Evaluation of Chest CT Versus Chest X-Ray for Lung Surveillance After Curative-Intent Resection of High-Risk Truncal-Extremity Soft Tissue Sarcoma

Not Applicable

Not yet recruiting

• Conditions: AJCC Grade 3 Sarcoma; Extraskeletal Ewing Sarcoma; Fibrosarcoma; Soft Tissue Sarcoma; Soft Tissue Sarcoma of the Trunk and Extremities; Alveolar Soft Part Sarcoma; Clear Cell Sarcoma of Soft Tissue; Leiomyosarcoma; Malignant Peripheral Nerve Sheath Tumor; Sarcoma
• Interventions: Procedure: Biopsy; Procedure: Chest Computed Tomography; Other: Quality-of-Life Assessment; Procedure: Chest Radiography; Other: Questionnaire Administration

• Registration Number: NCT06526897
• Lead Sponsor: ECOG-ACRIN Cancer Research Group

Brief Summary

This phase III trial compares chest computed tomography (CT) to chest x-ray (CXR) for lung surveillance after curative-intent resection of high-risk truncal-extremity soft tissue sarcoma. Currently, complete oncologic resection (with or without radiation therapy) is the standard of care for most high-risk soft tissue sarcoma that has not spread to other parts of the body (localized). However, despite curative-intent resection, 20-40% of patients will develop cancer that has spread from where it first started (primary site) to other places in the body (distant metastases), with the lungs being the most common site. Thus, lung surveillance is important for detection of lung metastases in order to facilitate timely treatment. Although there is general agreement about the usefulness of postoperative surveillance, consensus is lacking regarding the optimal modality for lung surveillance after curative-intent resection for high-risk soft tissue sarcoma. Current National Comprehensive Cancer Network guidelines recommend chest imaging with CT or CXR every 3-6 months for 2-3 years, then every 6 months for the next two years, and then annually after that for high-risk tumors. Data from across the United States and internationally indicate that there is considerable variation in clinical practice with regards to the use of CXR versus CT chest for lung surveillance. The information gained from this trial may allow researchers to determine the effectiveness of varying imaging modalities needed for optimal surveillance for patients with extremity or truncal soft tissue sarcoma.

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate whether the use of chest x-ray (CXR) for lung metastasis surveillance for the first five years after resection of a truncal or extremity soft tissue sarcoma is comparable to the use of chest computed tomography (CT) in terms of overall survival.

SECONDARY OBJECTIVES:

I. To evaluate whether the use of CXR for lung metastasis surveillance for the first five years after resection of a truncal or extremity soft tissue sarcoma is comparable to the use of CT in terms of disease-free survival.

II. To assess the primary and secondary objectives in the pediatric and adolescent and young adult subpopulations.

III. To assess overall survival difference between arms based on specific histiotypes in subgroup analysis.

IV. Patient-reported outcomes and quality of life IVa. Fear of cancer; IVb. Anxiety; IVc. Overall quality of life; IVd. Financial burden; IVe. Patient-reported direct and indirect costs associated with care received.

IMAGING OBJECTIVES (EXPLORATORY):

I. To assess whether CT-derived and CXR-derived radiomic features can be used to determine whether a pulmonary nodule is benign or malignant (metastasis).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo CXR every 3 months for years 1-2, and every 6 months years 3-5. Patients with a suspicious or new nodule undergo a CT and may undergo a biopsy on study.

ARM B: Patients undergo chest CT every 3 months for years 1-2, and every 6 months years 3-5. Patients with a suspicious or new nodule may undergo a biopsy on study.

Study Timeline

• Study First Submitted: 2023-10-10
• Status Verified: 2024-07
• Study First Submitted QC: 2024-07-24
• Last Update Submitted: 2024-07-24
• Study First Posted: 2024-07-30
• Last Update Posted: 2024-07-30
• Study Start: 2025-01-28
• Primary Completion: 2032-11-01
• Study Completion: 2032-11-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 1582

Inclusion Criteria

• Patient must be ≥ 1 and ≤ 85 years old on the day of randomization

• Patient must have and undergone curative-intent (R0 or R1) resection of an American Joint Committee on Cancer (AJCC) 8th edition stage III truncal or extremity soft tissue sarcoma

• Patient must have a high-risk (grade 2 or 3) soft tissue carcinoma according to the French Federation of Cancer Centers Sarcoma Group (FNCLCC)

