Pub Date : 2025-09-17DOI: 10.1016/j.jtocrr.2025.100905
Jennifer A. Lewis MD, MS, MPH , Lauren R. Samuels PhD , Lucy B. Spalluto MD, MPH , Christopher Lindsell PhD , Claudia I. Henschke PhD, MD , David F. Yankelevitz MD , Carol Callaway-Lane DNP, ACNP-BC , Robert S. Dittus MD, MPH , Hilary A. Tindle MD, MPH , Renda Soylemez Wiener MD, MPH , Christopher G. Slatore MD, MS , Drew Moghanaki MD, MPH , Carolyn M. Audet PhD , Christianne L. Roumie MD, MPH
Introduction
Implementation of lung cancer screening is suboptimal. Understanding health care provider preferences and behavior is important for implementation. In this work, provider preferences for lung cancer screening implementation and self-reported determinants of lung cancer screening behavior were reported using the theoretical domains framework.
Methods
In this mixed-methods evaluation, health care providers at nine Veterans Affairs were surveyed to list factors influencing their decision to screen patients for lung cancer in free-text responses and rank implementation strategies by usefulness in clinical practice. Free-text data were coded and mapped to the theoretical domains framework. Quantitative ranking data were descriptively analyzed overall and by specialty (primary care versus radiology), clinic setting (hospital versus community), and provider type (physician versus advanced practice provider).
Results
Of 234/254 eligible providers analyzed, most were primary care (83.8%), community-based (52.1%), and physicians (66.2%). Respondents identified social influences (69.2%), knowledge (55.6%), and environmental context and resources (15.4%) as influential behavioral determinants. Overall, patient reminders (29.9%), provider reminders (26.1%), and learning collaboratives (24.4%) were reported most frequently as useful implementation strategies. Strategy preferences differed by specialty, practice setting, and provider type: primary care (30.1%), physician (34.2%), and hospital-based (33.0%) providers most frequently ranked patient reminders; radiology providers most frequently ranked learning collaborative (42.1%); advanced practice providers (24.1%) and community-based providers (27.0%) most frequently ranked provider reminders as most useful.
Conclusions
Designing implementation strategies that target three behavioral determinants (social influences, knowledge, and environmental context and resources) and are tailored to providers’ preferences may effectively change providers’ lung cancer screening behavior.
{"title":"Provider Behavioral Determinants and Preferences for Lung Cancer Screening Implementation: A Brief Report","authors":"Jennifer A. Lewis MD, MS, MPH , Lauren R. Samuels PhD , Lucy B. Spalluto MD, MPH , Christopher Lindsell PhD , Claudia I. Henschke PhD, MD , David F. Yankelevitz MD , Carol Callaway-Lane DNP, ACNP-BC , Robert S. Dittus MD, MPH , Hilary A. Tindle MD, MPH , Renda Soylemez Wiener MD, MPH , Christopher G. Slatore MD, MS , Drew Moghanaki MD, MPH , Carolyn M. Audet PhD , Christianne L. Roumie MD, MPH","doi":"10.1016/j.jtocrr.2025.100905","DOIUrl":"10.1016/j.jtocrr.2025.100905","url":null,"abstract":"<div><h3>Introduction</h3><div>Implementation of lung cancer screening is suboptimal. Understanding health care provider preferences and behavior is important for implementation. In this work, provider preferences for lung cancer screening implementation and self-reported determinants of lung cancer screening behavior were reported using the theoretical domains framework.</div></div><div><h3>Methods</h3><div>In this mixed-methods evaluation, health care providers at nine Veterans Affairs were surveyed to list factors influencing their decision to screen patients for lung cancer in free-text responses and rank implementation strategies by usefulness in clinical practice. Free-text data were coded and mapped to the theoretical domains framework. Quantitative ranking data were descriptively analyzed overall and by specialty (primary care versus radiology), clinic setting (hospital versus community), and provider type (physician versus advanced practice provider).</div></div><div><h3>Results</h3><div>Of 234/254 eligible providers analyzed, most were primary care (83.8%), community-based (52.1%), and physicians (66.2%). Respondents identified social influences (69.2%), knowledge (55.6%), and environmental context and resources (15.4%) as influential behavioral determinants. Overall, patient reminders (29.9%), provider reminders (26.1%), and learning collaboratives (24.4%) were reported most frequently as useful implementation strategies. Strategy preferences differed by specialty, practice setting, and provider type: primary care (30.1%), physician (34.2%), and hospital-based (33.0%) providers most frequently ranked patient reminders; radiology providers most frequently ranked learning collaborative (42.1%); advanced practice providers (24.1%) and community-based providers (27.0%) most frequently ranked provider reminders as most useful.</div></div><div><h3>Conclusions</h3><div>Designing implementation strategies that target three behavioral determinants (social influences, knowledge, and environmental context and resources) and are tailored to providers’ preferences may effectively change providers’ lung cancer screening behavior.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100905"},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145271074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-17DOI: 10.1016/j.jtocrr.2025.100904
Matthew Lu MD , Hayden Byrd MD , Heidi Chen PhD , Wade Iams MD
Introduction
For patients with limited-stage SCLC (LS-SCLC), tumor burden is a predictor of clinical outcomes, but there are no known data exploring whether tumor burden is a predictor of clinical outcomes in relapsed SCLC.
Methods
In this retrospective correlative study analyzing a cohort of 93 patients with relapsed SCLC, total body tumor volume at time of relapse (TV), progression-free survival (PFS), and overall survival (OS) were calculated and a Cox proportional hazards model was used to evaluate the relationship between TV and PFS and OS.
