1. UK Clinical Sarcoma Research

2. Changes in UK Appointment of Cancer Tsar Use of NICE to evaluate care pathways and technology/drugs Minimum datasets established Collaboration between funding bodies Creation of NCRN/NCRI and CTAAC NTRAC Clinical Study Groups

3. Sarcoma is NICE - Expected date of issue September 2005 Title: Outcomes in sarcoma “To prepare service guidance for the NHS in England and Wales for sarcomas”.

4. NICE appraisals completed included Glivec in GIST

5. Other Resources NTRAC National Cancer Tissue Resource Bioinformatics Collaborative Database of Clinical Trials in association with U.S. Competitive tendering for status of Clinical Trials Unit.

6. NCRI-Accredited Clinical Trials Units *Cancer Research UK & UCL Cancer Trials Centre (London) *Cancer Research UK Clinical Trials Unit (Birmingham) *CTRU at Leeds University *MRC Clinical Trials Unit *Section of Clinical Trials Institute of Cancer Research *UK Children's Cancer Study Group (UKCCSG)

7. Investment into infrastructure of Oncology services 25 new linacs and 17 replacements. New scanners Investment into people NICE agreed drugs funded separately

8. National Cancer Research Network National Cancer Research Institute

9. NCRN 34 Networks Set up mid 2001 £200k per million investment in infrastructure Target from DOH to double accrual into trials by 2003-4  baseline April 2000 – April 2001 – approx 3.5%. Target was 7.5% (approx 15,000) of all incident cases. Achieved and exceeded.

10. NCRN Trial Accrual All Networks 1 April 2003 - 31 March 2004

11. Portfolio of NCRI Sarcoma Group Currently only collaborative studies  These include EORTC studies  EURAMOS  Euro-Ewings.

12. British Sarcoma Group Inaugural Annual Meeting 17th May 2004 Royal College of Pathologists 2 Carlton House Terrace London

13. Future studies of NCRI Sarcoma CSG VORTEX - large radiotherapy trial Proposal for follow up study.

14. VORTEX Randomised trial evaluating impact of changes in dose/volume of post- operative radiotherapy on limb function and local recurrence in adult patients with extremity soft tissue sarcoma.

15. VORTEX

16. What are the principal research questions to be addressed? How does the margin applied around the surgical bed when planning post-operative radiotherapy for adult extremity soft tissue influence limb function, quality of life and local control?

17. The proposed trial This will be a 2-arm trial. The patients will be stratified according to tumour size <10cm or no grade, adequacy of surgical margin primary or recurrent disease

18. Treatment A (control) The first 25 fractions (50Gy) will be given to a volume which gives a 7cm margin to the surgical bed longitudinally and 3cm laterally. The phase 2 of 14-16Gy in 7-8 fractions will treat a volume giving a 1.5cm margin to the surgical bed cranio- caudally and 2cm laterally.

19. Treatment B (experimental) A total of 32-33 fractions of 2Gy should be given once a day for 5 days per week over 6 weeks, totalling 64-66Gy. The entire treatment shall be given to the volume described as phase 2 in the control arm.

20. Primary endpoints Limb function as measured by TESS at 2 years. Local recurrence at 2 years.

21. A Primary endpoint!

22. Secondary endpoints Soft tissue and bone toxicity (RTOG) Disease free survival Overall survival Overall level of disability Quality of life Detailed radiotherapy QA

23. What is the proposed sample size? 400 patients in 4 years to demonstrate a 15% improvement in TESS score 80% probability of detecting 10% difference in local control.

24. Translational research Blood samples collected for national radiogenomics study from all radiotherapy studies. Study the association between common genetic variations in relevant candidate genes and normal tissue toxicity. Ideal data set to study the role of IMRT.