Whole brain radiation of brain metastases in lung cancer patients does not improve survival and quality of life more than treatment with steroids or other supportive care in most patients, a recent study reveals.
The findings, which surfaced during a clinical trial, will make it possible for patients to be spared the potentially harmful radiation treatment. Whole brain radiotherapy often causes side effects such as nausea and fatigue, and can be neurotoxic.
Researchers conducting the trial say that whole brain radiotherapy should no longer be considered a standard treatment for people with non-small cell lung cancer with brain metastases.
The study, “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,” was published in the journal The Lancet. The trial was designed and coordinated by the U.K. Medical Research Council Clinical Trials Unit at University College London.
Lung cancer patients who develop brain metastases usually have a poor prognosis. Most of these brain tumors are not possible to remove by surgery, and patients have traditionally been treated with supportive care, steroids such as dexamethasone, and whole brain radiation therapy.
The treatment is, however, linked to severe side effects, such as nausea, drowsiness, and fatigue, and radiation can also have toxic effects on the brain, damaging cognitive functions. Despite the widespread use, robust evidence that the procedure benefits patients has been lacking.
“Whole brain radiotherapy was widely adopted into clinical practice based on the assumption it improves tumor control in patients with brain metastases,” first author of the study Paula Mulvenna, consultant clinical oncologist at England’s Newcastle Hospitals NHS Foundation Trust said in a news release.
“But 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,” she added.
Mulvena and her team set up the Quality of Life after Treatment for Brain Metastases (QUARTZ) trial, registered with the ISRCTN registry (ISRCTN13826061). The study enrolled 538 adults with non-small cell lung cancer with brain metastases who were randomly assigned to get either standard care and dexamethasone, or the same treatment but with an addition of whole brain radiation treatment.
Researchers measured the outcome of the two treatment groups in QUALYS, or quality adjusted life years. This is a measure that takes into account both the time a person lives and the quality of life while living, and is a suitable tool to analyze cancer patients with a poor prognosis like those in the study.
The study showed that patients in the two groups lived for an almost equal time after treatment: 64.4 days in the whole brain radiotherapy group versus 59.5 days in the best supportive care alone group.
They also had a similar quality of life, so that the final difference in QUALYS between the groups was just 4.7 days. (People who received radiation had 46.4 days and those in the best supportive care alone group had 41.7 days).
Other factors, such as the amount of steroid drugs used or the rate of serious side effects, did not differ between the groups, although those who got radiation treatment experienced the typical side effects such as nausea, hair loss, and itchy scalp.
The average age of patients in the study was 66 years, and researchers noted that in those younger than 60, the treatment was linked to better survival. They also said that in people who had less impairment and a controlled primary lung cancer, the treatment increased survival, but the findings did not reach statistical significance.
The authors admit that the patients in the study had on average a poorer prognosis than those in earlier studies. It was these studies that suggested whole brain radiation as a good treatment option. But according to Mulvena, a poor prognosis is the most common scenario in clinical practice, where only 3.5 to 7.5 percent of patients have a better prognosis.
More than half of the patients in the study were deemed to have an intermediate prognosis — a group researchers previously believed were benefiting most from radiation.
Authors also admit that the results might have been affected by the fact that 11 percent of patients in the radiation treatment group were in too poor health to receive the treatment, or died before they received it. The quality of life assessment was also rather basic, so that patients would not be exhausted by the procedure.
In a linked comment, Dr. Cécile Le Péchoux from Gustave Roussy Cancer Campus in France stated that there might still be room for whole brain radiotherapy for some patients with non-small cell lung cancer brain metastases, but that the treatment needs to be optimized and adapted to individual cases.