Tarlatamab is a novel bispecific T-cell engager therapy with promising efficacy in patients with previously treated extensive-stage SCLC. Cytokine release syndrome (CRS) is the most common adverse event related to tarlatamab, although severe CRS remains rare, and grade 3 or higher adverse events have been reported to be less common with tarlatamab than with chemotherapy. Available clinical data on severe adverse events associated with tarlatamab remain limited. Herein, we report a case of a 55-year-old woman with extensive-stage-SCLC who was treated with tarlatamab. Severe CRS and liver injury rapidly developed in the patient after the first tarlatamab dose, which led to treatment discontinuation. This report also presents the temporal changes in serum interleukin-6 levels, highlighting its potential utility as a biomarker for the onset and severity of CRS.
{"title":"Rapid-onset Severe Cytokine Release Syndrome With Marked Interleukin-6 Increase and Acute Liver Injury After the First Tarlatamab Dose in SCLC: Case Report","authors":"Kento Takagi MD , Go Saito MD, PhD , Toshiaki Inazaki MD , Hikaru Shojima MD , Jun Miyakoshi MD , Akira Naito MD, PhD , Shun Sato MD, PhD , Takashi Shimazui MD, PhD , Haruka Anzai MD , Chiaki Imai PhD , Takuji Suzuki MD, PhD","doi":"10.1016/j.jtocrr.2025.100917","DOIUrl":"10.1016/j.jtocrr.2025.100917","url":null,"abstract":"<div><div>Tarlatamab is a novel bispecific T-cell engager therapy with promising efficacy in patients with previously treated extensive-stage SCLC. Cytokine release syndrome (CRS) is the most common adverse event related to tarlatamab, although severe CRS remains rare, and grade 3 or higher adverse events have been reported to be less common with tarlatamab than with chemotherapy. Available clinical data on severe adverse events associated with tarlatamab remain limited. Herein, we report a case of a 55-year-old woman with extensive-stage-SCLC who was treated with tarlatamab. Severe CRS and liver injury rapidly developed in the patient after the first tarlatamab dose, which led to treatment discontinuation. This report also presents the temporal changes in serum interleukin-6 levels, highlighting its potential utility as a biomarker for the onset and severity of CRS.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100917"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145576879","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 : 2025-11-01Epub Date: 2025-07-03DOI: 10.1016/j.jtocrr.2025.100876
Kai-Lin Liu BA, BS , Alex Watts MS , Connor B. Grady MPH , Geoffrey Liu MD, MSc , Devalben Patel BSc, MLT , Karmugi Balaratnam MD , Stephen V. Liu MD , Gabriela Bravo Montenegro MD , Yunan Nie MD , Jorge Nieva MD , Amanda Herrmann MD , Kristen Marrone MD , Vincent Lam MD , Fangdi Sun MD , Jonathan Dowell MD , William Schwartzman MD , Vamsidhar Velcheti MD , Olivia Fankuchen MD, MS , Tasfiq Ullah MD , Liza Villaruz MD , Melina E. Marmarelis MD, MSCE
Introduction
The prognostic significance of baseline and on-treatment brain and liver metastasis in ALK+ or ROS1+ metastatic NSCLC (mNSCLC) remains unclear. As we consider intensification strategies, it is critical to identify factors that predict high-risk disease.
Methods
Clinical characteristics and outcomes were abstracted from the electronic medical records of patients with ALK+ or ROS1+ mNSCLC. Baseline characteristics and the cumulative incidence (CI) of brain and liver metastases were compared (≥2-year survivors versus <2-year; pre-2017 versus post-2017). Multivariable Cox proportional hazard models were used to evaluate the association between factors and overall survival, and multivariable logistic regression models were used for the odds of death within 2 years.
Results
A total of 310 patients with ALK+ mNSCLC were identified (≥2-y: 229, <2-y: 81). There was no difference in cumulative incidence of brain metastases between survival groups (29% at 21 mo). However, the cumulative incidence of liver metastasis was higher in those who survived less than 2 years (20.9% versus 5.4% at 21 mo). The cumulative incidence of brain but not liver metastases has improved post-2017 with the newer generation of ALK tyrosine kinase inhibitors. There were 69 patients with ROS1+ mNSCLC who were identified (≥2-y: 46, < 2-y: 23). There was no significant difference in the cumulative incidence of brain or liver metastases between less-than-2-year and greater-than-or-equal-to-2-year survivor cohorts (p = 0.664, p = 0.201).
