Lung Cancer最新文献_第4页

Corrigendum to “Treatment and outcomes of limited stage small cell lung cancer in the Canadian small cell lung cancer database (CASCADE)” [Lung Cancer 210 (2025) 108840] “加拿大小细胞肺癌数据库（CASCADE）中有限期小细胞肺癌的治疗和结果”[肺癌210(2025)108840]的更正。

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2026-01-01 DOI: 10.1016/j.lungcan.2025.108875

William J. Phillips , Luna Jia Zhan , Deepro Chowdhury , Jeniszka Gill , Alexander Sun , Rebekah Rittberg , Victor Cohen , Amanda J.W. Gibson , Michael Yan , Daniel Liwski , Saritha Surapaneni , Marie Frederique D’Amours , Fabian P.S. Yu , YongJin Kim , Rana A. Qadeer , David E. Dawe , Jason Agulnik , Vishal Navani , Andrea S. Fung , Stephanie Snow , Sara Moore

引用次数: 0

Clinical impact of TP53 classifications in previously treated advanced driver-negative non-small cell lung cancer: A biomarker analysis of the OAK and POPLAR randomized clinical trials TP53分类对先前治疗过的晚期非小细胞肺癌的临床影响：OAK和POPLAR随机临床试验的生物标志物分析

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-29 DOI: 10.1016/j.lungcan.2025.108891

Deborah Di-Xin Zhou , Sarah J. Lord , Frank Po-Yen Lin , Wendy A. Cooper , Milita Zaheed , Robert John Simes , Thomas John , Chee Khoon Lee

Background

In NSCLC, TP53 mutations are heterogeneous with varied effects on protein synthesis, function and clinical outcomes. We hypothesize that a refined classification of TP53 mutations, beyond binary categorization, could improve prognostication. Furthermore, specific mutations could be associated with enhanced benefit from immune checkpoint inhibitors (ICI) versus chemotherapy. To investigate this, we analyzed data from randomized trials (OAK and POPLAR) which compared atezolizumab to chemotherapy in previously treated advanced driver-negative NSCLC.

Methods

Participants were classified as TP53 mutant or wild-type using baseline plasma, and by coding mutation, and Olivier’s and Poeta’s classification. We performed multivariable Cox regression analyses to evaluate the prognostic significance of TP53 mutations, and interaction tests to assess their predictive value.

Results

Among 762 participants, 49% harbored a TP53 mutation. TP53 mutations based on binary categorization were associated with poorer but not statistically significant OS compared to wild-type (adjusted-HR 1.15; 95 %CI 0.96–1.38; P = .12). However, nonsense mutations classified by coding mutations (adjusted-HR 1.71; 95% CI 1.22–2.39; P = .002), non-missense mutations classified by Olivier’s classification (adjusted-HR 1.33; 95% CI 1.03–1.74; P = .03) and disruptive mutations classified by Poeta’s classification (adjusted-HR 1.33; 95% CI 1.37–1.77; P = .03) were associated with statistically significant poorer OS. TP53 status did not predict differential benefit from ICI versus chemotherapy (interaction P = .45).

Conclusion

In advanced driver-negative NSCLC following progression on first-line chemotherapy, nonsense, non-missense and disruptive mutations of TP53 were strongly associated with inferior OS. These data support utilizing a nuanced classification of TP53 mutations as a stratification factor in future trials, and laboratory reporting to aid prognostication.

背景：在非小细胞肺癌中，TP53突变具有异质性，对蛋白质合成、功能和临床结果的影响各不相同。我们假设TP53突变的精确分类，超越二元分类，可以改善预后。此外，特异性突变可能与免疫检查点抑制剂（ICI）与化疗的获益增强有关。为了研究这一点，我们分析了随机试验（OAK和POPLAR）的数据，这些试验比较了atezolizumab与化疗在先前治疗的晚期驱动阴性NSCLC中的疗效。方法：通过基线血浆、编码突变、Olivier和Poeta分类，将参与者分为TP53突变型和野生型。我们通过多变量Cox回归分析来评估TP53突变的预后意义，并通过相互作用试验来评估其预测价值。结果：在762名参与者中，49%的人携带TP53突变。与野生型相比，基于二元分类的TP53突变与较差的OS相关，但无统计学意义（调整后危险度1.15;95% CI 0.96-1.38; P = 0.12）。然而，编码突变分类的无义突变（校正后危险度1.71,95% CI 1.22-2.39, P = 0.002）、Olivier分类的非错义突变（校正后危险度1.33,95% CI 1.03-1.74, P = 0.03）和Poeta分类的破坏性突变（校正后危险度1.33,95% CI 1.37-1.77, P = 0.03）与较差的OS有统计学意义相关。TP53状态不能预测ICI与化疗的获益差异（相互作用P = 0.45）。结论：在一线化疗进展的晚期驱动阴性NSCLC中，无义、非错义和破坏性TP53突变与不良OS密切相关。这些数据支持在未来的试验中利用TP53突变的细微分类作为分层因素，以及实验室报告来帮助预测。

