首页 > 最新文献

Journal of Thoracic Oncology最新文献

英文 中文
The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Application and Interpretation of the Residual Tumor Classification for Lung Cancer-Results from an International Survey Among Pathologists and Thoracic Surgeons. 国际肺癌研究协会肺癌分期项目:残余肿瘤(R)分类在肺癌中的应用与解释。病理学家和胸外科医生的国际调查结果。
IF 21 1区 医学 Q1 ONCOLOGY Pub Date : 2024-12-14 DOI: 10.1016/j.jtho.2024.12.007
Hans Hoffmann, Andrew G Nicholson, Frank C Detterbeck, Ming S Tsao, Marcin Ostrowski, Ramón Rami-Porta, Alain Borczuk, Mirella Marino, William D Travis, Paul E Van Schil, John Edwards

Objectives: The study aimed to assess the opinion of pathologists and thoracic surgeons of the International Association for the Study of Lung Cancer regarding the application and interpretation of the residual tumor (R) classification for lung cancer.

Methods: On the basis of their membership profiles, a total of 623 pathologists and thoracic surgeons were identified and contacted by email with a cover letter and a link to an online survey. The questionnaire consisted of 12 questions about various aspects of the application and interpretation of the R classification for lung cancer. The response rate (to at least one question) was 72% (144 pathologists and 303 surgeons).

Results: The frequency of use of the R classification varies by geographic region. Although R status is regularly reported in Europe and Asia, 70% of pathologists in the United States and Canada never include R status in reports. Similar variations exist about who assigns the R category for the resection-in Europe and the United Kingdom, it is mainly the pathologist, whereas in China, Japan and the United States, it is the surgeon. There are some good agreements about margins examined and how to manage staple lines. The category "uncertain resection" has not been practically implemented in most of the world, except at some centers in Japan and the United Kingdom.

Conclusion: This survey shows that surgical resection margins are part of routine reporting in most institutions; but the assignment of an R category is not always part of the pathology report, with considerable variation between countries. Despite the International Association for the Study of Lung Cancer proposals, the application of the uncertain resection category has not been taken up by most institutions, and further evidence is needed.

研究目的该研究旨在评估国际肺癌研究协会(IASLC)的病理学家和胸外科医生对肺癌残留肿瘤(R)分类的应用和解释的看法:根据他们的会员情况,共确定了 623 名病理学家和胸外科医生,并通过电子邮件与他们取得联系,同时附上一封求职信和一个在线调查的链接。调查问卷包括 12 个问题,涉及肺癌 R 分类的应用和解释的各个方面。回答率(至少回答一个问题)为 72%(144 名病理学家和 303 名外科医生):结果:R分类的使用频率因地理区域而异。欧洲和亚洲经常报告 R 状态,而美国或加拿大 70% 的病理学家从未在报告中列入 R 状态。在欧洲和英国,主要由病理学家指定切除术的 R 分类,而在中国/日本和美国,则由外科医生指定。在检查边缘和如何处理缝合线方面有一些很好的共识。除日本和英国的一些中心外,"不确定切除 "R(un)类别在世界大多数国家尚未实际实施:这项调查显示,手术切除边缘是大多数机构常规报告的一部分,但R类别的指定并不总是病理报告的一部分,各国之间存在很大差异。尽管国际癌症分类委员会(IASLC)提出了建议,但大多数机构并未采用R(un),因此还需要进一步的证据。
{"title":"The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Application and Interpretation of the Residual Tumor Classification for Lung Cancer-Results from an International Survey Among Pathologists and Thoracic Surgeons.","authors":"Hans Hoffmann, Andrew G Nicholson, Frank C Detterbeck, Ming S Tsao, Marcin Ostrowski, Ramón Rami-Porta, Alain Borczuk, Mirella Marino, William D Travis, Paul E Van Schil, John Edwards","doi":"10.1016/j.jtho.2024.12.007","DOIUrl":"10.1016/j.jtho.2024.12.007","url":null,"abstract":"<p><strong>Objectives: </strong>The study aimed to assess the opinion of pathologists and thoracic surgeons of the International Association for the Study of Lung Cancer regarding the application and interpretation of the residual tumor (R) classification for lung cancer.</p><p><strong>Methods: </strong>On the basis of their membership profiles, a total of 623 pathologists and thoracic surgeons were identified and contacted by email with a cover letter and a link to an online survey. The questionnaire consisted of 12 questions about various aspects of the application and interpretation of the R classification for lung cancer. The response rate (to at least one question) was 72% (144 pathologists and 303 surgeons).</p><p><strong>Results: </strong>The frequency of use of the R classification varies by geographic region. Although R status is regularly reported in Europe and Asia, 70% of pathologists in the United States and Canada never include R status in reports. Similar variations exist about who assigns the R category for the resection-in Europe and the United Kingdom, it is mainly the pathologist, whereas in China, Japan and the United States, it is the surgeon. There are some good agreements about margins examined and how to manage staple lines. The category \"uncertain resection\" has not been practically implemented in most of the world, except at some centers in Japan and the United Kingdom.</p><p><strong>Conclusion: </strong>This survey shows that surgical resection margins are part of routine reporting in most institutions; but the assignment of an R category is not always part of the pathology report, with considerable variation between countries. Despite the International Association for the Study of Lung Cancer proposals, the application of the uncertain resection category has not been taken up by most institutions, and further evidence is needed.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Screening for Lung Cancer, Overdiagnosis, and Healthcare Utilization: A Nationwide Population-Based Study. 肺癌筛查、过度诊断和医疗保健利用:一项基于全国人群的研究
IF 21 1区 医学 Q1 ONCOLOGY Pub Date : 2024-12-09 DOI: 10.1016/j.jtho.2024.12.006
So Yeon Kim, Gerard A Silvestri, Yeon Wook Kim, Roger Y Kim, Sang-Won Um, Yunjoo Im, Jung Hye Hwang, Seung Ho Choi, Jung Seop Eom, Kang Mo Gu, Yong-Soo Kwon, Shin Yup Lee, Hyun Woo Lee, Dong Won Park, Yeonjeong Heo, Seung Hun Jang, Kwang Yong Choi, Yeol Kim, Young Sik Park

