Pub Date : 2025-11-01DOI: 10.1016/j.jtocrr.2025.100879
Sheng-Han Tsai MD , Jui-Hung Tsai MD , Li-Jun Chen MS , Szu-Chun Yang MD, PhD
Introduction
In the ADRIATIC trial, durvalumab consolidation therapy improved the overall survival and progression-free survival of patients with limited-stage SCLC responding to chemoradiotherapy. Based on the data, we aim to assess the cost-effectiveness of the therapy from the perspective of the Taiwanese health care sector.
Methods
Simulated patients with limited-stage SCLC responding to chemoradiotherapy were entered into a partitioned survival model comparing durvalumab consolidation with no consolidation therapy. The model inputs were derived from the ADRIATIC trial (survival outcomes, adverse events, and subsequent therapies), National Health Insurance payments (costs of physician visits, monitoring, drug administration, and end-of-life care), and the hospital cohort (utility values). A lifetime horizon and annual discount rate of 3% were applied. Subgroup, one-way deterministic, and probabilistic analyses were performed.
Results
Durvalumab consolidation therapy incurred an additional $91,734 USD and brought about 0.90 quality-adjusted life years (QALYs) gained, resulting in an incremental cost-effectiveness ratio (ICER) of $101,734 USD per QALY. The ICER remained higher than the willingness-to-pay threshold of $70,000 USD per QALY across most patient subgroups. The most influential factor for the ICER was the cost of durvalumab. If the 4-week drug cost could be reduced to $3893 USD, the ICER would fall below 70,000 USD per QALY. At the willingness-to-pay threshold, durvalumab consolidation therapy had a probability of 0.3% being cost-effective.
Conclusions
Our analysis suggests that durvalumab consolidation therapy is not cost-effective for patients with limited-stage SCLC. Reducing the price of the therapy enhances cost-effectiveness.
{"title":"Cost-Effectiveness of Durvalumab After Chemoradiotherapy in Limited-Stage SCLC","authors":"Sheng-Han Tsai MD , Jui-Hung Tsai MD , Li-Jun Chen MS , Szu-Chun Yang MD, PhD","doi":"10.1016/j.jtocrr.2025.100879","DOIUrl":"10.1016/j.jtocrr.2025.100879","url":null,"abstract":"<div><h3>Introduction</h3><div>In the ADRIATIC trial, durvalumab consolidation therapy improved the overall survival and progression-free survival of patients with limited-stage SCLC responding to chemoradiotherapy. Based on the data, we aim to assess the cost-effectiveness of the therapy from the perspective of the Taiwanese health care sector.</div></div><div><h3>Methods</h3><div>Simulated patients with limited-stage SCLC responding to chemoradiotherapy were entered into a partitioned survival model comparing durvalumab consolidation with no consolidation therapy. The model inputs were derived from the ADRIATIC trial (survival outcomes, adverse events, and subsequent therapies), National Health Insurance payments (costs of physician visits, monitoring, drug administration, and end-of-life care), and the hospital cohort (utility values). A lifetime horizon and annual discount rate of 3% were applied. Subgroup, one-way deterministic, and probabilistic analyses were performed.</div></div><div><h3>Results</h3><div>Durvalumab consolidation therapy incurred an additional $91,734 USD and brought about 0.90 quality-adjusted life years (QALYs) gained, resulting in an incremental cost-effectiveness ratio (ICER) of $101,734 USD per QALY. The ICER remained higher than the willingness-to-pay threshold of $70,000 USD per QALY across most patient subgroups. The most influential factor for the ICER was the cost of durvalumab. If the 4-week drug cost could be reduced to $3893 USD, the ICER would fall below 70,000 USD per QALY. At the willingness-to-pay threshold, durvalumab consolidation therapy had a probability of 0.3% being cost-effective.</div></div><div><h3>Conclusions</h3><div>Our analysis suggests that durvalumab consolidation therapy is not cost-effective for patients with limited-stage SCLC. Reducing the price of the therapy enhances cost-effectiveness.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100879"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425160","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}
Immunotherapy has revolutionized the treatment of NSCLC. However, trials that led to approval of these agents and ongoing trials often include overly included overly restrictive exclusion criteria, limiting access for a significant proportion of patients. We propose the immunotherapy clinical trial inclusivity score (ICTIS), a scoring system to evaluate trial eligibility criteria for inclusivity.
