Lung Cancer最新文献

{"title":"Early experience with PEF in the setting of recalcitrant stage IV lung cancer","authors":"William H. Moore ,&nbsp;Mikhail Silk ,&nbsp;Priya Bhattacharji ,&nbsp;Bradley B. Pua ,&nbsp;Joseph Mammarappallil ,&nbsp;Daniel H. Sterman ,&nbsp;Abraham Chachoua","doi":"10.1016/j.lungcan.2025.108575","DOIUrl":"10.1016/j.lungcan.2025.108575","url":null,"abstract":"<div><h3>Background</h3><div>Advanced-stage non-small cell lung cancer treatment has evolved with the introduction of molecularly targeted therapy, immunotherapy and combination frontline therapies. Despite these advancements, most patients experience treatment failure, resulting in poor prognosis characterized by low median progression-free survival (PFS) and overall survival (OS). Second-line chemotherapy has demonstrated minimally improved survival compared to best supportive care. Exploring new mechanisms to enhance treatment response in this patient population is critical.</div></div><div><h3>Objective</h3><div>This retrospective study aims to assess if there is survival benefit in a cohort of patients with stage IV lung cancer who have failed previous systemic therapy treated with pulsed electrical fields (PEF) therapy compared to a propensity-matched cohort.</div></div><div><h3>Methods</h3><div>A retrospective review of patients treated with PEF at three academic institutions from January 1, 2023, to July 1, 2024, yielded 41 patients with progressive stage IV non-small cell lung cancer. Tumor response was evaluated by RECIST 1.1 criteria. A propensity matched cohort of 50 patients with advanced NSCLC undergoing systemic therapy was identified. Statistical analyses, including Kaplan-Meier survival estimates and Hazard ratios, were conducted.</div></div><div><h3>Results</h3><div>The PEF-treated cohort exhibited a 1-year PFS of 63.2 % and OS of 74.3 %. In contrast, the matched cohort demonstrated a 1-year PFS of 11.8 % and OS of 33 %. The hazard ratio for PFS in the PEF group was 3.66 (p &lt; 0.0001) and for OS was 3.5 (p = 0.0007), indicating a significant survival advantage for patients receiving PEF.</div></div><div><h3>Conclusion</h3><div>This study suggests that PEF therapy may be associated with significantly improved PFS and OS in patients with progressive stage IV non-small cell lung cancer compared to the matched cohort. Prospective controlled studies are required to confirm these preliminary findings, to better understand the mechanism of action of PEF, and to identify which patient populations would best benefit from this therapy.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108575"},"PeriodicalIF":4.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125199","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 prospective study on clinicians’ attitudes and survival outcomes for patients with advanced NSCLC and poor performance status in the immunotherapy era: PICASO (GOIRC-04-2020)","authors":"Francesco Facchinetti ,&nbsp;Andrea Camerini ,&nbsp;Chiara Bennati ,&nbsp;Paola Bordi ,&nbsp;Elisa De Carlo ,&nbsp;Francesca Mazzoni ,&nbsp;Giulio Metro ,&nbsp;Federica Bertolini ,&nbsp;Lucia Longo ,&nbsp;Serena Ricciardi ,&nbsp;Sara Pilotto ,&nbsp;Donatella Giardina ,&nbsp;Francesco Passiglia ,&nbsp;Vieri Scotti ,&nbsp;Paolo Piacentini ,&nbsp;Stefano Frega ,&nbsp;Luana Calabrò ,&nbsp;Annalisa Guida ,&nbsp;Maria Antonietta Grosso ,&nbsp;Jenny Longobardi ,&nbsp;Marcello Tiseo","doi":"10.1016/j.lungcan.2025.108580","DOIUrl":"10.1016/j.lungcan.2025.108580","url":null,"abstract":"<div><h3>Background</h3><div>Therapeutic strategies for patients with advanced NSCLC and an ECOG performance status (PS) 2 at diagnosis are supported by limited evidence.</div></div><div><h3>Patients and methods</h3><div>We led a prospective, observational study in 20 Italian centers on patients with advanced NSCLC and ECOG PS 2. Patients with <em>EGFR</em> mutations, <em>ALK</em> fusions or receiving first-line targeted treatments were excluded. We recorded physicians’ attitudes in addressing first-line treatments and clinical outcomes. The primary endpoint was progression-free rate at six months.