Conflict of Interest: DGK is a co-founder and receives research support from XRad Therapeutics, which is developing radiosensitizers. DGK is on the scientific advisory board and owns stock in Lumicell, Inc. which is developing intraoperative imaging technology. DGK receives research support from Merck, Bristol-Myers Squibb, and XRad Therapeutics. The remaining authors report no conflict of interest.

To evaluate the clinical feasibility of a new T2 weighted sequence to calculate T2 relaxation times (T2RT) of liver lesions using two-dimensional radial turbo spin echo (2DRTSE) and to evaluate this sequence by performing image quality and relaxation time comparison of multiple liver lesions. Materials and methods: This prospective analysis of 2DRTSE sequences (using 22 echoes) was performed in 19 patients with 36 liver lesions. Two radiologists independently obtained T2RTs for liver lesions and scored image quality and image artifacts. Lesions were classified as cyst, hemangioma, solid, or necrotic. T2RT values were compared. Inter-reader agreement was evaluated. Results: The 2DRTSE images were considered good quality with few artifacts by both radiologists. Nineteen patients were included in the study, with a total of 36 liver lesions. Two of the liver lesions were classified as cysts, 7 as hemangiomas, 4 as necrotic lesions, and 23 as solid lesions. The concordance correlation coefficient was 0.996 for the calculated T2RT of each liver lesion between the two readers, indicating good agreement. There was statically significant difference of the calculated T2RT for each lesion type. Conclusion:The 2DRTSE sequence can be performed and provides good T2W image quality and a quantitative T2RT map of the entire abdomen. The liver lesions can be distinguished based on the calculated T2RT using this technique. 2DRTSE could potentially supplant the current T2-weighted imaging sequence with the benefit of quantitative T2RTs.

Diffuse intrinsic pontine glioma (DIPG) kills more children than any other type of brain tumor. Despite clinical trials testing many chemotherapeutic agents, radiotherapy remains the standard treatment. Here, we utilized Cre/loxP technology to show that deleting Ataxia telangiectasia mutated (Atm) in primary mouse models of DIPG can enhance tumor radiosensitivity. Genetic deletion of Atm improved survival of mice with p53 deficient but not p53 wild-type gliomas following radiotherapy. Similar to patients with DIPG, mice with p53 wild-type tumors had improved survival after radiotherapy independent of Atm deletion. p53 wild-type tumor cell lines induced proapoptotic genes after radiation and repressed the NRF2 target, Nqo1. Tumors lacking p53 and Ink4a/Arf expressed the highest level of Nqo1 and were most resistant to radiation, but deletion of Atm enhanced the radiation response. These results suggest that tumor genotype may determine whether inhibition of ATM during radiotherapy will be an effective clinical approach to treat DIPGs.

The main deterrent to long-term space travel is the risk of Radiation Exposure Induced Death (REID). The National Aeronautics and Space Administration (NASA) has adopted Permissible Exposure Levels (PELs) to limit the probability of REID to 3% for the risk of death due to radiation-induced carcinogenesis. The most significant contributor to current REID estimates for astronauts is the risk of lung cancer. Recently updated lung cancer estimates from Japan's atomic bomb survivors showed that the excess relative risk of lung cancer by age 70 is roughly four-fold higher in females compared to males. However, whether sex differences may impact the risk of lung cancer due to exposure to high charge and energy (HZE) radiation is not well studied. Thus, to evaluate the impact of sex differences on the risk of solid cancer development post-HZE radiation exposure, we irradiated Rbfl/fl; Trp53fl/+ male and female mice infected with Adeno-Cre with various doses of 320 kVp X-rays or 600 MeV/n 56Fe ions and monitored them for any radiation-induced malignancies. We observed that lung adenomas/carcinomas and esthesioneuroblastomas (ENBs) were the most common primary malignancies in X-ray and 56Fe ion-exposed mice, respectively. In addition, 1 Gy 56Fe ion exposure compared to X-rays led to a significantly higher incidence of lung adenomas/carcinomas (p=0.02) and ENBs (p<0.0001). However, we did not find a significantly higher incidence of any solid malignancies in female mice as compared to male mice, regardless of radiation quality. Furthermore, gene expression analysis of ENBs suggested a distinct gene expression pattern with similar hallmark pathways altered, such as MYC targets and MTORC1 signaling, in X-ray and 56Fe ion-induced ENBs. Thus, our data revealed that 56Fe ion exposure significantly accelerated the development of lung adenomas/carcinomas and ENBs compared to X-rays, but the rate of solid malignancies was similar between male and female mice, regardless of radiation quality.

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