The PORTRAIT trial – Post-operative radiotherapy in surgically treated bone metastases

Research question Does post-operative radiotherapy following surgery for pathological fractures improve pain and quality of life? Background

Approximately 70% of people with advanced breast and prostate cancer develop bone metastases, causing ‘pathological’ fractures requiring surgery to stabilise or replace the affected bone. Following surgery, patients usually receive radiotherapy (RT). Despite widespread use, no high-quality evidence exists that post-operative RT improves pain, quality of life nor reduces the risk of re-operation.

RT has side-effects, requires additional hospital visits and scans, can delay other effective treatments which may cause patients anxiety and use scarce NHS resource. It is therefore essential to understand if any benefits justify additional harms and cost. Aims and objectives

To investigate whether no external beam radiotherapy, following surgery for impending or completed pathological fracture due to bone metastasis in adults is non-inferior to radiotherapy for pain, function, and quality of life. Methods

A multi-centre, two arm, parallel group, non-inferiority randomised controlled trial with an internal pilot and embedded economic evaluation. Health technologies assessed Post-operative radiotherapy: Delivered within standard care pathways 4-10 weeks post-operatively.

No post-operative radiotherapy: Routine clinical monitoring; if patients develop progressive local symptoms (defined in trial protocol) radiotherapy may be offered at this point. Setting

A minimum of 20 UK study sites from an established network of metastatic bone surgical centres [1] These sites are geographically broadly distributed and include sites within the top decile for deprivation. Site selection will ensure a diverse range of demographic and socio-economic groups participate.

Target population: Adults undergoing surgery for impending or completed pathological fractures due to (non-spinal) bone metastases. Outcome measurement: Primary outcome: Pain interference at four months post-randomisation (measured using the Brief Pain Inventory [BPI]).[[2,3] Secondary outcomes: - Pain severity measured using the BPI mean severity score[4]

- Pain response defined using ICPRE endpoints[5] - Quality of life, measured using EQ-5D-5L (using quality-adjusted life years)[6] - Patient-reported functional status using TESS[7] - Overall survival - Revision surgery and time to re-operation - Re-irradiation for pain and time to re-irradiation - Resource use and cost-effectiveness

Follow-up points:

Baseline (pre-randomisation) and at 4, 8, 12, and 18 months post-randomisation (limited to 12 months for those recruited at the end of the trial for efficiency) (median population survival approximately 12 months).[8] Randomisation:

Participants will be randomised 1:1 to the intervention or control group using block randomisation with varying block sizes stratified by type of fracture and cancer diagnosis. Timelines for delivery

Total study duration: Set up: 9 months. Recruitment: 30 months. Follow-up: 12 months (and 18 months for participants who reach that point). Analysis and dissemination: 6 months. Total: 57 months. Anticipated impact and dissemination

Evidence from this trial will allow NICE to update their guidance regarding the role and indications for post-operative radiotherapy for bone metastases. Dissemination will be through the media, conferences, peer reviewed journals and clinical guidelines.