</div></div><div><h3>Results</h3><div>From March 2022 to October 2023, 198 consecutive patients were included. Median age was 73 years (range 43–91). Forty-four patients (22%) were candidate to best supportive care, 49 (25%) to single agent chemotherapy, 14 (7%) to platinum doublet, 40 (20%) to mono-immunotherapy, 52 (26%) to chemo-immunotherapy. At a median follow-up of 9.4 months (95 % CI 7.2 – 11.7), 6-month progression-free rate was 15.3%, with a median progression-free survival of 1.6 months (95 % CI 1.3 – 1.9). Six-months overall survival (OS) rate was 27.7%, with a median OS of 2.8 months (95 % CI 2.0 – 3.6). Patients receiving chemo-immunotherapy (PD-L1 &lt; 50%) had 6-month progression-free and OS rates of 22.9% and 29.1% respectively, with median PFS 1.9 months and median OS 3.7 months; mono-immunotherapy for patients with PD-L1 ≥ 50% led to slightly better outcomes. Among 155 patients receiving active treatment, no clinical-pathological characteristic harbored a prognostic role. One third of patients receiving immunotherapy-containing regimens encountered early clinical progression or death before the first radiological evaluation. No relevant safety signals emerged across treatments.</div></div><div><h3>Conclusions</h3><div>Less than half of patients with NSCLC and ECOG PS 2 were candidates to the regimens recommended for fit pts, <em>i.e.</em> mono-immunotherapy or chemo-immunotherapy according to PD-L1. Even with immunotherapy, most of these patients have dismal outcomes, suggesting that trials dedicating to PS 2 perform an intrinsic patient selection.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108580"},"PeriodicalIF":4.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069856","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 durvalumab re-administration after moderate symptomatic pneumonitis in locally advanced non-small cell lung cancer","authors":"Yosuke Kakiuchi ,&nbsp;Koichi Saruwatari ,&nbsp;Takaaki Tokito ,&nbsp;Toyohisa Iriki ,&nbsp;Jun Iwakawa ,&nbsp;Yoshihiko Sakata ,&nbsp;Naoki Shingu ,&nbsp;Sho Saeki ,&nbsp;Megumi Inaba ,&nbsp;Akira Takaki ,&nbsp;Shunsuke Misono ,&nbsp;Takayuki Suetsugu ,&nbsp;Kenta Murotani ,&nbsp;Koichi Azuma ,&nbsp;Keiko Mizuno ,&nbsp;Takuro Sakagami","doi":"10.1016/j.lungcan.2025.108578","DOIUrl":"10.1016/j.lungcan.2025.108578","url":null,"abstract":"<div><h3>Background</h3><div>The standard of care for unresectable locally advanced non-small cell lung cancer (LA-NSCLC) includes post-chemoradiotherapy durvalumab consolidation therapy. However, moderate symptomatic pneumonitis (Grade 2) constitutes a significant adverse event that frequently leads to treatment interruption and warrants careful consideration of re-administration. We evaluated the efficacy and safety of durvalumab re-administration after recovery from grade 2 pneumonitis.</div></div><div><h3>Methods</h3><div>This retrospective study included 208 patients with LA-NSCLC who received post-chemoradiotherapy durvalumab consolidation therapy at seven institutions between July 2018 and March 2022. Among them, 62 developed Grade 2 pneumonitis that led to treatment interruption and were stratified into the durvalumab re-administration (n = 33) and durvalumab non-re-administration (n = 29) groups. Survival outcomes were analyzed using the Cox proportional hazards model.</div></div><div><h3>Results</h3><div>Participants in the durvalumab re-administration group had significantly longer progression-free survival (PFS; 32.0 months [95 % confidence interval (CI): 11.7–Not Available (NA)] vs. 5.3 months [95 % CI: 3.5–17.4], <em>P</em> = 0.003) and overall survival (OS; not reached [95 % CI: 29.0–NA] vs. 27.1 months [95 % CI: 12.1–NA], <em>P</em> = 0.012) than in the durvalumab non-re-administration group. Pneumonitis recurred in 30.3 % of the re-administration group, albeit without Grade ≥ 3 events. Multivariate analysis identified durvalumab re-administration as an independent predictor of improved survival, with hazard ratios of 0.31 (95 % CI: 0.15–0.65, <em>P</em> = 0.002) for PFS and 0.33 (95 % CI: 0.13–0.82, <em>P</em> = 0.017) for OS.