Conclusions
Among patients with ALK+ but not ROS1+ mNSCLC, the presence of liver metastases at baseline and on-treatment was associated with worse survival. In the ALK+ population, the cumulative incidence of brain but not liver metastases is improving, highlighting a need for therapies effective at the treatment and prevention of liver metastases.
{"title":"Characteristics of Short-Term Survivors With ALK or ROS1-Altered Metastatic NSCLC","authors":"Kai-Lin Liu BA, BS , Alex Watts MS , Connor B. Grady MPH , Geoffrey Liu MD, MSc , Devalben Patel BSc, MLT , Karmugi Balaratnam MD , Stephen V. Liu MD , Gabriela Bravo Montenegro MD , Yunan Nie MD , Jorge Nieva MD , Amanda Herrmann MD , Kristen Marrone MD , Vincent Lam MD , Fangdi Sun MD , Jonathan Dowell MD , William Schwartzman MD , Vamsidhar Velcheti MD , Olivia Fankuchen MD, MS , Tasfiq Ullah MD , Liza Villaruz MD , Melina E. Marmarelis MD, MSCE","doi":"10.1016/j.jtocrr.2025.100876","DOIUrl":"10.1016/j.jtocrr.2025.100876","url":null,"abstract":"<div><h3>Introduction</h3><div>The prognostic significance of baseline and on-treatment brain and liver metastasis in <em>ALK</em>+ or <em>ROS1</em>+ metastatic NSCLC (mNSCLC) remains unclear. As we consider intensification strategies, it is critical to identify factors that predict high-risk disease.</div></div><div><h3>Methods</h3><div>Clinical characteristics and outcomes were abstracted from the electronic medical records of patients with <em>ALK</em>+ or <em>ROS1</em>+ mNSCLC. Baseline characteristics and the cumulative incidence (CI) of brain and liver metastases were compared (≥2-year survivors versus <2-year; pre-2017 versus post-2017). Multivariable Cox proportional hazard models were used to evaluate the association between factors and overall survival, and multivariable logistic regression models were used for the odds of death within 2 years.</div></div><div><h3>Results</h3><div>A total of 310 patients with <em>ALK</em>+ mNSCLC were identified (≥2-y: 229, <2-y: 81). There was no difference in cumulative incidence of brain metastases between survival groups (29% at 21 mo). However, the cumulative incidence of liver metastasis was higher in those who survived less than 2 years (20.9% versus 5.4% at 21 mo). The cumulative incidence of brain but not liver metastases has improved post-2017 with the newer generation of ALK tyrosine kinase inhibitors. There were 69 patients with <em>ROS1</em>+ mNSCLC who were identified (≥2-y: 46, < 2-y: 23). There was no significant difference in the cumulative incidence of brain or liver metastases between less-than-2-year and greater-than-or-equal-to-2-year survivor cohorts (<em>p</em> = 0.664, <em>p</em> = 0.201).</div></div><div><h3>Conclusions</h3><div>Among patients with <em>ALK</em>+ but not <em>ROS1</em>+ mNSCLC, the presence of liver metastases at baseline and on-treatment was associated with worse survival. In the ALK+ population, the cumulative incidence of brain but not liver metastases is improving, highlighting a need for therapies effective at the treatment and prevention of liver metastases.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100876"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425161","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 : 2025-11-01Epub Date: 2025-07-03DOI: 10.1016/j.jtocrr.2025.100874
Sun Choi BHSc , Monisha Chawla HBSc, MPH , Payton Catherwood MPH , David Chen BMSc , Ryan S. Huang MSc , William Boateng BSc , Jennifer Do BSc , Maha Khan BHSc , Abdulrahman Alghabban MD , Naa Kwarley Quartey MSc , Srinivas Raman MD, MASc , Meredith E. Giuliani M.B.B.S., MEd, PhD, FRCPC , William K. Evans MD, FRCPC , Lawson Eng MD, SM, FRCPC
Introduction
Despite the importance of smoking cessation in cancer care, it remains unclear how much tobacco control and smoking-related content (TCSCR) is included in major oncology meetings. Developing an understanding of the amount of content can help to improve education and dissemination of the benefits of smoking cessation in cancer care.
