Sara Cassani

Association between single nucleotide polymorphisms in the XRCC1 and RAD51 genes and clinical radiosensitivity in head and neck cancer

PURPOSE Individual variability in radiosensitivity is large in cancer patients. Single nucleotide polymorphisms (SNPs) in genes involved in DNA repair and in protection against reactive oxygen species (ROS) could be responsible for such cases of radiosensitivity. We investigated the association between the occurrence of acute reactions in 101 patients with squamous cell carcinoma of the head and neck (SCCHN) after radiotherapy (RT) and five genetic polymorphisms: XRCC1 c.1196A>G, XRCC3 c.722C>T, RAD51 (c.-3429G>C, c.-3392G>T), and GSTP1 c.313A>G. MATERIALS AND METHODS Genetic polymorphisms were detected by high resolution melting analysis (HRMA). The development of acute reactions (oral mucositis, skin erythema and dysphagia) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for biologically effective dose (BED). RESULTS Development of grade ≥2 mucositis was increased in all patients (chemo-radiotherapy and radiotherapy alone) with XRCC1-399Gln allele (HR=1.72). The likelihood of developing grade ≥2 dysphagia was higher in carriers of RAD51 c.-3429 CC/GC genotypes (HR=4.00). The presence of at least one SNP or the co-presence of both SNPs in XRCC1 p.Gln399Arg /RAD51 c.-3429 G>C status were associated to higher likelihood of occurrence of acute toxicities (HR=2.03). CONCLUSIONS Our findings showed an association between genetic polymorphisms, XRCC1 c.1196A>G and RAD51 c.-3429 G>C, and the development of radiation-induced toxicities in SCCHN patients.

Organs at risk in the brain and their dose-constraints in adults and in children: A radiation oncologist’s guide for delineation in everyday practice

PURPOSE Accurate organs at risk definition is essential for radiation treatment of brain tumors. The aim of this study is to provide a stepwise and simplified contouring guide to delineate the OARs in the brain as it would be done in the everyday practice of planning radiotherapy for brain cancer treatment. METHODS Anatomical descriptions and neuroimaging atlases of the brain were studied. The dosimetric constraints used in literature were reviewed. RESULTS A Computed Tomography and Magnetic Resonance Imaging based detailed atlas was developed jointly by radiation oncologists, a neuroradiologist and a neurosurgeon. For each organ brief anatomical notion, main radiological reference points and useful considerations are provided. Recommended dose-constraints both for adult and pediatric patients were also provided. CONCLUSIONS This report provides guidelines for OARs delineation and their dose-constraints for the treatment planning of patients with brain tumors.

A PPAR-gamma agonist attenuates pulmonary injury induced by irradiation in a murine model.

PURPOSE/OBJECTIVE(S) Due to its anti-inflammatory, antifibrotic and antineoplastic properties, the PPAR-γ agonist rosiglitazone is of interest in the prevention and therapy of radiation-induced pulmonary injury. We evaluated the radioprotective effects of rosiglitazone in a murine model of pulmonary damage to determine whether radioprotection was selective for normal and tumor tissues. METHODS Lungs in C57BL/6J mice were irradiated (19 Gy) with or without rosiglitazone (RGZ, 5mg/kg/day for 16 weeks, oral gavage). Computed tomography (CT) was performed and Hounsfield Units (HU) were determined during the observation period. Histological analysis and evaluation of fibrosis/inflammatory markers by western blot were performed at 16 weeks. A549 tumor-bearing CD1 mice were irradiated (16 Gy) with or without RGZ, and tumor volumes were measured at 35 days. RESULTS Rosiglitazone reduced radiologic and histologic signs of fibrosis, inflammatory infiltrate, alterations to alveolar structures, and HU lung density that was increased due to irradiation. RGZ treatment also significantly decreased Col1, NF-kB and TGF-β expression and increased Bcl-2 protein expression compared to the irradiation group and reduced A549 clonogenic survival and xenograft tumor growth. CONCLUSIONS Rosiglitazone exerted a protective effect on normal tissues in radiation-induced pulmonary injury, while irradiated lung cancer cells were not protected in vivo and in vitro. Thus, rosiglitazone could be proposed as a radioprotective agent in the treatment of lung cancer.

A Case of Focal Haematopoietic Hyperplasia of a Vertebral Body and Review of the Modern Literature

We report on a case of focal haematopoietic hyperplasia occurring in the haematopoietic marrow in a lumbar vertebral body, of a young man. The PET scan performed showed high uptake of the radiotracer in the vertebral body of L3 and a MRI of the lumbar spine confirmed the vertebral lesion. A biopsy of the L3 vertebral body lesion was performed and the histological result was of chronic myeloproliferative disease but the analysis performed consequently excluded the diagnosis of chronic myeloproliferative disorder, according to the WHO criteria. Focal benign hyperplasia is regarded a late reactive process after trauma, as well as the case reported

P13.21ORGANS AT RISK IN THE BRAIN AND THEIR DOSE-CONSTRAINTS IN THE ADULTS AND IN THE CHILDREN: A RADIATION ONCOLOGIST'S GUIDE FOR DELINEATION

The aim of this study is to provide a stepwise contouring guide to delineate the organs at risk in the brain as it would be done in the everyday practice of planning radiotherapy for brain cancer treatment. Acute and late toxicity with risk of visual and hearing deficits, hormonal impairment and neurocognitive alterations, is a critical point in radiation treatment of patients affected by brain tumors. Moreover, accurate delineation of organ at risks is essential for the inverse-planning process of intensity modulated radiation treatment (IMRT). However, anatomic cerebral normal structures are not always easily recognizable either on simulation CT scan and on coregistered MRI scan used for radiotherapy planning. We have developed a detailed anatomy atlas on Computed tomography (CT) imaging and magnetic resonance (MR) imaging of brain. The following regions of interest were defined: optic chiasm, cochlea, pituitary gland, temporal lobe and hippocampus. Some main notions of anatomy of the organs at risk are provided together with some landmarks easily to be found on the imaging scans. Detailed contouring recommendations are provided in order to significantly improve the contour accuracy and concordance. This report also provides for all the above-mentioned organs at risk a systematic review for the recommended dose constraints both for adult and pediatric patients. This guide is a useful tool for improving daily practice and decreasing the differences in organs at risk delineation between radiation oncologists.