Liquid biopsy to inform non-small cell lung cancer treatment

A novel liquid biopsy test may help determine which patients with non-small cell lung cancer that has spread beyond the lungs are most likely to benefit from targeted, high-dose radiation, rather than drug-based therapy. That’s according to a new study presented this month at the American Society for Therapeutic Radiation Oncology (ASTRO) Annual Meeting and published in npj Precision Oncology.

Non-small cell lung cancer (NSCLC) accounts for about 84% of all lung cancers, which are the leading cause of cancer death worldwide. Patients diagnosed with NSCLC who have widespread metastatic disease — where cancer spreads past a person’s lungs and lymph nodes — generally cannot be cured. Some patients with oligometastatic disease — where the cancer has spread to just a few sites — do experience long periods of cancer-free survival when treated with high-dose radiation targeted to the individual tumour sites, but identifying which patients will benefit from this type of focused radiation treatment has been challenging.

Tumour tissue biopsy — long considered the gold standard for analysing solid tumours — only examines the site where the tissue sample was taken, and imaging tests also have limitations for detecting micro-metastatic disease. Senior study author Dr Aadel Chaudhuri, an assistant professor of radiation oncology at the Washington University School of Medicine in St. Louis, likened a visible tumour to an iceberg, saying it’s difficult for imaging tests to show “if the disease is just the part of the iceberg that’s visible above the water, or if there’s substantially more micro-metastatic disease beneath the surface”.

Liquid biopsy tests can detect elements of solid tumour cancers in blood, urine or cerebrospinal fluid. Blood tests are the most widely used type of liquid biopsy and can identify circulating tumour DNA (ctDNA), circulating tumour cells (CTC), circulating RNA and other biomarkers that signal the presence of cancer. According to Chaudhuri, “Liquid biopsy could help us know if there is micro-metastatic disease.”

Chaudhuri and his colleagues previously used liquid biopsy technology to monitor the status of patients with colorectal cancer, bladder cancer and peripheral nerve tumours. In the current study — a real-world, multi-institutional analysis — the researchers analysed data from 2016 to 2022 for 309 patients with oligometastatic NSCLC who received radiation therapy following liquid biopsy. Oligometastatic disease was defined in this study as metastatic disease in at least one, and up to five, organ systems.

Patients with detectable ctDNA prior to radiation therapy had worse overall survival than those whose blood showed no detectable ctDNA prior to treatment. For those whose blood showed traces of ctDNA, median overall survival was 16.8 months, compared to 25 months for patients with no ctDNA detected prior to treatment.

Likewise, progression-free survival was worse for those whose blood showed traces of ctDNA prior to radiation therapy. Median progression-free survival was 5.4 months for patients with detectable ctDNA, compared to 8.8 months for those with no detectable ctDNA prior to treatment. These findings were corroborated by multivariate models that included eight additional clinical and genomic parameters.

The findings indicate that patients with no or low levels of detectable ctDNA are most likely to benefit from radiation therapy, whereas those with higher detectable levels of ctDNA are more likely to need systemic therapy, such as chemotherapy or immunotherapy. Chaudhuri explained, “Our findings suggest the level of circulating tumour DNA, rather than the number of tumours themselves, is a more precise measure of disease burden.

“We can use this biomarker to support patient-centred treatment decisions in the oligometastatic cancer setting,” he said.

Image credit: iStock.com/Mohammed Haneefa Nizamudeen