Longitudinal Body Composition Identifies Hepatocellular Carcinoma With Cachexia Following Combined Immunotherapy and Target Therapy (CHANCE2213)

IF 9.4 1区医学 Q1 GERIATRICS & GERONTOLOGY Journal of Cachexia Sarcopenia and Muscle Pub Date : 2024-11-27 DOI:10.1002/jcsm.13615

Zhi-Cheng Jin, Jia-Wei Zhou, Jian-Jian Chen, Rong Ding, Bernhard Scheiner, Si-Na Wang, Hai-Liang Li, Qing-Xia Shen, Qing-Yun Lu, Yi Liu, Wei-Hua Zhang, Biao Luo, Hai-Bin Shi, Ming Huang, Ye-Ming Wu, Chun-Wang Yuan, Ming-Sheng Huang, Jia-Ping Li, Jian-Bing Wu, Xiao-Li Zhu, Bin-Yan Zhong, Hai-Feng Zhou, Yu-Qing Wang, Shan-Zhi Gu, Zhi-Yi Peng, Chuan-Sheng Zheng, Rui-Bao Liu, Guo-Hui Xu, Wei-Zhu Yang, Ai-Bing Xu, Dong-Fang Liu, Xiaolong Qi, Yee Hui Yeo, Hai-Dong Zhu, Yang Zhao, David J. Pinato, Fanpu Ji, Gao-Jun Teng

{"title":"Longitudinal Body Composition Identifies Hepatocellular Carcinoma With Cachexia Following Combined Immunotherapy and Target Therapy (CHANCE2213)","authors":"Zhi-Cheng Jin, Jia-Wei Zhou, Jian-Jian Chen, Rong Ding, Bernhard Scheiner, Si-Na Wang, Hai-Liang Li, Qing-Xia Shen, Qing-Yun Lu, Yi Liu, Wei-Hua Zhang, Biao Luo, Hai-Bin Shi, Ming Huang, Ye-Ming Wu, Chun-Wang Yuan, Ming-Sheng Huang, Jia-Ping Li, Jian-Bing Wu, Xiao-Li Zhu, Bin-Yan Zhong, Hai-Feng Zhou, Yu-Qing Wang, Shan-Zhi Gu, Zhi-Yi Peng, Chuan-Sheng Zheng, Rui-Bao Liu, Guo-Hui Xu, Wei-Zhu Yang, Ai-Bing Xu, Dong-Fang Liu, Xiaolong Qi, Yee Hui Yeo, Hai-Dong Zhu, Yang Zhao, David J. Pinato, Fanpu Ji, Gao-Jun Teng","doi":"10.1002/jcsm.13615","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Cancer cachexia can impact prognosis, cause resistance to anticancer treatments and affect the tolerability of treatments. This study aims to identify hepatocellular carcinoma (HCC) with cachexia by characterizing longitudinal body composition (<span>BC</span>) trajectories.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>This longitudinal, multicentre cohort study included unresectable HCC patients treated with first-line programmed death-(ligand)1 inhibitors plus anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors between 01/2018–12/2022. <span>BC</span> measurements including skeletal muscle mass (SMM) and total adipose tissue area (TATA) were evaluated by computed tomography at the third lumbar vertebra at baseline and follow-up imaging. Unsupervised latent class growth mixed models were applied to distinguish potential longitudinal SMM and TATA trajectories for identifying cachexia. The primary study endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS), objective response rate (ORR) and safety. Multiple Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) for survival.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>A total of 411 patients with 2138 time-point measurements were included. The median age was 56 years, and 50 (12.2%) patients were female. Two distinct trajectories were identified for SMM and TATA: sharp-falling and stable. SMM sharply declined in 58 patients (14.1%) and TATA in 71 of 406 patients (17.5%) with significant worse OS (for SMM, 17.0 vs. 24.9 months; <i>p</i> < 0.001; HR = 0.59; for TATA, 15.3 vs. 25.1 months; <i>p</i> < 0.001; HR = 0.44). Patients were categorized into three phases based on trajectories: pre-cachexia (SMM and TATA stable, <i>n</i> = 299, 73.6%), cachexia (SMM or TATA sharp-falling, <i>n</i> = 86, 21.2%) and refractory cachexia (SMM and TATA sharp-falling, <i>n</i> = 21, 5.2%). Patients with refractory cachexia exhibited the worst OS, PFS and ORR, followed by those with cachexia. The median OS was 11.5 months for refractory cachexia, 17.7 for cachexia and 26.0 for pre-cachexia; median PFS was 6.0, 7.9 and 10.9 months, respectively, with ORR of 4.8%, 39.5% and 54.2%, respectively (all <i>p</i>s < 0.001). Multivariable Cox analysis identified refractory cachexia as an independent risk factor for both OS (HR = 3.31; <i>p</i> < 0.001) and PFS (HR = 2.94; <i>p</i> < 0.001), with cachexia also showing significant impacts. Grade 3–4 adverse events were higher in patients with refractory cachexia (23.8%) and cachexia (8.1%) compared with pre-cachexia (6.0%; <i>p</i> = 0.010).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>HCC patients with cachexia and refractory cachexia were identified by longitudinal <span>BC</span> trajectories. Falling trajectories of <span>BC</span> identified refractory cachexia patients with worst response, survival and poor tolerability from systemic therapy combinations.</p>\n </section>\n \n <section>\n \n <h3> Trial Registration</h3>\n \n <p>ClinicalTrials.gov identifier: NCT05278195</p>\n </section>\n </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"15 6","pages":"2705-2716"},"PeriodicalIF":9.4000,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634469/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cachexia Sarcopenia and Muscle","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jcsm.13615","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Cancer cachexia can impact prognosis, cause resistance to anticancer treatments and affect the tolerability of treatments. This study aims to identify hepatocellular carcinoma (HCC) with cachexia by characterizing longitudinal body composition (BC) trajectories.