Results
A total of 93 patients with relapsed SCLC were analyzed, of whom 70% initially had extensive-stage SCLC (ES-SCLC) and 30% initially had LS-SCLC. Eastern Cooperative Oncology Group performance status and receipt of second-line therapy were significantly associated with OS in a linear fashion (p = 0.002 and p = 0.0457, respectively). TV was significantly associated with OS in a nonlinear fashion, even when controlling for Eastern Cooperative Oncology Group performance status, response to initial therapy, chemotherapy-free interval, and receipt of second-line therapy (p = 0.0031).
Conclusions
TV was observed to be a predictor of OS in patients with relapsed SCLC. Further studies are needed to evaluate whether initiation of standard systemic therapy at lower TV is able to consistently improve PFS and OS in relapsed SCLC.
{"title":"Brief Report: Relationship Between Tumor Volume and Clinical Outcomes in Relapsed SCLC","authors":"Matthew Lu MD , Hayden Byrd MD , Heidi Chen PhD , Wade Iams MD","doi":"10.1016/j.jtocrr.2025.100904","DOIUrl":"10.1016/j.jtocrr.2025.100904","url":null,"abstract":"<div><h3>Introduction</h3><div>For patients with limited-stage SCLC (LS-SCLC), tumor burden is a predictor of clinical outcomes, but there are no known data exploring whether tumor burden is a predictor of clinical outcomes in relapsed SCLC.</div></div><div><h3>Methods</h3><div>In this retrospective correlative study analyzing a cohort of 93 patients with relapsed SCLC, total body tumor volume at time of relapse (TV), progression-free survival (PFS), and overall survival (OS) were calculated and a Cox proportional hazards model was used to evaluate the relationship between TV and PFS and OS.</div></div><div><h3>Results</h3><div>A total of 93 patients with relapsed SCLC were analyzed, of whom 70% initially had extensive-stage SCLC (ES-SCLC) and 30% initially had LS-SCLC. Eastern Cooperative Oncology Group performance status and receipt of second-line therapy were significantly associated with OS in a linear fashion (<em>p</em> = 0.002 and <em>p</em> = 0.0457, respectively). TV was significantly associated with OS in a nonlinear fashion, even when controlling for Eastern Cooperative Oncology Group performance status, response to initial therapy, chemotherapy-free interval, and receipt of second-line therapy (<em>p</em> = 0.0031).</div></div><div><h3>Conclusions</h3><div>TV was observed to be a predictor of OS in patients with relapsed SCLC. Further studies are needed to evaluate whether initiation of standard systemic therapy at lower TV is able to consistently improve PFS and OS in relapsed SCLC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100904"},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145420052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The rationale underlying the benefits of the parenchyma-preserving nature of sublobar resection (SR) compared with lobectomy remains unclear. This study aimed to assess postoperative changes in cardiopulmonary function after lobectomy and SR using exercise stress testing.
Methods
This prospective, observational study enrolled patients scheduled for lobectomy or SR. Changes in cardiopulmonary function at 6 months postoperatively were evaluated using exercise stress echocardiography and cardiopulmonary exercise tests.
Results
Initially, 41 patients were enrolled, with 20 patients in the lobectomy group and 18 patients in the SR group (16 segmentectomies, two wedge resections) after excluding three ineligible patients. Preoperatively, all patients demonstrated well-preserved cardiopulmonary function. The systolic pulmonary artery pressure (SPAP) change at peak exercise was significantly higher for lobectomy (median 26.5%; interquartile range [IQR] 0.6–60.1) than for SR (median −8.2%; IQR −38.7–11.7; p = 0.001), despite nonsignificant differences at rest (p = 0.599). Postoperative exercise-induced pulmonary hypertension (exPH) occurred in nine patients (45%) in the lobectomy group but none in the SR group (0%, p = 0.010). Postoperative peak oxygen consumption during exercise decreased significantly in the lobectomy group (median −14.3%; IQR −24.0 to −4.2) compared with that in the SR group (median −7.8%; IQR −13.5–8.7; p = 0.024). The postoperative increase in SPAP at peak exercise (r = 0.402, p = 0.012), prevalence of postoperative exPH (r = 0.978, p = 0.004), and postoperative decrease in peak oxygen consumption (r = −0.330; p = 0.041) were correlated with the number of resected segments.
Conclusions
Lobectomy induces increased SPAP during exercise, exPH, and effort intolerance, compared with SR. This highlights the importance of preserving lung parenchyma in lung surgery.
Clinical Trial Registration
This trial is registered in the UMIN Clinical Trials Registry under the code UMIN000053694.
