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Predicting non-sentinel lymph node status after positive sentinel biopsy in breast cancer: What model performs the best in a Czech population?

Several models have previously been proposed to predict the probability of non-sentinel lymph node (NSLN) metastases after a positive sentinel lymph node (SLN) biopsy in breast cancer. The aim of this study was to assess the accuracy of two previously published nomograms (MSKCC, Stanford) and to develop an alternative model with the best predictive accuracy in a Czech population. In the basic population of 330 SLN-positive patients from the Czech Republic, the accuracy of the MSKCC and the Stanford nomograms was tested by the area under the receiver operating characteristics curve (AUC). A new model (MOU nomogram) was proposed according to the results of multivariate analysis of relevant clinicopathologic variables. The new model was validated in an independent test population from Hungary (383 patients). In the basic population, six of 27 patients with isolated tumor cells (ITC) in the SLN harbored additional NSLN metastases. The AUCs of the MSKCC and Stanford nomograms were 0.68 and 0.66, respectively; for the MOU nomogram it reached 0.76. In the test population, the AUC of the MOU nomogram was similar to that of the basic population (0.74). The presence of only ITC in SLN does not preclude further nodal involvement. Additional variables are beneficial when considering the probability of NSLN metastases. In the basic population, the previously published nomograms (MSKCC and Stanford) showed only limited accuracy. The developed MOU nomogram proved more suitable for the basic population, such as for another independent population from a mid-European country.

Detection and Long-Term In Vivo Monitoring of Individual Tumor-Specific T Cell Clones in Patients with Metastatic Melanoma

We investigated the presence of individual melanoma-specific T cell clones in patients with metastatic melanoma. Ten patients were examined for the presence of melanoma-reactive T cells using dendritic cells loaded with autologous tumor cells. Their specificity was tested using nonradioactive cytotoxicity test. Individual immunodominant T cell clones were identified by the clonotypic assay that combines in vitro cell culture, immunomagnetic sorting of activated IFN-γ+ T cells, TCRβ locus-anchored RT-PCR, and clonotypic quantitative PCR. All patients had detectable melanoma-reactive T cells in vitro. Expanded melanoma-reactive T cells demonstrated specific cytotoxic effect against autologous tumor cells in vitro. Three patients experienced objective responses, and their clinical responses were closely associated with the in vivo expansion and long-term persistence of individual CD8+ T cell clones with frequencies of 10−6 to 10−3 of all circulating CD8+ T cells. Five patients with progressive disease experienced no or temporary presence of circulating melanoma-reactive T cell clones. Thus, circulating immunodominant CD8+ T cell clones closely correlate with clinical outcome in patients with metastatic melanoma.

Interferon-alpha treatment may negatively influence disease progression in melanoma patients by hyperactivation of STAT3 protein

Interferon-alpha (IFN-alpha) is an important drug used in anti-melanoma therapy. However, metastases eventually reappear in almost 60% of melanoma patients, who have received adjuvant cytokine therapy suggesting that IFN-alpha can paradoxically promote disease progression in some cases, at least. In this study, we have investigated the possibility that a growth-promoting STAT3 protein might be activated by interferon-alpha in melanoma cells. We examined 24 primary cultures established from node metastases of melanoma patients who were monitored in a 5-year clinical follow-up. The patients differed in the course of disease and survival end-points. Using Western blot analyses, we show that interferon-alpha stimulated STAT3 phosphorylation at tyrosine (Y705) residue in 17% of cases. These over-reactive cell populations originated from patients who had the shortest disease-free intervals. A significant correlation was obtained between the length of survival end-points and a lack of STAT3 activation by IFN-alpha. No STAT3 induction was observed in normal melanocytes. The STAT1 activation at tyrosine (Y701) occurred at a similar frequency as that of STAT3 (17%) albeit in different patients, no clear correlation with the clinical status could be made. The interferon-alpha/beta receptors (IRFARs) were expressed irrespective to the signal transducers and activators of transcription (STATs) inducibility suggesting that signalling defects occur downstream from IRFAR. We propose that in some cases the application of IFN-alpha could increase the probability of disease progression via overactive STAT3. The tests for STAT3 inducibility prior to cytokine immunotherapy in the clinic are therefore warranted.

Lymphoedema Following Regional Lymph Node Surgery for Breast Cancer

BACKGROUND The treatment of breast cancer is based on the multimodal principle and surgery of regional lymph nodes is an inseparable part of this. Indication criteria are changing constantly folowing advances in other modalities. It is necessary to consider not only the diagnostic or therapeutic benefit but also to take into account adverse effects. Previous studies have demonstrated that axillary dissection (ALND) is burdened by a high frequency of chronic lymphoedema of the arm or chest wall; however, a considerable percentage of patients may also suffer from lymphoedema after sentinel lymph node biopsy (SLNB). AIM This paper focuses on the pathophysiology of lymphoedema, its potential predictive factors, and its complications. Furthermore, it presents an overview of published studies comparing the incidences of lymphoedema after current axillary surgery for breast cancer together with current trends designed to radically reduce the number of these operations. It also briefly refers to the possibilities of implementing preventive or therapeutic operations for lymphoedema. CONCLUSIONS Both ALND and SLNB are burdened by a clinically significant risk of lymphoedema. This risk is more serious after ALND. In the medium term, approximately 7-59% of operated patients suffer from lymphoedema. The incidence of lymphoedema after SLNB, considered a very gentle method, is also not negligible (0-14%). As the number of patients surviving breast cancer treatment continues to increase, monitoring the undesirable effects of axillary surgery over the long term will become more important. The results of published studies support research into treatment methods that have the potential to reduce the radicality of axillary surgery while preserving or improving total medical effectiveness.Key words: breast neoplasms - sentinel lymph node biopsy - axillary dissection - adverse effects - breast cancer lymphedemaThis work was supported by the grants MEYS - NPS I - LO1413 and MH CZ - DRO (MMCI, 00209- 805).The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 7. 11. 2016Accepted: 5. 12. 2016.