Pre-Surgical Exercise for Soft Tissue Sarcoma

Recruiting in Palo Alto (17 mi)

Overseen by William Eward, DVM, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Duke University

Must not be taking: Steroids, Chemotherapy

Disqualifiers: Severe cardiopulmonary disease, Diabetes, others

Stay on Your Current Meds

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing if doing specific exercises can help people with soft tissue cancer in their arms or legs recover better and heal faster after surgery.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on high-dose steroid therapy or have had recent chemotherapy, you may not be eligible to participate.

Is pre-surgical exercise therapy safe for soft tissue sarcoma patients?

Moderate-intensity exercise (30-60 minutes a day) is generally safe after surgery for sarcoma patients, even when they are receiving additional treatments like chemotherapy or radiotherapy. However, the safety of exercise before surgery is not well understood, and more research is needed to determine its impact. ^{1 2 3 4 5}

How is Neoadjuvant Exercise Therapy different from other treatments for soft tissue sarcoma?

Neoadjuvant Exercise Therapy is unique because it involves physical activity before surgery to potentially improve outcomes, unlike standard treatments that typically focus on surgery, chemotherapy, and radiotherapy. This approach aims to enhance physical function and quality of life, which is not a primary focus of traditional treatments. ^{1 4 6 7 8}

Research Team

William Eward, DVM, MD

Principal Investigator

Duke Orthopedic Oncology

Eligibility Criteria

Adults aged 18-85 with a confirmed diagnosis of soft tissue sarcoma in an arm or leg, who will undergo radiation and surgery as part of their treatment. Candidates must be able to attend follow-up visits and give consent. Excluded are those with severe heart/lung disease, poor blood flow in the affected limb, prior surgeries (except biopsy), uncontrolled diabetes, active deep vein thrombosis, pregnancy, or recent chemotherapy.

Inclusion Criteria

My blood flow in limbs hasn't been reduced by surgery.

My condition is at any stage.

Must be able to provide own consent

Exclusion Criteria

I have had surgery on a limb that affected its blood flow.

I have blood flow problems in my limbs due to vascular disease.

I have had radiation or surgery on the tumor area before this study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Radiation Therapy

Participants receive neoadjuvant radiation therapy (NRT) with or without an exercise regimen

10 weeks

Surgical Resection

Participants undergo surgical resection of the tumor

During surgery

Follow-up

Participants are monitored for wound complications and other outcomes post-surgery

24 weeks

Treatment Details

Interventions

• Neoadjuvant Exercise Therapy (Behavioural Intervention)

Trial Overview The trial is testing how pre-treatment exercise affects limb function and wound healing after surgery in patients with soft tissue sarcoma. Participants will engage in an exercise regimen before receiving standard care consisting of radiation therapy followed by surgical removal of the tumor.

Participant Groups

Group I: Neoadjuvant Exercise Regimen Experimental Treatment 1 Intervention

Subjects will receive conventional NRT in conjunction with a prescribed exercise regimen during the usual 10-week duration of NRT treatment prior to tumor resection.

Group II: Control Active Control 1 Intervention

Standard of care: neoadjuvant radiation therapy (NRT).

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Mary E. Klotman

Duke University

Chief Executive Officer since 2017

MD from Duke University School of Medicine

Michelle McMurry-Heath

Duke University

Chief Medical Officer since 2020

MD from Duke University School of Medicine

University of North Carolina, Chapel Hill

Collaborator

Trials

1,588

Recruited

4,364,000+

Dr. Peggy P. McNaull

University of North Carolina, Chapel Hill

Chief Medical Officer

MD from Louisiana State University School of Medicine

Dr. Lynne Fiscus

University of North Carolina, Chapel Hill

Chief Executive Officer since 2020

MD from Georgetown University, MPH from UNC

Findings from Research

Lower-extremities sarcoma patients should begin supportive rehabilitation and low-intensity physical activity after surgery to improve their quality of life, with a gradual increase in intensity during recovery.

Moderate-intensity resistance and endurance exercises (30-60 minutes per day) are safe for these patients post-surgery, even when undergoing adjuvant chemotherapy or radiotherapy, and a general goal of 150 minutes of combined exercise per week is achievable after 18-24 months of rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Practice of Physical Activity in the Setting of Lower-Extremities Sarcomas: A First Step toward Clinical Optimization. Assi, M., Ropars, M., Rébillard, A.[2020]

In a study of 66 patients with high-grade soft tissue sarcomas, those treated with neoadjuvant chemotherapy and preoperative radiotherapy showed promising long-term outcomes, with a 5-year overall survival rate of 71.2%.

