JTO Clinical and Research Reports最新文献_第8页

Incorporating High-Risk Individuals Beyond Smoking History Into Lung Cancer Screening in Hong Kong: A Cost-Effectiveness Study 将吸烟史以外的高危人群纳入香港肺癌筛查：成本效益研究

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-01 Epub Date: 2025-06-13 DOI: 10.1016/j.jtocrr.2025.100860

Herbert Ho-fung Loong MBBS, FRCP , Xuanqi Pan PhD , Carlos K.H. Wong PhD , Chao-Hua Chiu MD , Szu-Chun Yang MD , Matthew Shing Hin Chung BSc , Molly Siu Ching Li MBBS , Lisa de Jong PhD , Harry Groen MD, PhD , Maarten J. Postma PhD , Pan-Chyr Yang MD, PhD

Introduction

Lung cancer (LC) accounts for 26.4% of all cancer deaths in Hong Kong (HK). Lung cancer screening (LCS) with low-dose computed tomography (LDCT) can reduce LC mortality. The cost-effectiveness of LDCT screening in high-risk individuals on the basis of smoking history has previously been investigated. However, nearly half of patients with LC in HK never smoke, indicating a different LC epidemiology compared with Western countries, where most LC cases are associated with smoking. We conducted a cost-effectiveness analysis for LCS, utilizing local data and expanding the target population to include we not only high-risk individuals identified on the basis of smoking history but also those identified through other risk factors.

Methods

A decision tree combined with a state-transition Markov model was developed to simulate identification, diagnosis, and treatments for high-risk individuals, from a health care provider perspective. The selection criteria and screening effectiveness for high-risk individuals on the basis of smoking history were obtained from the Dutch-Belgian Lung Cancer Screening Study, targeting heavy smokers aged 50 to 74 years; whereas the Taiwan Lung Cancer Screening in Never-Smoker Trial was used to model high-risk individuals on the basis of factors other than smoking history. Local LC survival and cost data were used to populate the model. The willingness-to-pay threshold used in the study was US$24,302 to US$40,202 per quality-adjusted life-year (QALY).

Results

Screening led to additional early LC detected, and LC mortality reduction, compared with no screening. Over a lifetime horizon, the incremental cost-effectiveness ratio for high-risk individuals on the basis of smoking history was US$14,122 per QALY. The incremental cost-effectiveness ratio for high-risk individuals on the basis of factors other than smoking history was lower at US$9610 per QALY.

Conclusion

LCS with LDCT can be considered cost-effective in HK for high-risk individuals on the basis of smoking history and factors other than smoking history, contributing to the health benefits of the population. Our findings support a population-based LCS for all high-risk individuals identified through criteria beyond smoking history.

在香港，肺癌（LC）占所有癌症死亡人数的26.4%。肺癌筛查（LCS）与低剂量计算机断层扫描（LDCT）可以降低肺癌死亡率。基于吸烟史对高危人群进行LDCT筛查的成本-效果已经进行了调查。然而，香港近一半的LC患者从不吸烟，这表明与西方国家的LC流行病学不同，大多数LC病例与吸烟有关。我们对LCS进行了成本效益分析，利用当地数据并扩大目标人群，不仅包括根据吸烟史确定的高危人群，还包括通过其他风险因素确定的高危人群。方法从医疗服务提供者的角度，建立一种结合状态转移马尔可夫模型的决策树来模拟高风险个体的识别、诊断和治疗。基于吸烟史的高危人群的选择标准和筛查效果来自荷兰-比利时肺癌筛查研究，目标人群为50 - 74岁的重度吸烟者；而台湾不吸烟者肺癌筛查试验则是根据吸烟史以外的因素对高危人群进行建模。使用局部LC生存和成本数据填充模型。研究中使用的支付意愿阈值为每个质量调整生命年（QALY） 24,302美元至40,202美元。结果与未筛查相比，筛查可导致更多的早期LC检测，并且LC死亡率降低。在整个生命周期中，基于吸烟史的高风险个体的增量成本-效果比为每QALY 14122美元。基于吸烟史以外因素的高风险个体的增量成本-效果比较低，为每QALY 9610美元。结论基于吸烟史和吸烟史以外的因素，lcs联合LDCT可被认为是香港高危人群具有成本效益的，有助于人群的健康益处。我们的研究结果支持通过吸烟史以外的标准确定的所有高风险个体的基于人群的LCS。

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引用次数: 0

Shedding Phosphorylated Axl Receptor in Lung Adenocarcinoma: Dual-Domain Immunohistochemistry Approach 肺腺癌中磷酸化Axl受体的脱落：双结构域免疫组织化学方法

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-01 Epub Date: 2025-08-07 DOI: 10.1016/j.jtocrr.2025.100889

