Translational lung cancer research最新文献

{"title":"Surgical consensus for screening, diagnosis, staging, multimodal management and surveillance of early-stage resectable non-small cell lung cancer (NSCLC) in Malaysia.","authors":"Anand Sachithanandan, Adli Azam Mohammad Razi, Sivakumar Krishnasamy, Kok Meng John Chan, Hong Yoong Lam, Nguk Chai Diong, Narasimman Sathiamurthy, Adrian Seng Wae Ooi, Sing Yang Soon","doi":"10.21037/tlcr-2025-296","DOIUrl":"10.21037/tlcr-2025-296","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the most frequently diagnosed cancer globally. In Malaysia, it ranks as the second most common cancer among men and third among women. Presently, no local clinical practice guidelines exist for lung cancer care in Malaysia. Given the lack of consensus regarding the perioperative management of early-stage non-small cell lung cancer (NSCLC), this article seeks to harmonise surgical practices among thoracic physicians and surgeons in Malaysia by recommending best practices for screening, diagnosis and staging, as well as multimodal management and surveillance in early-stage disease (stages I to IIIB-N2).</p><p><strong>Methods: </strong>A local expert committee comprising nine high-volume actively practicing cardiothoracic or general thoracic surgeons gathered between February to July 2024 to deliberate existing evidence and formulate recommendations. A modified Delphi method comprising systematic review of published evidence and expert opinion based on local experience was utilised. The document was subsequently independently reviewed by two senior oncologists and two senior respiratory physicians, before incorporating their feedback into the final version.</p><p><strong>Results: </strong>This document comprises a surgical consensus of evidence-based guidelines to provide local recommendations on contemporary real-world best practices. The consensus statements were grouped into five domains of early-stage resectable NSCLC: (I) screening (3 statements); (II) diagnosis and staging (6 statements); (III) neoadjuvant/perioperative immunotherapy (3 statements); (IV) adjuvant therapy with tyrosine kinase inhibitors (TKIs) or immunotherapy (4 statements); and (V) operative metrics and post-operative surveillance (5 statements).</p><p><strong>Conclusions: </strong>These consensus statement guidelines will elevate and standardise the perioperative management of early-stage NSCLC in Malaysia, serve as a valuable educational and training tool for relevant medical professionals, and promote an inclusive, comprehensive multidisciplinary approach to integrated holistic patient care, aimed at improving both clinical outcomes and patients' quality of life with the best available evidence.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2403-2426"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837900","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":"Lorlatinib in ALK-positive non-small cell lung cancer: final survival data that reshape the therapeutic landscape.","authors":"Yuki Katayama","doi":"10.21037/tlcr-2025-466","DOIUrl":"10.21037/tlcr-2025-466","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2364-2368"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837864","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":"Navigating treatment sequencing in ALK-positive non-small cell lung cancer: lorlatinib as a key to prolonged survival?","authors":"Maiken Parm Ulhøi, Peter Meldgaard","doi":"10.21037/tlcr-2025-373","DOIUrl":"10.21037/tlcr-2025-373","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2359-2363"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837876","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":"Real-world efficacy of immune checkpoint inhibitors in PD-L1 negative non-small cell lung cancer: a multicenter retrospective study.","authors":"Suguru Muraoka, Nobuaki Kobayashi, Ayami Kaneko, Kohei Somekawa, Yukihito Kajita, Tomofumi Hirose, Anna Tanaka, Shuhei Teranishi, Kenji Miura, Kentaro Yumoto, Toshinori Tsukahara, Nobuhiko Fukuda, Ryuichi Nishihira, Nobuyuki Horita, Yu Hara, Makoto Kudo, Naoki Miyazawa, Takeshi Kaneko","doi":"10.21037/tlcr-2025-138","DOIUrl":"10.21037/tlcr-2025-138","url":null,"abstract":"<p><strong>Background: </strong>While immune checkpoint inhibitors (ICIs) have significantly improved outcomes for many non-small cell lung cancer (NSCLC) patients, phase 3 trials have shown limited efficacy in programmed cell death ligand 1 (PD-L1) negative subgroups. This study aimed to evaluate the real-world effectiveness and safety of ICI-containing regimens <i>vs.