This study aimed to clarify the relationship between preoperative adipopenia and clinicopathological factors, including sarcopenia and myosteatosis, in patients with surgically resected non-small cell lung cancer (NSCLC), and to evaluate short- and long-term outcomes.
Methods
We analyzed 300 patients who underwent complete resection of p-Stage I–IIIA NSCLC via lobectomy. Body composition was assessed by computed tomography at the L3 vertebral level, with fat and muscle areas normalized to height to calculate the total fat (TFI), visceral fat (VFI), subcutaneous fat (SFI), and skeletal muscle (SMI) indices. Adipopenia and sarcopenia were defined as the sex-specific lowest quartiles of these indices. Muscle quality was evaluated by paravertebral muscle density (PVMD) in Hounsfield units, with low quality (myosteatosis) defined by established sex-independent thresholds.
Results
The median age was 70 years; 184 patients were male. Median follow-up was 64 months. TFI, VFI, and SFI were strongly intercorrelated but showed limited correlation with SMI. Fat indices had weak-to-moderate negative correlations with PVMD. Adipopenia was not associated with postoperative complications. Overall survival (OS) was significantly worse in patients with adipopenia (TFI, VFI, SFI), whereas relapse-free survival was unaffected. Non-lung cancer-specific survival was significantly worse in males with adipopenia (TFI, VFI). In p-Stage I NSCLC, multivariable analysis identified adipopenia (VFI) and sarcopenia (SMI) as independent predictors of poor OS, regardless of myosteatosis.
Conclusions
Preoperative adipopenia independently predicts poor prognosis in p-Stage I NSCLC and may increase non-lung cancer-related mortality, particularly in males. Imaging-based body composition assessment may enhance perioperative risk and long-term outcome prediction.
{"title":"Clinical impact of preoperative adipopenia on postoperative outcomes in non-small cell lung cancer surgery","authors":"Atsuki Uchibori, Satoru Okada, Masanori Shimomura, Tatsuo Furuya, Chiaki Nakazono, Tomoki Nishimura, Kenji Kameyama, Masayoshi Inoue","doi":"10.1016/j.lungcan.2025.108810","DOIUrl":"10.1016/j.lungcan.2025.108810","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to clarify the relationship between preoperative adipopenia and clinicopathological factors, including sarcopenia and myosteatosis, in patients with surgically resected non-small cell lung cancer (NSCLC), and to evaluate short- and long-term outcomes.</div></div><div><h3>Methods</h3><div>We analyzed 300 patients who underwent complete resection of p-Stage I–IIIA NSCLC via lobectomy. Body composition was assessed by computed tomography at the L3 vertebral level, with fat and muscle areas normalized to height to calculate the total fat (TFI), visceral fat (VFI), subcutaneous fat (SFI), and skeletal muscle (SMI) indices. Adipopenia and sarcopenia were defined as the sex-specific lowest quartiles of these indices. Muscle quality was evaluated by paravertebral muscle density (PVMD) in Hounsfield units, with low quality (myosteatosis) defined by established sex-independent thresholds.</div></div><div><h3>Results</h3><div>The median age was 70 years; 184 patients were male. Median follow-up was 64 months. TFI, VFI, and SFI were strongly intercorrelated but showed limited correlation with SMI. Fat indices had weak-to-moderate negative correlations with PVMD. Adipopenia was not associated with postoperative complications. Overall survival (OS) was significantly worse in patients with adipopenia (TFI, VFI, SFI), whereas relapse-free survival was unaffected. Non-lung cancer-specific survival was significantly worse in males with adipopenia (TFI, VFI). In p-Stage I NSCLC, multivariable analysis identified adipopenia (VFI) and sarcopenia (SMI) as independent predictors of poor OS, regardless of myosteatosis.</div></div><div><h3>Conclusions</h3><div>Preoperative adipopenia independently predicts poor prognosis in p-Stage I NSCLC and may increase non-lung cancer-related mortality, particularly in males. Imaging-based body composition assessment may enhance perioperative risk and long-term outcome prediction.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108810"},"PeriodicalIF":4.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468740","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}
Pub Date : 2025-11-01DOI: 10.1016/j.lungcan.2025.108744
Justine H. Cuperus , Hanieh Abedian Kalkhoran , Henk Codrington , Loes E. Visser
Background
The treatment landscape for non-small cell lung cancer (NSCLC) has evolved with the introduction of immunotherapy, targeted therapy, and combinations with chemotherapy. However, therapy-related pneumonitis (TRP) poses a significant challenge, often leading to treatment discontinuation and respiratory failure. The incidence of TRP is frequently underestimated in clinical trials, and its associated risk factors remain underexplored. This study aimed to investigate the real-world incidence and risk factors for TRP across various NSCLC treatment regimens.
Methods
This retrospective cohort study included patients diagnosed with stage III or IV NSCLC and who started at least one of the 11 predefined systemic anti-cancer treatment regimens (comprising chemotherapy, immunotherapy, or targeted therapy) at Haga Teaching Hospital between January 2016 and January 2024. Clinical data were extracted from Electronic Health Records using text-mining based software. The objective was to determine the incidence rate (IR) per 100 person-years (PY) of grade ≥2 TRP requiring systemic corticosteroids across the treatment regimens. Risk factors for TRP were analyzed using Cox proportional hazards models.
Results
A total of 801 treatment regimens were followed on TRP in our cohort of 636 patients. The IRs varied across regimens, with the highest IR observed in patients receiving durvalumab following chemoradiotherapy (CRT) (27.7 per 100 PY). Among CRT regimens, the IR was higher in patients treated with etoposide compared to those receiving pemetrexed (20.5 vs. 8.5 per 100 PY). Pembrolizumab monotherapy exhibited a lower IR compared to its combination with platinum/paclitaxel or platinum/pemetrexed (6.6 vs. 16.6 and 8.9 per 100 PY, respectively). Certain chemotherapy and targeted therapy regimens reported no cases of TRP during the study period. Furthermore, the real-world incidence of TRP was higher than reported in pivotal clinical trials. Identified risk factors for TRP included higher body mass index and radiation fractions.
