Targeting tumours

A new radiotherapy treatment can significantly lower treatment time and reduce the side effects.

Stop for a moment and imagine that you are one of the 285,000 people given the devastating diagnosis of cancer each year in the UK. Your mind will soon turn from the likelihood of a cure to the possible side effects of your treatment, such as hair and weight loss, fatigue, and long treatment times. Now imagine that there is a new form of radiotherapy treatment for some cancers which has the potential to not only reduce those unwanted side effects, but also significantly lower treatment time. With a procedure known as volumetric modulated arc therapy (VMAT), this is a reality. 

Around 40 per cent of cancer patients receive radiotherapy as part of their treatment plan, sometimes in combination with other treatment such as chemotherapy or surgery. It has proved very successful in treating many forms of cancer, but can be inconvenient, time consuming and uncomfortable.

Radiotherapy is used to damage or destroy the cancer cells in the target tissue by changing their genetic makeup and preventing them from growing and dividing. Cancer treatment was revolutionised by the development of the medical linear particle accelerators (linac) in the 1950s, replacing the original gamma ray treatments using cobalt-60. This radioactive isotope of cobalt has a short half-life of 5.27 years, and necessitated frequent source replacement. Linacs enabled accurate and targeted external beam radiation to be used, as opposed to brachytherapy which is delivered internally and not normally suitable for outpatient treatment. 

Megapower

Medical grade linacs can produce megavoltage X-rays by accelerating electrons into a heavy metal target, and then using magnets to focus and bend the beam. The X-rays used in diagnostics have energies of around 100,000eV, whereas those used for treatment are between four million and 25 million eV (an eV - electron volt - is the unit of work required to move one electron through a potential of one volt). These high-energy X-rays are collected and shaped into a beam by a multi-leaf collimator (MLC) incorporated into the radiation head.

The MLC has up to 120 movable leaves, usually made from Tungsten, which are aligned parallel to the radiation field. They move under computer-control to block part of the radiation field, thus shaping the beam to match tumour shape. This is a vast improvement over older technology, which required staff to enter the treatment room and move cumbersome lead alloy blocks to shape the beam, and then reposition the patient sometimes multiple times during a radiotherapy session.

The accelerator is mounted on a gantry structure which can rotate 360° around the patient lying on a movable treatment couch at the centre. It is remarkable that these enormous pieces of engineering, which can weigh up to six tonnes, are able to move and direct the beam into an area only a few millimetres in diameter. To ensure precision operation and patient safety, the movements of the gantry structure and MLC have to operate within strict tolerances, in the case of the MLC to around 1mm throughout delivery. Accuracy of the gantry position is to within 3° at isocentre, the point at which treatment is focused, and normally much less. 

Radiation can be accurately delivered to the tumour by moving either the gantry or treatment couch following a pre-defined plan. Time can be spent positioning and immobilising the patient prior to each treatment, and markers or permanent tattoos can be used to achieve the required level of accuracy. For head or neck cancers, a plastic mask is shaped to the face to enable accurate repositioning of the patient during subsequent treatments.

Due to the high levels of radiation given off by the linac, it is housed in a room with walls made from concrete and lead, and is operated from outside the room during treatment.

Multiple treatments

It is a multi-skilled team who plan and deliver the treatment prescription given by the patient's oncologist. It is up to a radiation physicist and dosimetrist to determine the correct volume and radiation dosage plan, and therefore define the exact time required by the linac to deliver the appropriate daily dose.

Although MeVs are used to measure the strength of the electron beam from the linac, the unit used for therapeutic doses is Gray (Gy). Typical total treatment doses range between 70 and 75 Gy, usually fractionated into multiple smaller treatments of less than 2 Gy.

The radiation therapist delivers the daily treatment, typically five days a week for six to ten weeks depending upon the size, location and type of cancer, and the patients' general health. The small dose fractionated regimen is used to allow healthy cells the time to repair the damage caused by the radiation, although larger doses can be used in certain situations.

One of the main goals of radiation therapy is to target and destroy the cancerous cells, while minimising the damage to surrounding healthy tissue. This is done using a simulation session, where images are taken to accurately define the shape of the tumour, and formulate the treatment plan. It can be difficult to delineate the margins of cancerous and healthy cells using standard diagnostic X-rays.

In early radiotherapy treatment, either doses had to be low to protect surrounding tissues, or a border had to be left, possibly compromising treatment outcome. With the advent of specialist imaging techniques and planning software using MRI, CT or PET scans, doctors can use accurate anatomical 3D scans to ensure that treatment is as targeted as possible. Treatment planning can be very time consuming, sometimes taking several days to view all of the images and define an optimum plan.

Once the use of linacs to deliver radiotherapy treatment became widespread, new delivery techniques began to develop. Three-dimensional conformal radiation therapy (3DCRT) enabled the MLC to target a tumour more precisely within the radiation beam, while controlling the volume of the dose to 'conform' to the shape of the tumour.

With 3DCRT the tumour target was covered, but no consideration was given to protecting the surrounding tissue. The result was that patients began to survive, but frequently suffered with long- and short-term side-effects. 

Next generation

The late 1990s saw development of the next generation of 3DCRT, known as intensity-modulated radiation therapy (IMRT). The aim was to minimise the dose to tissue at risk, but still deliver a tumourcidal dose to the cancerous area.