Methods

This longitudinal, multicentre cohort study included unresectable HCC patients treated with first-line programmed death-(ligand)1 inhibitors plus anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors between 01/2018–12/2022. BC measurements including skeletal muscle mass (SMM) and total adipose tissue area (TATA) were evaluated by computed tomography at the third lumbar vertebra at baseline and follow-up imaging. Unsupervised latent class growth mixed models were applied to distinguish potential longitudinal SMM and TATA trajectories for identifying cachexia. The primary study endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS), objective response rate (ORR) and safety. Multiple Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) for survival.

Results

A total of 411 patients with 2138 time-point measurements were included. The median age was 56 years, and 50 (12.2%) patients were female. Two distinct trajectories were identified for SMM and TATA: sharp-falling and stable. SMM sharply declined in 58 patients (14.1%) and TATA in 71 of 406 patients (17.5%) with significant worse OS (for SMM, 17.0 vs. 24.9 months; p < 0.001; HR = 0.59; for TATA, 15.3 vs. 25.1 months; p < 0.001; HR = 0.44). Patients were categorized into three phases based on trajectories: pre-cachexia (SMM and TATA stable, n = 299, 73.6%), cachexia (SMM or TATA sharp-falling, n = 86, 21.2%) and refractory cachexia (SMM and TATA sharp-falling, n = 21, 5.2%). Patients with refractory cachexia exhibited the worst OS, PFS and ORR, followed by those with cachexia. The median OS was 11.5 months for refractory cachexia, 17.7 for cachexia and 26.0 for pre-cachexia; median PFS was 6.0, 7.9 and 10.9 months, respectively, with ORR of 4.8%, 39.5% and 54.2%, respectively (all ps < 0.001). Multivariable Cox analysis identified refractory cachexia as an independent risk factor for both OS (HR = 3.31; p < 0.001) and PFS (HR = 2.94; p < 0.001), with cachexia also showing significant impacts. Grade 3–4 adverse events were higher in patients with refractory cachexia (23.8%) and cachexia (8.1%) compared with pre-cachexia (6.0%; p = 0.010).

Conclusions

HCC patients with cachexia and refractory cachexia were identified by longitudinal BC trajectories. Falling trajectories of BC identified refractory cachexia patients with worst response, survival and poor tolerability from systemic therapy combinations.

Trial Registration

ClinicalTrials.gov identifier: NCT05278195

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

纵向身体成分鉴定联合免疫疗法和靶向疗法（CHANCE2213）后伴有恶病质的肝细胞癌。

背景：癌症恶病质会影响预后、导致抗癌治疗的耐药性并影响治疗的耐受性。本研究旨在通过描述纵向身体成分（BC）轨迹来识别伴有恶病质的肝细胞癌（HCC）：这项纵向多中心队列研究纳入了2018年1月至2022年12月期间接受一线程序性死亡（配体）1抑制剂加抗血管内皮生长因子抗体/酪氨酸激酶抑制剂治疗的不可切除HCC患者。在基线和随访成像时，通过第三腰椎的计算机断层扫描评估了BC测量值，包括骨骼肌质量（SMM）和总脂肪组织面积（TATA）。应用无监督潜类生长混合模型来区分潜在的纵向 SMM 和 TATA 轨迹，以识别恶病质。研究的主要终点是总生存期（OS），次要终点包括无进展生存期（PFS）、客观反应率（ORR）和安全性。采用多重考克斯比例危险模型计算调整后的生存危险比（HRs）：结果：共纳入了 411 名患者，2138 个时间点测量结果。中位年龄为 56 岁，女性患者为 50 人（12.2%）。SMM和TATA有两种不同的轨迹：急剧下降和稳定。SMM急剧下降的患者有58例（14.1%），TATA急剧下降的患者有71例（17.5%），406例患者的OS明显降低（SMM为17.0个月，TATA为24.9个月；P 结论：SMM和TATA的下降轨迹可能会影响患者的OS：通过纵向BC轨迹确定了有恶病质和难治性恶病质的HCC患者。BC的下降轨迹确定了难治性恶病质患者，这些患者的反应最差，生存期最短，对全身治疗组合的耐受性也最差：试验注册：ClinicalTrials.gov identifier：NCT05278195。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Journal of Cachexia Sarcopenia and Muscle MEDICINE, GENERAL & INTERNAL-

CiteScore

13.30

自引率

12.40%

发文量

234

审稿时长

16 weeks

期刊介绍： The Journal of Cachexia, Sarcopenia and Muscle is a peer-reviewed international journal dedicated to publishing materials related to cachexia and sarcopenia, as well as body composition and its physiological and pathophysiological changes across the lifespan and in response to various illnesses from all fields of life sciences. The journal aims to provide a reliable resource for professionals interested in related research or involved in the clinical care of affected patients, such as those suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis, or sepsis.