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Inhibition of the PI3K/AKT/mTOR pathway in pancreatic cancer: is it a worthwhile endeavor? 抑制胰腺癌中的 PI3K/AKT/mTOR 通路:这值得一试吗?
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-10-04 eCollection Date: 2024-01-01 DOI: 10.1177/17588359241284911
Al Jarroudi Ouissam, Chibani Hind, Brahmi Sami Aziz, Afqir Said

Pancreatic cancer (PC) is an aggressive disease that is challenging to treat and is associated with a high mortality rate. The most common type of PC is pancreatic ductal adenocarcinoma (PDAC), and the existing treatment options are insufficient for PDAC patients. Due to the complexity and heterogeneity of PDAC, personalized medicine is necessary for effectively treating this illness. To achieve this, it is essential to understand the mechanism of PDAC carcinogenesis. Targeted therapies are a promising strategy to improve patient outcomes. Aberrant activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway plays a crucial role in PC pathogenesis, from initiation to progression. This review provides a comprehensive overview of the current state of knowledge regarding the PI3K pathway in PDAC, summarizes clinical data on PI3K pathway inhibition in PDAC, and explores potential effective combinations that are a promising direction requiring further investigation in PDAC.

胰腺癌(PC)是一种侵袭性疾病,治疗难度大,死亡率高。最常见的胰腺癌类型是胰腺导管腺癌(PDAC),而现有的治疗方案不足以治疗 PDAC 患者。由于 PDAC 的复杂性和异质性,要想有效治疗这种疾病,就必须采用个性化药物。为此,了解 PDAC 癌变机制至关重要。靶向疗法是改善患者预后的一种有希望的策略。磷脂酰肌醇 3- 激酶/蛋白激酶 B/哺乳动物雷帕霉素靶标(PI3K/AKT/mTOR)信号通路的异常激活在 PC 的发病过程中起着至关重要的作用,从起始到发展。本综述全面概述了目前有关 PI3K 通路在 PDAC 中作用的知识,总结了 PI3K 通路抑制在 PDAC 中作用的临床数据,并探讨了潜在的有效组合,这些组合是 PDAC 中需要进一步研究的有希望的方向。
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引用次数: 0
Efficacy and safety of perioperative, neoadjuvant, or adjuvant immunotherapy alone or in combination with chemotherapy in early-stage non-small cell lung cancer: a systematic review and meta-analysis of randomized clinical trials. 早期非小细胞肺癌围手术期、新辅助或辅助免疫疗法单独或联合化疗的疗效和安全性:随机临床试验的系统回顾和荟萃分析。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-10-04 eCollection Date: 2024-01-01 DOI: 10.1177/17588359241284929
Yunchang Meng, Qingfeng Zhang, Ranpu Wu, Huijuan Li, Zhaofeng Wang, Yang Yao, Xinjing Li, Zhangxuan Chen, Yanzhuo Gong, Hongbing Liu

Background: Neoadjuvant (NE), adjuvant (AD), and perioperative (PE) immunotherapies have gained validation in early-stage non-small cell lung cancer (NSCLC) trials. However, a comprehensive assessment of their comparative efficacy and safety is lacking.

Objectives: To compare the efficacy and safety of NE, AD, and PE immunotherapies in early-stage NSCLC.

Design: A systematic review and network meta-analysis using a Bayesian framework.

Data sources and methods: We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) of immune checkpoint inhibitors plus chemotherapy (CT) for early-stage NSCLC. Hazard ratios (HRs) and odds ratios (ORs) for binary endpoints with 95% confidence intervals (CIs) were calculated.

Results: We included 10 RCTs involving 5569 NSCLC patients, categorized as NE, PE, or AD immunotherapy. Indirect comparisons highlighted differences in efficacy between PE and AD immunotherapy, specifically in event-free survival (EFS)/disease-free survival (DFS) (HR = 0.72, 95% CI: 0.53-0.96). NE/PE immunotherapies improved pathologic complete response (pCR) (OR = 7.56, 95% CI: 5.24-10.92), major pathologic response (MPR) (OR = 5.46, 95% CI: 3.97-7.51), and EFS (HR = 0.58, 95% CI: 0.52-0.65), while AD immunotherapy enhanced DFS (HR = 0.78, 95% CI: 0.69-0.90). Overall survival (OS) benefits were seen only with PE immunotherapy (HR = 0.66, 95% CI: 0.55-0.81). PE treatment improved EFS across various subgroups (PD-L1 < 1%, IIIB, squamous, female, without MPR/pCR, epidermal growth factor receptor (EGFR) mutant-negative), except EGFR mutant-positive NSCLC (HR = 0.54, 95% CI: 0.21-1.43). AD (OR = 1.81, 95% CI: 1.20-2.73) and PE (OR = 1.28, 95% CI: 1.10-1.50) immunotherapies were associated with higher grade ⩾3 adverse events.

Conclusion: In the three treatment modalities, PE immunotherapy appears to be more effective than AD immunotherapy, with PE showing significant advantages in certain subgroups that NE does not. NE and PE immunotherapy significantly improved pCR, MPR, and EFS, while AD immunotherapy significantly improved DFS in NSCLC patients compared to the control group. However, only PE immunotherapy significantly improved OS. Differences in efficacy between NE and PE across the entire population of resectable NSCLC remain to be explored in additional studies.

