How Liquid Biopsy Predicts Immunotherapy Success in Advanced Lung Cancer?

Researchers at the Johns Hopkins Kimmel Cancer Center, the Bloomberg~Kimmel Institute for Cancer Immunotherapy, and Allegheny Health Network Cancer Institute in Pittsburgh found that using the ‘liquid biopsy’ method to study genetic material from tumors shed in the blood, along with immune cells, can help doctors figure out which patients with advanced lung cancers are responding well to immunotherapies. This method can also indicate which patients might experience immune-related side effects several months down the line.

Scientists closely watched 30 patients undergoing immunotherapy for advanced non-small cell lung cancers, tracking changes in circulating tumor DNA (ctDNA). They found that when the genetic material from tumors in the bloodstream decreased (molecular response), it was linked to better progression-free and overall survival. The researchers also used regular blood tests to identify an increase in T cells (immune cells targeting tumor cells) in patients experiencing immune-related issues, like lung inflammation, up to five months before symptoms appeared. This pattern was confirmed in another group of 49 patients at the Allegheny Health Network Cancer Institute.

“Immunotherapy has revolutionized how we take care of patients with lung cancer, but it’s been challenging to determine how to assess response,” says lead study author Joseph Murray, M.D., Ph.D., an assistant professor of oncology and co-director of the Lung Cancer Precision Medicine Center of Excellence at Johns Hopkins. “We don’t have reliable biomarkers, so we rely a lot on imaging and patient symptoms to see how patients are clinically responding. Now, we can potentially use noninvasive tests like this to study response and predict side effects very early on, and change therapy regimens if necessary.”

The test was also useful in figuring out what might happen to patients who showed no changes in their disease when looked at through imaging, explained Dr. Valsamo “Elsa” Anagnostou. She’s a top researcher at Johns Hopkins, overseeing the thoracic oncology biorepository, leading Precision Oncology Analytics, co-leading the Johns Hopkins Molecular Tumor Board, and co-directing the Lung Cancer Precision Medicine Center of Excellence.

“All of the patients who appeared to have stable disease on imaging tests had very different DNA molecular response patterns that helped predict their overall clinical outcomes,” Anagnostou says. “This is a particular subset of patients for whom we may want to intervene and use liquid biopsies to guide therapeutic decision-making, as ctDNA can rapidly and accurately capture the amount of cancer present.” This liquid biopsy study aligns with the continuous work of the thoracic oncology team at Johns Hopkins, aiming to use liquid biopsy in making clinical decisions. They are conducting a clinical trial (NCT04093167) that adapts based on circulating tumor DNA (ctDNA) for patients with metastatic lung cancer, exploring chemo-immunotherapy.

Source: John Hopkins Medicine