</p></div><div><h3>Methods</h3><p><em>In vitro</em> T cell stimulation was performed in the presence of sPD-L1 to evaluate its immunomodulatory activity. Data from The Cancer Genome Atlas (TCGA) were investigated for PD-L1 splice variants and enzymes involved in proteolytic cleavage (<em>i.e.</em> ADAM10). Plasma from 74 NSCLC (stage IA-IIIB), as well as an additional 73 (control cohort) patients was collected prior to curative surgery. Thereafter sPD-L1 levels from an immunosorbent assay were correlated with patient outcome.</p></div><div><h3>Results</h3><p><em>In vitro</em> sPD-L1 inhibited IFN-γ production and proliferation of T cells and induced a terminal effector CD4 T cell subtype expressing CD27. Data from the TCGA demonstrated that elevated mRNA levels of ADAM10 is a negative predictor of outcome in NSCLC patients. To investigate the clinical relevance of these <em>in vitro</em> and TCGA findings, we quantified sPD-L1 in the plasma of early-stage NSCLC patients. In the first cohort we found significantly higher sPD-L1 levels in relapsing NSCLC patients, with a multivariate analysis revealing high sPD-L1 (&gt;1000 pg/mL) as an independent predictor of survival. However, these findings could not be validated in two independent control cohorts.</p></div><div><h3>Discussion</h3><p>Although <em>in vitro</em> and TCGA data support the suppressive effect of sPD-L1 we were unable to translate this in our clinical setting. These results may be due to the small patient number and their heterogeneity as well as the lack of a standardized sPD-L1 ELISA. Our inconclusive results regarding the value of sPD-L1 in early stage NSCLC warrant assay validation and further investigation in larger (neo-)adjuvant trials.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107955"},"PeriodicalIF":4.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0169500224004896/pdfft?md5=6fb15516e5a0f75c49b45de97233b970&pid=1-s2.0-S0169500224004896-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between lorlatinib blood concentration and adverse events and clinical impact of dose modification","authors":"Yukiko Shimoda Igawa ,&nbsp;Tatsuya Yoshida ,&nbsp;Reiko Makihara ,&nbsp;Masahiro Torasawa ,&nbsp;Akiko Tateishi ,&nbsp;Yuji Matsumoto ,&nbsp;Yuki Shinno ,&nbsp;Yusuke Okuma ,&nbsp;Yasushi Goto ,&nbsp;Hidehito Horinouchi ,&nbsp;Noboru Yamamoto ,&nbsp;Yuichiro Ohe","doi":"10.1016/j.lungcan.2024.107954","DOIUrl":"10.1016/j.lungcan.2024.107954","url":null,"abstract":"<div><h3>Objectives</h3><p>Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) inhibitor, causes distinct adverse events (AEs), including hyperlipidemia and central nervous system (CNS) disorders. Although dose modifications are recommended to manage these AEs, whether dose modifications can achieve optimal blood lorlatinib concentrations and reduce the incidence of lorlatinib-induced AEs remains unclear. Therefore, we investigated the association between lorlatinib exposure and AEs in each patient.</p></div><div><h3>Materials and methods</h3><p>We retrospectively reviewed patients with advanced ALK-rearranged non-small cell lung cancer treated with lorlatinib between November 2018 and July 2022. Serum lorlatinib concentrations were assessed using high-performance liquid chromatography–tandem mass spectrometry. All AEs were evaluated using the Common Terminology Criteria for Adverse Events version 5.0.</p></div><div><h3>Results</h3><p>The median age of the 55 eligible patients was 59 years (range: 23–79 years). All patients were administered lorlatinib after first line ALK-tyrosine kinase inhibitor failure. Grade ≥ 3 AEs occurred in 25 patients (25/55, 45 %), including hyperlipidemia in 17 (17/55, 31 %), CNS disorders in 7 (7/55, 13 %), and edema in 6 (6/55, 11 %). Dose modification was required in 23 patients (23/55, 42 %). Among the 36 patients with available data on serum lorlatinib levels at day 28 (±14) and no drug dose modifications, lorlatinib serum concentrations were significantly higher in patients with grade ≥ 3 AEs than in those without AEs (median: 462 ng/mL vs. 177 ng/mL, p &lt; 0.01). In eight patients with data on serial lorlatinib serum concentrations following dose modifications, lorlatinib serum concentrations were effectively reduced, facilitating the ongoing administration of lorlatinib. Additionally, no significant difference was observed in the landmark analysis of progression-free survival between patients with dose modification within the first 16 weeks and those without (median: 24.8 months vs. 10.1 months, p = 0.46).</p></div><div><h3>Conclusion</h3><p>Dose modification of lorlatinib was associated with successful management of AEs and decreased serum concentration of lorlatinib.