JTO Clinical and Research Reports最新文献_第5页

Long-term Survival Analysis From PERLA, A Phase II Randomized Trial of Dostarlimab With Chemotherapy Versus Pembrolizumab With Chemotherapy in Metastatic Nonsquamous NSCLC 来自PERLA的长期生存分析，一项多斯塔利单抗联合化疗与派姆单抗联合化疗治疗转移性非鳞状NSCLC的II期随机试验

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-09-04 DOI: 10.1016/j.jtocrr.2025.100900

Sun Min Lim MD, PhD , Ana Laura Ortega Granados MD , Gustavo dix Junqueira Pinto MD, MSc , Christian Sebastián Fuentes MD , Giuseppe Lo Russo MD , Michael Schenker MD , Jin Seok Ahn MD, PhD , Filippo de Marinis MD , Kenneth Locke Jr. PhD , Zsolt Szijgyarto PhD , Elena Buss MSc , Neda Stjepanovic MD, PhD , Ivan Diaz-Padilla MD, PhD , Solange Peters MD, PhD

Introduction

PERLA is a global, double-blind, phase II trial comparing anti–programmed cell death protein 1 antibodies, dostarlimab, and pembrolizumab in combination with chemotherapy (D+CT and P+CT, respectively) in patients with metastatic nonsquamous NSCLC without actionable genomic aberrations in the first-line setting.

Methods

Patients were randomized 1:1 to receive not more than 35 cycles of 500 mg dostarlimab or 200 mg pembrolizumab, with less than or equal to 35 cycles of 500 mg/m² pemetrexed and less than or equal to 4 cycles of cisplatin (75 mg/m²) or carboplatin (area under the curve 5 mg/mL/min) every 3 weeks. The primary end point was the overall response rate by blinded independent central review. The secondary end points included progression-free survival (PFS) on the basis of investigator assessment, overall survival (OS), and safety. Here, we reported on the long-term OS, PFS, and safety analyses.

Results

At the end of the study (September 10, 2024), the median follow-up time (mo) for PFS was 30.4 for D+CT and 30.4 for P+CT. The median PFS (mo [95% confidence interval (CI)]) was 8.8 (6.9–11.0) for D+CT and 6.8 (4.9–7.1) for P+CT (hazard ratio 0.77 [95% CI: 0.58–1.03] at 79% maturity). The median follow-up time (mo) for OS was 35.5 for D+CT and 35.2 for P+CT. The median OS (mo [95% CI]) was 20.2 (14.5–27.3) and 15.9 (11.6–19.3), respectively (hazard ratio 0.75 [95% CI: 0.55–1.02] at 70% maturity). Safety profiles were similar between arms and consistent with previous analyses.

Conclusions

This long-term analysis reaffirms previous observations that D+CT exhibited similar efficacy to P+CT and exhibits strong clinical efficacy as a first-line treatment for patients with metastatic nonsquamous NSCLC.

Clinical trial registration

NCT04581824.

perla是一项全球性、双盲、II期试验，比较抗程序性细胞死亡蛋白1抗体、多斯塔利单抗和派姆单抗联合化疗（分别为D+CT和P+CT）在一线环境中无可操作基因组异常的转移性非鳞状NSCLC患者中的疗效。方法患者按1:1随机分组，接受不超过35个周期的500 mg的多司来单抗或200 mg的派姆单抗，培美曲塞≤35个周期的500 mg/m2，顺铂≤4个周期（75 mg/m2）或卡铂（曲线下面积5mg /mL/min）每3周。主要终点是盲法独立中心评价的总缓解率。次要终点包括基于研究者评估的无进展生存期（PFS）、总生存期（OS）和安全性。在这里，我们报告了长期的OS、PFS和安全性分析。结果研究结束时（2024年9月10日），PFS的中位随访时间（mo） D+CT为30.4，P+CT为30.4。D+CT的中位PFS (mo[95%可信区间（CI）]为8.8 (6.9-11.0)，P+CT的中位PFS为6.8(4.9-7.1)（79%成熟度时风险比0.77 [95% CI: 0.58-1.03]）。D+CT组OS的中位随访时间为35.5，P+CT组为35.2。中位OS （mo [95% CI]）分别为20.2（14.5-27.3）和15.9(11.6-19.3)（70%成熟度时风险比为0.75 [95% CI: 0.55-1.02]）。两组的安全性相似，与之前的分析一致。这项长期分析证实了先前的观察结果，即D+CT与P+CT具有相似的疗效，并且作为转移性非鳞状NSCLC患者的一线治疗具有很强的临床疗效。临床试验注册号：nct04581824。

