Pub Date : 2026-03-01Epub Date: 2026-01-29DOI: 10.1016/j.cllc.2026.01.011
Daisuke Morinaga , Hidenori Kitai , Hanko Sato , Doppo Fukui , Wataru Harabayashi , Yukiko Yoshida , Shotaro Ito , Yuta Takashima , Megumi Furuta , Akihiko Kudo , Shintaro Fujii , Hisashi Uwatoko , Hiroaki Yaguchi , Keiko Tanaka , Ichiro Yabe , Jun Sakakibara-Konishi , Satoshi Konno
•
Tissue-based assays can reveal neuronal antibody reactivity and support the diagnosis of autoimmune or paraneoplastic encephalitis, especially when standard serum and cerebrospinal fluid antibody panels are negative.
•
In limited-stage small-cell lung cancer with paraneoplastic limbic encephalitis, immune checkpoint inhibitors can be a feasible option when both tumor regression and neurological stabilization are achieved following concurrent chemoradiotherapy.
{"title":"Limited-Stage Small-Cell Lung Cancer With Severe Paraneoplastic Limbic Encephalitis Successfully Treated With Chemoradiotherapy Followed by Immune Checkpoint Inhibitor Maintenance Therapy: A Case Report","authors":"Daisuke Morinaga , Hidenori Kitai , Hanko Sato , Doppo Fukui , Wataru Harabayashi , Yukiko Yoshida , Shotaro Ito , Yuta Takashima , Megumi Furuta , Akihiko Kudo , Shintaro Fujii , Hisashi Uwatoko , Hiroaki Yaguchi , Keiko Tanaka , Ichiro Yabe , Jun Sakakibara-Konishi , Satoshi Konno","doi":"10.1016/j.cllc.2026.01.011","DOIUrl":"10.1016/j.cllc.2026.01.011","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Tissue-based assays can reveal neuronal antibody reactivity and support the diagnosis of autoimmune or paraneoplastic encephalitis, especially when standard serum and cerebrospinal fluid antibody panels are negative.</div></span></li><li><span>•</span><span><div>In limited-stage small-cell lung cancer with paraneoplastic limbic encephalitis, immune checkpoint inhibitors can be a feasible option when both tumor regression and neurological stabilization are achieved following concurrent chemoradiotherapy.</div></span></li></ul></div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 121-125"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-09-01DOI: 10.1016/j.cllc.2025.08.018
M. Judy Lubas , Albi Vata , Jordan Fredette , Martin J. Edelman , Sameera Kumar
Purpose/Objectives
While stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy (HFRT) is routinely used to treat inoperable early-stage non-small lung cancer (esNSCLC) patients with peripheral tumors, SBRT or HFRT for central (cenT) and ultracentral tumors (UCT) remains controversial. To treat patients with tumors located within 0-2 cm of critical mediastinal structures (CMSTs), we employ an institution specific hypofractionated radiation regimen (isHFRT) with a biologically effective dose (BED) of 98.59 using 17 fractions to a dose of 6987 cGy.
Methods
We conducted a single-institution retrospective review of patients with esNSCLC treated with this isHFRT between 2011 and 2020, evaluating both tumor control rates and rates of treatment related toxicity.
Results
Of the 31 patients evaluated, 61.3% of patients had UCTs while 38.7% had cenTs. At 1- and 3 years, local control (LC) was noted to be 93.5% and 86.8% respectively. 1-year overall survival (OS) was 74.2% for all comers, 75.0% for patients with cenTs and 73.7% for patients with UCTs (p = 0.70). 3-year OS was 20.8%. Only 22.6% of patients who expired at 1-year experienced disease progression. At 12 months, adverse event free survival (AEFS) was 67.7%. While 25.8% (n = 8) of patients experienced a Grade 2 (G2) or greater toxicity, no patient experienced a G2 or greater cardiotoxicity. Only 1 patient (3.3%) experienced a Grade 5 toxicity (fatal hemoptysis 12-months following treatment). Review of the case demonstrated that the maximum tracheobronchial tree dose had been exceeded.
Conclusions
Our isHFRT for patients with esNSCLC proves a safe and effective treatment for medically inoperable esNSCLC patients with cenTs and UCTs with comparable rates of toxicity when compared to prior studies.
