Dose and fractionation in radiotherapy of curative intent for non-small-cell lung cancer: Meta-analysis of randomized trials

Publication date: Available online 25 July 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Johanna C. Rankin, David J. Cutter, Sarah C. Darby, Geoff S. Higgins, Paul McGale, Mike Partridge, Carolyn W. Taylor
PurposeThe optimum dose and fractionation in radiotherapy of curative intent for non-small-cell lung cancer remains uncertain. We undertook a published data meta-analysis of randomized trials to examine whether radiotherapy regimens with higher time-corrected biologically equivalent doses resulted in longer survival, either when given alone or when given with chemotherapy.Methods and materialsEligible studies were randomized comparisons of two or more radiotherapy regimens, with other treatments identical. Median survival ratios were calculated for each comparison and pooled.Results3,795 patients in 25 randomized comparisons of radiotherapy dose were studied. The median survival ratio, higher versus lower corrected dose, was 1.13 (95% CI 1.04-1.22) when radiotherapy was given alone, and 0.83 (95% CI 0.71-0.97) when it was given with concurrent chemotherapy (p for difference=0.001).In comparisons of radiotherapy given alone, the survival benefit increased with increasing dose difference between randomized treatment arms (p for trend=0.004). The benefit increased with increasing dose in the lower-dose arm (p for trend=0.01) without reaching a level beyond which no further survival benefit was achieved. The survival benefit did not differ significantly between randomized comparisons where the higher-dose arm was hyperfractionated and those where it was not.There was heterogeneity in the median survival ratio by geographical region (p<0.001), average age at randomization (p<0.001) and year trial started (p for trend=0.004), but not for proportion of patients with squamous cell carcinoma (p=0.2).ConclusionsIn trials with concurrent chemotherapy, higher radiotherapy doses resulted in poorer survival, possibly caused, at least in part, by high levels of toxicity. Where radiotherapy was given without chemotherapy, progressively higher radiotherapy doses resulted in progressively longer survival and no upper dose level was found above which there was no further benefit. These findings support consideration of further radiotherapy dose escalation trials, making use of modern treatment methods to reduce toxicity.

Teaser

We conducted a meta-analysis of overall survival in 3,795 patients with non-small-cell lung cancer who were randomized in 21 trials comparing higher versus lower radiotherapy doses of curative intent. In trials with chemotherapy, higher radiotherapy doses led to poorer survival but, in trials where chemotherapy was not given, higher time-corrected biologically equivalent doses resulted in longer survival. These findings support consideration of further trials of radiotherapy dose escalation within the context of toxicity reduction.


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