microRNA-Based Model Predicts SBRT Outcomes in Soft Tissue Sarcomas

At the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, Joanne Weidhaas, MD, PhD, MBM, shared a poster on a study that explored the potential of microRNA-based single-nucleotide polymorphisms (mirSNPs) to predict outcomes stemming from preoperative hypofractionated radiotherapy (SBRT) in patients with soft tissue sarcomas.

Ultimately, the study found that mirSNP-based models were able to identify those with favorable vs unfavorable responses. This demonstrated the capability of these signatures to aid clinicians in deciding whether patients should receive preoperative SBRT or hypofractionated standard radiation.

Weidhaas, a professor in the Department of Radiation Oncology, vice chair of the Division of Molecular and Cellular Oncology, and director of Translational Research at the David Geffen School of Medicine at UCLA Health Jonsson Comprehensive Cancer Center, co-founder of MiraDx, and founder of MiraKind, stated that the biomarkers were able to predict major wound toxicity.

Identifying which patients are at risk of distant failure, and for whom neoadjuvant radiation should be considered, would be, in Weidhaas’s words, “very important.”

Transcript:

We previously looked at a small group of patients treated this way—these are big doses of radiation before surgery—and we found that these biomarkers could predict major wound toxicity. After surgery, [there are] difficulties with the surgical site healing.

In this analysis, it was a larger, continued collection of patients treated this way, and we extended the work and, in addition, looked at any late toxicity. Those are toxicities 2 years out, where there could be difficulty, [such as] fibrosis with the leg or joint, or a fracture, or things like that. Distant recurrence [too], that’s when the tumor, after these interventions—radiation and surgery—has spread elsewhere, as well as the response rate at the time of surgery, and any local failure in the surgical bed; those are some additional end points that are important in sarcoma.

In the case of those identified at risk of distant failure, it’d be very important to consider incorporating neoadjuvant chemotherapy, which is being done in the second part of the clinical trial going on at UCLA. To identify the patients for whom that will be beneficial would be very important. Historically, radiation wasn’t part of sarcoma care, and we weren’t able to salvage the limb—there weren’t limb salvage approaches. Radiation has enabled smaller surgeries and [the possibility to] salvage the limb. In the great majority of cases, one form of radiation will be safe for patients—we've seen that in other cancers. It is probably safe for 99% of people, but it could be that big doses are safer for [some patients] than small doses, and vice versa. This is all a move towards making radiation personalized. Everyone's scared of radiation, but honestly, it's quite safe for most people if we just put our heads together and apply some biomarkers to identify which course is the safest.

Reference

Weidhaas JB, McGreevy K, Nikitas J, et al. MicroRNA-based biomarkers of outcome in soft tissue sarcoma treated with hypofractionated preoperative radiation therapy. J Clin Oncol. 2025;43(suppl 16):11538. doi:10.1200/JCO.2025.43.16_suppl.11538.