Abstract
BackgroundAlthough adjuvant chemotherapy is established for patients with non-small-cell lung cancer (NSCLC), the long-term survival remains to be improved. Postsurgical circulating tumor DNA (ctDNA) analysis of resectable NSCLC may identify patients at high risk of recurrence after adjuvant chemotherapy and facilitate personalized therapy.MethodsThis analysis included 38 patients who underwent curative-intent resection and received adjuvant chemotherapy for NSCLC. ctDNA analyses of tumor tissue, and pre- and post-operative plasma samples were performed with next-generation sequencing targeting 425 cancer-relevant genes. We define a ctDNA positive event as at least one shared mutation identified simultaneously in the plasma and tumor specimens. The primary endpoint was recurrence-free survival (RFS).ResultsAt least one somatic mutation was identified in the tumor tissue of all 38 patients. Tumor tissue-specific mutated ctDNA was detected in the preoperative plasma samples of 19 (50%) patients. ctDNA in preoperative plasma was in good accordance with that in tissue. ctDNA was detectable in the first post-operative pre-chemotherapy samples of 8 of 35 (22.9%) patients and was associated with inferior RFS (HR, 3.69; P = 0.033). ctDNA was detected in the first post-chemotherapy samples of 8 of 36 (22.2%) patients and was also associated with inferior RFS (HR, 8.76; P < 0.001).ConclusionsPostoperative and post-chemotherapy ctDNA is a promising prognostic marker for resected NSCLC. ctDNA analyses may define a subgroup that remains at high risk of relapse despite standard adjuvant chemotherapy, and may help to inform intensified therapeutic strategies.
Highlights
Lung cancer remains the most frequently diagnosed cancer and the leading cause of cancer mortality worldwide [1]
The samples analyzed in this study were collected as part of a registered study evaluating the value of Circulating tumor DNA (ctDNA) on resectable Non-small-cell lung cancer (NSCLC) (GASTO 1035, Clinical trial information: NCT03465241)
Key inclusion criteria for this study included a diagnosis of histopathologically confirmed resectable stage IB-III NSCLC; no metastasis evident on computed tomography (CT) of the chest and abdomen, and magnetic resonance imaging (MRI) of the brain before surgery; no history of previous anticancer therapy for lung cancer; and having a treatment plan for postoperative adjuvant chemotherapy
Summary
Lung cancer remains the most frequently diagnosed cancer and the leading cause of cancer mortality worldwide [1]. Studies have shown that detectable ctDNA following surgical resection for lung cancer [11,12,13], colorectal cancer [14,15,16,17], breast cancer [18, 19], melanoma [20], and pancreatic cancer [21], is associated with a high risk of recurrence. Post-chemotherapy detectable ctDNA detection may identify a patient subgroup that remains at high risk of relapse [22]. Adjuvant chemotherapy is established for patients with nonsmall-cell lung cancer (NSCLC), the long-term survival remains to be improved. Postsurgical circulating tumor DNA (ctDNA) analysis of resectable NSCLC may identify patients at high risk of recurrence after adjuvant chemotherapy and facilitate personalized therapy
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