CTRad March 2010

Different types of Radiotherapy

Radiotherapy is an important and cost-effective curative treatment for cancer,1 which is delivered to around 50% of cancer patients and is a key component of treatment for around 40% of those cured.2 In the UK just over 300,000 new cancer cases occur each year,3 and over 90,000 receive RT with curative intent. Radiotherapy has been considered one of the most effective ways of defeating cancer. Radiation will kill a tumour every time if sufficient dose can be delivered to the tumour itself, but Oncologists are limited in the dose they can deliver because of the need to spare healthy surrounding tissue from over-exposure. Giving a small dose each day gives more chance for the normal tissues to recover, while the cancer is not so good at repairing itself. This is why a typical dose of radiotherapy will involve around 30 daily treatments spread over a period of 5 - 6 weeks. Radiotherapy has improved in recent years with several major technological breakthroughs that have increased precision and limited 'collateral damage'. This means clinicians are able to boost doses, killing tumours more effectively, while further sparing surrounding healthy tissues. Today treatment can be tailored for the individual patient and doses can be 'sculpted' to match the shape of the tumour and take account of motion during treatment. External Beam Radiotherapy

With external beam radiotherapy the patient lies in a fixed position on a treatment table. Powerful and precisely paced radiation beams are directed at the tumour using a sophisticated device called a medical linear accelerator (referred to as a linac). The accelerator rotates around the patient, delivering beams from different angles. When these beams converge on the target, their combined effect is very powerful.

The patient's treatment will have been planned using three-dimensional diagnostic images from a CT scanner. Sophisticated software programmes use this image data to calculate the best approach for achieving the doctor's clinical goals of concentrating dose on the tumour with minimal exposure to surrounding healthy organs and tissue. In modern treatments all hardware and software interfaces are entirely automated and integrated.
1

Bentzen SM, Heeren G, Cottier B, Slotman B, Glimelius B, Lievens Y, van den Bogaert W. Towards evidence-based guidelines for radiotherapy infrastructure and staffing needs in Europe: the ESTRO QUARTS project. Radiother Oncol. 2005; 75(3): 355-65. 2 Price, P., Sikora, K., Treatment of Cancer, 5th edn, Arnold Hodder, London (2008). 3 Cancer Research UK CancerStats: Incidence 2008 UK. 2011. http://info.cancerresearchuk.org/prod_consump/groups/cr_common/@nre/@sta/documents/generalcontent/cr_072111.pdf

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Most hospitals accommodate patients in treatment slots of 10 - 20 minutes, depending on the complexity of the treatment.

For many years, clinicians treated a wide margin around the tumour site to ensure the whole tumour received the required dose. The margin meant that the doses had to be kept at a lower level to avoid damaging healthy tissue and critical organs during treatment.

The following details some advanced types of Radiotherapy: 1 Intensity-Modulated Radiation Therapy (IMRT)

IMRT is a process that enables clinicians to precisely shape the radiation beam so that it conforms to the three-dimensional shape of the targeted tumour. This is done by shaping and varying the dose as it is delivered from different angles around the patient and was made possible by the introduction of multi-leaf collimators. These devices sit in the head of the treatment machine and shape the beam to conform to the shape of the tumour. With IMRT, doses are often delivered from multiple angles to limit the dose on entry to the patient while creating a 'hot spot' at the tumour site. Dose can also be varied to deliver higher levels to more metabolically active parts of the tumour. The result is greater protection of surrounding healthy tissue, as well as the ability to deliver higher, more effective doses directly to the tumour. With radiotherapy beams focusing more tightly on the tumour thanks to IMRT, the question of motion has become increasingly important. Tumours move throughout the course of treatment through natural motion inside the body, or through the breathing process. The very tight margins used by IMRT make these movements a very real problem which is addressed by image guided radiotherapy. 2 Image Guided Radiotherapy (IGRT)

Prior to the introduction of IMRT, radiation oncologists had to contend with variations in patient positioning, internal movement and respiratory motion by treating a larger margin of healthy tissue around the tumour. Because they were uncertain of the precise position of the tumour at the time of treatment, they widened the treatment field to ensure the entire tumour was treated. In essence, they used a tennis ball sized beam to treat a golf ball sized tumour. With IGRT they can use a golf ball sized beam.

