Proton Radiotherapy for Palliative Cancer Care

Overseen By Anthony Apicelli, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must not be taking: Cytotoxic, VEGF inhibitors

Disqualifiers: Urgent surgery, Superficial lesions, Pregnancy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 1 week

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Spatially fractionated radiotherapy (SFRT or GRID) addresses some limitations of traditional stereotactic body radiation therapy by relying on beam collimation to create high-dose "peaks" and intervening low-dose "valleys" throughout the target volume. Standard palliative radiotherapy regimens provide limited durability of response, and there are challenges with delivery to large tumors or in previously irradiated fields. In this study, Proton GRID radiotherapy will be used to deliver three-fraction palliative radiotherapy to patients with tumors needing palliative radiation. The safety and efficacy of this approach will be assessed. It is hypothesized that GRID is highly effective, immunogenic, and associated with low rates of toxicity.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, if you are currently receiving cytotoxic cancer therapy or VEGF inhibitors, you cannot take them at the same time as the proton GRID treatment. A 2-week break from these medications is recommended but not required before starting the trial.

What data supports the effectiveness of Proton GRID Radiotherapy for palliative cancer care?

Research shows that palliative radiotherapy, including advanced techniques like Proton GRID Radiotherapy, is effective in relieving symptoms for patients with advanced cancer. It is a time-efficient treatment that can provide symptom relief with minimal side effects, making it a valuable option for improving quality of life in palliative care. ^{1 2 3 4 5}

Is proton radiotherapy safe for palliative cancer care?

Research on spatially fractionated radiotherapy (GRID) and its variations, including proton GRID therapy, suggests it is generally safe for treating large tumors, with studies reporting good safety profiles in patients. However, the understanding of its effects is still developing, and it is used in limited centers. ^{6 7 8 9 10}

How is Proton GRID Radiotherapy different from other cancer treatments?

Proton GRID Radiotherapy is unique because it uses a spatially fractionated approach, delivering high doses of radiation in a grid pattern, which helps protect healthy tissue while targeting large tumors. This method combines the precision of proton therapy with the benefits of GRID therapy, making it suitable for treating tumors near critical organs with reduced toxicity. ^{9 11 12 13 14}

Research Team

Anthony Apicelli, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults with confirmed cancer who need palliative radiation for large tumors or previously irradiated lesions. Participants must agree to use contraception and have an ECOG performance status ≤ 3. Excluded are those needing urgent surgery, pregnant women, patients on certain cancer therapies overlapping with the trial, and HIV-positive individuals with low CD4+ counts or recent opportunistic infections.

Inclusion Criteria

Histologically or cytologically confirmed cancer diagnosis

I am in a group of 10 patients with previously irradiated lesions.

I am planning to have radiotherapy for a large, inoperable cancer lesion.

Exclusion Criteria

Patients with HIV and CD4+ T-cell counts < 350 cells/mcL or history of AIDS-defining opportunistic infection within the 12 months prior to registration

I am not on any cancer treatments that would interfere with proton GRID therapy.

My tumor requires immediate surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 20 Gy proton GRID radiotherapy in 3 fractions for palliative treatment

1 week

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Visits at 2 weeks, 30 days, 90 days, 180 days, and 360 days

Treatment Details

Interventions

• Proton GRID Radiotherapy

Trial Overview The study tests Proton GRID Radiotherapy as a three-fraction palliative treatment for cancerous tumors. It aims to see if this method, which creates high-dose areas within the tumor while sparing surrounding tissue, is safe and effective compared to traditional radiotherapy.

Participant Groups

Group I: Cohort B: De Novo Radiation Treatment Fields Experimental Treatment 1 Intervention

Radiotherapy will consist of 20 Gy proton GRID radiotherapy x 3 fractions.

Group II: Cohort A: Reirradiation of Treatment Fields Experimental Treatment 1 Intervention

Radiotherapy will consist of 20 Gy proton GRID radiotherapy x 3 fractions.

Proton GRID Radiotherapy is already approved in United States, European Union for the following indications:

Approved in United States as Spatially Fractionated Radiotherapy for:

• Palliative treatment of large solid extracranial cancers
• Sarcomas
• Bulky tumors

Approved in European Union as GRID Radiotherapy for:

• Palliative treatment of advanced cancers
• Sarcomas
• Head and neck squamous cell carcinoma
• Melanoma

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Findings from Research

The study demonstrated that using diagnostic scan-based planning (DSBP) for proton therapy in 10 patients with thoracic metastatic cancer is technically feasible and provides effective treatment while sparing normal tissues, particularly the heart, compared to traditional photon therapy.

Proton DSBP not only maintains acceptable coverage and dose distribution but also offers a cost-effective alternative to standard photon regimens, making it a valuable option for palliative care in selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advancing the Role of Proton Therapy for Spine Metastases Through Diagnostic Scan-Based Planning. Swanick, CW., Shang, MH., Erhart, K., et al.[2023]

Single fraction radiotherapy (SFR) is effective for relieving symptoms in patients with advanced cancer, yet it remains underutilized, especially in those with limited life expectancy.

In a case study of four patients with advanced cancer and soft tissue lesions, SFR was successfully used, highlighting its potential as a palliative treatment option for frail patients or those with poor performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single dose radiotherapy in soft tissue tumoral masses: just enough palliation. Vargas, A.[2022]

Palliative radiotherapy has been an effective treatment for nearly 100 years, providing symptom relief for patients with metastatic or advanced cancer, often using short courses or single fractions to minimize side effects and enhance convenience.