</i> chemotherapy alone in PD-L1 negative NSCLC patients.</p><p><strong>Methods: </strong>This multicenter, retrospective study analyzed advanced or recurrent NSCLC patients treated between 2015 and 2022 in Japan. From an initial screening of 1,382 patients, we identified patients with PD-L1 negative [tumor proportion score (TPS) <1%] NSCLC. We excluded patients who received molecular targeted therapy, chemoradiotherapy, or had epidermal growth factor receptor (EGFR) mutations. Overall survival (OS), progression-free survival (PFS), response rates, and adverse events (AEs) were analyzed.</p><p><strong>Results: </strong>Among the 86 eligible patients identified, 54 received ICI-containing regimens (IC group) and 32 received chemotherapy alone (C group). No significant difference in OS (C <i>vs.</i> IC: median 14.9 <i>vs.</i> 23.8 months, P=0.87) and PFS (C <i>vs.</i> IC: median 6.6 <i>vs.</i> 7.8 months, P=0.20) was observed after covariates adjustment. The overall response rate was higher in the IC group (C <i>vs.</i> IC: 34.4% <i>vs.</i> 50.0%), as was the disease control rate (C <i>vs.</i> IC: 65.6% <i>vs.</i> 81.5%). AEs profiles were similar between groups, with grade 3-4 events occurring in 56.2% of C patients and 59.2% of IC patients. Treatment discontinuation rates due to AEs were comparable (C <i>vs.</i> IC: 21.9% <i>vs.</i> 24.1%, P=0.71).</p><p><strong>Conclusions: </strong>In this real-world study of PD-L1 negative NSCLC patients, ICI-containing regimens did not demonstrate significantly improved OS or PFS compared to chemotherapy alone. Limited efficacy in this population highlights the need for further investigation and advancement in treatment strategies.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2636-2645"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837894","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":"First-line immunotherapy in advanced non-squamous non-small cell lung cancer patients with rare mutations: a retrospective cohort study.","authors":"Wenli Cao, Furong Kou, Weiheng Hu, Li Hu, Jun Nie, Ling Dai, Jie Zhang, Jinqiu Rui, Magdalena Knetki-Wróblewska, Mara B Antonoff, Jian Fang, Yang Wang","doi":"10.21037/tlcr-2025-716","DOIUrl":"10.21037/tlcr-2025-716","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy has become the standard therapy for advanced non-small cell lung cancer (NSCLC), but its efficacy in patients with rare mutations remains unclear. This study aimed to evaluate the efficacy of first-line immunotherapy in NSCLC patients with rare mutations.</p><p><strong>Methods: </strong>This study selected 2,107 advanced non-squamous NSCLC patients who underwent genetic testing between January 2016 and April 2024 at Peking University Cancer Hospital. Inclusion criteria were patients with rare mutations (including <i>HER2, MET, BRAF, MET,</i> and <i>NTRK</i>) who received first-line immunotherapy or targeted therapy. Mutation-negative patients receiving first-line immunotherapy were also included as a control group. The log-rank test was used to compare progression-free survival (PFS) and overall survival (OS) between different groups.</p><p><strong>Results: </strong>A total of 66 patients with rare mutations and 142 patients with negative mutations were included. Among them, 39 rare mutation patients and 142 mutation-negative patients received first-line immunotherapy, while 27 rare mutation patients received first-line targeted therapy. For patients receiving first-line immunotherapy, there was no significant difference between the rare mutation group and the mutation-negative group in median PFS (14.53 <i>vs.</i> 12.43 months, P=0.93) and median OS (34.40 <i>vs.</i> 32.37 months, P=0.51). Among rare mutation patients, median OS was superior with first-line immunotherapy compared to targeted therapy (34.40 <i>vs.</i> 16.37 months, P=0.008), but median PFS showed no difference (14.53 <i>vs.</i> 7.03 months, P=0.10).