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  • br Materials and methods br Results br

    2019-09-02


    Materials and methods
    Results
    Discussion The immune system role in maintaining active surveillance against malignancies has been known for decades [34,35]. Pre-clinical and clinical data have demonstrated that immune-compromised hosts have a higher incidence of tumors that often show an aggressive behavior. Moreover, these subjects usually have a poorer response to treatments and a worse prognosis than immune-competent hosts [36]. The concept of immune activation against tumors has dramatically increased its relevance since ICIs introduction in the clinical practice. Indeed, the rationale for the use of these agents relies on the stimulation of systemic immunity against cancer, leading to an immune-mediated killing of malignant cells. In the last years there has been large increase of the therapeutic indications for IO, which is now part of the standard treatment in various malignancies [37]. In lung cancer, different agents have been approved or are in advanced phase of study for locally advanced and metastatic disease. In many trials ICIs have shown a benefit over traditional cytotoxic agents in terms of survival both in first and in subsequent line of therapy [[3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14]]. Despite the general validity of this observation, it is also well known that only a limited number of patients really benefit from IO [13,14,17,[19], [20], [21], [22]]. While about one-third of cases show disease response and may expect a quite long survival, the remaining two-thirds never respond to ICIs maintaining a dismal prognosis [13,14,17,[19], [20], [21], [22]]. Given the relevance of this topic, many studies have focused on potential variables able to predict the response to IO. Data obtained with different agents and in different settings have supported a role for PD-L1 expression, tumor mutation burden and microsatellite instability [13,14,17,[38], [39], [40]]. Nonetheless, it is likely that the majority of factors accounting for such a variability still remains unknown. In this field, research has recently been developed about gut microbiota and its imbalances due to antibiotics. As regards to the lack of association between antibiotic use in the EIOP and outcome, our results differ from most recent research data showing a significant negative impact of early Paxilline use on PFS. We can be made only hypotheses to explain this discrepancy, maybe due to the population characteristics and to the small sample size. In any case, a numerical trend towards superior PFS and OS in patients not receiving antibiotics was identified, in line with literature data. Nonetheless, it has to be underlined that also a previous retrospective work on 74 NSCLC cases treated with nivolumab did not find differences in RR and PFS according to antibiotic use in the 3 months before the beginning of the ICI treatment [41]. This underlines the lack of definitive evidence in the field of microbiota and IO, in particular for NSCLC, and the consequent need of further research.
    Funding
    Conflict of interest statement
    Acknowledgement
    Introduction Malignant tumor of the trachea (MTT) is a rare disease [1,2] comprising around 0.01-0.4% of all cancer cases. In the US, incidence of these tumors is less than 0.2 per 1, 00,000 population [3,4]. Frequently, these tumors are diagnosed late as they present with non-specific symptoms and are often mis-diagnosed as asthma or other respiratory disorder. A wide range of histological subtypes has been described in the literature adding to the heterogeneity of presentation, treatment and outcome of these tumors. Surgery is considered the cornerstone of therapy. Due to the peculiar anatomy and need for plastic surgical techniques achieving a clear surgical margin is often difficult and adjuvant radiation has been used by many clinicians to improve outcome especially in patients with close/positive margins after resection. But the exact benefit from adjuvant radiation has not been established. There are also a group of inoperable patients in whom definitive radiotherapy has been advocated. However, owing to the rarity, most of the data is derived from institutional practice, case reports or small case series with wide range of bias. Hence, we embarked on to do an individual patient data analysis of published literature to find patient characteristics, patterns of care, survival outcomes and impact of various prognostic factors in this rare tumor. We also planned to do a subset analysis of major histology with regard to various treatment strategies and survival outcomes. In addition, we aimed to look into “Whether adjuvant radiotherapy has a role in the management of these tumors”.