背景:新辅助(NE)、辅助(AD)和围手术期(PE)免疫疗法已在早期非小细胞肺癌(NSCLC)试验中得到验证。然而,目前还缺乏对其疗效和安全性的全面评估:比较NE、AD和PE免疫疗法在早期NSCLC中的疗效和安全性:设计:采用贝叶斯框架进行系统综述和网络荟萃分析:我们在PubMed、Embase和Cochrane数据库中检索了免疫检查点抑制剂加化疗(CT)治疗早期NSCLC的随机对照试验(RCT)。计算了二元终点的危险比(HRs)和几率比(ORs)以及95%置信区间(CIs):我们纳入了10项研究,涉及5569名NSCLC患者,分为NE、PE或AD免疫疗法。间接比较强调了PE和AD免疫疗法的疗效差异,特别是在无事件生存期(EFS)/无疾病生存期(DFS)方面(HR = 0.72,95% CI:0.53-0.96)。NE/PE免疫疗法可改善病理完全应答(pCR)(OR = 7.56,95% CI:5.24-10.92)、主要病理应答(MPR)(OR = 5.46,95% CI:3.97-7.51)和无事件生存期(EFS)(HR = 0.58,95% CI:0.52-0.65),而AD免疫疗法可提高无疾病生存期(DFS)(HR = 0.78,95% CI:0.69-0.90)。只有PE免疫疗法(HR=0.66,95% CI:0.55-0.81)能提高总生存期(OS)。PE治疗改善了不同亚组的EFS(PD-L1结论:PD-L1治疗改善了患者的EFS,而PD-L2治疗改善了患者的EFS):在三种治疗模式中,PE免疫疗法似乎比AD免疫疗法更有效,PE在某些亚组中显示出明显优势,而NE则没有。与对照组相比,NE和PE免疫疗法明显改善了NSCLC患者的pCR、MPR和EFS,而AD免疫疗法则明显改善了DFS。然而,只有 PE 免疫疗法能明显改善 OS。在所有可切除的 NSCLC 患者中,NE 和 PE 的疗效差异还有待更多的研究来探讨。
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引用次数: 0
Optimizing the combination of chemotherapeutic drugs along with radiotherapy for extranodal NK/T-cell lymphoma. 优化结节外 NK/T 细胞淋巴瘤化疗药物与放疗的组合。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-10-01 eCollection Date: 2024-01-01 DOI: 10.1177/17588359241285981
Fei Luo, Qiu-Zi Zhong, Xin Liu, Xiao-Rong Hou, Li-Ting Qian, Xue-Ying Qiao, Hua Wang, Yuan Zhu, Jian-Zhong Cao, Jun-Xin Wu, Tao Wu, Su-Yu Zhu, Mei Shi, Hui-Lai Zhang, Xi-Mei Zhang, Hang Su, Yu-Qin Song, Jun Zhu, Yu-Jing Zhang, Hui-Qiang Huang, Ying Wang, Xia He, Li-Ling Zhang, Bao-Lin Qu, Yong Yang, Chen Hu, Min Deng, Shu-Lian Wang, Shu-Nan Qi, Ye-Xiong Li

Background: Extranodal natural killer/T-cell lymphoma (ENKTCL) has a unique treatment principle. However, the optimal combination of drugs along with radiotherapy (RT) is unknown.

Design: Retrospective cohort study.

Objectives: We screened multiple drug combinations to identify the most efficacious therapeutic combinations.

Methods: We reviewed 3105 patients who received 40 chemotherapy regimens with different combinations of 9 drug classes and/or RT. Least absolute shrinkage and selection operator and multivariable Cox regression analyses were used to screen efficacious single drugs and identify optimal combinations for overall survival (OS). Inverse probability of treatment weighting (IPTW) and multivariable analyses were used to compare survival between treatment regimens.

Results: Screening and validation revealed RT, asparaginase (ASP), and gemcitabine (GEM) to be the most efficacious single modality/drug. RT remained an important component of first-line treatment, whereas ASP was a fundamental drug of non-anthracycline (ANT)-based regimens. Addition of RT to non-ANT-based or ASP/GEM-based regimens, or addition of an ASP-drug into ANT-based or GEM/platinum-based regimens, improved 5-year OS significantly. Use of ASP/GEM-based regimens was associated with significantly higher 5-year OS (79.9%) compared with ASP/ANT-based (69.2%, p = 0.001), ASP/methotrexate-based (63.5%, p = 0.011), or ASP/not otherwise specified-based (63.2%, p < 0.001) regimens. The survival benefit of ASP/GEM-based regimens over other ASP-based regimens was substantial across risk-stratified and advanced-stage subgroups. The survival benefits of a combination of RT, ASP, and GEM were consistent after adjustment for confounding factors by IPTW.

Conclusion: These results suggest that combining ASP/GEM with RT for ENKTCL is an efficacious and feasible therapeutic option and provides a rationale and strategy for developing combination therapies.

背景:结节外自然杀伤/T细胞淋巴瘤(ENKTCL)具有独特的治疗原理。然而,药物与放射治疗(RT)的最佳组合尚不清楚:设计:回顾性队列研究:我们筛选了多种药物组合,以确定最有效的治疗组合:我们对接受了 40 种化疗方案的 3105 例患者进行了回顾性研究,这些方案采用了 9 种药物和/或 RT 的不同组合。采用最小绝对缩小和选择算子以及多变量 Cox 回归分析筛选疗效好的单一药物,并确定总生存期(OS)的最佳组合。采用逆治疗概率加权(IPTW)和多变量分析比较不同治疗方案的生存率:筛选和验证结果表明,RT、天冬酰胺酶(ASP)和吉西他滨(GEM)是最有效的单一治疗方式/药物。RT仍是一线治疗的重要组成部分,而ASP则是以非蒽环类(ANT)为基础的治疗方案的基本药物。在非ANT疗法或ASP/GEM疗法中加入RT,或在ANT疗法或GEM/铂类疗法中加入ASP药物,可显著改善5年生存率。与基于ASP/ANT(69.2%,P = 0.001)、基于ASP/甲氨蝶呤(63.5%,P = 0.011)或基于ASP/未另作规定(63.2%,P 结论)的方案相比,使用基于ASP/GEM的方案与更高的5年OS(79.9%)相关:这些结果表明,将 ASP/GEM 与 RT 联合用于 ENKTCL 是一种有效、可行的治疗方案,并为开发联合疗法提供了理论依据和策略。
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引用次数: 0
New frontiers in radioembolization. 放射栓塞的新领域。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-09-30 eCollection Date: 2024-01-01 DOI: 10.1177/17588359241280692
Arian Mansur, Peiman Habibollahi, Adam Fang, Armeen Mahvash, Vahid Etezadi, Robert P Liddell, Juan C Camacho, Emil I Cohen, Nima Kokabi, Aravind Arepally, Christos Georgiades, Nariman Nezami