{"title":"An Institution-Specific Hypofractionated Radiation Therapy Regimen in the Treatment of Central and Ultracentral Non-small Cell Lung Cancer","authors":"M. Judy Lubas , Albi Vata , Jordan Fredette , Martin J. Edelman , Sameera Kumar","doi":"10.1016/j.cllc.2025.08.018","DOIUrl":"10.1016/j.cllc.2025.08.018","url":null,"abstract":"<div><h3>Purpose/Objectives</h3><div>While stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy (HFRT) is routinely used to treat inoperable early-stage non-small lung cancer (esNSCLC) patients with peripheral tumors, SBRT or HFRT for central (cenT) and ultracentral tumors (UCT) remains controversial. To treat patients with tumors located within 0-2 cm of critical mediastinal structures (CMSTs), we employ an institution specific hypofractionated radiation regimen (isHFRT) with a biologically effective dose (BED) of 98.59 using 17 fractions to a dose of 6987 cGy.</div></div><div><h3>Methods</h3><div>We conducted a single-institution retrospective review of patients with esNSCLC treated with this isHFRT between 2011 and 2020, evaluating both tumor control rates and rates of treatment related toxicity.</div></div><div><h3>Results</h3><div>Of the 31 patients evaluated, 61.3% of patients had UCTs while 38.7% had cenTs. At 1- and 3 years, local control (LC) was noted to be 93.5% and 86.8% respectively. 1-year overall survival (OS) was 74.2% for all comers, 75.0% for patients with cenTs and 73.7% for patients with UCTs (<em>p</em> = 0.70). 3-year OS was 20.8%. Only 22.6% of patients who expired at 1-year experienced disease progression. At 12 months, adverse event free survival (AEFS) was 67.7%. While 25.8% (<em>n</em> = 8) of patients experienced a Grade 2 (G2) or greater toxicity, no patient experienced a G2 or greater cardiotoxicity. Only 1 patient (3.3%) experienced a Grade 5 toxicity (fatal hemoptysis 12-months following treatment). Review of the case demonstrated that the maximum tracheobronchial tree dose had been exceeded.</div></div><div><h3>Conclusions</h3><div>Our isHFRT for patients with esNSCLC proves a safe and effective treatment for medically inoperable esNSCLC patients with cenTs and UCTs with comparable rates of toxicity when compared to prior studies.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 169-176.e2"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-08-31DOI: 10.1016/j.cllc.2025.08.014
Marta Brambilla , Francesca Barbetta , Giuseppe Nardo , Luca Agnelli , Giorgia Di Liberti , Paolo Ambrosini , Chiara Cavalli , Adele Busico , Iolanda Capone , Daniele Lorenzini , Filippo de Braud , Giancarlo Pruneri
Next-Generation Sequencing (NGS) has an increasing role in patients with advanced non–small-cell lung cancer (aNSCLC) and, in parallel, the use of targeted therapy dramatically improves the outcome of those with actionable alterations. In this scenario, the possible prognostic significance of some features provided by NGS testing and, among these, of Variant Allele Frequency (VAF), is still unclear. Herein, we report a real-world single-center prospective cohort of 88 consecutive patients with aNSCLC profiled by NGS and harboring a classic EGFR mutation, who were treated with the standard first-line tyrosine kinase inhibitor osimertinib. A subset of patients with shorter progression-free survival (PFS) was characterized by extremely high VAF/tumor cellularity, >1.7 adjusted VAF (aVAF). Median PFS was 5.3 months shorter in the high aVAF cohort; a similar trend was observed in overall survival too. No significant association between aVAF and TP53 mutations, Tumor Mutational Burden or other clinical, pathological or molecular features was found. Our findings suggest that NGS could improve the traditional binary classification of EGFR mutations in aNSCLC, highlighting a correlation between high EGFR mutations aVAF and worse outcome.
{"title":"Refining High-Risk EGFR-Mutant Lung Cancer Patients: The Role of Adjusted Variant Allele Frequency in First-Line Osimertinib Therapy","authors":"Marta Brambilla , Francesca Barbetta , Giuseppe Nardo , Luca Agnelli , Giorgia Di Liberti , Paolo Ambrosini , Chiara Cavalli , Adele Busico , Iolanda Capone , Daniele Lorenzini , Filippo de Braud , Giancarlo Pruneri","doi":"10.1016/j.cllc.2025.08.014","DOIUrl":"10.1016/j.cllc.2025.08.014","url":null,"abstract":"<div><div>Next-Generation Sequencing (NGS) has an increasing role in patients with advanced non–small-cell lung cancer (aNSCLC) and, in parallel, the use of targeted therapy dramatically improves the outcome of those with actionable alterations. In this scenario, the possible prognostic significance of some features provided by NGS testing and, among these, of Variant Allele Frequency (VAF), is still unclear. Herein, we report a real-world single-center prospective cohort of 88 consecutive patients with aNSCLC profiled by NGS and harboring a classic EGFR mutation, who were treated with the standard first-line tyrosine kinase inhibitor osimertinib. A subset of patients with shorter progression-free survival (PFS) was characterized by extremely high VAF/tumor cellularity, >1.7 adjusted VAF (aVAF). Median PFS was 5.3 months shorter in the high aVAF cohort; a similar trend was observed in overall survival too. No significant association between aVAF and <em>TP53</em> mutations, Tumor Mutational Burden or other clinical, pathological or molecular features was found. Our findings suggest that NGS could improve the traditional binary classification of <em>EGFR</em> mutations in aNSCLC, highlighting a correlation between high EGFR mutations aVAF and worse outcome.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 146-150.e2"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-10-02DOI: 10.1016/j.cllc.2025.09.014
Elisa Daffré , Samir Bouam , Salvatore Strano , Kim Blanc , Audrey Lupo-Mansuet , Emelyne Canny , Ludovic Fournel , Antonio Bobbio , Mathilde Prieto , Marco Alifano
Objectives
Lung cancer may require complex interventions such as pneumonectomy. This study investigates late survival after pneumonectomy and assesses the need for late rehospitalizations.