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引用次数: 0

The role of APOBEC in early-stage epidermal growth factor receptor-mutant non-small cell lung cancer APOBEC在早期表皮生长因子受体突变的非小细胞肺癌中的作用。

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-29 DOI: 10.1016/j.lungcan.2025.108892

Hyun Ae Jung , Jinyeong Lim , Yoon-La Choi , Yeong Jeong Jeon , Junghee Lee , Jong Ho Cho , Yong Soo Choi , Sehhoon Park , Jong-Mu Sun , Jin Seok Ahn , Myung-Ju Ahn , Woong-Yang Park , Hong Kwan Kim , Se-Hoon Lee

Background

APOBEC plays a crucial role in the mutation process and immune response of non-small cell lung cancer (NSCLC). This study evaluated the role of the APOBEC mutation signature in early-stage epidermal growth factor receptor (EGFR) mutant NSCLC. This study aimed to assess the impact of APOBEC enrichment on recurrence-free survival (RFS), post-recurrence tyrosine kinase inhibitor (TKI) progression-free survival (PFS), and post-recurrence survival (PRS).

Methods

We conducted whole-exome sequencing and whole-transcriptome sequencing in 100 patients diagnosed with pathologic stage II-IIIA non-squamous NSCLC.

Results

Among the 100 patients, 18 (18 %) exhibited APOBEC (≥2) enrichment, which did not show a significant association with RFS (P = 0.14). Patients with APOBEC enrichment showed a shorter post-recurrence TKI PFS compared to those without APOBEC enrichment (8.13 months vs. 24.57 months, P = 0.017). In multivariate analysis, poor post-recurrence TKI PFS was associated with the type of EGFR mutation (L858R vs. exon 19 deletion, HR = 1.91, P = 0.04), TP53 mutation (HR = 2.07, P = 0.03), and APOBEC enrichment (≥2 vs. < 2, HR = 2.23, P = 0.02). PRS was 61.10 months and 21.77 months for patients with APOBEC enrichment and patients without APOBEC enrichment, respectively (P = 0.029). In multivariate analysis, poor PRS of EGFR-TKI was associated with the type of EGFR mutation (L858R vs. exon 19 deletion, HR = 2.29, P = 0.04) and APOBEC enrichment (≥2 vs. < 2, HR = 2.71, P = 0.02).

Conclusions

APOBEC enrichment may present at initial diagnosis of early-stage EGFR mutant NSCLC and is associated with poor post-recurrence TKI PFS and PRS rather than RFS.

背景：APOBEC在非小细胞肺癌（NSCLC）的突变过程和免疫应答中起着至关重要的作用。本研究评估了APOBEC突变特征在早期表皮生长因子受体（EGFR）突变型非小细胞肺癌中的作用。本研究旨在评估APOBEC富集对无复发生存（RFS）、复发后酪氨酸激酶抑制剂（TKI）无进展生存（PFS）和复发后生存（PRS）的影响。方法：对100例诊断为病理II-IIIA期非鳞状NSCLC的患者进行全外显子组测序和全转录组测序。结果：100例患者中，18例（18%）出现APOBEC（≥2）富集，与RFS无显著相关性（P = 0.14）。与没有APOBEC富集的患者相比，APOBEC富集的患者复发后TKI PFS较短（8.13个月对24.57个月，P = 0.017）。在多因素分析中，复发后TKI PFS差与EGFR突变类型（L858R vs外显子19缺失，HR = 1.91, P = 0.04）、TP53突变（HR = 2.07, P = 0.03）和APOBEC富集（≥2）相关。结论：早期EGFR突变NSCLC的初始诊断可能存在APOBEC富集，并且与复发后TKI PFS差和PRS相关，而不是与RFS相关。