  • Patients with the following histiotypes are eligible: dedifferentiated liposarcoma, pleomorphic liposarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma, myxofibrosarcoma, fibrosarcomatous dermatofibrosarcoma protuberant variant, spindle cell sarcomas, pleomorphic sarcoma, fibrosarcoma,extra-skeletal myxoid chrondrosarcoma, extraskeletal Ewing and Ewing-like sarcoma, sarcoma not otherwise specified (NOS), or other grade 2 or grade 3 sarcomas not further classified
  • Patients with a high-risk histiotype that is typically not graded, including adult pleomorphic rhabdomyosarcoma, synovial sarcoma, angiosarcoma, malignant peripheral nerve sheath tumor, alveolar soft part sarcoma, epithelioid sarcoma, or clear cell sarcoma are eligible

• Patient must have a tumor size ≥ 5 cm

• Patient must have had a R0 or R1 oncologic resection on final pathologic report

• Patient must have a baseline chest CT obtained within 30 days prior to randomization that is negative or detecting only non-suspicious nodules ≤ 4 mm

• Patients receiving preoperative or post-operative chemotherapy and/or radiotherapy for the primary tumor are eligible. However, all chemotherapy and/or radiotherapy must be completed prior to randomization

• Patient must not be pregnant due to the potential harmful risks associated with CXR and CT imaging to the unborn fetus

  • All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy
  • A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

• Patient must not have a chest wall/upper truncal primary tumor requiring locoregional surveillance with CT or magnetic resonance imaging (MRI)

• Patient must not have retroperitoneal, mesenteric/abdominal sarcoma

• Patient must not have a primary bone sarcoma (including osteosarcomas, Ewings sarcoma, or chondrosarcomas), desmoid tumor, gastrointestinal stromal tumor (GIST), Kaposi sarcoma, pediatric rhabdomyosarcoma, nor uterine sarcoma

• Patient must not have had a palliative or R2 resection

• Patient must not require routine cross-sectional imaging of the chest/lungs with CT/MRI/positron emission tomography (PET)

• Patient must not have participation in another clinical trial that is incompatible with this study surveillance schema and follow-up regimen

• Patient must have the ability to understand and the willingness to sign a written informed consent document. Pediatric patients (< 18 years of age) and patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible. Child assent must be obtained as appropriate in accordance with institutional guidelines

• Patient must be English speaking to be eligible for the quality of life (QOL) component of the study

  • NOTE: Sites cannot translate the associated QOL forms

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (CXR)	Biopsy	Patients undergo CXR every 3 months for years 1-2, and every 6 months years 3-5. Patients with a suspicious or new nodule undergo a CT and may undergo a biopsy on study.
Arm B (CT)	Chest Computed Tomography	Patients undergo chest CT every 3 months for years 1-2, and every 6 months years 3-5. Patients with a suspicious or new nodule may undergo a biopsy on study.
Arm B (CT)	Quality-of-Life Assessment	Patients undergo chest CT every 3 months for years 1-2, and every 6 months years 3-5. Patients with a suspicious or new nodule may undergo a biopsy on study.
Arm A (CXR)	Chest Computed Tomography	Patients undergo CXR every 3 months for years 1-2, and every 6 months years 3-5. Patients with a suspicious or new nodule undergo a CT and may undergo a biopsy on study.
Arm A (CXR)	Questionnaire Administration	Patients undergo CXR every 3 months for years 1-2, and every 6 months years 3-5. Patients with a suspicious or new nodule undergo a CT and may undergo a biopsy on study.
Arm B (CT)	Biopsy	Patients undergo chest CT every 3 months for years 1-2, and every 6 months years 3-5. Patients with a suspicious or new nodule may undergo a biopsy on study.
Arm A (CXR)	Chest Radiography	Patients undergo CXR every 3 months for years 1-2, and every 6 months years 3-5. Patients with a suspicious or new nodule undergo a CT and may undergo a biopsy on study.
Arm A (CXR)	Quality-of-Life Assessment	Patients undergo CXR every 3 months for years 1-2, and every 6 months years 3-5. Patients with a suspicious or new nodule undergo a CT and may undergo a biopsy on study.
Arm B (CT)	Questionnaire Administration	Patients undergo chest CT every 3 months for years 1-2, and every 6 months years 3-5. Patients with a suspicious or new nodule may undergo a biopsy on study.

Primary Outcome Measures

Name	Time	Method
Overall survival (OS)	up to 5 years	Overall Survival will be evaluated across arms. Survival will be evaluated at least annually from randomization to death or up to 5 years.

