Lung Cancer最新文献

{"title":"Identification of key gene signatures for predicting chemo-immunotherapy efficacy in extensive-stage small-cell lung cancer using machine learning","authors":"Daichi Fujimoto ,&nbsp;Ryota Shibaki ,&nbsp;Keiichi Kimura ,&nbsp;Koji Haratani ,&nbsp;Motohiro Tamiya ,&nbsp;Takashi Kijima ,&nbsp;Yuki Sato ,&nbsp;Akito Hata ,&nbsp;Toshihide Yokoyama ,&nbsp;Yoshihiko Taniguchi ,&nbsp;Junji Uchida ,&nbsp;Hisashi Tanaka ,&nbsp;Naoki Furuya ,&nbsp;Satoru Miura ,&nbsp;Mihoko Imaji Onishi ,&nbsp;Shinya Sakata ,&nbsp;Eisaku Miyauchi ,&nbsp;Nobuyuki Yamamoto ,&nbsp;Yasuhiro Koh ,&nbsp;Hiroaki Akamatsu","doi":"10.1016/j.lungcan.2024.108079","DOIUrl":"10.1016/j.lungcan.2024.108079","url":null,"abstract":"<div><h3>Objectives</h3><div>The lack of definitive biomarkers presents a significant challenge for chemo-immunotherapy in extensive-stage small-cell lung cancer (ES-SCLC). We aimed to identify key genes associated with chemo-immunotherapy efficacy in ES-SCLC through comprehensive gene expression analysis using machine learning (ML).</div></div><div><h3>Methods</h3><div>A prospective multicenter cohort of patients with ES-SCLC who received first-line chemo-immunotherapy was analyzed. RNA sequencing was performed on tumor samples to assess gene expression levels. ML techniques were applied to identify key gene features associated with treatment efficacy. A panel of genes was then developed and validated using the nCounter system, and the model’s performance in predicting 180-day progression-free survival (PFS) was evaluated.</div></div><div><h3>Results</h3><div>A total of 93 patients were included in the analysis. ML-based gene selection identified a gene set comprising 83 genes from the comprehensive gene expression data. An nCounter panel was developed using these genes, and an ML model was developed based on their expression levels. In the validation set, the model achieved an accuracy of 0.93, precision of 1.00, a true positive rate of 0.83, and a true negative rate of 1.00. PFS was significantly longer in the high-efficacy group than in the low-efficacy group in the validation set (P &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>These findings provide a foundation for biomarker development in ES-SCLC and highlight the potential of this method as a cost-effective, simple, and rapid tool for assessing treatment efficacy in clinical practice.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"Article 108079"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950820","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":"A reproducibility study on invasion in small pulmonary adenocarcinoma according to the WHO and a modified classification, supported by biomarkers","authors":"Erik Thunnissen ,&nbsp;Hans Blaauwgeers ,&nbsp;Federica Filipello ,&nbsp;Birgit Lissenberg-Witte ,&nbsp;Yuko Minami ,&nbsp;Masayuki Noguchi ,&nbsp;John Le Quesne ,&nbsp;Mauro Giulio Papotti ,&nbsp;Douglas B. Flieder ,&nbsp;Giuseppe Pelosi ,&nbsp;Irene Sansano ,&nbsp;Sabina Berezowska ,&nbsp;Aleš Ryška ,&nbsp;Luka Brcic ,&nbsp;Noriko Motoi ,&nbsp;Yukio Nakatani ,&nbsp;Christiane Kuempers ,&nbsp;Paul Hofman ,&nbsp;Veronique Hofman ,&nbsp;Vibeke Grotnes Dale ,&nbsp;Albrecht Stenzinger","doi":"10.1016/j.lungcan.2024.108060","DOIUrl":"10.1016/j.lungcan.2024.108060","url":null,"abstract":"<div><h3>Objectives</h3><div>Evaluating invasion in non-mucinous adenocarcinoma (NMA) of the lung is crucial for accurate pT-staging. This study compares the World Health Organization (WHO) with a recently modified NMA classification.</div></div><div><h3>Materials and Methods</h3><div>A retrospective case-control study was conducted on small NMA pT1N0M0 cases with a 5-year follow-up. Seventy cases were reviewed by 42 pulmonary pathologists first according to the WHO classification and after tutorial according to a modified classification. A third round was conducted based on feedback from 41 peers of previous rounds. Additionally, orthogonal biomarker analysis was performed.