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引用次数: 0

Inavolisib for PIK3CA-mutant non-small cell lung cancer: A case report 对pik3ca突变的非小细胞肺癌的不可溶性：1例报告

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-26 DOI: 10.1016/j.lungcan.2025.108890

Lei Cheng , Dongying Wang , Xueyan Zhang , Baohui Han , Hua Zhong , Wei Nie

Introduction

PIK3CA mutations are oncogenic drivers in 2–4% of non-small cell lung cancers (NSCLC), often co-occurring with other drivers and conferring therapeutic resistance. This report is unique in describing the efficacy of the novel, highly selective PI3Kα inhibitor inavolisib in two heavily pre-treated patients with PIK3CA-mutant NSCLC harboring divergent co-drivers (EGFR and KRAS).

Case presentation

We present a 71-year-old male with EGFR/PIK3CA-mutant adenocarcinoma and brain metastases, and a 54-year-old female with KRAS/PIK3CA-mutant squamous cell carcinoma. Both patients reported rapid symptomatic improvement (hoarseness and shoulder pain, respectively) within two weeks of initiating inavolisib.

Diagnosis, intervention, and outcomes

Both patients received oral inavolisib (6 mg daily). Follow-up imaging after one month revealed significant tumor reduction. Notably, regressing intrapulmonary lesions exhibited tumor cavitation, and the male patient demonstrated a marked regression of central nervous system (CNS) metastases. The treatment was well-tolerated, with only Grade 1 oral mucositis reported.

Conclusion

The primary take-away lesson is that selective PI3Kα inhibition with inavolisib can induce potent systemic and intracranial responses in PIK3CA-mutant NSCLC, regardless of the primary oncogenic co-driver. The observed tumor cavitation suggests a potential anti-angiogenic mechanism, warranting further investigation.

pik3ca突变是2-4%的非小细胞肺癌（NSCLC）的致癌驱动因素，通常与其他驱动因素共同发生，并赋予治疗耐药性。该报告独特地描述了新型高选择性PI3Kα抑制剂inavolisib在两例重度预处理的pik3ca突变NSCLC患者中具有不同的共同驱动因素（EGFR和KRAS）的疗效。病例介绍：我们报告一名71岁男性患者患有EGFR/ pik3ca突变腺癌和脑转移，一名54岁女性患者患有KRAS/ pik3ca突变鳞状细胞癌。两名患者均报告在开始注射注射后两周内症状迅速改善（分别为声音嘶哑和肩部疼痛）。诊断、干预和结果：两例患者均接受口服inavolisib（每日6mg）。1个月后随访影像显示肿瘤明显缩小。值得注意的是，肺内病变的消退表现为肿瘤空化，男性患者表现为中枢神经系统（CNS）转移的明显消退。治疗耐受性良好，只有1级口腔黏膜炎的报道。结论：在pik3ca突变的非小细胞肺癌中，使用inavolisib选择性抑制PI3Kα可以诱导有效的全身和颅内反应，而不管主要的致癌共同驱动因素是什么。观察到的肿瘤空化提示潜在的抗血管生成机制，值得进一步研究。

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引用次数: 0

Effect of treatment sequencing on outcome of patients with non-small cell lung cancer with a synchronous solitary extrathoracic metastasis 治疗顺序对非小细胞肺癌合并胸外同步孤立转移患者预后的影响。

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-25 DOI: 10.1016/j.lungcan.2025.108889

Mandy Jongbloed , Ronald A.M. Damhuis , Wouter H. Van Geffen , Peter de Boer , Jarno W.J. Huijs , Safiye Dursun , Juliette Degens , Ben E.E.M. van den Borne , Magdolen Youssef-El Soud , Michelle Steens , Cordula Pitz , Dirk K.M. De Ruysscher , Lizza E.L. Hendriks

