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Trabectedin and low-dose radiation therapy in patients with advanced leiomyosarcoma
Javier Martin-Broto1,2,3, Alicia Olarte-García4, Ricardo Fernandéz-Rodríguez5
1Medical Oncology Department, Fundación Jimenez Diaz University Hospital, Av. de los Reyes Católicos, 2, Madrid 28040, Spain.
Background And Objectives:
Dimensional response is an unmet need in second lines of advanced soft tissue sarcomas (STS). Indeed, the three approved drugs, pazopanib, trabectedin, and eribulin, achieved an overall response rate (ORR) of less than 10%. This fact potentially hinders the options for fast symptomatic relief or surgical rescue. The combination of trabectedin plus low-dose radiation therapy (T-XRT) demonstrated a response rate of 60% in phase I/II trial, while real-life data achieved 32.5% ORR, probably due to a more relaxed timing between treatments. These results were obtained in progressing and advanced STS. In this study, the merged databases (trial plus real life) have been analyzed, with a special focus on leiomyosarcoma patients.
Design And Methods:
As responses were seen in a wide range of sarcoma histologies (11), this study planned to analyze whether leiomyosarcoma, the largest subtype with 26 cases (30.6%) in this series, exhibited a better clinical outcome with this therapeutic strategy. In addition, four advanced and progressing leiomyosarcoma patients, all with extraordinarily long progression-free survival of over 18 months, were collected.
Results:
A total of 847 cycles of trabectedin were administered to 85 patients, with the median number of cycles per patient being 7 (1-45+). A trend toward a longer progression-free survival (PFS) was observed in leiomyosarcoma patients with median PFS (mPFS) of 9.9 months [95% confidence interval (CI): 1.1-18.7] versus 5.6 months (95% CI: 3.2-7.9) for the remaining histologies, p = 0.25. When leiomyosarcoma and liposarcoma were grouped, this difference reached statistical significance, probably due to the special sensitivity of myxoid liposarcoma. The mPFS for L-sarcomas was 12.7 months (95% CI: 7-18.5) versus 4.3 months (95% CI: 3.3-5.3) for the remaining histologies, p = 0.001. Cases with long-lasting disease control are detected among leiomyosarcoma patients.
Conclusion:
Even when extraordinarily long-lasting responses do exist among leiomyosarcoma patients treated with T-XR, we were unable to demonstrate a significant difference favoring leiomyosarcoma patients in clinical outcomes.
Insights
The combination of trabectedin and radiation therapy (T-XRT) shows promise for advanced soft tissue sarcomas. While not statistically significant for leiomyosarcoma alone, grouping it with liposarcoma improved progression-free survival.
Area of Science:
- Oncology
- Medical Research
- Sarcoma Treatment
Background:
- Advanced soft tissue sarcomas (STS) have limited treatment options with low response rates for approved drugs.
- The combination of trabectedin and low-dose radiation therapy (T-XRT) has shown higher response rates in previous trials and real-world data.
- A need exists for effective second-line treatments offering symptomatic relief or surgical rescue in advanced STS.
Purpose of the Study:
- To analyze the clinical outcomes of advanced soft tissue sarcoma patients treated with trabectedin plus low-dose radiation therapy (T-XRT).
- To specifically investigate if leiomyosarcoma patients, a major subtype, benefit more from this T-XRT therapeutic strategy.
- To evaluate the efficacy of T-XRT in a combined dataset of clinical trial and real-world data.
Main Methods:
- A retrospective analysis of merged databases from a clinical trial and real-world data of patients with advanced STS treated with T-XRT.
- Evaluation of progression-free survival (PFS) and overall response rate (ORR) in the overall patient cohort.
- Subgroup analysis focusing on leiomyosarcoma patients and comparison with other histologies, including liposarcoma.
Main Results:
- A total of 85 patients received 847 cycles of trabectedin, with a median of 7 cycles per patient.
- A trend towards longer median PFS was observed in leiomyosarcoma patients (9.9 months) compared to other histologies (5.6 months), though not statistically significant (p=0.25).
- Grouping leiomyosarcoma and liposarcoma (L-sarcomas) demonstrated a statistically significant improvement in median PFS (12.7 months) compared to other histologies (4.3 months, p=0.001), likely due to myxoid liposarcoma sensitivity.
Conclusions:
- The T-XRT combination therapy shows potential for managing advanced STS, with some leiomyosarcoma patients achieving long-lasting disease control.
- While a significant difference favoring leiomyosarcoma alone was not demonstrated, grouping it with liposarcoma showed significant improvement in PFS.
- Further research may be warranted to optimize T-XRT for specific STS subtypes and improve clinical outcomes.
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