Methods
We performed a scoping review of TCSCR abstracts and educational sessions using online programs and abstract books from 2018 to 2023 for 12 major oncology meetings across different disciplines and disease sites.
Results
A total of 5178 TCSCR content was identified using our search criteria; 421 abstracts and 119 educational sessions met the inclusion criteria. Between 2018 and 2023, the World Cancer Congress (WCC) and the World Conference on Lung Cancer (WCLC) had the highest mean percentage of smoking-related abstracts (WCC: 4.96 ± 3.77%; WCLC: 1.81 ± 0.77%) and educational sessions (WCC: 3.48 ± 1.30%; WCLC: 3.15 ± 1.06%). Among the included abstracts, most (79%) first authors were from high-income countries. Around 39% percent of abstracts focused on tobacco as a cancer risk factor, 34% smoking cessation, and 26% cancer outcomes. Most abstracts were presented as posters (65%), as oral abstracts (27%), or as published abstracts (8%). The distribution of topic focus (p = 0.004) and session type (p < 0.001) differed between abstracts from high-income and low-middle-income countries.
Conclusions
Despite the importance of smoking cessation in oncology, TCSCR abstracts and educational content are limited at major oncology meetings. Organizers of oncology conferences should be encouraged to explore strategies to include sessions and attract submissions on these topics, particularly from underrepresented regions.
{"title":"Tobacco Control and Smoking Cessation–Related Content in Oncology Meetings: A Systematic Scoping Review","authors":"Sun Choi BHSc , Monisha Chawla HBSc, MPH , Payton Catherwood MPH , David Chen BMSc , Ryan S. Huang MSc , William Boateng BSc , Jennifer Do BSc , Maha Khan BHSc , Abdulrahman Alghabban MD , Naa Kwarley Quartey MSc , Srinivas Raman MD, MASc , Meredith E. Giuliani M.B.B.S., MEd, PhD, FRCPC , William K. Evans MD, FRCPC , Lawson Eng MD, SM, FRCPC","doi":"10.1016/j.jtocrr.2025.100874","DOIUrl":"10.1016/j.jtocrr.2025.100874","url":null,"abstract":"<div><h3>Introduction</h3><div>Despite the importance of smoking cessation in cancer care, it remains unclear how much tobacco control and smoking-related content (TCSCR) is included in major oncology meetings. Developing an understanding of the amount of content can help to improve education and dissemination of the benefits of smoking cessation in cancer care.</div></div><div><h3>Methods</h3><div>We performed a scoping review of TCSCR abstracts and educational sessions using online programs and abstract books from 2018 to 2023 for 12 major oncology meetings across different disciplines and disease sites.</div></div><div><h3>Results</h3><div>A total of 5178 TCSCR content was identified using our search criteria; 421 abstracts and 119 educational sessions met the inclusion criteria. Between 2018 and 2023, the World Cancer Congress (WCC) and the World Conference on Lung Cancer (WCLC) had the highest mean percentage of smoking-related abstracts (WCC: 4.96 ± 3.77%; WCLC: 1.81 ± 0.77%) and educational sessions (WCC: 3.48 ± 1.30%; WCLC: 3.15 ± 1.06%). Among the included abstracts, most (79%) first authors were from high-income countries. Around 39% percent of abstracts focused on tobacco as a cancer risk factor, 34% smoking cessation, and 26% cancer outcomes. Most abstracts were presented as posters (65%), as oral abstracts (27%), or as published abstracts (8%). The distribution of topic focus (<em>p</em> = 0.004) and session type (<em>p</em> < 0.001) differed between abstracts from high-income and low-middle-income countries.</div></div><div><h3>Conclusions</h3><div>Despite the importance of smoking cessation in oncology, TCSCR abstracts and educational content are limited at major oncology meetings. Organizers of oncology conferences should be encouraged to explore strategies to include sessions and attract submissions on these topics, particularly from underrepresented regions.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100874"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145334364","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 : 2025-11-01Epub Date: 2025-09-26DOI: 10.1016/j.jtocrr.2025.100911
Youling Gong MD , Qingsong Pang MD , Rong Yu MD , Zhengfei Zhu MD , Jiangqiong Huang MD , Yufeng Cheng MD , Diansheng Zhong MD , Hongbo Wu MD , Seung Soo Yoo PhD , Tracy Dobbs MD , Zinan Bao MD , Yunxia Zuo MD , Yujuan Gao PhD , Pu Sun PhD , You Lu MD
Introduction
Patients with limited-stage SCLC (LS-SCLC) have a substantial unmet clinical need for new treatments that delay disease progression and prolong survival.
