Pre-Surgical Exercise for Soft Tissue Sarcoma

Overseen By Elizabeth Sachs, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Must not be taking: Steroids, Chemotherapy

Disqualifiers: Severe cardiopulmonary disease, Diabetes, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether specific exercises before surgery can improve movement and aid wound healing for individuals with soft tissue sarcoma in their arms or legs. Participants will be divided into two groups: one will receive standard radiation therapy, while the other will follow a special exercise plan (neoadjuvant exercise therapy) alongside their radiation treatment. The trial seeks individuals diagnosed with soft tissue sarcoma in their arms or legs who will undergo radiation and surgery. Those untreated with radiation in the affected area and able to commit to follow-up visits may be suitable candidates. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could enhance future treatment strategies.

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.

What prior data suggests that this exercise regimen is safe for patients with soft tissue sarcoma?

Research has shown that high-intensity exercise before starting treatment is generally safe for patients. One study found that this exercise improved health outcomes without causing harm. Additionally, moderate exercise (30-60 minutes a day) is well-tolerated after surgery for patients with sarcoma, even when they receive other treatments. This suggests that exercise plans, like the one being tested, are likely safe and manageable for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using neoadjuvant exercise therapy for soft tissue sarcoma because it combines standard radiation treatment with a tailored exercise regimen, which is a novel approach. Unlike traditional pre-surgical treatments that rely solely on radiation, this method aims to enhance the body's response to treatment by incorporating physical activity. Exercise might improve blood flow to the tumor, making radiation more effective and potentially leading to better surgical outcomes. This dual approach could offer patients better chances of recovery and improved overall health during treatment.

What evidence suggests that neoadjuvant exercise therapy might be an effective treatment for soft tissue sarcoma?

Research has shown that exercising before surgery can enhance bodily function and speed up recovery after surgery for soft tissue sarcoma. In this trial, participants in the Neoadjuvant Exercise Regimen arm will follow a prescribed exercise regimen alongside conventional neoadjuvant radiation therapy (NRT) before tumor resection. Early findings suggest that patients who exercise before surgery may experience improved limb function and better wound healing after tumor removal. This approach is unique because it incorporates pre-surgery exercise, which is not typically part of standard treatments. While further research is necessary, these early results offer promise for individuals with sarcomas in their arms or legs. ^{3 6 7 8 9}

Who Is on the Research Team?

William Eward, DVM, MD

Principal Investigator

Duke Orthopedic Oncology

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Neoadjuvant Exercise Therapy

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.

How Is the Trial Designed?

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+

University of North Carolina, Chapel Hill

Collaborator

Trials

1,588

Recruited

4,364,000+

Published Research Related to This Trial

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]

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]

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 38 patients with soft tissue sarcoma, preoperative therapy, including neoadjuvant radiotherapy and chemotherapy, demonstrated effective local control with only 5.2% experiencing local recurrence after surgery.

The study showed that preoperative treatment was safe and feasible, with most patients undergoing limb-sparing surgeries, and the results suggest that lower limb involvement and marginal excision are associated with worse disease-free survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant treatment of soft tissue sarcoma. Greto, D., Livi, L., Saieva, C., et al.[2021]

Preoperative chemotherapy has been shown to improve outcomes for certain pediatric sarcomas, leading to interest in applying similar strategies to adult soft tissue sarcomas, especially for tumors larger than 10 cm.

Despite the potential benefits of neoadjuvant chemotherapy in reducing the risk of recurrence and death, there is significant concern about the toxicity of these treatments and a lack of consensus on when they should be used in adult soft tissue sarcoma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy: Does Neoadjuvant or Adjuvant Therapy Improve Outcomes? Canter, RJ.[2018]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11718807/

A Narrative Review of the Assessment and Treatment ... This review article aims to examine the physical impairments commonly seen in patients living with sarcoma during and after cancer therapy and their treatment

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7464514/

Neoadjuvant Treatment Options in Soft Tissue Sarcomas HFRT has other advantages such as shorter overall treatment time, better adherence to therapy, and higher cost-effectiveness [23,24]. However, HFRT has been ...

3. withpower.com withpower.com/trial/phase-sarcoma-3-2021-b091c

Pre-Surgical Exercise for Soft Tissue Sarcoma Neoadjuvant Exercise Therapy is unique because it involves physical activity before surgery to potentially improve outcomes, unlike standard treatments that ...

4. cancer.gov cancer.gov/clinicaltrials/NCI-2020-01389

Effect of Exercise on Patient Outcomes in Patients with Soft ... This trial studies the effects of a preoperative exercise regimen on extremity function and wound healing in patients with soft tissue sarcoma undergoing ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04921917/exercise-and-soft-tissue-sarcoma

Exercise and Soft Tissue Sarcoma | Clinical Research Trial ... The purpose of this study is to evaluate the effect of a neoadjuvant (i.e. pre-treatment) exercise regimen on extremity function and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6354184/

Safety and feasibility of preoperative exercise training ... The principal finding of this study is that high‐intensity exercise training performed during neoadjuvant treatment was safe and feasible and led to improved ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04921917

Study Details | Exercise and Soft Tissue Sarcoma The purpose of this study is to evaluate the effect of a neoadjuvant (i.e. pre-treatment) exercise regimen on extremity function and postoperative wound ...

8. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2672386

Effect of Neoadjuvant Chemotherapy Plus Regional ... Survival was significantly improved by adding regional hyperthermia to neoadjuvant chemotherapy with an absolute difference at 5 years of 11.4% and at 10 years ...

9. mdpi.com mdpi.com/2072-6694/17/1/6

A Narrative Review of the Assessment and Treatment ... This review article aims to examine the physical impairments commonly seen in patients living with sarcoma during and after cancer therapy and their treatment