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Radiobiology and the Impact to Proton Therapy

By Professor Ricky Sharma, MA, FRCP, FRCR, PhD
Chair of Radiation Oncology, University College London

Recent advancements in radiobiology research have revealed new opportunities for Proton Therapy. The application of radiobiology should allow us to further improve the therapeutic index for patients with cancer by maximising the effectiveness of proton therapy whilst minimising side effects to normal tissues. In order to achieve this, we need to translate scientific discoveries from the laboratory to clinical trials in patients with cancer and, at the same time, identify clinical needs which we can address in the research laboratory.

The level of precision achievable with proton beams makes it very attractive for conforming to the tumor target, whilst sparing neighbouring healthy tissues and organs. However, we still don’t fully understand the biological effectiveness of protons as they decelerate within the cancer target and deposit their energy to kill the cancer cells. We need to study proton therapy not only in cell lines derived from patients with cancer, but also in 3D models of cancer and in samples grown “live” from patients. These models will allow us to study the microstructure of a cancer, with specific reference to how protons damage DNA and how the cancer cell tries to repair that damage. We are learning how cancer cells vary in their composition throughout a cancer or in a seedling that has separated from the primary cancer and grown elsewhere, and how the body’s immune system might recognise the cancer in order to fight against it. The incredible advances in the science of studying single cells within the cancer, and cancer cells or cancer DNA collected in simple blood tests, and then deciphering the entire gene code from those samples will allow us to achieve this cutting edge research within the next few years.

A promising area of research that overlaps with precision proton therapy is the new forms of MRI scanning that are being developed which can tell us about a composition of a cancer without having to stick needles in to the body to obtain biopsy tissue. These new forms of imaging may help us to define the “biological target volume” for proton therapy, rather than relying only on what we can see on conventional imaging. In the future, we hope to be able to adapt proton therapy during a course of treatment, and the recent innovative developments in MRI should allow us to monitor what is happening in the tumor during a course of proton therapy and adapt the treatment appropriately.

In the clinical treatment of patients with cancer, a particular challenge for proton therapy is organ motion. Advances in imaging and new models for motion management will allow moving cancer targets to be treated even more accurately with proton therapy, allowing it to be used for a wider range of cancer types. As we develop these new solutions, it is really important that all the software interfaces, so that we can ensure that a patient’s treatment is seamless and it incorporates all of the imaging and biological information we have for that patient.

As you can see, this is a very exciting time for proton therapy. Cancer biology and imaging will play a key role in making this highly precise therapy even better!

Research Profile

Professor Ricky Sharma is Chair of Radiation Oncology at University College London and a Scientific Group Leader at the UCL Cancer Institute. He is also an Honorary Consultant in Clinical Oncology at University College London Hospitals and the Royal Free Hospital, where he has a clinical practice in radiotherapy and chemotherapy. He graduated in medicine from the University of Cambridge, United Kingdom. He trained in general internal medicine, medical oncology and radiation oncology and completed a PhD on DNA damage repair. Ricky Sharma is an international authority on the translation of radiobiology from the laboratory to the clinic and on the multi-modality treatment of cancer with precision radiotherapy.