Liquid biopsy predicts radiotherapy benefit in metastatic lung cancer
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Key takeaways:
- Detectable ctDNA before radiotherapy associated with worse OS and PFS.
- Liquid biopsy of ctDNA may serve as a biomarker of those who can benefit from radiotherapy.
A novel liquid biopsy test can help determine whether patients with oligometastatic non-small cell lung cancer will benefit more from targeted, high-dose radiation instead of drug-based therapy, according to study results.
The findings — presented during American Society for Radiation Oncology Annual Meeting and published in NPJ Precision Oncology — show how measuring circulating tumor DNA (ctDNA) prior to potential consolidative radiation therapy can reveal whether an individual’s cancer has spread to a few tumor sites or spread more widely throughout the body, thus helping physicians determine the appropriate treatment method more effectively.
“We have exciting real-world data suggesting that circulating tumor DNA detection and levels can risk-stratify oligometastatic non-small cell lung cancer,” Aadel Chaudhuri, MD, PhD, a physician-scientist and assistant professor of radiation oncology, genetics, biomedical engineering and computer science at Washington University School of Medicine in St. Louis, said during a presentation. “[Patients with oligometastatic disease] with low or undetectable circulating tumor DNA had improved survival outcomes with radiotherapy, which — I think — is exciting.”
Background and methodology
Patients with oligometastatic disease can experience prolonged PFS when treated with local consolidative radiotherapy, Chaudhuri said. However, he added, identifying who can benefit most from this approach can be a challenge, and current scanning technology may miss micrometastatic disease.
Researchers conducted a retrospective analysis of 309 patients diagnosed with oligometastatic NSCLC with the hypothesis that pre-radiotherapy liquid ctDNA analysis could risk-stratify individuals with such disease, allowing for earlier personalized selection for consolidative radiotherapy.
All patients had ctDNA analysis performed using the Tempus xF assay prior to radiotherapy.
OS and PFS served as the primary measurement outcomes for the study.
Results
Researchers observed significantly worse OS among patients with oligometastatic NSCLC with detectable ctDNA before radiotherapy compared with patients without detectable ctDNA before radiotherapy (16.8 months vs. 25 months; HR = 1.65: 95% CI, 1.05-2.61).
Researchers also noted a similar comparison for PFS, with median PFS of 5.4 months vs. 8.8 months in favor of patients without detectable ctDNA before radiotherapy (HR = 1.57; 95% CI, 1.15-2.13).
Investigators found ctDNA variant allele frequency levels demonstrated significant risk correlations, including increased risk for both disease progression (P = 0.0084) and death (P = 0.0073).
Multivariate Cox modeling did not show significant impact for other clinical parameters, such as gender, age at diagnosis, smoking status and squamous histology. However, ctDNA mutational burden showed significant associations with both PFS (HR = 1.16; 95% CI, 1.06-1.26) and OS (HR = 1.15; 95% CI, 1.04-1.25).
Next steps
The findings indicate that ctDNA detection is a powerful biomarker to risk-stratify patients with oligometastatic non-small cell lung cancer and potentially allow for personalized decision-making for local consolidative radiotherapy, Chaudhuri said. Nevertheless, additional research will be needed moving forward, he added.
“This was across several sites in the United States in both community and academic practice,” Chaudhuri said during the presentation. “We need to test circulating tumor DNA-based decision frameworks for consolidation [stereotactic ablative radiotherapy/stereotactic body radiation therapy] for oligometastatic disease in prospective clinical trials.”
References:
Semenkovich NP, et al. Abstract 149. Presented at: ASTRO Annual Meeting; Oct. 1-4, 2023; San Diego.
Semenkovich NP, et al. NPJ Precis Oncol. 2023;doi:10.1038/s41698-023-00440-6.
Perspective
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Sameera Kumar, MD
Oligometastatic disease is a disease state in which a patient has one to five areas of metastatic disease. In certain cancer histologies, such as NSCLC, treatment of these oligometastatic sites is associated with better PFS and OS. However, in the clinic we know that not all patients with oligometastatic disease do well once all diseases sites have been radiated. Some go on to develop more metastatic lesions elsewhere. Thus, it would be useful to know which patients with oligometastatic disease would benefit from radiation.
In this study, ctDNA was sampled prior to radiotherapy to the oligometastatic sites. The investigators found an association between undetectable ctDNA before radiation and better OS and PFS. This is important because it can one day help us better select patients that would benefit from radiotherapy. It will also help us spare our patients the toxicity of radiotherapy if they would not benefit.
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Semenkovich NP, et al. Abstract 149. Presented at: ASTRO Annual Meeting; Oct. 1-4, 2023; San Diego.
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