Intensive Pre-Operative Radiotherapy for Soft Tissue Sarcoma

(PRESTO Trial)

Not currently recruiting at 1 trial location

Overseen By Fabio Cury, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Disqualifiers: Prior malignancy, Lymph node involvement, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

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 for soft tissue sarcoma, a cancer that grows in soft tissues like muscle and fat. The study examines whether administering larger doses of radiation over a shorter period before surgery, known as hypofractionation, can be more effective and cause fewer complications than the usual method. It seeks participants with soft tissue sarcoma tumors on their arms, legs (above the knee), or trunk, who have not previously undergone radiation therapy and are eligible for surgery. Participants will receive five radiation treatments over approximately one and a half weeks, followed by surgery. As an unphased trial, this study provides a unique opportunity to explore innovative treatment options that could improve outcomes for future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that hypofractionated radiotherapy is safe for soft tissue sarcoma?

Research has shown that hypofractionated radiotherapy is generally safe for treating soft tissue sarcomas. This method uses fewer sessions with higher doses of radiation and achieves similar safety outcomes to traditional radiotherapy. Patients tolerate this treatment well, and it effectively controls tumors in the treated area. Although all treatments carry some risks, evidence suggests that hypofractionation does not increase the risk of severe side effects compared to standard treatments. This makes it a promising option for effective cancer care. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the hypofractionation technique for soft tissue sarcoma because it delivers a concentrated dose of radiation over a shorter period compared to the traditional approach. While standard treatments often involve daily sessions over several weeks, this method administers high-dose radiation in just five sessions across one and a half weeks. This not only shortens the treatment duration but also potentially enhances patient convenience and reduces hospital visits. Additionally, by targeting the tumor more precisely, it aims to minimize damage to surrounding healthy tissues, which could lead to fewer side effects.

What evidence suggests that hypofractionated radiotherapy is effective for soft tissue sarcoma?

Research has shown that hypofractionated radiotherapy, which participants in this trial will receive, effectively treats soft tissue sarcomas. Studies have found it prevents cancer from returning in the same area as effectively as standard radiation treatment, with similar side effects. In some cases, it even better prevents cancer recurrence. This treatment is also considered safe, with early reports indicating it does not damage nearby healthy tissues more than regular methods. Hypofractionated radiotherapy delivers higher doses of radiation in fewer sessions, potentially allowing patients to undergo surgery sooner. ^{1 3 5 6 7}

Who Is on the Research Team?

Fabio Cury, MD

Principal Investigator

Research Institute of McGill University Health Centre

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a specific type of cancer called soft tissue sarcoma, located above the knee or in the trunk. Candidates must have a tumor that can be surgically removed, no prior radiation therapy, and an ECOG score of 0-2 indicating they are relatively active. They cannot participate if they have other cancers (except certain skin cancers), lymph node involvement by cancer, previous radiation in the area to be treated, or major illnesses.

Inclusion Criteria

I have been active and mostly self-sufficient in the last 2 months.

I have not had any radiation therapy before.

Patient must be able to provide study-specific informed consent prior to study entry

Exclusion Criteria

I have had radiation therapy on the area that needs treatment now.

Other major medical illness deemed to preclude safe administration of protocol treatment or required follow-up

I have lesions below my knee.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment Evaluation

Standard pre-treatment evaluation including history, physical exam, radiology, and quality of life assessments

2 weeks

1 visit (in-person)

Radiation Treatment

Hypofractionated radiotherapy delivering five fractions of 7 Gy over one and a half weeks

1.5 weeks

5 visits (in-person)

Surgery

Surgery performed 4-6 weeks after completion of radiotherapy

4-6 weeks post-radiotherapy

Follow-up

Participants are monitored for acute and late toxicity, wound assessment, and quality of life

Up to 5 years

Multiple visits (in-person) at 1, 3, 6, 12, 18, 24 months, and yearly thereafter

What Are the Treatments Tested in This Trial?

Interventions

• Hypofractionation

Trial Overview The study is testing hypofractionated radiotherapy as pre-operative treatment for soft tissue sarcomas. This approach uses larger doses of radiation per session but fewer sessions overall compared to traditional methods. The goal is to deliver a higher effective dose more quickly and potentially reduce delays before surgery and wound complications.

How Is the Trial Designed?

Group I: Experimental : Short Course Pre-operative RadiothErapy Experimental Treatment 1 Intervention

As part of the planning process, you need to undergo a CT Simulation.It is special type of CT scan used to measure and design the radiation fields to precisely target the tumor.It is done at the Radiation Oncology Department at the MUHC. Some patients may be asked to also undergo an MRI Simulation, and the CT simulation. You may asked to provide a blood sample to ensure good kidney function prior to the CT and MRI scans. Both CT and MRI simulations are considered standard of care. Once the simulation studies are done, there is about a 2 week waiting period for radiation planning prior to starting the radiation treatments. The hypofractionation technique will be delivering five fractions (one fraction delivered every 2nd day) of 7 Gy daily of external beam radiotherapy (EBRT) over a period of one and half weeks for a total of 35 Gy. The treatment should last approximately 30 minutes. Once treatments are done, there is a 4 to 6 week wait for surgery.

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

Approved in European Union as Hypofractionation for:

• Soft tissue sarcomas
• Extremity soft tissue sarcomas
• Trunk soft tissue sarcomas

Approved in United States as Hypofractionation for:

• Soft tissue sarcomas
• Extremity soft tissue sarcomas
• Trunk soft tissue sarcomas

Approved in Canada as Hypofractionation for:

• Soft tissue sarcomas
• Extremity soft tissue sarcomas
• Trunk soft tissue sarcomas

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Published Research Related to This Trial

Neoadjuvant ultra-hypofractionation radiotherapy for soft tissue sarcoma shows a low wound complication rate of 30%, indicating it is a safe treatment option.

