REtroperitoneal SArcoma Registry: an International Prospective Initiative

Titre officiel

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

Sommaire:

La chirurgie est actuellement la seule modalité de traitement potentiellement curative dans les cas de sarcome rétropéritonéal localisé. Les études disponibles sur les résultats oncologiques sont principalement de nature rétrospective et le sarcome rétropéritonéal localisé est reconnu comme une maladie rare. Par conséquent, l’analyse prospective de données de haute qualité est une priorité absolue. Les principaux objectifs de cette étude sont les suivants : – recueillir de façon prospective des données cliniques normalisées et du matériel radiologique et pathologique auprès des patients atteints de sarcome rétropéritonéal primaire traités par chirurgie dans des centres de référence; – évaluer les résultats chez les patients en fonction de la survie globale (SG), de la survie sans maladie (SSM), de l’incidence cumulative brute (ICB) de récidive locale (RL) et de métastases à distance (MD). Objectifs secondaires : – estimer l’efficacité et l’innocuité du traitement chirurgical, y compris de l’approche chirurgicale étendue du sarcome rétropéritonéal primaire; – évaluer de façon prospective l’incidence des thérapies multimodales (y compris la radiothérapie et la chimiothérapie); - cerner les caractéristiques cliniques, radiologiques et pathologiques qui peuvent influer sur les résultats oncologiques ou être utilisées comme des facteurs prédictifs de RL/MD/SG (il peut s’agir de biomarqueurs importants de la maladie); – utiliser le matériel pathologique recueilli pour des collaborations de recherche.

Description de l'essai

Primary Outcome:

  • Disease-free Survival
Secondary Outcome:
  • Overall Survival
  • Crude cumulative incidence of Local recurrence
  • Crude cumulative incidence of Distant metastasis
  • Morbidity
Retroperitoneal sarcomas (RPS) are rare tumours 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 tumour (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 tumours (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 favourable overall survival. These tumours 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 tumours 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 tumour 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 tumour 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.

Radiation Therapy is an option for RPS, especially in the preoperative setting, but currently the best evidence for efficacy comes form retrospective, mainly single-centre, 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 tumours. So far, there is no agreement on the optimal treatment strategy, even within reference centres, regarding the use of both chemo- and radiation therapy. In the recent years European and North-American centres 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 centres 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 tumours. 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 centres. 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 tumour-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 centres.

Each participating reference centre 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 tumour). 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 centre 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 centre 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 multicentre 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 centre. Data will be collected in a standardized database, stored by every participating centre, 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.

Voir cet essai sur ClinicalTrials.gov

Intéressé(e) par cet essai?

Imprimez cette page et apportez-la chez votre médecin pour discuter de votre admissibilité à cet essai et des options de traitement. Seul votre médecin peut vous recommander pour un essai clinique.

Ressources

Société canadienne du cancer

Ces ressources sont fournies en partenariat avec Société canadienne du cancer