Related Experiment Video
Updated: Mar 18, 2026
Modeling Primary Bone Tumors and Bone Metastasis with Solid Tumor Graft Implantation into Bone
Published on: September 9, 2020
Clinical Implications of Isolated Bone Failure Without Systemic Disease Progression During EGFR-TKI Treatment
Ji An Hwang1, Ji Young Lee2, Woo Sung Kim1
1Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Background:
We investigated the characteristics of patients with epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) who had experienced isolated progression of bone metastases without aggravation of extraskeletal organs during EGFR-tyrosine kinase inhibitor (TKI) treatment.
Materials And Methods:
We retrospectively reviewed the data from 870 patients with EGFR-mutant NSCLC treated with EGFR-TKI from 2004 to 2014. Of these patients, 71 (8.2%), who had undergone radiation therapy to bone metastases because of skeletal-related events, impending skeletal-related events, or medically uncontrolled bone pain, were selected and defined as having bone failure (BF). BFs were classified into 2 categories according to the presence of accompanying disease progression in extraskeletal organs: isolated BF (IBF) and non-IBF.
Results:
Of the 71 BF patients, 33 (46.5%) experienced IBF without aggravation of disease in extraskeletal organs. IBF was more frequent in the clinical benefit group (responders and stable for ≥ 6 months) than in nonclinical benefit group (54.4% vs. 14.3%; P = .007). IBF was also more frequent in those with good performance status (82.5% vs. 42.9%; P = .005) and 19 deletion (68.4% vs. 35.7%; P = .024). Female sex, good performance status, and clinical benefit from TKI were more frequent in patients with IBF than in those with non-IBF (female sex, 69.7% vs. 44.7%; P = .034; Eastern Cooperative Oncology Group 0 or 1, 87.9% vs. 63.2%; P = .017; clinical benefit from TKI, 93.9% vs. 68.4%; P = .007). Clinical benefit from EGFR-TKI was an independent predictor of IBF (adjusted odds ratio, 6.647; 95% confidence interval, 1.328-33.262; P = .021). Patients with IBF tended to exhibit longer survival times from the initiation of the TKI (20.7 vs. 11.1 months; P = .2) and from the onset of BF (8.6 vs. 3.4 months; P = .186).
Conclusion:
IBF without systemic disease progression frequently occurs in patients with clinical benefits from EGFR-TKI and is associated with better survival. This finding requires future studies to explore the differential activity of EGFR-TKI in the bones over time or in preference to other organs.
Insights
Isolated bone failure in EGFR-mutant non-small-cell lung cancer patients treated with tyrosine kinase inhibitors is linked to better outcomes. This suggests EGFR-TKI may have preferential activity in bone metastases, warranting further investigation.
Area of Science:
- Oncology
- Medical Science
- Pharmacology
Background:
- Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) is a significant clinical challenge.
- Bone metastases are a common complication, leading to skeletal-related events and pain.
- Tyrosine kinase inhibitors (TKIs) targeting EGFR have improved outcomes, but patterns of resistance and progression vary.
Purpose of the Study:
- To investigate the characteristics of patients with EGFR-mutant NSCLC experiencing isolated bone failure (BF) during EGFR-TKI treatment.
- To determine factors associated with isolated BF (IBF) and its impact on patient survival.
- To explore the potential for differential EGFR-TKI activity in bone metastases.
Main Methods:
- Retrospective review of 870 patients with EGFR-mutant NSCLC treated with EGFR-TKI from 2004 to 2014.
- Identification of 71 patients (8.2%) with bone failure (BF) requiring radiation therapy for bone metastases.
- Classification of BF into isolated BF (IBF) and non-IBF based on extraskeletal organ involvement.
Main Results:
- Of 71 BF patients, 33 (46.5%) had IBF without extraskeletal progression.
- IBF was significantly more frequent in patients who benefited clinically from EGFR-TKI (54.4% vs. 14.3%, P = .007), had good performance status (82.5% vs. 42.9%, P = .005), and harbored the 19 deletion mutation (68.4% vs. 35.7%, P = .024).
- Clinical benefit from EGFR-TKI was an independent predictor of IBF (aOR, 6.647; P = .021), and IBF patients tended towards longer survival.
Conclusions:
- Isolated bone failure without systemic disease progression occurs frequently in patients benefiting from EGFR-TKI.
- IBF is associated with better survival, suggesting potential preferential activity of EGFR-TKI in bone metastases.
- Further research is needed to understand the differential activity of EGFR-TKI in bone over time or compared to other organs.
More Related Videos
10:49Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
09:32Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
Published on: October 17, 2025
Related Concept Videos
01:24Chronic Kidney Disease II: Clinical Manifestations
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:28Chronic Kidney Disease III: Interprofessional Care
01:29Bone Disorders
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
02:38Mitogens and the Cell Cycle
01:27Fractures: Bone Repair
Minor fractures with no bone displacement are treated by immobilizing the fractured bone using a cast or splint. However, in the case of fractures with displaced bones, the broken bones are repositioned before immobilization to ensure successful healing without deformation and loss of function. The realignment of fractured bone ends is performed through a process called reduction. If the...