Radioembolization is a locoregional transarterial therapy that combines radionuclide and micron-sized beads to deliver radiation internally to the target tumors based on the arterial blood flow. While initially developed as a palliative treatment option, radioembolization is now used for curative intent treatment, neoadjuvant therapy, and method to downstage or bridge for liver transplant. Radioembolization has become increasingly utilized and is an important therapeutic option for the management of hepatocellular carcinoma and liver metastasis. This article provides an overview of the techniques, challenges, and novel developments in radioembolization, including new dosimetry techniques, radionuclides, and new target tumors.

放射性栓塞疗法是一种局部经动脉疗法,它将放射性核素和微米大小的微珠结合在一起,根据动脉血流向靶肿瘤内部输送放射线。放射栓塞疗法最初是作为一种姑息治疗方法而开发的,但现在已被用于治愈性治疗、新辅助治疗以及肝脏移植的降期或桥接方法。放射栓塞疗法的应用越来越广泛,是治疗肝细胞癌和肝转移的重要治疗方法。本文概述了放射栓塞的技术、挑战和新进展,包括新的剂量测定技术、放射性核素和新的靶肿瘤。
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引用次数: 0
Advances in the mechanism of CDK4/6 inhibitor resistance in HR+/HER2- breast cancer. CDK4/6抑制剂在HR+/HER2-乳腺癌中耐药机制的研究进展。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-09-30 eCollection Date: 2024-01-01 DOI: 10.1177/17588359241282499
Sijia Wu, Junnan Xu, Yiwen Ma, Guilian Liang, Jiaxing Wang, Tao Sun

Among women, breast cancer is the most prevalent form of a malignant tumour. Among the subtypes of breast cancer, hormone receptor (HR) positive and human epidermal growth factor receptor (HER2) negative kinds make up the biggest proportion. The advent of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, which are dependent on cell cycle proteins, has greatly enhanced the prognosis of patients with advanced HR+/HER2- breast cancer. This is a specific treatment that stops the growth of cancer cells by preventing them from dividing. Nevertheless, the drug resistance of the disease unavoidably impacts the effectiveness of treatment and the prognosis of patients. This report provides a thorough analysis of the current research advancements about the resistance mechanism of CDK4/6 inhibitors in HR+/HER2- breast cancer. It presents an in-depth discussion from numerous viewpoints, such as aberrant cell cycle regulation and changes in signalling pathways. In response to the drug resistance problem, subsequent treatment strategies are also being explored, including switching to other CDK4/6 inhibitor drugs, a combination of novel endocrine therapeutic agents, an optimal combination of targeted therapies and switching to chemotherapy. An in-depth study of the resistance mechanism can assist in identifying creative tactics that can overcome or postpone drug resistance, alleviate the problem of restricted treatment strategies following drug resistance and enhance the prognosis of patients.

在女性中,乳腺癌是最常见的恶性肿瘤。在乳腺癌的亚型中,激素受体(HR)阳性和人类表皮生长因子受体(HER2)阴性占最大比例。依赖细胞周期蛋白的细胞周期蛋白依赖性激酶 4 和 6(CDK4/6)抑制剂的出现,大大改善了晚期 HR+/HER2- 乳腺癌患者的预后。这是一种通过阻止癌细胞分裂来阻止其生长的特殊疗法。然而,该疾病的耐药性不可避免地会影响治疗效果和患者的预后。本报告全面分析了目前有关 CDK4/6 抑制剂在 HR+/HER2- 乳腺癌中的耐药机制的研究进展。报告从细胞周期调控异常和信号通路变化等多个角度进行了深入探讨。针对耐药问题,后续的治疗策略也在不断探索中,包括改用其他 CDK4/6 抑制剂药物、联合使用新型内分泌治疗药物、靶向治疗的优化组合以及改用化疗等。对耐药机制的深入研究有助于找出克服或延缓耐药的创新策略,缓解耐药后治疗策略受限的问题,并改善患者的预后。
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引用次数: 0
Safety of dostarlimab in combination with chemotherapy in patients with primary advanced or recurrent endometrial cancer in a phase III, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY). 在一项III期随机安慰剂对照试验(ENGOT-EN6-NSGO/GOG-3031/RUBY)中,多司他利单抗与化疗联合治疗原发性晚期或复发性子宫内膜癌患者的安全性。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-09-28 eCollection Date: 2024-01-01 DOI: 10.1177/17588359241277656
Annika Auranen, Matthew A Powell, Vladyslav Sukhin, Lisa M Landrum, Graziana Ronzino, Joseph Buscema, Dirk Bauerschlag, Roy Lalisang, David Bender, Lucy Gilbert, Amy Armstrong, Tamar Safra, Nicole Nevadunsky, Alexandra Sebastianelli, Brian Slomovitz, Kari Ring, Robert Coleman, Iwona Podzielinski, Ashley Stuckey, Michael Teneriello, Sarah Gill, Bhavana Pothuri, Lyndsay Willmott, Sudarshan Sharma, Christine Dabrowski, Grace Antony, Shadi Stevens, Mansoor Raza Mirza, Evelyn Fleming

Background: In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting.