</div></div><div><h3>Results</h3><div>In the first two rounds, 42 pathologists from 13 countries assessed all 70 cases, while 36 pathologists evaluated 41 non-unanimous cases in the third round. Kappa values for invasiveness increased in rounds 1, 2, and 3 to 0.27, 0.45 and 0.62, respectively. In contrast to low variation in total tumor size measurements (6 %), a marked increase in invasive tumor size variation was observed (42 %), which was associated with high uncertainty. In the third round 10 cases were non-invasive, all without recurrence. The modified classification showed in the 3rd round marked reduction of the variation in pT staging compared to the current WHO classification. Proliferation rate, tumor mutational burden, and transcriptomic profiles supported the distinction between invasive cases and non-invasive cases of the modified classification.</div></div><div><h3>Conclusion</h3><div>The modified classification demonstrates essentially higher reproducibility compared to the current WHO classification in NMA. The modified classification proves valuable in identifying low-risk lesions that are entirely non-invasive, and is supported by biomarker analysis.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"Article 108060"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965524","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":"Improving the screening ability of neuron-specific enolase on small cell lung cancer","authors":"Yixian Wu ,&nbsp;Yingdan Tang ,&nbsp;Wen Huang ,&nbsp;Chen Zhu ,&nbsp;Huanyu Ju ,&nbsp;Juan Wu ,&nbsp;Qun Zhang ,&nbsp;Yang Zhao ,&nbsp;Hui Kong","doi":"10.1016/j.lungcan.2024.108078","DOIUrl":"10.1016/j.lungcan.2024.108078","url":null,"abstract":"<div><div>Neuron-specific enolase (NSE) is one of the most common biomarkers of small cell lung cancer (SCLC) and is widely used in lung cancer screening. But its specificity is affected by many factors. Using residual correction and machine learning, corrected NSE and its reference range were constructed based on metabolic factors and smoking history affecting NSE in the training set of 48,009 healthy individuals recruited from the First Affiliated Hospital of Nanjing Medical University. External validation including additional 64,553 healthy subjects and 105 SCLC patients were enrolled to evaluate the efficacy of NSE_corrected for SCLC screening. The reference range of NSE_corrected could significantly improve the specificity of NSE for SCLC and reduce false positives. In the external validation set, NSE_corrected increased the specificity from 85.71 % to 97.09 %(<em>P</em> &lt; 0.0001), and reduced the false positive rate from 14.26 % to 2.91 %(<em>P</em> &lt; 0.0001). ROC curve, calibration curve and decision analysis curve also showed that NSE_corrected had better screening performance. The calculation of NSE_corrected was converted into an online R-based app for more convenient use. NSE_corrected can improve the screening effect of SCLC, reduce the false positive rate, and is more suitable for large population screening and optimize the allocation of lung cancer resources.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"Article 108078"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927464","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 efficacy of the dabrafenib-trametinib (D-T) combination in BRAF V600E-mutated metastatic non-small cell lung cancer (NSCLC): Results from the IFCT-2004 BLaDE cohort","authors":"Aurélie Swalduz ,&nbsp;Michèle Beau-Faller ,&nbsp;David Planchard ,&nbsp;Julien Mazieres ,&nbsp;Sophie Bayle-Bleuez ,&nbsp;Didier Debieuvre ,&nbsp;Vincent Fallet ,&nbsp;Margaux Geier ,&nbsp;Alexis Cortot ,&nbsp;Sébastien Couraud ,&nbsp;Catherine Daniel ,&nbsp;Charlotte Domblides ,&nbsp;Eric Pichon ,&nbsp;Elizabeth Fabre ,&nbsp;Sébastien Larivé ,&nbsp;Ulrike Lerolle ,&nbsp;Pascale Tomasini ,&nbsp;Marie Wislez ,&nbsp;Pascale Missy ,&nbsp;Franck Morin ,&nbsp;Jean-Bernard Auliac","doi":"10.1016/j.lungcan.2024.108038","DOIUrl":"10.1016/j.lungcan.2024.108038","url":null,"abstract":"<div><h3>Background</h3><div>BRAF V600E mutations occur in 2–5 % of advanced non-small cell lung cancer (NSCLC) patients. The dabrafenib-trametinib (D-T) combination was associated with improved and durable OS in patients in phase II. This study (IFCT-2004 BLaDE study) reported the efficacy of D-T combination in a large retrospective French real-world multicenter cohort of patients with advanced BRAF V600E-mutated NSCLC.