Methods
We performed a retrospective analysis of 479 consecutive patients with lung cancer undergoing pneumonectomy at our institution between 2005 and 2015. Survival was assessed at 3, 5, and 8 years and Cox multivariate analysis was used to identify independent predictors. The National anonymized medico-economic database (PMSI) was used to study early and late (up to 10 years after surgery) postpneumonectomy hospital trajectories (excluding routine follow-up visits) of patients in the last 2 years of the study period (n = 179).
Results
The mean age of patients was 62.7 ± 9.9 years and 74.9% were men; 56.18% had FEV1 below 80% of predicted. Stage III accounted for 62.84% of patients. Overall survival at 3, 5 and 8 years was 58.9%, 47.6% and 39.6%, respectively. Male sex, active tobacco smoking, Charlson Comorbidity Index >5, stage III-IV, and occurrence of Clavien Dindo≥3 postoperative complications were independent predictors of worse survival.
After pneumonectomy, a total of 4845 hospitalisations were recorded in 179 patients, 886 for postoperative adjuvant treatments. Forty-five out of the 179 patients had a late hospitalisation for lung cancer recurrence, with an average delay of 23.3 months. There were 25 readmissions, involving 20/179 patients, for respiratory failure, whereas 15/179 patients were readmitted for cardiac failure. In addition, 9/179 patients were readmitted for a new nonpulmonary cancer.
Conclusions
Despite the strong physiological impact, pneumonectomy has satisfactory short and long-term results.
{"title":"Late Survival and Hospital Trajectory After Pneumonectomy for Non-small Cell Lung Cancer","authors":"Elisa Daffré , Samir Bouam , Salvatore Strano , Kim Blanc , Audrey Lupo-Mansuet , Emelyne Canny , Ludovic Fournel , Antonio Bobbio , Mathilde Prieto , Marco Alifano","doi":"10.1016/j.cllc.2025.09.014","DOIUrl":"10.1016/j.cllc.2025.09.014","url":null,"abstract":"<div><h3>Objectives</h3><div>Lung cancer may require complex interventions such as pneumonectomy. This study investigates late survival after pneumonectomy and assesses the need for late rehospitalizations.</div></div><div><h3>Methods</h3><div>We performed a retrospective analysis of 479 consecutive patients with lung cancer undergoing pneumonectomy at our institution between 2005 and 2015. Survival was assessed at 3, 5, and 8 years and Cox multivariate analysis was used to identify independent predictors. The National anonymized medico-economic database (PMSI) was used to study early and late (up to 10 years after surgery) postpneumonectomy hospital trajectories (excluding routine follow-up visits) of patients in the last 2 years of the study period (<em>n</em> = 179).</div></div><div><h3>Results</h3><div>The mean age of patients was 62.7 ± 9.9 years and 74.9% were men; 56.18% had FEV1 below 80% of predicted. Stage III accounted for 62.84% of patients. Overall survival at 3, 5 and 8 years was 58.9%, 47.6% and 39.6%, respectively. Male sex, active tobacco smoking, Charlson Comorbidity Index >5, stage III-IV, and occurrence of Clavien Dindo≥3 postoperative complications were independent predictors of worse survival.</div><div>After pneumonectomy, a total of 4845 hospitalisations were recorded in 179 patients, 886 for postoperative adjuvant treatments. Forty-five out of the 179 patients had a late hospitalisation for lung cancer recurrence, with an average delay of 23.3 months. There were 25 readmissions, involving 20/179 patients, for respiratory failure, whereas 15/179 patients were readmitted for cardiac failure. In addition, 9/179 patients were readmitted for a new nonpulmonary cancer.</div></div><div><h3>Conclusions</h3><div>Despite the strong physiological impact, pneumonectomy has satisfactory short and long-term results.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 249-258.e1"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-01DOI: 10.1016/j.cllc.2026.01.006
James Ryan , Zane Yang , Christina Brown , Michael J. Fulham , Wendy A. Cooper , Steven Kao
•
Thymic carcinoma is a rare, aggressive malignancy with limited systemic treatment options beyond platinum-based chemotherapy. Responses to chemotherapy, immunotherapy, and subsequent lines of therapy are often short-lived, and there are no well-established targeted therapies. The anti-apoptotic protein BCL-2 is frequently expressed in thymic carcinomas, but BCL-2 directed therapy is not part of current standard management. Venetoclax in combination with azacitidine is an established, well-tolerated regimen for older or unfit patients with acute myeloid leukemia (AML), where it enhances apoptosis through BCL-2 inhibition and epigenetic modulation.
