Are patient outcomes improved by surgery that uses a glowing dye to illuminate a cancerous tumour?
| ISRCTN | ISRCTN10805164 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10805164 |
| IRAS number | 324220 |
| Secondary identifying numbers | IRAS 324220, CPMS 58058, NIHR134276 |
- Submission date
- 02/10/2023
- Registration date
- 20/10/2023
- Last edited
- 17/12/2024
- Recruitment status
- Suspended
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English Summary
Background and study aims
Sarcomas are rare types of cancer, making up only 1% of all cancer cases in the UK, with about 5300 new diagnoses each year. What sets sarcomas apart is that they affect people across a wide range of ages, especially younger individuals. On average, patients are diagnosed with sarcomas at the age of 56. Unfortunately, the survival rates for sarcomas aren't great, with only about 65% of patients surviving five years after diagnosis. For those with higher grade sarcomas, the survival rate drops to 50%, and these numbers haven't improved much over the last 30 years.
The main treatment for sarcomas is surgery, with the goal of removing the tumor completely while preserving as much healthy tissue as possible. But here's the problem: during surgery, it's often challenging for the surgeon to distinguish between the tumor and healthy tissue by sight and touch alone.
One of the most critical factors in predicting a patient's outcome after surgery is the "resection margin." This margin is determined by pathologists who examine the removed tissue in a lab. A "negative margin" means that the tumor was completely surrounded by healthy tissue, suggesting that no cancer was left behind. On the other hand, a "positive margin" means that tumor cells are still present at the edge of the removed tissue. This is a bad sign because it's linked to a higher risk of cancer recurrence and poorer overall survival for the patient.
To improve outcomes for sarcoma patients, we're exploring a promising technology called fluorescence-guided surgery (FGS). FGS involves injecting a special dye called indocyanine green (ICG) into the patient before surgery. The tumor absorbs this dye, making it glow when viewed through a special camera during surgery. ICG has been used safely for years in other medical procedures. Recent research has shown that it can also help surgeons identify healthy tissue from diseased or poorly vascularized tissue during surgery.
A recent case series suggested that using FGS with ICG for high-grade sarcoma removal may reduce the rate of positive margins. Therefore, we're conducting a randomized controlled trial to investigate this further. This trial will include sarcoma patients of all ages and subtypes, except low-grade sarcomas that don't fluoresce. It's an important step toward improving outcomes for sarcoma patients by reducing the risk of positive margins, which are associated with worse short-term and long-term outcomes.
Our study aims to compare the rate of positive margins between FGS using ICG and standard surgery. This is crucial because positive margins are linked to a higher risk of cancer recurrence and poorer survival for patients. Ultimately, this research could lead to better surgical techniques and better outcomes for sarcoma patients.
Who can participate?
Any individual of any age who has been diagnosed with an intermediate to high-grade sarcoma in their bones or soft tissues, and can undergo surgery with the aim of curing the disease, can join the study. However, if someone is currently pregnant or breastfeeding, they won't be able to participate. Also, those with certain conditions won't be eligible. This includes individuals with tumors that have come back, tumors located in specific places like the inner organs, abdomen, or brain, anyone who's allergic to a substance called ICG, iodine, iodine dyes, or shellfish, and those who can't provide written consent for the study.
What does the study involve?
Once a patient has agreed to participate in the trial, the research team will use a method called "randomization" to decide which group they will be in. Both the patient and their doctor will be informed about this randomization outcome.
If a participant is placed in the group that gets the special surgery called "Fluorescence Guided Surgery using Indocyanine Green" (FGS with ICG), they will need to come to the hospital one day before their surgery.
On the other hand, participants in the control group will come to the hospital as inpatients either on the day before their surgery or on the day of surgery, depending on what their care team decides based on their specific medical needs.
For those in the FGS with ICG group, they'll come to the hospital a day before surgery to receive an injection of ICG dye. A nurse or doctor will give this injection through a vein, and it will be done 12-24 hours before the actual surgery.
For participants in the control group, they will receive the standard surgery. This involves surgeons using pre-operative images to locate the sarcoma in the body and using their hands to feel for the edges of the tumor to help with the removal.