Objectives: The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial.

Design: RUBY is a phase III, randomized, double-blind, multicenter study of dostarlimab plus CP compared with CP alone in patients with primary advanced or recurrent EC.

Methods: Patients were randomized 1:1 to dostarlimab 500 mg, or placebo, plus CP every 3 weeks for 6 cycles, followed by dostarlimab 1000 mg, or placebo, every 6 weeks for up to 3 years. Adverse events (AEs) were assessed according to Common Terminology Criteria for Adverse Events, version 4.03.

Results: The safety population included 487 patients who received ⩾1 dose of treatment (241 dostarlimab plus CP; 246 placebo plus CP). Treatment-emergent AEs were experienced by 100% of patients in both arms. TRAEs occurred in 97.9% of the dostarlimab arm and 98.8% of the placebo arm.The most common TRAEs occurred at similar rates between arms and were mostly low grade. IrAEs occurred in 58.5% of patients in the dostarlimab arm and 37.0% of patients in the placebo arm. Dostarlimab- or placebo-related irAEs were reported in 40.7% of patients in the dostarlimab arm and 16.3% of the placebo arm.

Conclusion: The safety profile of dostarlimab plus CP was generally consistent with that of the individual components. Dostarlimab plus CP has a favorable benefit-risk profile and is a new standard of care for patients with primary advanced or recurrent EC.

Trial registration: NCT03981796.

研究背景在针对原发性晚期或复发性子宫内膜癌(EC)患者的III期RUBY试验(NCT03981796)第一部分中,与单用卡铂-紫杉醇(CP)相比,多司他单抗联合卡铂-紫杉醇(CP)可显著改善无进展生存期和总生存期。在这种情况下,免疫疗法联合化疗的安全性数据有限:本分析旨在确定治疗相关不良事件(TRAE)和免疫相关不良事件(irAE)的发生情况,并描述RUBY试验第一部分中irAE的处理情况:RUBY是一项III期随机、双盲、多中心研究,在原发性晚期或复发性EC患者中,多斯他利单抗联合CP与单用CP进行比较:患者按1:1的比例随机接受多斯他利单抗500毫克或安慰剂加CP治疗,每3周1次,共6个周期;随后接受多斯他利单抗1000毫克或安慰剂治疗,每6周1次,共3年。不良事件(AEs)根据《不良事件通用术语标准》4.03版进行评估:安全人群包括487名接受了⩾1个剂量治疗的患者(241名多司他(dostarlimab)加CP;246名安慰剂加CP)。两组100%的患者都出现了治疗突发AEs。97.9%的多司他(dostarlimab)治疗组和98.8%的安慰剂治疗组患者发生了TRAE。58.5%的多斯他利单抗治疗组患者和37.0%的安慰剂治疗组患者发生了IrAEs。多斯他利单抗治疗组40.7%的患者和安慰剂治疗组16.3%的患者发生了多斯他利单抗或安慰剂相关的非器质性损伤:结论:多司他利单抗联合CP的安全性与单个成分的安全性基本一致。多斯他利单抗联合CP具有良好的收益风险特征,是治疗原发性晚期或复发性EC患者的新标准:试验注册:NCT03981796。
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引用次数: 0
Low pre-immunotherapy forced vital capacity is associated with poor outcomes in non-small cell lung cancer patients receiving immunotherapy regardless of prior treatment history. 在接受免疫疗法的非小细胞肺癌患者中,免疫疗法前强迫生命容量低与不良预后有关,与之前的治疗史无关。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-09-25 eCollection Date: 2024-01-01 DOI: 10.1177/17588359241281480
Jeong Uk Lim, Hye Seon Kang, Chang Dong Yeo, Ju Sang Kim, Sung Kyoung Kim, Jin Woo Kim, Seung Joon Kim, Sang Haak Lee

Background: Many patients with lung cancer have underlying chronic lung diseases. We assume that baseline lung functions might also affect the prognosis of non-small cell lung cancer (NSCLC) patients receiving immunotherapy.

Objectives: We aimed to assess the impact of pretreatment clinical parameters, including lung function measures such as forced vital capacity (FVC), on the prognosis of patients with NSCLC following immune checkpoint inhibitors (ICIs) therapy.

Design: Retrospective multicenter study.

Methods: Study subjects were consecutively selected from a multicenter cohort of patients with NSCLC who were undergoing immunotherapy. Patients were selected regardless of their initial cancer stage and prior treatment. The primary outcome was immunotherapy-related overall survival (iOS), defined as the duration from the initiation of immunotherapy to the time patients were censored. Spirometry values were acquired before bronchodilator application and were performed within the year before the first ICI treatment.

Results: We selected 289 patients for evaluation. The median iOS was 10.9 months (95% confidence interval (CI), 7.5-14.3). Programmed death-ligand 1 (PD-L1) expression, tested by SP263, was <1% in 20.9%, 1%-49% in 44.3%, and ⩾50% in 32.6% of the patients. ICI was used most often as second-line treatment (70.2%), followed by first line (13.1%), and third line (11.4%). In the Kaplan-Meier analysis, the median iOS of the low FVC group was significantly shorter than that in the preserved FVC group (6.10 (95% CI, 4.45-7.76) months vs 14.40 (95% CI, 10.61-18.34) months, p < 0.001)). A Cox regression analysis for iOS showed that age, poor performance status, PD-L1 expression measured by SP263, stage at diagnosis, and FVC (% predicted) were independent predictive factors. When we replaced FVC (%) in the multivariable analysis with forced expiratory volume in 1 s (%), diffusing lung capacity for carbon monoxide (DLco; %), or DLco (absolute), each of the pulmonary function factors showed a significant association with iOS.

