Reduced-Dose IMRT for Soft Tissue Sarcoma

Recruiting at 9 trial locations

Overseen By Kaled Alektiar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Positive margins, Superficial myxofibrosarcoma, Multifocal disease, Prior radiotherapy, Other cancer, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators are doing this study to find out whether lowering the dose of postoperative radiation therapy and targeting a smaller area of tissue for treatment is as effective as the standard dose and volume of radiation therapy to control soft tissue sarcoma after surgery. They also want to find out whether the study approach causes fewer and less severe long-term side effects than the standard approach.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, the use of chemotherapy is allowed and will be decided by your medical team.

What data supports the effectiveness of the treatment IMRT for soft tissue sarcoma?

Research shows that intensity-modulated radiation therapy (IMRT) helps improve local control of soft tissue sarcoma in the limbs after surgery, compared to older radiation methods. This means it can better target the tumor while reducing harm to nearby healthy tissues. ^{1 2 3 4 5}

Is reduced-dose IMRT generally safe for humans?

Research shows that intensity-modulated radiation therapy (IMRT) is generally safe for treating soft tissue sarcomas, with studies reporting low levels of side effects in patients. ^{2 3 6 7 8}

How is the treatment IMRT different from other treatments for soft tissue sarcoma?

Reduced-dose IMRT (Intensity-Modulated Radiation Therapy) for soft tissue sarcoma is unique because it precisely targets the tumor while minimizing damage to surrounding healthy tissues, potentially reducing side effects compared to traditional radiation therapies. This approach aims to maintain effective local control of the cancer while decreasing the risk of harm to nearby organs and tissues. ^{1 2 3 5 9}

Research Team

Kaled Alektiar, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with a confirmed diagnosis of soft tissue sarcoma in the arms or legs, who've had successful tumor removal surgery. They must start radiation within 3 months post-surgery or chemo and agree to use contraception if applicable. It's not for those with positive surgical margins, certain types of myxofibrosarcoma, multifocal disease, prior radiotherapy in the area, active treatment for another invasive cancer, or conditions making them unsuitable as per investigator judgment.

Inclusion Criteria

My sarcoma diagnosis in my arm or leg has been confirmed by a specialist.

I am a woman who can have children and have a recent negative pregnancy test.

I am 18 years old or older.

Exclusion Criteria

I am not receiving treatment for another type of invasive cancer.

Patients with any concurrent medical or psychiatric condition or disease which, in the investigator's judgment, would make them inappropriate candidates for entry into this study

My surgery for cancer left some cancer cells, as confirmed by a pathology review.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Postoperative radiation therapy to the primary site with a reduction in radiation dose and volume. The total dose will consist of 50 Gy in 25 fractions.

5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment. Imaging must take place at least annually for the first two years post-radiation.

2 years

Treatment Details

Interventions

• IMRT

Trial Overview The study tests whether a reduced dose and targeted area of postoperative radiation therapy are as effective as standard doses/volumes in controlling soft tissue sarcoma after surgery. The goal is also to see if this method results in fewer severe long-term side effects compared to the traditional approach.

Participant Groups

Group I: extremity soft tissue sarcoma (STS) Experimental Treatment 1 Intervention

Postoperative radiation therapy to the primary site with a reduction in radiation dose and volume. Specifically, the tumor bed plus a margin of 2cm craniocaudally and 1.5cm radially will be utilized to create the clinical target volume. The total dose will consist of 50 Gy in 25 fractions.