Shuji Mishima MD , Takashi Eguchi MD PhD , Yoshinori Sato MD , Shunichiro Matsuoka MD, PhD , Yuichi Oguchi MD , Mari Katsuno MD , Daisuke Nakamura MD , Yukihiro Terada MD , Hirotaka Kumeda MD , Kentaro Miura MD, PhD , Kazutoshi Hamanaka MD, PhD , Mai Iwaya MD, PhD , Takeshi Uehara MD, PhD , Kimihiro Shimizu MD, PhD

Introduction

Axl, a receptor tyrosine kinase, is linked to epithelial-mesenchymal transition (EMT). This study aimed to investigate the biologic implications of extracellular domain shedding of phosphorylated Axl (pAxl) in lung adenocarcinoma, focusing on spread through air spaces (STAS) as a potential pathologic representation of EMT.

Methods

This study included 202 patients with resected lung adenocarcinoma. A dual-domain immunohistochemistry approach using separate staining for the extracellular and intracellular domains was used to classify the tumors into shedding and nonshedding pAxl groups. Prognostic analysis was performed using recurrence-free probability (RFP) as the primary outcome. Furthermore, by using a public gene database, we developed the “shedding pAxl score” to experimentally investigate correlations with EMT-related genes.

Results

The shedding pAxl group exhibited significantly worse prognosis than the nonshedding pAxl group (5-year RFP, 54% and 80%, respectively; p < 0.001). This prognostic stratification of pAxl shedding was predominant in STAS-positive patients (5-year RFP, 37% and 75%, p < 0.001), but not in STAS-negative patients (5-year RFP, 73% and 84%, p = 0.3). Multivariate analysis revealed that pathologic stage and pAxl shedding were independent factors for recurrence (hazard ratio 2.28 [1.24–4.91], p = 0.008). The shedding pAxl score correlated strongly with the established EMT signature score (p < 0.001, R = 0.61).

Conclusions

Shedding pAxl has a prognostic impact on lung adenocarcinoma, with a significant effect modification related to STAS. The developed shedding pAxl score, strongly associated with EMT, provides foundational knowledge for further studies on this phenomenon in lung cancer progression.

axl是一种酪氨酸激酶受体，与上皮-间质转化（EMT）有关。本研究旨在探讨肺腺癌中磷酸化Axl （pAxl）细胞外结构域脱落的生物学意义，重点关注作为EMT潜在病理表征的通过空气间隙扩散（STAS）。方法本研究纳入202例肺腺癌切除术患者。采用双结构域免疫组化方法，分别对细胞外和细胞内结构域进行染色，将肿瘤分为脱落和非脱落pAxl组。以无复发概率（RFP）作为主要预后指标进行预后分析。此外，通过使用公共基因数据库，我们开发了“脱落pAxl评分”，以实验研究emt相关基因的相关性。结果pAxl脱落组预后明显差于非pAxl脱落组（5年RFP分别为54%和80%；p < 0.001）。这种pAxl脱落的预后分层在stas阳性患者中占主导地位（5年RFP分别为37%和75%，p < 0.001），但在stas阴性患者中不占主导地位（5年RFP分别为73%和84%，p = 0.3）。多因素分析显示，病理分期和pAxl脱落是复发的独立因素（危险比2.28 [1.24-4.91],p = 0.008）。脱落pAxl评分与建立的EMT特征评分密切相关（p < 0.001, R = 0.61）。结论pAxl脱落对肺腺癌的预后有影响，且与STAS相关的效应改变显著。已开发的pAxl脱落评分与EMT密切相关，为进一步研究这种现象在肺癌进展中的作用提供了基础知识。

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引用次数: 0

Predictive Factors for Smoking Cessation Among People With Lung Cancer Attending French Cessation Services, According to Sex 参加法国戒烟服务的肺癌患者戒烟的预测因素，按性别分列

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-01 Epub Date: 2025-08-07 DOI: 10.1016/j.jtocrr.2025.100888

Anne-Laurence Le Faou MD, PhD , Dalia Alleaume MSc , Ingrid Allagbé PhD

Background

Limited research exists on sex-specific smoking cessation interventions for patients with lung cancer. This study leverages data from the Consultations de Dépendance Tabagique, the French national database of smoking cessation services (SCS), to identify sex-specific factors influencing smoking cessation in people with lung cancer.

Methods

This retrospective observational study analyzed data from 3407 adults with lung cancer (31.2% women, 68.8% men) registered in the Consultations de Dépendance Tabagique between 2001 and 2018. Participants were people with active tobacco use with at least one follow-up SCS consultation. The primary outcome was 28-day smoking abstinence, confirmed by exhaled carbon monoxide less than 10 parts per million. Multivariate logistic regression identified predictors of abstinence, stratified by sex.