</div></div><div><h3>Method</h3><div>Patients with advanced BRAF V600E-mutated NSCLC diagnosed between 01.01.2016 and 31.12.2019 and treated with D-T in combination, regardless of the treatment line, were included. The primary endpoint was the 12-month OS rate (%) in patients receiving D-T as a second-line therapy or beyond.</div></div><div><h3>Results</h3><div>A total of 163 patients were included: 50.3 % were female, 30.2 % were never smokers, 95.1 % had adenocarcinoma, and 78.2 % had a PDL1 ≥ 1 %. The median age was 68.3 years. At D-T initiation, 80.8 % of patients had a PS of 0/1, 78.6 % had stage IV disease, and 20.9 % had brain metastasis. At the cutoff, the median follow-up was 27.4 months. The 12-month OS rate in patients receiving D + T as a second-line therapy or beyond (n = 119) was 67.4 %, with a median progression-free survival (mPFS) of 10.4 months. Among the 44 patients who received D + T as a first-line therapy, the 12-month OS rate was 67.4 %, with an mPFS of 18.2 months. D-T discontinuation for toxicity was reported in 10.3 % of patients.</div></div><div><h3>Conclusions</h3><div>To our knowledge, this is the largest retrospective cohort of <em>BRAF-</em>mutated patients reported. The findings confirmed the significant efficacy of D-T in combination with BRAF V600E-mutated metastatic NSCLC in pretreated and untreated patients. These results under real-world conditions are consistent with those of other registered studies.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"Article 108038"},"PeriodicalIF":4.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747220","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":"Difference in efficacy of osimertinib between patients with EGFR-positive NSCLC with postoperative recurrence and those with de novo unresectable disease: A prospective, observational study","authors":"Masato Karayama ,&nbsp;Takafumi Suda ,&nbsp;Kiyotaka Yoh ,&nbsp;Kazuhiro Usui ,&nbsp;Yukio Hosomi ,&nbsp;Kazuma Kishi ,&nbsp;Go Naka ,&nbsp;Kageaki Watanabe ,&nbsp;Shu Tamano ,&nbsp;Kohei Uemura ,&nbsp;Hideo Kunitoh","doi":"10.1016/j.lungcan.2024.108037","DOIUrl":"10.1016/j.lungcan.2024.108037","url":null,"abstract":"<div><h3>Background</h3><div>Although clinical trials of systemic chemotherapy for advanced non-small-cell lung cancer (NSCLC) have included both postoperative recurrence and <em>de novo</em> unresectable cases, postoperative recurrence is reported to have a better efficacy and prognosis. However, there are no efficacy data of first-line osimertinib for postoperative recurrence.</div></div><div><h3>Methods</h3><div>We conducted a post hoc analysis of a multicenter, prospective, observational study that evaluated the efficacy of first-line osimertinib in patients with <em>epidermal growth factor receptor (EGFR)</em>-positive NSCLC. The patients were divided into two groups: those with postoperative recurrence (recurrence group, n = 167) and those with <em>de novo</em> unresectable disease (<em>de novo</em> group, n = 385).</div></div><div><h3>Results</h3><div>The recurrence group had a significantly better Eastern Cooperative Oncology Group performance status (ECOG-PS, <em>p</em> &lt; 0.001) and fewer bone metastases (<em>p</em> &lt; 0.001), brain metastases (<em>p</em> &lt; 0.001), cancer pleurisy (<em>p</em> = 0.006), pleural dissemination (<em>p</em> = 0.003), liver metastases (<em>p</em> = 0.017), and adrenal metastases (<em>p</em> = 0.009) at the start of osimertinib than the <em>de novo</em> group. The recurrence group had a significantly better progression-free survival (PFS) and overall survival (OS) than the <em>de novo</em> group (hazard ratio [HR] = 0.62, 95 % confidence interval [CI], 0.49–0.81, <em>p</em> &lt; 0.001; and HR = 0.58, 95 % CI, 0.43–0.79, <em>p</em> &lt; 0.001, respectively). In a 1:1 propensity score-matching analysis, the matched recurrence group had significantly better PFS and OS than the matched de novo group (HR = 0.72, 95 % CI, 0.52–0.99, <em>p</em> = 0.034; and HR = 0.65, 95 % CI, 0.44–0.95, <em>p</em> &lt; 0.001, respectively).