Conclusion
As NSCLC treatment evolves, addressing TRP risks becomes pivotal for ensuring the best possible patient outcomes. This large-scale real-world study provides valuable insights into the association between NSCLC treatment regimens and TRP, as well as the risk factors of TRP.
{"title":"Real-world incidence of pneumonitis in different treatment modalities of advanced non-small cell lung carcinoma","authors":"Justine H. Cuperus , Hanieh Abedian Kalkhoran , Henk Codrington , Loes E. Visser","doi":"10.1016/j.lungcan.2025.108744","DOIUrl":"10.1016/j.lungcan.2025.108744","url":null,"abstract":"<div><h3>Background</h3><div>The treatment landscape for non-small cell lung cancer (NSCLC) has evolved with the introduction of immunotherapy, targeted therapy, and combinations with chemotherapy. However, therapy-related pneumonitis (TRP) poses a significant challenge, often leading to treatment discontinuation and respiratory failure. The incidence of TRP is frequently underestimated in clinical trials, and its associated risk factors remain underexplored. This study aimed to investigate the real-world incidence and risk factors for TRP across various NSCLC treatment regimens.</div></div><div><h3>Methods</h3><div>This retrospective cohort study included patients diagnosed with stage III or IV NSCLC and who started at least one of the 11 predefined systemic anti-cancer treatment regimens (comprising chemotherapy, immunotherapy, or targeted therapy) at Haga Teaching Hospital between January 2016 and January 2024. Clinical data were extracted from Electronic Health Records using text-mining based software. The objective was to determine the incidence rate (IR) per 100 person-years (PY) of grade <em>≥</em>2 TRP requiring systemic corticosteroids across the treatment regimens. Risk factors for TRP were analyzed using Cox proportional hazards models.</div></div><div><h3>Results</h3><div>A total of 801 treatment regimens were followed on TRP in our cohort of 636 patients. The IRs varied across regimens, with the highest IR observed in patients receiving durvalumab following chemoradiotherapy (CRT) (27.7 per 100 PY). Among CRT regimens, the IR was higher in patients treated with etoposide compared to those receiving pemetrexed (20.5 vs. 8.5 per 100 PY). Pembrolizumab monotherapy exhibited a lower IR compared to its combination with platinum/paclitaxel or platinum/pemetrexed (6.6 vs. 16.6 and 8.9 per 100 PY, respectively). Certain chemotherapy and targeted therapy regimens reported no cases of TRP during the study period. Furthermore, the real-world incidence of TRP was higher than reported in pivotal clinical trials. Identified risk factors for TRP included higher body mass index and radiation fractions.</div></div><div><h3>Conclusion</h3><div>As NSCLC treatment evolves, addressing TRP risks becomes pivotal for ensuring the best possible patient outcomes. This large-scale real-world study provides valuable insights into the association between NSCLC treatment regimens and TRP, as well as the risk factors of TRP.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"209 ","pages":"Article 108744"},"PeriodicalIF":4.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417847","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}
Pub Date : 2025-10-27DOI: 10.1016/j.lungcan.2025.108805
William Ricketts , Catherine Sandsund , Zoe Merchant , Kevin Franks , Cecilia Pompili , Andriana Petrova , Asanga Fernando , Pamela Dalrymple , Babu Naidu , Lucy Gossage , Matthew Evison
Introduction
Prehabilitation in patients with lung cancer has historically been focused on those undergoing surgical resection. However, its benefits could be applicable to those undergoing all forms of treatment both in the curative- and palliative-intent settings.
Materials and methods
Twelve healthcare professionals convened to discuss prehabilitation across the spectrum of lung cancer management, aiming to share best practice and provide practical guidance.
Results
Prehabilitation should be considered as part of a holistic treatment package for all patients diagnosed with lung cancer. A robust evidence base exists for patients undergoing surgery, with a developing and promising evidence base in other treatment pathways. Whilst further research is recommended, there is a strong ethical argument based on ‘distributive justice’ to adopt stage and treatment-agnostic delivery.
Prehabilitation should begin as early as possible, ideally when a patient enters the diagnostic pathway. The benefits outweigh any negatives of delivering prehabilitation to people who do not have cancer and can only be delivered with a stage and treatment-agnostic ethos. Prehabilitation in the palliative treatment setting differs from the curative-intent setting, with patients facing more prolonged fluctuations in functional capacity as well as the psychological and physiological impact of ongoing treatment.
Discussion
Stage and treatment-agnostic prehabilitation should become a standard of care within the lung cancer pathway.
