Impact of radiation dose and tumor hemodynamic variation on head and neck cancer response (Radiation Medicine and Markey Cancer Center Collaborative Bench to Bedside pilot) (RPA Pilot / Seed Project)

It is well known that the efficacy of radiation therapy is dependent on both the dosimetry and tumor oxygenation level. As head and neck cancers usually have low oxygenation levels such as hypoxia compared to normal tissues, the efficacy of radiation therapy is far below the expectation. While the necessity of overcoming hypoxia is well recognized, tumor oxygenation level is not considered in current clinical practice. Due partially to the difficulty of continuous monitoring of tumor oxygenation levels in patients, precise correlations between tumor oxygenation levels and optimal doses have not been established for clinical dosimetry. Over the past decade, Yu (Co-I in this application)’s group developed and applied noninvasive near-infrared spectroscopic technologies to continually monitor tumor hemodynamic changes during fractionated chemo-radiation therapy. The clinical study found that measured hemodynamic parameters exhibited high accuracy for early prediction of clinical outcomes in patients with head and neck cancer treated with a fixed prescribed dose. Given that different doses are used in radiation therapy depending on clinical applications, we propose in this preclinical study to investigate the effects of radiation doses and tumor hemodynamic variations on head and neck tumor responses in a mouse model. We hypothesize that tumors with different hemodynamic levels have different levels of sensitivity to radiation therapy with different doses, thus impacting treatment outcomes. To test the hypothesis, we will use an innovative, noncontact, portable, multi-wavelength speckle contrast diffuse correlation tomography (MW-scDCT) system, newly developed by Yu’s group, for continuously imaging tumor hemodynamic changes in mice with head and neck cancer xenografts treated with different radiation doses. Based on statistical power analyses, 40 immunodeficient Nod/Scid/Gamma (NSG) mice implanted with tumor cells will be divided into 3 treatment groups (n=10 in each group) and one control group (n=10) without radiation treatment. The three treatment groups will receive image-guided radiation therapy with three different doses (5×2Gy, 5×4Gy, and 5×8Gy) respectively using a new small animal radiation research platform (SARRP). Tumor response results in this pilot study would provide preliminary data for external grant applications to investigate hemodynamic adaptive radiation therapy (HART), which would adjust doses in response to hemodynamic changes to maximize the treatment efficacy. We have organized an outstanding interdisciplinary team including two clinical radiation medical physicists (Luo and Cheek), a biomedical imaging expert (Yu), a cancer biologist (Rangnekar), and a biostatistician (Huang). Our multidisciplinary expertise and unique resources (MW-scDCT, tumor-bearing NSG mice, SARRP) are ideal for not only conducting this pilot preclinical study but also translating the results in the future to the clinic.