</div></div><div><h3>Conclusion</h3><div>Durvalumab re-administration after grade 2 pneumonitis was associated with prolonged survival and a low recurrence rate of mild pneumonitis, which suggests that re-administration is a feasible, effective strategy with adequate monitoring.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108578"},"PeriodicalIF":4.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928642","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":"Feasibility, acceptability and clinical outcomes of a real-world, regional lung cancer prehabilitation programme for patients undergoing curative intent radiotherapy","authors":"Ewan Gourlay ,&nbsp;Kathryn Banfill ,&nbsp;Zoe Merchant ,&nbsp;Patrick Goodley ,&nbsp;Louise Brown ,&nbsp;Jack Murphy ,&nbsp;John Moore ,&nbsp;Matthew Evison","doi":"10.1016/j.lungcan.2025.108572","DOIUrl":"10.1016/j.lungcan.2025.108572","url":null,"abstract":"<div><h3>Introduction</h3><div>Prehabilitation improves both physiological measurements and clinical outcomes for patients undergoing surgery for lung cancer. The feasibility, acceptability and efficacy of prehabilitation for patients having curative-intent radiotherapy for lung cancer is uncertain.</div></div><div><h3>Methods</h3><div>Prehab4Cancer (P4C) is a regional, community-based prehabilitation service for patients with cancer in Greater Manchester in the United Kingdom. We present an evaluation of the P4C service for patients undergoing curative-intent radiotherapy for lung cancer over a 2-year period. Feasibility was evaluated against prespecified key performance indicators. Objective physiological and subjective functional assessments were recorded before and after completion. Effects on mortality in comparison to a non-prehab cohort were assessed in an exploratory regression analysis.</div></div><div><h3>Results</h3><div>A total of 381 patients were referred to P4C via a web-based portal. 86 % (329/381) were contacted by phone and 73 % (279/381) completed an initial assessment. 45 % (172/381) completed the prehab programme with a median of 7 (IQR 3–11) sessions during a median time to commencing treatment of 23 days (IQR 16–34). Median time from referral to assessment was 4 days (IQR 3–6) and 86 % (239/279) were completed within 7 days of referral. Six-Minute Walk Tests improved by an average of 30 m (95 % CI 20.6–41 m, p = &lt;0.001). 16 % (n = 21/132) of participants initially score “Medium” or “High” on IPAQ for weekly physical activity, improving to 52 % (n = 66/132) on programme completion. Participants had a median reduction in score of −2.5 (95 % CI −3.0 to −1.5) in WHODAS 2.0. There was an 8 % reduction in 1-year mortality in patients completing prehab (11 %, 17/160) vs those that did not complete prehab (19 %, 30/158, OR 0.5, 95 % CI 0.24–1.00, p = 0.054) after adjustment for age, gender, performance status and cancer staging.</div></div><div><h3>Conclusions</h3><div>The P4C programme has demonstrated feasibility, acceptability and effectiveness in patients with lung cancer undergoing curative-intent radiotherapy.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108572"},"PeriodicalIF":4.