Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a target of antibody-drug conjugate therapy for NSCLC. High expression of CEACAM5 has been reported in approximately 25% of patients with lung adenocarcinoma. However, CEACAM5 expression has not been systematically examined in a real-world and large patient population with NSCLC. There are also limited data on the prognostic impact of CEACAM5 protein expression.
Methods
We assessed CEACAM5 protein expression by immunohistochemistry in two separate cohorts of patients with NSCLC to include both routine clinical biopsy and resection specimens, using the anti-CEACAM5 clone 769 antibody assay protocol and scoring scheme for the tusamitamab ravtansine clinical trials. Expression levels were categorized as high (≥50% tumor cells at ≥2+ intensity), moderate (1%–49% tumor cells at ≥2+ intensity), and negative (0/1+ intensity) and scored independently by three thoracic pathologists. Interrater reliability was determined by Kendall’s coefficient of concordance and Fleiss’ kappa. Association with PD-L1 and driver mutation was calculated by Fisher exact or chi-square test. Correlation with recurrence-free survival and overall survival was determined by log-rank tests.
Results
The interrater reliability of CEACAM5 assessment was moderate among three pathologists. The overall prevalence of high CEACAM5 expression was 18%. CEACAM5 expression did not significantly correlate with tumor stage, PD-L1 expression, tumor mutation burden, and EGFR or KRAS mutations. There was no prognostic effect of CEACAM5 expression on recurrence-free survival or overall survival.
Conclusions
Our data revealed that 18% of routinely diagnosed clinical NSCLC samples had high CEACAM5 expression by immunohistochemistry, and its expression was not associated with oncogenic driver mutations or patient prognosis in a predominantly early stage NSCLC cohort.
{"title":"The Landscape of CEACAM5 Expression by Immunohistochemistry in NSCLC","authors":"Ying-Han R. Hsu MD, FRCPC , Amna Almutrafi MD , Katrina Hueniken MSc , Alhareth Azaizeh MD , Likun Hou MD, PhD , Quan Li PhD , Mackenzie Bates BSc , Nhu-An Pham PhD , Ming-Sound Tsao MD, FRCPC","doi":"10.1016/j.jtocrr.2025.100943","DOIUrl":"10.1016/j.jtocrr.2025.100943","url":null,"abstract":"<div><h3>Introduction</h3><div>Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a target of antibody-drug conjugate therapy for NSCLC. High expression of CEACAM5 has been reported in approximately 25% of patients with lung adenocarcinoma. However, CEACAM5 expression has not been systematically examined in a real-world and large patient population with NSCLC. There are also limited data on the prognostic impact of CEACAM5 protein expression.</div></div><div><h3>Methods</h3><div>We assessed CEACAM5 protein expression by immunohistochemistry in two separate cohorts of patients with NSCLC to include both routine clinical biopsy and resection specimens, using the anti-CEACAM5 clone 769 antibody assay protocol and scoring scheme for the tusamitamab ravtansine clinical trials. Expression levels were categorized as high (≥50% tumor cells at ≥2+ intensity), moderate (1%–49% tumor cells at ≥2+ intensity), and negative (0/1+ intensity) and scored independently by three thoracic pathologists. Interrater reliability was determined by Kendall’s coefficient of concordance and Fleiss’ kappa. Association with PD-L1 and driver mutation was calculated by Fisher exact or chi-square test. Correlation with recurrence-free survival and overall survival was determined by log-rank tests.</div></div><div><h3>Results</h3><div>The interrater reliability of CEACAM5 assessment was moderate among three pathologists. The overall prevalence of high CEACAM5 expression was 18%. CEACAM5 expression did not significantly correlate with tumor stage, PD-L1 expression, tumor mutation burden, and <em>EGFR</em> or <em>KRAS</em> mutations. There was no prognostic effect of CEACAM5 expression on recurrence-free survival or overall survival.</div></div><div><h3>Conclusions</h3><div>Our data revealed that 18% of routinely diagnosed clinical NSCLC samples had high CEACAM5 expression by immunohistochemistry, and its expression was not associated with oncogenic driver mutations or patient prognosis in a predominantly early stage NSCLC cohort.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 2","pages":"Article 100943"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980964","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 : 2026-02-01Epub Date: 2025-10-27DOI: 10.1016/j.jtocrr.2025.100923
Matthew Evison MD, MRCP , Shobhit Baijal MBBS, BSc (Hons) , Mayuri Basnet MBBS, FRCPath , Tim Batchelor MSc, FRCS (CTh) , Karen Clayton MSc ACP , Lorraine Dallas BA , Alastair Greystoke PhD , Adam Januszewski PhD , Neal Navani PhD , Riyaz Shah PhD , Annabel Sharkey PhD, FRCS (CTh) , Jyotika Singh MBA
{"title":"Curative-Intent Multimodality Treatment for NSCLC: Will Global Healthcare Systems Rise to the Challenge? A Perspective From the United Kingdom","authors":"Matthew Evison MD, MRCP , Shobhit Baijal MBBS, BSc (Hons) , Mayuri Basnet MBBS, FRCPath , Tim Batchelor MSc, FRCS (CTh) , Karen Clayton MSc ACP , Lorraine Dallas BA , Alastair Greystoke PhD , Adam Januszewski PhD , Neal Navani PhD , Riyaz Shah PhD , Annabel Sharkey PhD, FRCS (CTh) , Jyotika Singh MBA","doi":"10.1016/j.jtocrr.2025.100923","DOIUrl":"10.1016/j.jtocrr.2025.100923","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 2","pages":"Article 100923"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024149","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 : 2026-02-01Epub Date: 2025-10-27DOI: 10.1016/j.jtocrr.2025.100924
Grace Chazan FRACP , Marliese Alexander PhD , Fanny Franchini PhD , Maarten IJzerman PhD , Roma Shah MPH , Ani John PhD , Tim Spelman PhD , Malinda Itchins PhD , Nick Pavlakis PhD , Adnan Nagrial PhD , Lydia Warburton FRACP , Samantha Bowyer FRACP , Steven Kao PhD , Sagun Parakh PhD , Benjamin J. Solomon PhD
Introduction
Advanced lung cancer has historically been associated with poor survival. However, with the advent of targeted therapies, outcomes are improving. Among patients with ALK-rearranged advanced NSCLC (ALK+ aNSCLC), real-world data on treatment patterns, prognostic factors, and survival in the era of contemporary therapy remain limited.
Methods
We conducted a retrospective observational cohort study using deidentified patient, disease, and outcomes data from the AUstralasian thoRacic cancers lOngitudinal cohoRt study and biobAnk (AURORA; ACTRN12625000038493). Eligible patients were diagnosed with ALK+ aNSCLC between 2006 and 2025.
