In both the rodent models and human tissue, the team found that thestem cells were mainly located in the major ducts of the parotidgland. Dr. van Luijk explained: "We have found in previous work that these stem cells are capableof regenerating a parotid gland when they have been transplantedafter irradiation." After dissecting the parotid gland of the rat and culturing variousparts of the gland in Petri dishes, the researchers found that anabundant concentration of stem cells were located in the center ofthe gland where the major ducts are located. The team then directed high-precision irradiating to the center ofthe gland in living rats and discovered that it caused salivaproduction to decrease significantly, in contrast to the minimaleffects seen after irradiating other regions of the gland. |
Dr. van Luijk said: "The position of the stem cells in rats corresponds to thecranio-ventral extension of the gland in humans, where theexcretory duct leaves the gland on the ventral, or outward-facingside. So even though the glands have different shapes in rats andhumans, the stem cells are in the exact same anatomical structure." The team then created a mathematical model based on the treatmentof 36 patients in order to test their theory. This model allowedthem to estimate the expected parotid gland function depending onthe stem cell dose.
Dr. van Luijk explained: "Excitingly, dose to the cranio-ventral extension of the glandcontaining the major ducts was most predictive of damage to salivaproduction. In addition, we found that it was possible to reducethe dose by approximately 50% to this part of the gland, withoutincreasing the average dose to the whole gland or the dose to othercritical structures in the head and neck region, and withoutcompromising adequate target coverage. Using the mathematical model, we estimated that with such dosereduction none of the patients would have developed parotid glanddysfunction.
This is, however, a hypothesis that needs to be testedprospectively in a randomized clinical trial by comparing parotidgland function in a group of patients treated with current standardto a group in which, additionally, the dose to the stem cells isminimized using our proposed stem cell sparing technique. Thistechnique should only be implemented in radiotherapy clinics whensuch a trial proves there is a benefit as predicted by ourresearch." Dr. van Luijk continued: "Our findings can be seen as a proof-of-principle that elucidationof biological mechanisms in complications may lead to theidentification of critical sub-structures of organs, possiblyleading to new opportunities to reduce harm to normal tissue.Though we only show this for the parotid gland, such approach mayapply to other organs as well." According to the team it is easy to avoid the gland duringradiotherapy. Dr. van Luijk said: "The stem cell region is on the side of the gland that is normallyfurthest away from the target area containing the tumor cells.Since only this area needs a high radiation dose, this distancemakes avoiding the stem cell area easier than avoiding other partsof the gland.
Based on our results we hypothesize that sparing the parotid glandstem cell region, costing around €100 in extra man-hours, mayeffectively prevent salivary gland dysfunction. This will allowpatients to more readily lead their normal lives without having torely upon medical care and welfare." He concluded: "Maybe even more importantly, cancer patients will remainproductive members of society, realizing a cost reduction farbeyond the cost of medication. Finally, it will improve quality oflife of 500,000 patients treated with radiotherapy for head andneck cancer worldwide every year." Professor Bradly G. Wouters, Ph.D., a radiobiologist at the OntarioCancer Institute, Princess Margaret Hospital, Toronto, Canada, andchair of the conference radiobiology track, said:.
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