{"title":"Delivering equitable access to prehabilitation services to optimise outcomes for patients with lung cancer – Best practice recommendations from a UK roundtable event","authors":"William Ricketts , Catherine Sandsund , Zoe Merchant , Kevin Franks , Cecilia Pompili , Andriana Petrova , Asanga Fernando , Pamela Dalrymple , Babu Naidu , Lucy Gossage , Matthew Evison","doi":"10.1016/j.lungcan.2025.108805","DOIUrl":"10.1016/j.lungcan.2025.108805","url":null,"abstract":"<div><h3>Introduction</h3><div>Prehabilitation in patients with lung cancer has historically been focused on those undergoing surgical resection. However, its benefits could be applicable to those undergoing all forms of treatment both in the curative- and palliative-intent settings.</div></div><div><h3>Materials and methods</h3><div>Twelve healthcare professionals convened to discuss prehabilitation across the spectrum of lung cancer management, aiming to share best practice and provide practical guidance.</div></div><div><h3>Results</h3><div>Prehabilitation should be considered as part of a holistic treatment package for all patients diagnosed with lung cancer. A robust evidence base exists for patients undergoing surgery, with a developing and promising evidence base in other treatment pathways. Whilst further research is recommended, there is a strong ethical argument based on ‘distributive justice’ to adopt stage and treatment-agnostic delivery.</div><div>Prehabilitation should begin as early as possible, ideally when a patient enters the diagnostic pathway. The benefits outweigh any negatives of delivering prehabilitation to people who do not have cancer and can only be delivered with a stage and treatment-agnostic ethos. Prehabilitation in the palliative treatment setting differs from the curative-intent setting, with patients facing more prolonged fluctuations in functional capacity as well as the psychological and physiological impact of ongoing treatment.</div></div><div><h3>Discussion</h3><div>Stage and treatment-agnostic prehabilitation should become a standard of care within the lung cancer pathway.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108805"},"PeriodicalIF":4.4,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145459232","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}
Pub Date : 2025-10-21DOI: 10.1016/j.lungcan.2025.108802
Christian Rolfo , David E. Gerber , Rupesh Kotecha , Jeffrey P. Ward , Wallace Akerley , Lukas Weiss , Ariel Naveh , Nadav Shapira , Ticiana Leal , Corey J. Langer , on behalf of the LUNAR study investigators
Introduction
In the phase III LUNAR study, overall survival (OS) with PD-(L)1 inhibitor or docetaxel was improved by adding Tumor Treating Fields (TTFields) therapy in patients with metastatic non-small cell lung cancer progressing on/after platinum-based therapy. This post-hoc analysis evaluated the effects of body mass index (BMI) on TTFields delivery.
Methods
OS was assessed in LUNAR patients with BMI < 25 kg/m2 versus ≥ 25 kg/m2. TTFields intensity was evaluated via simulations using three array layouts in computerized phantom models with BMIs of 22, 26, and 30 kg/m2.
Results
In the BMI < 25 kg/m2 subgroup (n = 140), median OS was 11.6 versus 8.2 months (hazard ratio [HR] 0.70 [95 % CI, 0.47─1.04]; p = 0.08) in patients treated with TTFields + PD-(L)1 inhibitor/docetaxel versus PD-(L)1 inhibitor/docetaxel, respectively. In the BMI ≥ 25 kg/m2 subgroup (n = 119), median OS was 13.9 versus 10.1 months, respectively (HR 0.74 [95 % CI, 0.49─1.13]; p = 0.27). No significant interaction effect between BMI subgroups and treatment arm was identified for OS (p = 0.36). Device-related skin AEs occurred in 68 % and 64 % of BMI < 25 kg/m2 and ≥ 25 kg/m2 patients, respectively. Therapeutic field intensities (>1 V/cm) were achieved in all lung regions for all simulation models using appropriately sized arrays and layouts.
Conclusions
In this post-hoc analysis, we found no difference in OS benefit of TTFields therapy between patients with BMI < 25 kg/m2 versus ≥ 25 kg/m2. Simulation data demonstrated the feasibility of delivering TTFields at therapeutic intensities to the lungs regardless of BMI.
{"title":"The influence of body mass index on Tumor Treating Fields therapy in patients with metastatic non-small cell lung cancer: A post-hoc and simulation analysis from the phase III LUNAR study","authors":"Christian Rolfo , David E. Gerber , Rupesh Kotecha , Jeffrey P. Ward , Wallace Akerley , Lukas Weiss , Ariel Naveh , Nadav Shapira , Ticiana Leal , Corey J. Langer , on behalf of the LUNAR study investigators","doi":"10.1016/j.lungcan.2025.108802","DOIUrl":"10.1016/j.lungcan.2025.108802","url":null,"abstract":"<div><h3>Introduction</h3><div>In the phase III LUNAR study, overall survival (OS) with PD-(L)1 inhibitor or docetaxel was improved by adding Tumor Treating Fields (TTFields) therapy in patients with metastatic non-small cell lung cancer progressing on/after platinum-based therapy. This post-hoc analysis evaluated the effects of body mass index (BMI) on TTFields delivery.</div></div><div><h3>Methods</h3><div>OS was assessed in LUNAR patients with BMI < 25 kg/m<sup>2</sup> versus ≥ 25 <!--> <!-->kg/m<sup>2</sup>. TTFields intensity was evaluated via simulations using three array layouts in computerized phantom models with BMIs of 22, 26, and 30 kg/m<sup>2</sup>.</div></div><div><h3>Results</h3><div>In the BMI < 25 kg/m<sup>2</sup> subgroup (n = 140), median OS was 11.6 versus 8.2 months (hazard ratio [HR] 0.70 [95 % CI, 0.47─1.04]; p = 0.08) in patients treated with TTFields + PD-(L)1 inhibitor/docetaxel versus PD-(L)1 inhibitor/docetaxel, respectively. In the BMI ≥ 25 kg/m<sup>2</sup> subgroup (n = 119), median OS was 13.9 versus 10.1 months, respectively (HR 0.74 [95 % CI, 0.49─1.13]; p = 0.27). No significant interaction effect between BMI subgroups and treatment arm was identified for OS (p = 0.36). Device-related skin AEs occurred in 68 % and 64 % of BMI < 25 kg/m<sup>2</sup> and ≥ 25 kg/m<sup>2</sup> patients, respectively. Therapeutic field intensities (>1<!--> <!-->V/cm) were achieved in all lung regions for all simulation models using appropriately sized arrays and layouts.</div></div><div><h3>Conclusions</h3><div>In this post-hoc analysis, we found no difference in OS benefit of TTFields therapy between patients with BMI < 25 kg/m<sup>2</sup> versus ≥ 25 kg/m<sup>2</sup>. Simulation data demonstrated the feasibility of delivering TTFields at therapeutic intensities to the lungs regardless of BMI.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108802"},"PeriodicalIF":4.4,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425582","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}
Pub Date : 2025-10-20DOI: 10.1016/j.lungcan.2025.108800
Michael Abele , Anton Karelin , Michaela Pogoda , Ulrike Faust , Sorin Armeanu-Ebinger , Jakob Admard , Alexandra Liebmann , Irina Bonzheim , Nicolas Waespe , Margo Hoover-Regan , Andreas Block , Martin Reck , Ewa Bien , Malgorzata Krawczyk , Dominik T. Schneider , Stephan Ossowski , Ines B. Brecht , Christopher Schroeder
Background
Primary lung carcinomas are extremely rare in childhood, resulting in limited knowledge of their biology and potential therapeutic targets.
