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  • Overall the results of this analysis suggest that around


    Overall, the results of this analysis suggest that around 10% of patients with EGFRm + advanced NSCLC who receive first-line afatinib can achieve long-term clinical benefit, defined by the authors as continuous afatinib treatment for a period ≥ 3 years. We were unable to identify any patient or tumor characteristics that appeared to predict long-term response. Nevertheless, known indicators of poor prognosis, including presence of PFK-158 metastases at baseline or uncommon EGFR mutations, did not appear to preclude prolonged treatment. Long-term clinical benefit with afatinib was independent PFK-158 of tolerability-guided dose adjustment and was achieved without negatively impacting safety or PROs. Further studies to identify markers/characteristics that can predict long-term response to afatinib are warranted. r> Author contribution statement
    Data sharing statement
    Conflict(s) of interest
    Introduction Lung Cancer (LC) is the most common cancer worldwide and the most common cause of cancer-related deaths. In 2012, approximately 1.8 million patients had LC worldwide, with 1.6 million deaths occurring in the same year. Due to recent innovations and developments in LC treatment, mortality has started to decrease in both men and women, but even so prognosis is still poor, with a 5-year survival rate being less than 15%. Non-Small Cell Lung Cancer (NSCLC) accounts for 85% of all LC cases [1,2]. Stage I, II, and III patients are treated with surgery, chemotherapy (CT), radiotherapy, or combined-modality approach. In contrast, patients with stage IV disease are managed with palliative systemic treatment [2]. Allogeneic Blood Transfusion (ABT) may cause various immune system dysfunctions [3]. In renal transplant patients, ABT is known to be beneficial, possibly due to its immunosuppressive effects [4,5]. However, since immunosuppression is detrimental for cancer patients, the hypothesis that blood transfusions may be harmful due to possible immunosuppression effect has been investigated in various cancer types. ABT has been shown to adversely affect disease prognosis in a diverse range of cancer types such as early stage LC, stomach cancer, colorectal cancer, bladder cancer, and prostate cancer [[6], [7], [8], [9], [10]].
    Materials and methods
    Discussion In cancer patients, anemia may develop due to treatment effects as well as the tumor itself [11]. Although ABT may improve anemia symptoms in oncology patients, there are some disadvantages associated with blood transfusion, such as contagious infections, hemolytic reactions, transfusion-related lung injury, and Transfusion-Related Immunomodulation (TRI) [12]. In a variety of malignancies, it has been proposed that TRI including allo-immunization, tolerance, or immunosuppression may elucidate the relationship between perioperative ABT and survival [7,10,[13], [14], [15]]. Kim et al. reported that ABT was associated with shorter survival in prostatic cancer [10]. Likewise, Liu et al. also demonstrated that preoperative ABT was found to be an independent risk factor on survival in gastric cancer [7]. Tartter et al. first reported that perioperative ABT increases the risk of recurrence in LC [16]. Many studies showed that perioperative ABT had a negative effect on recurrence and survival in LC. Several subsequent studies also reported that perioperative ABT in LC had a negative effect on disease recurrence and patients’ survival [6,[17], [18], [19], [20], [21]]; however, this relation could not be shown in some other studies [[22], [23], [24], [25], [26], [27]]. Wan et al., who conducted a meta-analysis including 23 studies and 6474 patients, showed that ABT was significantly associated with earlier recurrence and worse survival in patients with resected LC [28]. In our study, performing ABT during the treatment period was shown to increase the risk of progression and mortality by 1.5 times and 1.3 times, respectively, compared with the untransfused patients. In subgroup analysis, ABT significantly shortened PFS and OS, particularly in AC subtype.