与肺叶切除术相比，叶下切除术（SR）保留实质的好处的基本原理尚不清楚。本研究旨在通过运动应激试验评估肺叶切除术和SR术后心肺功能的变化。方法：本前瞻性观察性研究纳入了计划行肺叶切除术或手术后6个月心肺功能变化的患者，采用运动应激超声心动图和心肺运动试验进行评估。结果最初纳入41例患者，其中肺叶切除术组20例，SR组18例（16节段切除术，2例楔形切除术），排除了3例不符合条件的患者。术前，所有患者均表现出良好的心肺功能。肺叶切除术患者在运动高峰时的肺动脉收缩压（SPAP）变化（中位数26.5%；四分位间距[IQR] 0.6-60.1）显著高于SR组（中位数- 8.2%;IQR - 38.7-11.7; p = 0.001），尽管静止时差异不显著（p = 0.599）。肺叶切除术组有9例（45%）患者出现术后运动性肺动脉高压（exPH）， SR组无一例（0%,p = 0.010）。肺叶切除术组术后运动时峰值耗氧量明显低于SR组（中位数为- 7.8%，IQR为- 13.5-8.7,p = 0.024）（中位数为- 14.3%，IQR为- 24.0 - - 4.2）。术后运动峰值SPAP升高（r = 0.402, p = 0.012）、术后exPH发生率（r = 0.978, p = 0.004）、术后峰值耗氧量下降（r = - 0.330, p = 0.041）与切除节段数相关。结论与手术相比，手术切除可导致运动时SPAP、exPH和力耐受增加，这突出了在肺手术中保留肺实质的重要性。临床试验注册本试验在UMIN临床试验注册中心注册，代码为UMIN000053694。
{"title":"Lobectomy Induces Exercise-Induced Pulmonary Hypertension and Effort Intolerance Compared With Sublobar Resection","authors":"Atsushi Kamigaichi MD , Yasuhiro Tsutani MD, PhD , Akane Tsuchiya MD , Hiroto Utsunomiya MD, PhD , Yoshihiro Miyata MD, PhD , Takahiro Mimae MD, PhD , Norifumi Tsubokawa MD, PhD , Yukiko Nakano MD, PhD , Morihito Okada MD, PhD","doi":"10.1016/j.jtocrr.2025.100903","DOIUrl":"10.1016/j.jtocrr.2025.100903","url":null,"abstract":"<div><h3>Introduction</h3><div>The rationale underlying the benefits of the parenchyma-preserving nature of sublobar resection (SR) compared with lobectomy remains unclear. This study aimed to assess postoperative changes in cardiopulmonary function after lobectomy and SR using exercise stress testing.</div></div><div><h3>Methods</h3><div>This prospective, observational study enrolled patients scheduled for lobectomy or SR. Changes in cardiopulmonary function at 6 months postoperatively were evaluated using exercise stress echocardiography and cardiopulmonary exercise tests.</div></div><div><h3>Results</h3><div>Initially, 41 patients were enrolled, with 20 patients in the lobectomy group and 18 patients in the SR group (16 segmentectomies, two wedge resections) after excluding three ineligible patients. Preoperatively, all patients demonstrated well-preserved cardiopulmonary function. The systolic pulmonary artery pressure (SPAP) change at peak exercise was significantly higher for lobectomy (median 26.5%; interquartile range [IQR] 0.6–60.1) than for SR (median −8.2%; IQR −38.7–11.7; <em>p</em> = 0.001), despite nonsignificant differences at rest (<em>p</em> = 0.599). Postoperative exercise-induced pulmonary hypertension (exPH) occurred in nine patients (45%) in the lobectomy group but none in the SR group (0%, <em>p</em> = 0.010). Postoperative peak oxygen consumption during exercise decreased significantly in the lobectomy group (median −14.3%; IQR −24.0 to −4.2) compared with that in the SR group (median −7.8%; IQR −13.5–8.7; <em>p</em> = 0.024). The postoperative increase in SPAP at peak exercise (r = 0.402, <em>p</em> = 0.012), prevalence of postoperative exPH (r = 0.978, <em>p</em> = 0.004), and postoperative decrease in peak oxygen consumption (r = −0.330; <em>p</em> = 0.041) were correlated with the number of resected segments.</div></div><div><h3>Conclusions</h3><div>Lobectomy induces increased SPAP during exercise, exPH, and effort intolerance, compared with SR. This highlights the importance of preserving lung parenchyma in lung surgery.</div></div><div><h3>Clinical Trial Registration</h3><div>This trial is registered in the UMIN Clinical Trials Registry under the code UMIN000053694.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100903"},"PeriodicalIF":3.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145271076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-04DOI: 10.1016/j.jtocrr.2025.100900
Sun Min Lim MD, PhD , Ana Laura Ortega Granados MD , Gustavo dix Junqueira Pinto MD, MSc , Christian Sebastián Fuentes MD , Giuseppe Lo Russo MD , Michael Schenker MD , Jin Seok Ahn MD, PhD , Filippo de Marinis MD , Kenneth Locke Jr. PhD , Zsolt Szijgyarto PhD , Elena Buss MSc , Neda Stjepanovic MD, PhD , Ivan Diaz-Padilla MD, PhD , Solange Peters MD, PhD
Introduction
PERLA is a global, double-blind, phase II trial comparing anti–programmed cell death protein 1 antibodies, dostarlimab, and pembrolizumab in combination with chemotherapy (D+CT and P+CT, respectively) in patients with metastatic nonsquamous NSCLC without actionable genomic aberrations in the first-line setting.
Methods
Patients were randomized 1:1 to receive not more than 35 cycles of 500 mg dostarlimab or 200 mg pembrolizumab, with less than or equal to 35 cycles of 500 mg/m2 pemetrexed and less than or equal to 4 cycles of cisplatin (75 mg/m2) or carboplatin (area under the curve 5 mg/mL/min) every 3 weeks. The primary end point was the overall response rate by blinded independent central review. The secondary end points included progression-free survival (PFS) on the basis of investigator assessment, overall survival (OS), and safety. Here, we reported on the long-term OS, PFS, and safety analyses.
Results
At the end of the study (September 10, 2024), the median follow-up time (mo) for PFS was 30.4 for D+CT and 30.4 for P+CT. The median PFS (mo [95% confidence interval (CI)]) was 8.8 (6.9–11.0) for D+CT and 6.8 (4.9–7.1) for P+CT (hazard ratio 0.77 [95% CI: 0.58–1.03] at 79% maturity). The median follow-up time (mo) for OS was 35.5 for D+CT and 35.2 for P+CT. The median OS (mo [95% CI]) was 20.2 (14.5–27.3) and 15.9 (11.6–19.3), respectively (hazard ratio 0.75 [95% CI: 0.55–1.02] at 70% maturity). Safety profiles were similar between arms and consistent with previous analyses.
Conclusions
This long-term analysis reaffirms previous observations that D+CT exhibited similar efficacy to P+CT and exhibits strong clinical efficacy as a first-line treatment for patients with metastatic nonsquamous NSCLC.