CTRad March 2010 Image guidance normally involves an imager being attached to the treatment machine, enabling near-diagnostic quality images to be taken immediately before the treatment, while the patient lies in the correct position on the couch. IGRT provides high resolution, threedimensional images to pinpoint tumour sites, adjust patient positioning when necessary, and complete a treatment - all within the standard treatment time slot.

IGRT enables Doctors to locate and target tumours more accurately during treatments. Image-guidance combined with IMRT has also enabled the breakthrough of fast and efficient approaches like volumetric modulated arc therapy treatments (VMAT). 3 Volumetric Modulated Arc Therapy (VMAT)

VMAT treatments improve dose conformity, while significantly shortening treatment times. This approach, introduced in 2008, is up to eight times faster than IMRT.

VMAT treatments deliver a precisely sculpted 3D dose distribution with a single or multiple 360-degree rotations of the medical linear accelerator gantry around the patient. Unlike IMRT where the machine stops at regular points and delivers beams from different angles to create a 'hot spot' on the tumour, VMAT treatments occur in continuous rotations. Sophisticated software ensures the dose is delivered according to the treatment plan. Machines achieve this by modifying three factors during the treatment: the speed at which the machine rotates around the patient; the shape of the treatment beam; and the strength of the dose being delivered at any point.

Radiosurgery

4.1 Stereotactic Whereas radiotherapy treatments take several weeks and up to 30 daily 'fractions' to deliver the full dose, radiosurgery treatments take place in just one to five hospital visits. By using super-skinny and highly powerful beams of radiation in the same way a surgeon would use a knife, radiosurgery techniques have been used to treat tumours and lesions for a number of years. They enable Oncologists to treat not just the primary disease site, but to quickly and efficiently 'zap' lesions that have developed elsewhere in the body.

Originally radiosurgery began by treating targets in the brain; however, they have now extended to targets in the spine and other extra-cranial organs. These treatments require very precise localisation so patients heads are help very still in a special immobilisation 3

CTRad March 2010 device. Recent studies have suggested that this strategy can be more effective at killing or controlling certain types of cancer.

The clinical targets for stereotactic radiosurgery are relatively small and well defined. Highresolution 3D imaging techniques such as MRI, CT and PET scans help identify and clinically define these targets and the critical structures surrounding them. Sometimes a small number of targets are treated simultaneously. As they involve a small number of fractions of radiation (hypofractionation), radiosurgical procedures are generally completed within the same week. This approach is sometimes called Gamma Knife.

4.2 Gamma Knife

Gamma Knife is a very precise and very effective instrument that uses radiation to treat the brain and is often called radiosurgery. Using this method, Doctors are able to focus radiation directly, and very precisely, on the target in the brain without affecting surrounding healthy tissue.

Radiosurgery uses high doses of radiation to kill cancer cells and shrink tumours, delivered precisely to avoid damaging healthy brain tissue. Gamma knife radiosurgery is able to accurately focus many beams of high-intensity gamma radiation to converge on one or more tumours. Each individual beam is relatively low energy, so the radiation has little effect on intervening brain tissue and is concentrated only at the tumour itself.

Through the use of three-dimensional, computer-aided planning and the high degree of immobilization of the patient, the treatment can minimize the amount of radiation to surrounding healthy brain tissue. There are approximately 200 sources of cobalt-60 loaded within the treatment unit. Thousands of radiation beams can be generated from these sources with a level of accuracy of more than 0.5mm, about the thickness of a strand of hair. Individually, each radiation beam is too weak to damage the normal tissues it crosses on the way to the target. But when focused precisely on that target, the beams intersect and the combined radiation is sufficient to treat the targeted area.