</div></div><div><h3>Conclusion</h3><div>Patients with <em>EGFR</em>-positive NSCLC and postoperative recurrence have a better ECOG-PS and fewer distant metastases at the start of first-line osimertinib, and better PFS and OS than those with <em>de novo</em> unresectable disease. Postoperative recurrence should be considered as a stratification factor in future clinical trials for advanced <em>EGFR</em>-positive NSCLC.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108037"},"PeriodicalIF":4.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721163","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":"Validation of the Lung Immune Prognostic Index in patients with untreated advanced non-small cell lung cancer: Post hoc analysis of the IMpower 130, 131 and 150 trials","authors":"Edouard Auclin ,&nbsp;Matthieu Roulleaux Dugage ,&nbsp;Teresa Gorria ,&nbsp;Charles Vauchier ,&nbsp;Constance Thibault ,&nbsp;Juan Carlos Laguna ,&nbsp;Lorena Lupinacci ,&nbsp;Carme Crous ,&nbsp;Marie Naigeon ,&nbsp;Stéphane Oudard ,&nbsp;Benjamin Besse ,&nbsp;Laura Mezquita","doi":"10.1016/j.lungcan.2024.108039","DOIUrl":"10.1016/j.lungcan.2024.108039","url":null,"abstract":"<div><h3>Introduction</h3><div>LIPI has been strongly correlated with immunotherapy (IT) outcomes in advanced NSCLC. Limited data is available for upfront chemotherapy (CT) + IT combinations. We aimed to study its prognostic value in 1st-line CT +/- IT +/- antiangiogenics.</div></div><div><h3>Methods</h3><div>Data from patients with wild-type <em>EGFR/ALK</em> aNSCLC included in IMpower150, IMpower131, and IMpower130 (international phase 3 multicenter studies) treated with 1st-line CT +/- atezolizumab and/or bevacizumab were retrospectively analysed. LIPI was calculated based on the neutrophil/(leucocytes-neutrophils) (dNLR) ratio and serum LDH: good (dNLR &lt; 3 and LDH &lt; ULN), intermediate (dNLR ≥ 3 or LDH ≥ ULN) and poor (dNLR ≥ 3 and LDH ≥ ULN).</div></div><div><h3>Results</h3><div>Out of 2540 patients, 48.6 % were LIPI good, 40.8 % intermediate and 10.6 % poor. LIPI was significantly associated with treatment outcomes (PFS, OS) in the overall cohort (p &lt; 0.001) and in each treatment cohort (all p &lt; 0.001). After adjustment for age, smoking status, number of metastatic sites, brain or liver involvement and performance status, LIPI remained an independent prognostic factor for PFS and OS. In the LIPI good group (n = 1235), longer PFS was observed in patients treated with CT + IT + AA (median [m] PFS 11.3 vs. &lt; 7.6 months with other regimens, p &lt; 0.001), with a trend for OS (mOS 26.1 vs 20.7 months, p = 0.08). No regimen demonstrated significant PFS benefit in the LIPI poor group compared to chemotherapy. LIPI-good + PD-L1 ≥ 50 % (n = 105) showed long responses (mPFS of 11.1 months, mOS not reached).</div></div><div><h3>Conclusions</h3><div>LIPI was prognostic for PFS and OS in prospective trials in aNSCLC, regardless of the treatment regimen. LIPI poor patients derived no benefit from combination treatment. LIPI combined to PD-L1 may improve the upfront treatment selection.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"Article 108039"},"PeriodicalIF":4.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747218","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":"The efficacy of continuing osimertinib with platinum pemetrexed chemotherapy upon progression in patients with metastatic non-small cell lung cancer harboring sensitizing EGFR mutations","authors":"Tejas Patil ,&nbsp;Dexiang Gao ,&nbsp;Alexander Watson ,&nbsp;Mandy Sakamoto ,&nbsp;Yunan Nie ,&nbsp;Amanda Gibson ,&nbsp;Michelle L Dean ,&nbsp;Benjamin A. Yoder ,&nbsp;Eliza Miller ,&nbsp;Margaret Stalker ,&nbsp;Dara L. Aisner ,&nbsp;Paul A. Bunn ,&nbsp;Erin L. Schenk ,&nbsp;Melina E. Marmarelis ,&nbsp;Chiara Bennati ,&nbsp;Vishal Navani ,&nbsp;Yongchang Zhang ,&nbsp;D. Ross Camidge","doi":"10.1016/j.lungcan.2024.108040","DOIUrl":"10.1016/j.lungcan.2024.108040","url":null,"abstract":"<div><h3>Introduction</h3><div>For patients with EGFR mutant NSCLC who progress on osimertinib, the clinical benefit of continuing osimertinib with next line platinum pemetrexed chemotherapy remains unknown.