Research Spotlight: Transforming Outcomes for a Subset of Liposarcoma Patients Through Preoperative Therapy

Mark Fairweather, MD, and Chandrajit P. Raut, MD, MSc, of Mass General Brigham Cancer Institute, are the lead and senior authors of a paper published in eClinicalMedicine, “Neoadjuvant radiotherapy for primary retroperitoneal well-differentiated liposarcoma: A Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) propensity score matched analysis.”

Q: What challenges or unmet needs make this study important?

Soft tissue sarcomas are a rare group of tumors with only about 12,000 new cases in the United States each year. These tumors can form anywhere in the body, with nearly 100 different types that vary widely in how they behave. About 15-20% of sarcomas occur in the retroperitoneum, the area behind the intestines that includes vital organs including the kidneys, pancreas, adrenal glands, aorta and inferior vena cava. Tumors in this location can grow quite large—up to the size of a watermelon— before presenting as a palpable mass or causing noticeable symptoms.

One common tumor in this area is well-differentiated liposarcoma (WDLPS). These tumors have a negligible risk of spreading elsewhere in the body, but local recurrence is the leading cause of death in these patients. Historically, these tumors have been treated with surgery alone, but a post hoc analysis conducted as part of a broader clinical trial suggested that this specific subgroup might benefit from preoperative radiation. Our study aimed to further investigate that possibility.

Q: What central question(s) were you investigating?

The central question our study asked was whether giving radiation therapy to patients with WDLPS before their surgery could significantly lower the chance of their tumor coming back in the same area. We wanted to test this in a large cohort of patients to get a clearer understanding of the potential benefits of adding radiation to the treatment plan.

Q: What methods or approach did you use?

This study was a multi-institutional collaboration conducted through the Transatlantic-Australasian Retroperitoneal Sarcoma Working Group (TARPSWG). Of note, Brigham and Women’s Hospital was one of the eight founding institutions of TARPSWG back in 2013, which has since grown to include institutions from over 50 countries across five continents. For this work, 24 member sites around the world contributed a total of 582 patients, making it the largest series of patients with retroperitoneal WDLPS to date.

We conducted a retrospective analysis of patients with primary retroperitoneal WDLPS treated between 2002 and 2017 at one of these sites. While the majority of the cohort underwent surgery alone, some were given neoadjuvant radiation therapy followed by surgery. Using a method called propensity score matching to control for variation among the diverse patients, we were able to reliably compare outcomes.

Q: What did you find?

The results of this study demonstrate that patients who received radiation therapy before their surgery had a much lower risk of local tumor recurrence than those who only had surgery. Specifically, five years after their surgery, about 26% of patients who only had surgery experienced a local recurrence of their tumor, compared to only 6% of patients who received the radiation first.

Q: What are the real-world implications, particularly for patients?

This landmark study is a significant development that should change how we treat patients with WDLPS. Conducting clinical trials for rare diseases like this can be challenging, so we often rely on large, high-quality studies involving multiple institutions to help guide treatment recommendations.

With the findings from this research, we now have clear evidence showing the benefits of using preoperative radiation, allowing us to have informed discussions with patients and help them understand their treatment options better. Ultimately, this study should improve patient care, provide a clearer path forward for managing WDLPS and enhance patients’ chances of a successful outcome without cancer return.

Q: What part of this work feels most meaningful to you personally?

There are two main aspects of this study that are personally meaningful. The motivation for this study was the lack of data to support the patients we see in clinic with this disease, as well as our discussions with colleagues about the best course of treatment, where we often couldn’t provide definitive evidence to support our recommendations. It is very gratifying to be able to discuss our own study with patients in clinic to further reassure them of our recommendations.

The other meaningful aspect of this study is the multi-institutional collaboration. The TARPSWG group has been monumental in supporting and conducting studies that have ultimately helped define treatment recommendations for retroperitoneal sarcomas. This study reflects the success of the group’s collaborative effort with the overall goal of improving outcomes in these patients.

Authorship: In addition to Fairweather and Raut, Mass General Brigham authors include Megan Sulciner, Joshua S. Jolissaint and Elizabeth Baldini.

Paper cited: Fairweather M., et al. “Neoadjuvant radiotherapy for primary retroperitoneal well-differentiated liposarcoma: a Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) propensity score matched analysis.” eClinicalMedicine. DOI:10.1016/j.eclinm.2026.103805

Funding: This paper was supported by the Susan and Habib Gorgi Family Fund for Sarcoma Research.

Disclosures: None.