From the Journals

Whole brain radiotherapy not beneficial for NSCLC metastasis

Key clinical point: Whole brain radiotherapy provided no clinically significant benefit for most patients with metastatic NSCLC.

Major finding: The primary outcome measure, quality-adjusted life-years, was 46.4 days with radiotherapy and 41.7 days without it.

Data source: An international, randomized, phase III noninferiority trial involving 538 patients treated during a 7-year period.

Disclosures: Cancer Research U.K., the Medical Research Council in the U.K., the Trans Tasman Radiation Oncology Group, and the Medical Research Council Australia supported the study. Dr. Mulvenna and her associates reported having no relevant financial disclosures.

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Large, well designed trial has limitations

Managing brain metastases from NSCLC is a challenge, because the lesions may well produce life-threatening symptoms and serious impairment, which could be ameliorated with whole brain radiotherapy.

This is a large and well designed trial, but it was limited in that the maximal benefit of radiotherapy is believed to occur 6 weeks after the end of treatment. Given that median overall survival was only 8 weeks and considering the time it took to deliver the treatment, approximately half of the patients in this study died before an optimal assessment of symptoms could be done.

This might also explain why radiotherapy didn’t have an effect on steroid use in this study. Many patients didn’t live long enough for radiotherapy’s steroid-sparing effect to be observed.

Cécile Le Pechoux, MD, is in the department of radiation oncology at Gustave Roussy Cancer Campus in Villejuif, France. She and her associates reported having no relevant financial disclosures. They made these remarks in a comment accompanying the report on the QUARTZ trial (Lancet 2016 Sep 4. doi: 10.1016/S0140-6736[16]31391-5).


 

FROM THE LANCET

Whole brain radiotherapy, a standard treatment for patients with metastatic non–small-cell lung cancer, provided no clinical benefit in a noninferiority trial specifically designed to assess both patient survival and quality of life.

The findings were published online Sept. 4 in the Lancet.

Whole brain radiotherapy, with or without concomitant steroid treatment, has been widely used for decades in that patient population, even though no sufficiently powered, definitive studies support the approach. It is likely that patients and clinicians alike continue to embrace it because of the absence of alternative treatment options.

The Quality of Life After Treatment for Brain Metastases (QUARTZ) trial was intended to assess whether any improvement in survival offered by whole brain radiotherapy is balanced by deterioration in quality of life, said Paula Mulvenna, MBBS, of the Northern Center for Cancer Care, Newcastle (England) Hospitals, and her associates (Lancet 2016 Sep 4. doi: 10.1016/S0140-6736(16)30825-X).

QUARTZ involved 538 adults seen during a 7-year period who had NSCLC with brain metastases and who were not suited for either brain surgery or stereotactic radiotherapy. The median age was 66 years (range, 35-85 years), and 38% had a Karnofsky Performance Status score of less than 70.

The participants were randomly assigned to receive either optimal supportive care plus whole brain radiotherapy (269 patients) or optimal supportive care alone (269 patients) at 69 U.K. and 3 Australian medical centers. They reported on 20 symptoms and adverse effects, as well as health-related quality of life, approximately once per week.

The primary outcome measure – quality-adjusted life-years (QALY), which combines overall survival and quality of life – was 46.4 days with radiotherapy and 41.7 days without it.

Symptoms, adverse effects, and quality of life (QOL) were similar between the two study groups at 4 weeks, except that the radiotherapy group reported more moderate or severe episodes of drowsiness, hair loss, nausea, and dry or itchy scalp. The number and severity of serious adverse events were similar through 12 weeks of follow-up.

The percentage of patients whose QOL was either maintained or improved over time was similar between the two groups at 4 weeks (54% vs. 57%), 8 weeks (44% vs. 51%), and 12 weeks (44% vs. 49%). Changes in Karnofsky scores also were similar.

The study refuted the widely held belief that whole brain radiotherapy allows patients to reduce or discontinue steroid treatment, averting the associated adverse effects. Steroid doses were not significantly different between the two study groups through the first 8 weeks of treatment, which “challenges the dogma that whole brain radiotherapy can be seen as a steroid-sparing modality,” the investigators said.

Taken together, the findings “suggest that whole brain radiotherapy can be omitted and patients treated with optimal supportive care alone, without an important reduction in either overall survival or quality of life,” Dr. Mulvenna and her associates said.

The approximately 5-day difference between the two study groups in median overall survival highlights both the limited benefit offered by radiotherapy and the poor prognosis of this patient population, the researchers added.

Whole brain radiotherapy did offer a small survival benefit to the youngest patients who had good performance status and a “controlled” primary NSCLC. “For all other groups, [it] does not significantly affect QALY or overall survival,” they said.

Cancer Research U.K., the Medical Research Council in the U.K., the Trans Tasman Radiation Oncology Group, and the National Health and Medical Research Council Australia supported the study. Dr. Mulvenna and her associates reported having no relevant financial disclosures.

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