Methods
Whole genome sequencing analysis was performed on 14 patients, thereof 13 pediatric patients. The cohort was grouped into pulmonary mucoepidermoid carcinoma (PMEC) and lung adenocarcinoma (LUAD) with an additional sample being adenosquamous carcinoma (ASC). DNA of tumor and normal tissue were isolated from FFPE and sequenced on a high-throughput sequencer. Data analysis was performed with an in-house validated data analysis pipeline.
Results
In the group of pediatric LUAD and ASC, ALK::EML4 fusions were confirmed in three of six tumors, prompting ALK-targeted treatment. We also found mutations frequently occurring in adult LUAD, such as TP53 (n = 3), KRAS and EGFR (each n = 1), but not other established druggable alterations. No smoking-related signatures were observed. One LUAD sample had a homologous recombination deficiency with a high amount of copy number alterations. In the PMEC group (n = 7), we found MAML2 fusions in all patients. Pathogenic germline variants and elevated polygenic risk scores for lung cancer were not detected in both groups.
Conclusions
This study provides crucial insights into the genomic landscape across different types of pediatric lung cancer. We observed frequent presence of ALK fusions in pediatric LUAD + ASC, which are less common in adult LUAD. Other alterations in this subgroup showed resemblance with adult LUAD findings. In pediatric PMEC, we demonstrated the ubiquitous presence of MAML2 translocations. However, the conclusions of the study are limited due to the small sample size and potential artifacts from formalin-fixed paraffin-embedded samples. In summary, the results provide better understanding of the development of rare pediatric tumors and approaches for targeted therapies.
{"title":"Distinct genomic profile of pediatric lung carcinoma: High frequency of ALK fusions and TP53 mutations compared to adults","authors":"Michael Abele , Anton Karelin , Michaela Pogoda , Ulrike Faust , Sorin Armeanu-Ebinger , Jakob Admard , Alexandra Liebmann , Irina Bonzheim , Nicolas Waespe , Margo Hoover-Regan , Andreas Block , Martin Reck , Ewa Bien , Malgorzata Krawczyk , Dominik T. Schneider , Stephan Ossowski , Ines B. Brecht , Christopher Schroeder","doi":"10.1016/j.lungcan.2025.108800","DOIUrl":"10.1016/j.lungcan.2025.108800","url":null,"abstract":"<div><h3>Background</h3><div>Primary lung carcinomas are extremely rare in childhood, resulting in limited knowledge of their biology and potential therapeutic targets.</div></div><div><h3>Methods</h3><div>Whole genome sequencing analysis was performed on 14 patients, thereof 13 pediatric patients. The cohort was grouped into pulmonary mucoepidermoid carcinoma (PMEC) and lung adenocarcinoma (LUAD) with an additional sample being adenosquamous carcinoma (ASC). DNA of tumor and normal tissue were isolated from FFPE and sequenced on a high-throughput sequencer. Data analysis was performed with an in-house validated data analysis pipeline.</div></div><div><h3>Results</h3><div>In the group of pediatric LUAD and ASC, <em>ALK</em>::<em>EML4</em> fusions were confirmed in three of six tumors, prompting ALK-targeted treatment. We also found mutations frequently occurring in adult LUAD, such as <em>TP53</em> (n = 3), <em>KRAS</em> and <em>EGFR</em> (each n = 1), but not other established druggable alterations. No smoking-related signatures were observed. One LUAD sample had a homologous recombination deficiency with a high amount of copy number alterations. In the PMEC group (n = 7), we found <em>MAML2</em> fusions in all patients. Pathogenic germline variants and elevated polygenic risk scores for lung cancer were not detected in both groups.</div></div><div><h3>Conclusions</h3><div>This study provides crucial insights into the genomic landscape across different types of pediatric lung cancer. We observed frequent presence of <em>ALK</em> fusions in pediatric LUAD + ASC, which are less common in adult LUAD. Other alterations in this subgroup showed resemblance with adult LUAD findings. In pediatric PMEC, we demonstrated the ubiquitous presence of <em>MAML2</em> translocations. However, the conclusions of the study are limited due to the small sample size and potential artifacts from formalin-fixed paraffin-embedded samples. In summary, the results provide better understanding of the development of rare pediatric tumors and approaches for targeted therapies.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"209 ","pages":"Article 108800"},"PeriodicalIF":4.4,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355149","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}
Pub Date : 2025-10-16DOI: 10.1016/j.lungcan.2025.108797
Igor Gomez-Randulfe , Federico Monaca , Ornella Cantale , Maria Lucia Reale , Loredana Mrak , Lodovica Zullo , Sofia Silva Diaz , Marta Zaragoza Bueno , Marya Alejandra Maridueña Moreno , Charlotte Davis , Samantha Cox , Daniel Lee , Riyaz Shah , Tom Geldart , Javier Baena , Jose Carlos Benitez , M.A. Rosario Garcia Campelo , Jordi Remon , David Planchard , Domenico Galetta , Raffaele Califano
Background
First-line osimertinib is one of the standards of care for EGFR-mutant advanced non-small cell lung cancer (NSCLC), but most patients eventually progress. After progression, carboplatin plus pemetrexed remains the most widely used second-line therapy, yet robust real-world data in this setting are scarce.
