Liquid biopsy may help determine which patients with oligometastatic non–small cell lung cancer (NSCLC) with metastases may be most likely to benefit from targeted, high-dose radiation therapy rather than drug-based therapy, according to findings simultaneously published by Semenkovich et al in npj Precision Oncology and presented at the 2023 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract 149).
Background
NSCLC accounts for about 84% of all lung cancer cases—the leading cause of cancer mortality in the United States and across the world. Patients diagnosed with NSCLC who have widespread metastatic disease generally cannot be cured. However, some patients with oligometastatic disease—characterized in the study as metastatic disease in at least one, and up to five, organ systems—may experience long periods of cancer-free survival when treated with high-dose radiation targeted to the individual tumor sites.
Identifying which patients with oligometastatic disease could benefit from this type of focused radiation treatment may be challenging. Tumor tissue biopsies, long considered the standard test for analyzing solid tumors, are only capable of examining the site where the tissue sample was taken; and imaging tests also have limitations for detecting micrometastatic disease.
Comparing a visible tumor to an iceberg, the researchers noted that it can be difficult for imaging tests to determine whether the disease is “just the part of the iceberg that’s visible above the water or if there’s substantially more micrometastatic disease beneath the surface.” Conversely, liquid biopsies can detect elements of solid tumors in the blood, urine, or cerebrospinal fluid. Blood tests, the most widely used type of liquid biopsies, can identify circulating tumor DNA (ctDNA), circulating tumor cells, circulating RNA, and other biomarkers that can indicate the presence of cancer.
“Liquid biopsies could help us know if there is micrometastatic disease,” explained senior study author Aadel Chaudhuri, MD, PhD, Assistant Professor of Radiation Oncology at the Siteman Cancer Center at the School of Medicine at the Washington University in St. Louis.
In previous studies, the researchers used liquid biopsy technology to monitor the status of patients with colorectal cancer, bladder cancer, and peripheral nerve tumors.
Study Methods and Results
In the new real-world, multi-institutional study, the researchers analyzed the data of 309 patients with an average age of 64.7 years who had oligometastatic NSCLC and received radiation therapy following a liquid biopsy from 2016 to 2022.
The researchers discovered that the patients with detectable ctDNA prior to radiation therapy experienced a median overall survival of 16.8 months compared with 25 months among those whose blood showed no detectable ctDNA prior to treatment (P = .030, hazard ratio [HR] = 1.65, confidence interval [CI] = 1.05–2.61).
Similarly, the patients with detectable ctDNA prior to radiation therapy experienced a median progression-free survival of 5.4 months compared with 8.8 months among those without detectable ctDNA (P = .004, HR = 1.57, CI = 1.15–2.13). The researchers validated the findings using multivariate models that included eight additional clinical and genomic parameters.
Conclusions
“Our findings suggest the level of [ctDNA], rather than the number of tumors themselves, is a more precise measure of disease burden,” stressed Dr. Chaudhuri. The researchers hypothesized that patients with no or low levels of detectable ctDNA may be the most likely to benefit from radiation therapy, whereas those with higher detectable levels of ctDNA may be more likely to require systemic therapy such as chemotherapy or immunotherapy.
“When you have a detectable ctDNA level, you have a higher burden of disease. Our findings indicate that we can use this biomarker to support patient-centered treatment decisions in the oligometastatic cancer setting,” Dr. Chaudhuri concluded.
Disclosure: For full disclosures of the study authors, visit nature.com.
