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

Publication Date

11-1-2023

Journal

Cancer Medicine

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.

Keywords

Humans, Adolescent, Young Adult, Mice, Animals, Anthracyclines, Muscle, Skeletal, Antibiotics, Antineoplastic, Doxorubicin, Hodgkin Disease, Sarcoma, chemotherapy, clinical observations, Hodgkin's lymphoma, pediatric cancer

Comments

Supplementary Materials

PMID: 37902220