Introduction: Guideline-discordant low-dose computed tomography (LDCT) screening may cause lung cancer (LC) overdiagnosis, but its extent and consequences are unclear. This study aimed to investigate the prevalence of self-initiated, non-reimbursed LDCT screening in a predominantly non-smoking population and its impact on LC epidemiology and healthcare utilization.

Methods: This nationwide cohort study analyzed data from Korea's National Health Information Database and 11 academic hospital screening centers (1999-2022). The overall analysis encompassed the entire Korean population. For non-reimbursed LDCT screening prevalence, which the National Health Information Database does not capture, a separate analysis was conducted on a cohort of 1.7 million adults to extrapolate nationwide rates. Outcomes included trends in self-initiated, non-reimbursed LDCT screening, LC incidence, mortality, stage and age at diagnosis, 5-year survival, and LC-related healthcare utilization, including surgeries and biopsies. Joinpoint regression assessed trend changes.

Results: Self-initiated, non-reimbursed LDCT screening during health check-ups increased from 29% to 60% in men and 7% to 46% in women, despite only 2.4% of men and 0.04% of women qualifying for risk-based screening. In women, localized-stage LC incidence nearly doubled (age-standardized incidence rate: from 7.6 to 13.7 per 100,000), whereas distant-stage incidence decreased (age-standardized incidence rate: from 16.1 to 15.0 per 100,000). LC mortality declined (age-standardized mortality rate: from 23.3 to 19.8 per 100,000), whereas 5-year survival rates improved substantially. LC diagnoses in women shifted towards earlier stages and younger ages. Lung surgeries for both malignant and benign lesions, frequently lacking nonsurgical biopsies, increased sharply in women.

Conclusions: Widespread guideline-discordant LDCT screening correlates with LC overdiagnosis and increased healthcare utilization, particularly in women. Randomized controlled trials are needed to assess the risks and benefits of screening in low-risk populations to determine its efficacy and consequences.