•
In this heavily pretreated patient with advanced thymic carcinoma who developed therapy-related AML, venetoclax plus azacitidine induced not only to hematologic remission of AML but also marked metabolic and radiologic regression of metastatic thymic carcinoma, accompanied by symptomatic improvement. The tumor demonstrated diffuse BCL-2 expression on immunohistochemistry, supporting a biologically plausible mechanism of response.
•
This case adds to the limited emerging evidence that BCL-2 blockade, particularly in combination with hypomethylating agents, may have clinically meaningful activity in thymic epithelial malignancies. These findings identify BCL-2 as a potential therapeutic target in thymic carcinoma and suggests that venetoclax-based regimens could be explored as a therapeutic strategy in selected patients, particularly those with BCL-2 expressing tumors or limited standard options. This case also supports prospective investigation of BCL-2 directed strategies in thymic epithelial tumors and highlights the value of biomarker driven treatment even in rare thoracic cancers.
{"title":"Advanced Thymic Carcinoma Responds to Venetoclax and Azacitidine","authors":"James Ryan , Zane Yang , Christina Brown , Michael J. Fulham , Wendy A. Cooper , Steven Kao","doi":"10.1016/j.cllc.2026.01.006","DOIUrl":"10.1016/j.cllc.2026.01.006","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Thymic carcinoma is a rare, aggressive malignancy with limited systemic treatment options beyond platinum-based chemotherapy. Responses to chemotherapy, immunotherapy, and subsequent lines of therapy are often short-lived, and there are no well-established targeted therapies. The anti-apoptotic protein BCL-2 is frequently expressed in thymic carcinomas, but BCL-2 directed therapy is not part of current standard management. Venetoclax in combination with azacitidine is an established, well-tolerated regimen for older or unfit patients with acute myeloid leukemia (AML), where it enhances apoptosis through BCL-2 inhibition and epigenetic modulation.</div></span></li><li><span>•</span><span><div>In this heavily pretreated patient with advanced thymic carcinoma who developed therapy-related AML, venetoclax plus azacitidine induced not only to hematologic remission of AML but also marked metabolic and radiologic regression of metastatic thymic carcinoma, accompanied by symptomatic improvement. The tumor demonstrated diffuse BCL-2 expression on immunohistochemistry, supporting a biologically plausible mechanism of response.</div></span></li><li><span>•</span><span><div>This case adds to the limited emerging evidence that BCL-2 blockade, particularly in combination with hypomethylating agents, may have clinically meaningful activity in thymic epithelial malignancies. These findings identify BCL-2 as a potential therapeutic target in thymic carcinoma and suggests that venetoclax-based regimens could be explored as a therapeutic strategy in selected patients, particularly those with BCL-2 expressing tumors or limited standard options. This case also supports prospective investigation of BCL-2 directed strategies in thymic epithelial tumors and highlights the value of biomarker driven treatment even in rare thoracic cancers.</div></span></li></ul></div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 135-139"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-09-26DOI: 10.1016/j.cllc.2025.09.011
Frank Detterbeck , Ramon Rami-Porta
The TNM classification of anatomic tumor extent is a prominent part of the clinical care of patients with lung cancer. As treatment increasingly involves a blend of local and systemic therapies there is an increasing desire for an “enhanced TNM” that includes other factors that impact clinical decision-making. Typically, this is expressed as a need to include prognostic factors in the TNM classification to better predict patient outcomes. A clear understanding of the issues involved is needed in order to satisfy this desire in a way that is useful in clinical practice. We aim to add to the discussion of the topic in the lung cancer medical community by offering a perspective on what the TNM classification is, what the prognosis of patients as defined by tumor stage represents, and an exploration of what is meant when people talk about needing better prognostic prediction.
