Adaptive Radiation Therapy for Sarcoma

Overseen By Maya Douglas

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Disqualifiers: Pregnancy, Prior radiation, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

43 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new method of targeting neoadjuvant radiation therapy for individuals with high-grade soft tissue sarcoma, a cancer that forms in tissues connecting, supporting, or surrounding other structures and organs. Advanced imaging identifies the tumor's resistant areas, delivering stronger radiation doses to these parts. This approach could enhance treatment effectiveness by concentrating on the most resistant tumor sections. Individuals with a confirmed diagnosis of resectable high-grade soft tissue sarcoma in the deep trunk or extremity may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group.

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 this radiation therapy technique is safe for treating sarcoma?

Research has shown that neoadjuvant radiation is generally safe. One study found that a shorter treatment schedule for neoadjuvant radiation is safe. In another study, patients who underwent a five-day neoadjuvant radiation treatment experienced positive results. Although they faced some side effects, such as wound issues and moderate adverse effects, these were manageable over two years.

Overall, many patients have tolerated neoadjuvant radiation well. Strong evidence supports its effectiveness before surgery for soft tissue sarcoma, a type of cancer, making it a promising treatment option. ^{1 2 3 4 5}

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

Researchers are excited about adaptive radiation therapy for sarcoma because it offers a personalized approach to tackling tumors. Unlike traditional radiation therapies that apply a uniform dose to the entire tumor, this method uses pretreatment MRI scans to identify radioresistant cells within the tumor. By tailoring the radiation dose specifically—using techniques like intensity modulated radiation therapy (IMRT) and dose painting—this treatment targets the tougher cancer cells with higher precision, potentially increasing effectiveness while reducing damage to surrounding healthy tissue. This precision could lead to better outcomes and fewer side effects for patients.

What evidence suggests that neoadjuvant radiation might be an effective treatment for sarcoma?

Research has shown that radiation therapy before surgery, known as neoadjuvant radiation, can effectively treat sarcomas. One study found that this method controlled cancer at its original site for many patients, achieving a success rate of 86.2%. Another study demonstrated that this treatment extended patients' survival after their treatment. In this trial, participants will receive neoadjuvant external beam radiation using the intensity modulated radiation (IMRT) technique, which precisely targets stubborn cancer cells. Neoadjuvant radiation can also shrink tumors, making surgery easier and more successful. While some side effects may occur, the benefits often outweigh the risks, especially with this precise targeting approach. ^{6 7 8 9 10}

Who Is on the Research Team?

Arash O Naghavi, MD, MS

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with high-grade Soft Tissue Sarcoma of the deep trunk/extremity, who haven't had prior radiation in the area or complete surgical removal. They must be able to undergo surgery after radiation, have no distant cancer spread, and agree to use effective contraception. Pregnant women and those unable to get MRI scans are excluded.

Inclusion Criteria

My cancer can be surgically removed.

Stated willingness to comply with all study procedures and availability for the duration of the study

I had an MRI before starting radiation therapy, within the last 4 weeks.

Exclusion Criteria

I've had radiation in the same area as my current cancer.

My sarcoma is just under my skin or in it.

Participants with a medical condition or social situation that, at the discretion of the principal investigator, would preclude them from completion of the trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive neoadjuvant external beam radiation using the intensity modulated radiation (IMRT) technique with dose painting to 70 Gy, 60 Gy, and 50 Gy in 25 fractions for different tumor habitats

5 weeks

Follow-up

Participants are monitored for safety and effectiveness after radiation treatment

3 weeks

Surgery

Surgical resection of the tumor to assess margins and pathologic response

1 week

Long-term Follow-up

Participants are monitored for overall survival and disease control rate

Up to 8 months

What Are the Treatments Tested in This Trial?

Interventions

• Neoadjuvant Radiation

Trial Overview The HEAT study tests a targeted radiation therapy approach using IMRT guided by radiomic images from MRIs. The goal is to escalate doses precisely at tumor sites while sparing healthy tissue, before patients proceed to surgery.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 2 Interventions

Participants will receive pretreatment diagnostic MRIs to generate MRI habitats (images of tumor regions/subregions in different sequences). These images will identify radioresistant cells within the tumor to allow for more precise and higher doses of radiation to the resistant cells. Participants will then be treated with neoadjuvant external beam radiation by using the intensity modulated radiation (IMRT) technique, with dose painting (simultaneous integrated boost/SIB) to 70 Gray Units (Gy), 60 Gy, and 50 Gy in 25 fractions for habitats 1, 2, and 3, respectively.