Secondary Outcome Measures

Name	Time	Method
Lung disease-free survival	up to 5 years	Lung disease-free survival is defined as time from randomization to time of distant lung recurrence. New invasive primary cancer or death from any cause will be censored At each follow-up surveillance examination, data will be collected on symptoms, lung imaging results, and any additional examinations or procedures performed for suspected recurrence. Histopathologically-confirmed recurrences and deaths will be reported at the time of the event.
Fear of cancer as measured by a modified Psychological Consequences Questionnaire (PCQ):	baseline and every 6 month up to 5 years	Fear of cancer associated with care received among those assigned to the CT arm compared to the CXR arm Will be measured using a Modified PCQ Response levels are rated on a four-point Likert scale from 0 (not at all) to 3 (quite a lot of the time). .; The sum of scores results in a total fear score between 0 and 36. Higher scores indicate more psychological dysfunction.
Financial toxicity from the Comprehensive Score for Financial Toxicity (COST)	baseline and every 6 month up to 5 years	Financial toxicity is defined as the rating given to a single item from the COST measure "My illness has been a financial hardship to my family and me". The rating is on a 5-point scale (0=Not at All 1=A little bit; 2=Somewhat; 3=Quite a bit; 4=Very Much) Lower scores indicate greater financial toxicity, while higher scores indicate better financial well-being.
Medical Expenditures Panel Surveys Reduction in material resources	baseline and every 6 month up to 5 years	Medical Expenditures Panel Surveys will be used to measure reduction in material resources associated with care received among those assigned to the CT arm compared to the CXR arm.; Reduction in material resources is a binary (Yes/No) outcome if any of the following responses is true: participant has taken on debt, sold a home, or declared bankruptcy;
PROMIS Global-10, Global Health Overall Quality of Life	baseline and every 6 month up to 5 years	Overall quality of life (OQOL) will be assessed among those assigned to the CT arm compared to the CXR arm. The PROMIS 10 adult, or parent proxy version for those under 18 years of age, will be collected at baseline and every 6 months, up to 5 years. OQOL will be modeled as the continuous outcome in the regression models.; PROMIS Global-10 is rated on a 5-point (as well as a single 11-point) rating scale. The results of the questions are used to calculate two summary scores: a Global Physical Health Score and a Global Mental Health score. These scores are then standardized to the general population, using the "T-Score". The average "T-Score" for the United States population is 50 points, with a standard deviation of 10 points. Higher scores indicate a healthier patient.
Care non-adherence	baseline and every 6 month up to 5 years	Care non-adherence will be measured by care non-adherence associated with care received among those assigned to the CT arm compared to the CXR arm. Care non-adherence is defined as any positive response to the care non-adherence questions: Did you forego or reduce medication doses due to to financial concerns? Did you forego tests or clinic visits due to financial concerns?
Patient-reported out-of-pocket and indirect costs of care	baseline and every 6 month up to 5 years	Will be measured by patient-reported out-of-pocket and indirect costs of care associated with care received among those assigned to the CT arm compared to the CXR arm. Patients were asked to estimate their out-of-pocket costs at the time of the clinic visit.; in addition to costs out-of-pocket costs for clinic visits, medication, and co-pays, indirect costs will include lost wages, care-giver substitutes, and transportation costs
Overall survival (OS) in the pediatric and adolescent and young adult subpopulations	up to 5 years	Overall Survival will be evaluated across arms in the pediatric and adolescent and young adult subpopulations Survival will be evaluated at least annually from randomization to death or up to 5 years .
Overall Survival (OS) based on specific histiotypes	Up to 5 years of imaging protocol	Will assess assess overall survival difference between arms based on specific histiotypes in subgroup analysis.
PROMIS Anxiety Score	baseline and every 6 month up to 5 years	Anxiety will be measured by anxiety associated with care received among those assigned to the CT arm compared to the CXR arm. The 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, or parent proxy version for those under 18 years of age, will be collected at baseline and every 6 months, up to 5 years during the relevant clinic visit. Anxiety will be modeled as the continuous outcome in the regression models.; Each item on the PROMIS Anxiety measure is rated on a 5-point scale (1=never; 2=rarely; 3=sometimes; 4=often; and 5=always) with a range in score from 7 to 35 with higher scores indicating greater severity of anxiety.
Lung disease-free survival in the pediatric and adolescent and young adult subpopulations	up to 5 years	Lung disease-free survival is defined as time from randomization to time of distant lung recurrence in the pediatric and adolescent and young adult subpopulations. New invasive primary cancer or death from any cause will be censored At each follow-up surveillance examination, data will be collected on symptoms, lung imaging results, and any additional examinations or procedures performed for suspected recurrence. Histopathologically-confirmed recurrences and deaths will be reported at the time of the event.