Conclusion: Pre-immunotherapy FVC (%) predicted immunotherapy-related outcomes in NSCLC patients, regardless of initial stage at diagnosis and prior treatment modalities.

背景:许多肺癌患者都有潜在的慢性肺部疾病。我们认为基线肺功能也可能影响接受免疫疗法的非小细胞肺癌(NSCLC)患者的预后:我们旨在评估接受免疫检查点抑制剂(ICIs)治疗的非小细胞肺癌患者在治疗前临床参数(包括肺功能指标,如用力肺活量(FVC))对预后的影响:回顾性多中心研究:研究对象从接受免疫疗法的 NSCLC 患者多中心队列中连续选出。患者的初始癌症分期和之前的治疗均不受限制。主要研究结果是免疫治疗相关总生存期(iOS),即从开始免疫治疗到患者剔除的时间。肺活量测定值是在使用支气管扩张剂之前获得的,并且是在首次接受 ICI 治疗前一年内进行的:我们选择了 289 名患者进行评估。中位 iOS 为 10.9 个月(95% 置信区间 (CI),7.5-14.3)。通过SP263检测的程序性死亡配体1(PD-L1)表达量为P:免疫治疗前的FVC(%)可预测NSCLC患者的免疫治疗相关结果,与诊断时的初始分期和之前的治疗方式无关。
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引用次数: 0
Landscape of C-MET overexpression in non-small cell lung cancer: a large-scale study of clinicomolecular features and prognosis based on Chinese data. 非小细胞肺癌中C-MET过表达的格局:基于中国数据的临床分子特征和预后的大规模研究
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-09-25 eCollection Date: 2024-01-01 DOI: 10.1177/17588359241279715
Shuting Zhan, Jianfu Li, Bo Cheng, Caichen Li, Yi Feng, Lei Fan, Shan Xiong, Wenchuang Zeng, Qi Cai, Yang Xiang, Huiting Wang, Chunyan Li, Peiling Chen, Xin Zheng, Wenhai Fu, Zhexue Hao, Jianxing He, Wenhua Liang

Background: Real-world data on C-MET protein overexpression in non-small cell lung cancer (NSCLC) patients, particularly among the Asian Chinese population, are limited.

Objectives: This study aimed to evaluate the clinicomolecular characteristics and prognosis of C-MET overexpression in Chinese NSCLC patients, focusing on those with positive C-MET overexpression (immunohistochemistry (IHC) 3+).

Design: A retrospective and observational study.

Methods: Data were collected from NSCLC patients diagnosed at the First Affiliated Hospital of Guangzhou Medical University between November 2006 and April 2021. We identified C-MET overexpression using IHC and C-MET overexpression positivity was defined as IHC 3+ with ⩾50% tumor cells. Additionally, patient genotypes were collected for subgroup analysis.

Results: Data from 9785 NSCLC patients were collected. C-MET (-) accounted for 5% (503/9785), C-MET (+) for 27% (2654/9785), C-MET (++) for 36% (3464/9785), and C-MET (+++) for 32% (3164/9785). Genetic testing was available for 4326 patients. Wild-type was observed in 37% (1591 cases), with epidermal growth factor receptor (EGFR) abnormalities being the most common at 49% (2127 cases). Positive C-MET overexpression correlated significantly with women (p < 0.001), early-stage (p = 0.003), adenocarcinoma (p < 0.001), and driver mutations (p < 0.001). Patients with anaplastic lymphoma kinase (ALK) alterations had a higher occurrence of C-MET overexpression positivity (57.1%). Positive C-MET overexpression was significantly associated with EGFR (p < 0.001), ALK (p < 0.001), and KRAS alterations (p = 0.024). Compared to C-MET overexpression (IHC 0), C-MET overexpression (IHC 2+) (hazard ratio (HR) = 0.455, p < 0.001) and C-MET overexpression (IHC 3+) (HR = 0.569, p < 0.001) were correlated with better overall survival in overall NSCLC patients, especially for C-MET overexpression (IHC 2+).

Conclusion: Our study elucidates the clinicomolecular characteristics and prognosis of C-MET overexpression in NSCLC patients, particularly those with positive C-MET overexpression (IHC 3+). This provides insight into the prevalence of C-MET overexpression in Chinese NSCLC patients and offers a basis for considering C-MET overexpression as a prognostic and predictive marker in NSCLC.

