Radical radiotherapy for stage I/II non-small cell lung cancer in patients not sufficiently fit for or declining surgery (medically inoperable): a systematic review

Objectives-To determine the effectiveness of radical radiotherapy in medically inoperable stage I/II non-small cell lung cancer (NSCLC) and the extent of treatment related morbidity. Methods-Randomised trials were sought by electronically searching the Cochrane Clinical Trials Register, and both randomised and non-randomised trials were sought by searching Medline and Excerpta Medica (Embase). Further studies were identified from references cited in those papers already identified by electronic searching. The studies included were those of patients of any age with stage I/II NSCLC receiving radiotherapy at a dose of > 40 Gy in 20 fractions over 4 weeks or its radiobiological equivalent. Results-Two randomised and 35 non-randomised studies were identified. One randomised and nine non-randomised studies did not meet the selection criteria, leaving one randomised and 26 non-randomised studies for analysis. In the randomised trial 2 year survival was higher following continuous hyperfractionated accelerated radiotherapy (CHART; 37%) than following 60 Gy in 30 fractions over 6 weeks (24%). An estimated 2003 patients were included in the 26 non-randomised studies; overall survival was 22-72% at 2 years, 17-55% at 3 years, and 0-42% at 5 years. Following treatment, 11-43% of patients died from causes other than cancer. Cancer specific survival was 54-93% at 2 years, 22-56% at 3 years, and 13-39% at 5 years. Complete response rates were 33-61% and local failure rates were 6-70%. Distant metastases developed in approximately 25% of patients. Better response rates and survival were seen in those with smaller tumours and in those receiving higher doses although the reasons for prescribing higher doses were not clearly stated. The outcome was worse in those with prior weight loss or poor performance status. Assessment of treatment related morbidity and effects on quality of life and symptom control were inconclusive because of the lack of prospective evaluation and paucity of data. Conclusions-No randomised trials compared a policy of immediate radical radiotherapy with palliative radiotherapy given when patients develop symptoms. In the absence of such trials, radical radiotherapy appears to result in a better survival than might be expected had treatment not been given. A substantial, though variable, proportion of patients died during follow up from causes other than cancer. The optimal radiation dose and treatment technique (particularly with respect to mediastinal irradiation) remain uncertain.