Results
Of the 4776 patients with thoracic malignancies enrolled across eight sites (as of April 2025), 218 met the inclusion criteria—the largest reported Australian cohort of ALK+ aNSCLC. All patients were treated in academic centers. The median age was 55 years; 54% were female, 66% were never-smokers, and 41% had participated in a clinical trial. The median overall survival was 90.8 months (95% CI: 69.8–not reached). Nearly all patients (99%) received an ALK inhibitor; 83% in the first-line setting. Treatment sequences evolved over time. Most (68%) received at least two lines of therapy; 21% received 4 or more lines. Smoking status, age, and Eastern Cooperative Oncology Group Performance Status were prognostically associated with survival.
Conclusion
This study highlights the remarkable survival achievable in the real-world setting for some patients with ALK+ aNSCLC, compared with historical cohorts. Several clinical factors associated with survival were identified. Larger studies are needed to investigate how treatment sequences may be optimized to further improve survival outcomes.
{"title":"Treatment Patterns, Prognostic Factors and Survival for ALK-Positive Advanced NSCLC In Australia: Results From the Australasian Thoracic Cancers Longitudinal Cohort Study and Biobank (AURORA)","authors":"Grace Chazan FRACP , Marliese Alexander PhD , Fanny Franchini PhD , Maarten IJzerman PhD , Roma Shah MPH , Ani John PhD , Tim Spelman PhD , Malinda Itchins PhD , Nick Pavlakis PhD , Adnan Nagrial PhD , Lydia Warburton FRACP , Samantha Bowyer FRACP , Steven Kao PhD , Sagun Parakh PhD , Benjamin J. Solomon PhD","doi":"10.1016/j.jtocrr.2025.100924","DOIUrl":"10.1016/j.jtocrr.2025.100924","url":null,"abstract":"<div><h3>Introduction</h3><div>Advanced lung cancer has historically been associated with poor survival. However, with the advent of targeted therapies, outcomes are improving. Among patients with <em>ALK-</em>rearranged advanced NSCLC (ALK+ aNSCLC), real-world data on treatment patterns, prognostic factors, and survival in the era of contemporary therapy remain limited.</div></div><div><h3>Methods</h3><div>We conducted a retrospective observational cohort study using deidentified patient, disease, and outcomes data from the AUstralasian thoRacic cancers lOngitudinal cohoRt study and biobAnk (AURORA; ACTRN12625000038493). Eligible patients were diagnosed with ALK+ aNSCLC between 2006 and 2025.</div></div><div><h3>Results</h3><div>Of the 4776 patients with thoracic malignancies enrolled across eight sites (as of April 2025), 218 met the inclusion criteria—the largest reported Australian cohort of ALK+ aNSCLC. All patients were treated in academic centers. The median age was 55 years; 54% were female, 66% were never-smokers, and 41% had participated in a clinical trial. The median overall survival was 90.8 months (95% CI: 69.8–not reached). Nearly all patients (99%) received an ALK inhibitor; 83% in the first-line setting. Treatment sequences evolved over time. Most (68%) received at least two lines of therapy; 21% received 4 or more lines. Smoking status, age, and Eastern Cooperative Oncology Group Performance Status were prognostically associated with survival.</div></div><div><h3>Conclusion</h3><div>This study highlights the remarkable survival achievable in the real-world setting for some patients with ALK+ aNSCLC, compared with historical cohorts. Several clinical factors associated with survival were identified. Larger studies are needed to investigate how treatment sequences may be optimized to further improve survival outcomes.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 2","pages":"Article 100924"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024079","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 : 2026-02-01Epub Date: 2025-10-30DOI: 10.1016/j.jtocrr.2025.100929
Niels Reinmuth MD , Sébastien Couraud MD, PhD , Luis Paz-Ares MD, PhD , Marina Chiara Garassino MD , Shobhit Baijal MBBS, BSc , Davey Daniel MD , Pilar Garrido MD, PhD , Terufumi Kato MD , Ivor Percent MD , Achim Rittmeyer MD , Hector Soto Parra MD , Sabeen Mekan MD , Mira Patel PhD , Matthew Radford PhD , Eric Zhang PhD , Christopher G. Pelligra MS , Shien Guo PhD , Enriqueta Felip MD, PhD
Introduction
In the phase 3 EVOKE-01 trial (NCT05089734), sacituzumab govitecan (SG) exhibited a numerical improvement in overall survival and tolerability compared with docetaxel in patients with metastatic NSCLC previously treated with platinum-based chemotherapy and programmed cell death protein (ligand) 1 inhibitors, although results were not statistically significant. This analysis evaluated health-related quality of life (HRQoL) data from EVOKE-01.
Methods
Patients (N = 603) were randomized 1:1 to SG (n = 299) or docetaxel (n = 304) in 21-day cycles. HRQoL was assessed by the NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ), European Organization for Research and Treatment of Cancer Quality of Life questionnaire–Core 30 (QLQ-C30), and EuroQol 5 Dimension 3-level questionnaire. Least square mean changes from baseline at week 25, time to first meaningful deterioration or death, and time to confirmed deterioration were analyzed.
Results
SG exhibited significantly and meaningfully better effects than docetaxel on NSCLC-SAQ shortness of breath (SoB), fatigue, total score, and on QLQ-C30 role functioning, fatigue, and dyspnea. Time to first meaningful deterioration or death favored SG over docetaxel for NSCLC-SAQ SoB (hazard ratio [95% confidence interval ]: 0.75 [0.61–0.91]), fatigue (0.70 [0.57–0.86]), and total score (0.80 [0.66–0.97]); QLQ-C30 fatigue (0.80 [0.66–0.96]) and dyspnea (0.74 [0.60–0.90]); and EuroQol visual analog scale (0.79 [0.65–0.96]). The time to confirmed deterioration favored SG over docetaxel for NSCLC-SAQ SoB (0.59 [0.44–0.77]) and fatigue (0.70 [0.52–0.95]), and QLQ-C30 fatigue (0.75 [0.59–0.95]).
Conclusions
These exploratory results suggest that SG may benefit HRQoL over docetaxel, supporting SG as an active therapeutic agent for metastatic NSCLC post platinum-based and programmed cell death protein (ligand) 1 inhibitor therapy.