Results

Abstinence rates were similar in women (35.2%) and men (35.4%) (p = 0.40). Women had higher psychological distress (19.8% with depression versus 13.1% in men; p < 0.001) and were more likely to seek SCS independently (19.4% versus 13.6%; p < 0.001). Men smoked more cigarettes daily (27 versus 25; p = 0.002) and had higher alcohol consumption (35.7% versus 13.9%; p < 0.001). Confidence in quitting (women: odds ratio [OR] = 1.91; 95% confidence interval [CI]: 1.27–2.87; men: OR = 1.50; 95% CI: 1.16–1.95) and follow-up consultations (≥7: women: OR = 8.86; 95% CI: 5.69–14.0; men: OR = 6.64; 95% CI: 4.88–9.13) predicted abstinence for both sexes. Among women, hospital referral (OR = 1.63; 95% CI: 1.10–2.43) and living with other persons who smoke (OR = 4.16; 95% CI: 1.70–10.4) increased abstinence, whereas in men, nicotine replacement therapy (OR = 1.46; 95% CI: 1.09–1.97) was beneficial.

Conclusions

The results indicate a need for further research into targeted interventions by sex to evaluate the efficacy of smoking cessation strategies in patients with lung cancer.

背景针对肺癌患者的性别戒烟干预措施的研究有限。这项研究利用了法国国家戒烟服务数据库（SCS）的数据，以确定影响肺癌患者戒烟的性别特异性因素。方法本回顾性观察性研究分析了2001年至2018年在Tabagique咨询中心登记的3407名成年肺癌患者（31.2%为女性，68.8%为男性）的数据。参与者是积极吸烟的人，至少有一次随访的SCS咨询。主要结果是戒烟28天，通过呼出的一氧化碳低于百万分之十来证实。多变量逻辑回归确定了禁欲的预测因素，按性别分层。结果女性（35.2%）和男性（35.4%）的戒断率相近（p = 0.40）。女性有更高的心理困扰（19.8%患有抑郁症，男性为13.1%;p < 0.001），并且更有可能独立寻求SCS（19.4%对13.6%;p < 0.001）。男性每天吸烟较多（27比25；p = 0.002），饮酒较多（35.7%比13.9%;p < 0.001）。戒烟的置信度（女性：优势比[OR] = 1.91； 95%可信区间[CI]: 1.27-2.87；男性：OR = 1.50; 95% CI: 1.16-1.95）和随访咨询（≥7：女性：OR = 8.86; 95% CI: 5.69-14.0；男性：OR = 6.64; 95% CI: 4.88-9.13）预测两性的戒断。在女性中，医院转诊（OR = 1.63; 95% CI: 1.10-2.43）和与其他吸烟者一起生活（OR = 4.16; 95% CI: 1.70-10.4）增加了戒断，而在男性中，尼古丁替代疗法（OR = 1.46; 95% CI: 1.09-1.97）是有益的。结论有必要进一步开展针对性干预研究，以评估肺癌患者戒烟策略的疗效。

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引用次数: 0

Durvalumab With or Without Tremelimumab in Combination With Chemoradiotherapy in Patients With Limited-Stage SCLC: Results from the Phase 1 CLOVER Study Durvalumab联合或不联合Tremelimumab联合放化疗治疗有限期SCLC患者：来自1期CLOVER研究的结果

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-01 Epub Date: 2025-08-05 DOI: 10.1016/j.jtocrr.2025.100884

Byoung Chul Cho MD, PhD , Myung-Ju Ahn MD , Makoto Nishio MD , Haruyasu Murakami MD , Dong Wan-Kim MD , Sang-We Kim MD , Sana D. Karam MD , Ana Estival PhD , Chia-Chi Lin MD, PhD , Jose Manuel Trigo MD , Rosa Alvarez MD , Chih Liang Wang MD , Mingchao Xie PhD , Sonia Iyer PhD , Jon Armstrong MSc , Priti Chugh PhD , Haiyi Jiang MD , Julie E. Bauman MD

Introduction

The phase 1 CLOVER study (NCT03509012) evaluated durvalumab with or without tremelimumab in combination with concurrent chemoradiotherapy (cCRT) in patients with advanced solid tumors; here, we report findings from the limited-stage SCLC (LS-SCLC) cohort.

Methods

Patients with pathologically confirmed LS-SCLC whose disease could be encompassed within a radical radiation portal received durvalumab (arms 1 and 2) or durvalumab plus tremelimumab (arms 3 and 4) in combination with cCRT (cisplatin-etoposide and either standard radiotherapy [arms 1 and 3] or hyperfractionated radiotherapy [arms 2 and 4]). The primary end point was safety and tolerability. Preliminary efficacy and candidate biomarkers of response were assessed.