</p><p><strong>Conclusions: </strong>Advanced non-squamous NSCLC patients with rare mutations may benefit from first-line immunotherapy.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2788-2798"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837859","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":"Upfront osimertinib and as sequential therapy in patients with <i>EGFR</i>-mutant non-small cell lung cancer (NSCLC): benefit across patients groups in a real-world retrospective cohort-the smile study.","authors":"Edouard Auclin, Pauline Du Rusquec, Victor Albarran-Artahona, Frank Aboubakar, Helena Gerber, Nicolas Epaillard, Gonzalo Recondo, Andrea De Giglio, Hugo Berthou, Juan Carlos Laguna, Teresa Gorria, Juan Bautista Blaquier, Beatriz Jimenez-Munarriz, Marco Tagliamento, Alessandro Di Federico, Gianluca Sacco, José Minatta, Nicolas Girard, Teresa Moran-Bueno, Rafael Lopez-Castro, Benjamin Besse, Laura Mezquita","doi":"10.21037/tlcr-24-881","DOIUrl":"10.21037/tlcr-24-881","url":null,"abstract":"<p><strong>Background: </strong>Osimertinib is the preferred first-line (L1) treatment for epidermal growth factor receptor-mutant (m<i>EGFR</i>) advanced non-small cell lung cancer (aNSCLC). Intensification of L1 with chemotherapy or amivantamab has shown improved outcomes at the cost of increased toxicity, raising questions about the optimal patients selection. A sequence involving first-generation tyrosine kinase inhibitor (TKI) (1G) followed by osimertinib might be considered. This study assessed the efficacy of these therapeutic strategies based on the clinical profiles of a real-life cohort.</p><p><strong>Methods: </strong>Retrospective multicenter study including consecutive patients with m<i>EGFR</i> (ex19/ex21) aNSCLC treated with either osimertinib or the sequence of 1G followed by osimertinib (\"sequence group\"). Central nervous system (CNS) metastases were permitted. We assessed progression-free survival (PFS) of the global strategy (PFSglob) defined as the time between L1 start and progression after L2 treatment or death. Secondary endpoints were overall survival (OS), PFS of the L1 treatment, and tumor response according to each center daily practice [objective response rate (ORR) and disease control rate (DCR)].</p><p><strong>Results: </strong>A total of 300 patients with m<i>EGFR</i> aNSCLC were enrolled (n=161 in the osimertinib group, n=139 in the sequence group). Baseline characteristics in both groups were similar except for baseline CNS involvement (41% in osimertinib-group <i>vs.</i> 25%), poor performance status (PS) ≥2 (21% <i>vs.</i> 10%) and high-tumor burden (TB), defined as >3 metastatic sites or CNS involvement (51% <i>vs.</i> 35%). The osimertinib group had longer median first-line PFS (PFS1; 19.0 <i>vs.</i> 16.8 months, P=0.03). The sequence group had improved PFSglob <i>vs.</i> the osimertinib-group (32.4 <i>vs.</i> 26.5 months, P=0.04) but this difference was not significant in multivariate Cox analysis (adjusted on age, smoking history, number of metastatic sites, liver, CNS and soft tissue metastasis, and PS) nor after a propensity score matching analysis, osimertinib upfront was associated with better PFSglob in the poor-prognosis groups: high-TB, CNS or liver involvement and poor PS.</p><p><strong>Conclusions: </strong>In this real-life study we showed that osimertinib upfront demonstrated prolonged PFS1 <i>vs.</i> 1G followed by osimertinib, with better PFSglob in patients with poor-prognosis m<i>EGFR</i> aNSCLC. This study raises the question of patients selection and treatment tailoring for the first line management of metastatic m<i>EGFR</i> non-small cell lung cancer (NSCLC).</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2427-2436"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837818","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":"MiR-200a regulates PD-L1 and predicts response to immune checkpoint inhibitors in advanced non-small cell lung cancer.","authors":"Ayami Kaneko, Nobuaki Kobayashi, Sousuke Kubo, Satoshi Nagaoka, Suguru Muraoka, Nobuhiko Fukuda, Kohei Somekawa, Hiromi Matsumoto, Seigo Katakura, Shuhei Teranishi, Keisuke Watanabe, Nobuyuki Horita, Yu Hara, Makoto Kudo, Takeshi Kaneko","doi":"10.21037/tlcr-2025-117","DOIUrl":"10.21037/tlcr-2025-117","url":null,"abstract":"<p><strong>Background: </strong>The microRNA (miR)-200 family is implicated in regulating the immune checkpoint protein programmed death-ligand 1 (PD-L1), a key factor in lung cancer progression and response to immunotherapy. This study investigates the relationship between miR-200 expression and PD-L1 in non-small cell lung cancer (NSCLC), aiming to clarify its potential as a prognostic biomarker and a therapeutic target in immune checkpoint inhibitor (ICI) treatment for NSCLC.