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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering radiation therapy to individuals with soft tissue sarcoma in their arms or legs. The researchers aim to determine if a lower radiation dose targeting a smaller area can control the cancer as effectively as standard treatment, while reducing long-term side effects. Individuals who have undergone surgery to remove their sarcoma and can start radiation within three months may qualify. This approach might provide a gentler treatment option with less impact on quality of life. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 prior data suggests that this method is safe for treating soft tissue sarcoma?

Research has shown that Intensity-Modulated Radiation Therapy (IMRT) can cause fewer severe side effects. One study found that only 12% of patients experienced serious side effects, compared to 18% with other treatments, suggesting that IMRT might be easier for patients to handle.

Another study examined the use of lower radiation doses targeting smaller areas for treating soft tissue sarcoma. This method aims to reduce side effects while still effectively combating cancer. Early results indicated that patients experienced fewer serious side effects with these lower doses.

Overall, evidence suggests that reduced-dose IMRT could be a safer option with fewer intense side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for soft tissue sarcoma?

Researchers are excited about the reduced-dose IMRT (Intensity-Modulated Radiation Therapy) for soft tissue sarcoma because it aims to limit radiation exposure compared to traditional high-dose radiation treatments. This approach reduces the radiation dose and volume, specifically targeting the tumor bed with precise margins. This precision may protect surrounding healthy tissues more effectively, potentially reducing side effects and improving patient quality of life. Overall, this method could offer a safer, yet still effective, alternative to existing radiation therapies for extremity soft tissue sarcoma.

What evidence suggests that reduced-dose IMRT is effective for soft tissue sarcoma?

Research has shown that Intensity-Modulated Radiation Therapy (IMRT) effectively treats soft tissue sarcomas. This trial will evaluate a reduced-dose IMRT approach for extremity soft tissue sarcoma (STS). Studies have found that IMRT can significantly reduce side effects. In one study, only 7.6% of patients experienced a local recurrence of cancer after five years of IMRT treatment. Another study demonstrated that IMRT results in low rates of serious thickening and scarring of connective tissue. Overall, the precision of IMRT helps protect healthy tissue while effectively controlling cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Kaled Alektiar, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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.

My cancer surgery removed all visible cancer, confirmed by a pathology review.

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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 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 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9985237/

Outcome of patients with soft tissue sarcomas ... Intensity-modulated radiation therapy (IMRT) is a conformal radiation technique and can significantly reduce toxicity [9]. In the context of ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2468294222001460

Real-world clinical outcomes with daily image-guided ... We report the clinical outcomes of patients with soft tissue sarcomas (STS) arising in extremities treated with image-guided intensity modulated radiotherapy ( ...

3. redjournal.org redjournal.org/article/S0360-3016(24)00687-4/fulltext

The IMRiS Trial: A Phase 2 Study of Intensity Modulated ... In conclusion, we have demonstrated that IMRT for limb sarcomas results in a low rate of grade ≥2 soft tissue fibrosis (subcutaneous tissue) at ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4178522/

Comparison of Local Recurrence With Conventional and ... In conclusion, based on this study, LR was only 7.6% at 5 years using IMRT in the management of primary extremity sarcoma, despite a preponderance of adverse ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2008.16.6249

Impact of Intensity-Modulated Radiation Therapy on Local ... This suggests that the precision with which IMRT dose is distributed has a beneficiary effect in sparing normal tissue and improving local control.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6689378/

Using Image-guided Intensity-modulated Radiotherapy on ... The incidence of grade 3 and 4 toxicities proved lower in patients treated with IMRT (12% vs. 18%, respectively; p=0.7). In terms of chronic AEs, 48% of ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04288375

Dose Reduction of Postoperative Radiation for Soft Tissue ... Study Overview. The investigators are doing this study to find out whether lowering the dose of postoperative radiation therapy and targeting a smaller area of ...

8. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.70049

Preoperative intensity‐modulated radiation therapy in lower ... In the current study, we evaluated the effect of the flap-sparing-IMRT technique on both acute and late toxicities, as well as functional and ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10997691/

Update on Dosing and Fractionation for Neoadjuvant ... While the low acute toxicity rate is promising; the local control rate of 86.2% compared to the 93% 5-year local control in the SR-2 study is a ...

10. thegreenjournal.com thegreenjournal.com/article/S0167-8140(25)04538-4/fulltext

Balancing the dose: A meta-analysis of preoperative ... These findings suggest that hypofractionation could also be safe in terms of long-term toxicity in the treatment of STS. The rationale for exploring ...