Can ctDNA guide radiation use in oligometastatic NSCLC?

SAN DIEGO — Liquid biopsy may predict which oligometastatic non-small cell lung cancer (NSCLC) patients are likely to benefit from integrated targeted high-dose radiation, researchers report here. .

In a retrospective study, median survival outcomes for these patients were significantly worse when circulating tumor DNA (ctDNA) was detected before radiation therapy compared with when it was not detected.

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

Real-world data show that ctDNA may aid in patent risk stratification of oligometastatic NSCLC and that a ctDNA-based decision-making framework for stereotactic body radiotherapy (SBRT) has been tested in prospective clinical trials. That suggests it should be tested, said Aadel Chaudhuri, MD. Siteman Cancer Center in St. Louis presented the study results at the annual meeting of the American Society of Radiation Oncology.

“I’m excited about this data, but I think this last point is important for us to really change our practice and make a significant change,” he said at a press conference.

Treatment of oligometastatic lung cancer is “a bit of a challenge,” Chaudhuri explained. “There are patients who can be treated very effectively at this stage of the disease. In some cases, it can be definitively treated with radiation therapy, but it is difficult to know which patients will benefit from radiation therapy.”

The problem, he said, is that images may not represent a patient’s true disease burden because there may be micrometastatic disease beyond what can be seen on images.

“In those cases, if you try to integrate what you see on the images, the patient may come back at three-month follow-up with more extensively metastatic disease,” Chaudhuri said. “We didn’t really do them any good. If anything, the time spent administering radiotherapy took away from time that could have been a more intense systemic treatment.” You can also claim that it is.”

“The question, therefore, is whether liquid biopsy can be used to improve precision and clarity in this field and truly enhance radiotherapy decision-making,” he added.

In this study, the researchers found that while the degree of mutational burden in ctDNA correlated with survival, the number of sites of metastatic disease did not, suggesting that “perhaps our selection criteria could at least incorporate ctDNA.” “This suggests that it is not purely dependent on the number of metastatic sites.” Imaging tests confirmed the metastatic site,” said Chaudhuri.

The findings presented are from a multicenter cohort of approximately 1,500 patients with oligometastatic NSCLC who underwent at least one ctDNA test.

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

Rohan J.M. Correa, MD, of the London Health Sciences Center in Ontario, who was not involved in the study, said that while the results are preliminary, the study involved a large number of real-world patients. He pointed out that he was doing so.

“Our motivation here is… how can we do better,” he said. “How do we identify patients who are at high risk of rapidly failing after treatment… [and] Wouldn’t it be better to choose who benefits and who doesn’t?”

“The signal is there, and this study provides important motivation to advance the biomarker-driven, biomarker-directed clinical trials that we have been dreaming of for some time,” Correa added. .