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Trial registered on ANZCTR


Registration number
ACTRN12615000862549
Ethics application status
Approved
Date submitted
21/07/2015
Date registered
18/08/2015
Date last updated
18/10/2019
Date data sharing statement initially provided
12/11/2018
Date results information initially provided
12/11/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Developing methods to allow adaptive radiotherapy for gynaecological cancers with Magnetic Resonance Imaging (MRI)
Scientific title
The use of MRI in radiotherapy planning to assess the feasibility of adaptive radiotherapy in gynaecological cancers.
Secondary ID [1] 286245 0
Nil
Universal Trial Number (UTN)
U1111-1167-5571
Trial acronym
Gynae MRI study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gynaecological Cancer 294300 0
Condition category
Condition code
Cancer 294619 294619 0 0
Cervical (cervix)
Cancer 294620 294620 0 0
Womb (Uterine or endometrial cancer)
Cancer 294622 294622 0 0
Other cancer types

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The study design is a prospective cohort study. Patients will receive standard treatment for their malignancy, this study does not involve a treatment intervention. Participants will be undergoing standard radiotherapy treatment. Each patient will have an MRI prior to treatment (planning MRI) and weekly MRIs during the course of treatment, to a maximum of 6 MRIs per patient. The weekly MRIs are additional to what is usually received as standard of care. Each MRI scan will take approximately 30 minutes.
The additional MRI scans will be de-identified and study co-investigators will outline normal tissues and the tumour. This information will then be used to develop software that will facilitate the adaptive radiotherapy workflow which will potentially reduce radiation dose to surrounding normal tissues and allow dose escalation (increase in dose delivered to the tumour).
Intervention code [1] 291261 0
Not applicable
Comparator / control treatment
No comparator
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294386 0
Development of gold-standard contours using STAPLE algorithm
Timepoint [1] 294386 0
From time of last MRI to time that contours are finalised and analysed
Primary outcome [2] 295692 0
Accuracy of autogenerated vs gold-standard contours through assessment of variability between contours computed using several metrics, including dice similarity co-efficient (DSC), Hausdorff distance, and average surface distance.
Timepoint [2] 295692 0
From time of last MRI to time that contours are finalised and analysed
Primary outcome [3] 295693 0
Development of atlas of the female pelvis using a series of MRI and CT images
Timepoint [3] 295693 0
From time of last MRI to time that contours are finalised and analysed
Secondary outcome [1] 313172 0
Accuracy of MRI based radiotherapy dose calculations assessed by comparison to current gold-standard dose calculations.
Timepoint [1] 313172 0
Assessed by comparison to CT based dose calculations following completion of planning of all patients
Secondary outcome [2] 316242 0
Generation of advanced MRI sequence database through compilation of all MRI study data and comparison of advanced MR sequences to standard MR sequences.
Timepoint [2] 316242 0
From time of last MRI to time that contours are finalised and analysed
Secondary outcome [3] 316464 0
Primary outcome - Development of autogenerated contours using an automated algorithm for cervix contours using atlas-based deformable image registration
Timepoint [3] 316464 0
From time of last MRI to time that contours are finalised and analysed
Secondary outcome [4] 316465 0
Primary Outcome - Time taken to create autogenerated vs gold-standard contours
Timepoint [4] 316465 0
From time of last MRI to time that contours are finalised and analysed

Eligibility
Key inclusion criteria
Eligible patients will have a gynaecological cancer for which they have been recommended a course of radiotherapy to the pelvis, in addition to:
1. Aged older than 18 years
2. ECOG 0-3
3. Histological diagnosis of malignant gynaecological tumour, including
a. Squamous cell carcinoma
b. Adenocarcinoma
c. Adenosquamous cell carcinoma
d. Endometrial carcinoma
e. Melanoma
f. Malignant mesenchymal tumours
g. Undifferentiated carcinomas
4. Written informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Contraindication for MRI
a. Cardiac pacemaker or defibrillator
b. Non MRI compatible implants
i.Metal rod, screw or plate
ii Aneurysm clip
iii Artificial heart valve
iv Cochlear implant
v Intravascular stent
c. Non-MRI compatible metallic foreign body
i Metallic fragment in the eye
ii Bullet or shrapnel injury
d. Severe claustrophobia
2. Prior hysterectomy
3. Women who are pregnant and the human foetus
4. Children and/or young people (ie. <18 years)
5. People with an intellectual or mental impairment
6. People highly dependent on medical care

