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Liquid Biopsy Could Guide Treatment Decisions for Oligometastatic Lung Cancer

Two vials of blood.
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A new study led by Washington University School of Medicine in St. Louis could help doctors decide the best treatment strategy for patients with lung cancer that has spread beyond the original tumor but has not spread all over the body. This type of non-small cell lung cancer is called oligometastatic disease, and the best treatment strategy for such patients is not always clear.

The study, published Oct. 2 in the journal npj Precision Oncology, describes a liquid biopsy test that can detect small amounts of tumor DNA circulating in the bloodstream. In a step toward precision medicine for oligometastatic lung cancer patients, the amount of tumor DNA measured in a blood sample could help doctors decide the best treatment strategy for a specific patient.

The research builds on earlier efforts to improve the process of diagnosing and monitoring disease. To date, the researchers have worked to develop liquid biopsy technology to diagnose or monitor the post-treatment status of colorectal cancer, bladder cancer and peripheral nerve tumors, among others. The team also is working to develop a liquid biopsy technology that can predict severe toxicity to immune checkpoint inhibitors. Such immunotherapy drugs are commonly used to treat lung cancer and melanoma.

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In the team’s latest work, the focus was on lung cancer. Localized lung cancer is typically treated with radiotherapy or surgery, while metastatic lung cancer that has spread throughout the body is typically treated with systemic therapy, including chemotherapy and checkpoint immunotherapy.

In patients with oligometastatic disease — a kind of in-between state — some do well with local radiation to the individual tumors, while in others, the disease spreads quickly, suggesting that the patient may have needed systemic therapy to eradicate cancer cells that spread elsewhere but were undetectable by standard imaging procedures.

“Oligometastatic disease can become a conundrum in our clinics,” said senior author Aadel Chaudhuri, MD, PhD, an assistant professor of radiation oncology who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “We can treat tumors that have spread, sometimes to other organs, with targeted radiation therapy. Sometimes it works very well, and patients will achieve a long-term disease-free interval. But sometimes they won’t. And in those cases, it may have been more effective to prioritize further systemic therapy. Our liquid biopsy technology can add information that could help make these treatment decisions more precise and effective in the future.”

The researchers analyzed blood samples from patients from multiple clinical sites, including academic medical centers and community oncology practices. The analysis included 1,487 patients with non-small cell lung cancer that can be categorized as oligometastatic. Of these, 309 patients had their circulating tumor DNA levels measured before undergoing radiation therapy.

Among these 309 patients, almost half (151 patients) saw their disease worsen, and 11% (34 patients) died during the study. Circulating tumor DNA was detected before radiotherapy in 74% of patients (230 people). And in 26% of patients (79 people), no circulating tumor DNA could be detected before radiation treatment.

Patients without detectable tumor DNA in the blood before radiation treatment survived longer than patients with detectable tumor DNA. For those with detectable tumor DNA, overall survival averaged less than 17 months compared with 25 months for those without tumor DNA in the blood before radiotherapy.

The research suggests that patients with low or undetectable tumor DNA circulating in the blood are most likely to benefit from radiation therapy in helping to achieve a long-term remission. In contrast, those with detectable or high circulating tumor DNA likely have a higher risk of disease spread, and it may be best to prioritize systemic therapy for these patients without taking a break for radiation treatment.

“Standard imaging technologies can miss some metastatic disease,” said first author Nicholas Semenkovich, MD, PhD, a clinical research fellow in Chaudhuri’s lab. “This liquid biopsy technology gives us a new and more sensitive way to detect whether the cancer has spread and to what extent. Depending on the levels of metastatic disease that are detected, we may find that a patient needs more aggressive radiation therapy to targeted sites, or that they would benefit from systemic chemotherapy, and it may even help decide which patients could benefit most from a clinical trial.”

The cell-free DNA liquid biopsies in this study were conducted using a commercially available test called Tempus xF. Chaudhuri and his colleagues optimized the analysis of this cell-free DNA test to improve the sensitivity of detecting circulating tumor DNA in this setting. The researchers have worked with Washington University’s Office of Technology Management to file intellectual property on this analytical method.

The researchers are working with clinical colleagues to plan a study to validate the liquid biopsy technology prospectively with the eventual goal of using it to guide treatment decisions to improve survival for patients with oligometastatic non-small cell lung cancer.

Reference: Semenkovich NP, Badiyan SN, Samson PP, et al. Pre-radiotherapy ctDNA liquid biopsy for risk stratification of oligometastatic non-small cell lung cancer. npj Precis Oncol. 2023;7(1):100. doi: 10.1038/s41698-023-00440-6

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