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935978","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":"Association of thyroid radiation dose with thyroid dysfunction in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy followed by maintenance immunotherapy","authors":"Gowoon Yang ,&nbsp;Hong In Yoon ,&nbsp;Sun Min Lim ,&nbsp;Min Hee Hong ,&nbsp;Jaeho Cho ,&nbsp;Chang Geol Lee ,&nbsp;Byoung Chul Cho ,&nbsp;Hye Ryun Kim ,&nbsp;Kyung Hwan Kim","doi":"10.1016/j.lungcan.2025.108574","DOIUrl":"10.1016/j.lungcan.2025.108574","url":null,"abstract":"<div><h3>Background and purpose</h3><div>We investigated whether incidental irradiation to the thyroid increased the risk of thyroid dysfunction among patients with non-small cell lung cancer (NSCLC) undergoing concurrent chemoradiotherapy (CCRT) followed by maintenance immunotherapy (IO).</div></div><div><h3>Materials and methods</h3><div>This was a retrospective study of 250 patients diagnosed with locally advanced NSCLC during 2014–2022 who were treated with definitive CCRT followed by maintenance IO. The primary endpoint was the incidence of thyroid dysfunction, which we compared between patients with irradiation of the supraclavicular fossa (the SCFi group) and those without (the non-SCFi group).</div></div><div><h3>Results</h3><div>By a median follow-up time of 16.6 months, 23/64 patients (35.9%) in the SCFi group and 27/186 patients (14.5%) in the non-SCFi group developed thyroid dysfunction (<em>P</em> &lt; 0.001). The 3-year cumulative incidence of thyroid dysfunction was 54.9% in the SCFi group and 17.0% in the non-SCFi group (<em>P</em> &lt; 0.001). A higher thyroid volume exposed to 10 Gy of radiation (V_10Gy) significantly and independently predicted an increased risk of thyroid dysfunction (hazard ratio, 2.82). The 3-year cumulative incidence of thyroid dysfunction was 67.9% in patients with V_10Gy ≥ 19.8% and 25.6% in patients with V_10Gy &lt; 19.8% (<em>P</em> &lt; 0.001). Via recursive-partitioning analysis, patients were classified into three risk groups based on the V_10Gy cutoff of &lt; 19.8% and age cutoff of ≥ 75 years. The 3-year cumulative incidence of thyroid dysfunction was the highest (74.0%) in the high-risk group (<em>P</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Incidental irradiation of the thyroid during CCRT is associated with an increased risk of thyroid dysfunction during maintenance IO. This supports the need to minimize the thyroid dose.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108574"},"PeriodicalIF":4.5,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924800","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":"Artificial intelligence in predicting EGFR mutations from whole slide images in lung Cancer: A systematic review and Meta-Analysis","authors":"Mai Hanh Nguyen ,&nbsp;Minh Huu Nhat Le ,&nbsp;Anh Tuan Bui ,&nbsp;Nguyen Quoc Khanh Le","doi":"10.1016/j.lungcan.2025.108577","DOIUrl":"10.1016/j.lungcan.2025.108577","url":null,"abstract":"<div><h3>Background</h3><div>Epidermal growth factor receptor (EGFR) mutations play a pivotal role in guiding targeted therapy for lung cancer, making their accurate detection essential for personalized treatment. Recently, artificial intelligence (AI) has emerged as a promising tool for identifying EGFR mutation status from digital pathology images. This systematic review and <em>meta</em>-analysis evaluate the diagnostic accuracy of AI models in predicting EGFR mutations from whole slide images (WSIs) in lung cancer patients.</div></div><div><h3>Methods</h3><div>A comprehensive search was conducted across four databases (EMBASE, PubMed, Web of Science, and Scopus) for studies published up to June 20th, 2024. Studies employing AI algorithms, including machine learning and deep learning techniques, to predict EGFR mutations from digital pathology images were included. The risk of bias and applicability concerns were assessed using the QUADAS-AI tool. Diagnostic accuracy metrics such as sensitivity, specificity, and the Area Under the Curve (AUC) were extracted. Random-effects models were applied to synthesize the AI model performance. This study is registered with PROSPERO (CRD42024570496).