1. Senior Trial Manager Wales Cancer Trials Unit Cardiff University 1
Integrating Radiotherapy Trials Quality Assurance (RTTQA) into National Cancer Research Institute (NCRI) clinical trials
Lisette Nixon
Senior Trial Manager
Wales Cancer Trials Unit
Cardiff University 1
Co-ordinator Cardiff RTTQA group
Velindre Cancer Centre 2
Lucy Wills 2, Emiliano Spezi 2, Sarah Gwynne 2, Rhydian Maggs 2, Tony Millin 2,
Chris Hurt 1, Geraint Lewis 2, John Staffurth 2 , Gareth Griffiths 1
1 Wales Cancer Trials Unit, Cardiff University, 6th Floor, Neuadd Meirionnydd, Heath Park, Cardiff CF14 4YS
2 Velindre Cancer Centre, Whitchurch, Cardiff, CF14 2TL
Thank you for invite to speak.
Mention been involved more than trial managers would be due to staffing problems
Great support from RTTQA group and the QA RT has been run from the coordinating centre rather than from within a MP department, and outside MVH or RMH.

2. Who’ who Wales Cancer Trials Unit (WCTU)
NCRI accredited Clinical Trials Unit who develop and run cancer clinical trials
National Cancer Research Institute
UK-wide partnership between the government, charity and industry which promotes co-operation in cancer research
Radiotherapy Trials Quality Assurance Group (RTTQA)
NCRI Group formed to provide central QA and advice for all RT trials
RTTQA Cardiff
Sub-group of the main RTTQA group
Velindre NHS Trust
NHS Trust within which the Cardiff RTTQA group sit and also sponsor for the SCOPE 1 trial

3. What is Radiotherapy?
With an 18 MeV accelerator, it is possible to irradiate up to 15cm deep tumours with little irradiation of healthy tissue situated on the beam path For a zone situated at a depth of 15cm, approximately 70% of the dose is delivered to the tumour. When using four field treatment, less than 50% of the dose is delivered to the neighbouring healthy tissue.
Linear accelerators
They comprise an electron source and an electromagnet which accelerates the electrons in a deep vacuum tube

4. Planning of Radiotherapy
Patient has a planning CT scan in treatment position
Clinician uses diagnostic information to draw round the tumour (GTV: Gross Tumour Volume)
Clinician or planner applies margins to allow for set up errors and movement of patient (PTV: Planning Treatment Volume)
Clinician or planner draws around other organs in proximity to the tumour (organs at risk)
Planner optimises beams and arrangement of wedges/MLCs to get optimal coverage of PTV (i.e. all the area inside PTV received as close to the prescribed dose as possible) and minimises dose to organs at risk

5. Outlining
Creating GTV and PTV

6. Organs at Risk

7. Creating the plan

8. The plan
Add picture of all beams

9. Dose to organs at risk and tumour

10. Dose Volume Histograms
Green – PTV
Pink – Heart
Red – lung
Cyan - SC PTV
Gold - liver

11. Patients with oesophageal cancer chosen to receive definitive CRT
SCOPE 1 Trial Design
Study of Chemoradiotherapy in Oesophageal Cancer plus of minus Erbitux
Stage 1
Stage 2
CRT
CRT + cetuximab
Treatment
failure rate
Overall
survival
Patients with oesophageal cancer chosen to receive definitive CRT
Randomise
n=180
n=240
(total of 420)
Stage 2
Overall survival
Toxicity
Quality Assurance - RT Quality of Life
Health Economics
Stage 1
Treatment failure rate
(endoscopic assessment, biopsy CT scan)
Toxicity
Feasibility
Primary Endpoint
Secondary Endpoint
A randomised phase II/III multi-centre clinical trial of definitive chemo-radiation, with or without Cetuximab, in carcinoma of the oesophagus
Objective:
To determine whether the addition of cetuximab to definitive chemoradiation (CRT) shows increased survival in the treatment of patients with non-metastatic carcinoma of the oesophagus.
Previous trials in oesophageal cancer have shown that CRT gives the best survival in patients not suitable for surgery. We hope to improve this by the addition of cetuximab. The trial design means that the data will be analyzed by an IDMC after 180 patients to establish activity and safety of the addition of cetuximab. Centres will not be aware of this transition from a phase II to III.
A7256