IMRT used small beams or beamlets of varying intensities and angles to effectively bend around a tumour, even if it was in a previously inaccessible location or wrapped around another structure. Typically, a number of intensity-modulated beams are sent from varying directions into the tumour, minimising radiation at the individual entry and exit points while maximising it where the beams cross. This allows differing doses of radiation to be given to small areas of tissue at the same time, with the beam changing shape hundreds of times. The downside of IMRT was the extended time spent planning and delivery. It was not used by many clinics, and has now been largely replaced.

The number of sessions given using conformal radiotherapy is often less than with conventional radiation treatment, although the sessions can be longer due to the complexity of the treatment.

Research is ongoing into newer treatment protocols including hyperfractionated radiotherapy where more than one treatment is given per day, or hypofractionated radiotherapy giving larger doses per fraction but fewer fractions.

As with all radiotherapy, there are questions on whether the duration or intensity of the radiation dose will increase the long-term susceptibility to subsequent cancers caused by the treatment itself.

Limitations in the success of 3DCRT and IMRT occur in situations where target sites can move between or during treatment, for instance while breathing. Exact tumour location is subject to daily variations, including shrinkage as it responds to treatment.

In the past, oncologists had to compensate for this movement by making the target area slightly larger, thus damaging otherwise healthy tissue. In 2003 this led to the development of dynamic image-guided radiation therapy (IGRT) to ensure that the tumour is in the same position before every session.

With IGRT, real-time CT, fluoroscopic or X-ray images are captured just prior to, or even during treatment, pinpointing the exact location of the tumour. Some tumours can move as much as 4cm during respiration, and the radiotherapy beam from the linac can be 'gated' to ensure that it takes account of breathing or motion, ensuring precise targeting of the cancerous cells.

Major enhancement

The latest exciting enhancement in radiotherapy treatment is called VMAT (volumetric modulated arc therapy) and enables higher quality treatments to be delivered in less time than with other delivery techniques.

Unlike conventional techniques, where the gantry rotates multiple times around the patient or stops several times to change beam angle, VMAT makes it possible to deliver the entire radiation dose in a limited number of revolutions.

Where as IMRT may take 10-20 minutes per treatment to deliver, this new technique can often be completed in less than five minutes, and sometimes just 90 seconds. Not only does this mean that the patient has to spend less time on the table, but it also gives hospital administrators the opportunity to increase the number of patients they can treat and improve workflow.

With VMAT, the sculpted radiotherapy dose is delivered within single or multiple arcs of the linear accelerator gantry. A computer-devised algorithm controls the position and rotation speed of the gantry, the beam shape using the multileaf collimator, and the dose rate.

One of the pioneers of VMAT technology has been Elekta Oncology Systems Ltd (Stockholm, Sweden), an international medical technology group. Their systems and solutions are used in over 4,500 hospitals around the world, particularly in the field of cancer care and the treatment of brain disorders.

The VMAT project team at Elekta collaborated closely with a number of research hospitals and, following CE designation of VMAT in Europe, the Royal Marsden Hospital (Sutton, Surrey, UK) successfully completed the first VMAT treatment in the world using a commercially produced product on 28 January this year. With FDA 510(K) approval granted in the USA in the middle of June, Seattle's Swedish Cancer Institute became the first to perform an Elekta VMAT treatment on 30 July, 2008.

VMAT is standard on Elekta's next generation of fully-digital linear accelerators, or can be purchased as a firmware and software upgrade to their existing systems.

At their site in Crawley, Sussex, UK, Elekta manufacture over 150 linear accelerators a year, and expect there to be strong demand for the new VMAT technology. One of their products, Elekta Synergy, is the first system of its kind to combine scanning using ultra low-dose high resolution X-ray volume imaging (XVI) and treatment delivery into one system.

With daily pre-treatment imaging scans, the system is able to increase accuracy and thus reduce the amount of adjacent healthy tissue affected by the radiation. This dose-sparing allows oncologists to either reduce the likelihood of unwanted side-effects using the previously prescribed doses, or increase the radiation dose used and potentially improve patient outcome. The reduced treatment times also increase patient comfort, and increase likelihood of accurate dose delivery.

Treatment of choice

Jim Warrington, head of Radiotherapy Physics at the Royal Marsden Hospital, where the first VMAT treatment was given to a lung cancer patient who found lying down difficult, reported: "The patient received a single 340° arc of six megavoltage X-rays, with simultaneously variable dose rate and dynamic multileaf collimator modulation.

"The treatment arc delivered a 2 Gy fraction to the target in 93 seconds, approximately half the time it would have taken normally."

VMAT has the potential to become the treatment of choice for many thousands of radiotherapy patients each year. One of the main advantages of Elektas' VMAT offering, as opposed to that of its key competitors, is its flexibility and lack of constraint.

Constraints are built in to all manufacturers systems to control factors such as how far a collimator leaf can move versus the gantry, or how close the individual leaves can come to each other. Reducing these constraints can improve treatment plan quality and reduce delivery time. 

"The efficiency and flexibility of this technique is impressive," adds Warrington, "and we hope to be able to expand the use of this cutting-edge technology to become a routine treatment method in the future."  

Elekta's complete solutionfor VMAT treatments also includes MOSAIQ, an image-enabled electronic medical records (EMR) software suite for efficient management of clinical and patient data, and the Ergo++ treatment planning system.

Significant gains have been made in treatment planning using software algorithms to control gantry position and speed, MLC beam shape, collimator angle and dosage rate throughout delivery while the radiation beam is on.

There is never a good time to receive a devastating cancer diagnosis, but with the latest VMAT treatments from companies such as Elekta, some patients can at least look forward to faster, more effective treatment.

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