Circulating tumor DNA guided therapeutic strategies for colorectal cancer patients with multiple small pulmonary-limited nodules: An open-label, prospective, phase II cohort study.

Abstract

e15645 Background: The clinical diagnosis and treatment of small pulmonary nodules (suspected to be lung metastases) in advanced colorectal cancer (CRC) patients remain controversy. Previous studies have shown that tumor-informed circulating tumor DNA (ctDNA) testing with blood sample can sensitively detect recurrence or metastasis of CRC patients. This study was designed to explore the clinical value of tumor-informed ctDNA test in metastatic CRC patients with small pulmonary-limited nodules. We aimed to identify the low-risk patients for de-escalation therapy, as well as high-risk patients with no evidence of disease (NED) for escalation therapy. Methods: This is an ongoing, open-label, prospective and phase II cohort study (NCT 05495672). According to the longest diameter of the pulmonary nodule, patients were divided into two cohorts: Cohort 1(0-1cm) and Cohort 2 (1-2cm). Tumor-informed ctDNA test (OriMIRACLE S) would be performed every three months until progression or 2 years. The treatment strategy of each patient is decided by a multidisciplinary team depending on ctDNA and lung CT scan results. In general, negative minimal residual disease (MRD) patients will receive only regular follow-up. Patients with positive MRD will receive intensive examination and local treatments for pulmonary nodules such as surgery, radio frequency ablation or stereotactic body radiotherapy combined with or without systemic therapeutic treatment, aiming to achieve NED or cure. Results: From June 2022 to December 2022, a total of 26 patients were screened in the group, one patient was eliminated (with extrapulmonary metastasis), and a total of 25 patients were successfully enrolled. At present, 1 patient died (by acute intestinal perforation), 4 patients were excluded from the group (with the emergence of extrapulmonary metastasis), and a total of 20 patients were in the group. The positive rate of MRD in baseline were 4/11(36.4%) for Cohort 1 and 10/14 (71.4%) for Cohort 2, respectively. Notably, in Cohort 1, 3 of 4 patients with positive MRD at baseline were examined extrapulmonary metastasis during the follow-up examination. Conclusions: Our preliminary results suggested that the positive rate of MRD were higher in Cohort 2 than Cohort 1. Patients with pulmonary nodule less than 1 cm tended to develop extrapulmonary metastasis if baseline MRD was positive. In such circumstances, more intensive follow-up examination is suggested to prevent early disease progression. Clinical trial information: NCT05495672 .