</div></div><div><h3>Results</h3><div>Out of 1,828 identified studies, 16 met the inclusion criteria, with 4 eligible for <em>meta</em>-analysis. The pooled results demonstrated that AI algorithms achieved an AUC of 0.756 (95% CI: 0.669–0.824), a sensitivity of 66.3% (95% CI: X–Y), and a specificity of 68.1% (95% CI: X–Y). Subgroup analyses revealed that AI models using in-house datasets, surgical resection samples, the ResNet architecture, and tumor-focused regions exhibited improved predictive performance.</div></div><div><h3>Conclusion</h3><div>AI models exhibit potential for non-invasive prediction of EGFR mutations in lung cancer patients using WSIs, although current accuracy and precision warrant further refinement. Future research should aim to enhance AI algorithms, validate findings on larger datasets, and integrate these tools into clinical workflows to optimize lung cancer management<strong>.</strong></div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108577"},"PeriodicalIF":4.5,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916472","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 outcomes of subsequent treatment strategies after durvalumab consolidation in stage III unresectable non-small cell lung cancer","authors":"Veronica Crespi ,&nbsp;Marco Donatello Delcuratolo ,&nbsp;Gabriele Minuti ,&nbsp;Michele Montrone ,&nbsp;Sara Pilotto ,&nbsp;Elisa Roca ,&nbsp;Giulio Metro ,&nbsp;Alessandro Leonetti ,&nbsp;Giacomo Pelizzari ,&nbsp;Carlo Genova ,&nbsp;Emanuela Olmetto ,&nbsp;Diego Cortinovis ,&nbsp;Alessandro Russo ,&nbsp;Giulia Pasello ,&nbsp;Alessandra Bulotta ,&nbsp;Francesco Grossi ,&nbsp;Roberta Buosi ,&nbsp;Alessandro Del Conte ,&nbsp;Claudio Sini ,&nbsp;Carlo Greco ,&nbsp;Francesco Passiglia","doi":"10.1016/j.lungcan.2025.108576","DOIUrl":"10.1016/j.lungcan.2025.108576","url":null,"abstract":"<div><h3>Background</h3><div>The PACIFIC trial established chemoradiation followed by 1-year durvalumab consolidation as standard of care for unresectable locally advanced non-small cell lung cancer (LA-NSCLC). This study aims to investigate therapeutic strategies and clinical outcomes after durvalumab failure in the real-world.</div></div><div><h3>Materials and methods</h3><div>Patients with stage III LA-NSCLC from 23 Italian centres were retrospectively enrolled at durvalumab progression. Subsequent treatments (Sub-Tx) were prospectively collected and classified as follows:<!--> <!-->chemo-immunotherapy (subgroup-1), platinum-based chemotherapy (subgroup-2), non-platinum-based chemotherapy (subgroup-3), and targeted therapy (subgroup-4). Durvalumab progression free survival (Dur-PFS) and overall survival (Dur-OS), as well as outcomes of Sub-Tx (Sub-PFS and Sub-OS) were estimated by using the Kaplan-Meier approach.</div></div><div><h3>Results</h3><div>A total of 122 patients were enrolled. Median Dur-PFS was 9.3 months (95 % CI: 7.1 – 11.4) and median Dur-OS 24.2 months (95 % CI: 18.7 – 29.7). Out of 93 patients receiving a Sub-Tx, 21.5 %, 43.0 %, 28.0 %, and 7.5 % were in the subgroup 1, 2, 3, and 4, respectively. Median Sub-PFS were 12.0, 4.1, 2.7, and 6.0 months, respectively. Patients who completed 12 months of durvalumab were 65.0 %, 27.5 %, 19.2 %, and 42.9 % across the four subgroups. In univariate analysis, the duration of durvalumab therapy was an independent factor for selecting Sub-Tx (p &lt; 0.007). Median time to next treatment (TTNT) was 6.7 months with chemo-immunotherapy and 2.1 with chemotherapy (p = 0.009). Out of 15 patients with a TTNT &gt; 1 year, 40 % were rechallenged with immunotherapy.</div></div><div><h3>Conclusion</h3><div>Platinum-based chemotherapy was the predominant treatment after durvalumab consolidation. Immunotherapy rechallenge was associated with the best survival outcome in selected cases, warranting further investigation.