{"title":"Patient-Reported Symptoms and Quality of Life With Sacituzumab Govitecan Versus Docetaxel in Metastatic NSCLC: The Phase 3, Randomized EVOKE-01 Trial","authors":"Niels Reinmuth MD , Sébastien Couraud MD, PhD , Luis Paz-Ares MD, PhD , Marina Chiara Garassino MD , Shobhit Baijal MBBS, BSc , Davey Daniel MD , Pilar Garrido MD, PhD , Terufumi Kato MD , Ivor Percent MD , Achim Rittmeyer MD , Hector Soto Parra MD , Sabeen Mekan MD , Mira Patel PhD , Matthew Radford PhD , Eric Zhang PhD , Christopher G. Pelligra MS , Shien Guo PhD , Enriqueta Felip MD, PhD","doi":"10.1016/j.jtocrr.2025.100929","DOIUrl":"10.1016/j.jtocrr.2025.100929","url":null,"abstract":"<div><h3>Introduction</h3><div>In the phase 3 EVOKE-01 trial (NCT05089734), sacituzumab govitecan (SG) exhibited a numerical improvement in overall survival and tolerability compared with docetaxel in patients with metastatic NSCLC previously treated with platinum-based chemotherapy and programmed cell death protein (ligand) 1 inhibitors, although results were not statistically significant. This analysis evaluated health-related quality of life (HRQoL) data from EVOKE-01.</div></div><div><h3>Methods</h3><div>Patients (N = 603) were randomized 1:1 to SG (n = 299) or docetaxel (n = 304) in 21-day cycles. HRQoL was assessed by the NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ), European Organization for Research and Treatment of Cancer Quality of Life questionnaire–Core 30 (QLQ-C30), and EuroQol 5 Dimension 3-level questionnaire. Least square mean changes from baseline at week 25, time to first meaningful deterioration or death, and time to confirmed deterioration were analyzed.</div></div><div><h3>Results</h3><div>SG exhibited significantly and meaningfully better effects than docetaxel on NSCLC-SAQ shortness of breath (SoB), fatigue, total score, and on QLQ-C30 role functioning, fatigue, and dyspnea. Time to first meaningful deterioration or death favored SG over docetaxel for NSCLC-SAQ SoB (hazard ratio [95% confidence interval ]: 0.75 [0.61–0.91]), fatigue (0.70 [0.57–0.86]), and total score (0.80 [0.66–0.97]); QLQ-C30 fatigue (0.80 [0.66–0.96]) and dyspnea (0.74 [0.60–0.90]); and EuroQol visual analog scale (0.79 [0.65–0.96]). The time to confirmed deterioration favored SG over docetaxel for NSCLC-SAQ SoB (0.59 [0.44–0.77]) and fatigue (0.70 [0.52–0.95]), and QLQ-C30 fatigue (0.75 [0.59–0.95]).</div></div><div><h3>Conclusions</h3><div>These exploratory results suggest that SG may benefit HRQoL over docetaxel, supporting SG as an active therapeutic agent for metastatic NSCLC post platinum-based and programmed cell death protein (ligand) 1 inhibitor therapy.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 2","pages":"Article 100929"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980962","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 : 2026-02-01Epub Date: 2025-12-12DOI: 10.1016/j.jtocrr.2025.100941
Kaiwen Wang PharmD , Ceylan Altintas Taslic MD , Patricia de Groot MD , Mitchell A. Parma MD , Alvaro Guimaraes Paula MD , Melody Caranto MSN , Komal Shah MD , Mukulika Bose PhD , Cole Ruoff BS , Loukia G. Karacosta PhD , Lauren A. Byers MD , Carl M. Gay MD, PhD , Jianjun Zhang MD, PhD , John V. Heymach MD, PhD , Bingnan Zhang MD, MBA
Small cell transformation has been described as a resistance mechanism to targeted therapy treated in patients with EGFR-mutated NSCLC and less often reported with those with other actionable oncogenic alterations, including ALK-rearranged NSCLC. Given lack of standard-of-care treatments for patients with actionable oncogenic alteration NSCLC transformed to SCLC, this remains a challenge and unmet need for treating these patients.
Here, we present a case of a patient with ALK-rearranged NSCLC with transformation to SCLC, who has progressed on several lines of therapies and successfully treated with tarlatamab to elicit and maintain clinical benefit, including intracranial response.
{"title":"First Report of Response to Tarlatamab in a Patient With Histologic-Transformed SCLC From ALK-Rearranged NSCLC: Case Report","authors":"Kaiwen Wang PharmD , Ceylan Altintas Taslic MD , Patricia de Groot MD , Mitchell A. Parma MD , Alvaro Guimaraes Paula MD , Melody Caranto MSN , Komal Shah MD , Mukulika Bose PhD , Cole Ruoff BS , Loukia G. Karacosta PhD , Lauren A. Byers MD , Carl M. Gay MD, PhD , Jianjun Zhang MD, PhD , John V. Heymach MD, PhD , Bingnan Zhang MD, MBA","doi":"10.1016/j.jtocrr.2025.100941","DOIUrl":"10.1016/j.jtocrr.2025.100941","url":null,"abstract":"<div><div>Small cell transformation has been described as a resistance mechanism to targeted therapy treated in patients with <em>EGFR</em>-mutated NSCLC and less often reported with those with other actionable oncogenic alterations, including <em>ALK</em>-rearranged NSCLC. Given lack of standard-of-care treatments for patients with actionable oncogenic alteration NSCLC transformed to SCLC, this remains a challenge and unmet need for treating these patients.</div><div>Here, we present a case of a patient with <em>ALK</em>-rearranged NSCLC with transformation to SCLC, who has progressed on several lines of therapies and successfully treated with tarlatamab to elicit and maintain clinical benefit, including intracranial response.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 2","pages":"Article 100941"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981051","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 : 2026-02-01Epub Date: 2025-02-28DOI: 10.1016/j.jtocrr.2025.100816
Madhusmita Behera PhD , Gregory Joseph MS , Manali Rupji MS , Zhonglu Huang MS , Becky Bunn MS , Murry W. Wynes PhD , Jeffrey Switchenko PhD , Giorgio V. Scagliotti MD , Ming S. Tsao MD , Chandra P. Belani MD , Lecia V. Sequist MD , Suresh S. Ramalingam MD
Introduction
Precision medicine has resulted in improved outcomes for non small cell lung cancer (NSCLC), whereas biomarker testing is considered critical for guiding treatment decisions for advanced-stage NSCLC, and adoption of testing in routine practice is variable. We studied the utilization of biomarker testing in advanced NSCLC.
Methods
The American Society of Clinical Oncology (ASCO) CancerLinQ Discovery data set was queried to identify patients diagnosed with lung cancer between 2010 and 2018. Data on demographics, tumor stage, histology, and treatments were extracted, and receipt of biomarker testing was investigated as the primary outcome. Univariate association of each clinicopathological variable with the biomarker testing outcome was performed using a chi-square test for categorical variables and an analysis of variance test for numerical variables. A multivariable logistic regression analysis with backward selection at an alpha of 0.05 was reported. All analyses were conducted using SAS 9.4.