{"title":"Striving for an Enhanced Tumor Classification System: Reflections on Cancer, Prognosis, Human Nature and Reality","authors":"Frank Detterbeck , Ramon Rami-Porta","doi":"10.1016/j.cllc.2025.09.011","DOIUrl":"10.1016/j.cllc.2025.09.011","url":null,"abstract":"<div><div>The TNM classification of anatomic tumor extent is a prominent part of the clinical care of patients with lung cancer. As treatment increasingly involves a blend of local and systemic therapies there is an increasing desire for an “enhanced TNM” that includes other factors that impact clinical decision-making. Typically, this is expressed as a need to include prognostic factors in the TNM classification to better predict patient outcomes. A clear understanding of the issues involved is needed in order to satisfy this desire in a way that is useful in clinical practice. We aim to add to the discussion of the topic in the lung cancer medical community by offering a perspective on what the TNM classification is, what the prognosis of patients as defined by tumor stage represents, and an exploration of what is meant when people talk about needing better prognostic prediction.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 237-241"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147449102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-09-05DOI: 10.1016/j.cllc.2025.09.001
Zetao Liu , Zhiyu Peng , Jie Cao , Zhaokang Huang , Xizhou Liao , Xiaorong Zong , Chenglin Guo , Jiandong Mei
Background
The prognosis of stage I non-small cell lung cancer (NSCLC) remains significant heterogeneity. It is not clear whether adjuvant epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy can reduce recurrence and improve survival in patients with stage I disease, especially stage IA.
Methods
This retrospective, single-center, observational, propensity score-matched study enrolled patients with completely resected pathological stage I invasive lung adenocarcinoma (LUAD) with sensitive EGFR mutations. Inverse probability of treatment weighting (IPTW) was applied to address the imbalance in baseline characteristics. The primary endpoint was relapse-free survival (RFS), and the secondary endpoint was overall survival (OS). RFS and OS were calculated using the Kaplan-Meier method, and the log-rank test was used to compare differences between the two groups. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox regression. Stratified analysis was performed according to the risk of recurrence determined by tumor characteristics and surgical procedure.
Results
A total of 819 eligible patients were included in the study. After IPTW, 823 patients were included in the analysis, of which 183 (22.2%) patients were in the EGKF-TKI group and 640 (77.8%) patients were in the observation group. In patients with stage I disease, the 5-year RFS was 92.6% in the EGFR-TKI group, compared with 77.0% in the observation group (HR = 0.26; 95% CI, 0.15–0.46; P < .001). Superior RFS was observed with adjuvant EGFR-TKI therapy in most predefined subgroups. There was no significant difference in OS between the two groups for patients with stage I, stage IA, or stage IB disease.
Conclusions
Our study demonstrates that adjuvant EGFR-TKI therapy improves RFS in patients with stage IA and IB invasive LUAD, but the difference in OS is not statistically significant.
背景：I期非小细胞肺癌（NSCLC）预后存在显著异质性。目前尚不清楚佐剂表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）治疗是否能减少I期，特别是IA期疾病患者的复发和提高生存率。方法：这项回顾性、单中心、观察性、倾向评分匹配的研究纳入了具有敏感EGFR突变的完全切除的病理I期浸润性肺腺癌（LUAD）患者。应用治疗加权逆概率（IPTW）来解决基线特征的不平衡。主要终点为无复发生存期（RFS），次要终点为总生存期（OS）。采用Kaplan-Meier法计算RFS和OS，采用log-rank检验比较两组间差异。采用Cox回归计算风险比（HR）和95%置信区间（CI）。根据肿瘤特征和手术方式确定的复发风险进行分层分析。结果：共有819例符合条件的患者纳入研究。IPTW后纳入823例患者，其中EGKF-TKI组183例（22.2%），观察组640例（77.8%）。在I期疾病患者中，EGFR-TKI组的5年RFS为92.6%，而观察组为77.0% （HR = 0.26; 95% CI, 0.15-0.46; P < .001）。在大多数预先确定的亚组中，辅助EGFR-TKI治疗的RFS均优于其他亚组。对于I期、IA期或IB期患者，两组间的OS无显著差异。结论：我们的研究表明，辅助EGFR-TKI治疗可改善IA期和IB期浸润性LUAD患者的RFS，但OS差异无统计学意义。
