# Efficacy analysis and survival prediction of unique chemotherapy regimens for osteosarcoma in China

**Authors:** Ruizhen Wang, Zhen Bao, Fengrong Chen, Fei Gao, Jing Yang, Wei Wang

PMC · DOI: 10.3389/fphys.2026.1692741 · Frontiers in Physiology · 2026-02-13

## TL;DR

This study evaluated a unique chemotherapy regimen for osteosarcoma in China and found that machine learning models, especially random forest and extra trees, accurately predict patient survival.

## Contribution

The study introduces a unique chemotherapy regimen and demonstrates the superior predictive power of random forest and extra trees for survival outcomes in osteosarcoma.

## Key findings

- The 3-year and 5-year survival rates were 76.00% and 65.00%, respectively.
- Random forest and extra trees showed the highest predictive accuracy (AUC = 0.960).
- Multiple clinical and pathological factors significantly influenced overall survival.

## Abstract

We aimed to evaluate the effectiveness of a unique chemotherapy regimen, identify factors influencing overall survival (OS), and compare the predictive performance of six machine learning models in Chinese osteosarcoma patients.

A retrospective analysis was conducted on 390 patients with osteosarcoma who were treated between 2009 and 2019. All patients received standardized neoadjuvant chemotherapy (ifosfamide + methotrexate + adriamycin or ifosfamide + adriamycin + cisplatin, depending on age) and subsequent surgery. Clinical and pathological data were collected. Survival analysis was performed using Kaplan–Meier curves and log-rank tests. Multivariate analysis and survival prediction were conducted using Cox proportional hazards models and six machine learning algorithms [random forest (RF), AdaBoost, CatBoost, Extra Trees, XGBoost, and LightGBM) validated via five-fold cross-validation. Clinical net benefit was assessed using decision curve analysis (DCA).

The cohort had a mean age of 19 years, with 62.47% male participants and 88.82% diagnosed at stage II. The 3-year and 5-year survival rates were 76.00% (95% CI: 71.60%–80.40%) and 65.00% (95% CI: 60.20%–69.80%), respectively. Multiple factors—including tumor type, surgical method, recurrence/metastasis, tumor necrosis rate, and serum biomarkers (lactate dehydrogenase (LDH), alkaline phosphatase (ALP), platelet count (PLT), white blood cell count (WBC), and red blood cell count (RBC))—were significantly associated with OS. Among the machine learning models, RF and Extra Trees demonstrated the highest predictive accuracy (AUC = 0.960), followed by CatBoost (0.942), AdaBoost (0.897), LightGBM (0.879), and XGBoost (0.853). Calibration curves showed excellent agreement between predicted and observed survival probabilities. DCA confirmed that RF and Extra Trees provided superior net benefit across a wide range of threshold probabilities.

The unique chemotherapy regimen showed superior survival outcomes. Prognostic evaluation should integrate multiple clinical and pathological indicators. Machine learning models, particularly RF and Extra Trees, offer powerful tools for individualized survival prediction and treatment planning in osteosarcoma.

## Linked entities

- **Chemicals:** ifosfamide (PubChem CID 3690), methotrexate (PubChem CID 4112), adriamycin (PubChem CID 31703), cisplatin (PubChem CID 5460033), alkaline phosphatase (PubChem CID 18985873)
- **Diseases:** osteosarcoma (MONDO:0002623)

## Full-text entities

- **Genes:** TNR (tenascin R) [NCBI Gene 7143] {aka NEDSTO, TN-R}, ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}
- **Diseases:** Cancer (MESH:D009369), pulmonary (MESH:D008171), GBM (MESH:D005910), Osteosarcoma (MESH:D012516), bone cancer (MESH:D001859), bone (MESH:D001847), metastases (MESH:D009362), OS (MESH:D011475), death (MESH:D003643), necrosis (MESH:D009336), axial skeleton (MESH:C537791)
- **Chemicals:** MTX (MESH:D008727), etoposide (MESH:D005047), DDP (MESH:D002945), ADM (MESH:D004317), IFO (MESH:D007069)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12945764/full.md

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12945764/full.md

## References

27 references — full list in the complete paper: https://tomesphere.com/paper/PMC12945764/full.md

---
Source: https://tomesphere.com/paper/PMC12945764