Optimized Proton Therapy for Pediatric Ependymoma

Recruiting at 1 trial location

Overseen By David Grosshans

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Previous brain radiation, Pregnancy, 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: 1

Duration: 6 weeks

48 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects of linear energy transfer (LET) optimized image modulated proton therapy (IMPT) in treating pediatric patients with ependymoma. Radiation therapy such as LET optimized IMPT, uses proton beams to kill tumor cells and shrink tumors without damaging surrounding normal tissues.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot receive chemotherapy at the same time as the radiation therapy in this study.

What data supports the effectiveness of the treatment LET Optimized IMPT for pediatric ependymoma?

Research shows that LET-guided optimization in proton therapy can improve treatment by reducing harmful effects on critical structures while maintaining effective doses to the tumor. This approach has shown potential benefits in similar treatments, suggesting it could be effective for pediatric ependymoma. ^{1 2 3 4 5}

Is Optimized Proton Therapy safe for children with ependymoma?

Research on intensity modulated proton therapy (IMPT) suggests that careful planning can help avoid high energy transfer to critical areas, which may reduce the risk of side effects like brain damage. However, there is concern about unintended increases in biological dose near sensitive areas, so safety depends on precise treatment planning. ^{2 3 4 6 7}

How is LET Optimized IMPT treatment different from other treatments for pediatric ependymoma?

LET Optimized IMPT is unique because it focuses on optimizing the linear energy transfer (LET) to minimize damage to critical structures near the tumor while maintaining effective radiation doses, potentially offering better protection for healthy tissues compared to traditional radiation therapies. ^{1 2 8 9 10}

Research Team

David R. Grosshans

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for children with a brain tumor called ependymoma, confirmed by previous tests. They should be able to perform daily activities at least half the time (Lansky score 50-100), have no tumor spread in the spine or previous brain radiation, and not be pregnant. They must also be able to undergo MRI scans and handle gadolinium contrast.

Inclusion Criteria

I can do most activities but may need help.

Signed informed consent by patient and/or parents or legal guardian

I am not receiving chemotherapy at the same time as radiation therapy.

Exclusion Criteria

I have had radiation therapy to my brain.

Inability to undergo MR imaging

I have ependymoma in my spine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LET optimized IMPT for up to 6 weeks

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

1 visit at 1 month, then every 3 months

Treatment Details

Interventions

• Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy

Trial Overview The study is testing LET Optimized IMPT, a type of precise radiation therapy that targets tumors while sparing healthy tissue. It's for kids who haven't had prior radiation and aren't on chemo during the trial. The effects on quality of life will also be assessed through questionnaires.

Participant Groups

Group I: Treatment (LET optimized IMPT) Experimental Treatment 3 Interventions

Patients receive LET optimized IMPT for up to 6 weeks.

Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Proton Therapy for:

• Pediatric cancers
• Ocular melanomas
• Chordomas
• Chondrosarcomas

Approved in United States as Proton Therapy for:

• Pediatric cancers
• Ocular melanomas
• Chordomas
• Chondrosarcomas
• Brain tumors
• Spinal tumors

Approved in Japan as Proton Therapy for:

• Pediatric cancers
• Ocular melanomas
• Chordomas
• Chondrosarcomas

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 17 pediatric patients treated with proton beam radiation for intracranial ependymoma, the median follow-up showed promising outcomes with local control at 86%, progression-free survival at 80%, and overall survival at 89%.

Proton therapy demonstrated significant advantages over intensity-modulated radiation therapy (IMRT) by providing similar tumor coverage while sparing more normal tissue, and intensity-modulated proton therapy (IMPT) may further enhance this sparing of critical structures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiotherapy for childhood ependymoma: initial clinical outcomes and dose comparisons. MacDonald, SM., Safai, S., Trofimov, A., et al.[2022]

A new optimization method for intensity modulated proton therapy (IMPT) effectively reduces high linear energy transfer (LET) in critical structures near tumor targets, enhancing treatment safety for patients with intracranial tumors.

In a study involving 5 patients with tumors overlapping sensitive areas like the brainstem and optic structures, the method successfully minimized high LET×D values while maintaining the physical dose distribution, potentially lowering the risk of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reoptimization of Intensity Modulated Proton Therapy Plans Based on Linear Energy Transfer. Unkelbach, J., Botas, P., Giantsoudi, D., et al.[2022]

The study explored a new method for optimizing intensity modulated proton therapy (IMPT) using linear energy transfer (LET) to improve treatment for 7 patients with head-and-neck and pancreatic cancers, showing significant variations in LET values that could impact treatment effectiveness.

By navigating between different treatment plans, the researchers found that accounting for LET could potentially improve the biological effectiveness of the treatment by up to 40%, suggesting a promising approach to enhance tumor targeting while protecting healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linear energy transfer-guided optimization in intensity modulated proton therapy: feasibility study and clinical potential. Giantsoudi, D., Grassberger, C., Craft, D., et al.[2022]

The use of proton track-end objectives in intensity modulated proton therapy (IMPT) significantly reduced the linear energy transfer (LET) in critical structures by an average of 37%, while increasing LET in the target volume by 23%, without altering the physical dose distribution.