Methods
In this phase 2, multicenter, randomized, multiarm, open-label trial, patients with untreated LS-SCLC received ociperlimab and tislelizumab plus concurrent chemoradiotherapy (cCRT) (arm A), tislelizumab plus cCRT (arm B), or cCRT (arm C). The primary objective was to compare progression-free survival (PFS) per investigator for arms A and B versus C (NCT04952597). The contribution of ociperlimab was explored by comparison of arms A versus B. Statistical analyses were descriptive, with no formal hypothesis testing.
Results
A total of 126 patients were randomized to arms A (N = 41), B (N = 42), and C (N = 43). The median PFS [95% confidence interval] exhibited a trend for improvement in arms A (12.6 [8.7–not estimable] months) and B (13.2 [8.5–not estimable]) compared with C (9.5 [8.3–14.4]); the PFS benefit was comparable between Arms A and B.
The objective response rate, complete response rate, and median duration of response were numerically higher in arms A and B than in C. The median overall survival was not reached in all three arms, and the median distant metastasis–free survival revealed no trend for improvement for arms A and B compared with C. All patients experienced at least one treatment-related treatment-emergent adverse event.
Conclusions
Ociperlimab and tislelizumab plus cCRT and tislelizumab plus cCRT exhibited a trend for improvement in PFS and numerically higher objective response rate compared with cCRT, with no new safety signals beyond the known profiles of immune checkpoint inhibitors and cCRT. Adding ociperlimab to tislelizumab plus cCRT was not associated with additional improvement in efficacy.
{"title":"AdvanTIG-204: A Phase 2, Randomized, Open-Label Study of Ociperlimab Plus Tislelizumab and Concurrent Chemoradiotherapy Versus Tislelizumab and Concurrent Chemotherapy Versus Concurrent Chemoradiotherapy in First-Line Limited-Stage SCLC","authors":"Youling Gong MD , Qingsong Pang MD , Rong Yu MD , Zhengfei Zhu MD , Jiangqiong Huang MD , Yufeng Cheng MD , Diansheng Zhong MD , Hongbo Wu MD , Seung Soo Yoo PhD , Tracy Dobbs MD , Zinan Bao MD , Yunxia Zuo MD , Yujuan Gao PhD , Pu Sun PhD , You Lu MD","doi":"10.1016/j.jtocrr.2025.100911","DOIUrl":"10.1016/j.jtocrr.2025.100911","url":null,"abstract":"<div><h3>Introduction</h3><div>Patients with limited-stage SCLC (LS-SCLC) have a substantial unmet clinical need for new treatments that delay disease progression and prolong survival.</div></div><div><h3>Methods</h3><div>In this phase 2, multicenter, randomized, multiarm, open-label trial, patients with untreated LS-SCLC received ociperlimab and tislelizumab plus concurrent chemoradiotherapy (cCRT) (arm A), tislelizumab plus cCRT (arm B), or cCRT (arm C). The primary objective was to compare progression-free survival (PFS) per investigator for arms A and B versus C (NCT04952597). The contribution of ociperlimab was explored by comparison of arms A versus B. Statistical analyses were descriptive, with no formal hypothesis testing.</div></div><div><h3>Results</h3><div>A total of 126 patients were randomized to arms A (N = 41), B (N = 42), and C (N = 43). The median PFS [95% confidence interval] exhibited a trend for improvement in arms A (12.6 [8.7–not estimable] months) and B (13.2 [8.5–not estimable]) compared with C (9.5 [8.3–14.4]); the PFS benefit was comparable between Arms A and B.</div><div>The objective response rate, complete response rate, and median duration of response were numerically higher in arms A and B than in C. The median overall survival was not reached in all three arms, and the median distant metastasis–free survival revealed no trend for improvement for arms A and B compared with C. All patients experienced at least one treatment-related treatment-emergent adverse event.</div></div><div><h3>Conclusions</h3><div>Ociperlimab and tislelizumab plus cCRT and tislelizumab plus cCRT exhibited a trend for improvement in PFS and numerically higher objective response rate compared with cCRT, with no new safety signals beyond the known profiles of immune checkpoint inhibitors and cCRT. Adding ociperlimab to tislelizumab plus cCRT was not associated with additional improvement in efficacy.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100911"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425159","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":"2025-11-01","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 : 2025-11-01Epub Date: 2025-07-03DOI: 10.1016/j.jtocrr.2025.100875
Sanjana Mullangi MD , Manidhar Reddy Lekkala MD , Sarah Blocker PharmD , Diana Kim PharmD , Jun Zhang MD , Chao Huang MD , Prakash Neupane MD , Haoran Li MD , Timothy Schieber PharmD
Introduction
SCLC remains the most aggressive lung cancer with a poor prognosis. Tarlatamab, a bispecific T-cell engager, is approved for use in extensive-stage SCLC after progression on a platinum-based chemotherapy on the basis of the DeLLphi-301 trial. Because of the restrictive inclusion criteria of this trial, substantial gaps remain in our understanding of treatment for many patients.
