Until very few years ago, the oncology community dogmatically excluded any clinical potential for immunotherapy in controlling brain metastases. Therefore, despite the significant therapeutic efficacy of monoclonal antibodies to immune check-point(s) across a wide range of tumor types, patients with brain disease were invariably excluded from clinical trials with these agents. Recent insights on the immune landscape of the central nervous system, as well as of the brain tumor microenvironment, are shedding light on the immune-biology of brain metastases. Interestingly, retrospective analyses, case series, and initial prospective clinical trials have recently investigated the role of different immune check-point inhibitors in brain metastases, reporting a significant clinical activity also in this subset of patients. These findings, and their swift translation in the daily practice, are driving fundamental changes in the clinical management of patients with brain metastases, and raise important neuroradiologic challenges. Along this line, neuro-oncology undoubtedly represents an additional area of active investigation and of growing interest to support medical oncologists in the evaluation of clinical responses of brain metastases to ICI treatment, and in the management of neurologic immune-related adverse events. Aim of this review is to summarize the most recent findings on brain metastases immunobiology, on the evolving scenario of clinical efficacy of ICI therapy in patients with brain metastases, as well as on the increasing relevance of neuroradiology in this therapeutic setting.

Considering the transversal unmet need for the counselling of advanced cancer patients treated with immune checkpoint inhibitors (CKI) about influenza vaccination, we planned an explorative study to assess the efficacy of influenza vaccine in this population, its potential impact on the severity and mortality of influenza syndrome (IS) and on of anticancer immunotherapy outcome. METHODS: INVIDIa was a retrospective, observational, multicenter, explorative study at 21 Italian centers, enrolling consecutive advanced cancer patients receiving treatment with CKI during the Italian influenza vaccinal season 2016-2017. All data regarding influenza vaccination, IS and treatment with CKI were collected. Subgroup analyses were pre-planned for elderly and lung cancer patients. RESULTS: The study enrolled 300 patients, 79 of which received flu vaccine; 221 unvaccinated patients constituted the control group. The incidence of IS was of 24.1% among vaccinated, vs 11.8% of controls; OR=2.4 (95%CI=1.23-4.59; p=0.009). Severity of

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Background: Immune-related adverse events (irAEs) are inflammatory side effects, which can occur during immune-checkpoint(s) inhibitors (ICIs) therapy. Steroids are the first-line agents to manage irAEs because of their immunosuppressive properties. However, it is still debated whether or when steroids can be administered without abrogating the therapeutic efforts of immunotherapy. Methods: We retrospectively evaluated 146 patients with metastatic non-small cell lung cancer (NSCLC), melanoma and renal cell carcinoma (RCC) treated with ICIs. We assessed the progression-free survival (PFS) of patients treated with steroids due to an irAE compared to a no-steroid group. Results: The early treatment with steroid (within the first 30 days from the beginning of immunotherapy) was not related to a shorter PFS (p = 0.077). Interestingly, patients who were treated with steroids after 30 days from the start of immunotherapy had significantly longer PFS (p = 0.017). In a multivariate analysis, treatment with steroids after 30 days was an independent prognostic factor for PFS (HR: 0.59 [95% CI 0.36–0.97], p = 0.037). Conclusions: This retrospective study points out that early systemic steroids administration to manage irAEs might not have a detrimental effect on patient clinical outcome in NSCLC, melanoma and RCC patients.

The identification of these subgroups of "real life" patients with a high prevalence of nonadherers might be functional in designing intervention studies aimed at improving adherence.