JTO Clinical and Research Reports最新文献_第2页

Safety and Efficacy of Sequential Chemoimmunotherapy Followed by Concurrent Chemoradiation in Unresectable Stage III NSCLC 序贯化学免疫治疗并发放化疗治疗不可切除III期NSCLC的安全性和有效性

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-11-01 DOI: 10.1016/j.jtocrr.2025.100890

Arthi Sridhar MD , Aditi Singh MD, MPH , Scott Hansen MD , Sydney Pulsipher MD , Kaushal Parikh MD , Aaron S. Mansfield MD , Anastasios Dimou MD , Julian R. Molina MD , Katherine E. Smith MD , Yolanda I. Garces MD , Sean S. Park MD , Aadel A. Chaudhuri MD, PhD , Kenneth W. Merrell MD , Kenneth R. Olivier MD , Konstantinos Leventakos MD , Dawn Owen MD, PhD , Mohamed Shanshal MD, MBBCh

Background

The eighth edition of the International Association for the Study of Lung Cancer staging project reports a 5-year overall survival (OS) for stage IIIA, B, and C NSCLC of 41%, 24%, and 12%, respectively, highlighting the need for improved treatment options. Induction chemotherapy and immune checkpoint inhibition (ID-chemo-ICI) followed by concurrent chemoradiation (cCRT) has not been adequately studied because of concerns about toxicity. We aim to describe the outcomes of patients with unresectable stage III NSCLC who received ID-chemo-ICI followed by cCRT with or without maintenance ICI.

Methods

We conducted a retrospective analysis of patients with unresectable stage III NSCLC who received ID-chemo-ICI with the intent to proceed with cCRT across all Mayo Clinic sites. Clinical end points included progression-free survival (PFS), OS, overall response rate per the Response Evaluation Criteria in Solid Tumors version 1.1, and treatment-related adverse events defined using Common Terminology Criteria for Adverse Events version 5.0.

Results

A total of 29 patients with unresectable stage III NSCLC, deemed unsuitable for upfront cCRT or surgery, with a plan to proceed with ID-chemo-ICI before cCRT, were identified. The median age was 66 years, 55% were male, most had a history of smoking (93.1%), and 100% identified as White. Tumor histologies were adenocarcinoma (69%), squamous cell carcinoma (24%), poorly differentiated NSCLC (3.4%), and sarcomatoid NSCLC (3.4%). Most were stage IIIB (44.8%), followed by IIIC (41.4%), and IIIA (13.8%). N2 and N3 disease were present in 37.9% and 55.2%, respectively. Programmed death-ligand 1 expression included less than 1% (n = 11, 38%), 1% to 49% (n = 9, 31%), greater than 50% (n = 5, 17%), and unknown (n = 4, 14%). Patients received ID-chemo-ICI with pembrolizumab (82.8%), nivolumab (13.8%), or atezolizumab (3.4%), with a median of four cycles. The overall response rate to ID-chemo-ICI was 93%. Of the cohort, 90% received cCRT, and 76% received maintenance ICI (pembrolizumab or durvalumab). The median PFS was 18 months, and the median OS was 24 months. Pneumonitis occurred in 37.9% (grade 1: 18.2%; grade 2: 63.6%; grade 3: 18%, no grade 4). Esophagitis occurred in 55.2% (grade 1–2: 93%; grade 3: 7%).

Conclusions

ID-chemo-ICI followed by cCRT seems feasible and safe for unresectable stage III NSCLC, particularly for patients unsuitable for upfront cCRT. Larger prospective trials are needed to validate these findings and optimize patient selection.

国际肺癌分期研究协会第八版报告称，IIIA期、B期和C期NSCLC的5年总生存率（OS）分别为41%、24%和12%，强调了改进治疗方案的必要性。诱导化疗和免疫检查点抑制（ID-chemo-ICI）随后同步放化疗（cCRT）尚未得到充分的研究，因为担心毒性。我们的目的是描述不可切除的III期NSCLC患者接受ID-chemo-ICI，然后cCRT伴或不伴维持ICI的结果。方法：我们对不可切除的III期NSCLC患者进行了回顾性分析，这些患者接受了ID-chemo-ICI，目的是在梅奥诊所的所有地点进行cCRT。临床终点包括无进展生存期（PFS）， OS，根据实体瘤1.1版反应评价标准的总缓解率，以及使用不良事件通用术语标准5.0版定义的治疗相关不良事件。结果共发现29例无法切除的III期NSCLC患者，认为不适合术前cCRT或手术，计划在cCRT前进行ID-chemo-ICI。中位年龄66岁，55%为男性，大多数有吸烟史（93.1%），100%为白人。肿瘤组织学为腺癌（69%）、鳞状细胞癌（24%）、低分化NSCLC（3.4%）和肉瘤样NSCLC（3.4%）。大多数是IIIB期（44.8%），其次是IIIC期（41.4%）和IIIA期（13.8%）。N2和N3病变发生率分别为37.9%和55.2%。程序性死亡配体1表达包括小于1% （n = 11,38%）、1%至49% （n = 9,31%）、大于50% （n = 5,17%）和未知（n = 4,14%）。患者接受ID-chemo-ICI联合派姆单抗（82.8%）、纳武单抗（13.8%）或阿特唑单抗（3.4%），中位数为4个周期。ID-chemo-ICI的总有效率为93%。在队列中，90%接受cCRT， 76%接受维持性ICI（派姆单抗或杜伐单抗）。中位PFS为18个月，中位OS为24个月。肺炎发生率为37.9%（1级：18.2%；2级：63.6%；3级：18%，无4级）。55.2%的患者发生食管炎（1-2级93%，3级7%）。结论对于不能切除的III期非小细胞肺癌，尤其是不适合行前期cCRT的患者，sid -chemo- ici加cCRT是可行且安全的。需要更大规模的前瞻性试验来验证这些发现并优化患者选择。