{"title":"Long-term Survival Analysis From PERLA, A Phase II Randomized Trial of Dostarlimab With Chemotherapy Versus Pembrolizumab With Chemotherapy in Metastatic Nonsquamous NSCLC","authors":"Sun Min Lim MD, PhD , Ana Laura Ortega Granados MD , Gustavo dix Junqueira Pinto MD, MSc , Christian Sebastián Fuentes MD , Giuseppe Lo Russo MD , Michael Schenker MD , Jin Seok Ahn MD, PhD , Filippo de Marinis MD , Kenneth Locke Jr. PhD , Zsolt Szijgyarto PhD , Elena Buss MSc , Neda Stjepanovic MD, PhD , Ivan Diaz-Padilla MD, PhD , Solange Peters MD, PhD","doi":"10.1016/j.jtocrr.2025.100900","DOIUrl":"10.1016/j.jtocrr.2025.100900","url":null,"abstract":"<div><h3>Introduction</h3><div>PERLA is a global, double-blind, phase II trial comparing anti–programmed cell death protein 1 antibodies, dostarlimab, and pembrolizumab in combination with chemotherapy (D+CT and P+CT, respectively) in patients with metastatic nonsquamous NSCLC without actionable genomic aberrations in the first-line setting.</div></div><div><h3>Methods</h3><div>Patients were randomized 1:1 to receive not more than 35 cycles of 500 mg dostarlimab or 200 mg pembrolizumab, with less than or equal to 35 cycles of 500 mg/m<sup>2</sup> pemetrexed and less than or equal to 4 cycles of cisplatin (75 mg/m<sup>2</sup>) or carboplatin (area under the curve 5 mg/mL/min) every 3 weeks. The primary end point was the overall response rate by blinded independent central review. The secondary end points included progression-free survival (PFS) on the basis of investigator assessment, overall survival (OS), and safety. Here, we reported on the long-term OS, PFS, and safety analyses.</div></div><div><h3>Results</h3><div>At the end of the study (September 10, 2024), the median follow-up time (mo) for PFS was 30.4 for D+CT and 30.4 for P+CT. The median PFS (mo [95% confidence interval (CI)]) was 8.8 (6.9–11.0) for D+CT and 6.8 (4.9–7.1) for P+CT (hazard ratio 0.77 [95% CI: 0.58–1.03] at 79% maturity). The median follow-up time (mo) for OS was 35.5 for D+CT and 35.2 for P+CT. The median OS (mo [95% CI]) was 20.2 (14.5–27.3) and 15.9 (11.6–19.3), respectively (hazard ratio 0.75 [95% CI: 0.55–1.02] at 70% maturity). Safety profiles were similar between arms and consistent with previous analyses.</div></div><div><h3>Conclusions</h3><div>This long-term analysis reaffirms previous observations that D+CT exhibited similar efficacy to P+CT and exhibits strong clinical efficacy as a first-line treatment for patients with metastatic nonsquamous NSCLC.</div></div><div><h3>Clinical trial registration</h3><div>NCT04581824.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100900"},"PeriodicalIF":3.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-04DOI: 10.1016/j.jtocrr.2025.100899
Giorgi Sabakhtarishvili MD, Mitchell B. Karpman PhD, Rahul Mishra MD, Teresa M. Putscher RN, BSN, Omer Bajwa MD, Rachel Hall DO, MS, Sahil Garg MD, Farshid Fargahi MD, Barry Meisenberg MD
Background
Mortality from lung cancer is reduced with low-dose computed tomography (LDCT) screening in high-risk persons. But screening uptake is low, especially among Black persons. Previous reports of LDCT had low participation of Black persons, which may inhibit wider adoption. In this study, we report on outcomes of LDCT screening in Black and White cohorts.
Methods
Retrospective observational cohort study using concurrent data from LDCT screening and tumor registries to compare the results of LDCT efficacy in reducing stage 4 lung cancer presentations in Black and White participant cohorts.
Results
Blacks comprised 13% of the 3647 unique eligible LDCT participants who had at least one LDCT. No statistically significant differences in LDCT category 4 were noted after screening. Lung cancers were diagnosed in 16 out of 466 (3.4%) Black LDCT participants and in 119 out of 3181 (3.7%) White LDCT participants. Black LDCT screening participants were 5.4 times less likely to be diagnosed with stage 4 lung cancers if diagnosed through screening compared to “usual care” (13% versus 44%, p <0.02). White LDCT participants were 3.5 times less likely to present with stage 4 lung cancer if diagnosed through screening compared to usual care (13% versus 35%, p < 0.0001).
Conclusions
LDCT reduced the number of stage 4 presentations in both cohorts. These findings should encourage attempts to increase LDCT utilization in all populations.
