Approximately 40% of individuals treated for head and neck cancer experience the distressing adverse-effects of dry mouth syndrome. However, researchers in the Netherlands may have found a way to prevent impairing salivary glands during radiotherapy treatment.
The researchers note this finding could enhance the quality of life of 500,000 individuals with head and neck cancer each year worldwide.
The team found that the stem cells needed for regenerating the parotid gland (the largest pair of salivary glands) were primarily located in the major ducts of the gland. According to the researchers, these cells could be easily avoided during radiotherapy or given a minimal radiation dose.
Dr. Peter van Luijk, a research associate at the University Medical Center Groningen, The Netherlands, explained:
“This would significantly reduce complications arising from radiotherapy for head and neck cancer.”
Findings from the study were presented at the 31st conference of the European Society for Radiotherapy and Oncology (ESTRO31).
Dry mouth syndrome is a condition in which there is not enough saliva in the mouth. The condition can occur when the parotid gland stops functioning properly after radiation damage.
Symptoms of dry mouth syndrome include difficulty sleeping, eating, tooth decay or loss, and bad breath. These symptoms lead to poorer quality of life and difficulty working, as well as social isolation.
The majority of treatments to treat the condition and its consequences are insufficient and can cost hundreds or even thousands of Euros per patient each year.
Dr. van Luijk said:
“Parotid gland dysfunction after radiotherapy for head and neck cancer was, and still is, a major clinical problem. During radiotherapy, attempts to minimize the risk of this complication have been aimed at reducing the average dose to the salivary gland, on the assumption that it would not make a difference where in the gland the radiation dose was reduced.
However, this does not seem logical according to the anatomy of the salivary gland and, in previous work, we discovered that reductions in radiotherapy dose to some parts of the gland allowed the parotid gland to regenerate, whereas a dose to other parts did not.
Therefore, we decided to investigate the reason for these regional differences. We hypothesized that our observations could be explained by a non-uniform distribution of stem cells necessary for the long-term maintenance of organ function and affected by irradiation.”
The team first used rodent (mouse & rat) models in order to research the location of stem cells and the effects of radiotherapy to specific regions of the gland. They then examined parotid and salivary gland tissue taken from individuals undergoing a neck dissection for head and neck cancer.
In both the rodent models and human tissue, the team found that the stem cells were mainly located in the major ducts of the parotid gland. Dr. van Luijk explained:
“We have found in previous work that these stem cells are capable of regenerating a parotid gland when they have been transplanted after irradiation.”
After dissecting the parotid gland of the rat and culturing various parts of the gland in Petri dishes, the researchers found that an abundant concentration of stem cells were located in the center of the gland where the major ducts are located.
The team then directed high-precision irradiating to the center of the gland in living rats and discovered that it caused saliva production to decrease significantly, in contrast to the minimal effects seen after irradiating other regions of the gland.
Dr. van Luijk said:
“The position of the stem cells in rats corresponds to the cranio-ventral extension of the gland in humans, where the excretory duct leaves the gland on the ventral, or outward-facing side. So even though the glands have different shapes in rats and humans, the stem cells are in the exact same anatomical structure.”
The team then created a mathematical model based on the treatment of 36 patients in order to test their theory. This model allowed them to estimate the expected parotid gland function depending on the stem cell dose.
Dr. van Luijk explained:
“Excitingly, dose to the cranio-ventral extension of the gland containing the major ducts was most predictive of damage to saliva production. In addition, we found that it was possible to reduce the dose by approximately 50% to this part of the gland, without increasing the average dose to the whole gland or the dose to other critical structures in the head and neck region, and without compromising adequate target coverage.
Using the mathematical model, we estimated that with such dose reduction none of the patients would have developed parotid gland dysfunction. This is, however, a hypothesis that needs to be tested prospectively in a randomized clinical trial by comparing parotid gland function in a group of patients treated with current standard to a group in which, additionally, the dose to the stem cells is minimized using our proposed stem cell sparing technique. This technique should only be implemented in radiotherapy clinics when such a trial proves there is a benefit as predicted by our research.”
Dr. van Luijk continued:
“Our findings can be seen as a proof-of-principle that elucidation of biological mechanisms in complications may lead to the identification of critical sub-structures of organs, possibly leading to new opportunities to reduce harm to normal tissue. Though we only show this for the parotid gland, such approach may apply to other organs as well.”
According to the team it is easy to avoid the gland during radiotherapy.
Dr. van Luijk said:
“The stem cell region is on the side of the gland that is normally furthest away from the target area containing the tumor cells. Since only this area needs a high radiation dose, this distance makes avoiding the stem cell area easier than avoiding other parts of the gland.
Based on our results we hypothesize that sparing the parotid gland stem cell region, costing around €100 in extra man-hours, may effectively prevent salivary gland dysfunction. This will allow patients to more readily lead their normal lives without having to rely upon medical care and welfare.”
He concluded:
“Maybe even more importantly, cancer patients will remain productive members of society, realizing a cost reduction far beyond the cost of medication. Finally, it will improve quality of life of 500,000 patients treated with radiotherapy for head and neck cancer worldwide every year.”
Professor Bradly G. Wouters, Ph.D., a radiobiologist at the Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Canada, and chair of the conference radiobiology track, said:
“This is an exciting clinical study that has identified a critical region of the salivary gland that contains stem cells that can regenerate the gland and preserve function in patients with head and neck cancer.
Using advanced radiation techniques the investigators show it is possible to spare this region and thus deliver higher therapeutic doses without causing more toxicity to patients.”
Written By Grace Rattue