Results
A total of 37,925 patients with stage IV NSCLC were analyzed. The patients had a median age of 65 years; meanwhile, 51% of the participants were male individuals, 68% were white, and 33.5% had adenocarcinoma. Approximately 22% of all patients with NSCLC had biomarker testing results. Among the patients with adenocarcinoma, 49% had biomarker testing results available. In the stage IV group, 47% were treated with chemotherapy, 16% with immunotherapy, and 3.5% with targeted therapy. On multivariable analysis, female patients were more likely to have molecular testing compared with male patients (OR = 1.29, 95% confidence interval [CI]: 1.21–1.36, p < 0.001). Compared with white patients, black patients were less likely to have biomarker testing (OR = 0.89, 95% CI: 0.81–0.97, p = 0.009), and Asians were more likely to undergo testing (OR = 2.21, 95% CI: 1.78–2.73, p < 0.001). Hispanic patients were more likely to undergo biomarker testing than non-Hispanic (OR = 1.23, 95% CI: 1.01–1.50, p = 0.03). In addition, treatment with immunotherapy (OR = 1.86, 95% CI: 1.72–2.02, p < 0.001) and targeted therapy (OR = 2.52, 95% CI: 2.21–2.88, p < 0.001) were associated with a significantly higher likelihood of having biomarker testing. These results were also confirmed in a subgroup analysis of patients with adenocarcinoma.
Conclusion
In this analysis of a United States–based real-world data set of patients with stage IV NSCLC, the Asian race and female sex were associated with a higher likelihood of having biomarker testing performed. The overall percentage of patients undergoing testing remained suboptimal.
精准医学已经改善了非小细胞肺癌(NSCLC)的预后,而生物标志物检测被认为是指导晚期NSCLC治疗决策的关键,在常规实践中采用检测是可变的。我们研究了生物标志物检测在晚期非小细胞肺癌中的应用。方法查询美国临床肿瘤学会(ASCO) CancerLinQ Discovery数据集,以确定2010年至2018年诊断为肺癌的患者。提取了人口统计学、肿瘤分期、组织学和治疗方面的数据,并将接受生物标志物检测作为主要结果进行了调查。每个临床病理变量与生物标志物检测结果的单变量关联使用分类变量卡方检验和数值变量方差分析检验。采用逆向选择的多变量logistic回归分析,alpha值为0.05。所有分析均采用SAS 9.4进行。结果共分析了37925例IV期NSCLC患者。患者的中位年龄为65岁;与此同时,51%的参与者是男性,68%是白人,33.5%患有腺癌。大约22%的NSCLC患者有生物标志物检测结果。在腺癌患者中,49%的人有生物标志物检测结果。在IV期组中,47%接受化疗,16%接受免疫治疗,3.5%接受靶向治疗。在多变量分析中,女性患者比男性患者更有可能进行分子检测(OR = 1.29, 95%可信区间[CI]: 1.21-1.36, p < 0.001)。与白人患者相比,黑人患者较少接受生物标志物检测(OR = 0.89, 95% CI: 0.81-0.97, p = 0.009),而亚洲人更容易接受检测(OR = 2.21, 95% CI: 1.78-2.73, p < 0.001)。西班牙裔患者比非西班牙裔患者更有可能接受生物标志物检测(OR = 1.23, 95% CI: 1.01-1.50, p = 0.03)。此外,免疫治疗(OR = 1.86, 95% CI: 1.72-2.02, p < 0.001)和靶向治疗(OR = 2.52, 95% CI: 2.21-2.88, p < 0.001)与进行生物标志物检测的可能性显著升高相关。这些结果也在腺癌患者的亚组分析中得到证实。在对美国IV期NSCLC患者真实数据集的分析中,亚洲种族和女性与进行生物标志物检测的可能性较高相关。接受检测的患者总体百分比仍未达到理想水平。
{"title":"Biomarker Testing and Patterns of Treatment in Patients with NSCLC: An International Association for The Study of Lung Cancer Analysis of American Society of Clinical Oncology CancerLinQ Discovery Data","authors":"Madhusmita Behera PhD , Gregory Joseph MS , Manali Rupji MS , Zhonglu Huang MS , Becky Bunn MS , Murry W. Wynes PhD , Jeffrey Switchenko PhD , Giorgio V. Scagliotti MD , Ming S. Tsao MD , Chandra P. Belani MD , Lecia V. Sequist MD , Suresh S. Ramalingam MD","doi":"10.1016/j.jtocrr.2025.100816","DOIUrl":"10.1016/j.jtocrr.2025.100816","url":null,"abstract":"<div><h3>Introduction</h3><div>Precision medicine has resulted in improved outcomes for non small cell lung cancer (NSCLC), whereas biomarker testing is considered critical for guiding treatment decisions for advanced-stage NSCLC, and adoption of testing in routine practice is variable. We studied the utilization of biomarker testing in advanced NSCLC.</div></div><div><h3>Methods</h3><div>The American Society of Clinical Oncology (ASCO) CancerLinQ Discovery data set was queried to identify patients diagnosed with lung cancer between 2010 and 2018. Data on demographics, tumor stage, histology, and treatments were extracted, and receipt of biomarker testing was investigated as the primary outcome. Univariate association of each clinicopathological variable with the biomarker testing outcome was performed using a chi-square test for categorical variables and an analysis of variance test for numerical variables. A multivariable logistic regression analysis with backward selection at an alpha of 0.05 was reported. All analyses were conducted using SAS 9.4.</div></div><div><h3>Results</h3><div>A total of 37,925 patients with stage IV NSCLC were analyzed. The patients had a median age of 65 years; meanwhile, 51% of the participants were male individuals, 68% were white, and 33.5% had adenocarcinoma. Approximately 22% of all patients with NSCLC had biomarker testing results. Among the patients with adenocarcinoma, 49% had biomarker testing results available. In the stage IV group, 47% were treated with chemotherapy, 16% with immunotherapy, and 3.5% with targeted therapy. On multivariable analysis, female patients were more likely to have molecular testing compared with male patients (OR = 1.29, 95% confidence interval [CI]: 1.21–1.36, <em>p</em> < 0.001). Compared with white patients, black patients were less likely to have biomarker testing (OR = 0.89, 95% CI: 0.81–0.97, <em>p</em> = 0.009), and Asians were more likely to undergo testing (OR = 2.21, 95% CI: 1.78–2.73, <em>p</em> < 0.001). Hispanic patients were more likely to undergo biomarker testing than non-Hispanic (OR = 1.23, 95% CI: 1.01–1.50, <em>p</em> = 0.03). In addition, treatment with immunotherapy (OR = 1.86, 95% CI: 1.72–2.02, <em>p</em> < 0.001) and targeted therapy (OR = 2.52, 95% CI: 2.21–2.88, <em>p</em> < 0.001) were associated with a significantly higher likelihood of having biomarker testing. These results were also confirmed in a subgroup analysis of patients with adenocarcinoma.</div></div><div><h3>Conclusion</h3><div>In this analysis of a United States–based real-world data set of patients with stage IV NSCLC, the Asian race and female sex were associated with a higher likelihood of having biomarker testing performed. The overall percentage of patients undergoing testing remained suboptimal.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 2","pages":"Article 100816"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145929321","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 : 2026-02-01Epub Date: 2025-12-12DOI: 10.1016/j.jtocrr.2025.100940
Gustavo Schvartsman MD, PhD , Yasmin M. Amirato MD , Frederico Monfardini MSc , Gustavo Prado dos Santos BSc , Diogo B.D. Gomes MD , Ludmila de O. M. Koch MD , Benoit J. Bibas MD, PhD , Oswaldo Gomes Jr. MD , Paulo V. Campregher MD, PhD , Patrícia Severino PhD , Luciana C. Marti PhD , Vitor R. Paes MD , Laura Leaden PhD , Rodrigo C. Chate MD , Jose M. Ribas MD, PhD , Victor.A.R. Sousa MD , Patrícia Taranto MD , Fernando Moura MD, PhD , Ricardo M. Terra MD, PhD , Ana Carolina Pires de Rezende MD , Marcos N. Samano MD, PhD
Introduction
Stereotactic ablative radiotherapy (SABR) is routinely used in patients with early stage NSCLC who are not candidates for surgery. Despite excellent local tumor control, it is associated with a high rate of regional and distant recurrences. Combining stereotactic radiotherapy with PD-1 inhibitors has demonstrated encouraging results for patients with curative intent, but how it affects the tumor microenvironment and pathologic response remains unclear.
