Methods	See the tables for each study
Participants	The pivotal presentation at the 2007 ASCO meeting was the earliest report. This describes 382 women. 12% had stage 1a (intra endometrial/noninvasive cancer) 26% stage 1b, 49% stage 1c, 6% stage 2 and 1.6% stage 3 cancer. 27% had grade 1 or 2 cancer, 53% had grade 3 endometrioid cancer, 14% had grade 3 serous papillary or clear cell morphology and more data are needed on the other 6%. Most women had two or more of the risk factors: grade 3, deep myometrial invasion, or DNA non-diploidy. 378 women are described in the report published in the European Journal of Cancer. This report adds that brachytherapy was used in less than half the cases and unfortunately, we do not know if lymphadenectomy was performed in two thirds of cases
Interventions	See the tables for each study
Outcomes	See the tables for each study
Results (OS & PFS)	The latest report combined the results from the two trials and includes data on 378 women, 191 randomised to radiotherapy only and 187 allocated chemotherapy with radiotherapy. The HR for overall survival depending on randomisation (intention to treat) = 0.66 (95% CI; 0.40-1.08; P = 0.10). The hazard ratio for progression-free survival depending on randomisation after censoring deaths from intercurrent causes was 0.64 (95% CI; 0.41-0.99; P = 0.04)
Results (site of recurrence)	The latest report quotes disease progression in 46/191 (24%) radiotherapy arm 28/187 (15%) in the radiotherapy with additional chemotherapy arm. Therefore, it is best to rely on the latest report and accept that data added together from 3 trials, MaNGO and Hogberg. This quotes a rate of initial recurrence in the pelvis 11/267 for women allocated radiotherapy versus 5/267 for women allocated radiotherapy with additional chemotherapy. This number of distal and multiple sites of recurrence for women allocated radiotherapy was 52 and 7 respectively from 267 women allocated radiotherapy only and 35 and 3 respectively from 267 women allocated radiotherapy with additional chemotherapy
Toxicity	There was one treatment-related death 3 months after randomisation in a woman allocated no chemotherapy. No further details are available. There were eight serious adverse events in the chemotherapy arm. Two women had diarrhoea, one combined with neutropenia. Three women had neutropenia, one acquired pneumonia requiring respirator treatment, and another with associated nausea and vomiting. One woman had an allergic reaction to paclitaxel, one had an episode associated atrial fibrillation and one developed bilateral pulmonary emboli 24 days after the first cycle There was one serious adverse event in the no chemotherapy arm; an intestinal reaction with diarrhoea which led to cessation of radiotherapy after 36 Gray All serious adverse events resolved after appropriate treatment
Notes
Risk of bias
Bias	Authors’ judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Central randomisation was employed in accordance with good practice
Allocation concealment (selection bias)	Low risk	Analysis was by statisticians who had treatment allocation concealed
Blinding (performance bias and detection bias) All outcomes	High risk	It was not possible to conceal the treatment allocation from the participants
Incomplete outcome data (attrition bias) All outcomes	High risk	The compliance to radiotherapy was high, 182/191 (95%) and 178/187 (95%) received P44 Gray in the radiotherapy arm and radiotherapy-chemotherapy arm, respectively. Of the 187 patients assigned to chemotherapy, 136 (73%) received four treatment cycles as planned. Eighteen (9.6%) received no chemotherapy and data were not available from three women
Selective reporting (reporting bias)	Low risk	The trials have been reported in accordance with the Consort criteria
Other bias	Low risk	There is no suggestion of any bias
Main problems with the trial as perceived by this analysis	High risk	Data collection is still ongoing and the data from the trials have been merged, rather than reported separately