Sarcoma Retroperitoneal, Sarcoma,Soft Tissue
Conditions
Keywords
Surveillance, Radiology, Surgery, Quality of life, Cost-effectiveness
Brief summary
The SARveillance trial is an efficient, pragmatic, multi-centre, international, stratified, partially-randomised, patient-preference trial within a registry of high versus lower intensity radiological surveillance following primary resection of retroperitoneal, abdominal and pelvic soft tissue sarcoma. The trial design is stratified by sarcoma tumour grade (high/intermediate grade and low grade).
Detailed description
The SARveillance trial is an efficient, pragmatic, multi-centre, international, stratified, partially-randomised, patient-preference trial within a registry of high versus lower intensity radiological surveillance following primary resection of retroperitoneal, abdominal and pelvic soft tissue sarcoma. The trial design is stratified by sarcoma tumour grade (high/intermediate grade and low grade). Both high and lower intensity follow-up represent current practice in different centres across the trial delivery network, with variation at a centre and surgeon level. SARveillance is co-produced in deep collaboration with a patient advisory group. The delivery network is trans-continental including major sarcoma centres in Europe, Asia, and the Americas with central coordination from Istituto Nazionale Tumori, Milan, Italy and Birmingham Centre for Observational and Prospective Studies (BiCOPS) University of Birmingham, UK. For centres that would otherwise be precluded from participating in SARveillance due to institutional level data sharing restrictions, provision has been made for prearranged Individual Participant Data Meta-Analysis (IPDMA). The IPDMA essentially replicates the instruments and processes of SARveillance at a single site level and allows for the PI to provide data for meta-analysis at the close of SARveillance, rather than sharing real-time data with the SARveillance servers at the coordinating institutions. Adult patients undergoing primary resection for retroperitoneal, abdominal and pelvic sarcoma will be eligible for inclusion. The trial design is innovative and efficient, implemented as a trial within an international registry, and adopting concepts from the pragmatic REaCT trial design methodology. Patients that are willing to be randomised will be allocated in a 1:1 ratio to a high or lower intensity follow-up schedule. For patients that decline randomisation, the trial has patient preference arms to maximise insight into decision-making processes in the context of a rare disease and maximise participant recruitment. The primary outcome measure is quality of life, measured as emotional functioning (EF) up to 5 years after surgery, measured 3-monthly, using the questions relating to the EF domain of the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life questionnaire (QLQ-C30). Secondary outcomes for the trial will be overall survival up to 5 years after surgery, the cancer worry scale (EORTC library), health utility calculated using EuroQol Group EQ-5D-5L and cost-effectiveness health utility, measured using EQ-5D-5L. The primary outcome measure for low grade tumours is health utility. Pre-planned sub-studies will be conducted including an economic analysis, and validation study for a prognostic risk model.
Interventions
DIAGNOSTIC_TESTHigh-intensity radiological surveillance
The standard approach to surveillance imaging will be contrasted CT (IV and oral contrast) of the chest, abdomen and pelvis. All patients require radiological assessment of the chest, abdomen and pelvis at each surveillance round. Tolerance will be given in the protocol for selected patients where CT is not suitable to receive alternative imaging such as MRI or combination of MRI and CT. Uncontrasted CT imaging is permissible where renal toxicity or allergy from intravenous contrast is of concern. The use of plain radiography is not permitted as an alternative to CT imaging of the chest.
DIAGNOSTIC_TESTLower-intensity radiological surveillance
The standard approach to surveillance imaging will be contrasted CT (IV and oral contrast) of the chest, abdomen and pelvis. All patients require radiological assessment of the chest, abdomen and pelvis at each surveillance round. Tolerance will be given in the protocol for selected patients where CT is not suitable to receive alternative imaging such as MRI or combination of MRI and CT. Uncontrasted CT imaging is permissible where renal toxicity or allergy from intravenous contrast is of concern. The use of plain radiography is not permitted as an alternative to CT imaging of the chest.
Sponsors
University of Birmingham
University Hospital Birmingham NHS Foundation Trust
Royal Marsden NHS Foundation Trust
University Hospital Padova
Campus Bio-Medico University
The Netherlands Cancer Institute
KU Leuven
Heidelberg University
Dana-Farber/Brigham and Women's Cancer Center
Emory University
Mayo Clinic
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
The Cleveland Clinic
M.D. Anderson Cancer Center
University of Southern California
Ohio State University
Ottawa Hospital Research Institute
McGill University
Peter MacCallum Cancer Centre, Australia
Royal Prince Alfred Hospital, Sydney, Australia
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Patients that are willing to be randomised will be allocated in a 1:1 ratio to a high or lower intensity follow-up schedule. The trial design is partially randomised controlled and partly patient choice with patient preference arms (PPAs) for those that decline randomisation. Patients fulfilling the inclusion criteria and willing to be recruited will be stratified by tumour grade and then randomised to either high or lower intensity surveillance. Patients who decline randomisation will subsequently be offered the opportunity to participate within the PPAs. The PPAs will allow participating patients to choose either high or lower intensity surveillance arms. The data generated from the PPAs will not be included in the comparison of randomised arms. However, they will give important insight into patients' motivations in choosing high or lower intensity surveillance.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients (greater than 18 years) * Primary resection * Histologically confirmed retroperitoneal, abdominal or pelvic soft tissue sarcoma * R0/R1 resection * Eligible whether or not the participant undergoes neoadjuvant treatment
Exclusion criteria
* Metastatic disease at time of randomisation * Recurrent, metastatic or residual disease identified on baseline CT imaging (3-4 months post primary resection) * Reoperation for recurrent soft tissue sarcoma * Re-resection following previous inadequate surgery * R2 resection * Patients receiving adjuvant therapy that will delay, interrupt or render radiological surveillance unpredictable * Uterine sarcomas, gastrointestinal stromal tumour (GIST), fibromatosis, epithelial tumours, multifocal disease, sarcomas of bony origin * Patient declined to consent to data sharing with RESAR (unless in a centre contributing via pre-planned IPDMA)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Emotional Functioning | 5 years | Quality of life, assessed using Emotional Functioning domain (items 21-24) of the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life questionnaire (QLQ-C30). Each of the four items for this functional domain are scored between 1 and 4 (range: 3) to a total of 16 points, scaled to a total out of 100 using a validated formula from the EORTC scoring manual. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Health utility | 5 years | EuroQol Group EQ-5D-5L. Each of the five items are scored between 1 and 5 (range: 4) to a total of 25 points, scaled to a weighted index between 0 and 1 using a validated formula from the EUROQOL scoring manual. |
| Overall survival | 5 years | From time of primary surgery to death (all-cause mortality) or last follow up |
| Cancer worry scale | 5 years | Cancer-worry, assessed using four specific items from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life item library. Each of the four items are scored between 1 and 4 (range: 3) to a total of 16 points, scaled to a total out of 100 using a validated formula from the EORTC scoring manual. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Disease free survival | 5 years | Defined as time from primary surgery to radiological evidence of disease recurrence as defined by the revised-RECIST criteria, by definition will be decreased in the high intensity follow-up group. This will be adopted as a process measure rather than an outcome measure. |
Countries
Italy, United Kingdom
Contacts
Primary ContactMarco Fiore, MD
Backup ContactDaniela Salvatore, PhD
Outcome results
None listed