{"title":"Effect of adjuvant EGFR-TKI therapy on the prognosis of pathological stage I invasive lung adenocarcinoma with sensitive EGFR mutations","authors":"Zetao Liu , Zhiyu Peng , Jie Cao , Zhaokang Huang , Xizhou Liao , Xiaorong Zong , Chenglin Guo , Jiandong Mei","doi":"10.1016/j.cllc.2025.09.001","DOIUrl":"10.1016/j.cllc.2025.09.001","url":null,"abstract":"<div><h3>Background</h3><div>The prognosis of stage I non-small cell lung cancer (NSCLC) remains significant heterogeneity. It is not clear whether adjuvant epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy can reduce recurrence and improve survival in patients with stage I disease, especially stage IA.</div></div><div><h3>Methods</h3><div>This retrospective, single-center, observational, propensity score-matched study enrolled patients with completely resected pathological stage I invasive lung adenocarcinoma (LUAD) with sensitive <em>EGFR</em> mutations. Inverse probability of treatment weighting (IPTW) was applied to address the imbalance in baseline characteristics. The primary endpoint was relapse-free survival (RFS), and the secondary endpoint was overall survival (OS). RFS and OS were calculated using the Kaplan-Meier method, and the log-rank test was used to compare differences between the two groups. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox regression. Stratified analysis was performed according to the risk of recurrence determined by tumor characteristics and surgical procedure.</div></div><div><h3>Results</h3><div>A total of 819 eligible patients were included in the study. After IPTW, 823 patients were included in the analysis, of which 183 (22.2%) patients were in the EGKF-TKI group and 640 (77.8%) patients were in the observation group. In patients with stage I disease, the 5-year RFS was 92.6% in the EGFR-TKI group, compared with 77.0% in the observation group (HR = 0.26; 95% CI, 0.15–0.46; <em>P</em> < .001). Superior RFS was observed with adjuvant EGFR-TKI therapy in most predefined subgroups. There was no significant difference in OS between the two groups for patients with stage I, stage IA, or stage IB disease.</div></div><div><h3>Conclusions</h3><div>Our study demonstrates that adjuvant EGFR-TKI therapy improves RFS in patients with stage IA and IB invasive LUAD, but the difference in OS is not statistically significant.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 177-188.e5"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145581665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-12-05DOI: 10.1016/j.cllc.2025.11.020
Jiawen Sun , Xin Dong , Zhixue Fu , Sen Han , Yuliang Liu , Anhui Shi , Huiming Yu , Yuting Zhao , Wei Deng , Leilei Jiang , Dan Yang , Xiao Chang , Liuhua Long , Jiayi Yu , Yue Teng , Rong Yu , Weihu Wang
Objectives
This study assessed the impact of immune checkpoint inhibitors (ICIs) addition and timing on the incidence of treatment-related pneumonitis (TRP) and explored type-specific risk factors in unresectable locally advanced non-small cell lung cancer (LA-NSCLC) patients receiving definitive chemoradiotherapy (CRT).
Methods
We retrospectively analyzed 449 LA-NSCLC patients receiving definitive CRT±ICIs from January 2019 to December 2021. Patients were grouped by CRT alone (n = 236) or CRT+ICIs (n = 213), with the latter stratified by ICIs timing (induction/concurrent/consolidation) relative to radiotherapy. TRP (including radiation pneumonitis [RP] and checkpoint inhibitor pneumonitis [CIP]) was graded per CTCAE v5.0 through multidisciplinary review. We applied inverse probability of treatment weighting (IPTW) to adjust baseline covariates, Fine-Gray competing-risk model to estimate cumulative incidence and risk factors.
Results
Grade ≥ 2 TRP incidence was significantly increased with CRT+ICIs than CRT (30.6% vs. 9.8%; IPTW-adjusted P < .001), highest with concurrent ICIs (51.5%), followed by induction (32.0%) and consolidation (24.2%). Grade ≥ 2 RP increased to 16.7% with ICIs (IPTW-adjusted P = .004), peaking in the concurrent subgroup (39.1%), while comparable between induction and consolidation (16.1% vs. 12.2%). Independent predictors of grade ≥ 2 RP included ICIs treatment, gemcitabine-based induction chemotherapy, and higher lung dosimetry, with cut-offs of lung V20 (volume receiving ≥ 20 Gy) = 26.8% and mean lung dose (MLD) = 14.05 Gy. Grade ≥ 2 CIP incidence (14.2%) was associated with pre-existing interstitial lung disease or emphysema, PD-1 inhibitors and elevated MLD.
Conclusions
ICIs addition and timing significantly affected TRP risk. Mitigating lung toxicity requires careful selection of ICIs strategy, chemotherapy agents, and optimizing lung radiation dosimetry.