</div></div><div><h3>Methods</h3><div>In this international, multi-center, retrospective cohort study, a total of 159 patients with EGFR mutant NSCLC who progressed on osimertinib and received platinum-pemetrexed therapy on progression from 2013 to 2023 were included. The data cutoff was December 31, 2023. Data analysis was conducted from January 2024 to June 2024. The primary endpoints were progression free survival (PFS) and overall survival (OS), analyzed using Kaplan-Meier methods. Multivariable Cox regression adjusting for patient-specific and cancer-specific factors was performed.</div></div><div><h3>Results</h3><div>421 patients with EGFR mutant NSCLC with progression on osimertinib were identified, of which159 patients who met pre-specified inclusion criteria were divided into two groups: Cohort 1 (osimertinib + platinum-pemetrexed) included 50 patients (median [IQR] age, 59 [30 – 83] years; 36 [72.0 %] female; 11 [22.4 %] Asian) and Cohort 2 (platinum-pemetrexed alone) included 109 patients (median [IQR] age, 54 [25 – 80] years; 62 [56.9 %] female; 74 [64.9 %] Asian). Most patients were never smokers (Cohort 1, 37 [74.0 %]; Cohort 2, 66 [60.6 %]). One third of patients had baseline brain metastases (Cohort 1, 19 [38.0 %]; Cohort 2, 36 [38.3 %]). Both cohorts had a median of two prior lines of anti-cancer therapy. The addition of bevacizumab or immune checkpoint inhibitors (ICI) to next-line platinum-pemetrexed chemotherapy was more common in Cohort 2 (bevacizumab use, 30.3 % vs 8.0 %, p = 0.002; ICI use, 33.0 % vs 2.0 %, p = 0.001). With a median duration of follow up of 30 months, there was a significant PFS benefit to continuing osimertinib with next line platinum pemetrexed chemotherapy (9.0 vs 4.5 months; HR 0.49, 95 % CI 0.32 – 0.74, p = 0.0032), also seen in subset analyses of patients who received first line osimertinib (n = 55, 11.0 vs 6.2 months; HR 0.41, 95 % CI 0.25 – 0.73, p = 0.002). Among patients with EGFR mutant NSCLC without brain metastases after progression on osimertinib, we found that continuing osimertinib with next line platinum pemetrexed significantly reduced the median time to CNS progression (n = 38; 7.0 vs 4.1 months; HR 0.47, 95 % CI 0.48 – 0.98, p = 0.01). After adjusted analysis, there was no significant OS difference between Cohorts 1 and 2 (19 months vs 13 months; HR 0.92, 95 % CI 0.60 – 1.39, p = 0.68).</div></div><div><h3>Conclusions and relevance</h3><div>For patients with EGFR mutant NSCLC who progress on osimertinib, there is a significant PFS, but not OS, benefit to continuing osimertinib with next line platinum pemetrexed chemotherapy. The continuation of osimertinib with next line platinum pemetrexed chemotherapy appears to reduce the risk of CNS progression.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"Article 108040"},"PeriodicalIF":4.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746977","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":"Impact of HA-PCI on self-reported cognitive functioning and brain metastases in small-cell lung cancer: Pooled findings of NCT01780675 and PREMER trials","authors":"Haiyan Zeng ,&nbsp;Sanne B. Schagen ,&nbsp;Lizza E.L. Hendriks ,&nbsp;Gonzalo Sánchez-Benavides ,&nbsp;Jaap P.M. Jaspers ,&nbsp;Rosa María Manero ,&nbsp;Yolande Lievens ,&nbsp;Mauricio Murcia-Mejía ,&nbsp;Marianne Kuenen ,&nbsp;Mikel Rico-Oses ,&nbsp;Elaine A.C. Albers ,&nbsp;Pilar Samper ,&nbsp;Ruud Houben ,&nbsp;Michiel B. de Ruiter ,&nbsp;Edith M.T. Dieleman ,&nbsp;José Luis López-Guerra ,&nbsp;Katrien De Jaeger ,&nbsp;Felipe Couñago ,&nbsp;Maarten Lambrecht ,&nbsp;Patricia Calvo-Crespo ,&nbsp;Núria Rodríguez de Dios","doi":"10.1016/j.lungcan.2024.108036","DOIUrl":"10.1016/j.lungcan.2024.108036","url":null,"abstract":"<div><h3>Background</h3><div>Cognitive decline is an arising concern in patients who need cranial irradiation. We used the pooled longitudinal individual patient data of two phase III trials: NCT01780675 and PREMER to investigate whether hippocampal avoidance (HA)-PCI is associated with improved self-reported cognitive functioning (SRCF) compared with PCI without increasing brain metastases (BM) development within the HA area.