Surgery With or Without Radiation Therapy in Untreated Nonmetastatic Retroperitoneal Sarcoma
- Conditions
- Sarcoma
- Interventions
- Procedure: therapeutic conventional surgeryRadiation: 3-dimensional conformal radiation therapy
- Registration Number
- NCT01344018
- Brief Summary
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether surgery is more effective with or without radiation therapy in treating nonmetastatic retroperitoneal soft tissue sarcoma.
PURPOSE: This randomized phase III trial is studying radiation therapy followed by surgery to see how well it works compared with surgery alone in treating patients with previously untreated nonmetastatic retroperitoneal soft tissue sarcoma.
- Detailed Description
OBJECTIVES:
Primary
* To assess whether there is a difference in abdominal recurrence-free survival between retroperitoneal soft tissue sarcoma patients undergoing curative intent surgery alone and those undergoing preoperative radiotherapy followed by curative-intent surgery.
Secondary
* To assess whether there is a difference in metastasis-free survival, abdominal recurrence-free interval, and overall survival between these patients.
* To assess tumor response in patients undergoing preoperative radiotherapy.
* To assess toxicity of preoperative radiotherapy given prior to curative-intent surgery in these patients.
OUTLINE: This is a multicenter study. Patients are stratified according to institution and WHO performance status (0-1 vs 2). Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients undergo surgical resection of the tumor mass within 4 weeks following randomization.
* Arm II: Patients undergo 3-dimensional conformal radiation therapy (RT) or intensity-modulated RT within 8 weeks after randomization. RT continues 5 days a week for approximately 5.5 weeks. Patients undergo surgical resection of the tumor mass within 4-8 weeks after the completion of RT.
Tumor tissue, normal abdominal wall fat, and peripheral blood may be collected during surgery to identify new prognostic factors for translational research.
After completion of study therapy, patients are followed at day 60 post-surgery and every 6 months thereafter.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 266
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Preoperative radiotherapy followed by en-bloc surgery therapeutic conventional surgery 3D-CRT or IMRT to a dose of 50.4 Gy/28 daily fractions Surgery alone therapeutic conventional surgery En-bloc resection of surrounding tissues and organs when located within 1 to 2 cm from the surface tumor, even when not infiltrated. Preoperative radiotherapy followed by en-bloc surgery 3-dimensional conformal radiation therapy 3D-CRT or IMRT to a dose of 50.4 Gy/28 daily fractions
- Primary Outcome Measures
Name Time Method Number of Patients With Abdominal Recurrence or Death ARFS was measured from date of randomization to date of abdominal relapse or death, whichever occurred first, up to a maximum of 7 years. Abdominal recurrence was defined by one of the following events: local/abdominal or distant progressive disease during preoperative radiotherapy (as per RECIST 1.1), tumor or patient becoming inoperable (ASA score of 3 or involvement of superior mesenteric artery, aorta, or bone), peritoneal metastasis found at surgery, macroscopic residual disease left in at surgery (R2 resection), or local relapse (after macroscopically complete resection). Liver metastases were regarded as distant metastatic events. Patients with distant metastases were followed until local failure was detected. Patients without one of these events were censored at the date of last follow-up.
- Secondary Outcome Measures
Name Time Method Acute Toxicity Profile of Preoperative Radiotherapy. From date of randomization to the date of surgical procedure, prior to surgery The acute toxicity was assessed in randomized patients who received at least one dose of preoperative radiotherapy (RT). It follows Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 in the RT safety population, assuming the following classification:
* Grade 0 No event reported
* Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.
* Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL.
* Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.
* Grade 4 Life-threatening consequences; urgent intervention indicated.
* Grade 5 Death related to AE. For each item of the CTCAE, the worst grade of acute toxicity from the data of randomization prior to surgery was takenPerioperative Complications From the date of surgery, up to 60 days following surgery Adverse events and side effects possibly related to surgery were assessed according to the Dindo's classification. This scales the observed side effects as Grade 0 No event Grade I Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions Grade II Requiring pharmacological treatment with drugs other than such allowed for grade I complications.
Grade III Requiring surgical, endoscopic or radiological intervention Grade IV Life-threatening complication (including CNS complications) requiring IC/ICU-management Grade V Death of a patient For each item, the frequency of the worst grade of the observed toxicity was tabulated by treatment group.