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引用次数: 0

Cost-Effectiveness of Durvalumab After Chemoradiotherapy in Limited-Stage SCLC Durvalumab在有限期SCLC放化疗后的成本-效果

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-11-01 DOI: 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.

在ADRIATIC试验中，durvalumab巩固治疗改善了对放化疗有反应的有限期SCLC患者的总生存期和无进展生存期。基于这些数据，我们的目的是从台湾医疗保健部门的角度评估该疗法的成本效益。方法模拟对放化疗有反应的有限期SCLC患者进入分区生存模型，比较杜伐单抗巩固治疗和无巩固治疗。模型输入来自亚得里亚海试验（生存结果、不良事件和后续治疗）、国民健康保险支付（医生就诊、监测、药物管理和临终关怀的费用）和医院队列（效用值）。使用寿命期限和3%的年贴现率。进行亚组分析、单向确定性分析和概率分析。结果durvalumab巩固治疗增加了91,734美元，增加了0.90质量调整生命年（QALY），导致每个QALY的增量成本-效果比（ICER）为101,734美元。在大多数患者亚组中，ICER仍然高于每个QALY 7万美元的支付意愿阈值。对ICER影响最大的因素是杜伐单抗的成本。如果4周的药费可以降低到3893美元，ICER将降至每QALY 7万美元以下。在支付意愿阈值下，杜伐单抗巩固治疗的成本效益概率为0.3%。结论我们的分析表明，durvalumab巩固治疗对于有限期SCLC患者并不具有成本效益。降低治疗价格可以提高成本效益。

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引用次数: 0

ICTIS: A Novel Scoring System to Assess the Inclusivity of Advanced NSCLC Immunotherapy Trials ICTIS：一种评估晚期NSCLC免疫治疗试验包容性的新型评分系统

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-11-01 DOI: 10.1016/j.jtocrr.2025.100878

Kira Nguyen , Ashley Wei , Srinivas Govindan MD , Eziafa Oduah MD, PhD , Nagashree Seetharamu MD , Wint Yan Aung MD

Introduction

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。

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引用次数: 0

Patient-Reported Symptoms and Quality of Life With Sacituzumab Govitecan Versus Docetaxel in Metastatic NSCLC: The Phase 3, Randomized EVOKE-01 Trial Sacituzumab Govitecan与Docetaxel治疗转移性NSCLC患者报告的症状和生活质量：3期随机EVOKE-01试验

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-30 DOI: 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.

在3期EVOKE-01试验（NCT05089734）中，与之前接受过铂基化疗和程序性细胞死亡蛋白（配体）1抑制剂治疗的转移性非小细胞肺癌患者相比，sacituzumab govitecan （SG）在总生存率和耐受性方面表现出数值改善，尽管结果没有统计学意义。该分析评估了来自EVOKE-01的健康相关生活质量（HRQoL）数据。方法603例患者以1:1的比例随机分为SG （N = 299）和多西他赛（N = 304），每21 d为一个周期。HRQoL采用NSCLC症状评估问卷（NSCLC- saq）、欧洲癌症研究与治疗组织生活质量问卷- core 30 （QLQ-C30）、EuroQol 5维度3级问卷进行评估。分析第25周基线的最小二乘平均值变化、到第一次有意义恶化或死亡的时间以及到确认恶化的时间。结果ssg在NSCLC-SAQ呼吸短促（SoB）、疲劳、总分、QLQ-C30功能功能、疲劳、呼吸困难等方面均优于多西他赛。距NSCLC-SAQ SoB首次有意义恶化或死亡的时间较多西他赛更有利于SG（风险比[95%可信区间]:0.75[0.61-0.91]）、疲劳（0.70[0.57-0.86]）和总分（0.80 [0.66-0.97]）；QLQ-C30疲劳（0.80[0.66-0.96]）和呼吸困难（0.74 [0.60-0.90]）；EuroQol视觉模拟量表（0.79[0.65 ~ 0.96]）。对于NSCLC-SAQ的SoB（0.59[0.44-0.77]）和疲劳（0.70[0.52-0.95]），以及QLQ-C30的疲劳（0.75[0.59 - 0.95]），证实恶化的时间优于多西他赛。这些探索性结果表明，SG可能比多西他赛更有利于HRQoL，支持SG作为转移性非小细胞肺癌铂基和程序性细胞死亡蛋白（配体）1抑制剂治疗后的有效药物。

