Abstract 49P
Background
Substantial heterogeneity exists in the benefits from local treatments for oligometastatic non-small cell lung cancer (NSCLC). We propose that circulating tumor DNA (ctDNA) can molecularly redefine populations with induced oligopersistence disease and those more likely to benefit from surgery in NSCLC.
Methods
In this prospective, observational study, we enrolled patients with oligometastatic NSCLC identified through 18F-FDG-PET/CT following systemic therapy. Patients underwent resection targeting residual lesions. Comprehensive ctDNA monitoring was conducted perioperatively. Tumor tissues were pathologically assessed per the IASLC multidisciplinary recommendations for neoadjuvant therapy assessment, and multi-region sampling and whole-exome sequencing (WES) were performed.
Results
A total of 68 patients with induced oligometastases were enrolled, predominantly with adenocarcinoma (n=63, 92.6%), EGFR mutations (n=44, 64.7%), and oligopersistence (n=58, 85.3%). Patients who achieved major pathological response had better prognosis compared to those who did not (HR=4.57, 95% CI 2.16-9.65, p<0.05). Patients with preoperative ctDNA negative status had significantly better outcomes than those with positive status (HR=3.42, 95% CI 1.19-9.87, p=0.001). Patients who maintained or transitioned to negative ctDNA 1 month after surgery exhibited better outcomes than those who maintained or transitioned to positive ctDNA (maintaining negative vs. transition to positive: HR=3.22, p=0.041; transition to negative vs. maintaining positive HR=4.57, p=0.03). Thus, patients who maintained or transitioned to ctDNA negative status may represent a subgroup with molecular-level oligometastases who were more likely to benefit from surgery. Moreover, WES of tumors revealed resistant clones to systemic therapy in a subset of patients, emphasizing the importance of surgery. Collectively, patients without acquired resistance mutations detected in tumor tissue had a better prognosis than those with detection (HR=3.67, 95% CI 0.92-14.7, p=0.006).
Conclusions
We redefine oligopersistence disease and identify a pre-respondent subgroup more likely to benefit from surgery in NSCLC through ctDNA at the molecular level.
Legal entity responsible for the study
W-Z. Zhong.
Funding
This research was supported by funding from the National Natural Science Foundation of China Major Joint Project on Key Scientific Issues of Lung Cancer(No.82241235), National Natural Science Foundation of China (81872510), Guangdong Provincial People's Hospital Young Talent Project (GDPPHYTP201902), Guangdong Basic and Applied Basic Research Foundation (No.2019B1515130002), High-level Hospital Construction Project (DFJH201801), and Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (Grant No. 2017B030314120).
Disclosure
Y. Xiong, M. Cai, F. Li, R. Chen: Financial Interests, Personal, Full or part-time Employment: Geneplus-Beijing. Y. Wu: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche Holdings AG; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, AstraZeneca, Eli Lilly, Roche Holdings AG, Pfizer, Sanofi, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Boehringer Ingelheim (Inst), Roche Holdings AG (Inst). W. Zhong: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, Pfizer, Roche Holdings AG, Sanofi, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol Myers Squibb. All other authors have declared no conflicts of interest.