Methods
We designed a phase II, open-label, single-arm study aimed to evaluate the efficacy and safety of neoadjuvant nivolumab combined with SABR in patients with NSCLC measuring up to 4 cm, without positive lymph nodes. Patients were required to be eligible for surgery, with adequate pulmonary and cardiovascular function. Nivolumab was administered at 360 mg every 21 days for three doses, combined with SABR, which was initiated concomitantly with the first cycle. Patients subsequently underwent surgical resection 10 weeks after the last dose of radiation. The primary end point was the pathologic complete response (pCR) rate at surgery. Secondary end points included major pathologic response (MPR) rate, safety, event-free survival, and overall survival at 12 months and a comprehensive biomarker analysis.
Results
A total of 25 patients were enrolled between November 2019 and February 2022. The mean age was 68 years, and 68% were female. The mean tumor size at baseline was 2.47 cm. A total of 24 patients fully completed the experimental therapy and proceeded with surgery. The primary end point of pCR was achieved by 19 of 24 patients (79.2%; 95% confidence interval: 57%–92%, p value 0.0875, in the per-protocol analysis). MPR was observed in 20 cases (83.3%; 95% confidence interval: 61.8%–94%). Four patients have not achieved an MPR, with one of them presenting with 100% residual viable tumor. No patient relapsed to date, with 12-month event-free survival and overall survival of 84%, with median not reached for both. One patient died from alcoholic hepatitis, unrelated to the treatment, and did not undergo resection. Two patients died from surgical complications.
Conclusions
The neoadjuvant combination of three doses of nivolumab and SABR produced a high pCR rate in stage I NSCLC. Further research is warranted to evaluate this treatment modality in patients with medically inoperable NSCLC and whether surgery could be safely omitted for patients who are candidates for resection.
{"title":"Pathologic Responses to Stereotactic Ablative Radiotherapy in Combination With Nivolumab for Early Stage NSCLC: A Phase 2 Study","authors":"Gustavo Schvartsman MD, PhD , Yasmin M. Amirato MD , Frederico Monfardini MSc , Gustavo Prado dos Santos BSc , Diogo B.D. Gomes MD , Ludmila de O. M. Koch MD , Benoit J. Bibas MD, PhD , Oswaldo Gomes Jr. MD , Paulo V. Campregher MD, PhD , Patrícia Severino PhD , Luciana C. Marti PhD , Vitor R. Paes MD , Laura Leaden PhD , Rodrigo C. Chate MD , Jose M. Ribas MD, PhD , Victor.A.R. Sousa MD , Patrícia Taranto MD , Fernando Moura MD, PhD , Ricardo M. Terra MD, PhD , Ana Carolina Pires de Rezende MD , Marcos N. Samano MD, PhD","doi":"10.1016/j.jtocrr.2025.100940","DOIUrl":"10.1016/j.jtocrr.2025.100940","url":null,"abstract":"<div><h3>Introduction</h3><div>Stereotactic ablative radiotherapy (SABR) is routinely used in patients with early stage NSCLC who are not candidates for surgery. Despite excellent local tumor control, it is associated with a high rate of regional and distant recurrences. Combining stereotactic radiotherapy with PD-1 inhibitors has demonstrated encouraging results for patients with curative intent, but how it affects the tumor microenvironment and pathologic response remains unclear.</div></div><div><h3>Methods</h3><div>We designed a phase II, open-label, single-arm study aimed to evaluate the efficacy and safety of neoadjuvant nivolumab combined with SABR in patients with NSCLC measuring up to 4 cm, without positive lymph nodes. Patients were required to be eligible for surgery, with adequate pulmonary and cardiovascular function. Nivolumab was administered at 360 mg every 21 days for three doses, combined with SABR, which was initiated concomitantly with the first cycle. Patients subsequently underwent surgical resection 10 weeks after the last dose of radiation. The primary end point was the pathologic complete response (pCR) rate at surgery. Secondary end points included major pathologic response (MPR) rate, safety, event-free survival, and overall survival at 12 months and a comprehensive biomarker analysis.</div></div><div><h3>Results</h3><div>A total of 25 patients were enrolled between November 2019 and February 2022. The mean age was 68 years, and 68% were female. The mean tumor size at baseline was 2.47 cm. A total of 24 patients fully completed the experimental therapy and proceeded with surgery. The primary end point of pCR was achieved by 19 of 24 patients (79.2%; 95% confidence interval: 57%–92%, <em>p</em> value 0.0875, in the per-protocol analysis). MPR was observed in 20 cases (83.3%; 95% confidence interval: 61.8%–94%). Four patients have not achieved an MPR, with one of them presenting with 100% residual viable tumor. No patient relapsed to date, with 12-month event-free survival and overall survival of 84%, with median not reached for both. One patient died from alcoholic hepatitis, unrelated to the treatment, and did not undergo resection. Two patients died from surgical complications.</div></div><div><h3>Conclusions</h3><div>The neoadjuvant combination of three doses of nivolumab and SABR produced a high pCR rate in stage I NSCLC. Further research is warranted to evaluate this treatment modality in patients with medically inoperable NSCLC and whether surgery could be safely omitted for patients who are candidates for resection.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 2","pages":"Article 100940"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078905","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 : 2026-02-01Epub Date: 2025-12-13DOI: 10.1016/j.jtocrr.2025.100942
Matthew Aizpuru MD , Jennifer M. Boland MD , Brendan W. Lunn MD , Sahar A. Saddoughi MD, PhD , K. Robert Shen MD , Stephen D. Cassivi MD , Dennis A. Wigle MD , Janani S. Reisenauer MD , Luis F. Tapias MD
Objectives
Risk stratification of pleuropulmonary solitary fibrous tumors (SFTs) is based on post-resection histopathologic scoring systems. We queried whether preoperative 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) maximum standardized uptake values (SUVmax) had prognostic value for recurrence or metastasis.