背景:关于非小细胞肺癌(NSCLC)患者C-MET蛋白过表达的真实世界数据有限,尤其是在亚洲华人群体中:关于非小细胞肺癌(NSCLC)患者C-MET蛋白过表达的真实世界数据有限,尤其是在亚洲华裔人群中:本研究旨在评估中国非小细胞肺癌患者C-MET蛋白过表达的临床分子特征和预后,重点关注C-MET蛋白过表达阳性(免疫组化(IHC)3+)的患者:设计:一项回顾性观察研究:数据来自2006年11月至2021年4月期间在广州医科大学附属第一医院确诊的NSCLC患者。我们使用IHC鉴定C-MET过表达,C-MET过表达阳性定义为IHC 3+且肿瘤细胞占50%。此外,还收集了患者的基因型以进行亚组分析:结果:共收集了9785名NSCLC患者的数据。C-MET(-)占5%(503/9785),C-MET(+)占27%(2654/9785),C-MET(++)占36%(3464/9785),C-MET(+++)占32%(3164/9785)。4326 名患者接受了基因检测。野生型占 37%(1591 例),表皮生长因子受体(EGFR)异常最常见,占 49%(2127 例)。C-MET 过表达阳性与女性有显著相关性(P P = 0.003),腺癌(P P ALK)改变的 C-MET 过表达阳性发生率更高(57.1%)。C-MET过表达阳性与表皮生长因子受体(EGFR)(p ALK)(p KRAS)改变明显相关(p = 0.024)。与C-MET过表达(IHC 0)相比,C-MET过表达(IHC 2+)(危险比(HR)= 0.455,p p 结论:我们的研究阐明了NSCLC患者C-MET过表达的临床分子特征和预后,尤其是C-MET过表达阳性(IHC 3+)的患者。这有助于了解C-MET过表达在中国NSCLC患者中的流行情况,并为将C-MET过表达作为NSCLC的预后和预测标志物提供依据。
{"title":"Landscape of C-MET overexpression in non-small cell lung cancer: a large-scale study of clinicomolecular features and prognosis based on Chinese data.","authors":"Shuting Zhan, Jianfu Li, Bo Cheng, Caichen Li, Yi Feng, Lei Fan, Shan Xiong, Wenchuang Zeng, Qi Cai, Yang Xiang, Huiting Wang, Chunyan Li, Peiling Chen, Xin Zheng, Wenhai Fu, Zhexue Hao, Jianxing He, Wenhua Liang","doi":"10.1177/17588359241279715","DOIUrl":"10.1177/17588359241279715","url":null,"abstract":"<p><strong>Background: </strong>Real-world data on C-MET protein overexpression in non-small cell lung cancer (NSCLC) patients, particularly among the Asian Chinese population, are limited.</p><p><strong>Objectives: </strong>This study aimed to evaluate the clinicomolecular characteristics and prognosis of C-MET overexpression in Chinese NSCLC patients, focusing on those with positive C-MET overexpression (immunohistochemistry (IHC) 3+).</p><p><strong>Design: </strong>A retrospective and observational study.</p><p><strong>Methods: </strong>Data were collected from NSCLC patients diagnosed at the First Affiliated Hospital of Guangzhou Medical University between November 2006 and April 2021. We identified C-MET overexpression using IHC and C-MET overexpression positivity was defined as IHC 3+ with ⩾50% tumor cells. Additionally, patient genotypes were collected for subgroup analysis.</p><p><strong>Results: </strong>Data from 9785 NSCLC patients were collected. C-MET (-) accounted for 5% (503/9785), C-MET (+) for 27% (2654/9785), C-MET (++) for 36% (3464/9785), and C-MET (+++) for 32% (3164/9785). Genetic testing was available for 4326 patients. Wild-type was observed in 37% (1591 cases), with epidermal growth factor receptor (<i>EGFR</i>) abnormalities being the most common at 49% (2127 cases). Positive C-MET overexpression correlated significantly with women (<i>p</i> < 0.001), early-stage (<i>p</i> = 0.003), adenocarcinoma (<i>p</i> < 0.001), and driver mutations (<i>p</i> < 0.001). Patients with anaplastic lymphoma kinase (<i>ALK</i>) alterations had a higher occurrence of C-MET overexpression positivity (57.1%). Positive C-MET overexpression was significantly associated with <i>EGFR</i> (<i>p</i> < 0.001), <i>ALK</i> (<i>p</i> < 0.001), and <i>KRAS</i> alterations (<i>p</i> = 0.024). Compared to C-MET overexpression (IHC 0), C-MET overexpression (IHC 2+) (hazard ratio (HR) = 0.455, <i>p</i> < 0.001) and C-MET overexpression (IHC 3+) (HR = 0.569, <i>p</i> < 0.001) were correlated with better overall survival in overall NSCLC patients, especially for C-MET overexpression (IHC 2+).</p><p><strong>Conclusion: </strong>Our study elucidates the clinicomolecular characteristics and prognosis of C-MET overexpression in NSCLC patients, particularly those with positive C-MET overexpression (IHC 3+). This provides insight into the prevalence of C-MET overexpression in Chinese NSCLC patients and offers a basis for considering C-MET overexpression as a prognostic and predictive marker in NSCLC.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241279715"},"PeriodicalIF":4.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular features of NSCLC patients with liver metastasis. 肝转移的 NSCLC 患者的分子特征。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-09-24 eCollection Date: 2024-01-01 DOI: 10.1177/17588359241275421
Jun Zhao, Jia Zhong, Yujie Chen, Zipei Chen, Huan Yin, Yuange He, Rongrong Chen, Renhua Guo

Background: Metastasis is the primary cause of lung cancer-related death. Primary cancer cells invade through the lymphatic or blood vessels to distant sites. Recently, it was proposed that lymphatic metastasis was more a hallmark of tumor aggressiveness or metastatic potential than a gateway to metastases. Therefore, the underlying molecular mechanism of metastasis is not entirely clear.

Objectives: This study aimed to explore the genetic mechanisms underlying liver metastases from lung cancer and to evaluate the efficacy of different therapies in these patients.

Design: We retrospectively analyzed the mutation spectrum of different biopsy samples including primary lung tumors, liver, lymph node metastasis, and circulating tumor DNA (ctDNA) from 1090 non-small-cell lung cancer (NSCLC) patients with liver metastasis between the years 2017 and 2022.

Methods: Demographic and disease characteristics were summarized using descriptive parameters. Time to treatment discontinuation was used to analyze the clinical outcome.

Results: More liquid biopsies were performed than tissue biopsies, especially in the treated advanced NSCLC patients. Liver metastasis before treatment was associated with poor response to immune checkpoint inhibitors and targeted therapy. Liver and lymph node metastasis had higher levels of single nucleotide variants and copy number variants than primary lung tumors. In paired lung and liver, lymph nodes, and simultaneous ctDNA, we found actionable mutations were always shared, while metastasis samples had multiple private mutations. Serial ctDNA analysis identifies potential resistant mutations and describes the evolution of tumor cells.