与指南不一致的低剂量计算机断层扫描(LDCT)筛查可能导致肺癌(LC)过度诊断,但其程度和后果尚不清楚。本研究旨在调查非吸烟人群中自发、不报销的LDCT筛查的流行程度及其对LC流行病学和医疗保健利用的影响。方法:这项全国性队列研究分析了韩国国家健康信息数据库(NHID)和11个学术医院筛查中心(1999-2022)的数据。整个分析涵盖了整个韩国人口。对于未报销的LDCT筛查流行率,NHID没有记录,对170万成年人的队列进行了单独的分析,以推断全国范围内的比率。结果包括自我发起的无报销LDCT筛查的趋势、LC发病率、死亡率、诊断时的分期和年龄、5年生存率和LC相关的医疗保健利用,包括手术和活检。接合点回归评估趋势变化。结果:尽管只有2.4%的男性和0.04%的女性有资格进行基于风险的筛查,但在健康检查期间,男性自我发起的、无报销的LDCT筛查从29%增加到60%,女性从7%增加到46%。在女性中,局部期LC发病率几乎翻了一番(年龄标准化发病率[ASIR],从7.6 / 10万增加到13.7 / 10万),而远期发病率下降(ASIR,从16.1 / 10万减少到15.0 / 10万)。LC死亡率下降(年龄标准化死亡率,从每10万人23.3人降至19.8人),5年生存率显著提高。女性的LC诊断转向早期和年轻。肺部恶性和良性病变的手术,往往缺乏非手术活检,在女性中急剧增加。结论:广泛的与指南不一致的LDCT筛查与LC过度诊断和医疗保健使用率增加相关,特别是在女性中。需要随机对照试验来评估在低风险人群中筛查的风险和益处,以确定其疗效和后果。
{"title":"Screening for Lung Cancer, Overdiagnosis, and Healthcare Utilization: A Nationwide Population-Based Study.","authors":"So Yeon Kim, Gerard A Silvestri, Yeon Wook Kim, Roger Y Kim, Sang-Won Um, Yunjoo Im, Jung Hye Hwang, Seung Ho Choi, Jung Seop Eom, Kang Mo Gu, Yong-Soo Kwon, Shin Yup Lee, Hyun Woo Lee, Dong Won Park, Yeonjeong Heo, Seung Hun Jang, Kwang Yong Choi, Yeol Kim, Young Sik Park","doi":"10.1016/j.jtho.2024.12.006","DOIUrl":"10.1016/j.jtho.2024.12.006","url":null,"abstract":"<p><strong>Introduction: </strong>Guideline-discordant low-dose computed tomography (LDCT) screening may cause lung cancer (LC) overdiagnosis, but its extent and consequences are unclear. This study aimed to investigate the prevalence of self-initiated, non-reimbursed LDCT screening in a predominantly non-smoking population and its impact on LC epidemiology and healthcare utilization.</p><p><strong>Methods: </strong>This nationwide cohort study analyzed data from Korea's National Health Information Database and 11 academic hospital screening centers (1999-2022). The overall analysis encompassed the entire Korean population. For non-reimbursed LDCT screening prevalence, which the National Health Information Database does not capture, a separate analysis was conducted on a cohort of 1.7 million adults to extrapolate nationwide rates. Outcomes included trends in self-initiated, non-reimbursed LDCT screening, LC incidence, mortality, stage and age at diagnosis, 5-year survival, and LC-related healthcare utilization, including surgeries and biopsies. Joinpoint regression assessed trend changes.</p><p><strong>Results: </strong>Self-initiated, non-reimbursed LDCT screening during health check-ups increased from 29% to 60% in men and 7% to 46% in women, despite only 2.4% of men and 0.04% of women qualifying for risk-based screening. In women, localized-stage LC incidence nearly doubled (age-standardized incidence rate: from 7.6 to 13.7 per 100,000), whereas distant-stage incidence decreased (age-standardized incidence rate: from 16.1 to 15.0 per 100,000). LC mortality declined (age-standardized mortality rate: from 23.3 to 19.8 per 100,000), whereas 5-year survival rates improved substantially. LC diagnoses in women shifted towards earlier stages and younger ages. Lung surgeries for both malignant and benign lesions, frequently lacking nonsurgical biopsies, increased sharply in women.</p><p><strong>Conclusions: </strong>Widespread guideline-discordant LDCT screening correlates with LC overdiagnosis and increased healthcare utilization, particularly in women. Randomized controlled trials are needed to assess the risks and benefits of screening in low-risk populations to determine its efficacy and consequences.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Use of Investigator-Assigned Subjective or Judgmental Efficacy and Toxicity Reporting in Early Phase Clinical Trials of Lung Cancer Treatments. 在肺癌治疗的早期临床试验中使用研究者指定的主观或判断的疗效和毒性报告。
IF 21 1区 医学 Q1 ONCOLOGY Pub Date : 2024-12-04 DOI: 10.1016/j.jtho.2024.12.003
William J Phillips, Alexander S Watson, D Ross Camidge