Methods
We performed a retrospective chart review of patients who were treated with tarlatamab at the University of Kansas Cancer Center from May 2024 through December 2024 for SCLC (cohort 1) or extrapulmonary small cell carcinoma (EPSCC) (cohort 2). Patients were included if they received at least one dose of tarlatamab regardless of baseline characteristics.
Results
A total of 21 patients were included in cohort 1, and three patients were included in cohort 2. In the SCLC cohort, 14 patients (66.6%) had central nervous system (CNS) involvement, five patients (23.8%) required baseline oxygen, and five patients (23.8%) had an Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or greater. There were 13 patients (61.9%) who developed cytokine release syndrome (CRS), with grade 3 or higher CRS noted in two patients (15.3%). There were 10 patients (47.6%) who developed immune effector cell–associated neurotoxicity syndrome (ICANS), with three patients (14.2%) developing grade 3 or higher ICANS. In the three patients with extrapulmonary small cell carcinoma, any-grade CRS occurred in two patients (66.7%), and grade 1 ICANS occurred in one patient (33.3%). Characteristics such as ECOG of 2 or higher, baseline oxygen use, and untreated CNS metastases are associated with high rates of CRS and ICANS. In 17 patients evaluable for best response in cohort 1, partial response was seen in six (35.2%) patients. No patients in cohort 2 had disease assessment performed at the time of data cutoff. Alternative CNS disease control using tarlatamab alone or with concurrent radiation provided clinical benefit to three patients.
Conclusions
Baseline risk factors such as oxygen dependence, poor ECOG performance status, bulky disease, and untreated CNS involvement may increase CRS and ICANS rates after tarlatamab. However, subsequent doses exhibited a more favorable safety profile, supporting outpatient administration and reduced observation time. CNS management strategies, including concurrent radiation or monotherapy with tarlatamab, exhibited promising efficacy. These findings highlight the need for further research into CRS and ICANS risk stratification, optimal CNS management, and efficacy in extrapulmonary small cell carcinoma through larger studies.
{"title":"Safety, Efficacy, and Central Nervous System Control in Patients with High Baseline Risk Factors Treated with Tarlatamab for SCLC or Extrapulmonary Small Cell Carcinoma","authors":"Sanjana Mullangi MD , Manidhar Reddy Lekkala MD , Sarah Blocker PharmD , Diana Kim PharmD , Jun Zhang MD , Chao Huang MD , Prakash Neupane MD , Haoran Li MD , Timothy Schieber PharmD","doi":"10.1016/j.jtocrr.2025.100875","DOIUrl":"10.1016/j.jtocrr.2025.100875","url":null,"abstract":"<div><h3>Introduction</h3><div>SCLC remains the most aggressive lung cancer with a poor prognosis. Tarlatamab, a bispecific T-cell engager, is approved for use in extensive-stage SCLC after progression on a platinum-based chemotherapy on the basis of the DeLLphi-301 trial. Because of the restrictive inclusion criteria of this trial, substantial gaps remain in our understanding of treatment for many patients.</div></div><div><h3>Methods</h3><div>We performed a retrospective chart review of patients who were treated with tarlatamab at the University of Kansas Cancer Center from May 2024 through December 2024 for SCLC (cohort 1) or extrapulmonary small cell carcinoma (EPSCC) (cohort 2). Patients were included if they received at least one dose of tarlatamab regardless of baseline characteristics.</div></div><div><h3>Results</h3><div>A total of 21 patients were included in cohort 1, and three patients were included in cohort 2. In the SCLC cohort, 14 patients (66.6%) had central nervous system (CNS) involvement, five patients (23.8%) required baseline oxygen, and five patients (23.8%) had an Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or greater. There were 13 patients (61.9%) who developed cytokine release syndrome (CRS), with grade 3 or higher CRS noted in two patients (15.3%). There were 10 patients (47.6%) who developed immune effector cell–associated neurotoxicity syndrome (ICANS), with three patients (14.2%) developing grade 3 or higher ICANS. In the three patients with extrapulmonary small cell carcinoma, any-grade CRS occurred in two patients (66.7%), and grade 1 ICANS occurred in one patient (33.3%). Characteristics such as ECOG of 2 or higher, baseline oxygen use, and untreated CNS metastases are associated with high rates of CRS and ICANS. In 17 patients evaluable for best response in cohort 1, partial response was seen in six (35.2%) patients. No patients in cohort 2 had disease assessment performed at the time of data cutoff. Alternative CNS disease control using tarlatamab alone or with concurrent radiation provided clinical benefit to three patients.