{"title":"A Retrospective Observational Cohort Study of Lung Cancer Screening Outcomes Among U.S. Blacks and Whites","authors":"Giorgi Sabakhtarishvili MD, Mitchell B. Karpman PhD, Rahul Mishra MD, Teresa M. Putscher RN, BSN, Omer Bajwa MD, Rachel Hall DO, MS, Sahil Garg MD, Farshid Fargahi MD, Barry Meisenberg MD","doi":"10.1016/j.jtocrr.2025.100899","DOIUrl":"10.1016/j.jtocrr.2025.100899","url":null,"abstract":"<div><h3>Background</h3><div>Mortality from lung cancer is reduced with low-dose computed tomography (LDCT) screening in high-risk persons. But screening uptake is low, especially among Black persons. Previous reports of LDCT had low participation of Black persons, which may inhibit wider adoption. In this study, we report on outcomes of LDCT screening in Black and White cohorts.</div></div><div><h3>Methods</h3><div>Retrospective observational cohort study using concurrent data from LDCT screening and tumor registries to compare the results of LDCT efficacy in reducing stage 4 lung cancer presentations in Black and White participant cohorts.</div></div><div><h3>Results</h3><div>Blacks comprised 13% of the 3647 unique eligible LDCT participants who had at least one LDCT. No statistically significant differences in LDCT category 4 were noted after screening. Lung cancers were diagnosed in 16 out of 466 (3.4%) Black LDCT participants and in 119 out of 3181 (3.7%) White LDCT participants. Black LDCT screening participants were 5.4 times less likely to be diagnosed with stage 4 lung cancers if diagnosed through screening compared to “usual care” (13% versus 44%, <em>p</em> <0.02). White LDCT participants were 3.5 times less likely to present with stage 4 lung cancer if diagnosed through screening compared to usual care (13% versus 35%, <em>p</em> < 0.0001).</div></div><div><h3>Conclusions</h3><div>LDCT reduced the number of stage 4 presentations in both cohorts. These findings should encourage attempts to increase LDCT utilization in all populations.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100899"},"PeriodicalIF":3.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145271075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-04DOI: 10.1016/j.jtocrr.2025.100898
Jandos Amankulov MD, PhD , David F. Yankelevitz MD , Amangeldi Mukhamejan MD , Rowena Yip PhD, MPH , Emanuela Taioli MD, PhD , Bruce Pyenson FSA, MAAA , James Mulshine MD , Claudia I. Henschke PhD, MD
The First Central Asian Forum on Lung Cancer was held at the National Academy of Sciences of the Republic of Kazakhstan on April 8 and 9, 2025. Organized by the Kazakhstan Cancer Society, KazIOR, and the I-ELCAP/IELCART consortia, the forum brought together regional and international experts to address the urgent challenge of late-stage lung cancer diagnosis in Central Asia. National data show that fewer than one-third of patients are diagnosed at stages I and II, while over 70% present with advanced disease. High smoking prevalence, environmental exposures such as radon, asbestos, and industrial pollution, and strong geographic variation in risk highlight the need for tailored screening programs. Kazakhstan is well-positioned to scale up low-dose CT (LDCT) screening given its CT scanner capacity, mobile units for underserved regions, and prior pilot screening successes. Conference sessions emphasized risk modeling, cost-effectiveness, artificial intelligence applications, and the added value of LDCT for detecting cardiovascular disease and emphysema. Plans are underway for collaborative projects and future conferences to strengthen regional capacity for early detection and treatment.
{"title":"First Central Asian Forum on Lung Cancer","authors":"Jandos Amankulov MD, PhD , David F. Yankelevitz MD , Amangeldi Mukhamejan MD , Rowena Yip PhD, MPH , Emanuela Taioli MD, PhD , Bruce Pyenson FSA, MAAA , James Mulshine MD , Claudia I. Henschke PhD, MD","doi":"10.1016/j.jtocrr.2025.100898","DOIUrl":"10.1016/j.jtocrr.2025.100898","url":null,"abstract":"<div><div>The First Central Asian Forum on Lung Cancer was held at the National Academy of Sciences of the Republic of Kazakhstan on April 8 and 9, 2025. Organized by the Kazakhstan Cancer Society, KazIOR, and the I-ELCAP/IELCART consortia, the forum brought together regional and international experts to address the urgent challenge of late-stage lung cancer diagnosis in Central Asia. National data show that fewer than one-third of patients are diagnosed at stages I and II, while over 70% present with advanced disease. High smoking prevalence, environmental exposures such as radon, asbestos, and industrial pollution, and strong geographic variation in risk highlight the need for tailored screening programs. Kazakhstan is well-positioned to scale up low-dose CT (LDCT) screening given its CT scanner capacity, mobile units for underserved regions, and prior pilot screening successes. Conference sessions emphasized risk modeling, cost-effectiveness, artificial intelligence applications, and the added value of LDCT for detecting cardiovascular disease and emphysema. Plans are underway for collaborative projects and future conferences to strengthen regional capacity for early detection and treatment.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 1","pages":"Article 100898"},"PeriodicalIF":3.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145651847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Low-dose computed tomography (LDCT) screening for lung cancer has been implemented in many municipalities in Nagano prefecture. We analyzed epidemiologic and survival data of patients with lung cancer among municipalities in Nagano prefecture to evaluate the impact of LDCT.
Methods
This was a retrospective cohort study. Data regarding the number of LDCT screenings, population, and lung cancer deaths in each municipality in 2011 to 2020 were collected and collated with information from the population-based cancer registry. These data were compared between municipalities that had continuously implemented LDCT (LDCT [+], n = 26) and those that had not (LDCT [−], n = 11).
Results
The mean lung cancer crude mortality rate and standardized mortality ratio were significantly lower in LDCT (+) (82.2 ± 14.1 per 100,000 (p < 0.02) and 69.7 ± 11.9 (p < 0.005), respectively) than LDCT (−) (92.0 ± 10.1 per 100,000 and 81.6 ± 11.5, respectively). In addition, the mortality rate in each municipality was significantly negative correlated with the numbers of LDCT implementation in each municipality (r = 0.39). With regard to the extent of lung cancer at diagnosis, the proportion of localized lung cancer was significantly higher in LDCT (+) (39.4 ± 7.4%) than in LDCT (−) (34.6 ± 7.4%), and the proportion of localized lung cancer in each municipality was positively correlated with the number of LDCT implementation.
Conclusion
This retrospective analysis in Nagano prefecture indicated that serial LDCT could contribute to a decrease in lung cancer mortality in the general population.