This method led to substantial reductions in the relative biological effectiveness (RBE)-weighted dose and normal tissue complication probabilities (NTCPs) by up to 19 percentage points, suggesting a safer and more effective approach to proton therapy that could be integrated into current clinical practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Introducing Proton Track-End Objectives in Intensity Modulated Proton Therapy Optimization to Reduce Linear Energy Transfer and Relative Biological Effectiveness in Critical Structures. Traneus, E., Ödén, J.[2019]

The distal-edge avoidance-guided optimization method (DEAOpt) for intensity-modulated proton therapy (IMPT) effectively increases the biological effect in tumor areas while significantly reducing harmful effects in critical structures, such as the brainstem, compared to conventional dose-based optimization methods.

DEAOpt not only provides similar biological effects to LET-based optimization methods but also reduces computation time by over 30%, making it a more efficient approach for optimizing proton therapy treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A biological effect-guided optimization approach using beam distal-edge avoidance for intensity-modulated proton therapy. Bai, X., Lim, G., Grosshans, D., et al.[2021]

Intensity-modulated proton therapy (IMPT) for pediatric posterior fossa tumors can lead to high linear energy transfer (LET) values in the brainstem, especially when the tumor is located away from the brainstem, which raises concerns about potential biological dose increases.

Interestingly, when tumors invade or are closer to the brainstem, the biological dose (D × RBELET) is higher, indicating that treatment planning must consider tumor location to minimize risks to critical structures like the brainstem.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linear energy transfer distributions in the brainstem depending on tumour location in intensity-modulated proton therapy of paediatric cancer. Fjæra, LF., Li, Z., Ytre-Hauge, KS., et al.[2018]

Using per-voxel constraints in intensity-modulated proton therapy (IMPT) significantly reduces harmful hot spots in the dose and linear energy transfer (LET) distribution, which can lead to brain necrosis in patients with base of skull cancer.

The LET-guided robust optimization method was shown to effectively minimize these hot spots compared to conventional dose-only optimization, resulting in lower xBD hot spots while maintaining comparable dose coverage for the target area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Per-voxel constraints to minimize hot spots in linear energy transfer-guided robust optimization for base of skull head and neck cancer patients in IMPT. Feng, H., Shan, J., Anderson, JD., et al.[2022]

The novel intensity modulated proton arc therapy (IMPAT) method showed improved plan quality for ependymoma patients, achieving better dose homogeneity and conformity compared to traditional intensity-modulated proton therapy (IMPT) plans.

IMPAT plans resulted in higher relative biological effectiveness (RBE) enhancement, indicating a potential dosimetric benefit for tumors near critical organs, while maintaining similar maximum doses to the brainstem.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity modulated proton arc therapy via geometry-based energy selection for ependymoma. Cao, W., Li, Y., Zhang, X., et al.[2023]

Proton therapy (PT) for children with localized ependymoma showed high effectiveness, with a 3-year overall survival rate of 93.7% and a median total dose of 59.4 Gy, indicating it is a viable treatment option for this age group.

The study found that while PT was generally well tolerated, multiple tumor surgeries negatively impacted progression-free survival, and new severe late toxicities were observed in 11 patients, highlighting the need for careful treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of dose, volume, and outcome in children with localized, intracranial ependymoma treated with proton therapy within the prospective KiProReg Study. Peters, S., Merta, J., Schmidt, L., et al.[2022]

In a study of 101 pediatric ependymoma patients, using a simultaneous integrated boost (SIB) with intensity-modulated proton therapy (IMPT) resulted in higher quality treatment indices and lower doses to organs at risk compared to standard radiation delivery methods.

The approach of dose escalation with SIB is feasible for certain patients, particularly those with supratentorial tumors, but caution is advised for infratentorial tumors due to potential risks to critical structures like the brainstem.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Dose Escalation in Patients With Intracranial Pediatric Ependymoma. Tensaouti, F., Ducassou, A., Chaltiel, L., et al.[2020]

References

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

Proton radiotherapy for childhood ependymoma: initial clinical outcomes and dose comparisons. [2022]

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

Reoptimization of Intensity Modulated Proton Therapy Plans Based on Linear Energy Transfer. [2022]

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

Linear energy transfer-guided optimization in intensity modulated proton therapy: feasibility study and clinical potential. [2022]

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

Introducing Proton Track-End Objectives in Intensity Modulated Proton Therapy Optimization to Reduce Linear Energy Transfer and Relative Biological Effectiveness in Critical Structures. [2019]

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

A biological effect-guided optimization approach using beam distal-edge avoidance for intensity-modulated proton therapy. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Linear energy transfer distributions in the brainstem depending on tumour location in intensity-modulated proton therapy of paediatric cancer. [2018]

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

Per-voxel constraints to minimize hot spots in linear energy transfer-guided robust optimization for base of skull head and neck cancer patients in IMPT. [2022]

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

Intensity modulated proton arc therapy via geometry-based energy selection for ependymoma. [2023]

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

Evaluation of dose, volume, and outcome in children with localized, intracranial ependymoma treated with proton therapy within the prospective KiProReg Study. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Feasibility of Dose Escalation in Patients With Intracranial Pediatric Ependymoma. [2020]