</p><p><strong>Methods: </strong>RNA sequencing (RNA-seq) data from public databases were analyzed for correlation between miR-200 family expression and PD-L1 levels in lung cancer. MiR-200 and PD-L1 expression were assessed in lung cancer cell lines by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and flow cytometry, respectively. To evaluate functional impact, miR-200 mimics were transfected into cell lines, and PD-L1 protein levels were measured. The influence of interferon gamma (IFN-γ) on miR-200 and PD-L1 expressions in cell lines were examined using RT-qPCR and flow cytometry. Serum samples and tumor biopsies were collected from advanced NSCLC patients before ICI therapy. Serum miR-200a was quantified by Droplet digital polymerase chain reaction (ddPCR), and its correlation with tumor PD-L1 and progression-free survival (PFS) was analyzed.</p><p><strong>Results: </strong>Analysis of RNA-seq data revealed a significant inverse correlation between miR-200 family expression and PD-L1 levels in lung cancer (P<0.001). This was corroborated in cell lines, where miR-200a and miR-200b levels were significantly higher in low-PD-L1 cells compared to high-PD-L1 cells (P=0.01 and P=0.003). MiR-200a mimic transfection significantly decreased PD-L1 protein in H1975 and OKa-C-1 cells (P<0.001). IFN-γ stimulation increased PD-L1 expression but did not alter miR-200 levels. In advanced NSCLC patients, low serum miR-200a was associated with higher tumor PD-L1 expression (P=0.042) and significantly prolonged PFS following ICI therapy (median PFS: miR-200a-high, 129 days <i>vs.</i> miR-200a-low, 200 days; P=0.008).</p><p><strong>Conclusions: </strong>This study shows that miR-200a regulates PD-L1 expression in NSCLC, affecting immune evasion. Serum miR-200a levels could serve as a non-invasive biomarker to predict PD-L1 expression and immunotherapy outcomes, helping identify patients who may benefit. Modulating miR-200a may also offer a new strategy to reduce PD-L1 in tumors, enhancing immune response.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2522-2536"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837875","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":"The pharmacokinetics of capmatinib and its efficacy in non-small cell lung cancer treatment: a narrative review.","authors":"Bingtian Bi, Jing Zhan, Beichen Fan, Wenfeng Fang, Su Li","doi":"10.21037/tlcr-2025-700","DOIUrl":"10.21037/tlcr-2025-700","url":null,"abstract":"<p><strong>Background and objective: </strong>Inhibitors of mesenchymal-epithelial transition (<i>MET</i>) receptor serve as significant therapeutic agents in <i>MET</i>-driven non-small cell lung cancer (NSCLC). Among these, capmatinib has demonstrated particularly notable efficacy and safety. However, the mechanisms responsible for its benefit remain unclear. This narrative review presents the pharmacokinetics (PK)-related evidence regarding the efficacy of <i>MET</i> inhibitors for NSCLC and examines the differences in capmatinib as compared to other type Ib <i>MET</i> inhibitors.</p><p><strong>Methods: </strong>We conducted an exhaustive search of the English-language literature on <i>MET</i> inhibitors in NSCLC published or presented from June 2010 to February 2025 in the PubMed and Foreign Medical Literature Retrieval Service (FMRS; China) databases. It also included literature presented at various international meetings. The key literatures were identified from this search. Further, the clinical PK and clinical efficacy of type Ib <i>MET</i> inhibitors were analyzed.