低剂量计算机断层扫描（LDCT）筛查肺癌已在长野县的许多城市实施。我们分析了长野县各市肺癌患者的流行病学和生存数据，以评估LDCT的影响。方法回顾性队列研究。收集了2011年至2020年每个城市LDCT筛查人数、人口和肺癌死亡人数的数据，并与基于人口的癌症登记处的信息进行了整理。将这些数据在连续实施LDCT的城市（LDCT [+], n = 26）和未实施LDCT的城市（LDCT [-], n = 11）之间进行比较。结果LDCT（+）组肺癌粗死亡率（82.2±14.1 / 10万）和标准化死亡率（69.7±11.9 / 10万）显著低于LDCT（-）组（92.0±10.1 / 10万）和（81.6±11.5）。此外，每个城市的死亡率与每个城市实施LDCT的数量呈显著负相关（r = 0.39）。在肺癌的诊断范围方面，LDCT（+）组肺癌的局限性比例（39.4±7.4%）明显高于LDCT（-）组肺癌的局限性比例（34.6±7.4%），各城市肺癌的局限性比例与LDCT实施次数呈正相关。结论：长野县的回顾性分析表明，连续的LDCT检查有助于降低普通人群的肺癌死亡率。
{"title":"Epidemiologic and Survival Analyses of Lung Cancer in Nagano Prefecture: Impact of Serial Low-Dose Computed Tomography Screening","authors":"Tomonobu Koizumi MD, PhD , Kengo Otsuki , Yuichiro Maruyama MD","doi":"10.1016/j.jtocrr.2025.100893","DOIUrl":"10.1016/j.jtocrr.2025.100893","url":null,"abstract":"<div><h3>Introduction</h3><div>Low-dose computed tomography (LDCT) screening for lung cancer has been implemented in many municipalities in Nagano prefecture. We analyzed epidemiologic and survival data of patients with lung cancer among municipalities in Nagano prefecture to evaluate the impact of LDCT.</div></div><div><h3>Methods</h3><div>This was a retrospective cohort study. Data regarding the number of LDCT screenings, population, and lung cancer deaths in each municipality in 2011 to 2020 were collected and collated with information from the population-based cancer registry. These data were compared between municipalities that had continuously implemented LDCT (LDCT [+], n = 26) and those that had not (LDCT [−], n = 11).</div></div><div><h3>Results</h3><div>The mean lung cancer crude mortality rate and standardized mortality ratio were significantly lower in LDCT (+) (82.2 ± 14.1 per 100,000 (<em>p</em> < 0.02) and 69.7 ± 11.9 (<em>p</em> < 0.005), respectively) than LDCT (−) (92.0 ± 10.1 per 100,000 and 81.6 ± 11.5, respectively). In addition, the mortality rate in each municipality was significantly negative correlated with the numbers of LDCT implementation in each municipality (<em>r</em> = 0.39). With regard to the extent of lung cancer at diagnosis, the proportion of localized lung cancer was significantly higher in LDCT (+) (39.4 ± 7.4%) than in LDCT (−) (34.6 ± 7.4%), and the proportion of localized lung cancer in each municipality was positively correlated with the number of LDCT implementation.</div></div><div><h3>Conclusion</h3><div>This retrospective analysis in Nagano prefecture indicated that serial LDCT could contribute to a decrease in lung cancer mortality in the general population.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100893"},"PeriodicalIF":3.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145469064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evidence of immune checkpoint inhibitors (ICIs) combined with chemotherapy for older patients with NSCLC is limited. This real-world study compared the efficacy and safety of atezolizumab plus chemotherapy (ACT) with those of pembrolizumab plus chemotherapy (PCT) for older patients with advanced nonsquamous NSCLC.
Methods
This multicenter, retrospective study included 288 patients 65 years or older with advanced or recurrent nonsquamous NSCLC who received PCT or ACT as first-line treatment at 13 institutions in Japan. After one-to-one propensity score matching, overall survival (OS), the incidence of grade 3 or higher treatment-related adverse events, and all-grade pneumonitis of the PCT and ACT groups were compared.
Results
After propensity score matching, 54 patients were included in each of the groups. OS did not significantly differ between the PCT and ACT groups. The median OS was 16.6 months for both groups. Compared with the PCT group, the ACT group had a hazard ratio of 1.09 (95% confidence interval [CI]: 0.68–1.74; p = 0.7). Grade 3 or higher adverse events occurred in 40.7% and 33.3% of patients in the PCT and ACT groups, respectively (p = 0.55). The incidence of treatment-related pneumonitis of the PCT group was significantly higher (29.6%, including 11 grade ≥3 cases) than that of the ACT group (5.6%, including two grade ≥3 cases) (p = 0.002).
Conclusions
ACT may be associated with a more favorable safety profile than that of PCT for the Japanese population; therefore, ACT could be considered a treatment option for older patients with advanced nonsquamous NSCLC.