Currently, guidelines advise local radical treatment (LRT) to all disease sites in addition to systemic therapy in patients with synchronous oligometastatic non-small cell lung cancer (NSCLC). However, the best order of treatments is unknown. This advice is largely based on expert opinion and on studies without immune checkpoint inhibitors (ICI), while an ICI-based regimen is now standard of care first-line treatment for stage IV NSCLC without an actionable genetic alteration (AGA). We conducted a retrospective study to evaluate the order of treatments in patients with synchronous oligometastatic NSCLC without an AGA, with a single extrathoracic metastasis treated with an ICI-based regimen between 2018 and 2022. We evaluated upfront LRT to the metastasis followed by ICI and if indicated LRT to the local disease (Netherlands Cancer Registry: cohort 1, n = 225), and ICI followed by LRT to all disease sites if no progression (regional retrospective series: cohort 2, n = 33). The primary endpoint was overall survival (OS). The median OS for cohort 1 and cohort 2 were 26 and 25 months, respectively, and 3-year OS rates of 45 % and 44 %, respectively. In cohort 1, better survival was seen for those with brain metastasis, good performance status, non-squamous histology and high PD-L1 expression. In cohort 2, better survival was seen for younger age and non-squamous histology. In conclusion, both upfront and delayed LRT combined with an ICI-based treatment can result in long-term survival in this patient population, however the most optimal sequence has yet to determined.

目前，指南建议除对同步少转移性非小细胞肺癌（NSCLC）患者进行全身治疗外，对所有疾病部位进行局部根治性治疗（LRT）。然而，治疗的最佳顺序尚不清楚。该建议主要基于专家意见和无免疫检查点抑制剂（ICI）的研究，而基于ICI的方案现在是无可操作遗传改变（AGA）的IV期非小细胞肺癌的标准护理一线治疗。我们进行了一项回顾性研究，以评估2018年至2022年期间无AGA的同步少转移性非小细胞肺癌患者的治疗顺序，这些患者有单一的胸外转移，采用基于ci的方案治疗。我们评估了转移后再进行ICI的前期LRT，以及是否表明对局部疾病进行LRT（荷兰癌症登记处：队列1，n = 225），如果没有进展，ICI后再进行LRT到所有疾病部位（区域回顾性系列：队列2，n = 33）。主要终点是总生存期（OS）。队列1和队列2的中位生存期分别为26个月和25个月，3年生存期分别为45%和44%。在队列1中，脑转移、良好的运动状态、非鳞状组织和高PD-L1表达的患者生存率更高。在队列2中，较年轻和非鳞状组织的患者生存率较高。总之，在这一患者群体中，前期和延迟LRT联合基于ci的治疗都可以导致长期生存，但最佳的顺序尚未确定。

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引用次数: 0

Is sublobar resection a valid option for radiologically pure-solid clinical stage IA non-small cell lung cancer?: insights from real-world data and current status 肺叶下切除术是放射学纯实性临床IA期非小细胞肺癌的有效选择吗？：来自真实世界数据和当前状态的见解

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-23 DOI: 10.1016/j.lungcan.2025.108886

Dong Woog Yoon , Sumin Shin , Chu Hyun Kim , Yeong Jeong Jeon , Junghee Lee , Seong Yong Park , Yong Soo Choi , Jong Ho Cho , Hong Kwan Kim , Ho Yun Lee

Objectives

We aimed to evaluate the oncologic outcomes of sublobar resection (SLR) compared with lobectomy in patients with radiologically pure-solid stage IA non–small cell lung cancer (NSCLC).

Methods

We retrospectively reviewed 363 patients with clinical stage IA pure-solid NSCLC who underwent curative-intent resection between 2018 and 2020. Patients were divided into SLR (n = 60) and lobectomy (n = 303) groups. Kaplan–Meier analysis was used to estimate overall survival (OS) and recurrence-free survival (RFS), and Cox regression identified prognostic factors. Subgroup analyses were performed for stage IA2 and IA3 patients.

Results

In the overall cohort, the SLR group had significantly worse 5-year OS (75.5 % vs. 93.3 %, p < 0.01) and RFS (58.3 % vs. 77.4 %, p < 0.01) compared with lobectomy. In stage IA2, OS was comparable (87.2 % vs. 91.7 %, p = 0.1), but RFS was inferior after SLR (65.9 % vs. 81.2 %, p = 0.02). In stage IA3, both OS (54.3 % vs. 94.4 %, p < 0.01) and RFS (40.6 % vs. 74.9 %, p < 0.01) were markedly worse after SLR. Segmentectomy showed outcomes similar to lobectomy in IA2 but was inferior in IA3, whereas wedge resection was consistently associated with poor survival.

