LONDON-Patients with non-small cell lung cancer (NSCLC) metastasized to the brain did not benefit from whole brain radiotherapy (WBRT) in a study reported at the European Respiratory Society (ERS) International Congress 2016 held in London and simultaneously published in The Lancet (http://dx.doi.org/10.1016/S0140-6736(16)30825-X).
Paula Mulvenna, MBBS, FRCP, FRCR, a Consultant Clinical Oncologist at the Newcastle Hospitals NHS Trust in Newcastle-upon-Tyne, U.K., reported final results from the QUARTZ (Quality of Life After Treatment for Brain Metastases) randomized controlled clinical trial to a joint ERS-Lancet session at the congress. She called for practice change and a revision of guidelines for therapy in these seriously ill patients.
"The main take-home message is that whole brain radiotherapy can no longer be seen as a standard for non-small cell lung cancer and brain metastases," she told Oncology Times.
She said her group decided to conduct the QUARTZ study because of uncertainties emerging from routine clinical work among patients with lung cancer. They wanted to establish whether WBRT could be omitted without a significant effect on survival or quality of life.
"The issue was that in our lung cancer clinics we were seeing patients who had developed metastatic brain disease who weren't doing as well as we hoped with whole brain radiotherapy," she said, adding that QUARTZ was able to address the question of whether such radiotherapy could even be harming these patients.
Limited Benefits With WBRT
Mulvenna recommendations about using WBRT in metastatic lung cancer had been equivocal. Before conducting QUARTZ her group had found only one relevant randomized clinical trial-which recruited 48 patients with brain metastases from a variety of primary cancers-and concluded that WBRT offered only limited benefit and that its use as standard practice was difficult to justify.
The 538 patients who were unsuitable for surgical resection or stereotactic radiotherapy were recruited into the QUARTZ study from 69 U.K. and three Australian centers and were randomized to treatment with or without WBRT using 20 gray in five daily fractions-with all patients receiving optimal supportive care and dexamethasone.
The primary outcome was patient reported quality-adjusted life years (QALYs). "We have shown that there was no clinically significant difference in the quality-adjusted life years between the patient groups," Mulvenna said. (46.4 QALY days for patients receiving radiation versus 41.7 QALY days for the control group.)
She also reported no clinically or statistically significant difference in overall survival between the two groups-with a median survival in the control arm of 9.2 weeks as compared with 8.5 weeks in the radiotherapy arm. Overall quality of life and dexamethasone use were the same for each group.
Changing Practice
When Mulvenna was asked how this should influence practice, she said the QUARTZ study had provided a higher level of evidence to create "higher grade" guidelines. "This is now level one evidence showing that for patients with non-small cell lung cancer and metastatic brain disease-not suitable for stereotactic or surgical approaches-whole brain radiotherapy should not be seen as a standard."
Mulvenna said steroids-at the lowest effective doses-were needed to reduce peri-tumoral edema and there was a need to investigate other methods of improving symptomatic control.
Co-chair of the joint Lancet-ERS session Klaus Rabe, MD, PhD, Former President of the ERS and Professor of Oncology at the LungenClinic Grosshansdorf near, Hamburg, Germany, told Oncology Times he agreed with her. "It does change clinical practice," he said.
He said the QUARTZ study findings clearly showed that using WBRT could no longer be recommended for most patients with lung cancer.
Rabe applauded the success of QUARTZ in collecting data on health status and symptoms in a very critically ill patient group and for answering the important question of whether whole-brain radiotherapy would help spare steroid use. "There was no interaction between these two treatments at all," he said. And he added that any hope WBRT would benefit patients or increase their life expectancy needed to be reconsidered.
But the door to the potential use of WBRT in this patient group was held ajar by Cecile Le Pechoux, MD, from the Institut Gustave Roussy Cancer Campus in Villejuif, France, and her colleagues in a linked Lancet article. "This trial might not rule out use of whole brain radiotherapy in all patients with NSCLC and brain metastases," they concluded, suggesting it could be a component of more individualized strategies if given at the right time to appropriate patients. But Le Pechoix and colleagues acknowledged the results of QUARTZ still needed to be taken into account along with classical prognostic factors and molecular status.
The QUARTZ authors concluded their report with a simple message. "The combined evidence suggests that WBRT offers no substantial benefit to most patients with brain metastases from NSCLC in terms of improved survival, overall quality of life, or reduction in steroid use."
Peter M. Goodwin is a contributing writer.