</div></div><div><h3>Conclusions</h3><div>Baseline risk factors such as oxygen dependence, poor ECOG performance status, bulky disease, and untreated CNS involvement may increase CRS and ICANS rates after tarlatamab. However, subsequent doses exhibited a more favorable safety profile, supporting outpatient administration and reduced observation time. CNS management strategies, including concurrent radiation or monotherapy with tarlatamab, exhibited promising efficacy. These findings highlight the need for further research into CRS and ICANS risk stratification, optimal CNS management, and efficacy in extrapulmonary small cell carcinoma through larger studies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100875"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425162","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 : 2025-11-01Epub 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":"2025-11-01","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}
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":"2025-11-01","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 : 2025-11-01Epub 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":"2025-11-01","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 : 2025-11-01Epub Date: 2025-08-21DOI: 10.1016/j.jtocrr.2025.100890
Arthi Sridhar MD , Aditi Singh MD, MPH , Scott Hansen MD , Sydney Pulsipher MD , Kaushal Parikh MD , Aaron S. Mansfield MD , Anastasios Dimou MD , Julian R. Molina MD , Katherine E. Smith MD , Yolanda I. Garces MD , Sean S. Park MD , Aadel A. Chaudhuri MD, PhD , Kenneth W. Merrell MD , Kenneth R. Olivier MD , Konstantinos Leventakos MD , Dawn Owen MD, PhD , Mohamed Shanshal MD, MBBCh
Background
The eighth edition of the International Association for the Study of Lung Cancer staging project reports a 5-year overall survival (OS) for stage IIIA, B, and C NSCLC of 41%, 24%, and 12%, respectively, highlighting the need for improved treatment options. Induction chemotherapy and immune checkpoint inhibition (ID-chemo-ICI) followed by concurrent chemoradiation (cCRT) has not been adequately studied because of concerns about toxicity. We aim to describe the outcomes of patients with unresectable stage III NSCLC who received ID-chemo-ICI followed by cCRT with or without maintenance ICI.
Methods
We conducted a retrospective analysis of patients with unresectable stage III NSCLC who received ID-chemo-ICI with the intent to proceed with cCRT across all Mayo Clinic sites. Clinical end points included progression-free survival (PFS), OS, overall response rate per the Response Evaluation Criteria in Solid Tumors version 1.1, and treatment-related adverse events defined using Common Terminology Criteria for Adverse Events version 5.0.
Results
A total of 29 patients with unresectable stage III NSCLC, deemed unsuitable for upfront cCRT or surgery, with a plan to proceed with ID-chemo-ICI before cCRT, were identified. The median age was 66 years, 55% were male, most had a history of smoking (93.1%), and 100% identified as White. Tumor histologies were adenocarcinoma (69%), squamous cell carcinoma (24%), poorly differentiated NSCLC (3.4%), and sarcomatoid NSCLC (3.4%). Most were stage IIIB (44.8%), followed by IIIC (41.4%), and IIIA (13.8%). N2 and N3 disease were present in 37.9% and 55.2%, respectively. Programmed death-ligand 1 expression included less than 1% (n = 11, 38%), 1% to 49% (n = 9, 31%), greater than 50% (n = 5, 17%), and unknown (n = 4, 14%). Patients received ID-chemo-ICI with pembrolizumab (82.8%), nivolumab (13.8%), or atezolizumab (3.4%), with a median of four cycles. The overall response rate to ID-chemo-ICI was 93%. Of the cohort, 90% received cCRT, and 76% received maintenance ICI (pembrolizumab or durvalumab). The median PFS was 18 months, and the median OS was 24 months. Pneumonitis occurred in 37.9% (grade 1: 18.2%; grade 2: 63.6%; grade 3: 18%, no grade 4). Esophagitis occurred in 55.2% (grade 1–2: 93%; grade 3: 7%).