{"title":"Cumulative Incidence and Type-Specific Risk Factors of Pneumonitis After Definitive Chemoradiotherapy With or Without Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer","authors":"Jiawen Sun , Xin Dong , Zhixue Fu , Sen Han , Yuliang Liu , Anhui Shi , Huiming Yu , Yuting Zhao , Wei Deng , Leilei Jiang , Dan Yang , Xiao Chang , Liuhua Long , Jiayi Yu , Yue Teng , Rong Yu , Weihu Wang","doi":"10.1016/j.cllc.2025.11.020","DOIUrl":"10.1016/j.cllc.2025.11.020","url":null,"abstract":"<div><h3>Objectives</h3><div>This study assessed the impact of immune checkpoint inhibitors (ICIs) addition and timing on the incidence of treatment-related pneumonitis (TRP) and explored type-specific risk factors in unresectable locally advanced non-small cell lung cancer (LA-NSCLC) patients receiving definitive chemoradiotherapy (CRT).</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 449 LA-NSCLC patients receiving definitive CRT±ICIs from January 2019 to December 2021. Patients were grouped by CRT alone (<em>n</em> = 236) or CRT+ICIs (<em>n</em> = 213), with the latter stratified by ICIs timing (induction/concurrent/consolidation) relative to radiotherapy. TRP (including radiation pneumonitis [RP] and checkpoint inhibitor pneumonitis [CIP]) was graded per CTCAE v5.0 through multidisciplinary review. We applied inverse probability of treatment weighting (IPTW) to adjust baseline covariates, Fine-Gray competing-risk model to estimate cumulative incidence and risk factors.</div></div><div><h3>Results</h3><div>Grade ≥ 2 TRP incidence was significantly increased with CRT+ICIs than CRT (30.6% vs. 9.8%; IPTW-adjusted <em>P</em> < .001), highest with concurrent ICIs (51.5%), followed by induction (32.0%) and consolidation (24.2%). Grade ≥ 2 RP increased to 16.7% with ICIs (IPTW-adjusted <em>P</em> = .004), peaking in the concurrent subgroup (39.1%), while comparable between induction and consolidation (16.1% vs. 12.2%). Independent predictors of grade ≥ 2 RP included ICIs treatment, gemcitabine-based induction chemotherapy, and higher lung dosimetry, with cut-offs of lung V20 (volume receiving ≥ 20 Gy) = 26.8% and mean lung dose (MLD) = 14.05 Gy. Grade ≥ 2 CIP incidence (14.2%) was associated with pre-existing interstitial lung disease or emphysema, PD-1 inhibitors and elevated MLD.</div></div><div><h3>Conclusions</h3><div>ICIs addition and timing significantly affected TRP risk. Mitigating lung toxicity requires careful selection of ICIs strategy, chemotherapy agents, and optimizing lung radiation dosimetry.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 14-24"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-12-04DOI: 10.1016/j.cllc.2025.11.019
Yuting Kuang , Ke Zu , Dezhi Xing , Aixue Liu , Jennifer Uyei , Arianna Nevo , Hsiu-Ching Chang , Christine M. Pierce
Pneumonitis is a notable toxicity of lung cancer therapies, particularly radiation and immune checkpoint inhibitors. Racial and ethnic disparities in pneumonitis risk exist, yet heterogeneity remains understudied. This study aimed to quantify pneumonitis incidence among East and Southeast Asian patients treated for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). A systematic literature review (SLR) and single-arm meta-analysis were conducted following Cochrane and PRISMA guidelines. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and 5 local language databases were searched for studies published from January 1, 2014 to August 2, 2023. Included were clinical trials in Asian patients undergoing pharmacological or radiation therapy for NSCLC or SCLC. The SLR included 218 trials (NSCLC: 202, SCLC: 16). Pooled incidence of all-grade, grade 1 to 2, and grade 3 to 5 pneumonitis in NSCLC was 5.42% (95% CI, 4.25-6.89), 3.58% (95% CI, 2.54-5.03) and 1.34% (95% CI, 1.06-1.70), respectively. For SCLC, pooled incidence was 12.21% (95% CI, 4.77-27.85), 7.64% (95% CI, 2.48-21.23), and 2.43% (95% CI, 1.47-3.97), respectively. Significantly higher rates of pneumonitis were observed in patients receiving chemoradiation or radiation-containing treatments, in general, compared to those not treated with radiation; grade 3 to 5 events in SCLC were not significantly different. This study establishes baseline pneumonitis risk in East and Southeast Asian patients treated for NSCLC and SCLC, highlighting higher incidence in those receiving radiation-containing treatments, particularly for lower-grade events. The results help contextualize safety data from clinical trials enrolling Asian patients.
