Radiotherapy 'provides no benefit for secondary brain tumours'

“‘Whole brain radiotherapy’ is of no benefit to people with lung cancer which has spread to the brain,” BBC News reports.

A UK study found radiotherapy did not significantly increase survival times and quality of life when compared with standard care.

Researchers investigated whether giving whole brain radiotherapy (WBRT) to people with advanced lung cancer that had spread to the brain had any different effect on overall survival and quality of life when compared with optimised care without radiotherapy.

The trial demonstrated that the cancer has a poor survival rate – about nine weeks regardless of treatment.

It showed that providing WBRT alongside standard care added only about an extra four to five days of life when adjusted for quality of life.

But this came at the cost of side effects like hair loss and nausea. While not painful, radiotherapy can be time consuming, involving multiple hospital visits.

Put together, all this can seem cruel when life expectancy is already short. These results suggest that this treatment approach needs to be reconsidered.

But these findings don’t apply to all lung cancers – only to non-small cell cancers.

The trial only included people who doctors felt there was no other suitable treatment for. And doctors weren’t sure whether radiotherapy would help, so there may still be people radiotherapy could help.

While it goes against the instincts of both doctors and patients, there may be some circumstances where choosing not to treat a condition is the better option when it comes to quality of life. 

Where did the story come from?

The study was carried out by researchers from the Northern Centre for Cancer Care, Newcastle Hospitals NHS Foundation Trust, University College London, and other institutions in the UK and Australia.

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

The study was published in the peer-reviewed journal The Lancet on an open access basis, so you can read it for free online.

BBC News’ coverage of this research is accurate, and includes a useful comment from Dr Paula Mulvenna, one of the study’s authors, who said: “In our lung cancer clinics, we were not seeing the improvements we had hoped for in our patients.

“Survival times are poor and have hardly changed since the 1980s. What’s more, the technique’s toxicity can be substantial and it can damage cognitive function.”

The reporting may have benefited from stating that this only applies to people with non-small cell lung cancer (the most common type) that has spread, and not small cell lung cancer, which accounts for around 15-20% of cases, and more commonly spreads to the brain than non-small cell lung cancer. Radiotherapy may still be of benefit in these cases.

What kind of research was this?

This randomised controlled trial (RCT) aimed to see whether WBRT affects quality of life and overall survival in people with non-small cell lung cancer that has spread to the brain.

WBRT combined with steroid therapy is commonly used to treat secondary brain tumours (metastases) of lung cancer, but even with treatment overall prognosis remains poor.

If this treatment isn’t having a meaningful effect on the person’s quality of life and survival, its continued use is questionable.

Aside from the issue of cost, the possible side effects and the use of a patient’s time could be detrimental at a point in their life when time is especially precious.  

A randomised controlled trial is the best way of investigating the effects and safety of this treatment.

What did the research involve?

The Quality of Life After Treatment for Brain Metastases (QUARTZ) study recruited 538 people with non-small cell lung cancer that had spread to the brain. The patients were from 69 hospitals in the UK and Australia.

They were randomised to receive either WBRT (20 Gy in five daily fractions) or optimal supporting care alone. Both groups were also treated with dexamethasone steroid therapy.  

The main outcome of interest was the additional years of life gained when adjusted for quality of life (QALYs).

This outcome was assessed by looking at overall survival rates combined with responses on the EQ-5D symptoms and quality of life questionnaires.

Questionnaire responses were collected each week for at least 12 weeks after randomisation, and then monthly.

What were the basic results?

There was no significant difference between groups in terms of overall survival (hazard ratio 1.06, 95% confidence interval [CI] 0.90 to 1.26).

Average survival was 9.2 weeks for those who received WBRT and 8.5 weeks for those who received standard care.

WBRT had a minimal effect on survival when adjusted for quality of life. QALYs gained with treatment were 46.4 days in the WBRT group and 41.7 for the standard care group – a difference of 4.7 days (90 % CI 12.7 to -3.3)

At four weeks there was no significant difference between groups in terms of overall symptoms and serious side effects, which were experienced by about a third of each group.

Non-serious side effects significantly more common in the WBRT group compared with the standard care group were:

• moderate to severe drowsiness – affecting 42% vs 28%
• hair loss – 34% vs 1%
• nausea – 10% vs 2%
• dry or itchy scalp – 7% vs 1%

How did the researchers interpret the results?

The researchers say that although their findings show WBRT didn’t give inferior or poorer outcomes than standard care, “The combination of the small difference in QALYs and the absence of a difference in survival and quality of life between the two groups suggest that WBRT provides little additional clinically significant benefit for this patient group”. 

Conclusion

This valuable trial questions the use of whole brain radiotherapy (WBRT) for people with non-small cell lung cancer that has spread to the brain.

It shows the poor outlook in these people, with average survival time only being about nine weeks regardless of treatment.

Providing WBRT alongside standard care adds only about four to five days to life when adjusted for quality of life.

But the possible side effects of radiotherapy, which include drowsiness, hair loss and nausea, can seem unnecessarily harsh when life expectancy is already short.

The trial had many strengths, however:

• It had a good sample size. Power calculation was made beforehand to ensure the researchers had a sufficient sample size to reliably detect differences in the main outcome of interest.
• It included people of any degree of illness and disability, provided they could respond to questions about symptoms and quality of life.
• Randomisation was stratified to balance for treatment centre, gender, and the severity of the illness. As a result, baseline characteristics were well balanced between groups.
• The analysis included all people randomised to the two treatment groups.

Patients and researchers could not be blinded to treatment allocation, but, as the researchers say, this was necessary for ethical reasons.

It wouldn’t be right to have people with advanced cancer regularly travelling to treatment centres to receive unnecessary sham radiotherapy treatment sessions, which could have further affected their quality of life.

Overall, the results suggest that this treatment approach may need to be reconsidered for people with cancer that has spread to the brain and a poor life expectancy.

However, there are a couple of important points to bear in mind. Doctors had concluded that no other treatment was possible for the people involved in this trial, and both doctors and patients were in two minds about whether WBRT would be any good for them.

This means this group does not represent people with non-small cell lung cancer and brain spread where the healthcare team and patient are sure of – and have decided on – a treatment approach.

Also, these results don’t apply to people with small cell lung cancer, or those with other types of cancer that have spread to the brain. There therefore may still be people brain radiotherapy could benefit – but they weren’t included in this trial.

If you’re uncertain about the potential risks and benefits of a treatment plan for yourself or a friend or relative, you should always feel free to ask.

A cancer nurse specialist, who is normally part of a hospital’s cancer team known as the multidisciplinary team, would probably be the best person to talk to first.  

Links To The Headlines

Brain radiotherapy ‘no benefit’ for lung cancer spread. BBC News, September 5 2016

Links To Science

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. The Lancet. Published online September 4 2016