Circulating Tumor DNA and T Cell Repertoire Predict Radiotherapeutic Outcomes in NSCLC Patients With Brain Metastasis

The scarcity of biopsies or focal resections for brain metastases limits the discovery of biomarkers for diagnosing and prognosis of NSCLC patients with brain metastases. Circulating tumor DNA (ctDNA) is derived from the necrosis, apoptosis, and secretion of tumor cells and is widely distributed in various body fluids, including peripheral blood and cerebrospinal fluid (CSF). Genomic alterations in blood and CSF ctDNA are prognostic markers in NSCLC patients with brain metastases. Still, they have limited predictive power. T cell-mediated immune responses are essential to suppress carcinogenesis and metastasis in NSCLC. Targeted sequencing in the highly variable complementarity determining region 3 (CDR3) region of the T cell receptor (TCR) β-chain provides a powerful approach to quantifying the diversity of T cells. Radiotherapy causes antigen exposure through direct local destruction of cancer cells, which activates the local and systemic immune system. Radiotherapy can also cause intracellular DNA damage, and the ensuing mutations in DNA mismatch repair defects may increase neoantigen load, triggering an immune response. The TCR, closely related to immune system modifications, can also be altered by radiotherapy. However, no clinical studies have explored ctDNA and TCR to predict the efficacy and prognosis of brain radiotherapy in patients with NSCLC brain metastases. Therefore, we retrieved the visit data of 50 patients with advanced NSCLC brain metastases who received brain radiotherapy through the hospital electronic medical record system and recorded the ctDNA and TCR values of patients' blood and CSF at baseline (within 2 weeks before radiotherapy), T0 (within 24 hours after the completion of radiotherapy) and T28 (28 days after the completion of radiotherapy), disease progression recurrence and survival time by examining. The dynamic changes of ctDNA and TCR during brain radiotherapy were studied to comprehensively assess the ability of ctDNA and TCR to predict the efficacy and prognosis of brain radiotherapy in patients with NSCLC brain metastases.