Results

Overall, 33 patients were enrolled: 12 in arm 1, 12 in arm 2, six in arm 3, and three in arm 4. No patients had dose-limiting toxicity. Grade 3 or 4 adverse events occurred in 79.2% of patients from arms 1 and 2 and 88.9% from arms 3 and 4; the most common were hematologic events. In arms 1, 2, 3, and 4, objective response rate was 66.7%, 66.7%, 83.3%, and 100.0%, disease control rate was 90.9%, 100.0%, 100.0%, and 100.0% at 18 weeks and 72.7%, 83.3%, 100.0%, and 100.0% at 48 weeks, and the median progression-free survival (PFS) (95% confidence interval) was 9.2 months (5.3‒not estimable [NE]), 16.6 months (8.4–NE), not reached (16.6–NE), and 9.3 months (6.3–NE), respectively. In exploratory biomarker analyses, no difference in PFS by programmed cell death-ligand 1 expression level was observed; median PFS was numerically greater in high versus low tumor inflammation signature and CD8A expression subgroups.

Conclusions

Durvalumab in combination with cCRT, with or without tremelimumab, was tolerable and active in patients with LS-SCLC.

1期CLOVER研究（NCT03509012）评估了durvalumab联合或不联合tremelimumab联合同步放化疗（cCRT）治疗晚期实体瘤患者；在这里，我们报告了来自有限期SCLC （LS-SCLC）队列的研究结果。方法病理证实的LS-SCLC患者接受durvalumab（第1组和第2组）或durvalumab + tremelimumab（第3组和第4组）联合cCRT（顺铂- etopo苷加标准放疗[第1组和第3组]或超分割放疗[第2组和第4组]）治疗。主要终点是安全性和耐受性。评估初步疗效和候选生物标志物。结果共纳入33例患者：1组12例，2组12例，3组6例，4组3例。没有患者出现剂量限制性毒性。3级或4级不良事件发生在第1组和第2组的79.2%和第3组和第4组的88.9%；最常见的是血液学事件。在1、2、3和4组中，客观缓解率分别为66.7%、66.7%、83.3%和100.0%，18周时疾病控制率分别为90.9%、100.0%、100.0%和100.0%，48周时疾病控制率分别为72.7%、83.3%、100.0%和100.0%，中位无进展生存期（PFS）（95%置信区间）分别为9.2个月（5.3 -不可估计[NE]）、16.6个月（8.4-NE）、未达到（16.6 - NE）和9.3个月（6.3-NE）。在探索性生物标志物分析中，程序性细胞死亡配体1表达水平与PFS无差异；肿瘤炎症特征和CD8A表达高亚组与低亚组的中位PFS数值更高。结论durvalumab联合cCRT，无论是否联合tremelimumab，在LS-SCLC患者中是可耐受的和有效的。

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引用次数: 0

Durable Response to Lenvatinib in Platinum-Refractory Metastatic High-Grade Thymic Mucoepidermoid Carcinoma: A Case Report Lenvatinib对铂难治性转移性高级别胸腺黏液表皮样癌的持久疗效：1例报告

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-01 Epub Date: 2025-08-22 DOI: 10.1016/j.jtocrr.2025.100894

Noa Amin PhD, MRCP , Thanika Ketpueak DM , Simon Jordan MBBCh, MD , Andrew G. Nicholson DM, FRCPath , Yu Zhi Zhang MBBS, PhD, FRCPath , Sanjay Popat PhD FRCP

Thymic mucoepidermoid carcinoma (MEC) is a rare thymic carcinoma subtype. Current metastatic thymic carcinoma guidelines recommend first-line platinum-based chemotherapy. However, evidence suggests that MECs, including those of the lung and salivary gland, are chemorefractory, highlighting a more nuanced approach to systemic therapy decision-making. Here, we report a case of durable partial response to second-line lenvatinib in a patient with metastatic high-grade thymic MEC, refractory to first-line platinum-based chemotherapy, suggesting a potentially preferred first-line role for lenvatinib for this subtype.

胸腺粘液表皮样癌（MEC）是一种罕见的胸腺癌亚型。目前的转移性胸腺癌指南推荐一线铂基化疗。然而，有证据表明，包括肺和唾液腺在内的mec是化疗难治性的，这突出了更细致入微的系统性治疗决策方法。在这里，我们报告了一例转移性高级别胸腺MEC患者对二线lenvatinib的持久部分反应，对一线铂基化疗难治，提示lenvatinib在一线治疗该亚型的潜在首选作用。

引用次数: 0

Older Adult Participation in Early-Phase Lung Cancer Clinical Trials, 1998 to 2020 老年人参与早期肺癌临床试验，1998年至2020年

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-01 Epub Date: 2025-07-03 DOI: 10.1016/j.jtocrr.2025.100873

Desirae Ehley MD , Lilit Vardanyan MS , Rebecca S. Boxer MD, MS , Alex J. Fauer PhD , Shiruyeh Schokrpur MD, PhD , David Gandara MD , Jonathan W. Riess MD, MAS , Surbhi Singhal MD

Objectives

Despite advances, lung cancer treatment remains associated with substantial toxicity. Early-phase clinical trials inform the safety and efficacy of novel lung cancer treatments. Although older adults represent most patients with lung cancer, and they are underrepresented in phase 3 trials, age disparity in early-phase lung cancer trials is ill-defined.