Methods
Retrospective review of patients who underwent FDG-PET/CT before resection of SFT between January 2002 and June 2023. Independent review of slides by a pulmonary pathologist and radiologist review of FDG-PET/CT were performed. Statistical analyses included nonparametric tests for correlations, receiver-operating characteristic (ROC) curves, and Kaplan-Meier analysis.
Results
There were 34 patients with a preoperative FDG-PET/CT before SFT resection. Median tumor SUVmax was 2.3 (range: 0.9–38.7). Recurrence occurred in five patients (14.7%) (three local, two metastatic). Tumor SUVmax was associated with tumor size (p < 0.001), parietal pleural origin (p = 0.027), hypercellularity (p = 0.049), mitoses (p < 0.001), and Ki67 (p = 0.015). SUVmax correlated with the modified Demicco score (p < 0.001) and Tapias score (p < 0.001). Prediction of recurrence was excellent with SUVmax (area under ROC curve [AUC] = 0.872, p < 0.001), Tapias score (AUC = 0.914, p < 0.001), and modified Demicco score (AUC = 0.821, p < 0.001). Time-dependent ROC analysis identified SUVmax more than or equal to 2.4 as high risk for recurrence. Recurrence-free survival at 1, 3, 5, and 10 years was 92.9%, 83.6%, 69.6%, and 46.4%, respectively, in patients with SUVmax more than or equal to 2.4, but it was 100% at all time points with SUVmax less than 2.4 (p = 0.002). SUVmax was not associated with overall survival in this small cohort.
Conclusions
Tumor metabolic activity on FDG-PET/CT is predictive of SFT recurrence. Preoperative SUVmax correlates with known histopathologic high-risk features and validated risk scores. Preoperative FDG-PET/CT should be performed before SFT resection to assist in prognostication.
{"title":"FDG-PET/CT SUVmax Predicts Recurrence Risk of Resected Pleuropulmonary Solitary Fibrous Tumors","authors":"Matthew Aizpuru MD , Jennifer M. Boland MD , Brendan W. Lunn MD , Sahar A. Saddoughi MD, PhD , K. Robert Shen MD , Stephen D. Cassivi MD , Dennis A. Wigle MD , Janani S. Reisenauer MD , Luis F. Tapias MD","doi":"10.1016/j.jtocrr.2025.100942","DOIUrl":"10.1016/j.jtocrr.2025.100942","url":null,"abstract":"<div><h3>Objectives</h3><div>Risk stratification of pleuropulmonary solitary fibrous tumors (SFTs) is based on post-resection histopathologic scoring systems. We queried whether preoperative 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) maximum standardized uptake values (SUVmax) had prognostic value for recurrence or metastasis.</div></div><div><h3>Methods</h3><div>Retrospective review of patients who underwent FDG-PET/CT before resection of SFT between January 2002 and June 2023. Independent review of slides by a pulmonary pathologist and radiologist review of FDG-PET/CT were performed. Statistical analyses included nonparametric tests for correlations, receiver-operating characteristic (ROC) curves, and Kaplan-Meier analysis.</div></div><div><h3>Results</h3><div>There were 34 patients with a preoperative FDG-PET/CT before SFT resection. Median tumor SUVmax was 2.3 (range: 0.9–38.7). Recurrence occurred in five patients (14.7%) (three local, two metastatic). Tumor SUVmax was associated with tumor size (<em>p</em> < 0.001), parietal pleural origin (<em>p</em> = 0.027), hypercellularity (<em>p</em> = 0.049), mitoses (<em>p</em> < 0.001), and Ki67 (<em>p</em> = 0.015). SUVmax correlated with the modified Demicco score (<em>p</em> < 0.001) and Tapias score (<em>p</em> < 0.001). Prediction of recurrence was excellent with SUVmax (area under ROC curve [AUC] = 0.872, <em>p</em> < 0.001), Tapias score (AUC = 0.914, <em>p</em> < 0.001), and modified Demicco score (AUC = 0.821, <em>p</em> < 0.001). Time-dependent ROC analysis identified SUVmax more than or equal to 2.4 as high risk for recurrence. Recurrence-free survival at 1, 3, 5, and 10 years was 92.9%, 83.6%, 69.6%, and 46.4%, respectively, in patients with SUVmax more than or equal to 2.4, but it was 100% at all time points with SUVmax less than 2.4 (<em>p</em> = 0.002). SUVmax was not associated with overall survival in this small cohort.</div></div><div><h3>Conclusions</h3><div>Tumor metabolic activity on FDG-PET/CT is predictive of SFT recurrence. Preoperative SUVmax correlates with known histopathologic high-risk features and validated risk scores. Preoperative FDG-PET/CT should be performed before SFT resection to assist in prognostication.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 2","pages":"Article 100942"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980965","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 : 2026-01-01Epub Date: 2025-10-29DOI: 10.1016/j.jtocrr.2025.100928
Adele Bonato MD , Claudia Parisi MD , Priscilla Cascetta MD , Anna Reni MD , May-Lucie Meyer MD , Mariona Riudavets MD, PhD , David Planchard MD, PhD , Benjamin Besse MD, PhD , Jordi Remon MD , Francesco Facchinetti MD, PhD , Lorenzo Belluomini MD, PhD , Lisa Derosa MD, PhD , Fabrice Barlesi MD, PhD
Background
Although most phase III pivotal trials have set the duration of immune checkpoint blockers (ICB) for advanced NSCLC at 2 years, the criteria for safely discontinuing ICB remain undefined. Growing evidence links ICB efficacy to gut microbiota, positioning gut microbial taxonomic profiling as a promising biomarker to guide treatment decisions. We performed a retrospective analysis exploring clinical outcomes and the utility of multiomic decision-making tools in patients with NSCLC at Gustave Roussy who completed 24 months of ICB-based therapy without disease progression (PD).