Conclusions
ID-chemo-ICI followed by cCRT seems feasible and safe for unresectable stage III NSCLC, particularly for patients unsuitable for upfront cCRT. Larger prospective trials are needed to validate these findings and optimize patient selection.
{"title":"Safety and Efficacy of Sequential Chemoimmunotherapy Followed by Concurrent Chemoradiation in Unresectable Stage III NSCLC","authors":"Arthi Sridhar MD , Aditi Singh MD, MPH , Scott Hansen MD , Sydney Pulsipher MD , Kaushal Parikh MD , Aaron S. Mansfield MD , Anastasios Dimou MD , Julian R. Molina MD , Katherine E. Smith MD , Yolanda I. Garces MD , Sean S. Park MD , Aadel A. Chaudhuri MD, PhD , Kenneth W. Merrell MD , Kenneth R. Olivier MD , Konstantinos Leventakos MD , Dawn Owen MD, PhD , Mohamed Shanshal MD, MBBCh","doi":"10.1016/j.jtocrr.2025.100890","DOIUrl":"10.1016/j.jtocrr.2025.100890","url":null,"abstract":"<div><h3>Background</h3><div>The eighth edition of the International Association for the Study of Lung Cancer staging project reports a 5-year overall survival (OS) for stage IIIA, B, and C NSCLC of 41%, 24%, and 12%, respectively, highlighting the need for improved treatment options. Induction chemotherapy and immune checkpoint inhibition (ID-chemo-ICI) followed by concurrent chemoradiation (cCRT) has not been adequately studied because of concerns about toxicity. We aim to describe the outcomes of patients with unresectable stage III NSCLC who received ID-chemo-ICI followed by cCRT with or without maintenance ICI.</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis of patients with unresectable stage III NSCLC who received ID-chemo-ICI with the intent to proceed with cCRT across all Mayo Clinic sites. Clinical end points included progression-free survival (PFS), OS, overall response rate per the Response Evaluation Criteria in Solid Tumors version 1.1, and treatment-related adverse events defined using Common Terminology Criteria for Adverse Events version 5.0.</div></div><div><h3>Results</h3><div>A total of 29 patients with unresectable stage III NSCLC, deemed unsuitable for upfront cCRT or surgery, with a plan to proceed with ID-chemo-ICI before cCRT, were identified. The median age was 66 years, 55% were male, most had a history of smoking (93.1%), and 100% identified as White. Tumor histologies were adenocarcinoma (69%), squamous cell carcinoma (24%), poorly differentiated NSCLC (3.4%), and sarcomatoid NSCLC (3.4%). Most were stage IIIB (44.8%), followed by IIIC (41.4%), and IIIA (13.8%). N2 and N3 disease were present in 37.9% and 55.2%, respectively. Programmed death-ligand 1 expression included less than 1% (n = 11, 38%), 1% to 49% (n = 9, 31%), greater than 50% (n = 5, 17%), and unknown (n = 4, 14%). Patients received ID-chemo-ICI with pembrolizumab (82.8%), nivolumab (13.8%), or atezolizumab (3.4%), with a median of four cycles. The overall response rate to ID-chemo-ICI was 93%. Of the cohort, 90% received cCRT, and 76% received maintenance ICI (pembrolizumab or durvalumab). The median PFS was 18 months, and the median OS was 24 months. Pneumonitis occurred in 37.9% (grade 1: 18.2%; grade 2: 63.6%; grade 3: 18%, no grade 4). Esophagitis occurred in 55.2% (grade 1–2: 93%; grade 3: 7%).</div></div><div><h3>Conclusions</h3><div>ID-chemo-ICI followed by cCRT seems feasible and safe for unresectable stage III NSCLC, particularly for patients unsuitable for upfront cCRT. Larger prospective trials are needed to validate these findings and optimize patient selection.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100890"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145474293","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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