Circulating tumor DNA kinetics: A future tool for radiation therapy personalization in lung cancer?

Locally advanced non-small cell lung cancer (NSCLC) is a highly diverse disease in terms of its histology, staging and molecular biology, yet chemoradiation treatment paradigms are currently not individualized for these factors. Circulating tumor DNA (ctDNA) in the plasma has clinical utility for several systemic therapies in advanced NSCLC, before, during and after treatment. However, in radiation oncology, the evidence for ctDNA in locally advanced NSCLC is largely limited to minimal residual disease (MRD) detection after treatment. In one study, all post-treatment MRD-positive patients developed disease relapse, compared with just 7% of ctDNA MRD-negative patients. As chemoradiation causes a bolus of tumor cell death with each treatment fraction, it has been posited that ctDNA levels fluctuate as well on a per-fraction basis. Indeed, four preliminary studies reveal a subgroup of patients with a transient elevation of ctDNA levels after the first radiotherapy fraction, followed by an overall ctDNA drop. To follow-up on these data suggesting an early ctDNA spike during chemoradiation, there is a need for larger and more systematic inter-fraction ctDNA studies, which if successful, could form the basis for more personalized and efficacious radiotherapy treatment paradigms.