However, participants in the FGS with ICG group will have an extra step during surgery. They will also use a special near-infrared camera that shows real-time images of the tumor, which has absorbed the ICG dye and glows. The surgeon will use these images to guide them during the tumor removal.
After the surgery, all participants will receive the usual post-operative care, just like any other patient in a standard care setting.
We will gather information about the surgery from the surgeon, including how long it took, how much of the tumor they think might still be in the patient, if there were any complications during surgery, and if using the camera had any impact on the surgeon's decisions.
Additionally, at baseline and 1, 3, 6, and 12 months after the surgery, participants will be asked to fill out some questionnaires like EQ-5D-5L/EQ-5D-Y and TESS/pTESS (if applicable) to help us track their progress and well-being.
What are the possible benefits and risks of participating?
There is no direct benefit to the participants for taking part in the trial. However, they may have access to a treatment (i.e., FGS using ICG) not normally provided as standard of care on the NHS. Patients in the future may potentially benefit from the information gained.
Both surgical methods for resection of sarcoma are used in NHS hospitals although FGS using ICG is not currently standard of care. Therefore the risk to patients taking part in the trial are no greater than their risks of having the surgery outside of the trial.
The burden to the participants are considered to be low. Aside from the surgery and follow up appointments at 6- and 12-months, which would be taking place in side or outside the trial, participants will be asked to complete some questionnaires. All participants will be asked to complete the quality of life questionnaire the EQ-5D-5L/ EQ-5D-Y and if they have had a sarcoma effect on of their extremities they will also be asked to complete the Toronto Extremity Salvage Score. Both questionnaires take about 10-15 minutes each to complete. The questionnaires will be completed at baseline, then at 1-, 3-, 6- and 12 months post surgery. Completing the questionnaires will not require extra hospital visits and will be sent to participants electronically.
Where is the study run from?
Newcastle Clinical Trials Unit, part of Newcastle University (UK)
When is the study starting and how long is it expected to run for?
July 2023 to April 2028
Who is funding the study?
1. NIHR Efficacy and Mechanism Evaluation Programme (UK)
2. Stryker (UK)
Who is the main contact?
Dr Stephanie Clutterbuck, steph.clutterbuck@newcastle.ac.uk
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-of-fluorescence-guided-surgery-for-sarcoma-sarcosight
Contact information
Scientific, Principal Investigator
Freeman Hospital
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
 ORCID ID |
0000-0001-6302-0269 |
|---|---|
| Phone | +44 (0) 191 213 9953 |
| kenneth.rankin1@nhs.net |
Public
Newcastle Clinical Trials Unit
1–4 Claremont Terrace
Newcastle University
Newcastle upon Tyne
NE2 4AE
United Kingdom
| Phone | +44 (0) 191 208 2525 |
|---|---|
| steph.clutterbuck@newcastle.ac.uk |
Study information
| Study design | Prospective two-arm open-label UK multi-centre randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment, Efficacy |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | SarcoSIGHT: a randomised controlled trial of fluorescence guided sarcoma surgery versus the standard of care |
| Study acronym | SarcoSIGHT |
| Study hypothesis | Fluorescence guided surgery (FGS) using indocyanine green (ICG) will reduce the unexpected positive margin (UPM) rate compared to the current standard of care (SoC) in patients with a histologically confirmed diagnosis of intermediate to high-grade bone or soft tissue sarcoma suitable for curative resection. |
| Ethics approval(s) |
Approved 21/09/2023, East Midlands - Nottingham 1 Research Ethics Committee (Health Research Authority, 2 Redman Place, London, E20 1JQ, United Kingdom; +44 (0)207 104 8000; Nottingham1.rec@hra.nhs.uk), ref: 23/EM/0212 |
| Condition | Patients with intermediate to high-grade bone or soft tissue sarcoma. |
