Title: Analysis of a national programme for selective internal radiation therapy for colorectal cancer

Patients with chemotherapy-refractory colorectal cancer liver metastases have limited therapeutic options. Selective internal radiation therapy (SIRT) delivers yttrium-90 microspheres as a minimally invasive procedure. This prospective, single arm, observational, service evaluation study was part of NHS England Commissioning through Evaluation. Patients eligible for treatment had histologically confirmed carcinoma with liver-only/liver-dominant metastases with clinical progression during or following oxaliplatin-based and irinotecan-based chemotherapy. All patients received SIRT plus standard of care. Primary outcome was overall survival; secondary outcomes included safety, progression-free survival (PFS) and liver-specific PFS (LPFS). Between December 2013 and March 2017, 399 patients were treated in 10 centres with median follow-up 14.3 months (95% CIs 9.2-19.4). Median overall survival was 7.6 months (95% CIs 6.9 -8.3). Median PFS and LSPFS were 3.0 months (95% CIs 2.8-3.1) and 3.7 months (95% CIs 3.2-4.3), respectively. During the followup period, 143 patients experienced an adverse event and 8% of the events were grade =3. Survival estimates from this pragmatic study demonstrate clinical outcomes attainable in the NHS comparable to previously published data. This study demonstrates the value of a registry-based commissioning model to aid national commissioning decisions for highly specialist cancer treatments. Analysis of a national programme for selective internal radiation therapy for colorectal cancer liver metastases Judith White, Grace Carolan-Rees, Megan Dale, Helen E. Morgan, Hannah E. Patrick, Teik Choon See, Emma L. Blades, Daniel E. B. Swinson, Jon K. Bell, Derek M. Manas, Adrian Crellin, Nicholas J. Slevin, *Ricky A. Sharma Cedar, Cardiff & Vale University Health Board, Cardiff Medicentre, Heath Park, Cardiff, CF14 4UJ Cedar, Cardiff University Cardiff Medicentre, Heath Park, Cardiff, CF14 4UJ Centre for Health Technology Evaluation, National Institute for Health and Care Excellence, 10 Spring Gardens, London, SW1A 2BU Cambridge University Hospitals NHS Foundation Trust, Box 218, Radiology, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ Nottingham University Hospitals NHS Trust, City Campus, Radiotherapy South, Hucknall Road, Nottingham NG5 1PB Leeds Teaching Hospitals NHS Trust, Level 4 Bexley Wing, St James's Hospital, Beckett Street Leeds, LS9 7TF The Christie NHS Foundation Trust, Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX The Newcastle upon Tyne Hospitals NHS Foundation Trust, Liver Unit, Room 161C Level 5, Freeman Hospital, Freeman Road, Newcastle upon Tyne, NE7 7DN NHS England, Institute of Oncology, Level 4 Bexley Wing, St James's University Hospital, Beckett Street, LEEDS, LS9 7TF The Christie NHS Foundation Trust, The Christie, Withington, Manchester, M204BX NIHR University College London Hospitals Biomedical Research Centre, UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6DD *CORRESPONDING AUTHOR: Professor R A Sharma, NIHR University College London Hospitals Biomedical Research Centre, UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6DD, UK. E-mail: ricky.sharma@ucl.ac.uk ABSTRACT (189 words)189 words) Patients with chemotherapy-refractory colorectal cancer liver metastases have limited therapeutic options. Selective internal radiation therapy (SIRT) delivers yttrium-90 microspheres as a minimally invasive procedure. This prospective, single arm, observational, service evaluation study was part of NHS England Commissioning through Evaluation. Patients eligible for treatment had histologically confirmed carcinoma with liver-only/liver-dominant metastases with clinical progression during or following oxaliplatin-based and irinotecan-based chemotherapy. All patients received SIRT plus standard of care. Primary outcome was overall survival; secondary outcomes included safety, progression-free survival (PFS) and liver-specific PFS (LPFS). Between December 2013 and March 2017, 399 patients were treated in 10 centres with median follow-up 14.3 months (95% CIs 9.219.4). Median overall survival was 7.6 months (95% CIs 6.9 – 8.3). Median PFS and LSPFS were 3.0 months (95% CIs 2.8-3.1) and 3.7 months (95% CIs 3.2-4.3), respectively. During the follow-up period, 143 patients experienced an adverse event and 8% of the events were grade =3. Survival estimates from this pragmatic study demonstrate clinical outcomes attainable in the NHS comparable to previously published data. This study demonstrates the value of a registry-based commissioning model to aid national commissioning decisions for highly specialist cancer treatments.