Methods
ICTIS was developed using national guidelines and validated with a Cohen’s Kappa statistics of 0.807. Eligibility criteria for advanced NSCLC immunotherapy trials on ClinicalTrials.gov were scored using a binary scale (0 = exclusive, 1 = inclusive), with higher summed scores indicating higher inclusivity. Mean ICTIS scores were compared across lines of treatment, start date, and trial phase.
Results
The mean ICTIS score among 142 trials was 12.7 (SD 4), with 28 trials (19.7%) rated as excellent and 34 trials (23.9%) rated poor. The most restrictive criteria were Eastern Cooperative Oncology Group performance status (78.8%), organ function criteria of bilirubin (76.1%), and absolute neutrophil count (65.5%). First-line trials were significantly more exclusive to patients with pneumonitis history, with 64% exclusion versus 45.5% in second-line (χ2 = 4.917, p = 0.027). The platelet count requirement was more stringent in monotherapy trials. Inclusion of treated leptomeningeal disease improved over time (χ2 = 7.99, p = 0.018), but eligibility criteria remained consistent across different time periods, lines of treatment, and trial phases.
Conclusions
Despite the release of national guidelines, immunotherapy trials have overall retained restrictive eligibility criteria. ICTIS provides a standardized framework for evaluating inclusivity and can assist in designing immunotherapy studies to be more inclusive.
免疫疗法已经彻底改变了非小细胞肺癌的治疗。然而，导致这些药物获得批准的试验和正在进行的试验通常包括过度纳入过于严格的排除标准，限制了很大一部分患者的使用。我们提出了免疫治疗临床试验包容性评分（ICTIS），这是一个评估试验包容性资格标准的评分系统。方法sictis采用国家指南开发，采用0.807的Cohen’s Kappa统计量进行验证。临床试验网站ClinicalTrials.gov上晚期NSCLC免疫治疗试验的资格标准采用二元评分（0 =排他，1 =包容），总得分越高，包容性越高。比较不同治疗线、开始日期和试验阶段的平均ICTIS评分。结果142项试验的ICTIS平均评分为12.7 (SD 4)，其中优28项（19.7%），差34项（23.9%）。最严格的标准是东部肿瘤合作组表现状态（78.8%）、胆红素器官功能标准（76.1%）和绝对中性粒细胞计数（65.5%）。一线试验对有肺炎史的患者的排他性更高，排他性为64%，二线试验为45.5% （χ2 = 4.917, p = 0.027）。单药治疗试验对血小板计数的要求更为严格。随着时间的推移，治疗后的轻脑膜疾病的纳入情况有所改善（χ2 = 7.99, p = 0.018），但不同时间段、治疗线和试验阶段的入选标准保持一致。尽管发布了国家指南，但免疫治疗试验总体上保留了限制性的资格标准。ICTIS提供了一个评估包容性的标准化框架，可以帮助设计更具包容性的免疫治疗研究。
{"title":"ICTIS: A Novel Scoring System to Assess the Inclusivity of Advanced NSCLC Immunotherapy Trials","authors":"Kira Nguyen , Ashley Wei , Srinivas Govindan MD , Eziafa Oduah MD, PhD , Nagashree Seetharamu MD , Wint Yan Aung MD","doi":"10.1016/j.jtocrr.2025.100878","DOIUrl":"10.1016/j.jtocrr.2025.100878","url":null,"abstract":"<div><h3>Introduction</h3><div>Immunotherapy has revolutionized the treatment of NSCLC. However, trials that led to approval of these agents and ongoing trials often include overly included overly restrictive exclusion criteria, limiting access for a significant proportion of patients. We propose the immunotherapy clinical trial inclusivity score (ICTIS), a scoring system to evaluate trial eligibility criteria for inclusivity.</div></div><div><h3>Methods</h3><div>ICTIS was developed using national guidelines and validated with a Cohen’s Kappa statistics of 0.807. Eligibility criteria for advanced NSCLC immunotherapy trials on <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> were scored using a binary scale (0 = exclusive, 1 = inclusive), with higher summed scores indicating higher inclusivity. Mean ICTIS scores were compared across lines of treatment, start date, and trial phase.</div></div><div><h3>Results</h3><div>The mean ICTIS score among 142 trials was 12.7 (SD 4), with 28 trials (19.7%) rated as excellent and 34 trials (23.9%) rated poor. The most restrictive criteria were Eastern Cooperative Oncology Group performance status (78.8%), organ function criteria of bilirubin (76.1%), and absolute neutrophil count (65.5%). First-line trials were significantly more exclusive to patients with pneumonitis history, with 64% exclusion versus 45.5% in second-line (χ<sup>2</sup> = 4.917, <em>p</em> = 0.027). The platelet count requirement was more stringent in monotherapy trials. Inclusion of treated leptomeningeal disease improved over time (χ<sup>2</sup> = 7.99, <em>p</em> = 0.018), but eligibility criteria remained consistent across different time periods, lines of treatment, and trial phases.