Efficacy of Whole Lung Irradiation in Rhabdomyosarcoma with Lung Metastases

Academic Background

Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma in children. Despite advancements in treatment, the prognosis for patients with metastatic RMS remains poor, especially for those with lung metastases, whose survival rates are significantly lower than those without metastases. Although treatment intensification and modifications have been ongoing over the past few decades, patient survival rates have not significantly improved. The lung is the most common site of metastasis in RMS and the most frequent site of metastasis at the time of death. Therefore, improving treatment strategies for lung metastases is crucial.

Whole Lung Irradiation (WLI) has been shown to improve Event-Free Survival (EFS) and Overall Survival (OS) in patients with isolated lung metastases. However, the efficacy of WLI in all patients with lung metastases remains unclear, and compliance with WLI in clinical practice is low. This study aims to investigate the efficacy of WLI in patients with RMS and lung metastases and to analyze factors influencing the implementation of WLI.

Source of the Paper

This paper was co-authored by Leo Y. Luo, Wei Xue, Amira Qumseya, Juan C. Vasquez, Rajkumar Venkatramani, Suzanne L. Wolden, and Dana L. Casey, affiliated with Vanderbilt University Medical Center, University of Florida, Yale School of Medicine, Baylor College of Medicine, Memorial Sloan Kettering Cancer Center, and University of North Carolina School of Medicine, respectively. The paper was published on September 10, 2024, in the Journal of Clinical Oncology (JCO), with the DOI: https://doi.org/10.1200/jco.24.00928.

Research Process

Study Population

This study retrospectively analyzed 143 newly diagnosed RMS patients with lung metastases enrolled in four Children’s Oncology Group (COG) clinical trials (D9802, D9803, ARST08P1, ARST0431) between 1999 and 2013. All patients provided informed consent, and the study was approved by the institutional review boards at each participating site.

Study Design

The primary objective was to compare EFS and OS between patients who received and did not receive WLI. WLI was administered at a dose of 15 Gy in 10 fractions, typically concurrent with radiotherapy to the primary tumor site. Central review ensured the accuracy of radiation records, and detailed data on radiation sites, doses, treatment dates, protocol compliance, and reasons for deviations were collected.

Statistical Analysis

Baseline characteristics of patients who received and did not receive WLI were compared using the chi-square test or Fisher’s exact test. The Kaplan-Meier method was used to estimate 5-year EFS and OS, and the log-rank test was used to compare survival rates between the two groups. Subgroup analyses were also conducted to explore the impact of various clinical factors on EFS and OS.

Key Results

Patient Characteristics

Among the 143 patients, 65 (45.5%) received WLI, while 78 (54.5%) did not. There were no significant differences in prognostic factors such as age, tumor histology, FOXO1 fusion status, primary site, tumor size, nodal status, number of metastatic sites, and Oberlin score between the two groups.

Survival Analysis

The 5-year EFS was 38.3% (95% CI, 24.8-51.8) in patients who received WLI, compared to 25.2% (95% CI, 13.8-36.6) in those who did not (p=0.0496). The 5-year OS was 45.5% (95% CI, 31.8-59.3) in patients who received WLI, versus 32.4% (95% CI, 20.4-44.4) in those who did not (p=0.08). Subgroup analysis showed that WLI significantly improved EFS and OS in patients aged 10 years and older.

Other Clinical Factors

Univariable analysis revealed that age, histology, FOXO1 fusion status, number of metastatic sites, location of metastatic sites, and Oberlin score were significantly associated with EFS. Multivariable analysis showed that a single metastatic site (i.e., isolated lung metastases) was associated with improved EFS and OS, while age less than 1 year was associated with worse EFS.

Conclusion

This study demonstrates that patients with RMS and lung metastases who received WLI had significantly higher 5-year EFS compared to those who did not. These results support the use of WLI in patients with lung metastases and highlight the importance of stricter protocol compliance in clinical trials.

Research Highlights

1. Key Finding: WLI significantly improved event-free survival in patients with RMS and lung metastases.
2. Clinical Significance: The study provides strong evidence for the use of WLI in patients with lung metastases, emphasizing its potential importance in improving patient outcomes.
3. Innovation: This is the largest study to date on the efficacy of WLI in patients with RMS and lung metastases, utilizing prospective data collection and central review to ensure data accuracy.

Research Value

This study not only provides scientific evidence for the use of WLI in patients with RMS and lung metastases but also highlights the importance of protocol compliance in clinical trials. The findings will guide future clinical practice and trial design, further optimizing treatment strategies for patients with RMS and lung metastases.

Additional Valuable Information

The study also notes that the implementation of WLI is influenced by various factors, including uncertainty about its efficacy and concerns about toxicity. Future research should further explore the optimal timing of WLI and develop strategies to improve compliance with WLI.