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108576"},"PeriodicalIF":4.5,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928641","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":"Equalizing prognostic disparities in KRAS-mutated stage III NSCLC patients: addition of durvalumab to combined chemoradiotherapy improves survival","authors":"Ella A. Eklund ,&nbsp;Mathilda Orgard ,&nbsp;Delice Wallin ,&nbsp;Sama I. Sayin ,&nbsp;Henrik Fagman ,&nbsp;Johan Isaksson ,&nbsp;Sukanya Raghavan ,&nbsp;Levent M. Akyürek ,&nbsp;Jan Nyman ,&nbsp;Clotilde Wiel ,&nbsp;Andreas Hallqvist ,&nbsp;Volkan I. Sayin","doi":"10.1016/j.lungcan.2025.108573","DOIUrl":"10.1016/j.lungcan.2025.108573","url":null,"abstract":"<div><h3>Introduction</h3><div>Stage III non-small cell lung cancer (NSCLC) is a heterogeneous group and identification of subgroups with differential treatment responses is crucial. Addition of durvalumab to concurrent chemoradiotherapy (cCRT) has previously been shown to improve survival outcomes. Meanwhile, subgroups harboring <em>KRAS</em> mutations have been shown to have worse prognosis. We investigated whether <em>KRAS</em> mutational status may affect survival outcomes after adjuvant durvalumab following cCRT in stage III NSCLC.</div></div><div><h3>Methods</h3><div>In this multi-center retrospective study, we present a real-world dataset of all stage III NSCLC patients treated with curative-intent cCRT with molecular assessment, between 2016 and 2021 in the Västra Götaland Region of western Sweden. The study period includes the standard practice prior to the introduction of durvalumab, enabling evaluation of the potential impact of immune checkpoint blockade (ICB). Primary study outcomes were overall survival (OS) and progression free survival (PFS).</div></div><div><h3>Results</h3><div>We identified 145 patients who received cCRT with curative intent, and 32 % harbored an activating mutation in the <em>KRAS</em> gene (<em>KRAS</em>^MUT; <em>n</em> = 46). Compared to patients with wild-type <em>KRAS</em> (<em>KRAS</em>^WT; <em>n</em> = 99), <em>KRAS</em>^MUT had worse OS (<em>p</em> = 0.047) and PFS (<em>p</em> = 0.038). This finding persisted on multivariate analysis with OS (HR 1.703, 95 % CI 1.074–2.702, <em>p</em> = 0.024) and PFS (HR 1.628, 95 % CI 1.081–2.453, <em>p</em> = 0.020). Within the subgroup that received cCRT alone, <em>KRAS</em>^MUT patients (<em>n</em> = 35) exhibited worse OS (<em>p</em> = 0.036) and PFS (<em>p</em> = 0.037) compared with <em>KRAS</em>^WT (<em>n</em> = 35). However, among those who received additional durvalumab after cCRT (<em>KRAS</em>^WT; <em>n</em> = 99. <em>KRAS</em>^MUT; <em>n</em> = 11) there were no significant differences in OS (0.788) or PFS (0.855) between the groups.</div></div><div><h3>Conclusions</h3><div><em>KRAS</em> mutations are a negative prognostic factor after cCRT in stage III NSCLC, and the addition of durvalumab ameliorates the negative impact of harboring this mutation.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108573"},"PeriodicalIF":4.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931621","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":"Therapeutic management of patients with advanced thymic malignancies: A review for clinicians","authors":"Valeria Pavese ,&nbsp;Federica Maria Carfì ,&nbsp;Enrica Capelletto ,&nbsp;Fabrizio Tabbò ,&nbsp;Francesco Leo ,&nbsp;Francesco Passiglia ,&nbsp;Luisella Righi ,&nbsp;Silvia Novello ,&nbsp;Alessandra Merlini ,&nbsp;Paolo Bironzo","doi":"10.1016/j.lungcan.2025.108554","DOIUrl":"10.1016/j.lungcan.2025.108554","url":null,"abstract":"<div><div>Thymic epithelial tumors (TETs) are a heterogeneous group of rare tumors that arise from thymic epithelial cells in the anterior mediastinum. They can be divided into three different histological subtypes: thymomas, thymic carcinomas (TC), and neuroendocrine carcinomas (TNET). TCs and TNETs are rarer but more aggressive entities with frequent distant metastasis. Thymomas occur in 90 % of cases in a localized/locally advanced stage, on the other hand about 70 % of TCs are locally advanced at the time of diagnosis.