PROCCA: Early effects of oral x-ray irradiation (pilot)
Damage to normal tissue following radiotherapy of head and neck (H&N) cancers causes severe early and late effects and reduction in quality of life. Side effects include salivary hypofunction, oral mucositis, and skin toxicity. This may lead to unplanned interruptions in treatment, and potentially treatment failure.
Proton therapy (PT) will be available to patients in Norway in 2023. PT reduces the dose to healthy tissues compared with conventional X-ray therapy (RT), and may thus cause fewer side effects. Although PT is already applied to H&N cancer patients abroad, clinical studies are limited. Side effects are well documented for both PT and RT, however, important questions regarding the mechanisms and cellular signaling pathways culminating in this damage remain unanswered. Knowledge of these mechanisms is vital for early detection of patients at risk and the development of strategies for mitigation. Such studies are not possible in human patients, and we therefore require the use of animals.
Nowadays there is no established protocol on how to evaluate the early effects in H&N region in mice as well as there are many ambiguities in the descriptions of the appearance of early effects. Most groups have published the results for radiation-induced early oral effects based on different score schemes without justification or histological support of their conclusions. Based on our preliminary results from an ongoing pilot on late effects (FOTS ID 20889) we observed that many published score schemes do not fully cover all the effects that might be seen after local irradiation in mice. Moreover, we found very mild symptoms in our ongoing pilot, indicating that the applied radiation doses were too low.
Therefore, it is important to conduct a new pilot in order to firmly establish a mouse model of the radiation-induced early oral effects and to investigate the mechanisms of RT-induced damage to normal tissues of the H&N region, as a baseline for later studies on PT.
We apply for a total of 16 C57BL/6 mice. This study will use a fractionated local RT design. Clinical symptoms on skin and in the oral cavity will be monitored and described by use of a high-resolution optic camera. Blood and saliva will be collected for cytokine screening. A subset of animals will be examined by MRI for optimization of imaging protocols. We will evaluate the possible development of acute erythema/edema of lips, inflammation/ulceration of skin/oral mucosa, fur loss on skin in the field of irradiation, anorexia and general malaise.
In this pilot, we will generate a radiation-induced early response model (normal tissue/skin and oral mucosa) in mice. Such a model will help refining the follow-up investigations and potential need for analgesia after irradiation in coming studies. This will prepare for optimized and refined studies in the future, where aims are to study long term effects of radiation on normal tissue damage following conventional RT and PT, and potential drug interventions. Animal welfare will be ensured through close monitoring during and post radiotherapy, with strict compliance with humane endpoints. Analgesia and alternative fodder will be provided to alleviate symptoms and ease feeding/maximize nutrition.
Proton therapy (PT) will be available to patients in Norway in 2023. PT reduces the dose to healthy tissues compared with conventional X-ray therapy (RT), and may thus cause fewer side effects. Although PT is already applied to H&N cancer patients abroad, clinical studies are limited. Side effects are well documented for both PT and RT, however, important questions regarding the mechanisms and cellular signaling pathways culminating in this damage remain unanswered. Knowledge of these mechanisms is vital for early detection of patients at risk and the development of strategies for mitigation. Such studies are not possible in human patients, and we therefore require the use of animals.
Nowadays there is no established protocol on how to evaluate the early effects in H&N region in mice as well as there are many ambiguities in the descriptions of the appearance of early effects. Most groups have published the results for radiation-induced early oral effects based on different score schemes without justification or histological support of their conclusions. Based on our preliminary results from an ongoing pilot on late effects (FOTS ID 20889) we observed that many published score schemes do not fully cover all the effects that might be seen after local irradiation in mice. Moreover, we found very mild symptoms in our ongoing pilot, indicating that the applied radiation doses were too low.
Therefore, it is important to conduct a new pilot in order to firmly establish a mouse model of the radiation-induced early oral effects and to investigate the mechanisms of RT-induced damage to normal tissues of the H&N region, as a baseline for later studies on PT.
We apply for a total of 16 C57BL/6 mice. This study will use a fractionated local RT design. Clinical symptoms on skin and in the oral cavity will be monitored and described by use of a high-resolution optic camera. Blood and saliva will be collected for cytokine screening. A subset of animals will be examined by MRI for optimization of imaging protocols. We will evaluate the possible development of acute erythema/edema of lips, inflammation/ulceration of skin/oral mucosa, fur loss on skin in the field of irradiation, anorexia and general malaise.
In this pilot, we will generate a radiation-induced early response model (normal tissue/skin and oral mucosa) in mice. Such a model will help refining the follow-up investigations and potential need for analgesia after irradiation in coming studies. This will prepare for optimized and refined studies in the future, where aims are to study long term effects of radiation on normal tissue damage following conventional RT and PT, and potential drug interventions. Animal welfare will be ensured through close monitoring during and post radiotherapy, with strict compliance with humane endpoints. Analgesia and alternative fodder will be provided to alleviate symptoms and ease feeding/maximize nutrition.