Methods
We conducted a retrospective multicentre cohort study from four European countries in patients with EGFR-mutant advanced NSCLC who received second-line carboplatin plus pemetrexed following osimertinib. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate (ORR), safety, and exploratory analyses of associations between baseline factors and outcomes.
Results
We identified a total of 252 patients. Median PFS and OS were 5.3 months (95 % CI 4.7–5.9) and 9.6 months (95 % CI 8.2–11.1), respectively. The ORR was 40.7 %, with grade ≥ 3 adverse events reported in 19.3 % of patients. ECOG ≥ 2 and liver metastases independently predicted worse OS; ECOG ≥ 2 and a history of smoking were associated with shorter PFS. Early progression on osimertinib (<18 months) correlated with shorter OS (8.3 vs 14.7 months; HR 1.66, P = 0.005). Neither the timing between osimertinib discontinuation and chemotherapy initiation nor EGFR mutation subtype influenced efficacy.
Conclusions
In real-world European practice, second-line carboplatin plus pemetrexed provides modest benefit post-osimertinib, with outcomes strongly influenced by ECOG status, metastatic burden, and prior osimertinib duration. Despite a clinically diverse cohort, outcomes were consistent with historical reports. These data help define benchmarks for future trials and underscore the need for personalised sequencing strategies, particularly in high-risk subgroups.
奥西替尼是egfr突变晚期非小细胞肺癌（NSCLC）的一线治疗标准之一，但大多数患者最终进展。进展后，卡铂加培美曲塞仍然是最广泛使用的二线治疗，但在这种情况下，可靠的现实数据很少。方法：我们对来自4个欧洲国家的egfr突变晚期NSCLC患者进行了一项回顾性多中心队列研究，这些患者在服用奥西替尼后接受了二线卡铂加培美曲塞治疗。主要终点为无进展生存期（PFS）和总生存期（OS）。次要结局包括客观缓解率（ORR）、安全性以及基线因素与结局之间相关性的探索性分析。结果共鉴定出252例患者。中位PFS和OS分别为5.3个月（95% CI 4.7-5.9）和9.6个月（95% CI 8.2-11.1）。ORR为40.7%，19.3%的患者报告了≥3级不良事件。ECOG≥2和肝转移独立预测较差的OS；ECOG≥2和吸烟史与较短的PFS相关。奥西替尼早期进展（18个月）与较短的OS相关（8.3个月vs 14.7个月；HR 1.66, P = 0.005）。奥西替尼停药和开始化疗之间的时间和EGFR突变亚型都不影响疗效。在真实的欧洲实践中，二线卡铂加培美曲塞在服用奥西替尼后可提供适度的获益，其结果受到ECOG状态、转移性负担和先前服用奥西替尼持续时间的强烈影响。尽管临床队列不同，但结果与历史报告一致。这些数据有助于确定未来试验的基准，并强调个性化测序策略的必要性，特别是在高风险亚组中。
{"title":"Real-world outcomes of second-line carboplatin plus pemetrexed after first-line osimertinib in EGFR-mutant advanced NSCLC: An international multicentre cohort study","authors":"Igor Gomez-Randulfe , Federico Monaca , Ornella Cantale , Maria Lucia Reale , Loredana Mrak , Lodovica Zullo , Sofia Silva Diaz , Marta Zaragoza Bueno , Marya Alejandra Maridueña Moreno , Charlotte Davis , Samantha Cox , Daniel Lee , Riyaz Shah , Tom Geldart , Javier Baena , Jose Carlos Benitez , M.A. Rosario Garcia Campelo , Jordi Remon , David Planchard , Domenico Galetta , Raffaele Califano","doi":"10.1016/j.lungcan.2025.108797","DOIUrl":"10.1016/j.lungcan.2025.108797","url":null,"abstract":"<div><h3>Background</h3><div>First-line osimertinib is one of the standards of care for <em>EGFR</em>-mutant advanced non-small cell lung cancer (NSCLC), but most patients eventually progress. After progression, carboplatin plus pemetrexed remains the most widely used second-line therapy, yet robust real-world data in this setting are scarce.</div></div><div><h3>Methods</h3><div>We conducted a retrospective multicentre cohort study from four European countries in patients with EGFR-mutant advanced NSCLC who received second-line carboplatin plus pemetrexed following osimertinib. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate (ORR), safety, and exploratory analyses of associations between baseline factors and outcomes.</div></div><div><h3>Results</h3><div>We identified a total of 252 patients. Median PFS and OS were 5.3 months (95 % CI 4.7–5.9) and 9.6 months (95 % CI 8.2–11.1), respectively. The ORR was 40.7 %, with grade ≥ 3 adverse events reported in 19.3 % of patients. ECOG ≥ 2 and liver metastases independently predicted worse OS; ECOG ≥ 2 and a history of smoking were associated with shorter PFS. Early progression on osimertinib (<18 months) correlated with shorter OS (8.3 vs 14.7 months; HR 1.66, P = 0.005). Neither the timing between osimertinib discontinuation and chemotherapy initiation nor <em>EGFR</em> mutation subtype influenced efficacy.</div></div><div><h3>Conclusions</h3><div>In real-world European practice, second-line carboplatin plus pemetrexed provides modest benefit post-osimertinib, with outcomes strongly influenced by ECOG status, metastatic burden, and prior osimertinib duration. Despite a clinically diverse cohort, outcomes were consistent with historical reports. These data help define benchmarks for future trials and underscore the need for personalised sequencing strategies, particularly in high-risk subgroups.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"209 ","pages":"Article 108797"},"PeriodicalIF":4.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145363942","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}
Pub Date : 2025-10-16DOI: 10.1016/j.lungcan.2025.108799
Alessio Cortellini , Edoardo Garbo , Giulia La Cava , Fabrizio Citarella , Valentina Santo , Leonardo Brunetti , David J Pinato , Jarushka Naidoo , Monica Loza , Carlo Genova , Scott Gettinger , So Yeon Kim , Ritujith Jayakrishnan , Talal El Zarif , Marco Russano , Federica Pecci , Alessandro Di Federico , Michele Montrone , Dwight H Owen , Diego Signorelli , Valerio Guarrasi
Background
The use of first-line single agent immunotherapy in patients with advanced NSCLC and ECOG PS ≥ 2 remains controversial, as this frail population has been largely excluded from pivotal clinical trials. Real-world evidence suggests that although median survival is poor, a subset of these patients may achieve long-term benefit.
