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BackgroundPoly (ADP-ribose) Polymerase (PARP) inhibitors are promising novel radiosensitisers. Pre-clinical models have demonstrated potent and tumour-specific radiosensitisation by PARP inhibitors. Olaparib is a PARP inhibitor with a favourable safety profile in comparison to clinically used radiosensitisers including cisplatin when used as single agent. However, data on safety, tolerability and efficacy of olaparib in combination with radiotherapy are limited.MethodsOlaparib is dose escalated in combination with radical (chemo-)radiotherapy regimens for non-small cell lung cancer (NSCLC), breast cancer and head and neck squamous cell carcinoma (HNSCC) in three parallel single institution phase 1 trials. All trials investigate a combination treatment of olaparib and radiotherapy, the NSCLC trial also investigates a triple combination of olaparib, radiotherapy and concurrent low dose cisplatin. The primary objective is to identify the maximum tolerated dose of olaparib in these combination treatments, defined as the dose closest to but not exceeding a 15% probability of dose limiting toxicity. Each trial has a separate dose limiting toxicity definition, taking into account incidence, duration and severity of expected toxicities without olaparib. Dose escalation is performed using a time-to-event continual reassessment method (TITE-CRM). TITE-CRM enables the incorporation of late onset toxicity until one year after treatment in the dose limiting toxicity definition while maintaining an acceptable trial duration. Olaparib treatment starts two days before radiotherapy and continues during weekends until two days after radiotherapy. Olaparib will also be given two weeks and one week before radiotherapy in the breast cancer trial and HNSCC trial respectively to allow for translational research. Toxicity is scored using common terminology criteria for adverse events (CTCAE) version 4.03. Blood samples, and tumour biopsies in the breast cancer trial, are collected for pharmacokinetic and pharmacodynamic analyses.DiscussionWe designed three parallel phase 1 trials to assess the safety and tolerability of the PARP inhibitor olaparib in combination with radical (chemo-)radiotherapy treatment regimens. PARP inhibitors have the potential to improve outcomes in patients treated with radical (chemo-)radiotherapy, by achieving higher locoregional control rates and/or less treatment associated toxicity.Trial registrationClinicalTrials.govIdentifiers: NCT01562210 (registered March 23, 2012), NCT02227082 (retrospectively registered August 27, 2014), NCT02229656 (registered September 1, 2014).

Contains fulltext : 247703.pdf (Publisher’s version ) (Open Access) Radboud University, 13 april 2022 Promotor : Verheij, M. Co-promotores : Triest, B. van, Vens, C. 153 p.

The rapid growth of Web usage for advertising job positions provides a great opportunity for real-time labour market monitoring. This is the aim of Labour Market Intelligence (LMI), a field that is becoming increasingly relevant to EU Labour Market policies design and evaluation. The analysis of Web job vacancies, indeed, represents a competitive advantage to labour market stakeholders with respect to classical survey-based analyses, as it allows for reducing the time-to-market of the analysis by moving towards a fact-based decision making model. In this paper, we present our approach for automatically classifying million Web job vacancies on a standard taxonomy of occupations. We show how this problem has been expressed in terms of text classification via machine learning. Then, we provide details about the classification pipelines we evaluated and implemented, along with the outcomes of the validation activities. Finally, we discuss how machine learning contributed to the LMI needs of the European Organisation that supported the project.

Contains fulltext : 74587.pdf (Publisher’s version ) (Open Access) RU Radboud Universiteit Nijmegen, 12 november 2009 Promotor : Begg, A.C. Co-promotor : Vens, C. 145 p.

Contains fulltext : 80268.pdf (Publisher’s version ) (Open Access) RU Radboud Universiteit Nijmegen, 09 januari 2009 Promotor : Begg, A.C. Co-promotor : Vens, C. 149 p.