Defining the mechanisms underlying Pelvic Radiotherapy Related Insufficiency Fractures

Radiotherapy is a type of cancer treatment using radiation. Every year, over 30,000 patients in the UK get this treatment for cancers in the pelvis, such as prostate, womb, bowel cancer. The good news is more people are surviving cancer because we are finding it early and treating it better.

But there is a problem. Cancer treatments, including radiotherapy, cause long-term health problems, which can be tough on patients and the NHS. Sometimes radiotherapy damages people's bones making them crack or break. This condition is called Radiotherapy-Related Insufficiency Fractures (RRIFs) and usually happens between 3 months and 3-years after radiotherapy. RRIFs can be very painful, make it hard for people to move around and reduce the quality of life.

We are not sure why RRIFs happen. We thought that radiotherapy causes osteoporosis (thinning of the bone) in the pelvis, making them easily breakable. However, I found that even people without bone thinning can get these fractures. Therefore, we need to dig deeper.

To understand why bones break after radiation, we have to study bones that have been treated with radiotherapy. But taking samples from people is risky because their bones are fragile. So, we use mice for our studies.

Mouse bones work a lot like human bones, so they are a good model for our tests. Previous studies have tested radiotherapy on long bones, like the thigh bone. However, the structure of the pelvis is very different, and I believe that radiotherapy may have different effects there. My early research showed this might be true.

For this reason, I will study the impact of radiotherapy on the pelvis of mice in more detail. I will use a special machine that gives radiotherapy to mice in a similar way to that in humans. I will study the mouse bones at different times after treatment to see how they change and what makes them more fragile and prone to breaks. I will also check the effect of chemotherapy in addition to radiotherapy on bone, for the first time.

My project has four main aims: 1. Check how bone structure changes after radiation 2. See how strong bones are after treatment 3. Count the cells that help to build or break down bone 4. Test the blood to measure bone health markers.

This research will help us understand why these bone problems happen, and how to prevent and treat them effectively. As a result, people who get radiotherapy will have better health and quality of life and we will save hospitals time and money.

For this project, I will work with experts in cancer and bone research from the Universities of Manchester and Sheffield. We have all the tools we need, and my supervisors are very experienced and committed to this research. Together, we hope to make a meaningful difference in how we understand and treat the long-term effects of cancer therapy.

In addition to my research, I have developed a specialized training program that is tailored to my needs. This program is designed to help me advance my career and become a leading expert in studying the long-term side effects of cancer treatments on bones and hormones. Right now, there are not many specialists in this field, but the need for them is growing quickly due to the increasing number of these types of problems.