Conclusions

Lobectomy remains the standard surgical procedure for pure-solid stage IA NSCLC, particularly IA3 disease. Segmentectomy may be considered in carefully selected IA2 patients, while it is advisable to avoid wedge resection. These findings emphasize the importance of selecting the most appropriate patients for SLR and support the need for prospective validation.

目的：比较纯实体期IA期非小细胞肺癌（NSCLC）患者行叶下切除术（SLR）和叶下切除术的肿瘤预后。方法回顾性分析2018年至2020年363例临床期IA型纯实体非小细胞肺癌患者行治愈性切除术。患者分为单叶切除组（n = 60）和肺叶切除组（n = 303）。Kaplan-Meier分析用于估计总生存期（OS）和无复发生存期（RFS）， Cox回归确定预后因素。对IA2期和IA3期患者进行亚组分析。结果在整个队列中，SLR组的5年OS （75.5% vs. 93.3%, p < 0.01）和RFS （58.3% vs. 77.4%, p < 0.01）明显低于肺叶切除术。在IA2期，OS相当（87.2% vs. 91.7%, p = 0.1），但SLR后RFS较差（65.9% vs. 81.2%, p = 0.02）。在IA3期，SLR后OS （54.3% vs. 94.4%, p < 0.01）和RFS （40.6% vs. 74.9%, p < 0.01）均明显恶化。在IA2中，节段切除术的结果与肺叶切除术相似，但在IA3中效果较差，而楔形切除术始终与较差的生存率相关。结论：对于纯固体期IA型非小细胞肺癌，尤其是IA3型非小细胞肺癌，手术切除仍是标准手术方法。在精心挑选的IA2患者中，可以考虑节段切除术，但建议避免楔形切除术。这些发现强调了选择最合适的单反患者的重要性，并支持前瞻性验证的必要性。

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引用次数: 0

Cost-effectiveness of adjuvant alectinib in the treatment of patients with resected stage IB-IIIA ALK-positive non-small lung cancer in France, based on the ALINA study 基于ALINA研究，辅助alectinib治疗法国IB-IIIA期alk阳性非小肺癌切除患者的成本-效果

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-23 DOI: 10.1016/j.lungcan.2025.108885

Romain Supiot , Alexandre Gherardi , Léopoldine du Manoir de Juaye , Olfa Doghri , Marine Sivignon , Michaël Duruisseaux , Christos Chouaid

Background and objective

Alectinib has demonstrated significant disease-free survival (DFS) benefits as adjuvant therapy for resected stage IB–IIIA ALK-positive non-small-cell lung cancer (NSCLC) in the ALINA study. This study aimed to assess the cost-effectiveness of introducing adjuvant alectinib into routine clinical practice in France compared with standard adjuvant platinum-based chemotherapy.

Methods

A cohort-based semi-Markov model was developed to simulate long-term health and economic outcomes for patients from the ALINA intention-to-treat population over a 40-year time horizon. Eight mutually exclusive health states were included, capturing DFS, non-metastatic recurrence, metastatic recurrence (first and second line), and death. Clinical inputs were sourced primarily from ALINA, while recurrence treatment patterns, cure assumptions, utilities, and costs reflected French clinical practice and French thoracic oncologists’ opinion. Costs (2024 euros) and outcomes were discounted following French HTA guidelines. Deterministic, probabilistic, and scenario analyses were conducted.

Results

Adjuvant alectinib would yield 17.6 life-years (LYs) and 15.4 quality-adjusted life-years (QALYs) per patient versus 12.4 LYs and 10.4 QALYs with chemotherapy, corresponding to incremental gains of 5.2 LYs and 5.0 QALYs. Total lifetime costs were estimated at €180,561 with alectinib and €237,011 with chemotherapy, resulting in a cost saving of €56,449. Higher upfront treatment costs with alectinib were offset by substantial reductions in recurrence-related expenditures. Across all deterministic, probabilistic, and scenario analyses, alectinib remained both more effective and less costly.

Conclusions

Adjuvant alectinib would provide substantial clinical benefits for patients with resected ALK-positive NSCLC and represent a dominant strategy over platinum-based chemotherapy in the French healthcare setting, improving outcomes while reducing overall costs.

