A doctoral thesis at the University of Oslo Faculty of Dentistry points to the possibility of reconsidering standard treatment routines, aiming to improve the quality of life for people who survive head and neck cancer. Author of the thesis, Dr Lisa Printzell works as a specialist in oral prosthetics at the ear, nose, and throat department at Rikshospitalet. Recently, she completed a doctorate at the University of Oslo, where she investigated an alternative rehabilitation pathway for head and neck cancer patients.
According to the news shared by the faculty, global head and neck cancer accounts for 5% of all cancer types, with a mortality rate of 50%. However, in the Nordic countries, head and neck cancer accounts for only 2.6% of all cancers, with a mortality rate of just 30%.
But more survivors mean that many must live with extensive damage and side effects after cancer and cancer treatment. “It is the exposed and vulnerable location that makes head and neck cancer one of the most mutilating types of cancer,” said Dr Printzell.
Dr Printzell explained that before patients can receive radiation therapy for head and neck cancer, a number of teeth often need to be removed to prevent infections.
“For most patients, this news comes as a great shock. Some find the news of having to pull teeth almost as brutal as the diagnosis of serious cancer. Damage from surgery and radiation therapy can make it difficult for patients to chew, swallow, and speak afterward,” said Dr Printzell.
In some cases, the appearance of patients changes significantly, which they may find incompatible with a normal or dignified life, where rehabilitation after head and neck cancer is challenging. Patients often have thin, dry, and very fragile oral mucosa after radiation therapy, making it difficult to use ordinary dental prostheses that rest on toothless jaws.
“Anatomical changes after cancer surgery can create significant functional and aesthetic challenges. However, the side effects of radiation therapy are perhaps what make oral rehabilitation most demanding. To achieve satisfactory oral rehabilitation in these patients, dental implants are often used to support and attach prostheses or other dental replacements,” Dr Printzell explained.
These so-called osseointegrated implants then serve as an attachment for various types of dental replacements. A major challenge in this context is that irradiated tissue has a reduced ability to heal, leading to reduced and uncertain integration, osseointegration, of dental implants.
“The survival of dental implants placed in irradiated jawbones is significantly lower than those placed in non-irradiated patients,” Dr Printzell added.
She noted that any surgical procedure in previously irradiated jawbone carries an increased risk of infection. Besides the lack of healing ability, it can, in the worst case, result in osteoradionecrosis, where the jawbone dies as a result of the radiation treatment.
Due to the risks involved, rehabilitation with dental implants for these patients is not considered until at least one year after the completion of radiation therapy. Patients experience this as a long waiting period with significantly reduced quality of life, according to the faculty.
Dr Printzell highlighted that research on alternative methods is needed which can provide a faster oral rehabilitation for the group of these patients who need it the most. One possibility for this is to install the implants before radiation therapy starts, in connection with cancer surgery or tooth extraction.
Dr Printzell explained that so-called primary installation of implants is not unknown. Studies have shown an increased use of this approach in the past decade, always justified by the increased quality of life for patients. However, despite the undeniable benefits of faster oral rehabilitation, clinicians remain somewhat hesitant and skeptical of this approach, according to the faculty.
One reason for this is the concern about the “backscatter effect,” which occurs when radiation hits the implants.
“When ionising radiation is directed at a cancerous tumour and there is a titanium implant in the radiation field, not all the radiation will penetrate the metal. Instead, it will reflect back to the surrounding tissue,” Dr Printzell explained. Healthy cells on the implant’s surface will then receive a higher radiation dose and may suffer more damage than they would if there were no implant present.
“There is a concern that this will negatively affect the ongoing osseointegration of the implant, and thereby also the survival of the implant,” said Dr Printzell.
She noted that very little is known about how harmful this backscatter effect really is. Therefore, she and her colleagues wanted to investigate this further. They assessed the effect of backscatter radiation from titanium on two of the most important cell types for bone healing and osseointegration of dental implants. These cell types are called human mesenchymal stem cells and osteoblasts.
Human mesenchymal stem cells have the potential to develop into many different cell types, including osteoblasts, which are the precursors to mature bone cells.
“In our experiments, these cells were seeded on two different titanium surfaces, as well as a plastic surface. The cells were then exposed to various doses of ionizing gamma radiation, relevant to what is used in cancer treatment. The titanium surfaces generated backscatter radiation to the cells, while the plastic surface represented ‘jawbone without an implant present’,” said Dr Printzell.
In cancer treatment, radiation doses are measured in gray (Gy), the international unit for measuring absorbed radiation dose. Patients typically receive radiation therapy in small doses, often 2Gy, five days a week until the total dose, 50-70Gy, is achieved after 5-7 weeks.
The purpose of administering many small doses over time is to give healthy cells in the radiation field time to repair minor DNA damage between doses.
“We found that backscatter radiation from titanium generated as much as a 40% increased radiation dose to the cells closest to the titanium surface. However, the lowest doses 2-6Gy caused minimal effect on the cells,” said Dr Printzell.
Higher radiation dose, 10Gy, significantly reduced the number of osteoblasts, bone-producing cells, on titanium surfaces compared to plastic surfaces but increased the surviving cells’ ability to develop into mature bone cells.
“We also found that the highest dose of 10Gy inhibited both cell types’ ability to move from one place to another on titanium, while lower doses, 2-6Gy, neither caused significant DNA damage nor affected the cells’ ability to move. The results indicate that backscatter radiation from titanium at doses of 2Gy does not cause greater cell damage than the same dose does without an implant present,” Dr Printzell said.
According to Dr Printzell, more research is needed to establish this treatment as the first choice for this patient group. “Nevertheless, we can conclude that our findings are important for the question of whether backscatter radiation from titanium implants should be a reason to avoid the so-called primary installation of implants in patients who are to undergo radiation therapy.”
Printzell explained that when the study started, an increased risk of placing implants in previously irradiated jawbone was known. The unknown was whether it involves greater, lower, or the same risk to insert implants in these patients just before they undergo radiation therapy.
“What we did know, and still know today, is that implant-supported dental replacements significantly increase the quality of life for head and neck cancer patients, and the earlier the patient can be rehabilitated in this way, the shorter the road back to a somewhat normal life,” Dr Printzell concluded.
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