</div><div>Surgery plays a primary role in the management of patients in whom complete resection is feasible. The benefit of post-operative radiotherapy (PORT) is still controversial, since it could be related to stage, histotype, and preoperative chemotherapy. If the tumor is unresectable at diagnosis, radiotherapy or concurrent chemoradiotherapy is the most commonly used approach. Cisplatin and anthracycline-based regimens are standard of care in patients with unresectable or metastatic thymomas, but, at the same time, regimens with carboplatin and paclitaxel are the most widely used especially in patients with contraindications to cisplatin/anthracyclines, due to better tolerance. Recently, the anti-VEGFR antibody Ramucirumab has shown promising activity in combination with carboplatin plus paclitaxel in previously untreated advanced TCs. Several clinical trials with chemotherapy combination, target therapy and immunotherapy are still ongoing to define the best therapeutic strategy in this disease, also for the second line treatment, for which in daily practice there is currently no standard of care for patients who went into progression to the first line.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108554"},"PeriodicalIF":4.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906799","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":"Beyond environmental risk: Genetic insights into lung cancer susceptibility through whole exome analysis","authors":"C. Lintas ,&nbsp;R. Petti ,&nbsp;G. Colella ,&nbsp;I. Cassano ,&nbsp;A. Azzarà ,&nbsp;A. Cortellini ,&nbsp;F. Longo ,&nbsp;L. Frasca ,&nbsp;F. Gurrieri ,&nbsp;P. Crucitti","doi":"10.1016/j.lungcan.2025.108560","DOIUrl":"10.1016/j.lungcan.2025.108560","url":null,"abstract":"<div><h3>Background</h3><div>unlike familial non polyposis colorectal cancer (Lynch syndrome) and familial breast cancer, no genes have been confidently associated with familial lung cancer with the exception of the EGFR and the TP53 genes. Germinal Pathogenetic Variants (GPV) in these two genes account for 0.34–0.9% and 0.8 % lung adenocarcinoma, respectively.</div></div><div><h3>Objective</h3><div>the aim of this study was to identify rare genetic variants associated with higher risk of developing lung cancer.</div></div><div><h3>Methods</h3><div>we performed exome sequencing in the germinal DNA of 16 patients who had a positive familial history of lung cancer: 14 patients had lung cancer at enrollment whereas 2 patients developed cancer during the course of the study.. Two families had two affected relatives (mother and daughter and two sisters).</div></div><div><h3>Results</h3><div>we identified rare clinically significant variants and VUS (Variant of Unknown Significance) in five well known cancer genes (POLE, PDGFRA, RTEL1, HNF1A and MITF) in five patients. One patient carried three variants and was exposed to environmental risk factors as smoking and asbestos. Common suscetibility variants in known cancer genes were also identified.</div><div>We also identified additional potentially clinically relevant rare variants in other genes not previously associated to lung cancer. These genes include HGS, NME4, HAPLN1, ATMIN, CEACAM, MPEG1, USP4, TP53BP2, ERAP1, TNFAIP8L3, CASP1, MCC, SERPINA3, VIRMA, FOXK2, DNAH8, RASA2, GLI3.</div></div><div><h3>Conclusions</h3><div>several lines of evidence suggest that these genes are of potential clinical impact in lung cancer even though they have not been correlated with lung cancer in the OMIM database or other genetic databases. Therefore, these genes deserve further investigations: segregation analysis, enlarged cohorts and in vitro/in vivo studies could help to clarify their role in lung cancer.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"204 ","pages":"Article 108560"},"PeriodicalIF":4.5,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891648","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}