</div></div><div><h3>Conclusions</h3><div>Despite the release of national guidelines, immunotherapy trials have overall retained restrictive eligibility criteria. ICTIS provides a standardized framework for evaluating inclusivity and can assist in designing immunotherapy studies to be more inclusive.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100878"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425195","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 : 2025-10-30DOI: 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":"2025-10-30","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}
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":"2025-10-30","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}
Pub Date : 2025-10-30DOI: 10.1016/j.jtocrr.2025.100927
Van-Anh Nguyen Hoang MSc , Ngoc Nguyen BSc , Tu Nguyen MSc , Duy Sinh Nguyen MD, PhD , Hoai-Nghia Nguyen PhD , Lan N. Tu PhD
Background
Circulating tumor DNA (ctDNA) is a promising prognostic biomarker in early-stage NSCLC. The typical tumor-informed method of ctDNA testing requires tissue specimens of high quality, which is a challenge in developing countries. Tumor-naive approach is an alternative, but the performance of the two methods has not been directly compared using the same samples and platform.
Methods
We retrospectively analyzed tumor and blood samples of patients with early-stage NSCLC enrolled in our published study. For analytical performance, pretreatment samples of 42 patients and 50 healthy donors were used to assess the accuracy of ctDNA detection. For clinical performance, 176 postsurgical blood samples of 76 patients with NSCLC were analyzed to compare the ctDNA status with recorded clinical recurrence. The tumor-informed method evaluated personalized mutations and a fixed 500-hotspot panel, whereas the tumor-naive method combined predesigned mutation panels and nonmutation genome-wide features of ctDNA.
Results
The tumor-informed assay had 66.7% sensitivity and 99.3% specificity for detecting ctDNA in early-stage NSCLC, higher than the tumor-naive assay with 52.6% sensitivity and 95.7% specificity. Postsurgical ctDNA status determined by both methods had significant prognostic value to predict recurrence ahead of clinical diagnosis (hazard ratio >100, p < 0.0001). Tumor-informed ctDNA achieved 86.7% sensitivity to detect recurrence, and the 500-hotspot panel improved the ctDNA detection rate for cases with suboptimal tissue specimens. Tumor-naive ctDNA had 80.0% sensitivity to detect recurrence, and integration of nonmutation features was crucial.
Conclusions
Both methods exhibited high accuracy in detecting residual cancer in NSCLC. The tumor-naive approach is a reliable alternative when high-quality tissue specimens are unavailable.
循环肿瘤DNA （ctDNA）是早期非小细胞肺癌预后的一种有前景的生物标志物。典型的肿瘤知情ctDNA检测方法需要高质量的组织标本，这在发展中国家是一个挑战。肿瘤初始方法是一种替代方法，但使用相同的样本和平台，两种方法的性能尚未直接进行比较。方法回顾性分析纳入本研究的早期非小细胞肺癌患者的肿瘤和血液样本。为了分析性能，使用42名患者和50名健康供体的预处理样本来评估ctDNA检测的准确性。在临床表现方面，我们分析了76例NSCLC患者的176份术后血液样本，将ctDNA状态与临床复发记录进行比较。肿瘤知情方法评估个性化突变和固定的500个热点面板，而肿瘤初始方法结合了预先设计的突变面板和ctDNA的非突变全基因组特征。结果肿瘤知情法检测早期NSCLC ctDNA的灵敏度为66.7%，特异性为99.3%，高于肿瘤未知情法检测ctDNA的灵敏度为52.6%，特异性为95.7%。两种方法检测的术后ctDNA状态对临床诊断前预测复发具有显著的预后价值（风险比>；100, p < 0.0001）。肿瘤知情ctDNA检测复发的敏感性达到86.7%，500热点面板提高了组织标本次优病例的ctDNA检出率。肿瘤初始ctDNA检测复发的敏感性为80.0%，非突变特征的整合至关重要。结论两种方法对非小细胞肺癌残留癌的检测准确率较高。当无法获得高质量的组织标本时，肿瘤原位方法是一种可靠的替代方法。
