Comparison of DCE-CT models for quantitative evaluation of K(trans) in larynx tumors.

Dynamic contrast enhanced CT (DCE-CT) can be used to estimate blood perfusion and vessel permeability in tumors. Tumor induced angiogenesis is generally associated with disorganized microvasculature with increased permeability or leakage. Estimated vascular leakage (K(trans)) values and their reliability greatly depend on the perfusion model used. To identify the preferred model for larynx tumor analysis, several perfusion models frequently used for estimating permeability were compared in this study. DCE-CT scans were acquired for 16 larynx cancer patients. Larynx tumors were delineated based on whole-mount histopathology after laryngectomy. DCE-CT data within these delineated volumes were analyzed using the Patlak and Logan plots, the Extended Tofts Model (ETM), the Adiabatic Approximation to the Tissue Homogeneity model (AATH) and a variant of AATH with fixed transit time (AATHFT). Akaike's Information Criterion (AIC) was used to identify the best fitting model. K(trans) values from all models were compared with this best fitting model. Correlation strength was tested with two-tailed Spearman's rank correlation and further examined using Bland-Altman plots. AATHFT was found to be the best fitting model. The overall median of individual patient medians K(trans) estimates were 14.3, 15.1, 16.1, 2.6 and 22.5 mL/100 g min( - 1) for AATH, AATHFT, ETM, Patlak and Logan, respectively. K(trans) estimates for all models except Patlak were strongly correlated (P < 0.001). Bland-Altman plots show large biases but no significant deviating trend for any model other than Patlak. AATHFT was found to be the preferred model among those tested for estimation of K(trans) in larynx tumors.

Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity.

Dendritic cells (DC) are professional antigen-presenting cells that play a pivotal role in the induction of immunity. Ex vivo-generated, tumour antigen-loaded mature DC are currently exploited as cancer vaccines in clinical studies. However, antigen loading and maturation of DC directly in vivo would greatly facilitate the application of DC-based vaccines. We formerly showed in murine models that radiofrequency-mediated tumour destruction can provide an antigen source for the in vivo induction of anti-tumour immunity, and we explored the role of DC herein. In this paper we evaluate radiofrequency and cryo ablation for their ability to provide an antigen source for DC and compare this with an ex vivo-loaded DC vaccine. The data obtained with model antigens demonstrate that upon tumour destruction by radiofrequency ablation, up to 7% of the total draining lymph node (LN) DC contained antigen, whereas only few DC from the conventional vaccine reached the LN. Interestingly, following cryo ablation the amount of antigen-loaded DC is almost doubled. Analysis of surface markers revealed that both destruction methods were able to induce DC maturation. Finally, we show that in situ tumour ablation can be efficiently combined with immune modulation by anti-CTLA-4 antibodies or regulatory T-cell depletion. These combination treatments protected mice from the outgrowth of tumour challenges, and led to in vivo enhancement of tumour-specific T-cell numbers, which produced more IFN-gamma upon activation. Therefore, in situ tumour destruction in combination with immune modulation creates a unique, 'in situ DC-vaccine' that is readily applicable in the clinic without prior knowledge of tumour antigens.