Study designs of evaluations included in the review
Randomised controlled trials of clinical effectiveness were eligible for inclusion in the review. Studies of resource use were eligible if based on costs in the UK. The authors did not provide detailed inclusion and exclusion criteria for study designs assessing resource use.
Specific interventions included in the review
Comparisons of non-conventional radiotherapy with standard radiotherapy were eligible for inclusion in the review. Non-conventional radiotherapy was defined as hyperfractionated, accelerated or combined hyperfractionated and accelerated regimens, with or without adjuvant chemotherapy. More specifically, studies were eligible for inclusion if they compared the clinical or cost effectiveness of:
accelerated radiotherapy, alone or combined with adjuvant chemotherapy, versus standard radiotherapy;
hyperfractionated radiotherapy, alone or combined with adjuvant chemotherapy, versus standard radiotherapy;
hyperfractionated split-course radiotherapy, alone or combined with adjuvant chemotherapy, versus standard radiotherapy; and
combined hyperfractionated and accelerated radiotherapy (CHART), alone or combined with adjuvant chemotherapy, versus standard radiotherapy.
The authors reported full details of the schedules and regimens used in the primary studies in the review. Although these differed somewhat, the general characteristics can be described as follows. Accelerated radiotherapy was defined as two or more fractions of standard fraction size daily, up to the conventional total dose. The number of fractions is increased each week, shortening the overall treatment time. One study included in the review used this method, with 60 Gy in 30 fractions of 2 Gy twice daily for 3 weeks.
Hyperfractionated (non-accelerated) radiotherapy was defined as two or more fractions daily of smaller than conventional fraction size. Three studies included in the review used this method, with total doses varying between 66 and 71.5 Gy over 6 weeks split between 60 and 52 fractions, respectively.
Hyperfractionated accelerated radiotherapy was defined as two or three fractions of smaller than standard fraction size daily, delivered over a shorter period of time than conventional radiotherapy. Variants include CHART and continuous hyperfractionated accelerated radiotherapy weekend-less (CHARTWEL). One study included in the review used this method, with 54 Gy in 36 fractions of 1.5 Gy three times daily for 12 continuous days.
Spilt-course radiotherapy divides the total dose into at least two separate courses with an interruption of 10 to 14 days. Two studies included in the review used hyperfractionated split-course treatment. These divided courses of 60 or 72 Gy by a 2-week rest period, using varying fractionation.
Standard radiotherapy was defined as a regimen considered 'conventional' within the United Kingdom (approximately 2 Gy fractions given once daily to a total of 60 to 70 Gy). Standard radiotherapy varied between the studies included in the review, but was predominantly 60 Gy in 30 fractions of 2 Gy once daily for 6 weeks.
The authors excluded studies of standard radiotherapy combined with chemotherapy.
Participants included in the review
Adults with inoperable, but not widespread (not stage IV) NSCLC were eligible for inclusion in the review. The authors did not report the overall descriptive characteristics (e.g. average age across all primary studies, or proportion of women), but characteristics of the participants in the individual primary studies were provided in an appendix. These were summarised by intervention and included age, histology, disease stage and gender. The characteristics of the participants varied widely. For example, between 63 and 97% of the participants in different primary studies were men.
Outcomes assessed in the review
Studies that assessed clinical effectiveness, cost- effectiveness/resource use, or both were eligible for inclusion in the review. The primary outcome for clinical effectiveness was overall survival, measured using definitions as per the primary studies. The secondary outcomes included adverse events, clinical response and quality of life (although few studies included data on quality of life). Studies that included an assessment of resource implications or costs were also eligible for inclusion. The primary outcome for cost-effectiveness, calculated for the review, was the cost per life-year gained. It was not possible to include the cost per quality-adjusted life-year as an outcome due to insufficient quality of life data.
How were decisions on the relevance of primary studies made?
One author assessed the abstracts of all potential studies using a list of inclusion criteria. The full text of studies was assessed where relevant information was not available in abstract form. Twenty per cent of potential papers were checked by a second author. A Kappa score was calculated to detect inter-rater agreement.