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Assessment of spatially inhomogeneous intra-organ radiation dose response in salivary glands Clark, Haley


Cancers treated with radiotherapy must be adequately irradiated to suppress growth at the site of origin. To achieve doses high enough to attain ‘local control’ and inhibit growth of metastases, surrounding normal tissues are selectively co-irradiated. Current clinical practice for head-and-neck cancers involves salivary gland irradiation. Threshold doses that minimize adverse induced toxicities are currently based on whole-organ mean dose. Modern radiation delivery techniques are able to sculpt the dose profile to accommodate sub-organ irradiation, but knowledge of the relative importance of sub-organ structures remains unknown. As tissue-sparing techniques improve, assessment of the normal tissue toxicity risk becomes increasingly important. Loss of salivary function and xerostomia (subjective dry mouth) are common normal tissue toxicities in head-and-neck cancer patients. Radiotherapy-induced dysfunction and xerostomia can drastically reduce oral hygiene and health and may negatively impact the ability to eat, speak, sleep, or swallow. These pervasive toxicities detract from overall quality of life and can be permanent, perpetuating the negative impact. The purpose of this work is to quantify the relative importance of spatial regions within the major salivary glands for late salivary function (i.e., ‘regional effects’). The ultimate aim is to improve knowledge of toxicity risk. Broad regional effects have been noted in rat parotid, and it has recently been claimed that a localized ‘critical region’ has been located in human parotid glands. Furthermore, a morphological dependence on the dose profile has been noted for subjective xerostomia. Clinical trials involving lobe and region sparing are underway, yet comprehensive quantification of the importance of sub-organ structures remains unknown. To this end, the association between radiation dose delivered to regions within the largest salivary glands and measurements of whole-mouth salivary flow is quantified. Independent analysis procedures are developed that are capable of quantifying the relative importance of sub-segments. Evidence is found that sub-segments are inhomogeneously important for maintenance of late salivary flow, with the caudal parotid aspects having greatest importance. An imaging protocol is developed which may help pinpoint specific tissues or functional units residing within these regions.

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