Advances in radiation therapy

Recent advances have resulted in more precise and effective treatments with fewer side effects

Radiation therapy (or radiotherapy) and surgery are the two main treatments available for curing solid tumour malignancies. Radiation therapy uses high-energy ionising radiation to destroy the DNA of cancer cells, and can be used to cure cancers, either alone or in conjunction with surgery or chemotherapy. According to the available evidence, one in two patients with cancer in Australia would benefit from receiving radiation therapy as part of their treatment.1 In cases of incurable disease, radiotherapy relieves distressing symptoms, such as pain, in two of three patients.

Radiation therapy is an effective, safe cancer treatment that is also cost-efficient. Data analysis by Medicare and the federal Department of Health indicate that less than 9 cents of each dollar spent on cancer care in Australia is for radiation therapy.2 In the past decade, major technological advances have transformed the field, allowing patients to be treated with greater precision than ever before.

New modalities

Intensity-modulated radiation therapy (IMRT) is an external-beam radiation treatment that allows the operator to closely conform the radiation dose to the shape of the tumour by modulating the intensity of the radiation beam.3 It is cost-effective because it reduces the side effects of treatment and improves tumour control.4 Fundamental to its safe delivery is its combination with image-guided radiation therapy (IGRT), which involves imaging of the tumour and its surrounding organs during treatment.

IMRT with IGRT has become the standard of care in radiation therapy for a wide spectrum of malignancies, including prostate cancer. Data from randomised trials indicate that IMRT is associated with fewer side effects than older techniques.5 For example, IMRT for head and neck cancer can cure patients without abolishing their salivary production. As techniques are rapidly evolving, with incremental gains in effectiveness, large observational studies provide important evidence for evaluating procedures. One study using data from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute (United States) found that IMRT was associated with a cause-specific survival benefit when compared with non-IMRT techniques for patients with head and neck cancers.6

Stereotactic ablative radiation therapy (SABR), also known as stereotactic body radiation therapy, is the precise image-guided delivery of a high radiation dose in a single or only a few radiation treatments (usually less than eight), while delivering the lowest possible dose to surrounding tissues (Box). Stereotactic radiation therapy has been successfully used for decades to treat intracranial lesions. Advances in software, hardware and real-time imaging now allow extracranial tumours to be treated with ablative doses using standard linear accelerators.

The application scope of SABR is growing, in large part because of its role in the treatment of oligometastases. Patients with oligometastatic disease are those who have a limited burden of metastatic disease (typically five or fewer metastases). There has recently been a shift in the treatment paradigm for these patients, with the recognition that carefully selected individuals may have more favourable prognoses, with 2- to 5-year progression-free survival of about 20% of patients with oligometastatic disease.7 Although a complete cure may be possible in some patients, the aim of SABR in this setting is rather to achieve local control (control of the tumour at the site treated) and to delay progression, thereby postponing the need for further treatment.8

SABR provides a curative treatment for patients with stage I non-small cell lung cancer who are unable to have surgery. The results are comparable with those achieved by surgery, with local control rates of 85%–90%.9 This treatment has very few side effects and provides a non-invasive alternative to surgical resection for patients who might have otherwise declined treatment. The other emerging role for lung SABR is in the treatment of patients with lung oligometastases.

Applications for spine SABR include treatment of oligometastases when longer-term control is required, or where disease progression occurs after previous low-dose radiation therapy. The largest study to date found a local control rate at 2 years of 83.9%.10

Liver SABR is effective in the treatment of hepatocellular carcinoma, particularly of lesions that cannot be resected. Favourable local control over 2 years and overall survival rates of 87% and 63% have been reported.11 This is important because hepatocellular carcinoma is now the second-ranked cause of global cancer mortality.12 Liver SABR is also safe and effective for treating liver metastases in patients with oligometastatic disease.13

Motion management

In many Australian departments, four-dimensional computed tomography (CT) scanners are now used for radiation therapy planning when treating tumours that move with breathing (eg, lung and liver tumours). These special scanners correlate CT images of the tumour with monitoring of the patient’s breathing by a surrogate device (eg, abdominal belt), accurately representing the location of the tumour throughout all phases of the breathing cycle.

There are also newer techniques that ensure radiation therapy is delivered only during a specific phase of the breathing cycle, allowing greater precision and reducing the radiation dose to the patient’s lungs and heart. These techniques include active breathing control, often used in breast cancer radiation therapy, and respiratory gating. More recent treatment devices can track and deliver radiotherapy to tumours, including a robotic system with six degrees of freedom of control.

Recent advances in the treatment of prostate cancer compensate for the motion of the gland that accompanies daily variations in bladder and rectal volume. Small gold seeds are implanted in the rectum as markers that can be seen on x-ray images prior to treatment, ensuring that the radiation beam precisely strikes the target cells in the prostate. Gel spacers may also be used to keep the rectum fixed away from regions receiving high-dose radiation during treatment.

Future developments

Recent discoveries in genomics and biomarkers mean that cancer treatment is becoming increasingly personalised, and the integration of radiation therapy with newer systemic therapies and immunotherapies is being explored. Current focuses of research include personalising radiation therapy and concurrent systemic therapies for recently discovered cancer subtypes (eg, human papilloma virus-related cancers). Where possible, patients from across Australia and New Zealand are offered participation in clinical trials, usually conducted under the auspices of the Trans-Tasman Radiation Oncology Group (TROG).

Another important development on the horizon is the combined use of magnetic resonance imaging (MRI) scanners and linear accelerators. Only one commercial system is currently available internationally, but a research project is underway at Liverpool in New South Wales: the MRI-linac program, a collaboration between seven universities and the Ingham Institute for Applied Medical Research. As a result of this project, MRI-based soft tissue functional imaging that shows both the anatomy and physiology of the tumour during radiation delivery could represent the ultimate breakthrough in real-time IGRT.

Another technology likely to become available locally in the next 5 to 10 years is particle-beam therapy (proton or carbon ion therapy) that delivers highly focused radiation, of particular value in treating paediatric patients.

Access to advanced radiation therapy

Ensuring that patients have access to these advances in radiation therapy is a key priority in Australian cancer planning. While the evidence indicates that, optimally, 48% of patients in Australia should receive radiation therapy,1 its actual use in NSW is as low as 26%.14 It is important that the wider medical community is given the opportunity to understand these advances and the opportunities they offer patients. Many, particularly those with prostate cancer, are never given the option of radiation therapy, although there is evidence that more patients with prostate cancer suffer decisional regret after undergoing surgery than following radiotherapy.15

To improve the awareness of both patients and medical practitioners of the available options, the Royal Australian and New Zealand College of Radiologists has initiated the Targeting Cancer (www.targetingcancer.com.au) resource. The landscape of radiation treatment will continue to evolve in the coming years, and it is the aim of radiation oncologists in Australia and New Zealand, through Targeting Cancer, to ensure that all patients are given equitable access to this highly beneficial treatment.

Box – An example of stereotactic ablative radiation therapy: x-ray beams from multiple angles targeting a lung tumour