ArticlesStereotactic ablative radiotherapy versus standard radiotherapy in stage 1 non-small-cell lung cancer (TROG 09.02 CHISEL): a phase 3, open-label, randomised controlled trial
Introduction
The standard of care for stage 1 non-small-cell lung cancer (NSCLC) is surgical resection, but many patients have smoking-related cardiac or respiratory comorbidities that make them unfit for an operation. For these patients, radiotherapy represents a safer and potentially curative option. Historically, a course of curative radiotherapy is given as 20 or more fractions delivered over a period of 4–6 weeks. Fractionating the treatment improves the therapeutic ratio by enabling escalation of the dose to tumouricidal amounts while allowing interfraction recovery of the incidentally irradiated dose-limiting normal tissues. Advances in radiotherapy technology, including image guidance and tumour motion management, have led to more precise conformal dose delivery to the tumour and substantially less dose delivery to the surrounding healthy tissues. As a result, safe delivery of extremely high (ablative) doses to smaller tumours without the need for protracted fractionation is possible. This technique, typically given as a hypofractionated course of one to five treatments over 1–2 weeks, is termed stereotactic ablative body radiotherapy (SABR), and its use for treating medically inoperable stage 1 NSCLC has increased rapidly since 2001.1
Single-arm studies have consistently shown high local control with the use of SABR. For example, in one prospective trial2 of SABR for inoperable early-stage NSCLC (RTOG 0236), the 3-year primary tumour control was 90%—far superior to the 30–40% control observed historically using fully fractionated techniques. Despite the high local control achieved, overall survival in RTOG 0236 was only 55·8% at 3 years, and no randomised trials have indicated that the high local control translates into improved overall survival compared with standard radiotherapy. The Scandinavian SPACE trial3 randomly assigned patients with medically inoperable non-central stage 1 NSCLC to SABR or standard fractionated radiotherapy. No significant differences in overall survival between the treatment groups were recorded, but any potential benefits of the SABR approach might have been masked by the inclusion of patients either with poor performance status, no pathological diagnosis, or incomplete staging due to omission of 18F-fluorodeoxyglucose (FDG)-PET in a substantial proportion of patients. We therefore did a randomised trial of SABR versus standard fractionated radiotherapy in patients with biopsy-confirmed FDG-PET stage 1 NSCLC that was either inoperable or the patient refused surgery to prospectively assess the effect of radiotherapy technique on local control, overall survival, toxicity, and quality of life.
Section snippets
Study design and participants
In this multicentre, phase 3, randomised controlled trial (Trans Tasman Radiation Oncology Group [TROG] 09.02, Australasian Lung Cancer Trials Group [ALTG] 09.05, acronym CHISEL), patients were recruited under the auspices of the TROG and ALTG from 14 participating hospitals, 11 in Australia and three in New Zealand (appendix pp 14). Eligible patients had cytologically or histologically proven stage T1N0M0 or T2aN0M0 NSCLC according to the seventh edition of the Union for International Cancer
Results
Between Dec 31, 2009, and June 22, 2015, 101 patients were enrolled and randomly assigned to either standard radiotherapy (35 patients) or SABR (66 patients; figure 1). Details of patients who withdrew, were removed from study or crossed over, and the reasons why are shown in figure 1. Delays in installation and provision of credentials for advanced technologies required for the experimental group of the trial at numerous sites resulted in a longer accrual period than planned. The accrual
Discussion
In this multicentre, randomised, controlled, phase 3 trial, we have shown that use of SABR with a dose of 48 Gy or 54 Gy results in better local control of peripherally located stage 1 (T1–T2aN0) NSCLC than standard radiotherapy with a dose of 50 Gy or 66 Gy. This finding was associated with an overall survival benefit for patients randomly assigned to SABR. To the best of our knowledge, this study is the first to make a direct comparison that indicates that SABR is associated with improved
Data sharing
We do not plan to share the data collected in this study. The study protocol and patient information consent forms are available in the appendix. Enquiries regarding access to the data should be directed to [email protected].
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