Critical appraisal:Porceddu SV, Bressel M, Poulsen MG, Stoneley A, Veness MJ, Kenny LM, et al 2018 5

Risk of bias assessment: Randomised Controlled Trial (Cochrane risk of bias tool)

Random sequence generation

Describe the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups.

Participants were randomly assigned in a ratio of 1:1 to RT or CRT. A stratified random assignment was used to balance the arms according to high-risk nodal disease and advanced primary/in-transit disease and institution. In cases where participants had both risk categories, patients were stratified to the high-risk nodal group.

What was the risk of bias from the random sequence generation?

High

Allocation concealment

Describe the method used to conceal the allocation sequence in sufficient detail to determine whether intervention allocations could have been foreseen in advance of or during, enrolment.

Participants were randomly assigned in a ratio of 1:1 to RT or CRT. A stratified random assignment was used to balance the arms according to high-risk nodal disease and advanced primary/in-transit disease and institution. In cases where participants had both risk categories, patients were stratified to the high-risk nodal group.

What was the risk of bias from the allocation concealment?

High

Blinding

Describe all measures used, if any, to blind outcome assessors from knowledge of which intervention a participant received. Provide any information relating to whether the intended blinding was effective.

allow for some censored observations, 265 patients were planned for recruitment. After a clinical impression by the Trial Management Committee (TMC) during the conduct of the study that the overall LRR rate seemed to be lower than expected, data relevant to the primary outcome for the RTarm only were extracted in August 2011 for the purpose of a sample size reassessment. The trial chairs and TMCwere blinded to this assessment, which was overseen by the independent Safety and Data Monitoring Committee.

What was the risk of bias from the blinding of participants and personnel and outcome assessors?

Unclear

Incomplete outcome data

Describe the completeness of outcome data for each main outcome, including attrition and exlusions from the analysis. State whether attrition and exclusions were reported, the numbers in each intervention group (compared with total randomized participants), reasons for attrition/exclusions where reported, and any re-inclusions in analyses performed by the review authors.

-freedom from locoregional relapse

-locoregional relapse
-Death without preceding LRR
-Disease-free survival
-Overall survival
-adverse events

All events were reported on as per the materials and methods

What was the risk of bias from incomplete outcome data?

Low