Methods
We analyzed data from the Pembro-Real 5Y registry, a global real-world dataset with > 5 years follow-up. The cohort included patients with advanced NSCLC, PD-L1 TPS ≥ 50 %, treated with first line pembrolizumab outside of clinical trials. Univariable analyses were conducted to identify descriptive characteristics associated with survival. To address the complexity of long-term outcome prediction, we integrated Elastic Net regression and a transformer-based AI model (NAIM). The Elastic Net model was employed to mitigate collinearity and select relevant prognostic factors, while NAIM was used to explore non-linear, time-dependent interactions between variables. Endpoints included overall survival (OS) and 5-year survival rates.
Results
Out of 1050 patients, 161 patients with ECOG PS ≥ 2 were included, showing a median OS of 5.4 months (95 % CI: 3.8–7.8), and a 5-year survival rate of 13.0 % (95 % CI: 8.1–19.9). Univariable analysis indicated that no single baseline variable was strongly predictive of 5-year survival, except for TMB, KRAS, and BRAF status, which were significantly limited by missingness. Elastic Net identified only two significant predictors of 5-year survival: high TMB (with unstable confidence intervals) and KRAS mutation. NAIM provided a dynamic perspective, confirming that bone metastases and baseline corticosteroid use were strong predictors of early mortality, whereas BMI increase and systemic health markers/host factors (e.g., hypertension and dyslipidemia) gained importance in long-term survivors. However, NAIM exhibited a notable performance drop from training to validation suggesting overfitting and the challenge of modeling long-term outcomes using baseline static variables.
Conclusions
Despite the overall poor prognosis, a subset of patients with ECOG PS ≥ 2 achieves long-term survival with pembrolizumab monotherapy, indicating that performance status alone should not preclude treatment in all cases. Our analysis highlights the limitations of traditional statistical approaches and AI-driven models in predicting long-term benefit in this heterogeneous population. Future efforts should focus on refining hybrid modeling strategies and incorporating prospective validation to better identify those who may benefit from immunotherapy beyond short-term expectations.
{"title":"Long-term outcomes from pembrolizumab monotherapy in patients with advanced NSCLC, PD-L1 expression ≥ 50 %, and poor performance status: Transformer-based AI to characterize prognostic complexity","authors":"Alessio Cortellini , Edoardo Garbo , Giulia La Cava , Fabrizio Citarella , Valentina Santo , Leonardo Brunetti , David J Pinato , Jarushka Naidoo , Monica Loza , Carlo Genova , Scott Gettinger , So Yeon Kim , Ritujith Jayakrishnan , Talal El Zarif , Marco Russano , Federica Pecci , Alessandro Di Federico , Michele Montrone , Dwight H Owen , Diego Signorelli , Valerio Guarrasi","doi":"10.1016/j.lungcan.2025.108799","DOIUrl":"10.1016/j.lungcan.2025.108799","url":null,"abstract":"<div><h3>Background</h3><div>The use of first-line single agent immunotherapy in patients with advanced NSCLC and ECOG PS ≥ 2 remains controversial, as this frail population has been largely excluded from pivotal clinical trials. Real-world evidence suggests that although median survival is poor, a subset of these patients may achieve long-term benefit.</div></div><div><h3>Methods</h3><div>We analyzed data from the Pembro-Real 5Y registry, a global real-world dataset with > 5 years follow-up. The cohort included patients with advanced NSCLC, PD-L1 TPS ≥ 50 %, treated with first line pembrolizumab outside of clinical trials. Univariable analyses were conducted to identify descriptive characteristics associated with survival. To address the complexity of long-term outcome prediction, we integrated Elastic Net regression and a transformer-based AI model (NAIM). The Elastic Net model was employed to mitigate collinearity and select relevant prognostic factors, while NAIM was used to explore non-linear, time-dependent interactions between variables. Endpoints included overall survival (OS) and 5-year survival rates.</div></div><div><h3>Results</h3><div>Out of 1050 patients, 161 patients with ECOG PS ≥ 2 were included, showing a median OS of 5.4 months (95 % CI: 3.8–7.8), and a 5-year survival rate of 13.0 % (95 % CI: 8.1–19.9). Univariable analysis indicated that no single baseline variable was strongly predictive of 5-year survival, except for TMB, KRAS, and BRAF status, which were significantly limited by missingness. Elastic Net identified only two significant predictors of 5-year survival: high TMB (with unstable confidence intervals) and KRAS mutation. NAIM provided a dynamic perspective, confirming that bone metastases and baseline corticosteroid use were strong predictors of early mortality, whereas BMI increase and systemic health markers/host factors (e.g., hypertension and dyslipidemia) gained importance in long-term survivors. However, NAIM exhibited a notable performance drop from training to validation suggesting overfitting and the challenge of modeling long-term outcomes using baseline static variables.</div></div><div><h3>Conclusions</h3><div>Despite the overall poor prognosis, a subset of patients with ECOG PS ≥ 2 achieves long-term survival with pembrolizumab monotherapy, indicating that performance status alone should not preclude treatment in all cases. Our analysis highlights the limitations of traditional statistical approaches and AI-driven models in predicting long-term benefit in this heterogeneous population. Future efforts should focus on refining hybrid modeling strategies and incorporating prospective validation to better identify those who may benefit from immunotherapy beyond short-term expectations.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"209 ","pages":"Article 108799"},"PeriodicalIF":4.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318425","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}
Pub Date : 2025-10-14DOI: 10.1016/j.lungcan.2025.108798
Mariana Brandão , Elena Prisciandaro , Eleni Xenophontos , Alessio Mariolo , Amir H. Sadeghi , Andrea R. Filippi , Antonin Levy , Artur Bandura , Caroline Caramella , Chris Dickhoff , Constance de Margerie-Mellon , Corinne Faivre-Finn , Daniel Portik , David Sanchez-Lorente , Dirk De Ruysscher , Egbert Smit , Elisa Gobbini , Elie Fadel , Enrico Ruffini , Emanuela Olmetto , Anne-Marie C. Dingemans