Introduction: Investigator-assigned Subjective or Judgmental Efficacy and Toxicity (ISJET) reporting represents language used to contextualize efficacy or toxicity data in clinical trials that may be inappropriate or misleading. In addition, pooling of grade 1 and 2 adverse events (AEs) may reflect a practice based on acute chemotherapy treatments rather than the expansion of chronic treatments that are now commonplace for many patients with lung cancer. In this study, we set out to evaluate the use of ISJETs and combined grade 1 and 2 reporting in early phase clinical trials of lung treatments at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

Methods: Phase I and II clinical trials of systemic treatments in adults with at least one patient with lung cancer presented at the 2024 ASCO Annual Meeting were reviewed. Baseline information and toxicity/efficacy reporting were collected. ISJETs were captured based on predefined phrases such as "tolerable," "manageable," "acceptable," or "favorable."

Results: A total of 100 eligible studies were identified. The median sample size was 43 (interquartile range 29-73), and 61 studies (61%) were phase I trials. Most studies reported any-grade (99%) and grade 3 (96%) AEs. Only 12% of the studies distinguished between grade 1 and 2 AEs. ISJETs were used to report toxicity in 88% and efficacy in 41% of the studies, respectively.

Conclusion: Most early phase lung cancer clinical trials presented at the 2024 ASCO Annual Meeting included ISJETs and did not distinguish between grade 1 and 2 AEs. Initiatives to increase objective efficacy and toxicity reporting language and more fit-for-purpose toxicity reporting are warranted.