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107954"},"PeriodicalIF":4.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional resilience and overall survival in adults treated for advanced non-small-cell lung cancer","authors":"Carolyn J. Presley ,&nbsp;Joy Tang ,&nbsp;Jason Benedict ,&nbsp;Madison Grogan ,&nbsp;Sarah Reisinger ,&nbsp;Sarah Janse ,&nbsp;Melisa L. Wong ,&nbsp;Nicole A. Arrato ,&nbsp;Ashley Davenport ,&nbsp;Peter G. Shields ,&nbsp;Barbara L. Andersen","doi":"10.1016/j.lungcan.2024.107953","DOIUrl":"10.1016/j.lungcan.2024.107953","url":null,"abstract":"<div><h3>Purpose</h3><p>As more treatments emerge for advanced, stage IV non-small-cell lung cancer (NSCLC), oncologists have difficulty predicting functional resiliency versus functional decline throughout cancer treatment. Our study evaluates functional resilience among patients with advanced NSCLC.</p></div><div><h3>Methods</h3><p>Functional status was evaluated through 12 months of follow-up based on disability score using the modified EQ-5D-5L (mEQ-5D-5L) survey. Participants were classified into 4 groups: functional maintenance, decline, resilient, or variable. Characteristics of 207 participants with newly diagnosed NSCLC included demographics, comorbidities, baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS), mEQ-5D-5L scores, psychological symptoms, and lung cancer-specific symptoms. Treatment toxicity and grade were recorded. Resilience was defined as improvement from baseline disability scores. A 1-point increase in functional status score represents a 0.5 standard deviation change on the mEQ-5D-5L. Differences between the 4 groups were determined through Fisher’s exact test or ANOVA. Kaplan-Meier curves describe overall survival (baseline through 18 months) stratified by baseline mEQ-5D-5L scores.</p></div><div><h3>Results</h3><p>Among participants, 42.0 % maintained functional status, 37.7 % experienced functional decline, 10.6 % were resilient, and 9.7 % had variable functional status. Participants with the best baseline function (score of 0) had the longest overall survival and participants with the worst baseline function (score of 5 + ) had the shortest overall survival. Among the healthiest patients, early score increases indicated shorter overall survival. Baseline ECOG PS was not associated with overall survival (p = 0.47).</p></div><div><h3>Conclusion</h3><p>Baseline functional status may help better predict functional resiliency and overall survival than ECOG PS among patients receiving treatment for advanced NSCLC.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107953"},"PeriodicalIF":4.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular profiling METex14+ non-small cell lung cancer (NSCLC): Impact of histology","authors":"Jennifer A. Marks ,&nbsp;Nishant Gandhi ,&nbsp;Balazs Halmos ,&nbsp;Melina E. Marmarelis ,&nbsp;So Yeon Kim ,&nbsp;Lyudmila Bazhenova ,&nbsp;Suresh S. Ramalingam ,&nbsp;Joanne Xiu ,&nbsp;Phillip Walker ,&nbsp;Matthew J. Oberley ,&nbsp;Patrick C. Ma ,&nbsp;Stephen V. Liu","doi":"10.1016/j.lungcan.2024.107935","DOIUrl":"10.1016/j.lungcan.2024.107935","url":null,"abstract":"<div><h3>Objectives</h3><p><em>MET</em> exon 14 skipping alterations (<em>MET</em>ex14+) represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) with distinct biological and genomic features. We characterized this heterogeneity in a large cohort, integrating genomic and transcriptomic profiling with clinical outcomes, to elucidate the histologic and molecular traits and survival patterns of <em>MET</em>ex14+ NSCLC.</p></div><div><h3>Materials and methods</h3><p>NSCLC tissue samples (n = 28,739) underwent DNA-based next-generation sequencing (592 genes, NextSeq) or whole-exome sequencing (NovaSeq), RNA-sequencing including whole transcriptome sequencing (WTS, NovaSeq), and PD-L1 IHC (Dako 22C3) at Caris Life Sciences. Immune cell fractions were estimated from bulk RNA sequencing (quanTIseq). Real-world survival data (mOS) was calculated from insurance claims. Statistical analyses employed Chi-square, Fisher’s exact, or Mann-Whitney U and log-rank tests and were corrected for hypothesis testing where applicable.