| Intervention | Patients of all ages with a histologically confirmed diagnosis of intermediate to high grade sarcoma will be screened for eligibility. Eligible patients will be randomised in a 1:1 ratio to standard of care surgery versus fluorescence guided surgery (FGS) using Indocyanine Green (ICG), stratified by acceptable/close positive margin, sarcoma sub-type and treating centre. Randomisation will be done using Sealed Envelope, which is a central secure 24-hour web-based randomisation system with concealed allocation. This is an unblinded trial, however the histopathology staff and senior statistician will be blind to the surgery type received by the patient. This is to allow for blinded measurement and analysis of primary outcome. Patients randomised to standard of care will undergo surgical resection without pre-operative ICG administration or intra-operative fluorescence guidance. This will be performed as per the preferences of the operating surgeon but will be planned based on pre-operative imaging of the tumour, with appropriate skin mark-up. Patients randomised to the FGS arm will be administered 1mg/kg ICG intravenously 12-24 hours prior to the procedure. The skin will be marked based on pre-operative imaging as per standard of care and prepped using chlorhexidine to reduce background fluorescence from iodine-based solutions. The surgeon should then proceed with their planned resection as per standard of care. As they proceed with the resection they must use the Stryker SPY-PHI camera to image areas of interest; interpretation of images and any influence on operative decision making is at the discretion of the operating surgeon. If fluorescence changes the procedure at any time, further images (in white light, overlay mode, SPY fluorescence mode and colour segmented overlay mode) should be taken as appropriate, and this must be noted by the operating room team. Following the resection, both the resected specimen and the wound bed should be imaged (in all modes as above), and a decision made regarding the requirement for the removal of any further tissue. Resected specimens should then be sent to the pathology laboratory to undergo trimming and margin assessment by a histopathologist as per standard practice. Once the pathology report is available and discussed at the MDT, the surgical team will complete a pathology specific trial report form, documenting the margin status. In the case of a UPM, plans for re-excision should also be documented, and the results of this also added to the 6- month follow up CRF. It is important to note that a single case may have both acceptable and unexpected positive margins if a positive margin is present in an area not adjacent to the preserved structure; in this case it should be recorded as a UPM. |
| Intervention type | Mixed |
| Primary outcome measure | The unexpected positive margin (UPM) rate, defined as the percentage of patients with an unexpected positive margin. The margin status of each tumour will be taken from the pathology report for each patient enrolled in the trial. This will be recorded at six months post-surgery and will be classified according to the R classification system. Positive margins will be classified as the visualisation of tumour cells at the inked margin and will then be classified as acceptable or unexpected. The UPM rate for each arm will be defined by calculating the percentage of patients in that arm with a UPM on histopathological assessment of the resection specimen. If a negative margin is recorded, the size of the closest margin should be recorded in millimetres |
| Secondary outcome measures | Measured using patient records unless noted otherwise: 1. Rates of intra- and postoperative complications as recorded in the clinical notes. 2. Length of operation in minutes 3. Length of inpatient stay in days. 4. The percentage of operations in which the surgeon stated FGS changed their planned resection. 5. Rate of local recurrence at 12 months. 6. Rate of regional/distal recurrence at 12 months. 7. Rate of overall survival at 12 months. 8. Rates of adjuvant and neo-adjuvant therapies as per clinical notes. 9. Quality of life measured using EQ-5D-5L/EQ-5D-Y at baseline and months 1-, 3-, 6- and 12 months post surgery 10. Disability measured using the Toronto extremity salvage score (TESS)/ Paediatric Toronto extremity salvage score (pTESS) at baseline and months 1-, 3-, 6- and 12 months post surgery |
| Overall study start date | 01/07/2023 |
| Overall study end date | 30/04/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | All |
| Lower age limit | 0 Years |
| Upper age limit | 120 Years |
| Sex | Both |
| Target number of participants | 500 |
| Participant inclusion criteria | 1. Patients of any age 2. Capacity to provide written, informed consent (or legal guardian if <16 years of age) 3. Histologically confirmed diagnosis of intermediate to high grade sarcoma 4. Amenable to curative surgical resection |