Methods
Patients receiving ICB between July 2016 and January 2023 were identified from the ONCOBIOTICS (NCT04567446) and STING (NCT04932525) study datasets. We selected those who reached 24 months of treatment without disease progression. Clinical characteristics and multiomic assessments, including gut microbiota profiling (TOPOSCORE by whole-genome sequencing), positron emission tomography–18-fluorodeoxyglucose imaging, and circulating tumor DNA, collected at 24 months, were analyzed. Key outcomes included overall survival (OS), progression-free survival (PFS), and PFS rates at 24 months after the completion of 2 years of ICB, stratified by molecular, metabolic, and microbial signatures.
Results
Out of 123 patients treated for at least 18 months, 35 completed 24 months, with 31 eligible for the analysis. Of these, 68% continued ICB, whereas 32% discontinued therapy at the physician’s decision. Clinical characteristics were similar across groups. After a median follow-up of 59.1 months, OS and PFS did not differ significantly between those who discontinued and those who continued treatment (OS p = 0.9012). Among all multiomic tools, gut microbiota composition exhibited a trend (though not statistically significant) association with PFS rates at 24 months after the completion of 2 years of ICB. Patients with a favorable microbiota profile had a higher rate of sustained response at 24 months compared with those with dysbiotic signatures (81% versus 44%, respectively, p = 0.0870).
Conclusions
Discontinuing ICB after 24 months did not negatively impact OS in our real-world cohort. Although limited by the small sample size, these findings support the potential of gut microbiota profiling as a promising tool to guide ICB duration. Integrating a translational multiomic algorithm, in particular microbial signals, may help personalize treatment strategies and safely shorten immunotherapy courses.
尽管大多数III期关键试验已将晚期NSCLC的免疫检查点阻断剂(ICB)的持续时间设定为2年,但安全停用ICB的标准仍未明确。越来越多的证据表明ICB疗效与肠道微生物群有关,将肠道微生物分类分析定位为指导治疗决策的有前途的生物标志物。我们进行了一项回顾性分析,探讨了Gustave Roussy非小细胞肺癌患者的临床结果和多组决策工具的实用性,这些患者完成了24个月的基于icb的无疾病进展(PD)治疗。方法从ONCOBIOTICS (NCT04567446)和STING (NCT04932525)研究数据集中筛选出2016年7月至2023年1月接受ICB治疗的患者。我们选择了那些治疗24个月无疾病进展的患者。临床特征和多组学评估,包括肠道微生物群分析(全基因组测序TOPOSCORE),正电子发射断层扫描- 18-氟脱氧葡萄糖成像,以及24个月时收集的循环肿瘤DNA进行分析。主要结局包括总生存期(OS)、无进展生存期(PFS)和完成2年ICB后24个月的PFS率,并根据分子、代谢和微生物特征进行分层。结果123例患者治疗至少18个月,35例完成24个月,其中31例符合分析条件。其中,68%的患者继续进行ICB治疗,而32%的患者在医生的决定下停止治疗。各组临床特征相似。中位随访59.1个月后,停止治疗组和继续治疗组的OS和PFS无显著差异(OS p = 0.9012)。在所有多组学工具中,在完成2年ICB后的24个月,肠道微生物群组成与PFS率显示出趋势(尽管没有统计学意义)。具有良好微生物群特征的患者在24个月时的持续缓解率高于具有不良微生物群特征的患者(分别为81%对44%,p = 0.0870)。结论:在我们的真实队列中,24个月后停用ICB对OS没有负面影响。尽管受样本量小的限制,这些发现支持肠道微生物群分析作为指导ICB持续时间的有前途的工具的潜力。整合翻译多组算法,特别是微生物信号,可能有助于个性化治疗策略和安全地缩短免疫治疗疗程。
{"title":"Gut Dysbiosis as a Potential Guide for Immunotherapy (Dis)Continuation After 2 Years in NSCLC: A Brief Report","authors":"Adele Bonato MD , Claudia Parisi MD , Priscilla Cascetta MD , Anna Reni MD , May-Lucie Meyer MD , Mariona Riudavets MD, PhD , David Planchard MD, PhD , Benjamin Besse MD, PhD , Jordi Remon MD , Francesco Facchinetti MD, PhD , Lorenzo Belluomini MD, PhD , Lisa Derosa MD, PhD , Fabrice Barlesi MD, PhD","doi":"10.1016/j.jtocrr.2025.100928","DOIUrl":"10.1016/j.jtocrr.2025.100928","url":null,"abstract":"<div><h3>Background</h3><div>Although most phase III pivotal trials have set the duration of immune checkpoint blockers (ICB) for advanced NSCLC at 2 years, the criteria for safely discontinuing ICB remain undefined. Growing evidence links ICB efficacy to gut microbiota, positioning gut microbial taxonomic profiling as a promising biomarker to guide treatment decisions. We performed a retrospective analysis exploring clinical outcomes and the utility of multiomic decision-making tools in patients with NSCLC at Gustave Roussy who completed 24 months of ICB-based therapy without disease progression (PD).</div></div><div><h3>Methods</h3><div>Patients receiving ICB between July 2016 and January 2023 were identified from the ONCOBIOTICS (NCT04567446) and STING (NCT04932525) study datasets. We selected those who reached 24 months of treatment without disease progression. Clinical characteristics and multiomic assessments, including gut microbiota profiling (TOPOSCORE by whole-genome sequencing), positron emission tomography–18-fluorodeoxyglucose imaging, and circulating tumor DNA, collected at 24 months, were analyzed. Key outcomes included overall survival (OS), progression-free survival (PFS), and PFS rates at 24 months after the completion of 2 years of ICB, stratified by molecular, metabolic, and microbial signatures.</div></div><div><h3>Results</h3><div>Out of 123 patients treated for at least 18 months, 35 completed 24 months, with 31 eligible for the analysis. Of these, 68% continued ICB, whereas 32% discontinued therapy at the physician’s decision. Clinical characteristics were similar across groups. After a median follow-up of 59.1 months, OS and PFS did not differ significantly between those who discontinued and those who continued treatment (OS <em>p</em> = 0.9012). Among all multiomic tools, gut microbiota composition exhibited a trend (though not statistically significant) association with PFS rates at 24 months after the completion of 2 years of ICB. Patients with a favorable microbiota profile had a higher rate of sustained response at 24 months compared with those with dysbiotic signatures (81% versus 44%, respectively, <em>p</em> = 0.0870).</div></div><div><h3>Conclusions</h3><div>Discontinuing ICB after 24 months did not negatively impact OS in our real-world cohort. Although limited by the small sample size, these findings support the potential of gut microbiota profiling as a promising tool to guide ICB duration. Integrating a translational multiomic algorithm, in particular microbial signals, may help personalize treatment strategies and safely shorten immunotherapy courses.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 1","pages":"Article 100928"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798012","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}
Preoperative immune-related adverse events (irAEs) during neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer (NSCLC) remain poorly characterized. We aimed to evaluate their frequency, clinical impact, and associated risk factors.
