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The mPEBev is an anticancer regimen which combines a chemotherapy doublet, based on cisplatin and oral etoposide (mPE), with bevacizumab (mPEBev), a mAb targeting the vasculo-endothelial growth factor (VEGF). In previous studies, this regimen showed powerful anti-angiogenetic effects and significant antitumor activity in metastatic non-small-cell lung cancer (mNSCLC) patients. We also recorded the best benefit in patients exhibiting low-systemic inflammatory profile at baseline. On these bases, we hypothesized that mPEBev antitumor activity could be partially related to bevacizumab-associated immunological effects. For this reason, we performed an immunological monitoring in 59 out of 120 stage IIIb-IV NSCLC patients enrolled in the BEVA2007 phase II trial, who received fractioned cisplatin (30 mg/sqm days 1-3q21) and oral etoposide (50 mg, days 1-15q21) (mPE doublet) ±bevacizumab. In this group of patients, 12 received the mPE doublet alone and 47 the doublet in combination with bevacizumab (5 mg/kg on the day 3q21; mPEBev regimen). Blood cell counts, serum analysis, multiplex cytokine assay and immunocytofluorimetric analysis, performed on baseline and post-treatment on blood samples from these patients, revealed that bevacizumab addition to the doublet decreased levels of pro-angiogenic (VEGF, Angiostatin-1 and Follistatin) and inflammatory cytokines (interferon (IFN)γ, IL4 and IL17), improved in vivo and in vitro cytotoxic T-lymphocytes (CTL) response and promoted dendritic cell activation. These results suggest that the mPEBev regimen improve the micro-environmental conditions for an efficient antigen-specific CTL response, making it a feasible candidate regimen to be assessed in combination with immune-checkpoint inhibitors in NSCLC patients.

Background The number of patients undergoing joint arthroplasty is increasing worldwide. An Enhanced Recovery After Surgery (ERAS) pathway for hip and knee arthroplasty was introduced in an Italian high-volume research hospital in March 2018. Methods The aim of this mixed methods observational study is to perform a health technology assessment (HTA) of the ERAS pathway, considering 938 procedures performed after its implementation, by means of a hospital-based approach derived from the EUnetHTA (European Network for Health Technology Assessment) Core Model. The assessment process is based on dimensions of general relevance, safety, efficacy, effectiveness, economic and financial impact, equity, legal aspects, social and ethical impact, and organizational impact. A narrative review of the literature helped to identify general relevance, safety and efficacy factors, and a set of relevant sub-dimensions submitted to the evaluation of the professionals who use the technology through a 7-item Likert Scale. The economic and financial impact of the ERAS pathway on the hospital budget was supported by quantitative data collected from internal or national registries, employing economic modelling strategies to identify the amount of resources required to implement it. Results The relevance of technology under assessment is recognized worldwide. A number of studies show accelerated pathways to dominate conventional approaches on pain reduction, functional recovery, prevention of complications, improvements in tolerability and quality of life, including fragile or vulnerable patients. Qualitative surveys on clinical and functional outcomes confirm most of these benefits. The ERAS pathway is associated with a reduced length of stay in comparison with the Italian hospitalization average for the same procedures, despite the poor spread of the pathway within the country may generate postcode inequalities. The economic analyses show how the resources invested in training activities are largely depreciated by benefits once the technology is permanently introduced, which may generate hospital cost savings of up to 2054,123.44 € per year. Conclusions Galeazzi Hospital’s ERAS pathway for hip and knee arthroplasty results preferable to traditional approaches following most of the HTA dimensions, and offers room for further improvement. The more comparable practices are shared, the before this potential improvement can be identified and addressed.