研究者指定的主观或判断性疗效和毒性(ISJET)报告代表了临床试验中用于将疗效或毒性数据置于背景下的语言,可能不适当或具有误导性。此外,1级和2级不良事件(ae)的汇总可能反映了一种基于急性化疗治疗的做法,而不是扩大慢性治疗,而慢性治疗现在对许多肺癌患者来说很常见。在这项研究中,我们在2024年ASCO年会上开始评估isjet和联合1级和2级报告在肺治疗早期临床试验中的使用。方法:回顾在2024年ASCO年会上发表的至少1例肺癌成人全身治疗的I期和II期临床试验。收集基线信息和毒性/疗效报告。is喷气机的捕获基于预定义的短语,如“可容忍的”、“可管理的”、“可接受的”或“有利的”。结果:确定了100项符合条件的研究。中位样本量为43例(IQR 29-73), 61例(61%)为I期试验。大多数研究报告了任何级别(99%)和3级(96%)ae。只有12%的研究区分了1/2级ae。分别在88%的研究中使用isjet报告毒性和41%的研究报告疗效。结论:在2024年ASCO年会上提交的大多数早期肺癌临床试验包括isjet,并且没有区分1级和2级ae。提高客观疗效和毒性报告语言以及更符合目的的毒性报告的倡议是必要的。
{"title":"The Use of Investigator-Assigned Subjective or Judgmental Efficacy and Toxicity Reporting in Early Phase Clinical Trials of Lung Cancer Treatments.","authors":"William J Phillips, Alexander S Watson, D Ross Camidge","doi":"10.1016/j.jtho.2024.12.003","DOIUrl":"10.1016/j.jtho.2024.12.003","url":null,"abstract":"<p><strong>Introduction: </strong>Investigator-assigned Subjective or Judgmental Efficacy and Toxicity (ISJET) reporting represents language used to contextualize efficacy or toxicity data in clinical trials that may be inappropriate or misleading. In addition, pooling of grade 1 and 2 adverse events (AEs) may reflect a practice based on acute chemotherapy treatments rather than the expansion of chronic treatments that are now commonplace for many patients with lung cancer. In this study, we set out to evaluate the use of ISJETs and combined grade 1 and 2 reporting in early phase clinical trials of lung treatments at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.</p><p><strong>Methods: </strong>Phase I and II clinical trials of systemic treatments in adults with at least one patient with lung cancer presented at the 2024 ASCO Annual Meeting were reviewed. Baseline information and toxicity/efficacy reporting were collected. ISJETs were captured based on predefined phrases such as \"tolerable,\" \"manageable,\" \"acceptable,\" or \"favorable.\"</p><p><strong>Results: </strong>A total of 100 eligible studies were identified. The median sample size was 43 (interquartile range 29-73), and 61 studies (61%) were phase I trials. Most studies reported any-grade (99%) and grade 3 (96%) AEs. Only 12% of the studies distinguished between grade 1 and 2 AEs. ISJETs were used to report toxicity in 88% and efficacy in 41% of the studies, respectively.</p><p><strong>Conclusion: </strong>Most early phase lung cancer clinical trials presented at the 2024 ASCO Annual Meeting included ISJETs and did not distinguish between grade 1 and 2 AEs. Initiatives to increase objective efficacy and toxicity reporting language and more fit-for-purpose toxicity reporting are warranted.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In Response 作为回应。
IF 21 1区 医学 Q1 ONCOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.jtho.2024.09.1382
Gaetano Rocco MD, FACS, FRCS(Ed), FEBTS
{"title":"In Response","authors":"Gaetano Rocco MD, FACS, FRCS(Ed), FEBTS","doi":"10.1016/j.jtho.2024.09.1382","DOIUrl":"10.1016/j.jtho.2024.09.1382","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 12","pages":"Pages e90-e91"},"PeriodicalIF":21.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy and Safety of KRAS G12C Inhibitor IBI351 Monotherapy in Patients With Advanced NSCLC: Results From a Phase 2 Pivotal Study KRAS G12C抑制剂IBI351单药治疗晚期非小细胞肺癌患者的疗效和安全性:2期关键性研究结果。
IF 21 1区 医学 Q1 ONCOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.jtho.2024.08.005
Qing Zhou MD , Xiangjiao Meng MD , Longhua Sun MD , Dingzhi Huang MD , Nong Yang MD , Yan Yu MD , Mingfang Zhao MD , Wu Zhuang MD , Renhua Guo MD , Yi Hu MD , Yueyin Pan MD , Jinlu Shan MD , Meili Sun MD , Ying Yuan MD , Yun Fan MD , Jianan Huang MD , Lian Liu MD , Qian Chu MD , Xiuwen Wang MD , Chongrui Xu MD , Yi-Long Wu MD