{"title":"Direct Comparison of Tumor-Informed and Tumor-Naive Circulating Tumor DNA Assays for Recurrence Detection in Early-Stage NSCLC","authors":"Van-Anh Nguyen Hoang MSc , Ngoc Nguyen BSc , Tu Nguyen MSc , Duy Sinh Nguyen MD, PhD , Hoai-Nghia Nguyen PhD , Lan N. Tu PhD","doi":"10.1016/j.jtocrr.2025.100927","DOIUrl":"10.1016/j.jtocrr.2025.100927","url":null,"abstract":"<div><h3>Background</h3><div>Circulating tumor DNA (ctDNA) is a promising prognostic biomarker in early-stage NSCLC. The typical tumor-informed method of ctDNA testing requires tissue specimens of high quality, which is a challenge in developing countries. Tumor-naive approach is an alternative, but the performance of the two methods has not been directly compared using the same samples and platform.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed tumor and blood samples of patients with early-stage NSCLC enrolled in our published study. For analytical performance, pretreatment samples of 42 patients and 50 healthy donors were used to assess the accuracy of ctDNA detection. For clinical performance, 176 postsurgical blood samples of 76 patients with NSCLC were analyzed to compare the ctDNA status with recorded clinical recurrence. The tumor-informed method evaluated personalized mutations and a fixed 500-hotspot panel, whereas the tumor-naive method combined predesigned mutation panels and nonmutation genome-wide features of ctDNA.</div></div><div><h3>Results</h3><div>The tumor-informed assay had 66.7% sensitivity and 99.3% specificity for detecting ctDNA in early-stage NSCLC, higher than the tumor-naive assay with 52.6% sensitivity and 95.7% specificity. Postsurgical ctDNA status determined by both methods had significant prognostic value to predict recurrence ahead of clinical diagnosis (hazard ratio >100, <em>p</em> < 0.0001). Tumor-informed ctDNA achieved 86.7% sensitivity to detect recurrence, and the 500-hotspot panel improved the ctDNA detection rate for cases with suboptimal tissue specimens. Tumor-naive ctDNA had 80.0% sensitivity to detect recurrence, and integration of nonmutation features was crucial.</div></div><div><h3>Conclusions</h3><div>Both methods exhibited high accuracy in detecting residual cancer in NSCLC. The tumor-naive approach is a reliable alternative when high-quality tissue specimens are unavailable.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 1","pages":"Article 100927"},"PeriodicalIF":3.5,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798010","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 : 2025-10-29DOI: 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":"2025-10-29","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}
Pub 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":"2025-10-27","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 : 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":"2025-10-27","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 : 2025-10-23DOI: 10.1016/j.jtocrr.2025.100921
Jurriaan Janssen MSc , Bárbara Andrade Barbosa MSc , Tim R. Mocking MSc , Hendrik F. van Essen MA , Paul P. Eijk BSc , Jacqueline Egthuijsen BSc , Anabela Ferro PhD , Jose-Pedro Parracha de Matos MSc , Swip Draijer PhD , Albrecht Stenzinger Dr. (Prof.) , Anke van den Berg Dr. (Prof.) , José Carlos Machado Dr. (Prof.) , Erik Thunnissen PhD , Yongsoo Kim PhD , Teodora Radonic PhD , Bauke Ylstra Dr. (Prof.)
Introduction
The incidence of patients presenting with multiple cancers (MCs) and pulmonary involvement is increasing. Although next-generation sequencing mutation panels can discern metastases (clonal) from separate primary cancers (nonclonal), it does not warrant a reliable diagnosis for all patients despite significant therapeutic implications. We evaluated the added value of genome-wide copy number aberrations (CNAs) for clonality diagnosis.
Methods
Two cohorts were assembled: 41 clonal and 41 nonclonal pairs from the TRACERx cohort and 21 MC pairs that had sufficient DNA for whole-exome sequencing (WES) from 120 patients diagnosed using CNA analysis in our routine pathology practice between 2016 and 2022. Clonality was determined by comparing tumor pairs using (1) WES mutations as a definitive standard, (2) a conventional mutation panel with an adapted 2024 International Association for the Study of Lung Cancer algorithm, and (3) CNAs with log-likelihood ratio and Pearson correlation metrics.
