EUROPEAN RADIATION RESEARCH 2012

Is late radiation toxicity dependant on genotype? A study of patients with osteoradionecrosis

17 Oct 2012, 16:33

1m

Poster Hall (Vietri sul Mare)

poster preferred Oxidative Stress Poster Session 2

Speaker

Mr Karl Brehwens (Centre for Radiation Protection Research, GMT Department, Stockholm University, Sweden)

Description

Approximately 20% of cancer patients undergoing radiotherapy (RT) experience some kind of adverse reaction and 5% experience severe reaction in healthy tissues. Recent data have highlighted the importance of individual radiosensitivity dependent on genotype, but there is a paucity of studies on late adverse effects, since these endpoints are difficult to determine. In this study, we investigated patients with mandibular osteoradionecrosis (ORN), a late adverse effect following RT in head & neck cancer. ORN is characterized by loss of blood supply leading to hypoxia, hypocellularity and tissue necrosis with severe pain and possible pathological fractures. Treatment for ORN is resection of necrotic tissue, often followed by free tissue transfer of vascularized bone. This procedure is demanding and the risk of recurrence is evident. Since ORN seems to be dependent on individual susceptibility, it is important to study the association with genotype, since ORN not only limits the patient´s quality of life, but also is tremendously costly for the healthcare system. As of today, there is no predictive assay available that could identify highly radiosensitive patients among the normally radiosensitive, which makes RT treatment plans based on individual radiosensitivity impossible. Several theories exist regarding mechanisms behind severe late adverse effects that occur after RT. Chronic inflammation/oxidative stress, dysregulated wound healing and reduced DNA repair capacity have all been proposed as key factors in the development of adverse late effects. However, the influence of genetic variations has never been studied for ORN, which is a well-defined adverse late effect of RT and probably dependent on individual susceptibility. In a study of 74 patients, blood was collected from 37 patients with ORN (RTOG score 4) along with 37 age-, dose- and TNM-matched controls (RTOG score 0) from the Department of Oral and Maxillofacial Surgery at the Karolinska Hospital in Stockholm. Blood was irradiated with 0, 0.005 and 2 Gy γ-rays and the levels of 8-oxo-dG 1 hour post irradiation were measured to assess the capacity to handle radiation-induced oxidative stress. Also, single nucleotide polymorphisms (SNPs) in candidate genes involved in oxidative stress (SOD2, eNOS), inflammation (HIF1A), wound healing (TGFβ1) and DNA repair (ATM, XRCC1, XRCC3) were investigated. The results (not yet available at this time) will be presented.