IMRT is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Intensity-Modulated Radiation Therapy for:

• Head and neck squamous cell carcinoma (HNSCC)
• Prostate cancer
• Breast cancer
• Lung cancer
• Brain tumors

Approved in European Union as Intensity-Modulated Radiation Therapy for:

• Head and neck squamous cell carcinoma (HNSCC)
• Prostate cancer
• Breast cancer
• Lung cancer
• Brain tumors

Approved in Canada as Intensity-Modulated Radiation Therapy for:

• Head and neck squamous cell carcinoma (HNSCC)
• Prostate cancer
• Breast cancer
• Lung cancer
• Brain tumors

Approved in Japan as Intensity-Modulated Radiation Therapy for:

• Head and neck squamous cell carcinoma (HNSCC)
• Prostate cancer
• Breast cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

In a study of 10 patients with lower extremity soft tissue sarcoma treated with adjuvant intensity-modulated radiation therapy (IMRT) after limb-sparing surgery, 40% of patients were disease-free, indicating potential effectiveness in maintaining local control of the disease.

The treatment was associated with manageable side effects, with only mild to moderate toxicity reported, such as edema and joint stiffness, and no severe complications like infections or nerve damage, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of limb salvage surgery with postoperative intensity-modulated radiation therapy for soft-tissue sarcoma and metastasis. Kawanami, K., Matsuo, T., Yuki, S., et al.[2022]

In a study of 16 patients with lower extremity soft tissue sarcoma, both sliding-window IMRT (SW-IMRT) and volumetric arc therapy (VMAT) provided excellent coverage of the target areas after surgery, but VMAT was more effective in reducing radiation exposure to critical organs-at-risk.

SW-IMRT was better at sparing the normal tissue corridor, which is important for minimizing the risk of lymphedema, highlighting the strengths of both techniques in postoperative radiotherapy planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric comparison of volumetric-arc therapy versus sliding window intensity-modulated radiotherapy in postoperative treatment for primary soft tissue sarcoma of the thigh. Ortiz González, I., Morera Cano, D., Roncero Sánchez, R., et al.[2020]

In a study of 41 adult patients with high-risk soft-tissue sarcoma of the extremity, intensity-modulated radiation therapy (IMRT) achieved a remarkable 5-year local control rate of 94%, indicating its efficacy in managing tumors while minimizing damage to surrounding healthy tissue.

Despite the challenges posed by large tumor sizes and positive margins in many patients, IMRT demonstrated excellent local control, suggesting that its precise dose distribution is beneficial for treating high-risk sarcomas without compromising tumor coverage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of intensity-modulated radiation therapy on local control in primary soft-tissue sarcoma of the extremity. Alektiar, KM., Brennan, MF., Healey, JH., et al.[2010]

In a study of 319 patients with primary nonmetastatic extremity soft tissue sarcoma, intensity-modulated radiation therapy (IMRT) was associated with a significantly reduced risk of local recurrence compared to conventional external-beam radiation therapy (EBRT), despite the IMRT group having more high-risk features.

IMRT showed a hazard ratio of 0.46 for local recurrence, indicating it is an effective treatment option for patients with challenging tumor characteristics, suggesting its potential benefits in improving outcomes for soft tissue sarcoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of local recurrence with conventional and intensity-modulated radiation therapy for primary soft-tissue sarcomas of the extremity. Folkert, MR., Singer, S., Brennan, MF., et al.[2022]

In a study of 31 adult patients with primary soft tissue sarcoma of the extremity, intensity modulated radiation therapy (IMRT) as an adjuvant treatment showed a high local control rate of 95% over a median follow-up of 23 months.

While some patients experienced side effects such as Grade 1 radiation dermatitis (71%) and Grade 1 neuropathy (28%), the overall morbidity profile was considered favorable, suggesting that IMRT is a promising option for high-risk sarcoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity modulated radiation therapy for primary soft tissue sarcoma of the extremity: preliminary results. Alektiar, KM., Hong, L., Brennan, MF., et al.[2007]

In a study of 59 patients with extremity soft tissue sarcomas, intensity-modulated radiotherapy (IMRT) resulted in late toxicities in 75% of patients, with the majority being mild to moderate (G1-2), including functional limitations and chronic pain.