The perioperative period commence at the time of surgery (at the time of the induction anaesthesia) to the complete closure of the wound.Late Complications From day 60 after surgery till end of follow-up, up to 7 years The late toxicities occurring more than 60 days after surgery. These were reported using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. This scales the observed toxicity from Grade 1 to 5, assuming the following classification:
* Grade 0 no event
* Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.
* Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL.
* Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.
* Grade 4 Life-threatening consequences; urgent intervention indicated.
* Grade 5 Death related to AE. Full AE reporting can be found in the Adverse Event Section.Tumor Response to Preoperative Radiotherapy Two weeks after completion of Pre-operative Radiotherapy, before Surgery For patients that received preoperative radiotherapy, the tumor response was assessed using RECIST 1.1. Response criteria were essentially based on a set of measurable lesions identified at baseline as target lesions, and followed at the end of the radiotherapy. Response was not the primary endpoint, so a confirmatory CT-scan was not mandatory.
Number of Patients With an Abdominal Recurrence ARFI was measured from the date of randomization to the date of abdominal relapse, up to a maximum of 7 years Abdominal recurrence was defined in the ARFS section. The following are considered competing events:
* death in the absence of abdominal failure
* distant metastases diagnosed before abdominal failure Patients without one of these events were censored at the date of last follow-up.Number of Patients With Metastases or Death Metastases free survival was measured from the date of randomization to the date of occurrence of distant metastases or death, whichever occurred first, up to a maximum of 7 years. Alive and metastases free patients will be censored at the date of last follow-up.
Number of Patients Alive Overall survival was measured from the date of randomization to the date of death, whatever the cause, up to a maximum of 7 years Alive patients were censored at the date of last follow-up. Causes of death were recorded and reported as a table.
Trial Locations
- Locations (37)
Radboud University Medical Center
🇳🇱Nijmegen, Netherlands
Radium Hospitalet
🇳🇴Oslo, Norway
U.Z. Gasthuisberg
🇧🇪Leuven, Belgium
Centro Di Riferimento Oncologico
🇮🇹Aviano, Italy
Institut Bergonie
🇫🇷Bordeaux, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Centre Leon Berard
🇫🇷Lyon, France
University Copenhagen
🇩🇰Herlev, Denmark
Dana-Farber Cancer Institute & Harvard Medical School
🇺🇸Boston, Massachusetts, United States
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
CHUM - Centre Hospitalier de l'Université de Montreal - Hopital Notre-Dame
🇨🇦Montreal QUEBEC, Quebec, Canada
Istituto Oncologico Veneto
🇮🇹Padova, Italy
Mount Sinai Hospital
🇨🇦Toronto, Ontario, Canada
Istituto Clinico Humanitas
🇮🇹Milano, Italy
Karolinska University Hospital
🇸🇪Stockholm, Sweden
Beatson-Gartnavel General Hospital
🇬🇧Glasgow, United Kingdom
Hospital General Vall d'Hebron
🇪🇸Barcelona, Spain
University Medical Center Groningen
🇳🇱Groningen, Netherlands
University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre
🇬🇧Bristol, United Kingdom
University College Hospital
🇬🇧London, United Kingdom
Royal Marsden Hospital - Chelsea, London
🇬🇧London, United Kingdom
Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Queen Elizabeth Medical Center
🇬🇧Birmingham, United Kingdom
Freeman Hospital
🇬🇧Newcastle, United Kingdom
Weston Park Hospital
🇬🇧Sheffield, United Kingdom
General Western Hospital
🇬🇧Edinburgh, United Kingdom
Leeds Teaching Hospitals NHS Trust - St. James'S University Hospital
🇬🇧Leeds, United Kingdom
Nottingham University Hospitals NHS Trust - City Hospital campus
🇬🇧Nottingham, United Kingdom
UniversitaetsMedizin Mannheim
🇩🇪Mannheim, Germany
Technische Universitaet Muenchen
🇩🇪Muenchen, Germany
Hospital Universitario San Carlos
🇪🇸Madrid, Spain
Universitaetsklinikum
🇩🇪Koeln, Germany
Klinikum der Universitaet
🇩🇪Muenchen, Germany
Maria Sklodowska-Curie Memorial Cancer Center
🇵🇱Warsaw, Poland
Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet (101)
🇧🇪Brussels, Belgium
The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
🇳🇱Amsterdam, Netherlands
Leiden University Medical Centre
🇳🇱Leiden, Netherlands