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引用次数: 0

A Retrospective Observational Cohort Study of Lung Cancer Screening Outcomes Among U.S. Blacks and Whites 美国黑人和白人肺癌筛查结果的回顾性观察队列研究

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-09-04 DOI: 10.1016/j.jtocrr.2025.100899

Giorgi Sabakhtarishvili MD, Mitchell B. Karpman PhD, Rahul Mishra MD, Teresa M. Putscher RN, BSN, Omer Bajwa MD, Rachel Hall DO, MS, Sahil Garg MD, Farshid Fargahi MD, Barry Meisenberg MD

Background

Mortality from lung cancer is reduced with low-dose computed tomography (LDCT) screening in high-risk persons. But screening uptake is low, especially among Black persons. Previous reports of LDCT had low participation of Black persons, which may inhibit wider adoption. In this study, we report on outcomes of LDCT screening in Black and White cohorts.

Methods

Retrospective observational cohort study using concurrent data from LDCT screening and tumor registries to compare the results of LDCT efficacy in reducing stage 4 lung cancer presentations in Black and White participant cohorts.

Results

Blacks comprised 13% of the 3647 unique eligible LDCT participants who had at least one LDCT. No statistically significant differences in LDCT category 4 were noted after screening. Lung cancers were diagnosed in 16 out of 466 (3.4%) Black LDCT participants and in 119 out of 3181 (3.7%) White LDCT participants. Black LDCT screening participants were 5.4 times less likely to be diagnosed with stage 4 lung cancers if diagnosed through screening compared to “usual care” (13% versus 44%, p <0.02). White LDCT participants were 3.5 times less likely to present with stage 4 lung cancer if diagnosed through screening compared to usual care (13% versus 35%, p < 0.0001).

Conclusions

LDCT reduced the number of stage 4 presentations in both cohorts. These findings should encourage attempts to increase LDCT utilization in all populations.

背景：对高危人群进行低剂量计算机断层扫描（LDCT）可降低肺癌死亡率。但筛查的接受程度很低，尤其是在黑人中。以前的LDCT报告中黑人的参与率很低，这可能会阻碍更广泛的采用。在这项研究中，我们报告了黑人和白人队列中LDCT筛查的结果。方法回顾性观察队列研究，使用来自LDCT筛查和肿瘤登记的并发数据，比较LDCT在减少黑人和白人参与者队列中4期肺癌发病的疗效。结果：在3647名至少有一次LDCT的独特合格LDCT参与者中，黑人占13%。筛查后LDCT第4类差异无统计学意义。466名黑人LDCT参与者中有16名（3.4%）被诊断出肺癌，3181名白人LDCT参与者中有119名（3.7%）被诊断出肺癌。如果通过筛查被诊断为4期肺癌，与“常规护理”相比，黑人LDCT筛查参与者被诊断为4期肺癌的可能性低5.4倍（13%对44%，p <0.02）。与常规护理相比，白人LDCT参与者通过筛查诊断为4期肺癌的可能性低3.5倍（13%对35%，p < 0.0001）。结论：sldct减少了两组患者的4期发病次数。这些发现应该鼓励在所有人群中增加LDCT的利用。

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引用次数: 0

First Central Asian Forum on Lung Cancer 首届中亚肺癌论坛

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-09-04 DOI: 10.1016/j.jtocrr.2025.100898

Jandos Amankulov MD, PhD , David F. Yankelevitz MD , Amangeldi Mukhamejan MD , Rowena Yip PhD, MPH , Emanuela Taioli MD, PhD , Bruce Pyenson FSA, MAAA , James Mulshine MD , Claudia I. Henschke PhD, MD

The First Central Asian Forum on Lung Cancer was held at the National Academy of Sciences of the Republic of Kazakhstan on April 8 and 9, 2025. Organized by the Kazakhstan Cancer Society, KazIOR, and the I-ELCAP/IELCART consortia, the forum brought together regional and international experts to address the urgent challenge of late-stage lung cancer diagnosis in Central Asia. National data show that fewer than one-third of patients are diagnosed at stages I and II, while over 70% present with advanced disease. High smoking prevalence, environmental exposures such as radon, asbestos, and industrial pollution, and strong geographic variation in risk highlight the need for tailored screening programs. Kazakhstan is well-positioned to scale up low-dose CT (LDCT) screening given its CT scanner capacity, mobile units for underserved regions, and prior pilot screening successes. Conference sessions emphasized risk modeling, cost-effectiveness, artificial intelligence applications, and the added value of LDCT for detecting cardiovascular disease and emphysema. Plans are underway for collaborative projects and future conferences to strengthen regional capacity for early detection and treatment.

