TORONTO – Nov 19, 2021 – Radical operation is a standard approach for early/mid-stage lung cancer patients. However, tumor recurrences or metastases may inevitably develop which can lead to treatment failures. Minimal residual disease (MRD), a small number of leftover cancer cells after curative-intent treatments, is often untraceable using conventional diagnostic methods like medical imaging. Therefore, there is an urgent need for a highly sensitive method to predict the risk of recurrence in early/mid-stage lung cancer population.

In the CALIBRATE(monitoring post-surgery CAncer recurrence by ctDNA LIquid Biopsy RATing)-NSCLC program, Geneseeq and the Chinese Academy of Medical Sciences published a recent prospective study in Nature Communications, employing SHIELDINGTM, Geneseeq’s newly launched MRD product to dynamically monitor residual circulating tumor DNA (ctDNA) in non-small cell lung cancer (NSCLC) patients who received surgery with/without adjuvant chemotherapy (ACT). The researchers demonstrated pioneering works of using residual ctDNA to guide ACT and applying cutting-edge mathematical models to predict recurrence risk.

This study enrolled 116 NSCLC patients who received surgical resection, including 71 patients who were treated with ACT after surgery. The serial ctDNA samples collected pre-treatments, post-treatments, and during disease surveillance were analyzed by an ultradeep sequencing technology called ATG-SeqTM . This technology is extremely sensitive to detect MRD at a mean coverage depth of ~30,000×. The sensitivity of ATG-SeqTM was further supported by the observation that the detection of ctDNA preceded imaging technology-determined recurrence by a median of 88 days, or 3 months in this study.

Notably, when residual ctDNAs remained detectable after surgery and/or ACT, the patient was less likely to have a recurrence-free survival than ctDNA-negative patients. The authors then specifically investigated stage II-III patients who were recommended to receive ACT after surgery. The results showed that only the postsurgical ctDNA-positive patients benefited from ACT. This suggests an important clinical implication of stratifying patients for adjuvant treatments, as ACT might be overtreatment for postsurgical ctDNA-negative patients. By using joint modeling that couples the information of longitudinal ctDNA and recurrence time, the authors could accurately predict personalized recurrence risk beyond one year after the surgical treatment.

“Postoperative ctDNA status shows to be a reliable marker to monitor tumor recurrence in lung cancer patients, guiding clinical decisions for better postoperative treatment”, says Dr. Hua Bao, author and R&D director of Geneseeq.  In 2021, Geneseeq launched its cutting-edge product SHIELDING TM with our self-developed ATG-SeqTM technology. So far, the company has successively published two important colorectal cancer studies under the CALIBRATE-CRC and CALIBRATE-RC-nCRT programs. For the third time, this CALIBRATE-NSCLC study once again demonstrates the application value of liquid biopsy in the perioperative management of early/mid-stage tumors, providing more support to evidence-based, personalized clinical management and treatment decisions.