Survival impact and risk factors of skeletal muscle loss during first-line EGFR-TKIs therapy in advanced lung adenocarcinoma patients
Abstract Purpose The impact of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) on muscle mass in individuals with advanced lung cancer has yet to be fully delineated. This study aimed to examine the dynamics of skeletal muscle mass during EGFR-TKIs targeted therapy, elucida...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-03-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-025-13775-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850252038489767936 |
|---|---|
| author | Xin Nie Mingzhu Zou Chenhui Song Ping Zhang Di Ma Di Cui Gang Cheng Lin Li |
| author_facet | Xin Nie Mingzhu Zou Chenhui Song Ping Zhang Di Ma Di Cui Gang Cheng Lin Li |
| author_sort | Xin Nie |
| collection | DOAJ |
| description | Abstract Purpose The impact of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) on muscle mass in individuals with advanced lung cancer has yet to be fully delineated. This study aimed to examine the dynamics of skeletal muscle mass during EGFR-TKIs targeted therapy, elucidate its clinical relevance, and explore the potential mechanisms. Methods We retrospectively recruited 104 patients with EGFR-mutant advanced lung adenocarcinoma who received icotinib or afatinib as first-line treatment. Skeletal muscle changes were assessed by abdominal CT obtained before and during treatment with EGFR-TKIs. The mean interval (± SD) between two CT scans was 109 days (± 16 days). Targeted panel sequencing of tumor tissue was used to detect genetic alterations. Functional enrichment analysis of genes interacting with EGFR-TKIs and muscle loss was performed to elucidate the potential toxicological mechanisms. Results A total of 42 (40.4%) patients experienced muscle loss during targeted therapy. Genetic analysis indicated muscle loss group had a higher proportion of MDM2 amplification and PIK3CA alterations (p = 0.011 & p = 0.045, respectively).Patients with baseline low muscle density and experienced ≥ Grade 2 diarrhea had higher rate of muscle loss (p = 0.005 & p < 0.001, respectively). Multivariate analysis revealed that muscle loss was independently associated with shorter PFS (hazard ratio [HR] 1.86, 95% confidence interval [CI]: 1.09 ∼ 3.18; p = 0.023). Besides, we found genes associated with icotinib, afatinib and muscle loss were significantly enriched in MAPK signaling pathway and calcium signaling pathway. Conclusions This study highlights the high prevalence and detrimental impact of muscle loss during EGFR-TKIs treatment. |
| format | Article |
| id | doaj-art-2745db0ffdff464192c9f7bbb9c0d94a |
| institution | OA Journals |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-2745db0ffdff464192c9f7bbb9c0d94a2025-08-20T01:57:45ZengBMCBMC Cancer1471-24072025-03-012511910.1186/s12885-025-13775-zSurvival impact and risk factors of skeletal muscle loss during first-line EGFR-TKIs therapy in advanced lung adenocarcinoma patientsXin Nie0Mingzhu Zou1Chenhui Song2Ping Zhang3Di Ma4Di Cui5Gang Cheng6Lin Li7Department of Medical Oncology Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical SciencesDepartment of Radiology Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical SciencesChongqing Kingbiotech CorporationDepartment of Medical Oncology Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical SciencesDepartment of Medical Oncology Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical SciencesDepartment of Pathology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical SciencesDepartment of Medical Oncology Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical SciencesDepartment of Medical Oncology Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical SciencesAbstract Purpose The impact of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) on muscle mass in individuals with advanced lung cancer has yet to be fully delineated. This study aimed to examine the dynamics of skeletal muscle mass during EGFR-TKIs targeted therapy, elucidate