A comparative study of machine learning methods for time-to-event survival data for radiomics risk modelling

Radiomics applies machine learning algorithms to quantitative imaging data to characterise the tumour phenotype and predict clinical outcome. For the development of radiomics risk models, a variety of different algorithms is available and it is not clear which one gives optimal results. Therefore, we assessed the performance of 11 machine learning algorithms combined with 12 feature selection methods by the concordance index (C-Index), to predict loco- regional tumour control (LRC) and overall survival for patients with head and neck squamous cell carcinoma. The considered algorithms are able to deal with continuous time-to-event survival data. Feature selection and model building were performed on a multicentre cohort (213 patients) and validated using an independent cohort (80 patients). We found several combinations of machine learning algorithms and feature selection methods which achieve similar results, e.g., MSR-RF: C-Index = 0.71 and BT-COX: C-Index = 0.70 in combination with Spearman feature selection. Using the best performing models, patients were stratified into groups of low and high risk of recurrence. Significant differences in LRC were obtained between both groups on the validation cohort. Based on the presented analysis, we identified a subset of algorithms which should be considered in future radiomics studies to develop stable and clinically relevant predictive models for time-to-event endpoints

Fludarabine modulates composition and function of the T cell pool in patients with chronic lymphocytic leukaemia

The combination of cytotoxic treatment with strategies for immune activation represents an attractive strategy for tumour therapy. Following reduction of high tumour burden by effective cytotoxic agents, two major immune-stimulating approaches are being pursued. First, innate immunity can be activated by monoclonal antibodies triggering antibody-dependent cellular cytotoxicity. Second, tumour-specific T cell responses can be generated by immunization of patients with peptides derived from tumour antigens and infused in soluble form or loaded onto dendritic cells. The choice of cytotoxic agents for such combinatory regimens is crucial since most substances such as fludarabine are considered immunosuppressive while others such as cyclophosphamide can have immunostimulatory activity. We tested in this study whether fludarabine and/or cyclophosphamide, which represent a very effective treatment regimen for chronic lymphocytic leukaemia, would interfere with a therapeutic strategy of T cell activation. Analysis of peripheral blood samples from patients prior and during fludarabine/cyclophosphamide therapy revealed rapid and sustained reduction of tumour cells but also of CD4+ and CD8+ T cells. This correlated with a significant cytotoxic activity of fludarabine/cyclophosphamide on T cells in vitro. Unexpectedly, T cells surviving fludarabine/cyclophosphamide treatment in vitro had a more mature phenotype, while fludarabine-treated T cells were significantly more responsive to mitogenic stimulation than their untreated counterparts and showed a shift towards TH1 cytokine secretion. In conclusion, fludarabine/cyclophosphamide therapy though inducing significant and relevant T cell depletion seems to generate a micromilieu suitable for subsequent T cell activation

Definition and validation of a radiomics signature for loco-regional tumour control in patients with locally advanced head and neck squamous cell carcinoma

Purpose: To develop and validate a CT-based radiomics signature for the prognosis of loco-regional tumour control (LRC) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated by primary radiochemotherapy (RCTx) based on retrospective data from 6 partner sites of the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG). Material and methods: Pre-treatment CT images of 318 patients with locally advanced HNSCC were col-lected. Four-hundred forty-six features were extracted from each primary tumour volume and then fil-tered through stability analysis and clustering. First, a baseline signature was developed from demographic and tumour-associated clinical parameters. This signature was then supplemented by CT imaging features. A final signature was derived using repeated 3-fold cross-validation on the discovery cohort. Performance in external validation was assessed by the concordance index (C-Index). Furthermore, calibration and patient stratification in groups with low and high risk for loco-regional recurrence were analysed. Results: For the clinical baseline signature, only the primary tumour volume was selected. The final sig-nature combined the tumour volume with two independent radiomics features. It achieved moderatel

Expression levels of CD38 in T cells predict course of disease in male patients with B-chronic lymphocytic leukemia

CD38 expression of tumor cells has been identified as an important prognostic factor in B-cell chronic lymphocytic leukemia (B-CLL). Although CD38 is involved in effector functions of T cells, the prognostic value of CD38+ T cells has not yet been addressed in B-CLL. In the present study, CD38-expression levels in B-CLL cells and T cells from 204 patients were analyzed by flow cytometry and correlated with clinical and molecular risk parameters. CD38 expression significantly differed in the neoplastic clone from patients with low versus advanced stage, irrespective of the sex of patients. In contrast, CD38 expression was generally higher in T cells from female compared with male patients but only increased in male patients in a stage-dependent manner. In male patients, combined analysis of CD38 in T cells and B-CLL cells identified 4 subgroups with significantly different treatment-free survival. Multivariate analysis including Rai stage and molecular risk parameters of the neoplastic clone identified CD38-expression levels in T cells as an independent prognostic factor in male patients. Combined analysis of CD38 in B-CLL and T cells is superior in predicting outcome of male B-CLL patients than either parameter alone. Further studies are needed to elucidate the underlying mechanisms of the sex-specific role of CD38+ T cells in B-CLL