首届中亚肺癌论坛于2025年4月8日至9日在哈萨克斯坦共和国国家科学院举行。该论坛由哈萨克斯坦癌症协会、KazIOR和I-ELCAP/IELCART联盟组织，汇集了区域和国际专家，以解决中亚晚期肺癌诊断的紧迫挑战。国家数据显示，不到三分之一的患者被诊断为I期和II期，而超过70%的患者患有晚期疾病。高吸烟率、环境暴露（如氡、石棉和工业污染）以及风险的强烈地理差异突出了有必要制定有针对性的筛查方案。鉴于其CT扫描仪的能力、为服务不足地区提供的移动设备以及先前试点筛查的成功，哈萨克斯坦处于扩大低剂量CT （LDCT）筛查的有利地位。会议强调了风险建模、成本效益、人工智能应用以及LDCT在检测心血管疾病和肺气肿方面的附加价值。正在计划开展合作项目和未来的会议，以加强区域早期发现和治疗的能力。

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引用次数: 0

Epidemiologic and Survival Analyses of Lung Cancer in Nagano Prefecture: Impact of Serial Low-Dose Computed Tomography Screening 长野县肺癌的流行病学和生存分析：系列低剂量计算机断层扫描的影响

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-08-22 DOI: 10.1016/j.jtocrr.2025.100893

Tomonobu Koizumi MD, PhD , Kengo Otsuki , Yuichiro Maruyama MD

Introduction

Low-dose computed tomography (LDCT) screening for lung cancer has been implemented in many municipalities in Nagano prefecture. We analyzed epidemiologic and survival data of patients with lung cancer among municipalities in Nagano prefecture to evaluate the impact of LDCT.

Methods

This was a retrospective cohort study. Data regarding the number of LDCT screenings, population, and lung cancer deaths in each municipality in 2011 to 2020 were collected and collated with information from the population-based cancer registry. These data were compared between municipalities that had continuously implemented LDCT (LDCT [+], n = 26) and those that had not (LDCT [−], n = 11).

Results

The mean lung cancer crude mortality rate and standardized mortality ratio were significantly lower in LDCT (+) (82.2 ± 14.1 per 100,000 (p < 0.02) and 69.7 ± 11.9 (p < 0.005), respectively) than LDCT (−) (92.0 ± 10.1 per 100,000 and 81.6 ± 11.5, respectively). In addition, the mortality rate in each municipality was significantly negative correlated with the numbers of LDCT implementation in each municipality (r = 0.39). With regard to the extent of lung cancer at diagnosis, the proportion of localized lung cancer was significantly higher in LDCT (+) (39.4 ± 7.4%) than in LDCT (−) (34.6 ± 7.4%), and the proportion of localized lung cancer in each municipality was positively correlated with the number of LDCT implementation.

Conclusion

This retrospective analysis in Nagano prefecture indicated that serial LDCT could contribute to a decrease in lung cancer mortality in the general population.

低剂量计算机断层扫描（LDCT）筛查肺癌已在长野县的许多城市实施。我们分析了长野县各市肺癌患者的流行病学和生存数据，以评估LDCT的影响。方法回顾性队列研究。收集了2011年至2020年每个城市LDCT筛查人数、人口和肺癌死亡人数的数据，并与基于人口的癌症登记处的信息进行了整理。将这些数据在连续实施LDCT的城市（LDCT [+], n = 26）和未实施LDCT的城市（LDCT [-], n = 11）之间进行比较。结果LDCT（+）组肺癌粗死亡率（82.2±14.1 / 10万）和标准化死亡率（69.7±11.9 / 10万）显著低于LDCT（-）组（92.0±10.1 / 10万）和（81.6±11.5）。此外，每个城市的死亡率与每个城市实施LDCT的数量呈显著负相关（r = 0.39）。在肺癌的诊断范围方面，LDCT（+）组肺癌的局限性比例（39.4±7.4%）明显高于LDCT（-）组肺癌的局限性比例（34.6±7.4%），各城市肺癌的局限性比例与LDCT实施次数呈正相关。结论：长野县的回顾性分析表明，连续的LDCT检查有助于降低普通人群的肺癌死亡率。

