Researchers refining radiation therapy to counter cancer

One in every three Irish people will develop cancer at some stage during their lifetimes with 30,000 new cases of the illness being diagnosed here, on average, each year. This figure is expected to rise to more than 40,000 cases per annum by 2020.

Radiation therapy is a mainstream treatment method that can significantly prolong life, but damage to healthy tissue is proving problematic.

Such is the conundrum facing Dr Sinéad O'Keeffe, of the University of Limerick (UL), whose work in radiotherapy is being funded by the European Commission's Marie Curie Research Fellowship.

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Dr Sinéad O’Keeffe of the University of Limerick demonstrating simulated light emission from the radiotherapy sensor. Photograph: Sean Curtin

“Research into the area of radiotherapy dosimetry has, to date, focused on external beam radiotherapy, delivered by linear accelerator machines [LINACs],” she says. “Here, the sensor is placed externally on the patient’s skin, in order to monitor the actual dose delivered, in comparison to that planned.

“We are now looking to test a groundbreaking sensor [called a dosimeter] which allows for real-time checks on prescribed versus delivered radiation doses. We are hoping to significantly improve quality assurance standards in clinical applications without extending treatment delivery times.

“Crucially, our device is smaller than current dosimeters, making it suitable for minimally invasive in vivo monitoring in internal applications, such as brachytherapy [a form of radioactive implant], while minimising any possible side effects.”

Optical fibre sensing technology

O’Keeffe’s radiotherapy dosimeter makes use of optical fibre sensing technology and is based on 19th-century principles of radio-luminescence.

An optical fibre is a flexible, transparent cable made of extruded glass or plastic, slightly thicker than a human hair. The UL’s device also uses a specific type of scintillation material (Phosphor), which is highly sensitive to different levels of radiation.

The UL team injects a small amount of this phosphor into the tip of an optical fibre so that various quantities of photons (particles of light) are given off in direct response to the radiation received.

“The device counts the number of photons transferred over a given timeframe. As the number of photons relates directly to the radiation present, specialised software can accurately calculate the dosage being received in real time,” she says.

One of the clinical complications arising from radiation treatment to the pelvic region results from high doses delivered to parts of the rectum and bladder, which are in close proximity to the tumour.

The UL sensor is designed to be placed either directly into, or in close proximity, to the tumour. Alternatively, in the case of a brachytherapy implant – which involves inserting radioactive “seeds” close to the tumour site – it is located alongside the radioactive seeds.

Peter Woulfe, principal medical physicist at the Galway Clinic, is undertaking a PhD in cooperation with UL, examining the dosimeter's ability to enhance prostate low dose rate (LDR) brachytherapy.

“LDR brachytherapy was developed to treat prostate cancer about 50 years ago. In our studies, LDR brachytherapy has consistently been shown to result in a favourable side-effect profile over the long term [up to a decade after treatment] with regard to avoiding any loss of sexual potency, erectile dysfunction, negative urinary symptoms or bowel toxicity.”

Woulfe adds: “Nevertheless, we are always anxious to improve the quality of our patients’ lives, and so are keen to pursue the role of optical fibre technologies in measuring levels of radiation within the urethra and along the rectal wall.

“Real-time feedback to radiation oncologists performing the LDR brachytherapy procedure is currently unavailable and would be an invaluable advance within our field of research.”

Similar devices, developed by the Optical Fibre Sensors Research Centre at the University of Limerick, use optical fibres as part of medical finger clips, for patients undergoing magnetic resonance imaging (MRI) scans.

Here, metal-based light-emitting diodes (LEDs) and photodiode detectors cannot be employed. As optical fibres are immune to the strong magnetic fields present in MRIs, they are ideal for the remote transmission of optical information to and from the LEDs and photodiodes.

This can be useful for blood oxygen and haemoglobin monitoring and also, in future, radiotherapy applications, that combine MRI with external beam radiotherapy.

“During the course of my research it became clear that radiotherapy technology was advancing at a very fast rate,” says O’Keeffe. “The treatment options and radiotherapy facilities are continually advancing, resulting in improved outcomes for cancer patients.

“Our sensors are developed in collaboration with world-leading hospitals [the Galway Clinic, the Northern Ireland Cancer Centre and the University of California, Los Angeles] to complement this advancing radiotherapy technology.”

Although the sensor is still in the early stages of development, ultimately the team hopes to optimise it to the highest levels of radiation sensitivity. Indeed, the provision of an early warning system to medical professionals detailing the possibility of healthy tissue damage has now become the “Holy Grail” of radiation therapy.

“To be involved in innovative research is hugely satisfying,” says O’Keeffe. “It is incredibly rewarding to work in an area where you can help people.

“The radiotherapy sensor we are developing is aimed at improving outcomes for people undergoing radiation treatment, ensuring that tumours – and not healthy tissue – receive the correct radiation dose.

“The drive to research new things, to be at the forefront of innovation, is a key factor in a person’s desire to pursue a research career.

“Sensor technology, in particular, has a very important role to play in the fight against cancer.”

To read more about this research, see ofsrc.ul.ie and iti.ms/1DcCvKN For women in science: iti.ms/1DcCAOy

What is cancer?

Our genetic blueprint, DNA, is written in a code that requires just four molecular letters. Receiving radiation therapy can trigger spelling mistakes that may disrupt the process of cell division, leading to cancer when cells multiply out of control.

Although DNA abnormalities occur routinely, caused by the sun's UV light and other causes, our bodies have the ability to repair and defend themselves against these spelling mistakes. However, if rogue cells continue to develop, another random DNA change can take place to create a single offshoot capable of bypassing these safeguards. This maverick multiplies to create a colony of related cells that require a regular supply of nutrients.

As these continue to divide, new mistakes in DNA formulation may occur causing the next stage in the process: the emergence of a third variant.

Here, mutated cells release factors that help infiltrate the blood supply and allow them to spread throughout the body. Thus, cancer evolves, rather than grows, with an arsenal of tricks that assist its cells to thrive.