</p></div><div><h3>Results</h3><p>A total of 711 <em>MET</em>ex14+ cases were detected. Of 575 cases of defined histology, 77 (13.6 %) were squamous (Sq), 474 (82.3 %) were nSq (non-squamous), and 24 (4.1 %) were adenosquamous. Mutations in <em>POT1</em> and <em>BRCA2</em> were enriched, and amplifications in <em>MDM2</em>, <em>HMGA2</em>, <em>CDK4,</em> and <em>MET</em> were common in <em>MET</em>ex14+ tumors. TMB-high and <em>TP53</em> mutated tumors were reduced in <em>MET</em>ex14+ independent of histology. <em>KEAP1</em> (2.1 vs 14.7 %) and <em>STK11</em> mutations (0.8 vs 17.1 %) were reduced only in <em>MET</em>ex14+ nSq (vs <em>MET</em>ex14+ Sq, q &lt; 0.05). While the prevalence of PD-L1 high tumors was enriched in <em>MET</em>ex14+ independent of histology, T-cell inflamed tumors were enriched only in nSq <em>MET</em>ex14+. B-cells and CD8+ T-cells (1.07–1.43-fold) were enriched in nSq <em>MET</em>ex14+, and dendritic cells (0.32 fold) were reduced only in <em>MET</em>ex14+ Sq. <em>MET</em>ex14+ tumors had a modest improvement in mOS compared to <em>MET</em>ex14- tumors (mOS = 22.9 m vs 18.6 m, HR = 0.914, p = 0.04). Moreover, <em>MET</em>ex14+ tumors who received immunotherapy (IO) had a modest improvement in survival (mOS = 27.5 m vs 21.8 m; HR = 0.803, p = 0.03) compared to those who did not receive IO. <em>MET</em>ex14+ nSq tumors were associated with improved mOS compared to <em>MET</em>ex14+ Sq tumors (mOS = 27.7 vs 8.9 m, HR = 0.493, p &lt; 0.0001).</p></div><div><h3>Conclusion</h3><p><em>MET</em>ex14+ alterations are a heterogeneous subgroup of NSCLC. Our analysis reveals that <em>MET</em>ex14+ nSq exhibit improved survival compared to <em>MET</em>ex14+ Sq. The distinct genomic and transcriptomic variations across histologies warrant clinical consideration.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107935"},"PeriodicalIF":4.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What’s behind thoracic surgery explosion in young patients under the age of 40 in Wuhan after COVID-19 outbreak?","authors":"Chang Zhu","doi":"10.1016/j.lungcan.2024.107937","DOIUrl":"10.1016/j.lungcan.2024.107937","url":null,"abstract":"<div><h3>Introduction</h3><p>The COVID-19 pandemic was associated with a dramatic increase of chest CT scanning in Wuhan. This was partly a COVID effect: some private and public employers required employees to have CT examinations to confirm they were healthy before going back to work. But it also likely reflects the growing enthusiasm for low-dose computed tomography (LDCT) screening. This investigation examines the resulting impact in the under 40 population.</p></div><div><h3>Methods</h3><p>The relevant de-identified information of the patients under age 40 who had also received thoracic surgery from 2018 to 2022 was analyzed using the medical record information system of Tongji Hospital in Wuhan.</p></div><div><h3>Results</h3><p>The volume of thoracic surgeries increased continuously in young patients under the age of 40, from 219 in 2018 to 732 in 2022. The number of surgeries for pulmonary nodules or masses in this group increased over 6-fold, from 91 to 576. The number of surgeries leading to a diagnosis of adenocarcinoma of the lung increased more than 15-fold, from 26 to 415. The median adenocarcinoma size fell in half (from 15 mm to 7 mm) and the most common stage changed from Stage I invasive (46 % of adenocarcinomas in 2018) to microinvasive (60 % of adenocarcinomas in 2022). 70 % of lung adenocarcinomas were found in females.</p></div><div><h3>Conclusions</h3><p>There had been an explosion of thoracic surgery for adenocarcinomas among the under-40 population in Wuhan. The decrease in tumor size and the increase in microinvasive and in situ lesions in this young age group suggest considerable overdiagnosis. We should be vigilant about the risk of overdiagnosis and overtreatment especially in young women.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107937"},"PeriodicalIF":4.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New diagnostic and nonsurgical local treatment modalities for early stage lung cancer","authors":"Stephanie Peeters ,&nbsp;Kelvin Lau ,&nbsp;Konstantinos Stefanidis ,&nbsp;Kazuhiro Yasufuku ,&nbsp;Tsukasa Ishiwata ,&nbsp;Christian Rolfo ,&nbsp;Didier Schneiter ,&nbsp;Georgia Hardavella ,&nbsp;Matthias Guckenberger ,&nbsp;Olivia Lauk","doi":"10.1016/j.lungcan.2024.107952","DOIUrl":"10.1016/j.lungcan.2024.107952","url":null,"abstract":"<div><p>This paper highlights developments in diagnostic and nonsurgical local treatment modalities that have changed the management of early-stage lung cancer. These innovations aim to enhance diagnostic accuracy, minimize invasiveness, and improve patient outcomes.</p><p>Liquid biopsies are emerging as promising tools for non-invasive diagnosis and monitoring, enabling earlier intervention without being standardized yet as well as not yet anchored in the guidelines. Endobronchial navigation has emerged as an innovative tool. By combining electromagnetic or GPS-like technology with 3D imaging and a steerable catheter, it enables accurate biopsy of small, peripheral lesions that were once challenging to sample, with a very low pneumothorax rate.