Yazid Belkacemi

Glioblastoma (GBM) is the most prevalent and deadliest form of primary malignant brain tumor in adults. Radiation associated with chemotherapy following maximal feasible surgery is the standard of care. However, it remains an incurable disease with inexorable recurrence after multimodal therapy due to several factors including tumor aggressiveness with high degree of tumor cell infiltration into surrounding brain tissue, high proliferation, molecular heterogeneity and radioresistance. A better understanding of the tumor biology may allow development of new strategies to overcome treatment resistance. Overcoming radioresistance in GBM has been considered as a challenge for decades. In this systematic review we aim to summarize biologic pathways and mechanisms of therapeutic resistance involved in GBM and try to define some potential future therapeutic perspectives. The main mechanisms of radioresistance that we will discuss are hypoxia, the subpopulation of cancer stem cells in GBM, and the epidermal growth factor receptor (EGFR) expression. We will also focus on the potential role of innovative approaches, such as targeted therapy, nanoparticles and non-photon radiotherapy. Keywords: glioblastoma multiforme brain tumors molecular pathways radioresistance nanoparticles proton therapy

Background: Radiation‐induced late fecal incontinence (LFI) is one of the most quality‐of‐life impairing symptoms in prostate cancer. We aimed to assess the impact of radiotherapy (RT) technique and dose‐volume effects on LFI using a robust score.Methods: We identified 409 patients who underwent curative intent using standard fractionated radiation therapy, 190 of them were finally included and analyzed. The severity of LFI was assessed using the Jorge & Wexner score.Results: With a median follow‐up of 55 months (range 15–96) months, LFI crude rate was 11.5%. In the multivariate analyses, image‐guided radiotherapy (IGRT), rectal maximum dose (Dmax) and anal canal minimum dose (Dmin) were significantly associated with LFI risk. The use of IGRT was associated with lower risk of LFI (p = 0.02); higher rectum Dmax (≥ 68.4 Gy; p = 0.02) and anal canal Dmin (≥ 6.4 Gy; p = 0.04) were associated with increased risk.Conclusion: Our results suggest a significant impact of the total dose delivered to the anorectal volumes and the use of IGRT to spare organs at risk during radiation delivery.