{"title":"Incidence of Pneumonitis in Asian Patients With Lung Cancer: A Systematic Literature Review and Meta-analysis","authors":"Yuting Kuang , Ke Zu , Dezhi Xing , Aixue Liu , Jennifer Uyei , Arianna Nevo , Hsiu-Ching Chang , Christine M. Pierce","doi":"10.1016/j.cllc.2025.11.019","DOIUrl":"10.1016/j.cllc.2025.11.019","url":null,"abstract":"<div><div>Pneumonitis is a notable toxicity of lung cancer therapies, particularly radiation and immune checkpoint inhibitors. Racial and ethnic disparities in pneumonitis risk exist, yet heterogeneity remains understudied. This study aimed to quantify pneumonitis incidence among East and Southeast Asian patients treated for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). A systematic literature review (SLR) and single-arm meta-analysis were conducted following Cochrane and PRISMA guidelines. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and 5 local language databases were searched for studies published from January 1, 2014 to August 2, 2023. Included were clinical trials in Asian patients undergoing pharmacological or radiation therapy for NSCLC or SCLC. The SLR included 218 trials (NSCLC: 202, SCLC: 16). Pooled incidence of all-grade, grade 1 to 2, and grade 3 to 5 pneumonitis in NSCLC was 5.42% (95% CI, 4.25-6.89), 3.58% (95% CI, 2.54-5.03) and 1.34% (95% CI, 1.06-1.70), respectively. For SCLC, pooled incidence was 12.21% (95% CI, 4.77-27.85), 7.64% (95% CI, 2.48-21.23), and 2.43% (95% CI, 1.47-3.97), respectively. Significantly higher rates of pneumonitis were observed in patients receiving chemoradiation or radiation-containing treatments, in general, compared to those not treated with radiation; grade 3 to 5 events in SCLC were not significantly different. This study establishes baseline pneumonitis risk in East and Southeast Asian patients treated for NSCLC and SCLC, highlighting higher incidence in those receiving radiation-containing treatments, particularly for lower-grade events. The results help contextualize safety data from clinical trials enrolling Asian patients.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 25-37"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In pleural mesothelioma (PM), platinum-based chemotherapy and immune checkpoint inhibitors including nivolumab and ipilimumab have been approved but have not shown sufficient therapeutic efficacy, and the development of new therapies is desired. Pembrolizumab, anti-PD-1 antibody and lenvatinib which has inhibitory effect of angiogenesis are also expected to have a therapeutic effect on PM.
Patients and Methods
Twenty-five patients will be enrolled in PENINSULA trial. In induction treatment, study interventions include oral lenvatinib, 8 mg QD, and pembrolizumab, 200 mg, carboplatin (AUC 5 mg/mL/min) or cisplatin (75 mg/m2), and pemetrexed, 500 mg/m2 all given by intravenous (IV) infusion. In maintenance treatment, participants may receive lenvatinib, 20 mg QD, and pembrolizumab, 200 mg. Lenvatinib and pembrolizumab may be given for up to a total of 35 courses. The primary endpoint is overall response rate. The secondary endpoints are progression-free survival, overall survival time, tumor shrinkage (disease control rate), duration of response, best overall response and safety evaluation.
Conclusion
The purpose of this clinical trial is to evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab and standard chemotherapy as first-line therapy in adult patients with PM.
{"title":"Pembrolizumab Plus Platinum Doublet Chemotherapy With Lenvatinib in Unresectable Pleural Mesothelioma as First-Line Treatment (PENINSULA): A Study Protocol for a Single-Arm, Multi-Institutional, Phase II Clinical Trial","authors":"Tetsuya Takagawa , Kanae Takahashi , Yuji Orimoto , Yukie Morisaki , Shinichiro Suna , Takashi Daimon , Takashi Kijima , Kozo Kuribayashi","doi":"10.1016/j.cllc.2025.12.010","DOIUrl":"10.1016/j.cllc.2025.12.010","url":null,"abstract":"<div><h3>Background</h3><div>In pleural mesothelioma (PM), platinum-based chemotherapy and immune checkpoint inhibitors including nivolumab and ipilimumab have been approved but have not shown sufficient therapeutic efficacy, and the development of new therapies is desired. Pembrolizumab, anti-PD-1 antibody and lenvatinib which has inhibitory effect of angiogenesis are also expected to have a therapeutic effect on PM.</div></div><div><h3>Patients and Methods</h3><div>Twenty-five patients will be enrolled in PENINSULA trial. In induction treatment, study interventions include oral lenvatinib, 8 mg QD, and pembrolizumab, 200 mg, carboplatin (AUC 5 mg/mL/min) or cisplatin (75 mg/m<sup>2</sup>), and pemetrexed, 500 mg/m<sup>2</sup> all given by intravenous (IV) infusion. In maintenance treatment, participants may receive lenvatinib, 20 mg QD, and pembrolizumab, 200 mg. Lenvatinib and pembrolizumab may be given for up to a total of 35 courses. The primary endpoint is overall response rate. The secondary endpoints are progression-free survival, overall survival time, tumor shrinkage (disease control rate), duration of response, best overall response and safety evaluation.</div></div><div><h3>Conclusion</h3><div>The purpose of this clinical trial is to evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab and standard chemotherapy as first-line therapy in adult patients with PM.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 75-79"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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