Methods

We queried ClinicalTrials.gov to identify early-phase interventional clinical trials conducted in adults with lung cancer since database conception. We calculated the difference in age (DA) between the clinical trial populations and U.S. populations, using t test and one-sided analysis of variance to evaluate trial characteristics associated with DA.

Results

We identified 141 clinical trials enrolling 7723 participants from 1998 to 2020. Early-phase lung cancer trial participants were, on average, 7.6 years younger than patients with lung cancer in the U.S. population (mean DA: −7.6 y, SD 4.2). Age disparities were magnified among clinical trials that were industry-sponsored (mean DA −8.5 versus −6.1, p = 0.001) and those limiting eligibility to Eastern Cooperative Oncology Group performance status less than or equal to 1 (mean DA –8.0 versus −6.0, p = 0.040). There was no association between the median age of trial participants and the proportion of patients with serious adverse events.

Conclusions

Older adults remain underrepresented in early-phase lung cancer clinical trials. With the rapid expansion of novel cancer therapies, focused efforts in the design of early-phase trials are warranted to reflect real-world populations. Otherwise, limitations in the generalizability of treatment safety and efficacy may increase in the future.

尽管取得了进展，但肺癌的治疗仍然存在很大的毒性。早期临床试验揭示了新型肺癌治疗方法的安全性和有效性。尽管老年人代表了大多数肺癌患者，但他们在3期试验中的代表性不足，但早期肺癌试验中的年龄差异尚不明确。方法：我们查询了ClinicalTrials.gov网站，以确定自数据库建立以来在成人肺癌患者中进行的早期介入临床试验。我们计算了临床试验人群和美国人群的年龄差异（DA），使用t检验和单侧方差分析来评估与DA相关的试验特征。结果从1998年到2020年，我们纳入了141项临床试验，纳入了7723名参与者。早期肺癌试验参与者平均比美国人群中的肺癌患者年轻7.6岁（平均DA: - 7.6 y, SD 4.2）。在行业资助的临床试验（平均DA为- 8.5对- 6.1,p = 0.001）和那些限制资格的临床试验（平均DA为-8.0对- 6.0,p = 0.040）中，年龄差异被放大了。试验参与者的中位年龄与发生严重不良事件的患者比例之间没有关联。结论在早期肺癌临床试验中，成年患者的代表性仍然不足。随着新型癌症疗法的迅速发展，早期试验设计的重点工作有必要反映现实世界的人群。否则，在治疗安全性和有效性的推广限制可能会增加在未来。

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引用次数: 0

Meta-Analysis Exploring Tyrosine Kinase Inhibitor-Induced Weight Gain in Oncogene-Addicted NSCLC 荟萃分析探讨酪氨酸激酶抑制剂诱导的癌基因依赖性非小细胞肺癌体重增加

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-01 Epub Date: 2025-07-22 DOI: 10.1016/j.jtocrr.2025.100881

Ilaria Mariangela Scaglione MD , Alice Avancini PhD , Serena Eccher MD , Anita Borsati MSc , Luca Pasqualin MD , Giulia La Cava MD , Ilaria Trestini RD , Daniela Tregnago PhD , Marco Sposito MD , Jessica Insolda MSc , Diana Giannarelli PhD , Michele Milella MD , Sara Pilotto PhD , Lorenzo Belluomini PhD

Background

For patients with oncogene-addicted NSCLC treated with tyrosine kinase inhibitors (TKIs), weight gain has recently gained attention as a frequent treatment-related effect. Identifying those TKIs more frequently associated with weight gain is crucial for further characterizing body composition-related modifications, deepening their metabolic impact, and guiding treatment decisions, considering the potential influence of weight gain on patients' quality of life and long-term outcomes.

Methods

A systematic search was conducted across PubMed, Scopus, Cochrane, and meeting resources. A meta-analysis was conducted to quantify the magnitude of weight gain, and meta-regression was applied to explore the association between this side effect, and demographic and clinical parameters.

Results

Among 7596 identified studies from January 2009 to December 2024, 18 pivotal trials reporting weight gain data were included in the final analysis, encompassing a total of 25 arms. Lorlatinib revealed the highest risk of treatment-induced weight gain [incidence 36%; 95% confidence interval (CI): 26%–46%; I² = 92%], followed by alectinib [incidence 15%; 95% CI: 12%–18%; I² = 52%] and crizotinib [incidence 5%; 95% CI: 0%–13%; I² = 93%]. Osimertinib and erlotinib indicated the lowest incidence of weight gain. The meta-regression revealed no significant correlation among weight gain, sex, age, and performance status, thus suggesting a drug-specific effect.