Conclusion: Liver and lymph node metastasis in NSCLC showed shared actionable mutations. Of note, the discrepancy of private mutations in liver and lymph node metastases indicated that liver metastases are mainly seeded by the primary tumor rather than the earlier colonized lymph node metastases.

背景:转移是肺癌相关死亡的主要原因。原发癌细胞通过淋巴或血管侵入远处部位。最近,有人提出淋巴转移与其说是转移的途径,不如说是肿瘤侵袭性或转移潜力的标志。因此,转移的潜在分子机制尚不完全清楚:本研究旨在探索肺癌肝转移的遗传机制,并评估不同疗法对这些患者的疗效:我们回顾性分析了2017年至2022年期间1090例非小细胞肺癌(NSCLC)肝转移患者不同活检样本的突变谱,包括原发性肺肿瘤、肝脏、淋巴结转移以及循环肿瘤DNA(ctDNA):采用描述性参数总结人口统计学和疾病特征。结果:进行液体活检的人数多于进行液体活检的人数:进行液体活检的人数多于组织活检,尤其是在接受治疗的晚期NSCLC患者中。治疗前的肝转移与免疫检查点抑制剂和靶向治疗的不良反应有关。与原发性肺肿瘤相比,肝脏和淋巴结转移瘤的单核苷酸变异和拷贝数变异水平更高。在配对的肺和肝脏、淋巴结以及同时进行的ctDNA中,我们发现可操作的突变总是共享的,而转移瘤样本则有多个私有突变。连续的ctDNA分析可确定潜在的耐药突变,并描述肿瘤细胞的进化过程:结论:NSCLC的肝转移和淋巴结转移显示出共享的可操作突变。值得注意的是,肝转移灶和淋巴结转移灶的个体突变差异表明,肝转移灶主要由原发肿瘤播种,而非早期定植的淋巴结转移灶。
{"title":"Molecular features of NSCLC patients with liver metastasis.","authors":"Jun Zhao, Jia Zhong, Yujie Chen, Zipei Chen, Huan Yin, Yuange He, Rongrong Chen, Renhua Guo","doi":"10.1177/17588359241275421","DOIUrl":"https://doi.org/10.1177/17588359241275421","url":null,"abstract":"<p><strong>Background: </strong>Metastasis is the primary cause of lung cancer-related death. Primary cancer cells invade through the lymphatic or blood vessels to distant sites. Recently, it was proposed that lymphatic metastasis was more a hallmark of tumor aggressiveness or metastatic potential than a gateway to metastases. Therefore, the underlying molecular mechanism of metastasis is not entirely clear.</p><p><strong>Objectives: </strong>This study aimed to explore the genetic mechanisms underlying liver metastases from lung cancer and to evaluate the efficacy of different therapies in these patients.</p><p><strong>Design: </strong>We retrospectively analyzed the mutation spectrum of different biopsy samples including primary lung tumors, liver, lymph node metastasis, and circulating tumor DNA (ctDNA) from 1090 non-small-cell lung cancer (NSCLC) patients with liver metastasis between the years 2017 and 2022.</p><p><strong>Methods: </strong>Demographic and disease characteristics were summarized using descriptive parameters. Time to treatment discontinuation was used to analyze the clinical outcome.</p><p><strong>Results: </strong>More liquid biopsies were performed than tissue biopsies, especially in the treated advanced NSCLC patients. Liver metastasis before treatment was associated with poor response to immune checkpoint inhibitors and targeted therapy. Liver and lymph node metastasis had higher levels of single nucleotide variants and copy number variants than primary lung tumors. In paired lung and liver, lymph nodes, and simultaneous ctDNA, we found actionable mutations were always shared, while metastasis samples had multiple private mutations. Serial ctDNA analysis identifies potential resistant mutations and describes the evolution of tumor cells.</p><p><strong>Conclusion: </strong>Liver and lymph node metastasis in NSCLC showed shared actionable mutations. Of note, the discrepancy of private mutations in liver and lymph node metastases indicated that liver metastases are mainly seeded by the primary tumor rather than the earlier colonized lymph node metastases.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241275421"},"PeriodicalIF":4.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of neoadjuvant chemotherapy response and prognosis among pegylated liposomal doxorubicin, epirubicin and pirarubicin in HR ⩽ 10%/HER2-negative breast cancer: an exploratory real-world multicentre cohort study. HR ⩽10%/HER2阴性乳腺癌患者接受聚乙二醇脂质体多柔比星、表柔比星和吡拉比星新辅助化疗的反应和预后比较:一项探索性真实世界多中心队列研究。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-09-23 eCollection Date: 2024-01-01 DOI: 10.1177/17588359241279695
Yue Hong, Jing Peng, Qitong Chen, Qin Zhou, Feng Xu, Jia Yao, Qiongyan Zou, Liqin Yuan, Lun Li, Qian Long, Liqiu Liao, Mingwen Liu, Xuan Liu, Danhua Zhang, Shouman Wang, Wenjun Yi

Background: Pegylated liposomal doxorubicin (PLD), epirubicin and pirarubicin are the main anthracyclines widely used in China. PLD demonstrates therapeutic response comparable to epirubicin and pirarubicin in neoadjuvant chemotherapy (NAC) of breast cancer.

Objectives: The objectives of our study were to retrospectively assess the real-world effectiveness and prognostic characteristics of PLD as NAC for HR ⩽ 10%/human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

Design: This was a retrospective study.

Methods: Our study enrolled patients with HR ⩽ 10%/HER2-negative breast cancer who received PLD-, epirubicin- or pirarubicin-based NAC from three centres in Hunan Province, China, between 2015 and 2022. We employed inverse probability of treatment weighting to balance the differences in patients' characteristics among the PLD, epirubicin, and pirarubicin groups. The endpoints were pathological complete response (pCR), event-free survival (EFS), and overall survival (OS).