<div><h3>Introduction</h3><div><em>KRAS glycine-to-cysteine substitution at codon 12 (G12C)</em> mutation is a well-recognized and increasingly promising therapeutic target with huge unmet clinical needs in NSCLC patients. IBI351 is a potent covalent and irreversible inhibitor of <em>KRAS G12C</em>. Here, we present the efficacy and safety of IBI351 from an open-label, single-arm, phase 2 pivotal study.</div></div><div><h3>Methods</h3><div>Eligible patients with NSCLC with <em>KRAS G12C</em> who failed standard therapy were enrolled. IBI351 was orally administered at a dose of 600 mg twice daily. The primary endpoint was confirmed objective response rate assessed by an independent radiological review committee (IRRC) as per Response Evaluation Criteria in Solid Tumors v1.1. Other endpoints were safety, IRRC-confirmed disease control rate, duration of response, progression-free survival (PFS), and overall survival.</div></div><div><h3>Results</h3><div>As of December 13, 2023, 116 patients were enrolled (Eastern Cooperative Oncology Group Performance Status 1: 91.4%; brain metastasis: 30.2%; prior treatments with both anti-PD-1 or anti-PD-L1 inhibitors and platinum-based chemotherapy: 84.5%). As per the IRRC assessment, the confirmed objective response rate was 49.1% (95% confidence interval [CI]: 39.7–58.6), and the disease control rate was 90.5% (95% CI: 83.7–95.2). The median duration of response was not reached whereas disease progression or death events occurred in 22 patients (38.6%), and the median PFS was 9.7 months (95% CI: 5.6–11.0). overall survival data was immature. Treatment-related adverse events (TRAEs) occurred in 107 patients (92.2%) whereas 48 patients (41.4%) had equal to or higher than grade three TRAEs. Common TRAEs were anemia (44.8%), increased alanine aminotransferase (28.4%), increased aspartate aminotransferase (27.6%), asthenia (26.7%) and presence of protein in urine (25.0%). TRAEs leading to treatment discontinuation occurred in nine patients (7.8%). In biomarker evaluable patients (n = 95), all patients had positive <em>KRAS G12C</em> in tissue whereas 72 patients were blood-positive and 23 were blood-negative for <em>KRAS G12C</em>. Patients with <em>KRAS G12C</em> in both blood and tissue had higher tumor burden at baseline (<em>p</em> < 0.05) and worse PFS (<em>p</em> < 0.05). Tumor mutation profiling identified <em>tumor protein p53</em> (45.3%), <em>serine/threonine kinase 11</em> (<em>STK11</em>) (30.5%), and <em>kelch-like ECH-associated protein 1</em> (21.1%) as the most common genes co-mutated with <em>KRAS G12C</em>. Among 13 genes with mutation frequency equal to or higher than 5%, mutations of six genes (<em>STK11, kelch-like ECH-associated protein 1, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma, DNA polymerase epsilon, SMAD family member 4,</em> and <em>BMP/retinoic acid-inducible neural-specific protein 3</em>) were significantly associated with worse PFS (<em>p</em> <
简介KRAS G12C 基因突变是一种公认的、越来越有前景的治疗靶点,NSCLC 患者的大量临床需求尚未得到满足。IBI351 是一种强效的 KRAS G12C 共价不可逆抑制剂。在此,我们介绍一项开放标签、单臂、2 期关键性研究中 IBI351 的疗效和安全性:方法:招募标准疗法失败的符合条件的 KRAS G12C NSCLC 患者。IBI351的口服剂量为600毫克,每天两次。主要终点是独立放射学审查委员会(IRRC)根据RECIST v1.1评估的确诊客观反应率(ORR)。其他终点为安全性、IRRC确认的疾病控制率(DCR)、反应持续时间(DoR)、无进展生存期(PFS)和总生存期(OS):截至2023年12月13日,共有116名患者入组(ECOG PS 1:91.4%;脑转移:30.2%;既往接受过治疗):30.2%;既往接受过抗PD-1/PD-L1抑制剂治疗和铂类化疗:84.5%)。根据 IRRC 评估,确诊 ORR 为 49.1%(95% CI:39.7-58.6),DCR 为 90.5%(95% CI:83.7-95.2)。22例(38.6%)患者未达到中位DoR,但出现了疾病进展或死亡事件,中位PFS为9.7个月(95% CI:5.6-11.0)。OS 数据尚不成熟。107例(92.2%)患者出现了治疗相关不良事件(TRAEs),48例(41.4%)患者的TRAEs≥3级。常见的不良反应包括贫血(44.8%)、丙氨酸氨基转移酶升高(28.4%)、天门冬氨酸氨基转移酶升高(27.6%)、气喘(26.7%)和蛋白尿(25.0%)。9例(7.8%)患者出现了导致停药的TRAE。在可进行生物标志物评估的患者(95 人)中,所有患者的组织中 KRAS G12C 阳性,72 人血液中 KRAS G12C 阳性,23 人血液中 KRAS G12C 阴性。血液和组织中均出现 KRAS G12C 的患者基线肿瘤负荷较高(PIBI351 单药治疗具有良好的持续疗效和可控的安全性,有望成为治疗 KRAS G12C 突变 NSCLC 的新选择。
