Author: Everett Moding, MD, PhD, Assistant Professor Department of Radiation Oncology, Stanford University School of Medicine

A combination of chemotherapy and radiation therapy (chemoradiation therapy) is the backbone of treatment for non-small cell lung cancer (NSCLC) that has spread to the lymph nodes in patients who are not candidates for surgery. Although chemoradiation therapy has the potential to be curative, most patients relapse after treatment. Furthermore, many patients are likely over-treated with higher than necessary radiation doses because there are currently no proven approaches to identify which patients could benefit from more or less treatment.

Analysis of DNA released from cancers into the blood using liquid biopsies is an emerging approach to track the response of tumors like lung cancer to treatment1. Several clinical trials are under way to determine if circulating tumor DNA (ctDNA) analysis can be used to personalize cancer treatment and improve patient outcomes. In addition to its use as a biomarker, ctDNA can be a powerful tool to understand why some patients with cancer respond well to treatment but other patients ultimately develop cancer progression2.

With support from GO2 for Lung Cancer’s Conquer Cancer Young Investigator Award, Everett Moding, MD, PhD at Stanford University used ctDNA analysis to help understand which tumor mutations in patients with NSCLC determine how patients will respond to chemoradiation therapy. By identifying tumor mutations that appear at the time of relapse after treatment, Dr. Moding has identified mechanisms that may contribute to chemotherapy and radiation resistance3. In addition, Dr. Moding used ctDNA changes during chemoradiation therapy to identify patients responding favorably to treatment and identify mutations that could be associated with chemoradiation therapy sensitivity4. In the future, Dr. Moding hopes to use the results from these studies to enable customized treatment approaches that increase efficacy and reduce side effects for patients with NSCLC.

References

1. Moding, E. J., Nabet, B. Y., Alizadeh, A. A. & Diehn, M. Detecting Liquid Remnants of Solid Tumors: Circulating Tumor DNA Minimal Residual Disease. Cancer Discov (2021) doi:10.1158/2159-8290.CD-21-0634.

2. Blomain, E. S. & Moding, E. J. Liquid Biopsies for Molecular Biology-Based Radiotherapy. International Journal of Molecular Sciences 22, 11267 (2021).

3. Moding, E. J. et al. Abstract 8533: Noninvasive identification of emergent mutations following cytotoxic therapy for lung cancer. J. Clin. Oncol. 39 :15_suppl, 8533–8533 (2021).

4. Moding, E. J. et al. Abstract PO-069: Circulating tumor DNA kinetics to identify genomic predictors of rapid response to chemoradiation in non-small cell lung cancer. Clin Cancer Res 27, PO-069 (2021).