背景和目的：在ALINA研究中，Alectinib作为IB-IIIA期alk阳性非小细胞肺癌（NSCLC）切除的辅助治疗显示出显著的无病生存（DFS）益处。本研究旨在评估在法国将辅助阿勒替尼引入常规临床实践与标准辅助铂基化疗的成本效益。方法：建立基于队列的半马尔可夫模型，模拟有意治疗的ALINA患者在40年时间范围内的长期健康和经济结果。包括8种相互排斥的健康状态，包括DFS、非转移性复发、转移性复发（一线和二线）和死亡。临床输入主要来自ALINA，而复发治疗模式、治愈假设、效用和成本反映了法国的临床实践和法国胸部肿瘤学家的意见。成本（2024欧元）和结果按照法国HTA的指导方针进行贴现。进行了确定性、概率和情景分析。结果：辅助alectinib将为每位患者带来17.6个生命年（LYs）和15.4个质量调整生命年（QALYs），而化疗为12.4个生命年和10.4个生命年，相应的增量收益为5.2个生命年和5.0个生命年。阿勒替尼的总生命周期成本估计为180,561欧元，化疗为237,011欧元，节省成本56,449欧元。阿勒替尼前期治疗费用的增加被复发相关支出的大幅减少所抵消。在所有的确定性、概率和情景分析中，alectinib仍然更有效，成本更低。结论：辅助alectinib将为切除的alk阳性非小细胞肺癌患者提供实质性的临床益处，并且在法国医疗保健机构中代表了以铂为基础的化疗的主导策略，改善了结果，同时降低了总体成本。

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引用次数: 0

Optimizing communication for ultrafast lung cancer biomarker testing: the UTOPIA pilot study 优化通信的超快速肺癌生物标志物检测：乌托邦试点研究。

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-23 DOI: 10.1016/j.lungcan.2025.108887

Susana Hernandez , Esther Conde , Marta Alonso , Daniel Curto , Fatima Duran , Abigail Ast , Javier Torres-Jimenez , Helena Bote-de Cabo , Maria Zurera , Javier Baena , Jon Zugazagoitia , Ricardo Garcia-Lujan , Dolores Isla , Javier De Castro , Luis Paz-Ares , Fernando Lopez-Rios

Background

Non–small cell lung carcinoma (NSCLC) is a leading example of precision oncology, with a growing number of actionable targets. However, long turnaround times (TAT) for biomarker results can delay optimal treatment decisions. We evaluated whether a streamlined workflow could deliver comprehensive molecular reports within 72 h.

Methods

In this prospective cohort study (UTOPIA protocol), 96 patients with early-stage or advanced NSCLC at Hospital Universitario 12 de Octubre underwent molecular tumor board (MTB)-centered triage, automated NGS processing, and integrated data review. TAT was defined (in working days) from MTB triage to electronic report validation. Communication was supported by daily operational huddles and intralaboratory pre-MTB meetings using a standardized checklist.

Results

All 96 NGS reports met the 72-hour TAT target (100%). The NGS failure rate was 1%. Potentially actionable genomic alterations were identified in 45.8% of patients, most frequently EGFR (24%) and KRAS G12C (8.3%). Other targetable alterations included six ALK fusions (6.3%), four MET exon 14 skipping mutations (4.2%), two BRAF V600E mutations (2.1%), and one RET fusion (1%).

Conclusion

An ultrafast biomarker testing workflow for lung cancer, enabled by MTB-driven triage and structured team communication, can reliably generate comprehensive molecular reports within 72 h. This approach may reduce TAT-related treatment delays and support timely biomarker-guided therapy for patients with NSCLC.