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引用次数: 0

A Multicenter, Retrospective, Real-World Study of Atezolizumab Plus Chemotherapy and Pembrolizumab Plus Chemotherapy for Older Patients With NSCLC Atezolizumab联合化疗和Pembrolizumab联合化疗治疗老年NSCLC患者的多中心、回顾性、真实世界研究

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-08-21 DOI: 10.1016/j.jtocrr.2025.100891

Kensuke Kanaoka MD , Kinnosuke Matsumoto MD , Takayuki Shiroyama MD, PhD , Akihiro Tsukaguchi MD , Nao Shoshihara MD , Koki Moritomo MD , Yuhei Kinehara MD, PhD , Yasuhiro Mihashi MD , Tomoki Kuge MD , Midori Yoneda MD , Soichiro Kato MD , Keijiro Yamauchi MD , Hirotomo Machiyama MD , Yuki Nishikawa MD , Osamu Morimura MD, PhD , Akito Miyazaki MD , Kiyohide Komuta MD , Kouji Azuma MD , Satoshi Tanaka MD , Toshie Niki MD, PhD , Atsushi Kumanogoh MD, PhD

Introduction

Evidence of immune checkpoint inhibitors (ICIs) combined with chemotherapy for older patients with NSCLC is limited. This real-world study compared the efficacy and safety of atezolizumab plus chemotherapy (ACT) with those of pembrolizumab plus chemotherapy (PCT) for older patients with advanced nonsquamous NSCLC.

Methods

This multicenter, retrospective study included 288 patients 65 years or older with advanced or recurrent nonsquamous NSCLC who received PCT or ACT as first-line treatment at 13 institutions in Japan. After one-to-one propensity score matching, overall survival (OS), the incidence of grade 3 or higher treatment-related adverse events, and all-grade pneumonitis of the PCT and ACT groups were compared.

Results

After propensity score matching, 54 patients were included in each of the groups. OS did not significantly differ between the PCT and ACT groups. The median OS was 16.6 months for both groups. Compared with the PCT group, the ACT group had a hazard ratio of 1.09 (95% confidence interval [CI]: 0.68–1.74; p = 0.7). Grade 3 or higher adverse events occurred in 40.7% and 33.3% of patients in the PCT and ACT groups, respectively (p = 0.55). The incidence of treatment-related pneumonitis of the PCT group was significantly higher (29.6%, including 11 grade ≥3 cases) than that of the ACT group (5.6%, including two grade ≥3 cases) (p = 0.002).

Conclusions

ACT may be associated with a more favorable safety profile than that of PCT for the Japanese population; therefore, ACT could be considered a treatment option for older patients with advanced nonsquamous NSCLC.

免疫检查点抑制剂（ICIs）联合化疗治疗老年非小细胞肺癌的证据有限。这项现实世界的研究比较了atezolizumab加化疗（ACT）和派姆单抗加化疗（PCT）对老年晚期非鳞状NSCLC患者的疗效和安全性。方法本多中心回顾性研究纳入了288例65岁及以上晚期或复发性非鳞状NSCLC患者，这些患者在日本13家机构接受了PCT或ACT作为一线治疗。一对一倾向评分匹配后，比较PCT组和ACT组的总生存率（OS）、3级及以上治疗相关不良事件发生率和全级别肺炎。结果经倾向评分匹配后，两组共纳入54例患者。PCT组和ACT组间OS无显著差异。两组的中位OS均为16.6个月。与PCT组相比，ACT组的风险比为1.09（95%可信区间[CI]: 0.68-1.74; p = 0.7）。PCT组和ACT组3级及以上不良事件发生率分别为40.7%和33.3% （p = 0.55）。PCT组治疗相关性肺炎的发生率（29.6%，包括11例≥3级）显著高于ACT组（5.6%，包括2例≥3级）（p = 0.002）。结论：在日本人群中，sact可能比PCT具有更有利的安全性；因此，ACT可以被认为是老年晚期非鳞状NSCLC患者的一种治疗选择。

