Neoadjuvant radiotherapy shows reduction in local recurrence for subset of liposarcoma patients

Well-differentiated liposarcoma (WDLPS) often originates in the retroperitoneum and rarely spreads elsewhere in the body. But local recurrence—which can happen repeatedly and historically has been treated with surgery alone—is the leading cause of death in these patients.

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STRASS, an international, randomized, phase III trial, found no significant benefit to neoadjuvant radiotherapy (RT) in most patients with primary retroperitoneal sarcoma. However, a post hoc exploratory analysis suggested a potential benefit for patients with liposarcoma, particularly primary retroperitoneal WDLPS (pRP-WDLPS), a result that was somewhat unexpected.

The subsequent STREXIT study pooled STRASS data with data gathered from STRASS-eligible patients who had not been enrolled in the trial but had been treated at STRASS-participating centers. STREXIT demonstrated a local control benefit for neoadjuvant RT in patients with pRP-WDLPS, confirming the data from STRASS.

Brigham and Women's Hospital was the lead site of a new study published in eClinicalMedicine showing that neoadjuvant RT followed by surgery significantly decreases the risk of local recurrence in pRP-WDLPS patients. To the best of the authors' knowledge, it is the largest study to report outcomes of neoadjuvant RT in this patient population.

Addressing uncertainty about efficacy of neoadjuvant RT

Mark Fairweather, MD, a surgical oncologist at the Brigham, is first author of the new study. He describes the impact of STRASS as "practice-changing" for his clinical group.

"Prior to STRASS, we gave preoperative radiation to most of our retroperitoneal sarcoma patients but not those with well-differentiated liposarcoma," he recalls. "Based on how our group interpreted the data, we now give preoperative radiation only to those with retroperitoneal sarcoma who have well-differentiated liposarcoma but not other histologies."

Many providers in the sarcoma community globally, though, were less certain about the efficacy of this treatment approach. Dr. Fairweather, one of the authors of STREXIT, led the research team that set out to clarify the role of neoadjuvant RT in pRP-WDLPS patients.

This study was conducted through the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG). The Brigham was one of the eight founding institutions of the group, which has grown to include sites from more than 50 countries since its launch in 2013.

For this work, 24 TARPSWG sites from around the world contributed data from 582 patients who underwent surgery for pRP-WDLPS. Of this group, 510 patients had surgery alone, and 72 had neoadjuvant RT plus surgery. A retrospective analysis of the data showed that neoadjuvant RT followed by surgery was associated with a five-year local recurrence rate of only 6%. In contrast, the rate was 26% with surgery alone.

"It was surprising to see that stark of a difference, but ultimately I think it makes sense," Dr. Fairweather says. "Well-differentiated liposarcomas have a negligible risk of distance spread but recur locally, so we're maximizing local therapy with both radiation and surgery in these patients."

Reducing recurrence, reducing future surgeries

Senior author Chandrajit P. Raut, MD, MSc, surgical oncologist and chief of the Mass General Brigham Division of Surgical Oncology, says that lowering the recurrence rate so dramatically would provide a major boost to the quality of life of pRP-WDLPS patients.

"Traditionally, these patients have required surgery every time there is a recurrence," says Dr. Raut, who was a lead investigator on both STRASS and STREXIT. "Reducing the recurrence rate will reduce the number of operations they need over what we hope will be a long lifetime—and maybe even eliminate the need for further operations after the initial one for this condition."

"And if you're saving patients from further operations and the morbidity associated with surgery, there will eventually be an impact on overall survival," adds Dr. Fairweather, who hopes to see longer-term follow-up to investigate this topic further. In the new study, the 10-year overall survival was 80% in patients getting neoadjuvant RT and 71% in those getting surgery alone—not a significant statistical difference.

Drs. Fairweather and Raut contend that the study provides further evidence that neoadjuvant RT should be strongly considered in the management of pRP-WDLPS patients.

"We now have data from STRASS, a prospective, randomized trial; STREXIT, which utilized prospectively maintained data sets during the same timeframe that STRASS was enrolling patients; and now this study, which is retrospective," Dr. Raut says. "It's hard to argue against three lines of evidence, all supporting the same conclusion."

Given the rarity of pRP-WDLPS, a study of this nature could not be done without the multi-institution collaboration that the TARPSWG makes possible.

"Work like this requires extensive collaboration to create robust data sets that enable investigators to ask such histologic-specific questions," Dr. Fairweather says. "It's one more example of how TARPSWG has changed the landscape of sarcoma research and treatment over the past 13 years."

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