</div></div><div><h3>Methods</h3><div>Patients with stage I-IV small cell lung cancer (SCLC) were randomized to PCI or HA-PCI. SRCF was assessed and contrast enhanced brain magnetic resonance imaging (MRI) was performed at baseline and up to 24 months follow-up. SRCF and BM incidence after (HA)-PCI were compared between arms. Self reported cognitive impairment was defined as SCRF &lt; 75.</div></div><div><h3>Results</h3><div>In total, 318 patients were randomized. Longitudinal generalized estimating equation (GEE) analysis showed that HA-PCI neither had a significant impact on SRCF (β = 1.41, <em>p</em> = 0.52) nor on cognitive impairment (OR 0.81, 95 %CI 0.53–1.25, <em>p</em> = 0.34). The median follow up was 41.7 (95 %CI 35.7–47.6) months, during which 61 patients developed BM (PCI arm: 30, HA-PCI arm: 31<em>, p</em> = 0.9). BM site was solitary in 15 patients (PCI arm: 7, HA-PCI arm: 8<em>, p</em> = 0.8). Nine of the 61 patients had BM within the HA area (PCI arm: 4, HA-PCI arm: 5<em>, p</em> = 1.0). The BM incidence was not significantly different between arms (subdistribution hazard ratio [sHR] 1.03, 95 %CI 0.62–1.70, <em>p</em> = 0.91).</div></div><div><h3>Conclusion</h3><div>HA-PCI did not preserve longitudinal SRCF but did also not increase the risk of BM. Additional strategies should be investigated to further improve the therapeutic ratio of PCI.</div><div>Trials registration:</div><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (NCT01780675)</div><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (NCT02397733).</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"Article 108036"},"PeriodicalIF":4.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747219","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":"Addressing knowledge and attitude barriers to lung cancer screening: Development and evaluation of web-based decision aid","authors":"Wonyoung Jung ,&nbsp;In Young Cho ,&nbsp;Keun Hye Jeon ,&nbsp;Yohwan Yeo ,&nbsp;Jongho Cho ,&nbsp;Kyu-Won Jung ,&nbsp;Kui Son Choi ,&nbsp;Dong Wook Shin ,&nbsp;Jungkwon Lee","doi":"10.1016/j.lungcan.2024.108031","DOIUrl":"10.1016/j.lungcan.2024.108031","url":null,"abstract":"<div><h3>Objective</h3><div>Low-dose computed tomography screening reduces lung cancer and overall mortality, but the participation rate remains low. The objective of this study was to develop a decision aid (DA) that addresses the overabundance of healthcare options and barriers to participation in lung cancer screening (LCS) among the general population aged 40–79 years in Korea.</div></div><div><h3>Materials and Methods</h3><div>The DA was developed by following the International Patient Decision Aid Standards process. To evaluate the DA, participants aged 40–79 years were purposively sampled from four districts of the Seoul metropolitan area, with 25 individuals from each decade of the age range. Participants used the DA for LCS, and pre–post comparison was conducted. The primary outcome was a change in intention to undergo LCS after completing the DA. The secondary outcomes were changes in knowledge and attitude about LCS, decisional conflict, and the perceived usefulness of the DA.</div></div><div><h3>Results</h3><div>The DA prototype contained lung cancer risk assessment and decision-making components that addressed knowledge, risks, benefits, costs, and personal values. In a pilot study of 100 participants (mean age 59.0 [SD 11.1] years, 80 % male, 25 % of whom had undergone LCS), knowledge about LCS increased (mean [SD] score [out of 100] before vs. after: 68.3 [13.4] vs. 73.6 [18.0], p &lt; 0.001). A positive change in attitude was observed (p = 0.004), but the intention to screen remained consistent (70 % before vs. 72 % after; p = 0.650). Eighty-eight participants reported the lowest level of conflict in decision-making, and most reported that the DA was useful (mean [SD] score 78.8 [9.0] out of 100). 