REtroperitoneal SArcoma Registry: an International Prospective Initiative

Retroperitoneal Sarcoma Clinical Trial

— RESAR  

Official title:

REtroperitoneal SArcoma Registry (RESAR): Prospective Collection of Primary Retroperitoneal Sarcoma Patient's Data, Radiological and Pathological Material for the TransAtlantic Retroperitoneal Sarcoma Working Group

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03838718
• Other study ID #: 201/16
• Status: Recruiting
• Start date: September 1, 2016
• Est. completion date: December 31, 2030

Study information

• Verified date: February 2019
• Source: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Contact: Alessandro Gronchi, MD
• Phone: +39022390
• Email: alessandro.gronchi[@]istitutotumori.mi.it
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Surgery is currently the only potentially curative treatment modality for localized retroperitoneal sarcoma (RPS). Available studies regarding oncologic outcomes are mainly retrospective in nature, and RPS are recognized as a rare disease. Therefore, prospective analysis of high quality data is a top priority.

Primary Objectives of this study are:

• to prospectively collect standardized clinical data and radiological and pathological material from primary RPS patients treated with surgery at reference centers.

• patient outcome will be evaluated in terms of overall survival (OS), disease-free survival (DFS), crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM).

Secondary Objectives:

• to estimate the efficacy and safety of surgical treatment, including extended surgical approach to primary RPS;

• to prospectively evaluate the impact of multimodality therapy, including radiation therapy and chemotherapy;

• to identify clinical, radiological and pathological characteristics that may influence the oncological outcome or may be used as predictors of LR/DM/OS. These may be important biomarkers of disease;

• to utilize collected pathological material for research collaborations.

Description:

Retroperitoneal sarcomas (RPS) are rare tumors accounting for 10-15% of all soft tissue sarcomas (STS). They arise between retroperitoneal organs and among vital structures (ie major abdominal vessels) in an anatomical compartment that is not readily accessible by physical examination. Four main histotypes account for about 80% of all cases: well-differentiated liposarcoma (WDLPS), dedifferentiated liposarcoma (DDLPS), leiomyosarcoma (LMS) and solitary fibrous tumor (SFT).

Compared to sarcomas at other anatomic sites, RPS are burdened by a higher local recurrence (LR) rate (50% at 5 years) and a poorer overall survival (OS) rate (50% at 5-years). The natural history of RPS as a whole group reflects the strong tendency of lipomatous tumors (WDLPS and DDLPS, which account for about 50% of RPS) to recur locally. Indeed, outcome of primary RPS is highly related to the histological subtype.

WDLPS are characterized by a relatively lower LR rate, negligible metastatic potential and a favorable overall survival. These tumors however, still may recur locally even years after the primary resection. Intermediate grade DDLPS are characterized by a strong tendency to recur locally and low metastatic potential. High grade DDLPS has a high risk of both local recurrence and distant metastasis. LMS are usually intermediate or high-grade tumors with a strong tendency to develop distant metastasis; with an adequate resection, it is relatively common to obtain a durable local control. Classic SFT usually fare well after surgery, with a low rate of local recurrence and distant metastasis.

Historically, surgery emerged as the only potentially curative option in the localized setting. In the last few years there has been lively debate as to how far should a surgeon resect in order to obtain a margin that could be considerate adequate. This issue is particularly challenging in this anatomical compartment where widening the surgical margins means resecting adjacent organs.

Since 2002 an 'extended' surgical approach has been proposed for primary RPS patients. The concept was that surgical margins could be improved by encompassing the tumor with en-bloc resection of adjacent organs. The aim was to obtain reduced local recurrence and improved survival. This approach has proven to be effective. In particular, this surgical approach has been supported by an experimental model, retrospective comparisons, pathology studies demonstrating adjacent organ involvement, and reports of high rates of residual tumor at re-excision after conventional (non-extended) primary surgery. Finally, this approach has been shown to be safe after both short and long term follow-up.

Radiotherapy is an option for RPS, especially in the preoperative setting, but currently the best evidence for efficacy comes form retrospective, mainly single-center, small size series. The results of such studies are controversial and high quality data are lacking. A randomized prospective study led by EORTC (STRASS) is ongoing but results are not expected for several years.

