Whole brain radiotherapy for non-small cell lung cancer

Abstract

We read with interest the results of the QUARTZ randomised trial by Paula Mulvenna and colleagues (Oct 22, p 2002)1Mulvenna 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: 2004-2014Summary Full Text Full Text PDF PubMed Scopus (434) Google Scholar assessing whole brain radiotherapy (WBRT) versus optimal supportive care in patients with non-small cell lung cancer (NSCLC) and brain metastases. We commend the authors on undertaking this important study. This study validates the practice pattern of withholding WBRT in patients that will not live long enough to derive benefit from intracranial control. However, we caution against overgeneralisation of the results to all patients. This multicentre study1Mulvenna 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: 2004-2014Summary Full Text Full Text PDF PubMed Scopus (434) Google Scholar randomised 538 patients between March, 2007, and August, 2014, from 72 centres in the UK and Australia. These numbers suggest that, on average, only one patient per centre was enrolled annually, and might reflect selection bias in which only patients with the poorest of expected outcomes were enrolled. This hypothesis is consistent with a median survival among the entire cohort of 2 months and that approximately 10% of patients assigned to WBRT either died before receiving WBRT or declined to the point that WBRT could no longer be given. Patients were enrolled on this trial if they were “unsuitable for surgical resection or stereotactic radiotherapy”, yet approximately two-thirds of patients had four lesions or fewer; recently published randomised trials2Aoyama H Shirato H Tago M et al.Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial.JAMA. 2006; 295: 2483-2491Crossref PubMed Scopus (1696) Google Scholar, 3Brown PD Jaeckle K Ballman KV et al.Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial.JAMA. 2016; 316: 401-409Crossref PubMed Scopus (923) Google Scholar, 4Soffietti R Kocher M Abacioglu UM et al.A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results.J Clin Oncol. 2013; 31: 65-72Crossref PubMed Scopus (458) Google Scholar, 5Chang EL Wefel JS Hess KR et al.Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial.Lancet Oncol. 2009; 10: 1037-1044Summary Full Text Full Text PDF PubMed Scopus (1755) Google Scholar indicate that few situations exist in which patients with four brain metastases or fewer should be treated with WBRT as opposed to stereotactic radiation. Had this study started enrolment in 2016, it is plausible that few patients would have met eligibility criteria. Despite the patient selection issues noted above, some groups of patients appeared to show potential survival benefit with WBRT, including patients younger than 70 years of age, those with a Karnofsky Performance Status of at least 70, and those with controlled systemic disease. Given that only 10–25% of patients with brain metastases die of neurological disease,2Aoyama H Shirato H Tago M et al.Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial.JAMA. 2006; 295: 2483-2491Crossref PubMed Scopus (1696) Google Scholar an improvement in overall survival with WBRT is reflective of the substantial benefit that radiation can provide when used appropriately. In conclusion, Mulvenna and colleagues' trial shows that for patients with very limited expected survival, WBRT provides no survival benefit. This result is a valuable contribution that aids in clinical decision making, but the results should not be overgeneralised to patients with longer expected survival times. BMA is a practicing radiation oncologist with a compensation model associated with treatment of patients. AAA reports grants from Varian Medical Systems, outside of the submitted work. DNC declares no competing interests. 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 trialAlthough the primary outcome measure result includes the prespecified non-inferiority margin, the combination of the small difference in QALYs and the absence of a difference in survival and quality of life between the two groups suggests that WBRT provides little additional clinically significant benefit for this patient group. Full-Text PDF Open AccessWhole brain radiotherapy for non-small cell lung cancer – Authors' replyWe welcome discussion of the QUARTZ trial1 results, which demonstrated that survival and quality of life for patients with brain metastases from non-small cell lung cancer (NSCLC) were similar regardless of whether whole brain radiotherapy (WBRT) was used in addition to optimal supportive care. 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