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

Approved in European Union as Neoadjuvant Radiation for:

• Soft tissue sarcoma
• High-grade sarcoma
• Large or deep sarcomas

Approved in United States as Neoadjuvant Radiation for:

• Soft tissue sarcoma
• High-grade sarcoma
• Stage 2 and stage 3 soft tissue sarcomas

Approved in Canada as Neoadjuvant Radiation for:

• Soft tissue sarcoma
• High-grade sarcoma
• Large or deep sarcomas

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Viewray Inc.

Industry Sponsor

Trials

13

Recruited

1,100+

Published Research Related to This Trial

In a study of 181 patients with soft-tissue sarcoma treated with neoadjuvant radiation therapy (RT) alone, achieving a favorable pathologic response (fPR) was linked to a higher rate of complete surgical resection (R0) and a significant improvement in 5-year progression-free survival (PFS) rates (74% vs. 43%).

The study found that only 19% of patients achieved fPR, but this outcome was an independent predictor of better PFS, suggesting that improving fPR rates could enhance clinical outcomes for patients with this rare cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Favorable Pathologic Response After Neoadjuvant Radiation Therapy Alone in Soft-tissue Sarcoma. Palm, RF., Liveringhouse, CL., Gonzalez, RJ., et al.[2022]

In a study of 22 soft tissue sarcoma patients, preoperative adaptive radiotherapy (ART) was shown to be beneficial, particularly for tumors that grew more than 1 cm during treatment, as it helped ensure adequate tumor coverage and prevent underdosage.

The study found that while growing tumors had a significant risk of underdosage, shrinking tumors could allow for sparing of normal tissues, suggesting that ART could optimize treatment outcomes by adapting to tumor changes during radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The value of adaptive preoperative radiotherapy in management of soft tissue sarcoma. Dickie, C., Parent, A., Griffin, AM., et al.[2022]

In a study of 204 patients with stage II-B high-grade soft tissue sarcoma, adjuvant radiation therapy (RT) did not significantly improve local control rates compared to those who did not receive RT, with local control rates of 84% for RT and 80% for no RT.

The study identified that central tumor location and age over 50 years were independent predictors of poor local control, highlighting the need for tailored treatment strategies for these high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant radiation for stage II-B soft tissue sarcoma of the extremity. Alektiar, KM., Leung, D., Zelefsky, MJ., et al.[2017]

In a study of 17 patients with lower extremity soft tissue sarcoma undergoing preoperative radiotherapy, significant tumor volume changes were observed, with 41% of tumors growing and 59% shrinking during treatment.

Despite these volume changes, significant reductions in dosimetric coverage were rare, indicating that while monitoring tumor size is important, most patients did not require a change in their treatment plan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of tumor volume changes during preoperative radiotherapy for extremity soft tissue sarcoma: a new strategy of adaptive radiotherapy. De Lamarliere, MG., Lusque, A., Khalifa, JA., et al.[2023]

Preoperative external beam radiotherapy (RT) is typically administered in 25-28 fractions totaling 50-50.4 Gy over 5-6 weeks to improve local control of extremity soft tissue sarcomas, but this standard regimen can cause both acute and late toxicities.

Individualized treatment approaches, including hypofractionated regimens or combinations with chemotherapy and targeted agents, may enhance efficacy while potentially reducing long-term side effects, suggesting a need for flexibility in treatment based on ongoing research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative radiotherapy in soft tissue sarcoma: from general guidelines to personalized medicine. Haas, RL.[2018]

In a phase II study involving 52 patients with high-risk primary soft tissue sarcoma, a 5-day neoadjuvant radiotherapy regimen resulted in a low rate of grade ≥2 late radiation toxicity (16%) and a 32% incidence of major wound complications.

The study identified a potential germline biomarker that could predict major wound complications, which may help improve the safety and effectiveness of radiotherapy in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Trial of 5-Day Neoadjuvant Radiotherapy for Patients with High-Risk Primary Soft Tissue Sarcoma. Kalbasi, A., Kamrava, M., Chu, FI., et al.[2021]

Neoadjuvant chemotherapy, particularly with anthracyclines and ifosfamide, may help reduce the extent of surgery and improve limb salvage rates in high-risk soft tissue sarcoma patients, although evidence from phase III trials is lacking.

Current studies on neoadjuvant chemotherapy are varied and show conflicting results, but it remains a consideration for improving long-term outcomes in patients with high-risk disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Looking for answers: the current status of neoadjuvant treatment in localized soft tissue sarcomas. Nathenson, MJ., Sausville, E.[2020]

Preoperative chemotherapy with epirubicin and ifosfamide is feasible for patients with localized, high-risk soft tissue sarcomas, showing excellent dose intensity even in older patients, with 90% or higher in most cases.

