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SAN DIEGO -- A liquid biopsy may predict which patients with oligometastatic non-small cell lung cancer (NSCLC) are likely to benefit from consolidative targeted high-dose radiation, a researcher reported here.

In a retrospective study, median survival outcomes in these patients were significantly worse when circulating tumor DNA (ctDNA) was detected prior to radiotherapy versus when it was not:

• Overall survival: 16.8 vs 25 months (P=0.03)
• Progression-free survival: 5.4 vs 8.8 months (P=0.004)

The real-world data suggest that ctDNA can help risk-stratify patents with oligometastatic NSCLC and that ctDNA-based decision frameworks for consolidative stereotactic body radiation therapy (SBRT) should be tested in prospective trials, according to Aadel Chaudhuri, MD, PhD, of the Siteman Cancer Center in St. Louis, who presented the findings at the annual meeting of the American Society for Radiation Oncology.

"As excited as I am about this data, I think this last point is critical for us to truly change practice and move the needle," he said during a press briefing.

Treatment for oligometastatic lung cancer "represents a bit of a conundrum," Chaudhuri explained. "We all have patients where this stage of disease can be treated quite effectively -- and in some cases rather definitively with radiotherapy -- but it's challenging to know which patients will benefit from it."

The problem, he said, is that imaging may not represent a patient's true burden of disease, because there could be micrometastatic disease beyond what is seen on imaging.

"In those cases, when we try to consolidate what we see on imaging, the patient can come back on a 3-month follow-up with more widely metastatic disease," said Chaudhuri. "We haven't really done them a service, and if anything you could argue that the time spent delivering radiotherapy was time taken away from what could have been stronger systemic therapy."

"So the question is whether liquid biopsy can be used to improve the precision and clarity in this space, and really enhance radiotherapy decision-making," he added.

In the study, the researchers found that the degree of mutational burden on ctDNA correlated with survival, while the number of metastatic disease sites did not, "suggesting that perhaps our selection criteria could at least incorporate ctDNA and not be purely reliant on the number of metastatic sites on imaging," Chaudhuri said.

The findings presented came from a multi-institutional cohort of nearly 1,500 oligometastatic NSCLC patients who underwent ctDNA testing at least once.

Of those, 309 patients (mean 65 years) underwent radiotherapy after the liquid biopsy and after their oligometastatic disease was diagnosed by the treating physician. Patients were treated at both academic and community practices between 2016 and 2022. Oligometastatic disease was defined as metastatic disease in one to five organ systems, and overall and progression-free survival were measured from the start of radiation therapy.

Rohann J.M. Correa, MD, PhD, of the London Health Sciences Centre in Ontario, who was not involved in the research, noted that while the results are preliminary, the study involved a large number of patients in the real world.

"Our motivation here ... is how can we do better?" he said. "How can we identify those at high risk of rapid failure after treatment ... [and] better select who is going to benefit and who may not?"

"There is a signal there -- and this study gives us some key motivation to move forward with the biomarker-driven, biomarker-directed trials we've been dreaming up for some time," Correa added.

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