GRID Therapy for Sarcoma

Overseen By Erin Jennings

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: UNC Lineberger Comprehensive Cancer Center

Disqualifiers: Prior radiotherapy, Tumor resection, Non-healing wound, Lymphedema, Lupus, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients with extremity soft tissue sarcoma (STS) are at high risk of recurrence. Pre-operative radiotherapy is used to increase the safe removal of tumors and improve local control in these patients. Increasing the preoperative radiotherapy dose with standard techniques might lead to normal tissue toxicity and postoperative wound complications. GRID radiation therapy is a technique that may increases radiation dose with minimal added toxicity. It is hypothesized that GRID radiation dose will improve tumor response without increasing post-operative wound complications. While GRID has been used in many patients, there have been few formal studies to evaluate the safety and efficacy of the technique. In this study, a single priming dose of GRID will be administered to subjects with high-risk extremity soft tissue sarcoma prior to standard radiotherapy and tumor resection to determine the safety and clinical efficacy of the GRID dose. This single-arm pilot study will assess the safety of spatially fractionated grid radiation therapy (GRID) on 20 subjects with resectable extremity soft tissue sarcoma, followed by standard-of-care conventional radiotherapy (XRT) and tumor resection.

Do I need to stop my current medications for the GRID Therapy trial?

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

What data supports the effectiveness of the treatment GRID Therapy for Sarcoma?

Research shows that GRID Therapy, which involves delivering high-dose radiation in a grid pattern, has been effective in treating large and bulky tumors, including sarcomas. It has shown promising results in delaying tumor growth and achieving good pathologic responses, with an acceptable safety profile. ^{1 2 3 4 5}

Is GRID Therapy safe for humans?

GRID Therapy, also known as Spatially Fractionated Grid Radiation Therapy (SFGRT), has been used in clinical studies and shown to have an acceptable safety profile with low toxicity in treating large and bulky tumors. It has been reported to be safe in 26 patients with high-risk sarcomas and has shown promise in other studies as well. ^{1 2 4 5 6}

What makes GRID Therapy unique for treating sarcoma?

GRID Therapy is unique because it delivers high-dose radiation in a single session to large, bulky tumors, using a pattern that spares some healthy tissue. This approach can enhance the effects of traditional radiation therapy and potentially stimulate the immune system, offering a novel way to manage difficult-to-treat sarcomas. ^{1 2 3 4 5}

Research Team

Theodore K Yanagihara, MD. PhD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults over 18 with extremity soft tissue sarcoma, who can perform daily activities (ECOG status 0-2). They must have a biopsy confirming the diagnosis and agree to study procedures. Excluded are those with prior radiotherapy at the tumor site, complete tumor resection, serious wounds or bone fractures in the limb within 5 years, significant lymphedema, or certain autoimmune diseases.

Inclusion Criteria

Written informed consent was obtained to participate in the study and HIPAA authorization for the release of personal health information. Subjects are willing and able to comply with study procedures based on the judgment of the investigator.

I am 18 years old or older.

I can take care of myself but may not be able to do heavy physical work.

Exclusion Criteria

I have had a serious wound, ulcer, or bone fracture in the last 5 years.

I have had severe swelling in a limb that was treated.

I have a condition like lupus or Ehlers-Danlos that might react badly to radiation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

GRID Radiation Therapy

A single priming dose of GRID radiation therapy is administered to subjects with high-risk extremity soft tissue sarcoma

1 week

Standard Radiotherapy and Tumor Resection

Participants receive standard-of-care conventional radiotherapy followed by tumor resection

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of post-operative wound complications

6 months

Treatment Details

Interventions

• GRID Therapy

Trial Overview The trial tests GRID therapy—a radiation technique that may increase dose without added toxicity—on patients with high-risk sarcoma before standard radiotherapy and surgery. The goal is to see if GRID improves tumor response without increasing wound complications after surgery.

Participant Groups

Group I: Fractionated grid radiation therapy Experimental Treatment 1 Intervention

Subjects with resectable extremity soft tissue sarcoma received neoadjuvant grid radiation therapy (GRID), followed by standard-of-care conventional radiotherapy (XRT) and tumor resection.

GRID Therapy is already approved in United States for the following indications:

Approved in United States as GRID Therapy for:

• Extremity Soft Tissue Sarcoma

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Radiation Oncology Institute

Collaborator

Trials

3

Recruited

30+

Findings from Research

Proton spatially fractionated GRID radiation (SFGRT) was successfully used to treat 10 patients with large tumors that could not be treated with photon GRID due to critical organ proximity, showing an 80% rate of tumor regression or local symptom improvement.