背景：非小细胞肺癌（NSCLC）是精确肿瘤学的一个主要例子，具有越来越多的可操作靶点。然而，生物标志物结果的长周转时间（TAT）可能会延迟最佳治疗决策。我们评估了一个简化的工作流程是否可以在72小时内提供全面的分子报告。方法：在这项前瞻性队列研究（乌托邦方案）中，96名早期或晚期非小细胞肺癌患者于10月12日在Universitario医院接受了以分子肿瘤委员会（MTB）为中心的分诊、自动NGS处理和综合数据回顾。TAT定义（以工作日为单位）从结核分枝杆菌分类到电子报告验证。通过使用标准化清单的日常业务会议和实验室内部mtb前会议来支持沟通。结果：96例NGS报告均达到72小时TAT指标（100%）。NGS的失败率为1%。45.8%的患者发现了潜在的可操作的基因组改变，最常见的是EGFR（24%）和KRAS G12C（8.3%）。其他可靶向的改变包括6个ALK融合（6.3%），4个MET外显子14跳变突变（4.2%），2个BRAF V600E突变（2.1%）和1个RET融合（1%）。结论：通过mtb驱动的分类和结构化的团队沟通，一个超快速的肺癌生物标志物检测工作流程可以在72小时内可靠地生成全面的分子报告。这种方法可以减少与tat相关的治疗延误，并支持对非小细胞肺癌患者进行及时的生物标志物引导治疗。

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引用次数: 0

External evaluation of the Manchester score in a contemporary SCLC cohort 当代SCLC队列中曼彻斯特评分的外部评价。

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-23 DOI: 10.1016/j.lungcan.2025.108884

Charlie Cunniffe , Matthew Sperrin , Gerard Walls , Fiona Blackhall , Gareth Price

Objectives

The Manchester Score, a prognostic model developed in 1987, was used to stratify patients with Small Cell Lung Cancer (SCLC) by mortality risk, including stage, performance status, and three blood tests as risk factors. Many tools have since been developed for this purpose, but few have seen clinical use, with lack of robust external validation frequently cited as a barrier. In this study we apply a robust and pragmatic external validation approach to the Manchester Score to understand if it remains valid in an unselected modern patient cohort.

Methods

SCLC patients treated in an academic centre between 2013 and 2022 (N = 1783) were included in the validation cohort. Discrimination was assessed using Kaplan-Meier curves, AUC, and Harrell’s C-index for the Manchester score and its underlying Cox model. Three levels of Cox model updating were used to address missing baseline hazard data: recalibration, recalibration with rescaling, and model refitting. Calibration was then evaluated with optimism adjustment at 6-, 12-, and 24-months post-diagnosis.

Results

The Manchester score shows good discrimination in the modern patient cohort. There is clear separation between risk groups in the Kaplan-Meier curves, with AUC = 0.75 and C-index = 0.68 for the Manchester Score and (AUC = 0.79, C-index = 0.70) for the underlying Cox model. Median survival in the ‘good’ prognostic group (meeting < 2/5 risk criteria) has increased compared to that from 1987. All model updating methods reported good calibration, with recalibration alone providing the best observed-to-expected ratio at 6 months (1.012 [0.978,1.045]).

Conclusion

The original Manchester Score prognostic groups remain discriminative of survival, and when updated can predict survival probability at multiple timepoints.

目的：曼彻斯特评分是1987年开发的一种预后模型，用于根据死亡风险对小细胞肺癌（SCLC）患者进行分层，包括分期、表现状态和三种血液检查作为危险因素。此后，为此目的开发了许多工具，但很少有临床应用，缺乏可靠的外部验证经常被认为是一个障碍。在这项研究中，我们应用了一个强大的和务实的外部验证方法来曼彻斯特评分，以了解它是否仍然有效，在一个未选择的现代患者队列。方法：将2013年至2022年间在某学术中心接受治疗的SCLC患者（N = 1783）纳入验证队列。使用Kaplan-Meier曲线、AUC和Harrell的曼彻斯特评分c指数及其基础Cox模型来评估歧视。三个级别的Cox模型更新被用来解决缺失的基线危险数据：重新校准、重新校准和重新调整模型。然后在诊断后6个月、12个月和24个月用乐观调整对校准进行评估。结果：曼彻斯特评分在现代患者队列中具有良好的辨别性。Kaplan-Meier曲线中风险组之间存在明显的分离，Manchester Score的AUC = 0.75, C-index = 0.68，基础Cox模型的AUC = 0.79, C-index = 0.70。结论：最初的曼彻斯特评分预后组仍然具有判别生存的能力，更新后可以预测多个时间点的生存概率。

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引用次数: 0

Tarlatamab in routine clinical care: How much safety is enough? 塔拉他单抗在常规临床护理中的应用：多少安全性才足够？

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-23 DOI: 10.1016/j.lungcan.2025.108888

Ernest Nadal , Jordi Bruna

引用次数: 0