Results
All tumor pairs classified as definite “clonal” or “nonclonal” by mutation analysis (TRACERx: 35 of 82 [43%], MC cohort: 6 of 21 [29%]) were in concordance with WES and CNAs. Of the tumor pairs classified as “probable nonclonal” or “inconclusive” by mutation analysis (TRACERx: 47 of 82 [57%], MC cohort: 15 of 21 [71%]), most could be correctly reclassified by CNAs (TRACERx: 46 of 47 [98%], MC cohort: 15 of 16 [94%]). For each cohort, one tumor pair remained inconclusive. Furthermore, we present a CNA clonality workflow for implementation in molecular diagnostics.
Conclusion
Genome-wide CNA analysis provides complementary information to resolve clonality of MCs with ambiguous mutational clonality status, enhancing clinical decision-making.
{"title":"The Added Value of Genome-Wide Copy Numbers to Objectively Resolve Clonality of Multiple Tumors With Pulmonary Involvement and Ambiguous or Inconclusive Mutational Diagnosis","authors":"Jurriaan Janssen MSc , Bárbara Andrade Barbosa MSc , Tim R. Mocking MSc , Hendrik F. van Essen MA , Paul P. Eijk BSc , Jacqueline Egthuijsen BSc , Anabela Ferro PhD , Jose-Pedro Parracha de Matos MSc , Swip Draijer PhD , Albrecht Stenzinger Dr. (Prof.) , Anke van den Berg Dr. (Prof.) , José Carlos Machado Dr. (Prof.) , Erik Thunnissen PhD , Yongsoo Kim PhD , Teodora Radonic PhD , Bauke Ylstra Dr. (Prof.)","doi":"10.1016/j.jtocrr.2025.100921","DOIUrl":"10.1016/j.jtocrr.2025.100921","url":null,"abstract":"<div><h3>Introduction</h3><div>The incidence of patients presenting with multiple cancers (MCs) and pulmonary involvement is increasing. Although next-generation sequencing mutation panels can discern metastases (clonal) from separate primary cancers (nonclonal), it does not warrant a reliable diagnosis for all patients despite significant therapeutic implications. We evaluated the added value of genome-wide copy number aberrations (CNAs) for clonality diagnosis.</div></div><div><h3>Methods</h3><div>Two cohorts were assembled: 41 clonal and 41 nonclonal pairs from the TRACERx cohort and 21 MC pairs that had sufficient DNA for whole-exome sequencing (WES) from 120 patients diagnosed using CNA analysis in our routine pathology practice between 2016 and 2022. Clonality was determined by comparing tumor pairs using (1) WES mutations as a definitive standard, (2) a conventional mutation panel with an adapted 2024 International Association for the Study of Lung Cancer algorithm, and (3) CNAs with log-likelihood ratio and Pearson correlation metrics.</div></div><div><h3>Results</h3><div>All tumor pairs classified as definite “clonal” or “nonclonal” by mutation analysis (TRACERx: 35 of 82 [43%], MC cohort: 6 of 21 [29%]) were in concordance with WES and CNAs. Of the tumor pairs classified as “probable nonclonal” or “inconclusive” by mutation analysis (TRACERx: 47 of 82 [57%], MC cohort: 15 of 21 [71%]), most could be correctly reclassified by CNAs (TRACERx: 46 of 47 [98%], MC cohort: 15 of 16 [94%]). For each cohort, one tumor pair remained inconclusive. Furthermore, we present a CNA clonality workflow for implementation in molecular diagnostics.</div></div><div><h3>Conclusion</h3><div>Genome-wide CNA analysis provides complementary information to resolve clonality of MCs with ambiguous mutational clonality status, enhancing clinical decision-making.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100921"},"PeriodicalIF":3.5,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145576878","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 : 2025-10-15DOI: 10.1016/j.jtocrr.2025.100919
Patrick Goodley MBBChir , Matthew Evison MD
{"title":"Addressing Global Disparities in Lung Cancer Screening: Lessons From Puerto Rico and Beyond","authors":"Patrick Goodley MBBChir , Matthew Evison MD","doi":"10.1016/j.jtocrr.2025.100919","DOIUrl":"10.1016/j.jtocrr.2025.100919","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100919"},"PeriodicalIF":3.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145576880","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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