{"title":"A Multicenter, Retrospective, Real-World Study of Atezolizumab Plus Chemotherapy and Pembrolizumab Plus Chemotherapy for Older Patients With NSCLC","authors":"Kensuke Kanaoka MD , Kinnosuke Matsumoto MD , Takayuki Shiroyama MD, PhD , Akihiro Tsukaguchi MD , Nao Shoshihara MD , Koki Moritomo MD , Yuhei Kinehara MD, PhD , Yasuhiro Mihashi MD , Tomoki Kuge MD , Midori Yoneda MD , Soichiro Kato MD , Keijiro Yamauchi MD , Hirotomo Machiyama MD , Yuki Nishikawa MD , Osamu Morimura MD, PhD , Akito Miyazaki MD , Kiyohide Komuta MD , Kouji Azuma MD , Satoshi Tanaka MD , Toshie Niki MD, PhD , Atsushi Kumanogoh MD, PhD","doi":"10.1016/j.jtocrr.2025.100891","DOIUrl":"10.1016/j.jtocrr.2025.100891","url":null,"abstract":"<div><h3>Introduction</h3><div>Evidence of immune checkpoint inhibitors (ICIs) combined with chemotherapy for older patients with NSCLC is limited. This real-world study compared the efficacy and safety of atezolizumab plus chemotherapy (ACT) with those of pembrolizumab plus chemotherapy (PCT) for older patients with advanced nonsquamous NSCLC.</div></div><div><h3>Methods</h3><div>This multicenter, retrospective study included 288 patients 65 years or older with advanced or recurrent nonsquamous NSCLC who received PCT or ACT as first-line treatment at 13 institutions in Japan. After one-to-one propensity score matching, overall survival (OS), the incidence of grade 3 or higher treatment-related adverse events, and all-grade pneumonitis of the PCT and ACT groups were compared.</div></div><div><h3>Results</h3><div>After propensity score matching, 54 patients were included in each of the groups. OS did not significantly differ between the PCT and ACT groups. The median OS was 16.6 months for both groups. Compared with the PCT group, the ACT group had a hazard ratio of 1.09 (95% confidence interval [CI]: 0.68–1.74; <em>p</em> = 0.7). Grade 3 or higher adverse events occurred in 40.7% and 33.3% of patients in the PCT and ACT groups, respectively (<em>p</em> = 0.55). The incidence of treatment-related pneumonitis of the PCT group was significantly higher (29.6%, including 11 grade ≥3 cases) than that of the ACT group (5.6%, including two grade ≥3 cases) (<em>p</em> = 0.002).</div></div><div><h3>Conclusions</h3><div>ACT may be associated with a more favorable safety profile than that of PCT for the Japanese population; therefore, ACT could be considered a treatment option for older patients with advanced nonsquamous NSCLC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100891"},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145271077","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

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 : 2025-08-07 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

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 : 2025-08-07 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

Local Ablative Therapy Followed by Osimertinib Rechallenge in Oligoprogressive, EGFR-Mutated NSCLC: A Phase 2 Study 在少进展、egfr突变的非小细胞肺癌中，局部消融治疗后再注射奥西替尼：一项2期研究

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-08-06 DOI: 10.1016/j.jtocrr.2025.100886

Azam Ghafoor MD , Nitin Roper MD , Chul Kim MD, MPH , Chuong D. Hoang MD , Aparna H. Kesarwala MD, PhD , Kevin A. Camphausen MD , Kamran Farouq BS , Elizabeth Akoth RN, BSN, MSN , Corrine Keen RN, BSN, MS , Eva Szabo MD , Hadi Bhageri MD , Arun Rajan MD , Udayan Guha MD, PhD

Introduction

Osimertinib has exhibited impressive efficacy in advanced EGFR-mutated NSCLC; however, resistance is inevitable. We hypothesized that local ablative therapy (LAT) for oligoprogressive disease (up to five sites), followed by osimertinib rechallenge, would be safe and provide additional second progression-free survival (PFS2) benefit.

