Posted: Tuesday, January 17, 2023
According to a study in the journal Nature Cancer, researchers have identified the first biomarker that may be able to predict response to the combination of radiotherapy and immune checkpoint blockade. In the current study, patients with non–small cell lung cancer (NSCLC) who had high tumor aneuploidy were found to have significantly better survival with concurrent radiotherapy plus immune checkpoint blockade than with sequential ablative radiotherapy and immune checkpoint blockade.
“By giving immunotherapy with radiation, we believe that radiation becomes more effective at killing tumor cells by helping immune cells find the damaged tumor that’s dying off,” said Sean P. Pitroda, MD, of the University of Chicago Medicine, in an institutional press release. “Our findings highlight that radiation therapy alone is not enough to trigger a localized immune response in metastatic NSCLC, and the timing of radiation and immunotherapy is critical to this process.”
Dr. Pitroda and colleagues performed a comprehensive molecular analysis of a randomized phase I clinical trial of patients with NSCLC treated with concurrent or sequential ablative radiotherapy and immune checkpoint blockade. The results indicated that concurrent treatment is superior to sequential treatment in augmenting local and distant tumor responses. The treatment also improved overall survival in a subset of patients with “immunologically cold,” highly aneuploid tumors but not in those that had less aneuploidy.
These findings challenge the prevailing paradigm that local ablative radiotherapy beneficially stimulates the immune response. Dr. Pitroda and colleagues proposed the use of tumor aneuploidy as a biomarker and therapeutic target in personalizing treatment approaches for patients with NSCLC treated with radiotherapy and immune checkpoint blockade.
Disclosure: For full disclosures of the study authors, visit www.nature.com.