A larger volume of healthy soft tissue surrounding the treatment area (greater than 3500 cm³) was associated with reduced late toxicities, suggesting that careful planning of radiotherapy can help minimize side effects for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of intensity-modulated radiotherapy toxicity in extremity soft tissue sarcomas patients: A role for irradiated healthy soft tissue volume? Bourdais, R., Achkar, S., Honoré, C., et al.[2022]

Postoperative intensity-modulated radiation therapy (IMRT) for patients with soft tissue sarcomas (STSs) in the extremities and trunk wall resulted in an impressive 5-year local control rate of 88.1%, especially for patients with negative surgical margins (90% local control) compared to those with positive margins (64.8%).

The treatment demonstrated low toxicity, with only 17.6% of patients experiencing edema and 9.8% experiencing joint stiffness, indicating that IMRT is a safe and effective option for managing STSs post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative intensity-modulated radiation therapy provides favorable local control and low toxicities in patients with soft tissue sarcomas in the extremities and trunk wall. Wang, J., Wang, S., Song, Y., et al.[2020]

In a study of 67 patients with head and neck soft-tissue sarcoma, image-guided intensity-modulated radiotherapy (IG-IMRT) resulted in a significantly lower locoregional relapse rate of 21% compared to 70% for conventional radiation therapy (CRT), indicating better efficacy for IG-IMRT.

Patients treated with IG-IMRT experienced fewer acute and chronic adverse events, suggesting that this technique not only improves treatment outcomes but also enhances patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using Image-guided Intensity-modulated Radiotherapy on Patients With Head and Neck Soft-tissue Sarcoma. Elsayad, K., Stockmann, D., Channaoui, M., et al.[2020]

In a study of 274 patients with nonmetastatic soft tissue sarcoma, those treated with postoperative intensity-modulated radiation therapy (IMRT) showed significantly better survival outcomes compared to those receiving two-dimensional radiotherapy (2D-RT), including higher rates of local recurrence-free survival (91.1% vs 80.8%) and overall survival (90.2% vs 81.0%).

Patients receiving IMRT also experienced fewer late toxicities, such as lower rates of joint stiffness (3.9% vs 12.3%) and no cases of severe fractures, suggesting that IMRT is not only more effective but also safer than traditional 2D-RT for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of outcome and toxicity of postoperative intensity-modulated radiation therapy with two-dimensional radiotherapy in patients with soft tissue sarcoma of extremities and trunk. Wang, J., Song, Y., Liu, X., et al.[2021]

References

1. India pubmed.ncbi.nlm.nih.gov

Clinical outcomes of limb salvage surgery with postoperative intensity-modulated radiation therapy for soft-tissue sarcoma and metastasis. [2022]

2. Australia pubmed.ncbi.nlm.nih.gov

Dosimetric comparison of volumetric-arc therapy versus sliding window intensity-modulated radiotherapy in postoperative treatment for primary soft tissue sarcoma of the thigh. [2020]

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

Impact of intensity-modulated radiation therapy on local control in primary soft-tissue sarcoma of the extremity. [2010]

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

Comparison of local recurrence with conventional and intensity-modulated radiation therapy for primary soft-tissue sarcomas of the extremity. [2022]

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

Intensity modulated radiation therapy for primary soft tissue sarcoma of the extremity: preliminary results. [2007]

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

Prospective evaluation of intensity-modulated radiotherapy toxicity in extremity soft tissue sarcomas patients: A role for irradiated healthy soft tissue volume? [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Postoperative intensity-modulated radiation therapy provides favorable local control and low toxicities in patients with soft tissue sarcomas in the extremities and trunk wall. [2020]

8. Greece pubmed.ncbi.nlm.nih.gov

Using Image-guided Intensity-modulated Radiotherapy on Patients With Head and Neck Soft-tissue Sarcoma. [2020]

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

Comparison of outcome and toxicity of postoperative intensity-modulated radiation therapy with two-dimensional radiotherapy in patients with soft tissue sarcoma of extremities and trunk. [2021]