its clinical relevance, and explore the potential mechanisms. Methods We retrospectively recruited 104 patients with EGFR-mutant advanced lung adenocarcinoma who received icotinib or afatinib as first-line treatment. Skeletal muscle changes were assessed by abdominal CT obtained before and during treatment with EGFR-TKIs. The mean interval (± SD) between two CT scans was 109 days (± 16 days). Targeted panel sequencing of tumor tissue was used to detect genetic alterations. Functional enrichment analysis of genes interacting with EGFR-TKIs and muscle loss was performed to elucidate the potential toxicological mechanisms. Results A total of 42 (40.4%) patients experienced muscle loss during targeted therapy. Genetic analysis indicated muscle loss group had a higher proportion of MDM2 amplification and PIK3CA alterations (p = 0.011 & p = 0.045, respectively).Patients with baseline low muscle density and experienced ≥ Grade 2 diarrhea had higher rate of muscle loss (p = 0.005 & p < 0.001, respectively). Multivariate analysis revealed that muscle loss was independently associated with shorter PFS (hazard ratio [HR] 1.86, 95% confidence interval [CI]: 1.09 ∼ 3.18; p = 0.023). Besides, we found genes associated with icotinib, afatinib and muscle loss were significantly enriched in MAPK signaling pathway and calcium signaling pathway. Conclusions This study highlights the high prevalence and detrimental impact of muscle loss during EGFR-TKIs treatment.https://doi.org/10.1186/s12885-025-13775-zEpidermal growth factor receptor tyrosine kinase inhibitorsSkeletal muscle massLung adenocarcinoma |
| spellingShingle | Xin Nie Mingzhu Zou Chenhui Song Ping Zhang Di Ma Di Cui Gang Cheng Lin Li Survival impact and risk factors of skeletal muscle loss during first-line EGFR-TKIs therapy in advanced lung adenocarcinoma patients BMC Cancer Epidermal growth factor receptor tyrosine kinase inhibitors Skeletal muscle mass Lung adenocarcinoma |
| title | Survival impact and risk factors of skeletal muscle loss during first-line EGFR-TKIs therapy in advanced lung adenocarcinoma patients |
| title_full | Survival impact and risk factors of skeletal muscle loss during first-line EGFR-TKIs therapy in advanced lung adenocarcinoma patients |
| title_fullStr | Survival impact and risk factors of skeletal muscle loss during first-line EGFR-TKIs therapy in advanced lung adenocarcinoma patients |
| title_full_unstemmed | Survival impact and risk factors of skeletal muscle loss during first-line EGFR-TKIs therapy in advanced lung adenocarcinoma patients |
| title_short | Survival impact and risk factors of skeletal muscle loss during first-line EGFR-TKIs therapy in advanced lung adenocarcinoma patients |
| title_sort | survival impact and risk factors of skeletal muscle loss during first line egfr tkis therapy in advanced lung adenocarcinoma patients |
| topic | Epidermal growth factor receptor tyrosine kinase inhibitors Skeletal muscle mass Lung adenocarcinoma |
| url | https://doi.org/10.1186/s12885-025-13775-z |
| work_keys_str_mv | AT xinnie survivalimpactandriskfactorsofskeletalmusclelossduringfirstlineegfrtkistherapyinadvancedlungadenocarcinomapatients AT mingzhuzou survivalimpactandriskfactorsofskeletalmusclelossduringfirstlineegfrtkistherapyinadvancedlungadenocarcinomapatients AT chenhuisong survivalimpactandriskfactorsofskeletalmusclelossduringfirstlineegfrtkistherapyinadvancedlungadenocarcinomapatients AT pingzhang survivalimpactandriskfactorsofskeletalmusclelossduringfirstlineegfrtkistherapyinadvancedlungadenocarcinomapatients AT dima survivalimpactandriskfactorsofskeletalmusclelossduringfirstlineegfrtkistherapyinadvancedlungadenocarcinomapatients AT dicui survivalimpactandriskfactorsofskeletalmusclelossduringfirstlineegfrtkistherapyinadvancedlungadenocarcinomapatients AT gangcheng survivalimpactandriskfactorsofskeletalmusclelossduringfirstlineegfrtkistherapyinadvancedlungadenocarcinomapatients AT linli survivalimpactandriskfactorsofskeletalmusclelossduringfirstlineegfrtkistherapyinadvancedlungadenocarcinomapatients |