Critical appraisal:Henderson MA, Burmeister BH, Ainslie J, Fisher R, Di Iulio J, Smithers BM, et al 2015 4

Critical Appraisal

Article being appraised

Henderson MA, Burmeister BH, Ainslie J, Fisher R, Di Iulio J, Smithers BM, et al. Adjuvant lymph-node field radiotherapy versus observation only in patients with melanoma at high risk of further lymph-node field relapse after lymphadenectomy (ANZMTG 01.02/TROG 02.01): 6-year follow-up of a phase 3, randomised controlled trial. Lancet Oncol 2015 Jul 20 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26206146.

Applicable clinical question

Is adjuvant radiotherapy of value following resection of involved lymph nodes?

Key Facts

Study Design

randomised controlled trial - Cochrane tool

Study aims:

To provide updated follow-up analyses of lymph-node field relapse, relapse-free survival, and overall survival, and reports late toxic effects(occurring more than 90 days after surgery or initiation of radiotherapy), lymphoedema, and quality of life data for the first time.

Number of Patients:

250

2 withdrew consent

intention to treat population = 248
126 in observation group
122 in adjuvant radiotherapy group

eligible population = 217
109 in adjuvant radiotherapy group

108 in observation group

Reported outcome(s):

lymph-node relapse
overall survival
relapse-free survival

Results of outcome(s):

ELIGIBLE POPULATION RESULTS -
LYMPH-NODE RELAPSE: after 3y, 2 patients in the observation group had a lymph-node field relapse.
patients in the observation group had more frequent first relapses in the lymph-node field than patients in the adjuvant radiotherapy arm (HR 0.52, 95%CI 0.31-0.88), p=0.23, adjusted for lymph-node field region
lymph-node field relapse at any time was also more common in the observation group HR 0.54 (95%CI 0.33-0.89), p=0.021
5-year cumulative incidence of lymph-node field relapse as a site of first relapse was 18% (95%CI 11-26) vs 33% (95%CI 24-42); difference: 15% (95%CI 3.5-27), p=0.011.
5-year cumulative incidence for isolated lymph-node field relapse as a site of first relapse was 8.3% (95%CI 3.0-13.5) for adjuvant radiotherapy and 23% (95%CI 15-31) for observation; difference 15% (95%CI 5.4-4.25), p=0.002. Multivariate analysis results for treatment arm is as follows: HR 0.49 (95%CI 0.28-0.85), p=0.011

RISK OF DISTANT RELAPSE: comparison between radiotherapy and observation only
- any relapse: HR 1.07 (95%CI 0.77-1.50), p=0.73
- first relapse: HR 1.12 (95%CI 0.77-1.50), p=0.56
- relapse-free survival: HR 0.89 (95%CI 0.65-1.22), p=0.51
- overall survival: HR 1.27 (95%CI 0.89-1.79), p=0.21

5-Y SURVIVAL: 40% (95% CI 31-50%) vs 45% (95%CI 36-55); HR 1.27 (95%CI 0.89-1.79), p=0.21

Comments on results:

eligible population extracted
intention to treat population results reported but not extracted from study

Quality of life outcomes were reported but not extracted from study

Includes an economic evaluation

no

Evidence ratings

Level of evidence

II

Risk of bias

Unclear risk of bias

Comments: outcomes not blinded, randomisation concealed, elgible population reported in this paper

Show/Hide Risk of bias assessment

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.

No response

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

Low

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.

At time of randomisation, the identity of the assigned treatment groups was unknown to anyone until assignment.

What was the risk of bias from the allocation concealment?

Low

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.

Participants, those giving treatment and assessors were not blinded to treatment allocation.

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.

analysis populations were described (exclusions reported, numbers available, reasons reported).

What was the risk of bias from incomplete outcome data?

Low