{"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}

引用次数: 0

Preoperative Immune-Related Adverse Events in Resectable NSCLC Treated With Neoadjuvant Nivolumab Plus Chemotherapy: A Multicenter Retrospective Analysis 可切除NSCLC术前新辅助纳武单抗加化疗免疫相关不良事件：一项多中心回顾性分析

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-30 DOI: 10.1016/j.jtocrr.2025.100930

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

Introduction

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。

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引用次数: 0

Direct Comparison of Tumor-Informed and Tumor-Naive Circulating Tumor DNA Assays for Recurrence Detection in Early-Stage NSCLC 早期非小细胞肺癌复发检测中肿瘤知情和肿瘤初始循环肿瘤DNA检测的直接比较

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-30 DOI: 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。

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引用次数: 0

Gut Dysbiosis as a Potential Guide for Immunotherapy (Dis)Continuation After 2 Years in NSCLC: A Brief Report 肠道生态失调作为非小细胞肺癌2年后继续免疫治疗（Dis）的潜在指南：简要报告

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-29 DOI: 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}

引用次数: 0

Curative-Intent Multimodality Treatment for NSCLC: Will Global Healthcare Systems Rise to the Challenge? A Perspective From the United Kingdom 非小细胞肺癌的多模式治疗：全球医疗保健系统将面临挑战吗？从英国的角度看问题

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-27 DOI: 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

引用次数: 0

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) 澳大利亚alk阳性晚期NSCLC的治疗模式、预后因素和生存率：来自澳大利亚胸部癌症纵向队列研究和生物库（AURORA）的结果

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-27 DOI: 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.

晚期肺癌历来与低生存率相关。然而，随着靶向治疗的出现，结果正在改善。在ALK重排晚期NSCLC （ALK+ aNSCLC）患者中，当代治疗时代有关治疗模式、预后因素和生存率的真实数据仍然有限。方法：我们进行了一项回顾性观察性队列研究，使用来自澳大利亚胸部癌症纵向队列研究和生物样本库（AURORA; ACTRN12625000038493）的未确定患者、疾病和结局数据。2006年至2025年间诊断为ALK+ aNSCLC的合格患者。结果在8个地点（截至2025年4月）入组的4776例胸部恶性肿瘤患者中，218例符合纳入标准，这是澳大利亚报道的最大的ALK+ aNSCLC队列。所有患者均在学术中心接受治疗。中位年龄为55岁；其中54%为女性，66%从不吸烟，41%参加过临床试验。中位总生存期为90.8个月（95% CI: 69.8 -未达到）。几乎所有患者（99%）接受了ALK抑制剂治疗；83%在一线。治疗顺序随着时间的推移而演变。大多数（68%）接受了至少两种治疗；21%的人收到了4条或更多的邮件。吸烟状况、年龄和东部肿瘤合作组表现状况与生存预后相关。结论：与历史队列相比，本研究强调了一些ALK+ aNSCLC患者在现实环境中可实现的显着生存率。确定了与生存相关的几个临床因素。需要更大规模的研究来研究如何优化治疗序列以进一步提高生存结果。

{"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}

引用次数: 0

The Added Value of Genome-Wide Copy Numbers to Objectively Resolve Clonality of Multiple Tumors With Pulmonary Involvement and Ambiguous or Inconclusive Mutational Diagnosis 全基因组拷贝数的附加价值，客观地解决肺部累及的多发性肿瘤的克隆性和不明确或不确定的突变诊断

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-23 DOI: 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.

以多发性癌症（MCs）和肺部受累为表现的患者的发病率正在增加。虽然下一代测序突变小组可以从不同的原发癌症（非克隆）中识别转移（克隆），但尽管具有重要的治疗意义，但它并不能保证对所有患者进行可靠的诊断。我们评估了全基因组拷贝数畸变（CNAs）在克隆诊断中的附加价值。方法收集了两个队列：来自TRACERx队列的41对克隆和41对非克隆对，以及来自2016年至2022年在我们的常规病理实践中使用CNA分析诊断的120例患者的21对具有足够DNA进行全外显子组测序（WES）的MC对。通过比较肿瘤对来确定克隆性，使用(1)WES突变作为最终标准，(2)采用改编的2024年国际肺癌研究协会算法的传统突变面板，以及(3)采用对数似然比和Pearson相关指标的CNAs。结果通过突变分析确定为“克隆”或“非克隆”的肿瘤对（TRACERx: 82例中35例[43%]，MC队列：21例中6例[29%]）与WES和CNAs一致。在通过突变分析被分类为“可能的非克隆”或“不确定”的肿瘤对中（TRACERx: 82例中有47例[57%]，MC队列：21例中有15例[71%]），大多数可以通过CNAs正确地重新分类（TRACERx: 47例中有46例[98%]，MC队列：16例中有15例[94%]）。对于每个队列，有一对肿瘤仍然是不确定的。此外，我们提出了一个CNA克隆工作流程的实施分子诊断。结论全基因组CNA分析为确定突变克隆状态不明确的MCs的克隆性提供了补充信息，有助于临床决策。

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引用次数: 0