Conclusions

Our findings confirmed the unique profile of lorlatinib regarding weight gain, regardless of patient characteristics. Considering the impressive prognostic horizons achievable with TKIs in oncogene-addicted NSCLC, adequate reporting in clinical trials, assessment and monitoring of weight gain, body composition modifications, and impact on quality of life should be prioritized, together with adequate lifestyle-based strategies for its management.

背景：对于接受酪氨酸激酶抑制剂（TKIs）治疗的癌基因依赖性非小细胞肺癌患者，体重增加作为一种常见的治疗相关效应最近引起了人们的关注。考虑到体重增加对患者生活质量和长期预后的潜在影响，识别那些与体重增加更频繁相关的tki对于进一步表征身体成分相关改变、深化其代谢影响和指导治疗决策至关重要。方法系统检索PubMed、Scopus、Cochrane和会议资源。我们进行了一项荟萃分析来量化体重增加的幅度，并应用荟萃回归来探讨这种副作用与人口统计学和临床参数之间的关系。在2009年1月至2024年12月的7596项研究中，18项报告体重增加数据的关键试验被纳入最终分析，共包括25个组。Lorlatinib显示治疗引起的体重增加的风险最高[发生率36%；95%置信区间（CI）： 26%-46%；I2 = 92%]，其次是阿勒替尼[发生率15%；95% ci: 12%-18%；I2 = 52%]和克唑替尼[发病率5%；95% ci: 0%-13%；I2 = 93%]。奥西替尼和厄洛替尼体重增加的发生率最低。meta回归显示体重增加、性别、年龄和运动状态之间无显著相关性，因此提示药物特异性作用。结论：我们的研究结果证实了氯拉替尼在体重增加方面的独特特征，与患者的特征无关。考虑到TKIs在癌基因成瘾的非小细胞肺癌中可实现的令人印象深刻的预后前景，应优先考虑充分的临床试验报告、体重增加的评估和监测、身体成分改变和对生活质量的影响，以及适当的基于生活方式的管理策略。

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引用次数: 0

What Is On the Horizon for the Diagnosis and Treatment of SCLC and Large Cell Neuroendocrine Cancer? SCLC和大细胞神经内分泌癌的诊断和治疗前景如何？

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-09-01 Epub Date: 2025-06-28 DOI: 10.1016/j.jtocrr.2025.100871

Sun Min Lim MD, PhD , Joo Sung Gabriel Shim MD , Hyo Sup Shim MD, PhD , Junko Tanizaki MD, PhD , Jorn Nutzinger MD , Byoung Chul Cho MD, PhD , Ross A. Soo MBBS, PhD

SCLC is a high-grade neuroendocrine malignancy associated with poor prognosis, comprising 15% of lung cancer cases globally. Advances in genetic profiling have revealed that SCLC is a molecularly heterogeneous disease, categorized into subtypes such as SCLC-A, SCLC-N, SCLC-P, and SCLC-I, on the basis of their neuroendocrine and immune-related characteristics. This heterogeneity underscores the need for tailored therapeutic strategies.

Large cell neuroendocrine carcinoma (LCNEC) shares histologic and molecular similarities with SCLC but remains a distinct entity. LCNEC is categorized into two major subtypes: Type I, characterized by STK11 and KEAP1 mutations and a neuroendocrine phenotype, and Type II, defined by TP53 and RB1 alterations with higher proliferative indices. LCNEC's rarity and molecular diversity present challenges for standardized treatment, further highlighting the need for comparative research with SCLC.

In this review, we highlight the genetic and clinicopathologic features of SCLC and LCNEC. Furthermore, we discuss emerging therapeutics and future directions in the treatment of SCLC and LCNEC.

SCLC是一种预后不良的高级别神经内分泌恶性肿瘤，占全球肺癌病例的15%。遗传图谱的进展表明，SCLC是一种分子异质性疾病，根据其神经内分泌和免疫相关特征可分为SCLC- a、SCLC- n、SCLC- p和SCLC- i等亚型。这种异质性强调了定制治疗策略的必要性。大细胞神经内分泌癌（LCNEC）与SCLC具有组织学和分子相似性，但仍然是一个不同的实体。LCNEC分为两大亚型：I型，以STK11和KEAP1突变和神经内分泌表型为特征；II型，以TP53和RB1改变为特征，具有较高的增殖指数。LCNEC的罕见性和分子多样性为标准化治疗带来了挑战，进一步强调了与SCLC进行比较研究的必要性。在这篇综述中，我们强调SCLC和LCNEC的遗传和临床病理特征。此外，我们还讨论了SCLC和LCNEC治疗的新疗法和未来发展方向。

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引用次数: 0

Impact of the COVID-19 Pandemic on Diagnosis and Multidisciplinary Treatment of NSCLC in Ontario, Canada COVID-19大流行对加拿大安大略省非小细胞肺癌诊断和多学科治疗的影响