免疫检查点抑制剂（ICIs）联合化疗治疗老年非小细胞肺癌的证据有限。这项现实世界的研究比较了atezolizumab加化疗（ACT）和派姆单抗加化疗（PCT）对老年晚期非鳞状NSCLC患者的疗效和安全性。方法本多中心回顾性研究纳入了288例65岁及以上晚期或复发性非鳞状NSCLC患者，这些患者在日本13家机构接受了PCT或ACT作为一线治疗。一对一倾向评分匹配后，比较PCT组和ACT组的总生存率（OS）、3级及以上治疗相关不良事件发生率和全级别肺炎。结果经倾向评分匹配后，两组共纳入54例患者。PCT组和ACT组间OS无显著差异。两组的中位OS均为16.6个月。与PCT组相比，ACT组的风险比为1.09（95%可信区间[CI]: 0.68-1.74; p = 0.7）。PCT组和ACT组3级及以上不良事件发生率分别为40.7%和33.3% （p = 0.55）。PCT组治疗相关性肺炎的发生率（29.6%，包括11例≥3级）显著高于ACT组（5.6%，包括2例≥3级）（p = 0.002）。结论：在日本人群中，sact可能比PCT具有更有利的安全性；因此，ACT可以被认为是老年晚期非鳞状NSCLC患者的一种治疗选择。
{"title":"A Multicenter, Retrospective, Real-World Study of Atezolizumab Plus Chemotherapy and Pembrolizumab Plus Chemotherapy for Older Patients With NSCLC","authors":"Kensuke Kanaoka MD , Kinnosuke Matsumoto MD , Takayuki Shiroyama MD, PhD , Akihiro Tsukaguchi MD , Nao Shoshihara MD , Koki Moritomo MD , Yuhei Kinehara MD, PhD , Yasuhiro Mihashi MD , Tomoki Kuge MD , Midori Yoneda MD , Soichiro Kato MD , Keijiro Yamauchi MD , Hirotomo Machiyama MD , Yuki Nishikawa MD , Osamu Morimura MD, PhD , Akito Miyazaki MD , Kiyohide Komuta MD , Kouji Azuma MD , Satoshi Tanaka MD , Toshie Niki MD, PhD , Atsushi Kumanogoh MD, PhD","doi":"10.1016/j.jtocrr.2025.100891","DOIUrl":"10.1016/j.jtocrr.2025.100891","url":null,"abstract":"<div><h3>Introduction</h3><div>Evidence of immune checkpoint inhibitors (ICIs) combined with chemotherapy for older patients with NSCLC is limited. This real-world study compared the efficacy and safety of atezolizumab plus chemotherapy (ACT) with those of pembrolizumab plus chemotherapy (PCT) for older patients with advanced nonsquamous NSCLC.</div></div><div><h3>Methods</h3><div>This multicenter, retrospective study included 288 patients 65 years or older with advanced or recurrent nonsquamous NSCLC who received PCT or ACT as first-line treatment at 13 institutions in Japan. After one-to-one propensity score matching, overall survival (OS), the incidence of grade 3 or higher treatment-related adverse events, and all-grade pneumonitis of the PCT and ACT groups were compared.</div></div><div><h3>Results</h3><div>After propensity score matching, 54 patients were included in each of the groups. OS did not significantly differ between the PCT and ACT groups. The median OS was 16.6 months for both groups. Compared with the PCT group, the ACT group had a hazard ratio of 1.09 (95% confidence interval [CI]: 0.68–1.74; <em>p</em> = 0.7). Grade 3 or higher adverse events occurred in 40.7% and 33.3% of patients in the PCT and ACT groups, respectively (<em>p</em> = 0.55). The incidence of treatment-related pneumonitis of the PCT group was significantly higher (29.6%, including 11 grade ≥3 cases) than that of the ACT group (5.6%, including two grade ≥3 cases) (<em>p</em> = 0.002).</div></div><div><h3>Conclusions</h3><div>ACT may be associated with a more favorable safety profile than that of PCT for the Japanese population; therefore, ACT could be considered a treatment option for older patients with advanced nonsquamous NSCLC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100891"},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145271077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-07DOI: 10.1016/j.jtocrr.2025.100888
Anne-Laurence Le Faou MD, PhD , Dalia Alleaume MSc , Ingrid Allagbé PhD
Background
Limited research exists on sex-specific smoking cessation interventions for patients with lung cancer. This study leverages data from the Consultations de Dépendance Tabagique, the French national database of smoking cessation services (SCS), to identify sex-specific factors influencing smoking cessation in people with lung cancer.
Methods
This retrospective observational study analyzed data from 3407 adults with lung cancer (31.2% women, 68.8% men) registered in the Consultations de Dépendance Tabagique between 2001 and 2018. Participants were people with active tobacco use with at least one follow-up SCS consultation. The primary outcome was 28-day smoking abstinence, confirmed by exhaled carbon monoxide less than 10 parts per million. Multivariate logistic regression identified predictors of abstinence, stratified by sex.
Results
Abstinence rates were similar in women (35.2%) and men (35.4%) (p = 0.40). Women had higher psychological distress (19.8% with depression versus 13.1% in men; p < 0.001) and were more likely to seek SCS independently (19.4% versus 13.6%; p < 0.001). Men smoked more cigarettes daily (27 versus 25; p = 0.002) and had higher alcohol consumption (35.7% versus 13.9%; p < 0.001). Confidence in quitting (women: odds ratio [OR] = 1.91; 95% confidence interval [CI]: 1.27–2.87; men: OR = 1.50; 95% CI: 1.16–1.95) and follow-up consultations (≥7: women: OR = 8.86; 95% CI: 5.69–14.0; men: OR = 6.64; 95% CI: 4.88–9.13) predicted abstinence for both sexes. Among women, hospital referral (OR = 1.63; 95% CI: 1.10–2.43) and living with other persons who smoke (OR = 4.16; 95% CI: 1.70–10.4) increased abstinence, whereas in men, nicotine replacement therapy (OR = 1.46; 95% CI: 1.09–1.97) was beneficial.
Conclusions
The results indicate a need for further research into targeted interventions by sex to evaluate the efficacy of smoking cessation strategies in patients with lung cancer.
