Our study suggests significant correlations between both tCEC and rCEC baseline levels and the antitumor efficacy of a bevacizumab-based combination therapy in mCRC patients, thus confirming that these biomarkers could be used in the clinical setting as an early predictor of tumor response.

BackgroundThe overall risk of some cancers is increased in patients receiving regular dialysis treatment due to chronic oxidative stress, a weakened immune system and enhanced genomic damage. These patients could benefit from the same antineoplastic treatment delivered to patients with normal renal function, but a better risk/benefit ratio could be achieved by establishing specific guidelines. Key considerations are which chemotherapeutic agent to use, adjustment of dosages and timing of dialysis in relation to the administration of chemotherapy.MethodsWe have reviewed available data present in the literature, including recommendations and expert opinions on cancer risk and use of chemotherapeutic agents in patients with end-stage renal disease. Experts selected by the boards of the societies provided additional information which helped greatly in clarifying some issues on which clear-cut information was missing or available data were conflicting.ResultsData on the optimal use of chemotherapeutic agents or on credible schemes of polychemotherapy in haemodialysed patients are sparse and mainly derive from case reports or small case series. However, recommendations on dosing and timing of dialysis can be proposed for the most prescribed chemotherapeutic agents.DiscussionThe use of chemotherapeutic agents as single agents, or in combination, can be safely given in patients with end-stage renal disease. Appropriate dosage adjustments should be considered based on drug dialysability and pharmacokinetics. Coordinated care between oncologists, nephrologists and pharmacists is of pivotal importance to optimise drug delivery and timing of dialysis.

Objective: The efficacy of bevacizumab in metastatic colorectal cancer (mCRC) could be related not only to its well-known antiangiogenetic properties but also to a hypothetical effect on the immune system of the host. Methods: We enrolled mCRC patients treated with a bevacizumab-based first-line therapy. Lymphocyte and dendritic cell subsets were evaluated at baseline, 3rd and 6th cycle. The clinical efficacy was estimated as response rate and progression-free survival. Forty healthy subjects were used as reference. Results: Fifty-one patients were enrolled. In comparison with healthy subjects, they showed a decrease of T and B cell compartments. Bevacizumab ameliorated the impairment of lymphocyte subsets, especially for T cells. Responders showed a trend toward an increase of CD3 (p = 0.07) and CD4 (p = 0.05). Among patients with a progression-free survival >1 year, only CD19 (p = 0.033) and CD20 (p = 0.013) showed a significant increase. No baseline impairment and no significant modification of dendritic cells were found. Conclusion: Bevacizumab-based therapy is able to increase B and T cell compartments. The expansion of T lymphocytes could imply an amelioration of dendritic cell-presenting capacity. These effects correlate with a more favourable clinical outcome and could be taken into account in clinical protocols aimed at combining antiangiogenetic-therapy with immunotherapy in mCRC.

Dendritic cells (DCs) are the key antigen-presenting cells controlling the initiation of the T cell- dependent immune response. Currently, two peripheral blood DC subsets have been identified on the basis of their CD11c expression. The CD11c-negative (CD11c–) DCs (expressing high levels of CD123) are designated as lymphoid-derived DCs (DC2), whereas the CD11c+/CD123– cells, do identify the myeloidderived DCs (DC1). A growing number of studies have been conducted in recent years on both the quantitative and functional alterations of DCs and their subsets in different pathological conditions. In the present study we assessed, using two different flow cytometric (FCM) techniques, the normal profile of blood DCs in 50 italian adult healthy subjects (M/F: 25/25, median age 42.5 years, range 20-65). The percentage and the absolute number of DCs and their subsets, were obtained starting from whole blood samples in two ways: 1) by calculating the number of DCs when gated as lineage-negative/ HLA-DR+ and identifing the two subsets as CD11c+ (DC1) and CD123+ (DC2) and 2) by using three specific markers: BDCA.1 (CD11c+ high/CD123+ low, myeloid DCs); BDCA.2 (CD11c-/ CD123+high, lymphoid DCs); BDCA.3 (CD11c+low /CD123–, myeloid DCs). Six parameters, 4-color FCM analysis were perfomed with a BD FACSCanto equipment. The mean values of the percentage and of the absolute number were: 0.5±0.2% and 30±11 cells/?L for DCs; 0.2±0.1% and 15±6 cells/?L for DC1; 0.2±0.1% and 15±7 cells/?L for DC2. The same values were: 0.2±0.1% and 16±7 cells/?L for BDCA.1; 0.2±0.1% and 12±7 cells/?L for BDCA.2; 0.02±0.01% and 2±1 cells/?L for BDCA.3, respectively. Our study confirmes that the two types of FCM analysis are able to identify the DC population. We also provides the first reference values on normal rates and counts of blood DCs in italian adult healthy subjects