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-09-01 Epub Date: 2025-06-19 DOI: 10.1016/j.jtocrr.2025.100869

Kirstin Perdrizet MD , Lisa W. Le MSc , Anthea Lau BSc , Xiaochen Tai MSc , Mary R. Rabey BMBS , Jennifer H. Law MSc , Donna Maziak MD , Natasha Leighl MD

Introduction

The coronavirus disease 2019 pandemic disrupted cancer care delivery globally, with many jurisdictions reporting reductions in lung cancer diagnoses and delays in treatment. In Ontario, Canada, both institutional and provincial data have reported mixed trends in NSCLC presentation and care. This study aimed to assess the short-term impact of the coronavirus disease 2019 pandemic on NSCLC diagnoses and treatment pathways across Ontario using population-level data from Cancer Care Ontario administrative health databases.

Methods

We conducted a retrospective cohort study of patients diagnosed with NSCLC in Ontario between January 1, 2019 and December 31, 2020. The cohort was created using relevant diagnostic codes and linked provincial databases to evaluate diagnostic trends and access to surgical, medical, and radiation oncology services. Statistical analyses included Poisson regression to assess changes in diagnosis rates and multivariable linear regressions to evaluate wait times, adjusting for age, sex, income quintile, and geographic region.

Results

A total of 13,407 NSCLC cases were identified. There was a 6% overall decline in diagnoses in 2020, with a 31% drop during quarter 2 (April–June 2020). The mean wait times for surgical consultation and treatment and also medical and radiation oncology consults improved or remained stable. No delays were found in systemic therapy initiation. Multivariable analyses confirmed these findings.

Conclusions

NSCLC care delivery in Ontario remained stable during the early pandemic period. Declines in diagnosis warrant further investigation using longer-term data. Real-time data systems are essential for future pandemic preparedness and response.

2019年冠状病毒病大流行扰乱了全球癌症护理服务，许多司法管辖区报告肺癌诊断减少和治疗延误。在加拿大安大略省，机构和省级数据都报告了非小细胞肺癌的表现和治疗的混合趋势。本研究旨在利用安大略省癌症护理行政卫生数据库的人口水平数据，评估2019年冠状病毒病大流行对安大略省非小细胞肺癌诊断和治疗途径的短期影响。方法：我们对2019年1月1日至2020年12月31日在安大略省诊断为NSCLC的患者进行了回顾性队列研究。该队列是使用相关诊断代码和关联的省级数据库创建的，以评估诊断趋势和获得外科、医疗和放射肿瘤学服务的机会。统计分析包括泊松回归来评估诊断率的变化，多变量线性回归来评估等待时间，调整年龄、性别、收入五分位数和地理区域。结果共检出NSCLC病例13407例。2020年的诊断总体下降了6%，第二季度（2020年4月至6月）下降了31%。外科会诊和治疗以及内科和放射肿瘤学会诊的平均等待时间有所改善或保持稳定。未发现全身治疗开始延迟。多变量分析证实了这些发现。结论安大略省snsclc的护理在大流行早期保持稳定。诊断率的下降需要使用长期数据进行进一步调查。实时数据系统对于未来的大流行防范和应对至关重要。

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引用次数: 0

Parallel Phase II Clinical Trials of Selinexor in Patients With Advanced Thymoma and Thymic Carcinoma 塞利那索治疗晚期胸腺瘤和胸腺癌的平行II期临床试验

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-09-01 Epub Date: 2025-05-15 DOI: 10.1016/j.jtocrr.2025.100848

Chul Kim MD , Vanya Aggarwal MD , Gedske Daugaard MD, DMSc , Tianzhi Tang MD , Jaeil Ahn PhD , Benjamin Besse MD, PhD , Nicolas Girard MD, PhD , Giuseppe Giaccone MD, PhD , Peter Meidahl Petersen MD, PhD