{"title":"Efficacy and Safety of KRAS G12C Inhibitor IBI351 Monotherapy in Patients With Advanced NSCLC: Results From a Phase 2 Pivotal Study","authors":"Qing Zhou MD ,&nbsp;Xiangjiao Meng MD ,&nbsp;Longhua Sun MD ,&nbsp;Dingzhi Huang MD ,&nbsp;Nong Yang MD ,&nbsp;Yan Yu MD ,&nbsp;Mingfang Zhao MD ,&nbsp;Wu Zhuang MD ,&nbsp;Renhua Guo MD ,&nbsp;Yi Hu MD ,&nbsp;Yueyin Pan MD ,&nbsp;Jinlu Shan MD ,&nbsp;Meili Sun MD ,&nbsp;Ying Yuan MD ,&nbsp;Yun Fan MD ,&nbsp;Jianan Huang MD ,&nbsp;Lian Liu MD ,&nbsp;Qian Chu MD ,&nbsp;Xiuwen Wang MD ,&nbsp;Chongrui Xu MD ,&nbsp;Yi-Long Wu MD","doi":"10.1016/j.jtho.2024.08.005","DOIUrl":"10.1016/j.jtho.2024.08.005","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;&lt;em&gt;KRAS glycine-to-cysteine substitution at codon 12 (G12C)&lt;/em&gt; mutation is a well-recognized and increasingly promising therapeutic target with huge unmet clinical needs in NSCLC patients. IBI351 is a potent covalent and irreversible inhibitor of &lt;em&gt;KRAS G12C&lt;/em&gt;. Here, we present the efficacy and safety of IBI351 from an open-label, single-arm, phase 2 pivotal study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Eligible patients with NSCLC with &lt;em&gt;KRAS G12C&lt;/em&gt; who failed standard therapy were enrolled. IBI351 was orally administered at a dose of 600 mg twice daily. The primary endpoint was confirmed objective response rate assessed by an independent radiological review committee (IRRC) as per Response Evaluation Criteria in Solid Tumors v1.1. Other endpoints were safety, IRRC-confirmed disease control rate, duration of response, progression-free survival (PFS), and overall survival.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;As of December 13, 2023, 116 patients were enrolled (Eastern Cooperative Oncology Group Performance Status 1: 91.4%; brain metastasis: 30.2%; prior treatments with both anti-PD-1 or anti-PD-L1 inhibitors and platinum-based chemotherapy: 84.5%). As per the IRRC assessment, the confirmed objective response rate was 49.1% (95% confidence interval [CI]: 39.7–58.6), and the disease control rate was 90.5% (95% CI: 83.7–95.2). The median duration of response was not reached whereas disease progression or death events occurred in 22 patients (38.6%), and the median PFS was 9.7 months (95% CI: 5.6–11.0). overall survival data was immature. Treatment-related adverse events (TRAEs) occurred in 107 patients (92.2%) whereas 48 patients (41.4%) had equal to or higher than grade three TRAEs. Common TRAEs were anemia (44.8%), increased alanine aminotransferase (28.4%), increased aspartate aminotransferase (27.6%), asthenia (26.7%) and presence of protein in urine (25.0%). TRAEs leading to treatment discontinuation occurred in nine patients (7.8%). In biomarker evaluable patients (n = 95), all patients had positive &lt;em&gt;KRAS G12C&lt;/em&gt; in tissue whereas 72 patients were blood-positive and 23 were blood-negative for &lt;em&gt;KRAS G12C&lt;/em&gt;. Patients with &lt;em&gt;KRAS G12C&lt;/em&gt; in both blood and tissue had higher tumor burden at baseline (&lt;em&gt;p&lt;/em&gt; &lt; 0.05) and worse PFS (&lt;em&gt;p&lt;/em&gt; &lt; 0.05). Tumor mutation profiling identified &lt;em&gt;tumor protein p53&lt;/em&gt; (45.3%), &lt;em&gt;serine/threonine kinase 11&lt;/em&gt; (&lt;em&gt;STK11&lt;/em&gt;) (30.5%), and &lt;em&gt;kelch-like ECH-associated protein 1&lt;/em&gt; (21.1%) as the most common genes co-mutated with &lt;em&gt;KRAS G12C&lt;/em&gt;. Among 13 genes with mutation frequency equal to or higher than 5%, mutations of six genes (&lt;em&gt;STK11, kelch-like ECH-associated protein 1, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma, DNA polymerase epsilon, SMAD family member 4,&lt;/em&gt; and &lt;em&gt;BMP/retinoic acid-inducible neural-specific protein 3&lt;/em&gt;) were significantly associated with worse PFS (&lt;em&gt;p&lt;/em&gt; &lt; ","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 12","pages":"Pages 1630-1639"},"PeriodicalIF":21.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In the Era of Precision Medicine, Is Invasive Mediastinal Restaging Really Not Required Before Lung Resection? 精准医疗时代,肺切除术前真的不需要纵隔修补手术吗?
IF 21 1区 医学 Q1 ONCOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.jtho.2024.08.037
