br Conclusion Survival estimates from this pragmatic study s
Conclusion: Survival estimates from this pragmatic study show clinical outcomes attainable in the National Health Service comparable with previously pub-lished data. This study shows the value of a registry-based commissioning model to aid national commissioning decisions for highly specialist cancer treat-ments.
2018 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.
Key words: Brachytherapy; colorectal cancer; commissioning models; liver metastases; molecular radiotherapy; transarterial radio-embolisation
Author for correspondence: R.A. Sharma, NIHR University College Lon-don Hospitals Biomedical Research Centre, UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6DD, UK.
E-mail address: [email protected] (R.A. Sharma).
Colorectal cancer (CRC) is the fourth most common can-cer in the UK. Liver metastases are common among patients with CRC; resection of the primary and metastatic tumours is favoured where possible, but most (70e80%) patients are unsuitable for liver surgery . Systemic chemotherapy is
the standard treatment for unresectable metastatic disease, which may be combined with biological agents such as epidermal growth factor receptor inhibitors (cetuximab or panitumumab) or vascular endothelial growth factor in-hibitors (bevacizumab). For patients with advanced meta-static CRC (mCRC) who have progressed after standard first-and second-line therapies, the aim of third-line treatments is to prolong life, improve symptoms and maintain an acceptable quality of life. Currently there are limited options available for patients with unresectable, chemotherapy-refractory mCRC (termed the ‘salvage setting’).
Selective internal radiation therapy (SIRT), also called transarterial radio-embolisation or radio-embolisation, is a form of arterially delivered brachytherapy. It involves delivering microspheres containing a beta-emitting radio-nuclide, yttrium 90 (Y-90), directly into the tumour via the hepatic artery using a percutaneous transarterial approach [2,3]. The efficacy of SIRT is supported by an evidence Midostaurin (PKC412) comprised largely of single-arm studies and three comparative studies (Supplementary Table S1).
Commissioning through Evaluation (CtE) is a national programme led by National Health Service (NHS) England that enables highly specialist treatments to be commis-sioned in selected provider centres with a planned evalua-tion phase . The evaluation is commissioned by the National Institute for Health and Care Excellence (NICE) and carried out by an independent research group, which as-sesses the clinical and cost-effectiveness of the intervention in a specific population. The aim of the programme was to evaluate the impact of SIRT on overall survival, progression-free survival (PFS) and liver-specific PFS (LPFS), and to assess safety.
Materials and Methods
This prospective, single-arm, observational, service-evaluation study was carried out between December 2013 and February 2017 in 10 NHS hospitals in England (Cam-bridge University Hospitals NHS Foundation Trust, Kings College Hospital NHS Foundation Trust, Leeds Teaching Hospitals NHS Trust, Newcastle-upon-Tyne Hospitals NHS Trust, Nottingham University Hospitals NHS Trust, Oxford University Hospitals NHS Foundation Trust, The Christie NHS Foundation Trust, The Royal Free London NHS Foun-dation Trust, University Hospital Southampton NHS Foun-dation Trust, University Hospitals Birmingham NHS Foundation Trust). SIRT was provided as routine care at these centres and therefore this study was designated as a service-evaluation project within the NHS; patient consent for all procedures therefore used the sites’ routine NHS clinical governance processes. The SIRT registry is an online registry hosted by the British Society of Interventional Radiology incorporating national data on radio-embolisation of primary and secondary liver tumours. It holds de-identified data, and only those data relevant to this CtE study were extracted for analysis and transferred to an independent research group, Cedar (Cardiff and Vale Uni-versity Health Board), for analysis.
Adults with unresectable, chemotherapy-refractory, CRC liver metastases were eligible for treatment. Inclusion criteria included: histologically confirmed carcinoma with liver-specific or liver-dominant metastases not amenable to curative liver surgical resection; unequivocal and measur-able computed tomography evidence of liver metastases not treatable by surgical resection or local ablation with curative intent; World Health Organization performance status 0e2; life expectancy >3 months; evidence of clinical progression during or after both oxaliplatin-based and irinotecan-based chemotherapy, unless the patient had a specific contraindication to chemotherapy or did not tolerate either regimen; adequate haematological and he-patic function as follows: serum bilirubin ¼ 1.5 upper limit of normal; absolute neutrophil count >1.5 109/l, platelets >100 109/l; albumin ¼ 30 g/l; no central nervous system metastases or bone metastases, but patients were permitted to have limited extrahepatic disease (e.g. lung metastases, multiple lymph nodes or low-volume perito-neal disease, but the multidisciplinary team must have agreed that the extrahepatic disease was probably not life-threatening or a cause for significant morbidity if the liver metastases can be controlled with locally directed therapy); no evidence of ascites or cirrhosis.