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
This is a pilot study and the statistical considerations regarding the number of participants was decided based on relevant published literature and clinical input on expected patient recruitment and time frames.
Statistical analyses of outcomes are as follows;
- A gold standard contour dataset will be generated with use of the STAPLE algorithm which generates a weighted average position of contours, to determine a consensus volume from all observers.
- Variability between manual contours will be computed using several metrics, including DSC, Hausdorff distance, and average surface distance. Hypothesis 1 will be confirmed if the automatic contours are within the inter-rater variability of the expert contourers. A DSC greater than 0.7 is expected as a minimum performance from our previous studies and current literature.
- The time taken to manually generate the contours (Aim 1) will be compared to the time taken to generate the auto-contours (Aim 2) in order to provide an estimation of the clinical time-saving impact the auto-contouring software would provide
- A conjugate CT(electron density)/MRI atlas set will be developed from the MRI and CT treatment planning images. After mapping of the MRI atlas developed for auto-contouring, the same transformation and deformation will be applied to the electron density atlas to generate a pseudo-CT. DRRs will also be generated using standard radiotherapy treatment planning software for both the pseudo-CTs and the true CTs.
- A chi analysis will be undertaken for the calculation error. The hypothesis that Radiotherapy dose calculations using Pseudo-CTs, generated from MRI, are similar to using actual CT will be considered accepted if this chi criteria is >95% of voxels for all patients.
- The optimisation error will also be assessed with dose and radiobiological metrics, utilising software developed by PI Holloway
- A database of advanced MRI sequences will be developed. The hypothesis that advanced MRI sequences provide superior anatomical and physiological information for radiotherapy planning will be considered proven if for at least one advanced MRI sequence the image quality score is higher than or the variability in expert contours is reduced from that of the diagnostic gold standard.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 3505 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 3506 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 3507 0
St George Hospital - Kogarah
Recruitment hospital [4] 3508 0
Westmead Hospital - Westmead
Recruitment hospital [5] 3509 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [6] 4188 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 9270 0
2170 - Liverpool
Recruitment postcode(s) [2] 9271 0
2298 - Waratah
Recruitment postcode(s) [3] 9272 0
2217 - Kogarah
Recruitment postcode(s) [4] 9273 0
2145 - Westmead
Recruitment postcode(s) [5] 9274 0
2560 - Campbelltown
Recruitment postcode(s) [6] 10103 0
4029 - Royal Brisbane Hospital

Funding & Sponsors
Funding source category [1] 290806 0
Hospital
Name [1] 290806 0
Liverpool Cancer Services Trust Fund
Address [1] 290806 0
1 Elizabeth St, Liverpool NSW 2170
Country [1] 290806 0
Australia
Primary sponsor type
Individual
Name
Dr Karen Lim
Address
Liverpool Cancer Therapy Centre
1 Elizabeth St, Liverpool NSW 2170
Country
Australia
Secondary sponsor category [1] 289493 0
None
Name [1] 289493 0
Address [1] 289493 0
Country [1] 289493 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292432 0
South Western Sydney Local Health District
Ethics committee address [1] 292432 0
Research and Ethics Office
Locked Bag 7103
Liverpool BC
NSW 1871
Ethics committee country [1] 292432 0
Australia
Date submitted for ethics approval [1] 292432 0
Approval date [1] 292432 0
06/08/2013
Ethics approval number [1] 292432 0
HREC/13/LPOOL/264

Summary
Brief summary
The objective of this project is to develop methods to allow adaptive radiotherapy for cervical and other gynaecological cancers. Adaptive radiotherapy refers to incorporating patient specific changes over time to tailor the delivery of radiotherapy throughout the course of treatment. Who is it for? You may be eligible to join this study if you are aged 18 years or older, and have been diagnosed with a gynaecological cancer for which you have been recommended radiotherapy to the pelvis. Study details Participants will undergo usual radiotherapy treatment, with additional Magnetic Resonance Imaging (MRI) scans taken just prior to beginning treatment, and weekly during radiotherapy treatment until a maximum of 6 scans have been taken. The results of these scans will not alter the treatment received by participants. Data will be used to aid development of new radiotherapy treatment protocols. It is hoped that the findings of this study will lead to the development of the technical requirements required to implement adaptive radiotherapy using MRI. The potential benefit of this is to improve outcomes for women with gynaecological cancers, and reduce the rates of side effects from treatment.
Trial website
n/a
Trial related presentations / publications
n/a
Public notes

Contacts
Principal investigator
Name 55254 0
Dr Karen Lim
Address 55254 0
Liverpool Cancer Therapy Centre,
Locked Bag 7103
Liverpool BC
1871 NSW
Country 55254 0
Australia
Phone 55254 0
+61 (0)2 8738 5222
Fax 55254 0
Email 55254 0
karen.lim@health.nsw.gov.au
Contact person for public queries
Name 55255 0
Dr Karen Lim
Address 55255 0
Liverpool Cancer Therapy Centre,
Locked Bag 7103
Liverpool BC
1871 NSW
Country 55255 0
Australia
Phone 55255 0
+61 (0)2 8738 5222
Fax 55255 0
Email 55255 0
karen.lim@health.nsw.gov.au
Contact person for scientific queries
Name 55256 0
Dr Karen Lim
Address 55256 0
Liverpool Cancer Therapy Centre,
Locked Bag 7103
Liverpool BC
1871 NSW
Country 55256 0
Australia
Phone 55256 0
+61 (0)2 8738 5222
Fax 55256 0
Email 55256 0
karen.lim@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data will be analysed to show trends within the cohort
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary