Early skeletal muscle loss in adolescent and young adult cancer patients treated with anthracycline chemotherapy

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2023-10-30 DOI:10.1002/cam4.6646

Savannah V. Wooten, Fei Wang, Michael E. Roth, Guanshu Liu, J. Andrew Livingston, Behrang Amini, Susan C. Gilchrist, Michelle Hildebrandt, Eugenie S. Kleinerman

{"title":"Early skeletal muscle loss in adolescent and young adult cancer patients treated with anthracycline chemotherapy","authors":"Savannah V. Wooten, Fei Wang, Michael E. Roth, Guanshu Liu, J. Andrew Livingston, Behrang Amini, Susan C. Gilchrist, Michelle Hildebrandt, Eugenie S. Kleinerman","doi":"10.1002/cam4.6646","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Early skeletal muscle loss has been observed in adolescent and young adult (AYA) sarcoma patients undergoing treatment. Identification of individuals within the AYA populace that are at greatest risk of anthracycline-induced skeletal muscle loss is unknown. Moreover, investigations which seek out underlying causes of skeletal muscle degradation during chemotherapy are critical for understanding, preventing, and reducing chronic health conditions associated with poor skeletal muscle status.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Computed tomography (CT) scans were used to investigate changes in skeletal muscle of 153 AYA sarcoma and Hodgkin lymphoma patients at thoracic vertebra 4 after anthracycline treatment. Images were examined at three time points during the first year of treatment. In parallel, we used translational juvenile mouse models to assess the impact of doxorubicin (DOX) in the soleus and gastrocnemius on muscle wasting.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Significant reductions in total skeletal muscle index and density were seen after chemotherapy in AYA cancer patients (<i>p</i> < 0.01 & <i>p</i> = 0.04, respectively). The severity of skeletal muscle loss varied by subgroup (i.e., cancer type, sex, and treatment). Murine models demonstrated a reduction in skeletal muscle fiber cross-sectional area, increased apoptosis and collagen volume for both the soleus and gastrocnemius after DOX treatment (all <i>p</i> < 0.05). After DOX, hindlimb skeletal muscle blood flow was significantly reduced (<i>p</i> < 0.01).</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Significant skeletal muscle loss is experienced early during treatment in AYA cancer patients. Reductions in skeletal muscle blood flow may be a key contributing factor to anthracycline doxorubicin induced skeletal muscle loss.</p>\n </section>\n </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"12 22","pages":"20798-20809"},"PeriodicalIF":2.9000,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.6646","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cam4.6646","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Early skeletal muscle loss has been observed in adolescent and young adult (AYA) sarcoma patients undergoing treatment. Identification of individuals within the AYA populace that are at greatest risk of anthracycline-induced skeletal muscle loss is unknown. Moreover, investigations which seek out underlying causes of skeletal muscle degradation during chemotherapy are critical for understanding, preventing, and reducing chronic health conditions associated with poor skeletal muscle status.

Methods

Computed tomography (CT) scans were used to investigate changes in skeletal muscle of 153 AYA sarcoma and Hodgkin lymphoma patients at thoracic vertebra 4 after anthracycline treatment. Images were examined at three time points during the first year of treatment. In parallel, we used translational juvenile mouse models to assess the impact of doxorubicin (DOX) in the soleus and gastrocnemius on muscle wasting.

Results

Significant reductions in total skeletal muscle index and density were seen after chemotherapy in AYA cancer patients (p < 0.01 & p = 0.04, respectively). The severity of skeletal muscle loss varied by subgroup (i.e., cancer type, sex, and treatment). Murine models demonstrated a reduction in skeletal muscle fiber cross-sectional area, increased apoptosis and collagen volume for both the soleus and gastrocnemius after DOX treatment (all p < 0.05). After DOX, hindlimb skeletal muscle blood flow was significantly reduced (p < 0.01).

Conclusion

Significant skeletal muscle loss is experienced early during treatment in AYA cancer patients. Reductions in skeletal muscle blood flow may be a key contributing factor to anthracycline doxorubicin induced skeletal muscle loss.

Abstract Image

查看原文本刊更多论文

接受蒽环类药物化疗的青少年和青年癌症患者的早期骨骼肌损失。

背景：在接受治疗的青少年和年轻成人（AYA）肉瘤患者中观察到早期骨骼肌损失。AYA人群中蒽环类药物引起的骨骼肌损失风险最大的个体的识别尚不清楚。此外，寻找化疗期间骨骼肌退化的根本原因的研究对于理解、预防和减少与骨骼肌状况不佳相关的慢性健康状况至关重要。方法：应用计算机断层扫描（CT）对153例胸4椎体AYA肉瘤和霍奇金淋巴瘤患者蒽环类药物治疗后骨骼肌的变化进行研究。在治疗的第一年中，在三个时间点检查图像。同时，我们使用转化幼年小鼠模型来评估比目鱼肌和腓肠肌中阿霉素（DOX）对肌肉萎缩的影响。结果：AYA癌症患者化疗后骨骼肌总指数和密度显著降低（p 结论：在AYA癌症患者的早期治疗过程中，骨骼肌明显缺失。骨骼肌血流量的减少可能是蒽环类药物阿霉素诱导的骨骼肌损失的关键因素。

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分钟内获得全文求助全文

来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.