The role of chemotherapy in the localized disease is also still under investigation, especially in high grade tumors. So far, there is no agreement on the optimal treatment strategy, even within reference centers, regarding the use of both chemo- and radiotherapy. In the recent years European and North-American centers joined the panel of expert and this led to the formation of the TransAtlantic Retroperitoneal Sarcoma Working Group (TARPSWG), which now consists of more than 50 representatives from sarcoma centers from all over the world.

The aim of this collaboration is to expand the knowledge of the disease and formulate shared, standardized principles of treatment. A retrospective study has been carried out and recently published by the group to better define patients' outcome and prognostic factors after surgical resection of primary tumors. Other retrospective studies have been published focusing on post-relapse outcome, postsurgical morbidity and local recurrence treatment. This collaboration has also just recently led to the development of consensus guidelines for the treatment of primary and recurrent and metastatic RPS.

To take advantage of the group collaboration, TARPSWG promoted a prospective collection of clinical, radiological and pathologic data for RPS.

This study is aimed to prospectively collect standardized clinical data and radiological and pathological material from primary RPS patients treated with surgery at reference centers. Patient outcome will be evaluated in terms of overall survival (OS), disease-free survival (DFS), crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM).

STUDY DESIGN

This is a prospective, multicentric observational study under the supervision of TARPSWG (TransAtlantic Retroperitoneal Sarcoma Working Group) aimed to prospectively collect clinical data and prospectively store radiological and pathological material from patients affected by primary RPS treated with surgery.

Patients with a diagnosis of primary RPS who meet the eligibility criteria will be invited to participate to the current study.

Eligible patients will receive full information on the type of surgery proposed and on the data and material (radiological and pathological) that will be collected. Eligible and informed patients who give their consent to participate will be included in the Prospective Cohort Study (PCS) and will be followed-up prospectively.

A data collection form including patient and tumor-related factors, treatment variables, follow-up findings, development of and time to local recurrence and status at follow-up has been constructed and shared among all the participating centers.

Each participating reference center will individually be able to have access to both cross sectional imaging (CT or MRI images) and pathological material (a representative formalin block of the tumor). Whenever possible patient identifiers will be removed and patient confidentiality will be maintained. Any data shared between institutions will be deidentified and all measures to conceal patient identifiers will be taken.

Each center will be responsible for data-entry and storage of its own patients' data, radiological examinations and pathological samples. At the time of the analysis each center is committed to provide the requested updated data to the group.

Follow-up will be based on clinical evaluation and on cross sectional imaging (CT scan of the thorax and abdomen and/or contrast enhanced MRI of the abdomen) every 4 months for the first 2 years, every 6 months until the 5th year and yearly thereafter.

The overall duration of the project has not been fixed.

Sample size

The number of patients we plan to include in this prospective multicenter study will be 400 patients per year.

STATISTICAL CONSIDERATIONS Continuous variables will be summarized with appropriate summary statistics such as the mean, median, standard deviation, minimum and maximum. Categorical variables will be tabulated with frequencies and percentages. We will evaluate OS, DFS, CCI of DM and LR and correlate this with clinicopathologic factors such as histology, grade, type of surgery, etc.

DATA COLLECTION Data entry will be performed by every participating center. Data will be collected in a standardized database, stored by every participating center, and shared with the group at the time of future studies. Data shared between institutions will be deidentified and whenever possible all measures to conceal patient identifiers and maintain patient confidentiality will be taken.