Introduction
Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease, leading to ambiguity in resectability criteria. This has prompted the EORTC Lung Cancer Group to establish a standardized definition of resectability for clinical trials. A Delphi consensus process was initiated, including a systematic review, survey, and clinical cases review. Here, we report exclusively the results of the clinical cases review, aimed to categorize cases based on tumor and lymph node factors, to identify those deemed surgically resectable upfront.
Methods
Consecutive patients with clinical stage III NSCLC (8th TNM edition) treated at Institut Jules Bordet between 2016–2021 were identified. These cases underwent evaluation by multidisciplinary panels (MDT), comprising thoracic surgeons, radiation oncologists, medical oncologists/pulmonologists and imaging specialists. The MDT determined the resectability of each tumor, and non-consensual cases underwent a second and a third discussion rounds. A TNM-subset was classified as “resectable” if ≥75 % of cases within that category were deemed “resectable” following multiple rounds of review.
Results
Among 105 cases, 52 % of tumors were stage IIIA, 36 % stage IIIB and 11 % stage IIIC. After the first two review rounds, 13 % of cases were classified as “no consensus” and moved to a third round. The main reasons were suboptimal imaging (n = 8), incomplete invasive mediastinal staging to assess the N factor (n = 3), and disagreement on the resectability of T4 tumors invading thoracic structures or with multi-station/bulky N2 disease (n = 3). After the third review round, T3-T4 tumors based on size/satellite nodules and/or with N1-N2 single-station involvement were considered resectable. In contrast, many invasive T4-tumors were considered unresectable, especially if combined with N2-N3 disease. N2-multi-station, N2-bulky or N3 involvement were generally considered unresectable (100 %/95 %/95 % respectively).
Conclusions
After a multiple-round multidisciplinary review of real-world cases, consensus was reached for most TNM-subsets, except for invasive T4N0 tumors. This case review informed the Consensual Definition of Resectable stage III NSCLC in clinical trials.
{"title":"Definition of resectable stage III non-small cell lung cancer (NSCLC) for inclusion in clinical trials: A clinical case review by a pan-European multidisciplinary expert panel led by the EORTC Lung Cancer Group","authors":"Mariana Brandão , Elena Prisciandaro , Eleni Xenophontos , Alessio Mariolo , Amir H. Sadeghi , Andrea R. Filippi , Antonin Levy , Artur Bandura , Caroline Caramella , Chris Dickhoff , Constance de Margerie-Mellon , Corinne Faivre-Finn , Daniel Portik , David Sanchez-Lorente , Dirk De Ruysscher , Egbert Smit , Elisa Gobbini , Elie Fadel , Enrico Ruffini , Emanuela Olmetto , Anne-Marie C. Dingemans","doi":"10.1016/j.lungcan.2025.108798","DOIUrl":"10.1016/j.lungcan.2025.108798","url":null,"abstract":"<div><h3>Introduction</h3><div>Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease, leading to ambiguity in resectability criteria. This has prompted the EORTC Lung Cancer Group to establish a standardized definition of resectability for clinical trials. A Delphi consensus process was initiated, including a systematic review, survey, and clinical cases review. Here, we report exclusively the results of the clinical cases review, aimed to categorize cases based on tumor and lymph node factors, to identify those deemed surgically resectable upfront.</div></div><div><h3>Methods</h3><div>Consecutive patients with clinical stage III NSCLC (8th TNM edition) treated at Institut Jules Bordet between 2016–2021 were identified. These cases underwent evaluation by multidisciplinary panels (MDT), comprising thoracic surgeons, radiation oncologists, medical oncologists/pulmonologists and imaging specialists. The MDT determined the resectability of each tumor, and non-consensual cases underwent a second and a third discussion rounds. A TNM-subset was classified as “resectable” if ≥75 % of cases within that category were deemed “resectable” following multiple rounds of review.</div></div><div><h3>Results</h3><div>Among 105 cases, 52 % of tumors were stage IIIA, 36 % stage IIIB and 11 % stage IIIC. After the first two review rounds, 13 % of cases were classified as “no consensus” and moved to a third round. The main reasons were suboptimal imaging (n = 8), incomplete invasive mediastinal staging to assess the N factor (n = 3), and disagreement on the resectability of T4 tumors invading thoracic structures or with multi-station/bulky N2 disease (n = 3). After the third review round, T3-T4 tumors based on size/satellite nodules and/or with N1-N2 single-station involvement were considered resectable. In contrast, many invasive T4-tumors were considered unresectable, especially if combined with N2-N3 disease. N2-multi-station, N2-bulky or N3 involvement were generally considered unresectable (100 %/95 %/95 % respectively).</div></div><div><h3>Conclusions</h3><div>After a multiple-round multidisciplinary review of real-world cases, consensus was reached for most TNM-subsets, except for invasive T4N0 tumors. This case review informed the Consensual Definition of Resectable stage III NSCLC in clinical trials.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"209 ","pages":"Article 108798"},"PeriodicalIF":4.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318475","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}
Pub Date : 2025-10-14DOI: 10.1016/j.lungcan.2025.108795
Prashasti Agrawal , Julia Rotow , Gaetano Rocco , William Travis , Eduardo Ortiz , Rebecca Scalabrino , Jaclyn LoPiccolo , Francesco Facchinetti , Mark G. Kris , Helena A. Yu , David Jones , Jamie E. Chaft
Background
EGFR-inhibitors are currently not approved for neoadjuvant treatment of resectable EGFR-mutant non-small cell lung cancers (NSCLC). We report a real-world multi-institutional analysis of surgical and pathologic outcomes in patients with resectable EGFR-mutant NSCLC treated with neoadjuvant therapies.