Methods
This prespecified subanalysis of the multicenter CReGYT-04 Neo-Venus study retrospectively examined 130 patients with resectable NSCLC (stage IIA-IIIB, Union for International Cancer Control, eighth edition) treated with neoadjuvant nivolumab plus platinum-doublet chemotherapy. Clinical data were collected from 29 Japanese institutions. Patients were stratified according to the presence or absence of preoperative irAEs. Exploratory logistic regression was used to identify predictive factors.
Results
Preoperative irAEs were observed in 18.5% of the patients (n = 24). Patients with irAEs had a significantly lower neoadjuvant therapy completion rate (58.3% versus 92.5%, p <0.001) and a higher incidence of cancelled surgery (21.7% versus 5.8%, p = 0.029) than those without irAEs. There were 18 patients (78.3%) with irAEs who underwent surgical resection. R0 resection was achieved in 94.4%. The postoperative complication rates and length of hospital stay were comparable between the groups. The major pathologic response rate (38.9% versus 63.1%) and pathologic complete response rate (27.8% versus 36.8%) were lower in patients with preoperative irAEs. Tumor size greater than 3.8 cm and eosinophil fraction greater than or equal to 2.0% were identified as exploratory predictors of preoperative irAEs.
Conclusion
Preoperative irAEs occurred in approximately 20% of patients with resectable NSCLC treated with neoadjuvant nivolumab plus chemotherapy and were associated with treatment discontinuation and cancellation of surgery. Nevertheless, curative-intent surgery remained feasible and achieved acceptable perioperative outcomes in most patients with preoperative irAEs.
在可切除的非小细胞肺癌(NSCLC)的新辅助化疗免疫治疗期间,术前免疫相关不良事件(irAEs)的特征仍然很差。我们的目的是评估其发生频率、临床影响和相关危险因素。方法:这项预先指定的多中心CReGYT-04 Neo-Venus研究回顾性分析了130例接受新辅助纳武单抗加铂双药化疗的可切除非小细胞肺癌(iiia - iiib期,国际癌症控制联盟,第八版)患者。临床数据收集自日本29家机构。根据术前是否有irae对患者进行分层。采用探索性逻辑回归确定预测因素。结果24例患者(18.5%)术后出现irae。irAEs患者的新辅助治疗完成率(58.3% vs . 92.5%, p <0.001)明显低于无irAEs患者,而取消手术的发生率(21.7% vs . 5.8%, p = 0.029)高于无irAEs患者。有18例(78.3%)的irae患者接受了手术切除。R0切除率为94.4%。术后并发症发生率和住院时间在两组间具有可比性。术前irae患者的主要病理缓解率(38.9%对63.1%)和病理完全缓解率(27.8%对36.8%)较低。肿瘤大小大于3.8 cm和嗜酸性粒细胞分数大于或等于2.0%被确定为术前irae的探索性预测因子。结论在接受新辅助纳武单抗加化疗的可切除NSCLC患者中,约20%的患者发生了术前irae,并且与治疗停止和手术取消有关。尽管如此,以治愈为目的的手术仍然是可行的,并且在大多数术前irae患者中获得了可接受的围手术期结果。
{"title":"Preoperative Immune-Related Adverse Events in Resectable NSCLC Treated With Neoadjuvant Nivolumab Plus Chemotherapy: A Multicenter Retrospective Analysis","authors":"Takuya Watanabe MD , Kotaro Nomura MD , Shinkichi Takamori MD , Shinya Tane MD , Shuta Ohara MD , Hana Oiki MD , Shinya Katsumata MD , Makoto Endo MD , Satoshi Takamori MD , Marina Nakatsuka MD , Hironori Tenpaku MD , Ryuji Nakamura MD , Hirotsugu Notsuda MD , Kei Namba MD , Kentaro Minegishi MD , Masayuki Tanahashi MD , Masahiro Tsuboi MD , Junichi Soh MD , Mototsugu Shimokawa MD , Yasuhisa Ohde MD","doi":"10.1016/j.jtocrr.2025.100930","DOIUrl":"10.1016/j.jtocrr.2025.100930","url":null,"abstract":"<div><h3>Introduction</h3><div>Preoperative immune-related adverse events (irAEs) during neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer (NSCLC) remain poorly characterized. We aimed to evaluate their frequency, clinical impact, and associated risk factors.</div></div><div><h3>Methods</h3><div>This prespecified subanalysis of the multicenter CReGYT-04 Neo-Venus study retrospectively examined 130 patients with resectable NSCLC (stage IIA-IIIB, Union for International Cancer Control, eighth edition) treated with neoadjuvant nivolumab plus platinum-doublet chemotherapy. Clinical data were collected from 29 Japanese institutions. Patients were stratified according to the presence or absence of preoperative irAEs. Exploratory logistic regression was used to identify predictive factors.</div></div><div><h3>Results</h3><div>Preoperative irAEs were observed in 18.5% of the patients (n = 24). Patients with irAEs had a significantly lower neoadjuvant therapy completion rate (58.3% versus 92.5%, <em>p</em> <0.001) and a higher incidence of cancelled surgery (21.7% versus 5.8%, <em>p</em> = 0.029) than those without irAEs. There were 18 patients (78.3%) with irAEs who underwent surgical resection. R0 resection was achieved in 94.4%. The postoperative complication rates and length of hospital stay were comparable between the groups. The major pathologic response rate (38.9% versus 63.1%) and pathologic complete response rate (27.8% versus 36.8%) were lower in patients with preoperative irAEs. Tumor size greater than 3.8 cm and eosinophil fraction greater than or equal to 2.0% were identified as exploratory predictors of preoperative irAEs.</div></div><div><h3>Conclusion</h3><div>Preoperative irAEs occurred in approximately 20% of patients with resectable NSCLC treated with neoadjuvant nivolumab plus chemotherapy and were associated with treatment discontinuation and cancellation of surgery. Nevertheless, curative-intent surgery remained feasible and achieved acceptable perioperative outcomes in most patients with preoperative irAEs.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 1","pages":"Article 100930"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798011","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}