12. Maximum percentage of the OAR to receive max dose
SCOPE 1
Study of Chemotherapy in Oesophageal Cancer plus of minus Erbitux
PTV Dose Coverage
Target Dose
Volume of PTV receiving 95% of dose
>99% of PTV to get 95% of dose
Minimum dose to PTV
Minimum dose to PTV should be greater than 93%
Maximum dose to PTV
Should be less than107%
Organ at Risk
Maximum Dose
Maximum percentage of the OAR to receive max dose
Combined Lungs
20Gy
25%
Heart
40Gy
30%
Spinal cord PRV
No part
Liver
30Gy
60%
Right or Left Kidney
25% (single kidney)
The protocol gives limits on the doses including the coverage of the PTV and dose to organs at risk. We have pre-defined minor and major deviations which means that deviations from the protocol can quickly and consistently be assessed as to how serious they are.
A7256

13. Why implement a QA RT programme?
improve
Share experience to help establish best practice
accuracy
Ensure consistent approach across all centres with a pre-trial test case (e.g. clinical outlines, planning techniques)
Ensure protocol adherence with on-trial QA (e.g. use of contrast, position verification)
Ensure treatment accuracy (e.g. audit visit to verify RT plan delivery)
support
Provide ongoing support to clinicians and planners for difficult cases
Regular review of the protocol to incorporate new concepts of RT delivery
The key message from good clinical practice is that the patient comes first. If the standard is consistent across the UK, especially if this means the standard has been improved in some centres, then this has to be good for patients.
For the trial it is important, when comparing 2 arms, that there is consistency and accuracy across common treatments in both arms. Dose of RT should be considered as important as dose of CT.
The protocol was written using the best available information at the time. There is the possibility that research shows certain aspects need to be updated in the future.

14. QA RT Process Site Visit Pre-trial test case Educational
Questionnaires
Baseline
Staff
Trial specific
Educational
RT specific protocol with planning tips
CD ROM with example cases
Site Visit
Equipment audit
Dosimetry check
Pre-trial test case
Assessment of outlines
Assessment of plan
Assessment of form completion
Assessment of patient cases
1st case from each consultant and 10% sample
Plan Assessment Form for all patients
Check data is readable in VODCA
There are a number of aspects to the QA process such as questionnaires, educational component, site visit, pre-trial test case and on trial assessment of patient cases.
Emphasis pre- trial and on-trial and explain differences

15. QA process – who does what
Site
WCTU
Velindre (CI / MP)
Completes pre-trial educational exercise and test case
Trials office chase up test cases, patient PAFs and plan data
Pre-trial MP checks test case plan, drafts report including feedback on possible areas of improvement/advice
Completes Plan Assessment Form (pre and on-trial)
TM performs system check for readability of data (pre- and on-trial)
On- trial advice where requested by WCTU
Plans patient and exports DICOM data (pre- and on-trial)
Checks PAF and highlights any out of range values (on-trial)
On- trial assessment of patient cases
Sends data(ftp server / CD) to trials office
Patient data where deviation appears on PAF, full plan is sent to MP for assessment (on-trial)
On-trial investigates deviations

16. System check for the readability of exported data

17. Examples of GTV
Consistency
Variation
Images exported from VODCA

18. Pros and Cons Pros Cons Ensures the quality of data
Provides data on consistency of dose and treatment
Assesses adherence to protocol
Educational component ensures minimum standard of treatment planning
Helps improve networking and relationship with sites
Pre-trial can take time complete and lengthen set up times
May put centres off taking part
Can be time consuming chasing up data
Additional resources needed to evaluate plans

19. Conclusions – SCOPE 1
60 test case outlines and 40 plans have been returned, which means that the SCOPE 1 protocol and RT guidance document has been read and followed in all these centres
The data collected suggest this has been a good educational exercise and highlights that there are variations between centres which can be addressed to improve consistency between both consultants and centres.
A comprehensive QA programme can be implemented within a clinical trials unit with good collaboration and medical physics support.

20. Conclusions
The RTTQA group should be involved in all NIHR trials involving Radiotherapy
Including a RTQA programme into a clinical trial should:
provide consistency in RT treatment,
raise the standards and consistency of RT
give validity to the results
Collaborative working between WCTU and the Cardiff RTTQA group has provided a set of standards to use for subsequent trials and has proved to be a successful model

21. Thank You Any Questions?
Thank you for listening and any questions.