Because Gamma Knife radiosurgery is so accurate, the full dose of radiation can be delivered during a single session, compared with multiple visits for linear accelerator treatments, which use lower doses delivered in fractions (fractionated treatment).

CTRad March 2010 The reduction of excess radiation is important to everyone, but particularly to cancer patients who are receiving other radiotherapy treatments. For these patients, treatment of a metastatic brain tumour a cancer that has spread from the original site might have to be delayed by up to six weeks if certain less precise treatments are used.

Proton Therapy

Proton therapy is a type of particle therapy which uses a beam of protons to irradiate diseased tissue, most often in the treatment of cancer. The chief advantage of proton therapy is the ability to more precisely localize the radiation dosage when compared with other types of external beam radiotherapy. The development of proton therapy began in the 1950s at accelerator laboratories, and in the last 20 years has expanded to hospital based facilities built specifically to perform this type of treatment. Because protons are particles, they slow down and stop within the target tissue. This delivers a large amount of radiation energy to a very precise point which gives proton therapy the advantage over X-ray beams for some circumstances.

The types of treatments for which protons are used can be separated into 2 broad categories. The first are those for disease sites that favour the delivery of higher doses of radiation, i.e. dose escalation. In some instances dose escalation has been shown to achieve a higher probability of 'cure' (i.e. local control), rather than conventional radiotherapy. These include (but are not limited to) uveal melanoma (ocular [eye] tumours), skull base and paraspinal tumours and unresectable sarcomas. In all these cases proton therapy can achieve significant improvements in the probability of local control over conventional radiotherapy.

The second broad class are those treatments where the increased precision of proton therapy is used to reduce unwanted side effects, by limiting the dose to normal tissue. In these cases the tumour dose is the same that is used in conventional radiotherapy, and thus there is no expectation of an increased probability of curing the disease. Instead the emphasis is on the reduction of the dose to normal tissue, and thus a reduction of unwanted side effects.

You can find out more about the NHS Specialised Services Proton Overseas Programme here: http://www.specialisedservices.nhs.uk/info/proton-beam-therapy

CTRad March 2010 6 Brachytherapy

Brachytherapy also known as internal radiotherapy, sealed source radiotherapy, curietherapy or endocurietherapy, is a form of radiotherapy where a radiation source is placed inside or next to the area requiring treatment. Brachytherapy is commonly used as an effective treatment for cervical, prostate, breast, and skin cancer and can also be used to treat tumours in many other body sites. Brachytherapy can be used alone or in combination with other therapies such as surgery, External Beam Radiotherapy (EBRT) and chemotherapy.

In contrast to EBRT in which high-energy x-rays are directed at the tumour from outside the body, brachytherapy involves the precise placement of radiation sources directly at the site of the cancerous tumour. A key feature of brachytherapy is that the irradiation only affects a very localised area around the radiation sources. Exposure to radiation of healthy tissues further away from the sources is therefore reduced. In addition, if the patient moves or if there is any movement of the tumour within the body during treatment, the radiation sources retain their correct position in relation to the tumour. These characteristics of brachytherapy provide advantages over EBRT - the tumour can be treated with very high doses of localised radiation, whilst reducing the probability of unnecessary damage to surrounding healthy tissues.

A course of brachytherapy can be completed in less time than other radiotherapy techniques. This can help reduce the chance of surviving cancer cells dividing and growing in the intervals between each radiotherapy dose Patients typically have to make fewer visits to the radiotherapy clinic compared with EBRT, and the treatment is often performed on an outpatient basis. This makes treatment accessible and convenient for many patients. These features of brachytherapy reflect that most patients are able to tolerate the brachytherapy procedure very well.

Brachytherapy represents an effective treatment option for many types of cancer. Treatment results have demonstrated that the cancer cure rates of brachytherapy are either comparable to surgery and EBRT, or are improved when used in combination with these techniques. In addition, brachytherapy is associated with a low risk of serious adverse side effects.

Put together by Mrs Linda Taylor and Prof Tim Maughan, March 2010 NCRI Clinical and Translational Radiotherapy Research Working Group (CTRad) 6