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  • USP7/USP47 inhibitor Despite the safety of SBRT

    2019-09-03

    Despite the safety of SBRT, as demonstrated by the low 30-day mortality rate, overall survival in patients receiving SBRT for early-stage NSCLC is poor. In retrospective analyses, SBRT was associated with 3-year survival of 45–50% for elderly patients with T 1-2 N0 NSCLC [26,41,42]. Small prospective trials have reported 3-year overall survival at 49–82% after SBRT for Stage I NSCLC [6,10,[43], [44], [45]]. In comparison, our study found a 3-year survival of 29.4%. However, the patients in our registry USP7/USP47 inhibitor had more advanced disease, with 20% having N1 disease, and 48% having T3N0 disease. Studies reviewing outcomes of SBRT for tumors > 5 cm reported median survival between 19.9 months and 25.1 months [25,46,47], similar to the median survival of 23.7 months reported in our study. For patients with T3N0 NSCLC with chest wall invasion treated with SBRT, median survival was lower at 13.3 months [24]. In our study, higher T and N classification were not significantly associated with decreased survival, but our analysis was likely underpowered given the relatively small sizes of the T1N1 and T2N1 groups. Our study was subject to the limitations associated with analyses using large retrospective datasets such as the NCDB. In addition to the aforementioned lack of data on local control, toxicity, and tumor location, NCDB does not capture cause of death, pulmonary function, medical operability, and patient USP7/USP47 inhibitor preferences, such that selection biases in treatment decision cannot be excluded. We also could not explain why node-positive patients received SBRT without other therapy. Furthermore, SBRT details including prescription isodose and target volume coverage are not collected. We also acknowledge that the strict definition of lung SBRT in the United States does not include hypofractionated regimens. We queried NCDB for treatments that were considered SBRT up to eight fractions and found only 13 patients treated with 6–8 fractions (data not shown). While other hypofractionated regimens may be employed as definitive treatment for early stage NSCLC, we limited our analysis to five fractions since any course of radiation treatment extending beyond five fractions is generally not considered SBRT in the United States and is not billed as such per the American Society for Radiation Oncology (ASTRO) Model Policy [48]. This report nevertheless provides novel information on the patterns of practice of SBRT in up to five fractions in Stage II NSCLC across the United States, identifying a large number of Stage II NSCLC patients treated with SBRT in a recent timeframe. Lastly, with the implementation of the new AJCC 8th edition Lung Cancer Stage Classification adopted in 2018, there will be stage migration with some Stage I cancers now defined as Stage II NSCLC, and some Stage II cancers now Stage III. This could potentially impact the treatment approach and decision to use SBRT, and survival outcomes as a result. We hypothesize that the new staging system will affect practice trends and survival, and look forward to updating these analyses for patients diagnosed in 2018 and afterwards.
    Conclusions To our knowledge, this is the first study to describe a dose-response relationship in patients treated with SBRT for Stage II NSCLC. We found that increasing BED10 was associated with improved survival, with this benefit significant in node-negative but not node-positive disease on multivariate analysis. As Stage II NSCLC represents a heterogeneous group of diseases, patient selection is important in identifying those who may benefit from SBRT. Prospective studies are warranted to further explore the role of SBRT in management of Stage II NSCLC, as well as determining the optimal dose fractionation of these regimens.
    Funding
    Conflict of interest statement
    Acknowledgement
    Introduction Modulation of the immune system through programmed cell death protein-1 (PD-1) inhibitors, i.e. nivolumab and pembrolizumab, can provide impressive clinical responses in non-small cell lung cancer (NSCLC) patients [1]. Blocking interactions between the inhibitory PD-1 on T cells with its ligand PD-L1 on the tumor or antigen presenting cells can reverse T-cell exhaustion and enhance tumor regression [2]. The striking results seen with checkpoint inhibitors highlights the importance of the immune system in treating cancer.