Results: A total of 267 patients were included. After NAC, the pCR rates in PLD group were superior to epirubicin group (PLD, 34.1%; epirubicin, 20.8%, p = 0.038). The differences in EFS (log-rank p = 0.99) and OS (log-rank p = 0.33) among the three groups were not statistically significant. Among the three groups, non-pCR patients had worse EFS than pCR patients (log-rank p = 0.014). For patients with pCR, the differences in EFS (log-rank p = 0.47) and OS (log-rank p = 0.38) were not statistically significant among the three groups, and the EFS (log-rank p = 0.59) and OS (log-rank p = 0.14) of non-pCR patients in the PLD group were similar to those in the epirubicin and pirarubicin groups.

Conclusion: PLD had a similar therapeutic response and prognosis compared to epirubicin or pirarubicin in NAC for patients with HR ⩽ 10%/HER2 negative breast cancer, which means that PLD represents a potential NAC option.

背景:聚乙二醇脂质体多柔比星(PLD)、表柔比星和吡拉比星是中国广泛使用的主要蒽环类药物。在乳腺癌新辅助化疗(NAC)中,PLD的治疗反应与表柔比星和吡柔比星相当:我们的研究旨在回顾性评估PLD作为HR⩽10%/人表皮生长因子受体2(HER2)阴性乳腺癌新辅助化疗的实际疗效和预后特征:这是一项回顾性研究:我们的研究纳入了中国湖南省三个中心在2015年至2022年间接受以PLD、表柔比星或吡拉比星为基础的新农合治疗的HR⩽10%/HER2阴性乳腺癌患者。我们采用了逆治疗概率加权法来平衡PLD组、表柔比星组和吡拉比星组之间患者特征的差异。研究终点为病理完全反应(pCR)、无事件生存期(EFS)和总生存期(OS):结果:共纳入 267 例患者。NAC后,PLD组的病理完全反应率优于表柔比星组(PLD,34.1%;表柔比星,20.8%,P = 0.038)。三组患者的 EFS(log-rank p = 0.99)和 OS(log-rank p = 0.33)差异无统计学意义。在三组患者中,非 pCR 患者的 EFS 差于 pCR 患者(log-rank p = 0.014)。对于pCR患者,三组的EFS(log-rank p = 0.47)和OS(log-rank p = 0.38)差异无统计学意义,PLD组非CR患者的EFS(log-rank p = 0.59)和OS(log-rank p = 0.14)与表柔比星组和吡拉比星组相似:结论:对于HR⩽10%/HER2阴性乳腺癌患者,与表柔比星或吡拉比星相比,PLD在新农合中具有相似的治疗反应和预后,这意味着PLD是一种潜在的新农合选择。
{"title":"Comparison of neoadjuvant chemotherapy response and prognosis among pegylated liposomal doxorubicin, epirubicin and pirarubicin in HR ⩽ 10%/HER2-negative breast cancer: an exploratory real-world multicentre cohort study.","authors":"Yue Hong, Jing Peng, Qitong Chen, Qin Zhou, Feng Xu, Jia Yao, Qiongyan Zou, Liqin Yuan, Lun Li, Qian Long, Liqiu Liao, Mingwen Liu, Xuan Liu, Danhua Zhang, Shouman Wang, Wenjun Yi","doi":"10.1177/17588359241279695","DOIUrl":"https://doi.org/10.1177/17588359241279695","url":null,"abstract":"<p><strong>Background: </strong>Pegylated liposomal doxorubicin (PLD), epirubicin and pirarubicin are the main anthracyclines widely used in China. PLD demonstrates therapeutic response comparable to epirubicin and pirarubicin in neoadjuvant chemotherapy (NAC) of breast cancer.</p><p><strong>Objectives: </strong>The objectives of our study were to retrospectively assess the real-world effectiveness and prognostic characteristics of PLD as NAC for HR ⩽ 10%/human epidermal growth factor receptor 2 (HER2)-negative breast cancer.</p><p><strong>Design: </strong>This was a retrospective study.</p><p><strong>Methods: </strong>Our study enrolled patients with HR ⩽ 10%/HER2-negative breast cancer who received PLD-, epirubicin- or pirarubicin-based NAC from three centres in Hunan Province, China, between 2015 and 2022. We employed inverse probability of treatment weighting to balance the differences in patients' characteristics among the PLD, epirubicin, and pirarubicin groups. The endpoints were pathological complete response (pCR), event-free survival (EFS), and overall survival (OS).</p><p><strong>Results: </strong>A total of 267 patients were included. After NAC, the pCR rates in PLD group were superior to epirubicin group (PLD, 34.1%; epirubicin, 20.8%, <i>p</i> = 0.038). The differences in EFS (log-rank <i>p</i> = 0.99) and OS (log-rank <i>p</i> = 0.33) among the three groups were not statistically significant. Among the three groups, non-pCR patients had worse EFS than pCR patients (log-rank <i>p</i> = 0.014). For patients with pCR, the differences in EFS (log-rank <i>p</i> = 0.47) and OS (log-rank <i>p</i> = 0.38) were not statistically significant among the three groups, and the EFS (log-rank <i>p</i> = 0.59) and OS (log-rank <i>p</i> = 0.14) of non-pCR patients in the PLD group were similar to those in the epirubicin and pirarubicin groups.</p><p><strong>Conclusion: </strong>PLD had a similar therapeutic response and prognosis compared to epirubicin or pirarubicin in NAC for patients with HR ⩽ 10%/HER2 negative breast cancer, which means that PLD represents a potential NAC option.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241279695"},"PeriodicalIF":4.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Therapeutic Advances in Medical Oncology
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