The treatment was well-tolerated, with 50% of patients experiencing only mild acute side effects, indicating that proton SFGRT is a feasible and effective alternative for patients who cannot receive photon-based treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early clinical results of proton spatially fractionated GRID radiation therapy (SFGRT). Mohiuddin, M., Lynch, C., Gao, M., et al.[2022]

Spatially fractionated radiotherapy (GRID) has shown promising results in treating large, high-risk tumors, particularly soft tissue and osteosarcomas, by allowing for safe dose escalation and enhancing the effects of conventional radiotherapy.

In a study of 26 patients, incorporating a single fraction of GRID radiation before standard treatment resulted in excellent pathologic responses and demonstrated an apparent safety profile, suggesting its potential as an effective treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spatially Fractionated Radiotherapy (GRID) Prior to Standard Neoadjuvant Conventionally Fractionated Radiotherapy for Bulky, High-Risk Soft Tissue and Osteosarcomas: Feasibility, Safety, and Promising Pathologic Response Rates. Snider, JW., Molitoris, J., Shyu, S., et al.[2021]

The study developed novel mini-GRID radiation therapy methods that achieved high peak-to-valley ratios, indicating a potential for more targeted treatment while sparing healthy tissue, with ratios significantly higher than those reported for conventional methods.

In a pre-clinical mouse study, both GRID therapy and hemi-irradiation effectively delayed tumor growth compared to controls, but neither was as effective as traditional whole-tumor irradiation, suggesting that while promising, GRID therapy may need to be combined with other treatments to enhance its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An investigation of kV mini-GRID spatially fractionated radiation therapy: dosimetry and preclinical trial. Johnson, TR., Bassil, AM., Williams, NT., et al.[2023]

Spatially fractionated radiation therapy (GRID) effectively targets advanced bulky tumors with high doses in a single treatment, aiming for either curative or palliative outcomes.

Clinical data shows that GRID therapy not only helps manage large tumors with an acceptable level of toxicity but also induces systemic effects that increase cytokines associated with better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spatially fractionated (GRID) therapy for large and bulky tumors. Peñagarícano, JA., Griffin, R., Corry, P., et al.[2018]

The study successfully implemented a grid block for spatially fractionated grid radiation therapy (SFGRT), demonstrating that it can effectively treat bulky tumors with a significant reduction in treatment time compared to traditional methods, improving patient throughput.

Dosimetric measurements showed that the grid block technique has clinically acceptable accuracy, with discrepancies in dose calculations being minimal (less than 4% in the build-up region and less than 2% at deeper levels), supporting its safe and effective use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective spatially fractionated GRID radiation treatment planning for a passive grid block. Nobah, A., Mohiuddin, M., Devic, S., et al.[2022]

Spatially fractionated radiation therapy (SFRT), such as GRID radiation therapy, shows promise in improving treatment responses for bulky primary and metastatic cancers by using a highly heterogeneous dose distribution, which allows for higher prescription doses than conventional radiotherapy.

The Physics Working Group of the Radiosurgery Society has developed consensus recommendations to standardize GRID therapy practices, which is crucial for enhancing clinical outcomes and facilitating rigorous clinical trials in this innovative treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photon GRID Radiation Therapy: A Physics and Dosimetry White Paper from the Radiosurgery Society (RSS) GRID/LATTICE, Microbeam and FLASH Radiotherapy Working Group. Zhang, H., Wu, X., Zhang, X., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Early clinical results of proton spatially fractionated GRID radiation therapy (SFGRT). [2022]

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

Spatially Fractionated Radiotherapy (GRID) Prior to Standard Neoadjuvant Conventionally Fractionated Radiotherapy for Bulky, High-Risk Soft Tissue and Osteosarcomas: Feasibility, Safety, and Promising Pathologic Response Rates. [2021]

3. England pubmed.ncbi.nlm.nih.gov

An investigation of kV mini-GRID spatially fractionated radiation therapy: dosimetry and preclinical trial. [2023]

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

Spatially fractionated (GRID) therapy for large and bulky tumors. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Effective spatially fractionated GRID radiation treatment planning for a passive grid block. [2022]

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

Photon GRID Radiation Therapy: A Physics and Dosimetry White Paper from the Radiosurgery Society (RSS) GRID/LATTICE, Microbeam and FLASH Radiotherapy Working Group. [2021]