Despite experiencing significant short-term toxicities (97% had grade 3 or higher), most of these resolved within a year, indicating that the treatment regimen, while harsh, can lead to favorable long-term results in high-risk cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results of a phase 2 study of neoadjuvant chemotherapy and radiotherapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: Radiation Therapy Oncology Group Trial 9514. Kraybill, WG., Harris, J., Spiro, IJ., et al.[2022]

The standard treatment for high-risk extremity soft tissue sarcomas (ESTS) typically involves a combination of surgery and radiation therapy, with chemotherapy sometimes added to improve outcomes.

This paper highlights the importance of chemotherapy and radiation therapy in reducing the risk of local or metastatic relapse in high-grade ESTs, suggesting that the pathological response to neoadjuvant treatment can provide valuable prognostic information.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the optimal (neo)adjuvant strategy of extremity high-risk soft tissue sarcomas (ESTS)? Kharmoum, S., Kharmoum, J., Chraibi, M., et al.[2023]

In a study of 3422 patients with large high-grade soft tissue sarcoma, the addition of radiotherapy reduced the risk of death by 35% and chemotherapy by 24% compared to surgery alone, highlighting the importance of adjunctive therapies in improving survival rates.

Combining chemotherapy and radiotherapy resulted in a 5-year survival rate of 62.1%, significantly higher than the 51.4% survival rate for either treatment alone, indicating that these therapies work synergistically regardless of their sequencing or timing relative to surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall survival advantage of chemotherapy and radiotherapy in the perioperative management of large extremity and trunk soft tissue sarcoma; a large database analysis. Mahmoud, O., Tunceroglu, A., Chokshi, R., et al.[2018]

Preoperative radiotherapy (RT) significantly increases the rates of R0 resection (90.1%) in patients with extremity soft tissue sarcoma (STS) compared to postoperative RT (74.9%) and no RT (79.9%), based on a study of 27,969 patients.

Both achieving R0 resection and receiving RT (either pre- or post-operative) are linked to improved overall survival (OS), highlighting the importance of RT in surgical management of STS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Radiotherapy is Associated with R0 Resection and Improved Survival for Patients with Extremity Soft Tissue Sarcoma Undergoing Surgery: A National Cancer Database Analysis. Gingrich, AA., Bateni, SB., Monjazeb, AM., et al.[2022]

Neoadjuvant treatment significantly improves the integrity of the fibrous capsule surrounding soft-tissue sarcomas, with 76.9% of treated tumors showing intact capsules compared to only 35.1% of untreated tumors.

The study found that neoadjuvant therapies, especially combinations like chemotherapy and radiotherapy, not only enhance the capsular integrity but also increase the width of the fibrous capsule and reactive zone, suggesting a stabilizing effect on the tumor periphery that could influence surgical decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant treatment improves capsular integrity and the width of the fibrous capsule of high-grade soft-tissue sarcomas. Grabellus, F., Podleska, LE., Sheu, SY., et al.[2012]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

The Practice of Physical Activity in the Setting of Lower-Extremities Sarcomas: A First Step toward Clinical Optimization. [2020]

2. Italy pubmed.ncbi.nlm.nih.gov

Neoadjuvant treatment of soft tissue sarcoma. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Long-term results of a phase 2 study of neoadjuvant chemotherapy and radiotherapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: Radiation Therapy Oncology Group Trial 9514. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

What is the optimal (neo)adjuvant strategy of extremity high-risk soft tissue sarcomas (ESTS)? [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Chemotherapy: Does Neoadjuvant or Adjuvant Therapy Improve Outcomes? [2018]

6. Ireland pubmed.ncbi.nlm.nih.gov

Overall survival advantage of chemotherapy and radiotherapy in the perioperative management of large extremity and trunk soft tissue sarcoma; a large database analysis. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Neoadjuvant Radiotherapy is Associated with R0 Resection and Improved Survival for Patients with Extremity Soft Tissue Sarcoma Undergoing Surgery: A National Cancer Database Analysis. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant treatment improves capsular integrity and the width of the fibrous capsule of high-grade soft-tissue sarcomas. [2012]