ETHICS It is the responsibility of the investigator to have prospective approval of the trial protocol, informed consent forms, and other relevant documents, from the IRB/IEC. All correspondence with the IRB/IEC should be retained in the Investigator File.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: December 31, 2030
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• primary RPS operated on in the participating center;

• age>18 years at the time of the first treatment (pediatric patients can not be included)

• histological confirmed diagnosis according to the WHO criteria done on biopsy or surgical specimen by dedicated sarcoma pathologist;

• radiological examinations performed (contrast enhanced abdominal CT scan and/or MRI) prior to surgical resection;

• signed informed consent form;

• adequate compliance of the patients to the plan of follow-up

Exclusion Criteria:

• age<18 years;

• recurrent tumor;

• benign retroperitoneal tumors;

• serious psychiatric disease that precludes informed consent or limits compliance;

• impossibility to ensure adequate follow-up

Related Conditions & MeSH terms

• Retroperitoneal Sarcoma
• Sarcoma

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Center	Melbourne
Canada	Maisonneuve-Rosemont Hospital / University of Montreal	Montréal
Canada	The Ottawa Hospital	Ottawa
Canada	Mount Sinai / Princess Margaret	Toronto
France	Institut Curie	Paris
Germany	University Medical Center and Medical Faculty Mannheim, University of Heidelberg	Mannheim
Germany	Ludwig Maximilian University	Munich
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milan
Italy	Veneto Institute of Oncology	Padova
Italy	Ospedale Borgo Roma	Verona
Korea, Republic of	Samsung Medical Center	Seoul
Poland	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology	Warsaw
Slovenia	Institute of Oncology Ljubljana	Ljubljana
Spain	Hospital Clinico Universitario "Virgen de la Arrixaca"	Murcia
United Kingdom	University Hospital Birmingham (Queen Elizabeth)	Birmingham
United Kingdom	Royal Marsden Hospital	London
United States	Brigham and Women's Hospital/Dana-Farber Cancer Institute	Boston	Massachusetts
United States	The Ohio State University	Columbus	Ohio
United States	Winship Cancer Institute	Emory	Georgia
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Southern California (USC)	Los Angeles	California
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano	TransAtlantic Retroperitoneal Sarcoma Working Group

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Italy,  Korea, Republic of,  Poland,  Slovenia,  Spain,  United Kingdom, 

References & Publications (3)

Gronchi A, Strauss DC, Miceli R, Bonvalot S, Swallow CJ, Hohenberger P, Van Coevorden F, Rutkowski P, Callegaro D, Hayes AJ, Honoré C, Fairweather M, Cannell A, Jakob J, Haas RL, Szacht M, Fiore M, Casali PG, Pollock RE, Raut CP. Variability in Patterns of Recurrence After Resection of Primary Retroperitoneal Sarcoma (RPS): A Report on 1007 Patients From the Multi-institutional Collaborative RPS Working Group. Ann Surg. 2016 May;263(5):1002-9. doi: 10.1097/SLA.0000000000001447. — View Citation

MacNeill AJ, Gronchi A, Miceli R, Bonvalot S, Swallow CJ, Hohenberger P, Van Coevorden F, Rutkowski P, Callegaro D, Hayes AJ, Honoré C, Fairweather M, Cannell A, Jakob J, Haas RL, Szacht M, Fiore M, Casali PG, Pollock RE, Barretta F, Raut CP, Strauss DC. Postoperative Morbidity After Radical Resection of Primary Retroperitoneal Sarcoma: A Report From the Transatlantic RPS Working Group. Ann Surg. 2018 May;267(5):959-964. doi: 10.1097/SLA.0000000000002250. — View Citation

Trans-Atlantic RPS Working Group. Management of primary retroperitoneal sarcoma (RPS) in the adult: a consensus approach from the Trans-Atlantic RPS Working Group. Ann Surg Oncol. 2015 Jan;22(1):256-63. doi: 10.1245/s10434-014-3965-2. Epub 2014 Oct 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free Survival	Survival after surgery for primary RPS resection; any disease recurrence, local or distant, will be considered as an event at time of first radiological appearance.	10 years
Secondary	Overall Survival	Overall Survival computed from date of surgery	10 years
Secondary	Crude cumulative incidence of Local recurrence	CCI of Local recurrence computed from date of surgery, and defined as intrabdominal recurrent disease after complete resection	10 years
Secondary	Crude cumulative incidence of Distant metastasis	CCI of distant metastasis computed from date of surgery, and defined as hepatic recurrence and / or extrabdominal recurrent disease	10 years
Secondary	Morbidity	Postsurgical morbidity according to Clavien-Dindo classification	60 days

External Links

•   website of Trans-Atlantic Retroperitoneal Sarcoma Working Group