Sparing the region of the salivary gland containing stem cells preserves saliva production after radiotherapy for head and neck cancer

Abstract

Each year, 500,000 patients are treated with radiotherapy for head and neck cancer, resulting in relatively high survival rates. However, in 40% of patients, quality of life is severely compromised because of radiation-induced impairment of salivary gland function and consequent xerostomia (dry mouth). New radiation treatment technologies enable sparing of parts of the salivary glands. We have determined the parts of the major salivary gland, the parotid gland, that need to be spared to ensure that the gland continues to produce saliva after irradiation treatment. In mice, rats, and humans, we showed that stem and progenitor cells reside in the region of the parotid gland containing the major ducts. We demonstrated in rats that inclusion of the ducts in the radiation field led to loss of regenerative capacity, resulting in long-term gland dysfunction with reduced saliva production. Then we showed in a cohort of patients with head and neck cancer that the radiation dose to the region of the salivary gland containing the stem/progenitor cells predicted the function of the salivary glands one year after radiotherapy. Finally, we showed that this region of the salivary gland could be spared during radiotherapy, thus reducing the risk of post-radiotherapy xerostomia.

Diffusion-weighted magnetic resonance imaging for evaluation of salivary gland function in head and neck cancer patients treated with intensity-modulated radiotherapy

“…To minimize the uncertainty caused by this distortion, we registered each time series manually to the scans. Finally, earlier publications [3,24] have reported on regional differences in radiosensitivity inside the salivary glands. According to them, it is suggested that acinic cell progenitors are located exclusively within the parotid ducts, particularly the larger ones, and that irradiating these regions to high doses is very likely to cause irreversible xerostomia due to RT-induced stem cell loss and consequential inability of the salivary glands to regenerate.…”

Effects of Radioiodine Treatment on Salivary Gland Function in Patients with Differentiated Thyroid Carcinoma: A Prospective Study

“…These processes can lead to obstruction of the ductal system, causing an inflammatory response in the secretory tissue (sialoadenitis), and glandular degeneration (5). Moreover, salivary gland stem cells, which have been proposed to mainly reside in the excretory ducts (6), may be affected because of the exposure to b-radiation resulting in a reduced regenerative potential (2).…”

Understanding mechanisms yields novel approaches to reduce radiotherapy-related xerostomia

“…First, we would like to thank Dr. Eisbruch for his interest in and balanced discussion of our paper (1). The main finding was that stem cells that were previously identified to be responsible for the regeneration of salivary glands after a radiation insult (2), are predominantly localized in the major ducts of the gland.…”

“…Moreover, we showed that sparing of that region leads to function loss proportional to the irradiated volume, which is consistent to the classically hypothesized parallel organization of the gland. However, if this region is irradiated, this results in global degeneration (1,3). Such response is more representative of an organ with serial organization.…”