Noa Amin PhD, MRCP , Thanika Ketpueak DM , Simon Jordan MBBCh, MD , Andrew G. Nicholson DM, FRCPath , Yu Zhi Zhang MBBS, PhD, FRCPath , Sanjay Popat PhD FRCP
{"title":"Durable Response to Lenvatinib in Platinum-Refractory Metastatic High-Grade Thymic Mucoepidermoid Carcinoma: A Case Report","authors":"Noa Amin PhD, MRCP , Thanika Ketpueak DM , Simon Jordan MBBCh, MD , Andrew G. Nicholson DM, FRCPath , Yu Zhi Zhang MBBS, PhD, FRCPath , Sanjay Popat PhD FRCP","doi":"10.1016/j.jtocrr.2025.100894","DOIUrl":"10.1016/j.jtocrr.2025.100894","url":null,"abstract":"<div><div>Thymic mucoepidermoid carcinoma (MEC) is a rare thymic carcinoma subtype. Current metastatic thymic carcinoma guidelines recommend first-line platinum-based chemotherapy. However, evidence suggests that MECs, including those of the lung and salivary gland, are chemorefractory, highlighting a more nuanced approach to systemic therapy decision-making. Here, we report a case of durable partial response to second-line lenvatinib in a patient with metastatic high-grade thymic MEC, refractory to first-line platinum-based chemotherapy, suggesting a potentially preferred first-line role for lenvatinib for this subtype.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100894"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220589","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}
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
{"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}
{"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}
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
{"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}
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
{"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}
{"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}
Anne-Laurence Le Faou MD, PhD , Dalia Alleaume MSc , Ingrid Allagbé PhD
{"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}
{"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}
Azam Ghafoor MD , Nitin Roper MD , Chul Kim MD, MPH , Chuong D. Hoang MD , Aparna H. Kesarwala MD, PhD , Kevin A. Camphausen MD , Kamran Farouq BS , Elizabeth Akoth RN, BSN, MSN , Corrine Keen RN, BSN, MS , Eva Szabo MD , Hadi Bhageri MD , Arun Rajan MD , Udayan Guha MD, PhD
{"title":"Local Ablative Therapy Followed by Osimertinib Rechallenge in Oligoprogressive, EGFR-Mutated NSCLC: A Phase 2 Study","authors":"Azam Ghafoor MD , Nitin Roper MD , Chul Kim MD, MPH , Chuong D. Hoang MD , Aparna H. Kesarwala MD, PhD , Kevin A. Camphausen MD , Kamran Farouq BS , Elizabeth Akoth RN, BSN, MSN , Corrine Keen RN, BSN, MS , Eva Szabo MD , Hadi Bhageri MD , Arun Rajan MD , Udayan Guha MD, PhD","doi":"10.1016/j.jtocrr.2025.100886","DOIUrl":"10.1016/j.jtocrr.2025.100886","url":null,"abstract":"<div><h3>Introduction</h3><div>Osimertinib has exhibited impressive efficacy in advanced EGFR-mutated NSCLC; however, resistance is inevitable. We hypothesized that local ablative therapy (LAT) for oligoprogressive disease (up to five sites), followed by osimertinib rechallenge, would be safe and provide additional second progression-free survival (PFS2) benefit.</div></div><div><h3>Methods</h3><div>This prospective phase 2 trial enrolled <em>EGFR</em>-mutated NSCLC patients in three cohorts: tyrosine kinase inhibitor (TKI)–naive (cohort 1), previously treated with TKI and developed acquired T790M resistance mutation (cohort 2), or previously treated with osimertinib and developed resistance (cohort 3). Patients in cohorts 1 and 2 received upfront osimertinib followed by LAT on oligoprogression, followed by osimertinib rechallenge. Cohort 3 patients underwent LAT on enrollment, followed by osimertinib rechallenge. The primary end points were safety, tolerability, and PFS2 among the patients who underwent LAT across all three cohorts combined. Secondary end points were PFS1 and overall response rates.</div></div><div><h3>Results</h3><div>A total of 37 patients with EGFR-mutated NSCLC were enrolled; 25 in cohort 1, nine in cohort 2, and three in cohort 3. A total of 21 patients received LAT across all three cohorts combined, yielding a median PFS2 of 3.7 months (95% confidence interval: 1.9–4.6 mo) for this population. A subgroup with exceptionally long PFS2 was identified that achieved lower tumor burden and circulating tumor DNA–negative minimal residual disease of the EGFR clone with osimertinib before undergoing LAT. Most adverse events related to LAT were grades 1 and 2.</div></div><div><h3>Conclusions</h3><div>This is the first prospective trial exploring local therapy and osimertinib rechallenge on oligoprogression on osimertinib. Interim analysis revealed that PFS2 in the intention-to-treat patients did not meet its primary goal when compared with historical data on continuation of first-generation EGFR TKIs after LAT. However, definite LAT can be carefully considered in patients using circulating tumor DNA–negative minimal residual disease status as a biomarker for predicting who will benefit from continuation of osimertinib post-LAT.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100886"},"PeriodicalIF":3.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096128","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}