Surveillance AFter Extremity Tumor surgerY (SAFETY)

McMaster University

Status: Active, not recruiting

Conditions: Soft Tissue Sarcoma; Lung Metastases

Treatments: Other: Frequency: Every 6 Months; Other: Frequency: Every 3 Months; Other: Imaging Modality: Chest CT; Other: Imaging Modality: Chest Radiograph (CXR)

Study type: Interventional

Funder types: Other

Identifiers

NCT03944798

GHRT02

Details and patient eligibility

About

Following treatment for a primary extremity sarcoma, patients remain at risk for the development of local and systemic disease recurrence. Metastasis (distant recurrence) to the lung is the most frequent single location of disease recurrence in sarcoma patients, occurring in almost half of all patients. Therefore, careful post-operative surveillance is an integral element of patient care. However, the detection of metastases does not necessarily affect long-term survival and may negatively impact quality of life. Surveillance strategies have not been well researched and have been identified as the top research priority in the extremity sarcoma field. Using a 2X2 factorial design to maximize efficiency and reduce overall trial costs, the SAFETY trial randomized 310 extremity soft-tissue sarcoma (STS) patients to determine the effect of surveillance strategy on overall patient survival after surgery for a STS of the extremity by comparing the effectiveness of both surveillance frequency (every 3 vs. every 6 months) and imaging modality (CT scans vs. chest radiographs).

Full description

Post-treatment STS surveillance is an integral element of patient care. Although earlier detection of metastatic disease may improve long-term survival, no study has yet provided definitive evidence to support this assumption. A thorough systematic review of the literature has identified only a single limited randomized controlled trial (RCT) evaluating this clinical question, and surveys of sarcoma surgeons have determined that surgeons typically follow their patients based on the way in which they were trained. The orthopaedic oncology field has identified sarcoma surveillance strategy as the top research priority in the field. In order to fill the evidence gap in sarcoma surveillance, a large international RCT is required. The investigators, therefore, propose the Surveillance AFter Extremity Tumor surgerY (SAFETY) trial. In preparation for the SAFETY trial, the SAFETY investigators have completed the following preparatory work: A) establishment of a worldwide research collaborative group that spans 6 continents; B) collection of data from international sarcoma patients to determine their perceptions of sarcoma surveillance and their willingness to participate in a study in which randomization will determine their follow-up protocols; and C) the organization of a large Protocol Development Meeting with international and multidisciplinary participation, including sarcoma patient involvement, where critical aspects of the protocol were discussed and finalized.

The international, multi-center SAFETY trial will determine the effect of surveillance strategy on patient-important outcomes after surgery for a STS of the extremity by comparing the effectiveness of both surveillance frequency (every 3 vs. every 6 months) and imaging modality (CT scans vs. chest radiographs). Ultimately, the SAFETY trial will provide the necessary evidence to develop evidence-based surveillance guidelines, and is poised to have a significant impact on the post-operative care and outcomes of extremity STS patients.

Enrollment: 310 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• The patient is 18 years of age or older;
• The patient has been diagnosed with a primary extremity grade II or III soft-tissue sarcoma (STS);
• The patient has undergone surgical excision of the tumor with curative intent and with no evidence of gross residual disease based on the pathology report;
• The patient has completed all planned neoadjuvant or adjuvant radiation and / or chemotherapy, if applicable;
• The tumor size is greater than or equal to (≥) five centimeters according to the pathology report or based on the pre-treatment MRI if neoadjuvant radiation and / or chemotherapy are given; and
• The patient provides informed consent.

Exclusion criteria

• The patient has metastases at initial presentation based on the radiology report of the initial thoracic imaging†;

• The patient has recently undergone surgical excision of a local recurrence;

• The patient has been diagnosed with one of the special sub-types, myxoid / round cell liposarcoma or extra-skeletal Ewing's sarcoma*;

• The patient has been previously diagnosed with a genetic syndrome with an elevated risk of malignancy, such as Li-Freumeni Syndrome‡;

• The patient has been previously diagnosed with a co-morbid condition that has a life expectancy of less than (<) one year;

• The site-specific surveillance protocol for the patient's disease is not compatible with the study protocol (i.e., regular planned whole-body imaging with positron emission tomography [PET] scans);

• Likely problems, in the judgment of the investigator, with the patient maintaining follow-up (with the specific reasoning requiring approval of the Methods Center);

• The patient is currently enrolled in a study that does not permit co-enrolment; and

• The patient has already been enrolled in the SAFETY trial.

  • A second CT scan may be required to confirm that indeterminate nodules are false positives before the patient can be enrolled (provided that the second CT scan shows no evidence of metastatic disease);

    • Myxoid liposarcoma and extra-skeletal Ewing's sarcoma have different metastatic patterns, which necessitate different surveillance protocols;

      • Individuals with Li-Freumeni Syndrome, or other genetic syndromes with an elevated risk of malignancy, appear to be at an elevated risk for radiation-induced cancers, so the use of CT scans should be limited.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Single Blind

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310 participants in 4 patient groups

Surveillance Arm I

Active Comparator group

Description:

Clinical assessment and chest radiograph (CXR) every six months for two years

Treatment:

Other: Imaging Modality: Chest Radiograph (CXR)

Other: Frequency: Every 6 Months

Surveillance Arm II

Experimental group

Description:

Clinical assessment and CXR every three months for two years

Treatment:

Other: Imaging Modality: Chest Radiograph (CXR)

Other: Frequency: Every 3 Months

Surveillance Arm III

Experimental group

Description:

Clinical assessment and chest computed tomography (CT) every six months for two years

Treatment:

Other: Imaging Modality: Chest CT

Other: Frequency: Every 6 Months

Surveillance Arm IV

Experimental group

Description:

Clinical assessment and chest CT every three months for two years

Treatment:

Other: Imaging Modality: Chest CT

Other: Frequency: Every 3 Months