Methods

This prospective phase 2 trial enrolled EGFR-mutated NSCLC patients in three cohorts: tyrosine kinase inhibitor (TKI)–naive (cohort 1), previously treated with TKI and developed acquired T790M resistance mutation (cohort 2), or previously treated with osimertinib and developed resistance (cohort 3). Patients in cohorts 1 and 2 received upfront osimertinib followed by LAT on oligoprogression, followed by osimertinib rechallenge. Cohort 3 patients underwent LAT on enrollment, followed by osimertinib rechallenge. The primary end points were safety, tolerability, and PFS2 among the patients who underwent LAT across all three cohorts combined. Secondary end points were PFS1 and overall response rates.

Results

A total of 37 patients with EGFR-mutated NSCLC were enrolled; 25 in cohort 1, nine in cohort 2, and three in cohort 3. A total of 21 patients received LAT across all three cohorts combined, yielding a median PFS2 of 3.7 months (95% confidence interval: 1.9–4.6 mo) for this population. A subgroup with exceptionally long PFS2 was identified that achieved lower tumor burden and circulating tumor DNA–negative minimal residual disease of the EGFR clone with osimertinib before undergoing LAT. Most adverse events related to LAT were grades 1 and 2.

Conclusions

This is the first prospective trial exploring local therapy and osimertinib rechallenge on oligoprogression on osimertinib. Interim analysis revealed that PFS2 in the intention-to-treat patients did not meet its primary goal when compared with historical data on continuation of first-generation EGFR TKIs after LAT. However, definite LAT can be carefully considered in patients using circulating tumor DNA–negative minimal residual disease status as a biomarker for predicting who will benefit from continuation of osimertinib post-LAT.

奥西替尼在晚期egfr突变的NSCLC中显示出令人印象深刻的疗效；然而，阻力是不可避免的。我们假设对于少进展性疾病（最多5个部位）的局部消融治疗（LAT），随后再用奥西替尼治疗，将是安全的，并提供额外的第二次无进展生存期（PFS2）获益。该前瞻性2期试验纳入了egfr突变的NSCLC患者，分为三个队列：酪氨酸激酶抑制剂（TKI）初治（队列1），先前接受过TKI治疗并发生获得性T790M耐药突变（队列2），或先前接受过奥西替尼治疗并发生耐药（队列3）。第1组和第2组的患者首先接受奥西替尼治疗，然后在进展缓慢时接受LAT治疗，然后再接受奥西替尼治疗。队列3患者在入组时接受LAT，随后接受奥西替尼再挑战。主要终点是所有三个队列中接受LAT的患者的安全性、耐受性和PFS2。次要终点为PFS1和总有效率。结果共纳入37例egfr突变的NSCLC患者；1组25人，2组9人，3组3人。在所有三个队列中，共有21例患者接受了LAT治疗，该人群的中位PFS2为3.7个月（95%置信区间：1.9-4.6个月）。发现了一个具有异常长PFS2的亚组，在接受LAT之前使用奥西替尼实现了较低的肿瘤负荷和循环肿瘤dna阴性的EGFR克隆的最小残留病。与LAT相关的大多数不良事件为1级和2级。结论：这是首个探索局部治疗和奥西替尼再挑战对奥西替尼寡进展的前瞻性试验。中期分析显示，与LAT后继续使用第一代EGFR TKIs的历史数据相比，意向治疗患者的PFS2未达到其主要目标。然而，在使用循环肿瘤dna阴性最小残留疾病状态作为预测谁将从LAT后继续使用奥西替尼获益的生物标志物的患者中，可以仔细考虑明确的LAT。

{"title":"Local Ablative Therapy Followed by Osimertinib Rechallenge in Oligoprogressive, EGFR-Mutated NSCLC: A Phase 2 Study","authors":"Azam Ghafoor MD , Nitin Roper MD , Chul Kim MD, MPH , Chuong D. Hoang MD , Aparna H. Kesarwala MD, PhD , Kevin A. Camphausen MD , Kamran Farouq BS , Elizabeth Akoth RN, BSN, MSN , Corrine Keen RN, BSN, MS , Eva Szabo MD , Hadi Bhageri MD , Arun Rajan MD , Udayan Guha MD, PhD","doi":"10.1016/j.jtocrr.2025.100886","DOIUrl":"10.1016/j.jtocrr.2025.100886","url":null,"abstract":"<div><h3>Introduction</h3><div>Osimertinib has exhibited impressive efficacy in advanced EGFR-mutated NSCLC; however, resistance is inevitable. We hypothesized that local ablative therapy (LAT) for oligoprogressive disease (up to five sites), followed by osimertinib rechallenge, would be safe and provide additional second progression-free survival (PFS2) benefit.</div></div><div><h3>Methods</h3><div>This prospective phase 2 trial enrolled <em>EGFR</em>-mutated NSCLC patients in three cohorts: tyrosine kinase inhibitor (TKI)–naive (cohort 1), previously treated with TKI and developed acquired T790M resistance mutation (cohort 2), or previously treated with osimertinib and developed resistance (cohort 3). Patients in cohorts 1 and 2 received upfront osimertinib followed by LAT on oligoprogression, followed by osimertinib rechallenge. Cohort 3 patients underwent LAT on enrollment, followed by osimertinib rechallenge. The primary end points were safety, tolerability, and PFS2 among the patients who underwent LAT across all three cohorts combined. Secondary end points were PFS1 and overall response rates.</div></div><div><h3>Results</h3><div>A total of 37 patients with EGFR-mutated NSCLC were enrolled; 25 in cohort 1, nine in cohort 2, and three in cohort 3. A total of 21 patients received LAT across all three cohorts combined, yielding a median PFS2 of 3.7 months (95% confidence interval: 1.9–4.6 mo) for this population. A subgroup with exceptionally long PFS2 was identified that achieved lower tumor burden and circulating tumor DNA–negative minimal residual disease of the EGFR clone with osimertinib before undergoing LAT. Most adverse events related to LAT were grades 1 and 2.</div></div><div><h3>Conclusions</h3><div>This is the first prospective trial exploring local therapy and osimertinib rechallenge on oligoprogression on osimertinib. Interim analysis revealed that PFS2 in the intention-to-treat patients did not meet its primary goal when compared with historical data on continuation of first-generation EGFR TKIs after LAT. However, definite LAT can be carefully considered in patients using circulating tumor DNA–negative minimal residual disease status as a biomarker for predicting who will benefit from continuation of osimertinib post-LAT.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100886"},"PeriodicalIF":3.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096128","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

Lung Cancer in Patients of African Descent: A Transcontinental Review of Epidemiology, Disparities, Outcomes, and Opportunities for Equity in Africa, North America, South America, and the Caribbean 非裔肺癌患者：非洲、北美、南美和加勒比地区流行病学、差异、结果和公平机会的跨大陆回顾

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-08-06 DOI: 10.1016/j.jtocrr.2025.100887

Elvis Obomanu MD , Colton Jones MD , Verna Vanderpuye MD , Nazik Hammad MD

Lung cancer in people of African descent is characterized by transcontinental disparities driven by epidemiologic heterogeneity, systemic inequities, and unequal access to health care. Globally, lung cancer incidence and mortality rates vary; however, underdiagnosis and late-stage presentation in low- and middle-income countries obscure the true prevalence of lung cancer because of limited cancer registries and diagnostic infrastructure. In Africa, most patients with lung cancer present at an advanced stage, primarily because of health illiteracy, misdiagnosis, delayed referrals, and inadequate treatment infrastructure. Although tobacco smoking remains a dominant risk factor worldwide, African populations are disproportionately exposed to environmental and occupational hazards, which substantially elevate their lung cancer risk. In North America, Black people experience disproportionately poor outcomes, including lower rates of lung cancer screening, early diagnosis, surgical intervention, and higher mortality rates compared with their White counterparts. In the Caribbean and South America, Black people continue to face racial infrastructural constraints, racial inequities, and elevated exposure to environmental and occupational carcinogens. Systemic barriers perpetuate these disparities, including limited access to screening, genomic testing, and guideline-concordant therapies.

Achieving equity in lung cancer outcomes requires strategic initiatives, including the expansion of lung cancer registries in Africa, the Caribbean, and South America, to inform evidence-based interventions. Urgent national and international measures focused on prevention and care for populations of African descent, implementing robust tobacco control policies, addressing systemic and racial inequities, and strengthening health care systems to report and manage lung cancer efficiently are essential steps toward reducing disparities. A transcontinental collaborative approach that includes establishing lung cancer research consortia is vital to share best practices in screening protocols, optimize early detection strategies and treatment, and advocate for policy reforms that address the global burden of lung cancer in populations of African descent.

非洲人后裔肺癌的特点是由流行病学异质性、系统性不平等和获得卫生保健机会不平等造成的跨大陆差异。在全球范围内，肺癌发病率和死亡率各不相同；然而，由于癌症登记和诊断基础设施有限，低收入和中等收入国家的诊断不足和晚期表现掩盖了肺癌的真实患病率。在非洲，大多数肺癌患者处于晚期，主要原因是卫生文盲、误诊、转诊延误和治疗基础设施不足。尽管吸烟仍然是世界范围内的一个主要风险因素，但非洲人口不成比例地暴露于环境和职业危害中，这大大提高了他们患肺癌的风险。在北美，与白人相比，黑人经历了不成比例的不良结果，包括肺癌筛查、早期诊断、手术干预的比例较低，死亡率较高。在加勒比和南美洲，黑人继续面临着种族基础设施限制、种族不平等以及环境和职业致癌物暴露的增加。系统性障碍使这些差异持续存在，包括筛查、基因组检测和符合指南的治疗的有限机会。实现肺癌结果的公平需要采取战略举措，包括扩大非洲、加勒比和南美洲的肺癌登记，为循证干预措施提供信息。紧急采取国家和国际措施，重点关注非洲人后裔的预防和护理，实施强有力的烟草控制政策，解决系统性和种族不平等问题，以及加强卫生保健系统以有效报告和管理肺癌，这些都是缩小差距的重要步骤。包括建立肺癌研究联盟在内的跨洲合作方法对于分享筛查方案的最佳做法、优化早期发现战略和治疗以及倡导政策改革以解决非洲人后裔肺癌的全球负担至关重要。

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引用次数: 0

Complete Response to BET Inhibitor in Primary Pulmonary NUT Carcinoma With Single-Cell Sequencing-Based Analysis: A Case Report 基于单细胞测序分析的原发性肺NUT癌对BET抑制剂的完全缓解：一例报告

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-08-05 DOI: 10.1016/j.jtocrr.2025.100885

Zhuomiao Ye MD , Xin Li PhD , Minghui Zhang PhD , Fei Xie MD , Xiangwen Luo MSc , Chao Deng MD , Dan Yang MSc , Mingzhu Yin PhD

NUT carcinoma is a rare and highly aggressive malignancy characterized by rapid progression, resistance to conventional therapies, and an extremely poor prognosis. This report presents a 36-year-old patient with stage IIIB primary pulmonary NUT carcinoma who achieved remarkable clinical outcomes with NHWD-870 monotherapy, a novel BET inhibitor. After just 1 month of treatment, imaging revealed a partial response, and a complete response was achieved within 5 months. Postoperative pathologic examination confirmed no residual cancer cells, and the patient has remained disease-free without recurrence or metastasis to date. To explore the underlying mechanisms of this therapeutic response, single-cell RNA sequencing was performed on the tumor tissue, revealing enhanced activity of immune cells, particularly effector CD8+ T-cells, within the tumor microenvironment. This suggests that NHWD-870 exerts its effects through both direct tumor suppression and modulation of the immune microenvironment. This case highlights the exceptional efficacy of BET inhibitors in the treatment of NUT carcinoma, as evidenced by the first report of complete response achieved with BET inhibitor monotherapy, and supports their potential as a personalized therapeutic strategy.

NUT癌是一种罕见的高侵袭性恶性肿瘤，其特点是进展迅速，对常规治疗有耐药性，预后极差。本文报道了一位36岁的IIIB期原发性肺NUT癌患者，他通过NHWD-870单药治疗（一种新型BET抑制剂）取得了显著的临床效果。仅在治疗1个月后，影像学显示部分缓解，并在5个月内达到完全缓解。术后病理检查证实无残留癌细胞，患者至今无复发或转移。为了探索这种治疗反应的潜在机制，对肿瘤组织进行了单细胞RNA测序，揭示了肿瘤微环境中免疫细胞，特别是效应CD8+ t细胞的活性增强。这表明NHWD-870通过直接抑制肿瘤和调节免疫微环境发挥作用。该病例强调了BET抑制剂治疗NUT癌的特殊疗效，首次报道的BET抑制剂单药治疗完全缓解证明了这一点，并支持其作为个性化治疗策略的潜力。

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引用次数: 0