Cervical cancer is a life threatening disease occurring world-wide, but affecting especially women in developing countries. Standard treatment for cevical cancer varies per FIGO stage and patient related factors. In general patients with non bulky (<4 cm) FIGO stage IB and IIA are treated with a radical hysterectomy and pelvic lymph node dissection. In case of prognostic unfavorable factors surgery is is followed by irradiation or chemoradiation. In patients with cervical cancer FIGO stage >IIA or bulky disease (locally advanced) radiation combined with chemotherapy is standard of care since 1999. The addition of chemotherapy to radiotherapy (with or without surgery) improves overall survival by 12% in patients with cervical cancer FIGO stage !B-IVA disease. This improvement is reached by the combination of two treatment modalities with each their own side effects. Therefore extra attention needs to be paid to short-term and long term side effects. This is of even more relevance as happily the percentage of patients who become long term survivors' increases, which exposes more survivors longer at long-term treatment related morbidity. In addition there is still ample space for further improvement of treatment results for these patients, preferable with fewer side effects. We therefore explored in preclinical models the role of tumor necrosis factor (TNF) related apoptosis inducing ligand (TRAIL) pathway for its capacity to potentiate the effects of standard treatment in cervical cancer. The aim of this thesis is to assess treatment related toxicity in cervical cancer patients and to explore in preclinical studies the potential of targeting the TRAIL pathway to improve antitumor effect of radiotherapy in cervical cancer.
|Qualification||Doctor of Philosophy|
|Publication status||Published - 2009|