Recent advancements in imaging and radiotherapy techniques, such as intensity-modulated radiotherapy (IMRT) and stereotactic radiotherapy (SRT), allow for more effective local control and longer-lasting palliative responses, even in patients who may not yet show symptoms of advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palliative radiotherapy: current status and future directions. Sharma, S., Hertan, L., Jones, J.[2022]

In a systematic review of 16 randomized trials involving over 5,000 patients with painful bone metastases, single fraction (SF) and multiple fraction (MF) radiotherapy showed similar overall and complete response rates for pain relief, indicating both methods are equally effective.

Patients receiving SF radiotherapy had a significantly higher likelihood (2.5 times more) of needing re-treatment compared to those receiving MF, suggesting that while SF is effective, it may not provide long-lasting relief as compared to MF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palliative radiotherapy trials for bone metastases: a systematic review. Chow, E., Harris, K., Fan, G., et al.[2022]

Palliative radiotherapy (PRT) is a common and effective treatment for managing cancer complications, with about one third of cancer patients receiving it in their last two years of life, highlighting its importance in end-of-life care.

There is significant variation in PRT practices due to inconsistent guidelines and physician differences, which can lead to unnecessary treatment burdens on frail patients, suggesting a need for better case selection and standardization in treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health Economic and Health Service Issues of Palliative Radiotherapy. Barton, M., Batumalai, V., Spencer, K.[2021]

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]

Grid radiotherapy effectively targets infiltrated melanoma cells while minimizing damage to surrounding normal tissues, making it a promising treatment option for melanoma patients.

The therapeutic ratio and effectiveness of grid therapy depend on factors such as dose size, tumor size, and location, with doses of 15 Gy or higher showing significant advantages in sparing normal cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of dose size in single fraction spatially fractionated (grid) radiotherapy for melanoma. Zhang, H., Zhong, H., Barth, RF., 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]

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]

Megavoltage grid therapy delivers a high dose of radiation (15-20 Gy) in a single treatment to large, deeply seated tumors, making it a viable option for patients who have already received maximum conventional radiation or have large tumor burdens.

The study measured key dosimetric properties of this therapy, revealing that the dose distribution varies significantly, with valley-to-peak ratios indicating effective dose delivery in shielded and open areas, which supports its clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric properties of megavoltage grid therapy. Reiff, JE., Huq, MS., Mohiuddin, M., et al.[2022]

Proton pencil-beam-scanning (PBS) GRID therapy demonstrated a higher peak-to-edge ratio and better dose distribution compared to volumetric modulated arc therapy (VMAT) in a study involving 5 patients with bulky tumors, indicating more precise targeting of the tumor while sparing surrounding healthy tissue.

PBS GRID resulted in significantly lower doses to normal tissues compared to VMAT, suggesting that PBS could allow for higher radiation doses to be safely delivered to tumors, potentially improving treatment outcomes for patients with large tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Planning of Bulky Tumors Using Pencil Beam Scanning Proton GRID Therapy. Halthore, A., Fellows, Z., Tran, A., et al.[2023]

The study demonstrates that using a dynamic collimation system (DCS) with proton therapy can optimize GRID radiation therapy, enhancing the therapeutic benefits while sparing healthy tissue, particularly with spot spacings below 2.0 cm and collimation widths under 1.0 cm.

Experimental results showed that the dose distributions predicted by Monte Carlo simulations closely matched actual measurements, achieving over 98.7% agreement, indicating that these models can reliably guide the customization of GRID treatments for improved efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dosimetric enhancement of GRID profiles using an external collimator in pencil beam scanning proton therapy. Smith, BR., Nelson, NP., Geoghegan, TJ., et al.[2023]

The study explored innovative GRID therapy techniques using kilovoltage x-rays, high-energy electrons, and protons, demonstrating high peak-to-valley dose ratios (PVDR) in healthy tissue, which is crucial for minimizing damage during radiotherapy.

All three techniques showed a reduction in penumbra compared to traditional radiosurgery, suggesting they could effectively treat tumors while sparing surrounding healthy tissue, warranting further biological experiments to evaluate their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric evaluation of new approaches in GRID therapy using nonconventional radiation sources. Martínez-Rovira, I., Fois, G., Prezado, Y.[2018]

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]

References

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

Advancing the Role of Proton Therapy for Spine Metastases Through Diagnostic Scan-Based Planning. [2023]

2. Poland pubmed.ncbi.nlm.nih.gov

Single dose radiotherapy in soft tissue tumoral masses: just enough palliation. [2022]

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

Palliative radiotherapy: current status and future directions. [2022]

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

Palliative radiotherapy trials for bone metastases: a systematic review. [2022]

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

Health Economic and Health Service Issues of Palliative Radiotherapy. [2021]

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]

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

Impact of dose size in single fraction spatially fractionated (grid) radiotherapy for melanoma. [2022]

8. 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]

9. England pubmed.ncbi.nlm.nih.gov

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

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

Dosimetric properties of megavoltage grid therapy. [2022]

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

Treatment Planning of Bulky Tumors Using Pencil Beam Scanning Proton GRID Therapy. [2023]

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

The dosimetric enhancement of GRID profiles using an external collimator in pencil beam scanning proton therapy. [2023]

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

Dosimetric evaluation of new approaches in GRID therapy using nonconventional radiation sources. [2018]

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

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