In our previous research we developed highly conformal radiation treatment for head/neck and brain tumors usingsculpted dose distributions and demonstrated the ability to escalate tumor dose with minimal complications(brain), and maintain high control rates while decreasing a major complication (xerostomia) for head/neck cancers.Our long-term goal is to increase tumor control and reduce complication rates by individualizing the timing andintensity of therapy based on innovative imaging. We propose to intensify treatment for glioblastoma by escalatingthe daily fraction doses while also utilizing effective chemotherapy (temozolomide). We will test the hypothesisthat diffusion MRI (dMRI), which may predict tumor response early after therapy is started, will be a useful basisfor re-optimization during the course of treatment, allowing the escalation of dose to non-responding parts of thetumor. We will also make use of our preliminary MRI results which suggest that radiation can open the bloodtumor-barrier (BTB) to chemotherapeutic and radiosensitizing agents (like gemitabine). We will test whetherconcurrent conformal radiation and gemcitabine (administered after the BTB is opened) will be safer and improveresponse rates for grade 3 gliomas, and whether we can improve the outcome by escalating the doses to the parts ofthe tumor demonstrating lack of increased permeability of the BTB early after the start of therapy. In head andneck cancer, we will test strategies that promise to decrease treatment-related late dysphagia and aspiration. Wewill test if reducing dose to the swallowing structures can reduce the severity of late dysphagia, and test the utility ofinnovative imaging (FLT-PET, and dMRI) to predict (early after the start of therapy) which tumors are likely to failtreatment, as well as directing individualized dose intensification using re-optimization plans. We expect thatthe Project will show improving non-complicated tumor control rates in brain and head and neck cancer bycustomizing treatment intensity following analysis of possible early predictors of response.
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