72 % reported that the DA facilitated self-decision-making, but 27 % felt the DA recommended LCS.</div></div><div><h3>Conclusions</h3><div>This study highlights the potential of a well-designed DA to enhance knowledge and attitudes about LCS, but those improvements did not translate to a significant change in screening intentions.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108031"},"PeriodicalIF":4.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699628","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":"Lorlatinib-associated weight gain and dyslipidaemia: A retrospective analysis and implications for future care","authors":"A. John ,&nbsp;D.J. McMahon ,&nbsp;D. Chauhan ,&nbsp;S. Mullings ,&nbsp;N. Samuel ,&nbsp;F. Kalofonou ,&nbsp;C. Milner-Watts ,&nbsp;N. Tokaca ,&nbsp;N. Yousaf ,&nbsp;M. Davidson ,&nbsp;J. Bhosle ,&nbsp;A. Minchom ,&nbsp;O’Brien MER ,&nbsp;S. Popat","doi":"10.1016/j.lungcan.2024.108034","DOIUrl":"10.1016/j.lungcan.2024.108034","url":null,"abstract":"<div><h3>Objectives</h3><div>The objective of our study was to benchmark the incidence and severity of lorlatinib-related weight gain and dyslipidaemia in a real-world context, to guide future therapeutic strategies to mitigate these toxicities.</div></div><div><h3>Methods</h3><div>We conducted a retrospective, observational analysis of patients with <em>ALK</em> and <em>ROS1</em>-positive NSCLC at a single institution in the UK who were commenced on lorlatinib from 11/2016 to 11/2022. Non-small cell lung cancer (NSCLC) patients prescribed lorlatinib were identified through institutional electronic pharmacy records. Descriptive analyses were conducted. Patients without recorded baseline weight were excluded from the analysis. Changes in weight, body mass index (BMI), triglycerides, and total/low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol were calculated from serial measurements and graded in accordance with CTCAE v5.0.</div></div><div><h3>Results</h3><div>43 patients were evaluated. 81 % of patients developed weight gain on lorlatinib (median: 4.5 kg, 6.5 % increase from baseline); Grade &lt; 1 in 37 % (<em>n</em> = 16/43), Grade 1 in 23 % (<em>n</em> = 10/43), Grade 2 in 12 % (<em>n</em> = 5/43), and Grade ≥ 3 in 9 % (<em>n</em> = 4/43). BMI increase was observed in 79 % of patients. 35 % of patients with healthy baseline BMI moved into overweight/obese categories.</div><div>Of patients with recorded baseline lipid levels, 91 % developed increase in total cholesterol, and 68 % an increase in triglycerides, respectively. 7 % (<em>n</em> = 1/15) patients with normal baseline total cholesterol developed Grade ≥ 3 elevated cholesterol; no patients with normal baseline triglycerides developed Grade ≥ 3 elevated hypertriglyceridaemia (<em>n</em> = 12). Median time to onset of total cholesterol elevation was 21 days. Lipid-lowering therapy was required in most patients (86 %). One patient developed a non-ST elevation myocardial infarction (NSTEMI) which may have been attributable to lorlatinib.</div></div><div><h3>Conclusion</h3><div>Weight gain and dyslipidaemia are commonly observed with lorlatinib, highlighting the need for effective pharmacologic and non-pharmacologic strategies to manage these toxicities. Rates were similar to those reported in the CROWN trial. Given the 60 % 5-year progression-free survival (PFS) demonstrated in CROWN, mitigation of treatment-related toxicities is paramount to minimise impact on patient quality of life (QOL) and cancer-independent morbidity in this subgroup of NSCLC patients with favourable outcomes.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108034"},"PeriodicalIF":4.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682123","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}