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NIHR Signal Whole brain radiotherapy provides little benefit for lung cancer that has spread

Published on 10 January 2017

doi: 10.3310/signal-000360

Radiotherapy to the whole brain makes little difference to people with the commonest type of lung cancer that has spread to the brain and cannot be operated on.

This mainly UK-based trial found no difference in overall survival and quality of life among people who had whole brain radiotherapy plus usual supportive care compared with people who received supportive care alone.

This is the largest trial to assess the effect of this treatment in people with non-small cell lung cancer and multiple brain metastases (cancer deposits in the brain). Practice has been changing since early results of the trial were released. The final results reinforce the message that this treatment has little to offer most patients in this situation.

  •   Cancers, Medicines, Nervous system disorders, Respiratory disorders, Acute and general medicine
Whole brain radiotherapy provides little benefit for lung cancer that has spread

Why was this study needed?

Non-small cell is the most common type of lung cancer. In about one third of these people the cancer spreads to the brain. Since the 1960s, standard treatment has included radiotherapy to the whole brain. However, people with brain metastases from lung cancer have poor survival outlook, and there’s been little research to show whether this type of radiotherapy makes an important difference.

This is the first large randomised study comparing whole brain radiotherapy and supportive care to supportive care alone in this patient group. The trial was designed to show whether supportive care alone was at least as good as that combined with whole brain radiotherapy. The researchers were interested in this because if radiotherapy does not improve length or quality of life, patients could be spared having to attend radiotherapy treatments and the associated side effects in their final stages of life.

What did this study do?

The QUARTZ randomised controlled trial included 538 people with lung cancer with brain metastases which could not be treated by surgery or targeted radiotherapy. Recruitment was from 69 UK and three Australian hospitals.

Patients were randomly assigned to supportive care alone or whole brain radiotherapy plus supportive care. Planned radiotherapy involved five treatments over five to eight days. Supportive care included the steroid dexamethasone, plus whatever palliative care treatment the cancer specialists thought necessary.

Quality of life was assessed by weekly telephone questionnaire. Researchers also looked at overall length of survival. They said they would consider supportive care as good as radiotherapy if radiotherapy gave fewer than seven additional days of life, adjusted for the quality of that extended life.

What did it find?

  • People who had radiotherapy had an average 4.7 additional quality-adjusted days of life compared to those who had supportive care alone. This fell short of the margin needed to show a difference and could have been down to chance (46.4 quality-adjusted days with radiotherapy compared with 41.7 with supportive care, 90% confidence interval [CI] -12.7 to 3.3).
  • When the researchers looked at length of life alone, there was also little difference between the two groups. People who had radiotherapy lived on average 9.2 weeks compared to 8.5 weeks for supportive care.
  • People who had radiotherapy were more likely to have episodes of drowsiness, to lose their hair, feel nauseous and have a dry or itchy scalp. There was no difference in the number with serious adverse events, which affected around a third of each group.
  • Younger people (under 60) and those who had better prognostic outlook at study start seemed more likely to benefit from radiotherapy. However, the numbers of patients in these groups were small so this finding should be interpreted with some caution.

What does current guidance say on this issue?

NICE guidance from 2011 states: “Consider palliative whole-brain radiotherapy for patients with symptomatic brain metastases with good performance status (WHO 0 or 1)”. This means people who have symptoms from their brain tumours but who are either fully active, or can carry out all but heavy physical work.

This study does not report on the WHO scale, but it included people with any level of functional impairment as defined by Karnofsky Performance Status (KPS). Over a third had KPS of less than 70, equivalent to being unable to carry out normal activity or any active work. Therefore the study was more inclusive.

What are the implications?

Cancer care is already changing after early reports from this trial. The full results provide confirmation to professionals, commissioners and patients that whole brain radiotherapy offers little benefit. Gain for most people is measured in days, rather than months of life.

The evidence might inform the NICE guidance on treatment of lung cancer. Avoiding radiotherapy if it doesn’t work could be better for patients and save the NHS some costs.

Citation and Funding

Mulvenna P, Nankivell M, Barton R, et al. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial. Lancet. 2016;388(10055):2004-2014.

This study was funded by Cancer Research UK, the Medical Research Council Clinical Trials Unit at University College London and the National Health and Medical Research Council in Australia.

Bibliography

NICE. Lung cancer: diagnosis and management. CG121. London: National Institute for Health and Care Excellence; April 2011.

Tsao MN, Lloyd N, Wong RKS, et al. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev. 2012;(4):CD003869.

Expert commentary

Patients with brain metastases from non-small cell lung cancer have a poor prognosis. Treatment should focus on improving quality of life and survival, and reducing unnecessary interventions. Dexamethasone and whole brain radiotherapy have often been used with previously unknown benefit and harms. If whole brain radiotherapy does not increase survival or quality-of-life and causes drowsiness, hair loss, nausea, and dry/itchy scalp, then for many people this might not be a helpful intervention. For fitter patients, there may be a small survival advantage with whole brain radiotherapy. In this case, a discussion with their oncologist about the benefits and risks is needed.

Dr Jason Boland, Senior Clinical Lecturer and Honorary Consultant in Palliative Medicine, Wolfson Palliative Care Research Centre, Hull York Medical School, University of Hull

Definitions

Quality adjusted life years are calculated to help people standardise the value of time. For example, someone in pain, or with little consciousness of their surroundings, might live longer than someone who was pain-free and alert to the end of their life, but most people would not say that their quality of life was as good. Treatment may increase quality of life due to fewer symptoms, or decrease quality of life due to more side effects or treatment burden. In this study this was combined with differences in length of life to give a quality adjusted day of life.