Can Lung Cancer Relapse After Radiotherapy Be Predicted with a Simple Blood Test?

Treating localized lung cancer with radiotherapy can save lives, but nearly four out of ten patients see their disease reappear within the following year. A new approach could help identify these relapses earlier. Researchers have shown that a simple blood test can detect those most at risk by analyzing three biological indicators: the activity of natural killer cells, an immunity-related protein, and fragments of tumor DNA.

Natural killer cells play a key role in the body’s defense against tumors. When they are less active than normal, the risk of relapse after treatment increases significantly. Similarly, the presence in the blood of small pieces of DNA derived from the tumor, called circulating tumor DNA, often signals that cancer cells persist or return. Finally, a soluble protein called PD-L1, which influences the immune response, also appears linked to a less favorable prognosis.

The study followed sixty-eight patients with non-small cell lung cancer treated with radiotherapy. The results reveal that those with reduced natural killer cell activity before treatment had an increased risk of relapse within twelve months. Detecting tumor DNA in the blood at the start of follow-up or six months after radiotherapy also confirmed this risk. By combining these three markers, doctors obtain a much more reliable prediction than with a single indicator.

Circulating tumor DNA is particularly interesting because it comes directly from cancer cells. Scientists looked for specific chemical modifications in four genes often altered in this type of cancer. These modifications, called methylations, act as unique signatures of the disease. Their presence in the blood indicates that the tumor is still active or about to reappear.

The advantage of this method lies in its simplicity. Unlike a biopsy, a blood test is painless and can be repeated regularly. It allows monitoring the progression of the disease without waiting for symptoms or visible signs on imaging. Patients whose blood markers remain abnormal could benefit from closer monitoring or early additional treatments.

This approach paves the way for more personalized medicine. By identifying high-risk individuals, healthcare teams could tailor management to prevent the cancer from progressing again. Patients with a more advanced form of the disease seem to benefit the most from this type of monitoring. For those whose tumor is detected at an early stage, the results are less clear and require further research.

If these findings are confirmed on a larger scale, they could change the way patients are monitored after radiotherapy. Instead of waiting for the disease to reappear, it would become possible to act beforehand, relying on invisible but revealing signs in the blood. This could improve the chances of recovery and reduce the number of relapses, especially in people whose cancer is already advanced at the time of diagnosis.

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Official Study Source

DOI: https://doi.org/10.1007/s12094-026-04317-5

Title: The prognostic value of methylated ctDNA, soluble PD-L1, and NK-cell activity on the risk of relapse after curative radiotherapy of non-small cell lung cancer

Journal: Clinical and Translational Oncology

Publisher: Springer Science and Business Media LLC

Authors: Thomas Leth Fink; Rikke Fredslund Andersen; Cecilie Mondrup Jacobsen; Line Nederby; Mads Malik Aagaard Jørgensen; Charlotte Kristiansen; Torben Schjødt Hansen; Sara Witting Christensen Wen; Christa Haugaard Nyhus; Rune Slot Thing; Signe Timm; Torben Frøstrup Hansen