The treatment also demonstrates high efficacy with an 87% R0 resection rate and a 96% local control rate over two years, suggesting it effectively prepares patients for surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative ultra-hypofractionation radiotherapy in extremity/trunk wall soft tissue sarcoma - A meta-analysis of prospective studies. Kao, YS.[2023]

In a phase II study involving 32 patients with soft tissue sarcomas, a 5-fraction hypofractionated preoperative radiation therapy regimen resulted in no local recurrences and a 3-year overall survival rate of 82.2%.

While the treatment showed excellent local control and survival outcomes, 25% of patients experienced major acute postoperative wound complications, indicating a need for careful monitoring of toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is 5 the New 25? Long-Term Oncologic Outcomes From a Phase II, Prospective, 5-Fraction Preoperative Radiation Therapy Trial in Patients With Localized Soft Tissue Sarcoma. Bedi, M., Singh, R., Charlson, JA., et al.[2022]

In a study of 272 patients with soft tissue sarcomas, hypofractionated preoperative radiotherapy (5 Gy per fraction) demonstrated similar local control rates (81%) compared to conventional radiotherapy, suggesting it is an effective treatment option.

The treatment was associated with manageable early toxicity, with 42% of patients experiencing some form of treatment-related side effects, and only 7% requiring surgical intervention for complications, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative hypofractionated radiotherapy in the treatment of localized soft tissue sarcomas. Koseła-Paterczyk, H., Szacht, M., Morysiński, T., et al.[2018]

A phase 2 trial involving 120 patients with non-metastatic soft tissue sarcomas showed that a shorter, moderately hypofractionated preoperative radiotherapy regimen (42.75 Gy in 15 fractions) resulted in a major wound complication rate of 31%, which is comparable to the historical rate of 35% for standard treatment.

The study found no significant acute radiation toxicity (grade 3 or worse) during or shortly after treatment, indicating that this hypofractionated approach is safe and may offer a more convenient alternative to traditional radiotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated, 3-week, preoperative radiotherapy for patients with soft tissue sarcomas (HYPORT-STS): a single-centre, open-label, single-arm, phase 2 trial. Guadagnolo, BA., Bassett, RL., Mitra, D., et al.[2023]

Preoperative hypofractionated radiotherapy (HFRT) for soft tissue sarcomas (STS) shows comparable local control rates and similar or lower toxicity compared to traditional normofractionated radiotherapy, based on a systematic review of 13 studies including phase II trials and retrospective analyses.

Shortening the duration of preoperative radiotherapy may improve treatment adherence and cost-effectiveness without increasing adverse effects, making HFRT a promising option for patients with high-grade STS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative hypofractionated radiotherapy for soft tissue sarcomas: a systematic review. Roohani, S., Ehret, F., Kobus, M., et al.[2022]

In a study of 16 patients with soft tissue sarcoma, preoperative hypofractionated radiation therapy (30 Gy in 5 fractions) followed by immediate surgical resection resulted in no local failures and a median time of 20 days from biopsy to treatment completion.

Wound healing complications occurred in 31% of patients, with only 19% requiring additional surgery, indicating that this treatment approach has a favorable safety profile in terms of wound healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Outcomes of Preoperative 5-Fraction Radiation Therapy for Soft Tissue Sarcoma Followed by Immediate Surgical Resection. Parsai, S., Lawrenz, J., Kilpatrick, S., et al.[2022]

A survey of 47 sarcoma specialists revealed that local control is the most critical outcome for considering hypofractionated preoperative radiation therapy (RT) as standard care, with 78% willing to accept local control rates of 85% or higher based on phase II data.

Only 17% of providers require randomized phase III evidence to adopt hypofractionated RT, indicating a significant openness to change practice based on emerging data, but there is a need for consensus on acceptable thresholds for complications and toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating Thresholds to Adopt Hypofractionated Preoperative Radiotherapy as Standard of Care in Sarcoma. Valle, LF., Bernthal, N., Eilber, FC., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11987773/

Hypofractionated Radiotherapy for Soft Tissue Sarcomas Hypofractionated radiotherapy may offer similar local control and toxicity outcomes in the management of soft tissue sarcomas (STS) compared to standard ...

2. thegreenjournal.com thegreenjournal.com/article/S0167-8140(24)04306-8/abstract

Hypofractionated accelerated radiation dose-painting ... The HARD regimen for unresected STS resulted in excellent local control. HARD improved local control compared to standard fractionation. HARD was safe.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11110037/

Novel Definitive Hypofractionated Accelerated Radiation ... The purpose of this study was to evaluate the safety and efficacy of the HARD regimen for unresected STS patients. Methods and Materials.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03972930

Hypofractionated Radiotherapy for Soft Tissue Sarcomas One of the main challenges in treating sarcomas with radiation is the toxicity to normal structures around the sarcoma. Early reports suggest Hypofractionated ...

5. redjournal.org redjournal.org/article/S0360-3016(24)02975-4/abstract

Hypofractionated Preoperative Radiation Therapy for Soft ... There is a growing body of evidence supporting hypofractionation as safe and effective in the preoperative treatment of STS.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39192597/

Updated local control, late toxicities, and patient-reported ... Long-term follow up suggests that moderately hypofractionated preoperative RT for patients with STS is safe and effective.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03972930

Hypofractionated Radiotherapy for Soft Tissue Sarcomas One of the main challenges in treating sarcomas with radiation is the toxicity to normal structures around the sarcoma. Early reports suggest Hypofractionated ...