Circulating tumor DNA (ctDNA) may transform disease monitoring and guide treatment for soft-tissue sarcomas, according to data presented at the 2023 Society of Surgical Oncology (SSO) International Conference on Surgical Cancer Care.¹

Findings of a retrospective review showed that 85% of patients with documented disease progression or recurrence had ctDNA levels rise accordingly, and all patients with positive assays had changes in their treatment plans. After treatment, ctDNA levels also dropped in correlation with radiographic findings in 83% of patients.

“Overall, our study shows that ctDNA may help predict recurrence or measurable residual disease in patients with soft-tissue sarcomas,” said Beatrice Sun, MD, a general surgery resident in the Department of Surgery, Stanford University. “This highlights the potential role of ctDNA in both monitoring and personalizing disease management for these patients.” Currently, ctDNA is used in the postoperative setting to predict relapse and survival in patients with solid tumors such as colorectal and lung cancers.

Beatrice Sun, MD

For this study, Dr. Sun and colleagues aimed to evaluate whether personalized ctDNA profiling could aid in identifying recurrence and alter treatment paradigms in soft-tissue sarcomas, which exhibit a high rate of relapse. Early detection of recurrence in soft-tissue sarcomas is currently limited to cross-sectional imaging, she added.

High Sensitivity and Specificity

The single-institution, retrospective review included 45 patients diagnosed with leiomyosarcoma, pleomorphic sarcoma, and dedifferentiated liposarcoma, which were chosen because of their propensity for high mutational burden. A total of 228 ctDNA assays were sent among the group, and the study showed an 85% sensitivity rate in detecting disease progression or recurrence, with a specificity of 100%.

Of 34 patients with documented disease progression or recurrence, 29 had ctDNA levels rise accordingly, and all these patients had changes in their treatment plans. After treatment, ctDNA levels dropped in correlation with radiographic findings in 24 of the 29 patients (83%). All 11 patients with no known recurrence of soft-tissue sarcoma had no detectable levels of ctDNA.

Dr. Sun’s presentation detailed four cohorts of patients, categorized by their ctDNA trends. Cohort 1 included 22 patients with a median of 9 ctDNA levels each. Most of these patients had prior sarcoma surgery and prior medical therapy. All 22 patients had ctDNA levels that became negative after treatment, said Dr. Sun, and all but 1 of these patients had undergone surgical resection.

Two of these patients continue to have no evidence of disease, whereas the remaining 20 experienced recurrence. With recurrence, all patients had positive ctDNA levels that correlated with the presence of disease on imaging. The median time to recurrence for these patients was 4.5 months. All these patients, except for the two most recent recurrences, underwent treatment for the recurrence, and those who underwent surgery and radiation therapy had a corresponding decrease in ctDNA levels, said Dr. Sun.

Cohort 2 included seven patients with a median of six ctDNA levels each. These patients had a positive ctDNA at all time points, which corresponded with persistent disease on imaging. All these patients had both local and distant recurrences and are currently maintained on therapy, with variable response in ctDNA. Cohort 3 consisted of three patients with a median of five ctDNA levels. These patients had negative ctDNA levels despite the presence of disease on imaging. Finally, cohort 4 included 13 patients with a median of 5 ctDNA levels. All these patients had prior sarcoma resection followed by negative ctDNA and negative imaging.

“Almost all these patients are observed right now and are not on maintenance therapy,” said Dr. Sun. She noted that the median follow-up for this group is 13 months.

Clinical Implications

In addition to the potential benefits of ctDNA profiling in predicting recurrence, the study also raises questions about the possible use of ctDNA for evaluating treatment response and guiding treatment decisions. According to Dr. Sun, some patients in the study experienced changes in their treatment plans based on ctDNA results. This suggests that ctDNA profiling may potentially be used to make more informed decisions about the best course of treatment for individual patients.

“The use of ctDNA for the early detection of recurrence in soft-tissue sarcomas offers the potential for more personalized and targeted treatment approaches, leading to improved outcomes for patients,” Dr. Sun concluded. “However, larger-scale studies are needed to validate longitudinal ctDNA trends and determine which sarcoma subtypes will benefit most from monitoring.” 

DISCLOSURE: Dr. Sun reported no conflicts of interest.

REFERENCE

1. Sun BJ, Li A, Alobuia W, et al: Detection of circulating tumor DNA predicts recurrence in soft tissue sarcomas. 2023 Society of Surgical Oncology International Conference on Surgical Cancer Care. Abstract 78. March 22, 2023.