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  • Tumor histology Non squamous NSCLC br Lymph nodes


    Tumor histology Non-squamous NSCLC5
    Lymph nodes Lung Bone Other viscera CNS4 Smoking history
    1 2 Number of metastatic sites (at IO)
    Male Female Age, median (range) [years] Basal PS2 (at IO3)
    Table 1 Patient characteristics.
    anti-PD1 (nivolumab in 88 cases, pembrolizumab in 10 cases); 33.1% of patients received an anti-PD-L1 (durvalumab in 31 cases, atezolizumab in 16 cases, avelumab in 4 cases, MSB0011359C in 1 case); 1 patient received an anti-CTLA4 (tremelimumab); 6 patients received a com-bined IO (durvalumab + tremelimumab).
    Eighty-two patients (52.2%) discontinued IO due to disease pro-gression, 30 (19.1%) for physician’s decision as a consequence of clinical deterioration, 10 (6.4%) after regular conclusion of the planned treatment program, one (0.6%) for patient’s withdrawal of consent. IO was still ongoing at the time of database lock in 34 cases (21.7%).
    3.2. Antibiotic treatment characteristics
    A total number of 46 patients (29.3%) received at least one ad-ministration of antibiotic through the WIOP.
    Twenty-seven patients (17.2%) received 94885-02-6 during the
    EIOP. In 7 cases (25.9%), more than one antibiotic was subsequently
    administered. All patients received single agent antibiotic therapy.
    Considering all the 46 patients receiving antibiotics, the prescrip-
    tion was due to a respiratory tract infection in almost all cases. Four
    100.0 patients (8.7%) received an antibiotic for a reactivation of diverticular
    bowel disease, one for colitis, and one for urinary tract infection; all
    59.9 these cases were also treated with a different antibiotic for pneumonia.
    40.1 According to the etiology, the most commonly prescribed antibiotic
    was levofloxacin (30 cases, 65.2%), followed by amoxicillin/clavula-
    84.7 The median duration of single cycle antibiotic was 6 days (range:
    49.7 2–17 days). Considering the cumulative duration of the antibiotic
    treatment, thus summing the length of single cycles, the median value
    had an AIER higher than the median one. The median duration of an-
    77.1 tibiotic treatment was significantly different between the 2 subgroups
    clinical and pathological variables were balanced between the 2 sub-
    Median follow-up was 28.6 months.
    Table 2
    Clinical and pathologic characteristics according to AIER.
    Number of metastatic sites (at IO)
    Smoking history
    Tumor histology
    PD-L1 expression
    Line of IO
    1 Antibiotic-Immunotherapy Exposure Ratio.
    3 Performance Status.
    4 Immunotherapy.
    5 Non small Cell Lung Cancer.
    At univariate analyses, no impact on PFS was evidenced for smoking status, ICI mechanism of action, gender and age. A significant detri-mental effect on PFS was observed for basal PS ≥ 1 and for second or more advanced IO lines. Similarly, no significant differences in median OS were seen when stratifying patients according to smoking status, ICI mechanism of action, gender, age, and IO line. The only variable ne-gatively impacting on OS was the basal PS (p < 0.0001) (Table 3).
    Regarding the antibiotics effects, the use of one or more anti-mi-crobic agents in the EIOP did not influence either PFS (3.3 months in non-treated patients versus 2.2 months in treated patients; p = 0.1772) or OS (11.9 months for non-treated patients versus 5.9 months for treated patients; p = 0.2492), although a numeric trend towards a better prognosis was seen for cases not receiving antibiotics (Table 3 and Fig. 1).
    When considering a different time cutoff of 2 instead of 3 months after the first ICI administration, the results did not change (median PFS 3.35 in non-treated patients versus 2.2 in treated patients; p = 0.0992; median OS 11.9 months in non-treated patients versus 5.6 months in treated patients; p = 0.2147).
    At multivariate analyses, the impact of AIER on PFS retained sig- nificance after correction for the effects of basal PS (HR 1.053,
    4. 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].