Papers

Immediate versus delayed palliative thoracic radiotherapy in patients with unresectable locally advanced non-small cell lung cancer and minimal thoracic symptoms: randomised controlled trial

Stephen J Falk, clinical oncologist, ^a David J Girling, senior scientist, ^b Roger J White, respiratory physician, ^c Penelope Hopwood, consultant in psychiatry and psycho-oncology, ^d Angela Harvey, clinical trials manager, ^b Wendi Qian, medical statistician, ^b Richard J Stephens, research scientist, ^b on behalf of the Medical Research Council Lung Cancer Working Party.

^a Department of Oncology, Bristol Oncology Centre, Bristol BS2 8ED, ^b Cancer Division, MRC Clinical Trials Unit, London NW1 2DA, ^c Department of General Medicine, Frenchay Hospital, Bristol BS16 1LE, ^d Christie Hospital NHS Trust, Manchester M20 4BX

Correspondence to: R J Stephens rs{at}ctu.mrc.ac.uk

Objective: To determine whether patients with locally advanced non-small cell lung cancer unsuitable for resection or radical radiotherapy, and with minimal thoracic symptoms, should be given palliative thoracic radiotherapy immediately or as needed to treat symptoms.
Design: Multicentre randomised controlled trial.
Setting: 23 centres in the United Kingdom, Ireland, and South Africa.
Participants: 230 patients with previously untreated, non-small cell lung cancer that is locally too advanced for resection or radical radiotherapy with curative intent, with minimal thoracic symptoms, and with no indication for immediate thoracic radiotherapy.
Interventions: All patients were given supportive treatment and were randomised to receive palliative thoracic radiotherapy either immediately or delayed until needed to treat symptoms. The recommended regimens were 17 Gy in two fractions one week apart or 10 Gy as a single dose.
Main outcome measures: Primarypatients alive and without moderate or severe cough, chest pain, haemoptysis, or dyspnoea six months from randomisation, as recorded by clinicians. Secondaryquality of life, adverse events, survival.
Results: From December 1992 to May 1999, 230 patients were randomised. 104/115 of the patients in the immediate treatment group received thoracic radiotherapy (90 received one of the recommended regimens). In the delayed treatment group, 48/115 (42%) patients received thoracic radiotherapy (29 received one of the recommended regimens); 64 (56%) died without receiving thoracic radiotherapy; the remaining three (3%) were alive at the end of the study without having received the treatment. For patients who received thoracic radiotherapy, the median time to start was 15 days in the immediate treatment group and 125 days in the delayed treatment group. The primary outcome measure was achieved in 28% of the immediate treatment group and 26% of patients from the delayed treatment group (27/97 and 27/103, respectively; absolute difference 1.6%, 95% confidence interval -10.7% to 13.9%). No evidence of a difference was observed between the two treatment groups in terms of activity level, anxiety, depression, and psychological distress, as recorded by the patients. Adverse events were more common in the immediate treatment group. Neither group had a survival advantage (hazard ratio 0.95, 0.73 to 1.24; P=0.71). Median survival was 8.3 months and 7.9 months, and the survival rates were 31% and 29% at 12 months, for the immediate and delayed treatment groups, respectively.
Conclusion: In minimally symptomatic patients with locally advanced non-small cell lung cancer, no persuasive evidence was found to indicate that giving immediate palliative thoracic radiotherapy improves symptom control, quality of life, or survival when compared with delaying until symptoms require treatment.

What is already known on this topic Radiotherapy is commonly given to patients with inoperable non-small cell lung cancer in the United Kingdom One or two fractions of palliative radiotherapy can control thoracic symptoms What this study adds In the group of patients with no symptoms or only minimal symptoms, palliative thoracic radiotherapy can be safely deferred until significant thoracic symptoms appear Compared with immediate, palliative radiotherapy, no evidence exists that such a policy affects patients' survival or levels of activity, anxiety, or depression