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Stanford University School of Medicine

Predicting lung cancer recurrence by analyzing circulating tumor DNA

I've mentioned before how circulating tumor DNA, or ctDNA, is likely to be a valuable tool for predicting disease recurrence in patients with lymphoma. Now two researchers working in this area -- hematologist and oncologist Ash Alizadeh, MD, PhD, and radiation oncologist Maximilian Diehn, MD, PhD, collaborating with postdoctoral scholar and radiation oncology resident Aadel Chaudhuri, MD, PhD -- have extended their studies to patients with localized lung cancer.

Studying 255 blood samples taken at various times after treatment from 40 patients, the team found they were able to distinguish people in whom the disease would recur from those who had been cured of their cancer. In particular, they were able to detect the ctDNA in the blood of most of the patients about five months before the disease was otherwise clinically detectable.

They published their findings in Cancer Discovery and presented their research at the American Society for Radiation Oncology's annual meeting in San Diego last weekend.

As Diehn explained in an email to me:

It is currently difficult to distinguish patients with localized lung cancer who have been cured by treatment from those who have residual disease using standard radiologic scans that are available clinically. In this study, we set out to test if analysis of circulating tumor DNA in patients with early stage lung cancer can distinguish those who have likely been cured from those who still harbor cancer cells in their bodies after treatment. Strikingly, we observed that all patients in whom we could detect circulating tumor DNA after treatment developed recurrence, while the vast majority of patients who were circulating tumor DNA negative remained disease free.

Furthermore, about half of the patients whose disease ultimately recurred harbored mutations in their ctDNA often associated with a positive response to specific anti-cancer treatments such as tyrosine kinase inhibitors or immune checkpoint blockades. The researchers envision a time when ctDNA will be used not just to predict disease recurrence but also to help clinicians make the best treatment decisions for each patient.

Alizadeh elaborated:

Our study is among the first to demonstrate the utility of detectable molecular evidence of residual disease in patients with lung cancer using circulating tumor DNA, as well as the high specificity and sensitivity of this approach. We are hopeful that these results help inform future studies that allow us to target such risk in patients with evidence of residual ctDNA, using clinical trials of novel agents as adjuvant therapies to improve the outcomes of patients with lung cancer.

Alizadeh and Diehn are both investigators at the Ludwig Center for Cancer Stem Cell Research and Medicine at Stanford.

Previously: Tracking resistance mutations in lung cancer patients, Lymphoma shares secrets in its circulating tumor DNA and Nowhere to hide: Blood-based cancer monitoring gets ever more sensitive
Photo by Shannan Muskopf


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