Immunotherapy has revolutionized the treatment of various solid tumors by harnessing the body’s immune system to recognize and destroy cancer cells. However, its role in mesothelioma remains understudied and controversial. Prior large-scale trials incorporating surgery with systemic therapies failed to demonstrate consistent survival benefits, casting doubt on the utility of surgical resection. This study challenges that paradigm by incorporating immune checkpoint blockade in a strategic perioperative timeline, attempting to augment antitumor immunity when tumor burden is minimized.
One of the study’s most innovative features lies in its use of circulating tumor DNA (ctDNA) profiling. ctDNA refers to fragments of tumor-derived genetic material released into the bloodstream, offering a minimally invasive biomarker for real-time disease monitoring. Mesothelioma’s low mutational burden complicates traditional ctDNA detection, but the researchers applied an ultra-sensitive genome-wide sequencing approach. This technique enabled the detection of microscopic residual disease that imaging alone could not reveal, providing unprecedented insight into tumor dynamics at a molecular level.
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Perioperative nivolumab or nivolumab plus ipilimumab in resectable diffuse pleural mesothelioma: a phase 2 trial and ctDNA analyses