Methods
We identified patients with clinical stage II-IIIB NSCLC with sensitizing EGFR mutations who received neoadjuvant osimertinib and/or platinum-based doublet chemotherapy with intent for definitive surgical resection. Clinicopathologic characteristics and treatment outcomes were annotated. Event-free survival (EFS) was defined from the start of neoadjuvant treatment.
Results
We identified 51 patients who received neoadjuvant osimertinib (N = 23, 45 %), chemotherapy alone (N = 18, 35 %), or osimertinib and chemotherapy (N = 10, 20 %). R0 resection rates were 91 % with osimertinib, 72 % with chemotherapy, and 90 % with osimertinib and chemotherapy. Rates of pathologic complete response were 17 % with osimertinib, 0 % with chemotherapy, and 0 % with osimertinib and chemotherapy. Rates of major pathologic response were 44 % with osimertinib, 0 % with chemotherapy, and 10 % with osimertinib and chemotherapy. Pathologic tumor downstaging occurred in 48 % with osimertinib, 44 % with chemotherapy, and 40 % with osimertinib and chemotherapy; pathologic lymph node downstaging occurred in 35 % with osimertinib, 28 % with chemotherapy, and 40 % with osimertinib and chemotherapy. Median follow up time was 19 months. Median EFS was 61 months with osimertinib, 32 months with chemotherapy, and 20 months with osimertinib and chemotherapy.
Conclusions
Pathologic complete responses and major pathologic responses were only observed in patients with EGFR-mutant NSCLC treated with osimertinib. EGFR-inhibitors may play an important role in the preoperative management of EGFR-mutant lung cancer.
{"title":"Outcomes with neoadjuvant osimertinib and/or chemotherapy in patients with EGFR-mutant resectable non-small cell lung cancers","authors":"Prashasti Agrawal , Julia Rotow , Gaetano Rocco , William Travis , Eduardo Ortiz , Rebecca Scalabrino , Jaclyn LoPiccolo , Francesco Facchinetti , Mark G. Kris , Helena A. Yu , David Jones , Jamie E. Chaft","doi":"10.1016/j.lungcan.2025.108795","DOIUrl":"10.1016/j.lungcan.2025.108795","url":null,"abstract":"<div><h3>Background</h3><div>EGFR-inhibitors are currently not approved for neoadjuvant treatment of resectable <em>EGFR</em>-mutant non-small cell lung cancers (NSCLC). We report a real-world multi-institutional analysis of surgical and pathologic outcomes in patients with resectable <em>EGFR</em>-mutant NSCLC treated with neoadjuvant therapies.</div></div><div><h3>Methods</h3><div>We identified patients with clinical stage II-IIIB NSCLC with sensitizing <em>EGFR</em> mutations who received neoadjuvant osimertinib and/or platinum-based doublet chemotherapy with intent for definitive surgical resection. Clinicopathologic characteristics and treatment outcomes were annotated. Event-free survival (EFS) was defined from the start of neoadjuvant treatment.</div></div><div><h3>Results</h3><div>We identified 51 patients who received neoadjuvant osimertinib (N = 23, 45 %), chemotherapy alone (N = 18, 35 %), or osimertinib and chemotherapy (N = 10, 20 %). R0 resection rates were 91 % with osimertinib, 72 % with chemotherapy, and 90 % with osimertinib and chemotherapy. Rates of pathologic complete response were 17 % with osimertinib, 0 % with chemotherapy, and 0 % with osimertinib and chemotherapy. Rates of major pathologic response were 44 % with osimertinib, 0 % with chemotherapy, and 10 % with osimertinib and chemotherapy. Pathologic tumor downstaging occurred in 48 % with osimertinib, 44 % with chemotherapy, and 40 % with osimertinib and chemotherapy; pathologic lymph node downstaging occurred in 35 % with osimertinib, 28 % with chemotherapy, and 40 % with osimertinib and chemotherapy. Median follow up time was 19 months. Median EFS was 61 months with osimertinib, 32 months with chemotherapy, and 20 months with osimertinib and chemotherapy.</div></div><div><h3>Conclusions</h3><div>Pathologic complete responses and major pathologic responses were only observed in patients with <em>EGFR</em>-mutant NSCLC treated with osimertinib. EGFR-inhibitors may play an important role in the preoperative management of <em>EGFR</em>-mutant lung cancer.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"209 ","pages":"Article 108795"},"PeriodicalIF":4.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145325090","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}
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