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  • Secondly serum was used to isolate cfDNA rather than plasma


    Secondly, serum was used to isolate cfDNA rather than plasma. Compared to plasma, cfDNA isolated from serum tends to be at a higher concentration because of the extra release of DNA during the coagulation process [32]. cfDNA from serum has superior correlation and concordance rates according to various quantification methods [33]. In addition, we analyzed total cfDNA concentration rather than investigating allelic frequencies of NSCLC oncogenic drivers. However, to reduce the bias introduced by interfering factors, we used stringent purification methods to minimize the contamination from serum samples and to obtain high quality cfDNA. Thirdly, only Korean patients were analyzed with the retrospective study design, and hence, ethnic differences might alter the results. Larger prospective trials including various races GSK126 needed for further validation.
    Author contributions
    Source of funding and support This research was supported in part by the Korea Health Technology R&D Project of the Korea Health Industry Development Institute, Republic of Korea (HI14C0066; to Y. H. Kim); the Bio & Medical Technology Development Program of the National Research Foundation, Republic of Korea (NRF-2015M3A9D7031070; to Y. H. Kim); and Korea University Grant (K1813121; to J. S. Eo).
    Introduction Cytotoxic chemotherapy remains an important treatment for patients with non-small cell lung cancer (NSCLC) either alone or in combination with immunotherapy. Studies demonstrating the efficacy of first line treatment with immune checkpoint inhibitors (ICI) alone and in combination with chemotherapy have led to new first-line treatment options for patients with NSCLC [[1], [2], [3]]. Carboplatin, pembrolizumab and either paclitaxel or nab-paclitaxel are now standard first line options for patients with lung squamous cell carcinoma (LSCC) [4]. With multiple treatment options now available, patient selection will be key to guide clinical decision making. A better understanding of the genomic landscape of NSCLC has led to novel treatments for patients with select targetable mutations (i.e. EGFR, ALK, ROS, and BRAF among others), and in many cases targeted therapy offers improved response rates compared to chemotherapy [[5], [6], [7]]. Targeted therapies have so far shown clinical benefit primarily in patients with lung adenocarcinoma where driver mutations are more common than in patients with LSCC [8]. Mutations in TP53 represent the most common alteration in LSCC; mutations in CDKN2A, PIK3CA, KEAP1, MLL2, NFE2L2, and RB1 are also frequently observed [8,9]. Mutations in MLL2, CDH8, NFE2L2 or RB1 have been associated with a worse prognosis for patients with early stage LSCC [9]. Mutations in NFE2L2 and KEAP1 have also been associated with resistance to chemotherapy and targeted therapies as well as radiation therapy [10,11]. For patients whose tumors do not harbor actionable driver mutations, platinum-based chemotherapy remains a backbone of treatment with or without ICI [12]. For these patients, PD-L1 and tumor mutational burden (TMB) have been the primary biomarkers to guide therapy [2,13]. However, these have been predominantly studied in patients receiving ICI alone, and not in the context of chemotherapy-ICI combinations. There is an ongoing need to develop predictive biomarkers for chemotherapy to enhance patient selection for novel combination therapies. The mechanism by which platinum agents exert antineoplastic effect is largely through the creation of stable DNA adducts, leading to DNA damage and cell death [14]. This has led to DNA repair mechanisms being evaluated as a possible predictive biomarker for platinum-based therapy [15,16]. Understanding the role of DNA repair pathway mutations in response to platinum based chemotherapy is vital to determine optimal treatment approaches for patients with NSCLC. In this study we retrospectively performed next-generation DNA-sequencing on NSCLC patients who received first-line chemotherapy with carboplatin and nanoparticle albumin-bound (nab)-paclitaxel on an NCCN-sponsored clinical trial to evaluate the predictive value of DNA repair pathway mutations in this patient population.