<div><h3>Introduction</h3><div>Thymic epithelial tumors (TETs) are rare and include thymomas (T) and thymic carcinomas (TC). Effective treatment options are needed for patients with progressive disease after platinum-based chemotherapy. Preclinical studies demonstrated antitumor activity of selinexor, an inhibitor of the nuclear receptor exportin-1 (XPO1/CRM1), supporting the clinical development of XPO1-targeted therapy for the treatment of TETs. To further assess the safety and efficacy of selinexor in TETs, we conducted two coordinated parallel phase II clinical trials.</div></div><div><h3>Methods</h3><div>This report includes two nearly identical phase II trials, designed to run in parallel, conducted in the United States (NCT03193437) and Europe (Denmark and France; NCT03466827). Analysis was performed on data pooled from both trials. Both trials were nonrandomized, open-label, two-armed phase II trials (arm A: thymoma, arm B: thymic carcinoma) with the same study design. Patients with histologically confirmed, advanced, inoperable TETs who had progressive disease after treatment with at least one platinum-containing chemotherapy regimen were included. In each 4-week cycle, patients received selinexor 60 mg twice weekly for 3 weeks. To improve tolerability, the starting dose was reduced to 40 mg twice weekly during the study. The primary objective was overall response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors 1.1, with secondary objectives including progression free survival (PFS), overall survival (OS), and adverse events (AEs) assessed per Common Terminology Criteria for Adverse Event version 4.03.</div></div><div><h3>Results</h3><div>A total of 31 patients were enrolled between the two trials: 16 with T and 15 with TC. The median age was 57 (range: 41–81) years, with 17 men and 14 women. The median number of previous systemic therapies was 2 (range: 1–9). The starting dose was 60 mg twice weekly for 29 patients (93.5%) and 40 mg twice weekly for two patients (6.5%). There was one complete response in the TC group (ORR 6.7%; 95% confidence interval [CI]: 1.2%–29.8%) and two partial responses (ORR 12.5%; 95% CI: 3.5%–36.0%) in the T group. Stable disease as the best response was observed in 11 patients (68.6%) with T and 12 patients (80%) with TC. The median duration of selinexor therapy was 4.5 (range: 0.1–44.3) months. The most common treatment-related adverse events (TRAEs) were nausea (83.8%), vomiting (45.2%), anemia (41.9%), fatigue (38.7%), and asthenia (38.7%). The most common grade 3 or higher TRAEs were anemia (16.1%), thrombocytopenia (12.9%), and asthenia (12.9%). Furthermore, 20 patients (64.5%) required dose reductions due to AEs and 20 patients (64.5%) required dose interruptions. In the T group, the median PFS was 13.6 months (95% CI: 6.3–44.3), and the median OS was not reached. In the TC group, the median PFS was 7.8 months (95% CI: 4.3–15.5) and the median OS was 15.5 months (95% CI: 13.0–29.9).

胸腺上皮肿瘤（TETs）是罕见的，包括胸腺瘤(T)和胸腺癌（TC）。在以铂为基础的化疗后，病情进展的患者需要有效的治疗方案。临床前研究表明，核受体输出素-1 （XPO1/CRM1）抑制剂selinexor具有抗肿瘤活性，支持XPO1靶向治疗TETs的临床开发。为了进一步评估selinexor在TETs中的安全性和有效性，我们进行了两项协调平行的II期临床试验。方法：本报告包括两个几乎相同的II期试验，设计为并行运行，分别在美国（NCT03193437）和欧洲(丹麦和法国；NCT03466827)。对两项试验的汇总数据进行分析。两项试验均为非随机、开放标签、双臂II期试验（A组：胸腺瘤，B组：胸腺癌），具有相同的研究设计。组织学证实的晚期不能手术的tet患者在接受至少一种含铂化疗方案治疗后病情进展。在每个4周的周期中，患者接受selinexor 60mg，每周2次，持续3周。为了提高耐受性，在研究期间，起始剂量减少到40毫克，每周两次。主要目标是根据实体瘤1.1的反应评价标准评估总体缓解率（ORR），次要目标包括根据不良事件通用术语标准4.03评估的无进展生存期（PFS）、总生存期（OS）和不良事件（ae）。结果两项试验共纳入31例患者：T组16例，TC组15例。中位年龄为57岁（范围：41-81岁），男性17人，女性14人。既往全身治疗的中位数为2次（范围：1-9次）。起始剂量为60 mg，每周两次，29例（93.5%），40 mg，每周两次，2例（6.5%）。TC组有1例完全缓解(ORR 6.7%；95%可信区间[CI]: 1.2%-29.8%)和两个部分反应(ORR 12.5%；95% CI: 3.5%-36.0%)。在11例（68.6%）T患者和12例（80%）TC患者中，病情稳定为最佳反应。selinexor治疗的中位持续时间为4.5个月（范围：0.1-44.3个月）。最常见的治疗相关不良事件（TRAEs）是恶心（83.8%）、呕吐（45.2%）、贫血（41.9%）、疲劳（38.7%）和虚弱（38.7%）。最常见的3级及以上trae是贫血（16.1%）、血小板减少（12.9%）和虚弱（12.9%）。此外，20名患者（64.5%）因ae需要减少剂量，20名患者（64.5%）需要中断剂量。T组中位PFS为13.6个月（95% CI: 6.3-44.3），中位OS未达到。TC组中位PFS为7.8个月（95% CI: 4.3-15.5），中位OS为15.5个月（95% CI: 13.0-29.9）。由于总体orr较低和预算限制，试验过早停止。结论selinexor在晚期TETs患者中表现出适度的抗癌活性。由于trae发生率高，治疗变得复杂，导致频繁的剂量减少和中断。

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引用次数: 0