UK Clinical Sarcoma Research

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

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.

National Cancer Research Network

National Cancer Research Institute

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.

Portfolio of NCRI Sarcoma Group

Currently only collaborative studies These include EORTC studies EURAMOS Euro-Ewings.

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.

VORTEX

Resected extremity sarcomaPhase I 50Gy/25

Phase II 14-16Gy/7-8Single phase treatment

to Phase II volume64-66Gy/32-34

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?

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

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.

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.

Primary endpoints

Limb function as measured by TESS at 2 years.

Local recurrence at 2 years.

Secondary endpoints

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

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.

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.