{"title":"Predictive Factors for Smoking Cessation Among People With Lung Cancer Attending French Cessation Services, According to Sex","authors":"Anne-Laurence Le Faou MD, PhD , Dalia Alleaume MSc , Ingrid Allagbé PhD","doi":"10.1016/j.jtocrr.2025.100888","DOIUrl":"10.1016/j.jtocrr.2025.100888","url":null,"abstract":"<div><h3>Background</h3><div>Limited research exists on sex-specific smoking cessation interventions for patients with lung cancer. This study leverages data from the Consultations de Dépendance Tabagique, the French national database of smoking cessation services (SCS), to identify sex-specific factors influencing smoking cessation in people with lung cancer.</div></div><div><h3>Methods</h3><div>This retrospective observational study analyzed data from 3407 adults with lung cancer (31.2% women, 68.8% men) registered in the Consultations de Dépendance Tabagique between 2001 and 2018. Participants were people with active tobacco use with at least one follow-up SCS consultation. The primary outcome was 28-day smoking abstinence, confirmed by exhaled carbon monoxide less than 10 parts per million. Multivariate logistic regression identified predictors of abstinence, stratified by sex.</div></div><div><h3>Results</h3><div>Abstinence rates were similar in women (35.2%) and men (35.4%) (<em>p</em> = 0.40). Women had higher psychological distress (19.8% with depression versus 13.1% in men; <em>p</em> < 0.001) and were more likely to seek SCS independently (19.4% versus 13.6%; <em>p</em> < 0.001). Men smoked more cigarettes daily (27 versus 25; <em>p</em> = 0.002) and had higher alcohol consumption (35.7% versus 13.9%; <em>p</em> < 0.001). Confidence in quitting (women: odds ratio [OR] = 1.91; 95% confidence interval [CI]: 1.27–2.87; men: OR = 1.50; 95% CI: 1.16–1.95) and follow-up consultations (≥7: women: OR = 8.86; 95% CI: 5.69–14.0; men: OR = 6.64; 95% CI: 4.88–9.13) predicted abstinence for both sexes. Among women, hospital referral (OR = 1.63; 95% CI: 1.10–2.43) and living with other persons who smoke (OR = 4.16; 95% CI: 1.70–10.4) increased abstinence, whereas in men, nicotine replacement therapy (OR = 1.46; 95% CI: 1.09–1.97) was beneficial.</div></div><div><h3>Conclusions</h3><div>The results indicate a need for further research into targeted interventions by sex to evaluate the efficacy of smoking cessation strategies in patients with lung cancer.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100888"},"PeriodicalIF":3.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Axl, a receptor tyrosine kinase, is linked to epithelial-mesenchymal transition (EMT). This study aimed to investigate the biologic implications of extracellular domain shedding of phosphorylated Axl (pAxl) in lung adenocarcinoma, focusing on spread through air spaces (STAS) as a potential pathologic representation of EMT.
Methods
This study included 202 patients with resected lung adenocarcinoma. A dual-domain immunohistochemistry approach using separate staining for the extracellular and intracellular domains was used to classify the tumors into shedding and nonshedding pAxl groups. Prognostic analysis was performed using recurrence-free probability (RFP) as the primary outcome. Furthermore, by using a public gene database, we developed the “shedding pAxl score” to experimentally investigate correlations with EMT-related genes.
Results
The shedding pAxl group exhibited significantly worse prognosis than the nonshedding pAxl group (5-year RFP, 54% and 80%, respectively; p < 0.001). This prognostic stratification of pAxl shedding was predominant in STAS-positive patients (5-year RFP, 37% and 75%, p < 0.001), but not in STAS-negative patients (5-year RFP, 73% and 84%, p = 0.3). Multivariate analysis revealed that pathologic stage and pAxl shedding were independent factors for recurrence (hazard ratio 2.28 [1.24–4.91], p = 0.008). The shedding pAxl score correlated strongly with the established EMT signature score (p < 0.001, R = 0.61).
Conclusions
Shedding pAxl has a prognostic impact on lung adenocarcinoma, with a significant effect modification related to STAS. The developed shedding pAxl score, strongly associated with EMT, provides foundational knowledge for further studies on this phenomenon in lung cancer progression.
{"title":"Shedding Phosphorylated Axl Receptor in Lung Adenocarcinoma: Dual-Domain Immunohistochemistry Approach","authors":"Shuji Mishima MD , Takashi Eguchi MD PhD , Yoshinori Sato MD , Shunichiro Matsuoka MD, PhD , Yuichi Oguchi MD , Mari Katsuno MD , Daisuke Nakamura MD , Yukihiro Terada MD , Hirotaka Kumeda MD , Kentaro Miura MD, PhD , Kazutoshi Hamanaka MD, PhD , Mai Iwaya MD, PhD , Takeshi Uehara MD, PhD , Kimihiro Shimizu MD, PhD","doi":"10.1016/j.jtocrr.2025.100889","DOIUrl":"10.1016/j.jtocrr.2025.100889","url":null,"abstract":"<div><h3>Introduction</h3><div>Axl, a receptor tyrosine kinase, is linked to epithelial-mesenchymal transition (EMT). This study aimed to investigate the biologic implications of extracellular domain shedding of phosphorylated Axl (pAxl) in lung adenocarcinoma, focusing on spread through air spaces (STAS) as a potential pathologic representation of EMT.</div></div><div><h3>Methods</h3><div>This study included 202 patients with resected lung adenocarcinoma. A dual-domain immunohistochemistry approach using separate staining for the extracellular and intracellular domains was used to classify the tumors into shedding and nonshedding pAxl groups. Prognostic analysis was performed using recurrence-free probability (RFP) as the primary outcome. Furthermore, by using a public gene database, we developed the “shedding pAxl score” to experimentally investigate correlations with EMT-related genes.</div></div><div><h3>Results</h3><div>The shedding pAxl group exhibited significantly worse prognosis than the nonshedding pAxl group (5-year RFP, 54% and 80%, respectively; <em>p</em> < 0.001). This prognostic stratification of pAxl shedding was predominant in STAS-positive patients (5-year RFP, 37% and 75%, <em>p</em> < 0.001), but not in STAS-negative patients (5-year RFP, 73% and 84%, <em>p</em> = 0.3). Multivariate analysis revealed that pathologic stage and pAxl shedding were independent factors for recurrence (hazard ratio 2.28 [1.24–4.91], <em>p</em> = 0.008). The shedding pAxl score correlated strongly with the established EMT signature score (<em>p</em> < 0.001, R = 0.61).</div></div><div><h3>Conclusions</h3><div>Shedding pAxl has a prognostic impact on lung adenocarcinoma, with a significant effect modification related to STAS. The developed shedding pAxl score, strongly associated with EMT, provides foundational knowledge for further studies on this phenomenon in lung cancer progression.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100889"},"PeriodicalIF":3.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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