</p><p>Regarding nonsurgical treatments, stereotactic body radiotherapy (SBRT) continues to shine as a non-invasive local treatment modality for early-stage lung cancer and is the guideline-recommended standard-of-care for inoperable patients and patients refusing the risk of surgical resection. The low toxicity and excellent local control has made it an attractive alternative to surgery even in fitter patients. Percutaneous ablative techniques utilising energies such as microwave or pulse-field electroporation are options for patients who are not candidates for surgery or SBRT. Bronchoscopic ablation delivers the same energies but with a very lower pneumothorax rate and it is therefore also open to patients with multiple and bilateral lesions.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107952"},"PeriodicalIF":4.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world overall survival after alternative dosing for pembrolizumab in the treatment of non-small cell lung cancer: A nationwide retrospective cohort study with a non-inferiority primary objective","authors":"Geeske F Grit ,&nbsp;Esmée van Geffen ,&nbsp;Ruben Malmberg ,&nbsp;Roelof van Leeuwen ,&nbsp;Stefan Böhringer ,&nbsp;Hans JM Smit ,&nbsp;Pepijn Brocken ,&nbsp;Job FH Eijsink ,&nbsp;Esther Dronkers ,&nbsp;Pim Gal ,&nbsp;Eva Jaarsma ,&nbsp;Regine JHM van Drie-Pierik ,&nbsp;Anne MP Eldering-Heldens ,&nbsp;AN Machteld Wymenga ,&nbsp;Peter GM Mol ,&nbsp;Juliëtte Zwaveling ,&nbsp;Doranne Hilarius","doi":"10.1016/j.lungcan.2024.107950","DOIUrl":"10.1016/j.lungcan.2024.107950","url":null,"abstract":"<div><h3>Background</h3><p>High and increasing expenses on pembrolizumab ask for more cost-effective and sustainable treatment strategies to improve affordability of healthcare. Therefore, a part of the Dutch hospitals implemented an alternative, partially lower, weight-based dosing protocol for pembrolizumab. This provided the unique opportunity to compare the overall survival (OS) of the alternative pembrolizumab dosing protocol to standard dosing using a nationwide registry in non-small cell lung cancer (NSCLC) patients.</p></div><div><h3>Methods</h3><p>This is a retrospective cohort study with a non-inferiority primary objective. Forty hospitals in the Dutch Medication Audit and Dutch Lung Cancer Audit treated 1966 patients with NSCLC with first line pembrolizumab (mono- or combination therapy) between Jan 1st 2021, and Mar 31st, 2023. Alternative weight-based pembrolizumab dosing (100/150/200 mg Q3W or 200/300/400 mg Q6W) was administered to 604 patients, and 1362 patients received standard pembrolizumab dosing (200 mg Q3W or 400 mg Q6W). A Cox proportional hazard model with selected covariates was used to compare the OS between alternative and standard dosing protocols. The non-inferiority margin was set at a hazard ratio (HR) of 1.2 for OS. Non-inferiority is established by showing that the upper limit of the 95 % confidence interval (CI) of the HR of OS is smaller or equal to 1.2.</p></div><div><h3>Results</h3><p>Distribution of age (66.7 years +/-9.4), sex (45 % female) and treatment combinations were similar for both groups, comorbidity score was higher in the standard group. Median daily dose in the alternative dosing group was 22 % lower compared to the standard dosing group, 7.14 mg/day (interquartile range (IQR):5.48–8.04 mg/day) vs. 9.15 mg/day (IQR:8.33–9.52 mg/day), respectively. Alternative dosing was non-inferior to standard dosing regarding overall survival (adjusted HR 0.83, 95 %CI:0.69–1.003).</p></div><div><h3>Conclusion</h3><p>This large, retrospective real-world analysis supports the hypothesis that the alternative, partially lower pembrolizumab dosing protocol in NSCLC maintains treatment effectiveness while reducing treatment costs.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107950"},"PeriodicalIF":4.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0169500224004847/pdfft?md5=bf8a047be08faefbf97a909981240bde&pid=1-s2.0-S0169500224004847-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: Effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules","authors":"Guanyu Yang,&nbsp;Qinjun Chu","doi":"10.1016/j.lungcan.2024.107938","DOIUrl":"10.1016/j.lungcan.2024.107938","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107938"},"PeriodicalIF":4.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142117393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}