| Participant exclusion criteria | 1. Tumour not amenable to curative resection or recommended for non-operative management 2. Recurrent tumours 3. Intracranial, retroperitoneal and visceral anatomical locations 4. Females that are currently pregnant (as confirmed by urine pregnancy test) 5. Females who are currently breastfeeding 6. Known allergy to ICG, iodine, iodine dyes or shellfish. 7. Unable to provide written, informed consent |
| Recruitment start date | 01/03/2024 |
| Recruitment end date | 30/04/2026 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Oxford Road
Manchester
M13 9WL
United Kingdom
Oswestry
SY10 7AG
United Kingdom
Bristol Road South
Northfield
Birmingham
B31 2AP
United Kingdom
Birmingham
B4 6NH
United Kingdom
Stanmore
HA7 4LP
United Kingdom
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
Beckett Street
Leeds
LS9 7TF
United Kingdom
Herries Road
Sheffield
S5 7AU
United Kingdom
Queens Medical Centre
Derby Road
Nottingham
NG7 2UH
United Kingdom
Southmead Road
Westbury-on-trym
Bristol
BS10 5NB
United Kingdom
Derriford Road
Derriford
Plymouth
PL6 8DH
United Kingdom
Barrack Road
Exeter
EX2 5DW
United Kingdom
London
SW3 6JJ
United Kingdom
Withington
Manchester
M20 4BX
United Kingdom
Seaway Parade Industrial Estate
Baglan
Port Talbot
SA12 7BR
United Kingdom
2 Eday Road
Aberdeen
AB15 6RE
United Kingdom
2-4 Waterloo Place
Edinburgh
EH1 3EG
United Kingdom
Gartnavel Royal Hospital
1055 Great Western Road Glasgow
Glasgow
G12 0XH
United Kingdom
A Floor - Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
United Kingdom
Upper Newtownards Road
Dundonald
Belfast
BT16 1RH
United Kingdom
Sponsor information
Hospital/treatment centre
Level 1 Regent Point
Regent Farm Road
Gosforth
Newcastle upon Tyne
NE3 3HD
England
United Kingdom
| Phone | +44 (0) 191 28 25959 |
|---|---|
| tnu-tr.sponsormanagement@nhs.net | |
| Website | https://newcastlejro.com/ |
"ROR" |
https://ror.org/05p40t847 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Stryker Corporation
- Location
- United States of America
Results and Publications
| Intention to publish date | 30/04/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The data will be the property of the CI, Co-Is and PIs. Publication will be the responsibility of the CI and will follow published guidelines. Authorship of all publications will be on a named individual authorship basis. For each publication all individuals who fulfil the authorship definition for the publishing journal or site will be included as individually named authors. Authorship order will be decided by the CI. Any disputes regarding authorship will be adjudicated by the TSC. Non-author contributors will be acknowledged as part of the ‘SarcoSIGHT trial group’. To safeguard the integrity of the main trial, reports of explanatory or sub-studies will not be submitted for publication without prior agreement from the Trial Management Group and Trial Steering Committee. It is planned to publish this trial in peer-reviewed articles and to present data at national and international meetings. Results of the trial will also be reported to the Sponsor, Funder and REC within one year of the end of trial. All manuscripts, abstracts or other modes of presentation will be reviewed by the Funder prior to submission. Trial participants will not be identified from any trial report. Trial participants will be informed about the trial results at the end of the trial via a lay summary sent to them in the post or by email. |
| IPD sharing plan | The data set will be the property of the CI. Any requests to access the final trial dataset may be considered under the NCTU data sharing policy. The final data set will be stored electronically in secure files on the Newcastle University server. Initially the final trial data set will be accessible only to the trial statisticians. Upon completion of the final analysis the final trial data set will be made available to the CI. Following completion of the analysis, relevant copies of the data will be sent to the PI at each site. It will remain the responsibility of the PI to ensure that the site-specific data set is securely stored and retained for the specified arching period. |
Editorial Notes
17/12/2024: Recruitment to the SarcoSIGHT trial was paused on 14th November 2024 and will remain paused for recruitment while certain MHRA requirements are being addressed. The study team are continuing to follow-up existing trial patients and to collect information from them. An update on the status of the trial will be provided as soon as it becomes available.
24/09/2024: Website link added.
24/04/2024: Cancer Research UK link added to plain English summary field.
12/02/2024: The recruitment start date was changed from 01/02/2024 to 01/03/2024.
08/11/2023: The recruitment start date was changed from 01/11/2023 to 01/02/2024.
03/10/2023: Trial's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).