Sergi Call MD, Nina Reig-Oussedik MD, Bruno García-Cabo MD, José Sanz-Santos MD, Ramón Rami-Porta MD
{"title":"In the Era of Precision Medicine, Is Invasive Mediastinal Restaging Really Not Required Before Lung Resection?","authors":"Sergi Call MD,&nbsp;Nina Reig-Oussedik MD,&nbsp;Bruno García-Cabo MD,&nbsp;José Sanz-Santos MD,&nbsp;Ramón Rami-Porta MD","doi":"10.1016/j.jtho.2024.08.037","DOIUrl":"10.1016/j.jtho.2024.08.037","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 12","pages":"Pages e96-e97"},"PeriodicalIF":21.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","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 Mozambique 莫桑比克的肺癌。
IF 21 1区 医学 Q1 ONCOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.jtho.2024.08.013
Assucena Guisseve BS, MS , Albertino Mualinque MD , Matchecane Cossa MD , Ariel Durañones Jerez MD , Satish Tulsidás MD , Vania Cabrá MD , Edília Botão MD , Narciso Sitoe MD , Adriano Tivane MD , Anilsa Daniel MD , Alberto Gudo Morais MD , Atílio Morais MD, MPH, PhD , Fabíola Fernandes MD, MPH, PhD , Cesaltina Lorenzoni MD, MPH, PhD , Fátima Carneiro MD, PhD , Elizabete Nunes MD, PhD , Rita Barros PhD , Carla Carrilho MD, MS, PhD
{"title":"Lung Cancer in Mozambique","authors":"Assucena Guisseve BS, MS ,&nbsp;Albertino Mualinque MD ,&nbsp;Matchecane Cossa MD ,&nbsp;Ariel Durañones Jerez MD ,&nbsp;Satish Tulsidás MD ,&nbsp;Vania Cabrá MD ,&nbsp;Edília Botão MD ,&nbsp;Narciso Sitoe MD ,&nbsp;Adriano Tivane MD ,&nbsp;Anilsa Daniel MD ,&nbsp;Alberto Gudo Morais MD ,&nbsp;Atílio Morais MD, MPH, PhD ,&nbsp;Fabíola Fernandes MD, MPH, PhD ,&nbsp;Cesaltina Lorenzoni MD, MPH, PhD ,&nbsp;Fátima Carneiro MD, PhD ,&nbsp;Elizabete Nunes MD, PhD ,&nbsp;Rita Barros PhD ,&nbsp;Carla Carrilho MD, MS, PhD","doi":"10.1016/j.jtho.2024.08.013","DOIUrl":"10.1016/j.jtho.2024.08.013","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 12","pages":"Pages 1599-1605"},"PeriodicalIF":21.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Why and When Do We Invasively Restage After Neoadjuvant Chemoimmunotherapy? 在新辅助化疗免疫治疗后,我们为什么和何时进行有创性复发?
IF 21 1区 医学 Q1 ONCOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.jtho.2024.09.1436
Jonathan D. Spicer MD, PhD, Tina Cascone MD, PhD, Murry W. Wynes PhD, Karen L. Kelly MD
{"title":"Why and When Do We Invasively Restage After Neoadjuvant Chemoimmunotherapy?","authors":"Jonathan D. Spicer MD, PhD,&nbsp;Tina Cascone MD, PhD,&nbsp;Murry W. Wynes PhD,&nbsp;Karen L. Kelly MD","doi":"10.1016/j.jtho.2024.09.1436","DOIUrl":"10.1016/j.jtho.2024.09.1436","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 12","pages":"Pages e98-e99"},"PeriodicalIF":21.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In This Issue/Research Watch/News in Brief
IF 21 1区 医学 Q1 ONCOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.jtho.2024.10.008
{"title":"In This Issue/Research Watch/News in Brief","authors":"","doi":"10.1016/j.jtho.2024.10.008","DOIUrl":"10.1016/j.jtho.2024.10.008","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 12","pages":"Pages 1581-1584"},"PeriodicalIF":21.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143180044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Defining the Pathway to Precision Therapies for Squamous Lung Cancers 定义鳞状肺癌精确治疗途径。
IF 21 1区 医学 Q1 ONCOLOGY Pub Date : 2024-12-01 DOI: 10.1016/j.jtho.2024.09.1423
Malinda Itchins M.B.B.S., PhD, FRACP , Aaron C. Tan M.B.B.S., PhD, FRACP
{"title":"Defining the Pathway to Precision Therapies for Squamous Lung Cancers","authors":"Malinda Itchins M.B.B.S., PhD, FRACP ,&nbsp;Aaron C. Tan M.B.B.S., PhD, FRACP","doi":"10.1016/j.jtho.2024.09.1423","DOIUrl":"10.1016/j.jtho.2024.09.1423","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 12","pages":"Pages 1591-1593"},"PeriodicalIF":21.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of Thoracic Oncology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1