While the addition of concurrent radiation therapy (RT) increased the rates of severe hematologic toxicities, such as grade 4 leucopenia and grade 3 or 4 thrombocytopenia, it remains a safe option, though it may lead to a higher incidence of wound complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Preoperative Chemotherapy With or Without Radiation Therapy in Localized Soft Tissue Sarcomas of Limbs and Superficial Trunk in the Italian Sarcoma Group/Grupo Español de Investigación en Sarcomas Randomized Clinical Trial: Three Versus Five Cycles of Full-Dose Epirubicin Plus Ifosfamide. Palassini, E., Ferrari, S., Verderio, P., et al.[2022]

Neoadjuvant radiotherapy (50Gy in 25 fractions) followed by surgery was well-tolerated in 36 patients with soft tissue sarcomas, with no severe acute radiation-induced toxicity observed.

A significant pathological response to the neoadjuvant radiotherapy was achieved in 61% of patients, but no specific predictive factors for this response were identified, indicating variability in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Predictive factors assessment of pathological response to neoadjuvant radiotherapy of soft tissue sarcomas]. Hanslik, N., Bourgier, C., Thezenas, S., et al.[2023]

The study found almost perfect agreement among sarcoma radiation oncologists in defining the gross tumor volume (GTV) for both lower and upper extremity cases, indicating a high level of consistency in tumor delineation practices.

While the clinical target volume (CTV) showed almost perfect agreement for the lower extremity, there was significant variability in the upper extremity CTV, likely due to differences in patient positioning between the planning CT and diagnostic MRI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variation in the gross tumor volume and clinical target volume for preoperative radiotherapy of primary large high-grade soft tissue sarcoma of the extremity among RTOG sarcoma radiation oncologists. Wang, D., Bosch, W., Kirsch, DG., et al.[2021]

Preoperative radiation therapy combined with brachytherapy or intraoperative radiation therapy allows for higher radiation doses to be safely delivered during surgery for retroperitoneal sarcomas, which can improve local control rates.

This approach aims to enhance the chances of curing the tumor while reducing damage to surrounding healthy tissues, addressing the historically poor prognosis associated with these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of radiation therapy in retroperitoneal sarcomas. Clark, JA., Tepper, JE.[2005]

In a study of 70 patients with extremity soft tissue sarcoma, a 20% increase in tumor size during preoperative radiotherapy did not negatively impact disease-specific or metastasis-free survival outcomes compared to patients whose tumors remained stable or decreased in size.

The findings suggest that tumor size increase during radiotherapy may not be a poor prognostic indicator, allowing for more conservative surgical approaches without compromising patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor size increase following preoperative radiation of soft tissue sarcomas does not affect prognosis. Delisca, GO., Alamanda, VK., Archer, KR., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4345136/

Long-term Oncologic Outcomes After Neoadjuvant ... Neoadjuvant RT was administered to 696 patients (6.1%). During the study period, preoperative RT use increased from 4% to nearly 15%. Male sex, tumor size ...

2. 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 ...

3. thegreenjournal.com thegreenjournal.com/article/S0167-8140(23)89829-2/abstract

Meta-analysis of 5-day preoperative radiotherapy for soft ... 5-day RT preoperative courses in sarcomas have acceptable complication rates, although some studies show a higher wound complication rate.

4. ascopubs.org ascopubs.org/doi/10.1200/GO.23.00110

Should Neoadjuvant Treatment Be Adopted More Widely ... ... trial from the Italian and Spanish Sarcoma groups. The authors also report an OS of 50%, a DFS rate of 63%, and a median DFS of 8 months ...

5. advancesradonc.com advancesradonc.com/article/S2452-1094(22)00192-0/fulltext

Effect of Favorable Pathologic Response After ... A more recent retrospective study of 330 patients, with two-third of patient treated with neoadjuvant RT alone, demonstrated improvements in OS ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12010885/

Feasibility and safety study of ultra-hypofractionated ... This feasibility study showed that hypofractionated neoadjuvant radiotherapy to margins-at-risk is safe. We have demonstrated early results to ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7189949/

A Phase 2 Trial of Five-Day Neoadjuvant Radiation ... A shorter five-day neoadjuvant RT regimen results in favorable rates of wound complications and grade ≥2 toxicity after two years follow-up. Five-day RT ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0972978X24000758

A randomized comparative clinical trial This study aims to prospectively assess and compare the early complications associated with radiotherapy in both techniques.

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

Balancing the dose: A meta-analysis of preoperative ... Complete pathologic response to neoadjuvant radiotherapy is predictive of oncological outcome in patients with soft tissue sarcoma. Anticancer Res. 2012; 32 ...

10. 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.