Active Surveillance Still the Best Bet in Desmoid-Type Fibromatosis

After a period of active surveillance (AS), most patients with non-intraabdominal desmoid-type fibromatosis (DTF) did not have to progress to active treatment, a researcher reported.

In the GRAFITI trial at a median follow-up of 33.7 months, about 30% of patients started some form of active treatment following AS, reported Anne-Rose W. Schut, a PhD candidate at Erasmus Medical Center, in Rotterdam, the Netherlands.

In 105 patients with DTF initially managed with AS, 40% exhibited initial tumor progression during AS, 32% had stable disease, and 28% had tumor regression. Of the patients who initially progressed on AS, 21 continued with the strategy, with 13 experiencing a decrease in tumor size after that initial progression, she stated in a presentation at the Connective Tissue Oncology Society (CTOS) virtual meeting.

“This study indicated that after active surveillance, only a minority of DTF patients will need active treatment,” Schut said. “A majority of DTF patients essentially develop stable or regressive disease, even after initial progression.”

These results “nicely confirm our recommendations we gave from the Desmoid Tumor Working Group and published last year,” commented CTOS session chair Bernd Kaspar, MD, PhD, of Mannheim University Medical Center in Germany.

In those recommendations, Kaspar and colleagues observed that an AS approach “does not appear to influence the efficacy of subsequent treatments when needed” and should be considered the first step after diagnosis.

DTF is a rare soft tissue tumor, which can be located at virtually any body site, with an incidence of about five patients per million people per year, according to Schut’s group.

“It is classified as an intermediate tumor, but has an unpredictable and variable disease course,” she explained. “It cannot metastasize, but it can display local infiltrative growth and has a tendency to recur locally after surgery. It has an unpredictable biological behavior, displaying progressive growth, stable disease, or even spontaneous regression, making DTF difficult to treat.”

“Up until 10 years ago surgery was the main DTF strategy, but high local recurrence rates and the high numbers of spontaneous regression, caused a shift to a more conservative approach,” she added. “Active surveillance is now recommended as initial management for DTF patients. However, prospective data regarding the results of active surveillance are lacking.”

The GRAFITI trial was conducted at seven sarcoma centers in the Netherlands and included adults with non-intra-abdominal DTF who had no previous treatment for a current lesion. They were followed with an initial AS approach (continuous monitoring with imaging) for a minimum of 3 years.

The patients in the study had a median age of 37. The median tumor size at baseline was 4.1 cm, and more than half (54%) had a CTNNB1 mutation. The most common tumor locations were the abdominal wall, and the trunk and back.

Schut and colleagues found that 31 patients started with some form of active treatment during follow-up, mostly due to a combination of progressive disease and an increase in symptoms. The cumulative incidence of the start of active treatment was 18% (95% CI 10-25) at 1 year, and 30% (95% CI 21-30) at 3 years. Progression-free survival was 69% (95% CI 60-78) at 1 year, and 58% (95% CI 49-69) at 3 years.

“Multivariable analysis using tumor size and CTNNB1 mutation status only identified the presence of S45F mutation as a predictive factor for the start of active treatment, although a trend towards statistical significance was seen for tumor size,” Schut reported. She suggested that CTNNB1 mutation status and tumor size could be used to select patients who will benefit from either AS or active treatment.