I. Minárik

FOCUS on FOCIS: combined chemo-immunotherapy for the treatment of hormone-refractory metastatic prostate cancer.

Immunotherapy has emerged as another treatment modality in cancer. The goal of immunotherapy in advanced cancer patients does not have to be the complete eradication of tumor cells but rather the restoration of a dynamic balance between tumor cells and the immune response. Appropriate combination of tumor mass reduction (by surgery and/or chemotherapy) and neutralization of tumor-induced immunosuppression might set the right conditions for the induction of anti-tumor immune response by active immunotherapy. We review experimental basis and key concepts of combined chemo-immunotherapy and document its principles in the case report of patient with hormone refractory metastatic prostate cancer with sinister prognosis. More than four hundred prostate cancer patients have been treated with DC-based immunotherapy and tumor-specific immune responses have been reported in two-thirds of them. In half of these patients, DC immunotherapy resulted in transient clinical responses. Tregs, among other factors, potently inhibit tumor-specific T cells. Prostate cancer patients have elevated numbers of circulating and tumor infiltrating Tregs and there is evidence that Tregs increase tumor growth in vivo. Because of the high frequency of circulating Tregs in our patients, we first administered metronomic cyclophosphamide. After obtaining IRB approval, we started regular vaccinations with dendritic cells (DCs) loaded with killed prostate cancer cells. In accordance with the principles of combined immunotherapy, we continued palliative chemotherapy with docetaxel to reduce the tumor cell burden. DC-based vaccination induced prostate cancer cell-specific immune response. Combined chemo-immunotherapy consisting of alternate courses of chemotherapy and vaccination with mature DCs pulsed with LNCap prostate cancer cell line led to the marked improvement in the clinical and laboratory presentation and to the decrease of PSA levels by more than 90%.

Regulatory T cells, dendritic cells and neutrophils in patients with renal cell carcinoma

We evaluated dendritic cells (DC), regulatory T lymphocytes (Treg) and neutrophils in 37 patients with newly diagnosed renal cell carcinoma (RCC) in the tumor and peripheral blood (PB) and correlated these parameters with tumor staging (early-T1, 2, late-T3, 4 and metastatic disease). The number of myeloid and plasmacytoid DC in blood of RCC patients was higher than in healthy controls. The percentage of myeloid dendritic cells (mDC) from CD45+ cells in tumors was higher in comparison with peripheral blood irrespective of disease stage. Higher percentage of these cells expressed a maturation marker in the periphery in the early stage (CD83 expressing cells). The number of plasmacytoid dendritic cells (pDC) in PB was similar in both early and late stage groups, but the early group displayed a significantly higher percentage of pDC in tumor cell suspension. Neutrophil counts in the peripheral blood of RCC patients were higher than in healthy controls, but the counts in both tumor stage groups were similar. The proportion of neutrophils from CD45+ cells was higher in late stage tumors. Higher percentage of Treg from CD4+ cells was detected in renal carcinoma tissue in comparison to PB with no difference between stages of the disease. Our results reflect the complex interplay between various cells of the immune system and the tumor microenvironment. Activation of dendritic cell subpopulations at early stages of the disease course is counterbalanced by the early appearance of T regulatory cells both in the periphery and tumor tissue. Later stages are characterized by the accumulation of neutrophils in the tumor. Appropriate timing of anticancer strategies, especially immunotherapy, should take these dynamics of the immune response in RCC patients into account.

Sampling density as a predictor of prostate cancer in repeat prostate biopsy

Background : Currently, it is recommended to take 8-12 cores in the first prostate biopsy, because it has been shown, that this scheme leads to a higher detection rate than in sextant biopsy1. Adjusting the number of cores according to prostate volume and patient’s age was one of the principles of the Vienna nomogram2. Some of current nomograms for the prediction of positive prostate biopsy include also sampling density, which is a variable of number of cores related to prostate volume3. However, the optimal sampling density value has not been defined and little is known about its performance in different patient subgroups, including prostate re-biopsies.

External validation of extended prostate biopsy nomogram

Introduction Historical nomograms for the prediction of cancer on prostate biopsy, developed in the sextant biopsy era are no more accurate today. The aim of this study was an independent external validation of a 10-core biopsy nomogram by Chun et al. (2007). Material and methods A total of 322 patients who presented for their initial biopsy in a tertiary care center and had all the necessary data available were included in the retrospective analysis. To validate the nomogram, receiver operator characteristic (ROC) curves and calibration plots were constructed. Results Area under the ROC curve calculated for our data using the nomogram was 0.773, similar to that reported originally. However, the nomogram systematically overestimated prostate cancer risk, which, for our data, could be resolved by subtracting 24 points from the total number of points of the nomogram. Conclusions The nomogram yielded overall good predictive accuracy as measured by the area under the ROC curve, but it systematically overestimated PC probability in individual patients. However, we showed how the nomogram could easily be adapted to our patient sample, resolving the bias issue.