Concurrent chemoradiotherapy reduces risk of death at two years compared to sequential chemoradiotherapy or radiotherapy alone in patients with stage III non small cell lung cancer

The use of chemotherapy concurrent with radiotherapy in locally advanced non-small cell lung cancer may enhance the benefits of radiotherapy in terms of local and regional control and thus improve survival. A total of twenty-five randomised studies (including 3752 patients) were included in this updated review: nineteen trials (2728 patients) comparing concurrent chemoradiotherapy with radiotherapy alone and six trials (1024 patients) comparing concurrent with sequential chemoradiotherapy. Both comparisons demonstrated significant reduction in risk of death with use of concurrent chemoradiation, with an associated increase in incidence of acute oesophagitis.

Authors' conclusions: 

This update of the review published in 2004 incorporates additional trials and more mature data. It demonstrates the benefit of concurrent chemoradiation over radiotherapy alone or sequential chemoradiotherapy. Patient selection is an important consideration in view of the added toxicity of concurrent treatment. Uncertainty remains as to how far this is purely due to a radiosensitising effect and whether similar benefits could be achieved by using modern radiotherapy techniques and more dose intensive accelerated and/ or hyperfractionated radiotherapy regimens.

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Background: 

This is an updated version of the original review published in Issue 4, 2004. The use of concurrent chemotherapy and radiotherapy in non-small cell lung cancer (NSCLC) might be seen as a way of increasing the effectiveness of radical radiotherapy at the same time as reducing the risks of metastatic disease.

Objectives: 

To determine the effectiveness of concurrent chemoradiotherapy as compared to radiotherapy alone with regard to overall survival, tumour control and treatment-related morbidity. To determine the effectiveness of concurrent versus sequential chemoradiotherapy.

Search strategy: 

For this update we ran a new search in October 2009, using a search strategy adapted from the design in the original review. We searched: CENTRAL (accessed through The Cochrane Library, 2009, Issue 4), MEDLINE (accessed through PubMed), and EMBASE (accessed through Ovid).

Selection criteria: 

Randomised trials of patients with stage I-III NSCLC undergoing radical radiotherapy and randomised to receive concurrent chemoradiotherapy versus radiotherapy alone, or concurrent versus sequential chemoradiotherapy.

Data collection and analysis: 

Study selection, data extraction and assessment of risk of bias was performed independently by two authors. Pooled hazard ratios and relative risks were calculated according to a random-effects model.

Main results: 

Nineteen randomised studies (2728 participants) of concurrent chemoradiotherapy versus radiotherapy alone were included. Chemoradiotherapy significantly reduced overall risk of death (HR 0.71, 95% CI 0.64 to 0.80; I2 0%; 1607 participants) and overall progression-free survival at any site (HR 0.69, 95% CI 0.58 to 0.81; I2 45%; 1145 participants). Incidence of acute oesophagitis, neutropenia and anaemia were significantly increased with concurrent chemoradiation.
Six trials (1024 patients) of concurrent versus sequential chemoradiation were included. A significant benefit of concurrent treatment was shown in overall survival (HR 0.74, 95% CI 0.62 to 0.89; I2 0%; 702 participants). This represented a 10% absolute survival benefit at 2 years. More treatment-related deaths (4% vs 2%) were reported in the concurrent arm without statistical significance (RR 2.02, 95% CI 0.90 to 4.52; I2 0%; 950 participants). There was increased severe oesophagitis with concurrent treatment (RR 4.96, 95%CI 2.17 to 11.37; I2 66%; 947 participants).

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