</p><p><strong>Key content and findings: </strong>The review provides a comparison of the PK for type Ib <i>MET</i> inhibitors in clinical practice. Specifically, capmatinib is absorbed more quickly in humans and exhibits the highest level of exposure compared to other <i>MET</i> inhibitors. Capmatinib has greater efficacy as assessed via the ratio of half maximal inhibitory concentration, and there is no requirement for dosage adjustment based on any level of hepatic impairment. Capmatinib has a faster clearance time, minimizing the likelihood of accumulation and the occurrence of adverse events (AEs). Its exposure levels are minimally impacted by food intake and drug-drug interaction. Capmatinib has a good PK profile after combination with gefitinib, constituting a promising option for patients with epidermal growth factor receptor (<i>EGFR</i>)-mutated NSCLC. Moreover, capmatinib exerts marked effects for brain metastases (BMs) in patients with NSCLC due its lipophilicity and permeability. Furthermore, capmatinib and tepotinib demonstrate extraordinary efficacy for patients with NSCLC and <i>MET</i> exon 14 (<i>MET</i>ex14) skipping mutation, and the combination of capmatinib and gefitinib in particular can achieve remarkable therapeutic effects in patients with <i>EGFR</i>-mutated, <i>MET</i>-dysregulated (amplified/overexpressing) NSCLC.</p><p><strong>Conclusions: </strong><i>MET</i> inhibitors, especially capmatinib, are the preferred treatment choice for patients with NSCLC and <i>MET</i>ex14 mutation and BM. The administration of capmatinib can help mitigate potential food-intake and drug-drug interactions in clinical settings. This facilitates the optimization of long-term medication schedules, enhancing the clinical efficacy of the treatment.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2842-2852"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837816","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":"Successful rechallenge of immune checkpoint inhibitors after severe immune-related hepatitis, thyroiditis and hypophysitis in TMB-high NSCLC: a case report.","authors":"Zixiang Zhou, Hanping Wang","doi":"10.21037/tlcr-2025-341","DOIUrl":"10.21037/tlcr-2025-341","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are frequently associated with immune-related adverse events (irAEs), which complicate treatment decisions. Patients who experience severe irAEs are often excluded from further immunotherapy due to concerns of recurrence. However, rechallenging ICIs in selected patients under close monitoring may offer long-term benefits, although evidence remains limited and heterogeneous.</p><p><strong>Case description: </strong>We report a case of a 65-year-old man with stage IVB pulmonary adenocarcinoma harboring <i>TP53</i> mutation and high tumor mutational burden. He initially received pembrolizumab-based chemoimmunotherapy but developed grade 4 hepatitis, requiring immunosuppressive treatment and discontinuation of ICIs. Subsequent tumor progression led to a rechallenge with ICIs alongside prophylactic tocilizumab. Although the patient experienced further grade 2 thyroiditis and grade 2 hypophysitis, all toxicities were manageable with hormone replacement and corticosteroids. A pacemaker was implanted for unrelated sick sinus syndrome. Despite intermittent symptoms, pembrolizumab monotherapy was maintained over a prolonged period, achieving durable tumor control with no progression noted at 4-year follow-up.</p><p><strong>Conclusions: </strong>This case highlights that ICI rechallenge can be a viable and effective treatment strategy in selected patients with prior high-grade irAEs, especially when initial toxicities are well controlled and alternative causes of symptoms are carefully excluded. The prophylactic use of agents like tocilizumab may reduce the risk of irAE recurrence. This underscores the need for individualized risk-benefit assessment and close clinical monitoring in rechallenge scenarios.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2875-2879"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837899","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":"Targeting arachidonic acid-modulated autophagy: a novel axis in crizotinib resistance.","authors":"Shameer Tahir","doi":"10.21037/tlcr-2025-524","DOIUrl":"10.21037/tlcr-2025-524","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2891-2892"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837815","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}