Integrated circulating tumor DNA and T cell repertoire predict radiotherapeutic response and outcome in non‐small cell lung cancer patients with brain metastasis

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Integrated circulating tumor DNA and T cell repertoire predict radiotherapeutic response and outcome in non-small cell lung cancer patients with brain metastasisDear editor, The scarcity of routine metastatic biopsies or resection limits the finding of biomarkers of diagnosis and prognosis in patients with brain metastases.Derived from necrosis, apoptosis, and secretion of tumor cells, circulating tumor DNA (ctDNA) is widely distributed in various body fluids, including peripheral blood and cerebrospinal fluid (CSF), as an alternative biomarker for tumor-associated analysis [1].Fortunately, genomic alterations of blood ctDNA and CSF ctDNA have been proven as prognostic markers in non-small cell lung cancer (NSCLC) patients with brain metastasis [2, 3].T cell-mediated immunity is critical in suppressing oncogenesis and metastasis of NSCLC.Targeted sequencing in the highly variable complementarity-determining region 3 (CDR3) region of the beta chain of the T cell repertoire (TCR) provides a robust method to quantify T cell diversity [4].Casarrubios et al. [5] reported that the evenness of pretreatment TCR was related to the clinical response of NSCLC patients receiving neoadjuvant chemotherapy plus immunotherapy.Radiotherapy may stimulate immune responses against malignancies.Locally, irradiation causes antigen exposure by directly destroying cancer cells, which activates both the local and systemic immune systems.Irradiation can also cause DNA damage, and the ensuing mutations in cells with DNA mismatch repair deficiencies might increase the load of neoantigens, triggering an immunological response [6].The PACIFIC trial demonstrated that combining radiotherapy and immunotherapy was effective in prolonging