Craniospinal Irradiation for Breast and Lung Cancer

Overseen By Lia M. Halasz

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Disqualifiers: Neurologic deficits, Extensive systemic disease, 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

Compensation: Varies

Number of Visits: 15

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new radiation therapy approach for patients with breast cancer or non-small cell lung cancer (NSCLC) that has spread to the brain and spinal cord. The treatment combines craniospinal irradiation (CSI) with a technique that avoids the hippocampus, aiming to target cancer spread while minimizing damage to memory-related brain areas. Participants will receive this treatment daily for ten days, using either proton beam therapy (a type of craniospinal irradiation) or a special radiation method (VMAT). Those diagnosed with leptomeningeal metastases (cancer spread to cerebrospinal fluid and brain coverings) and eligible for radiation therapy may be suitable for the trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer therapy.

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

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 craniospinal irradiation with hippocampal avoidance is safe for treating leptomeningeal metastases?

Research has shown that proton craniospinal irradiation (CSI) is generally safe for patients with cancer that has spread to the brain and spine from solid tumors like breast or non-small cell lung cancer (NSCLC). Studies have found that this treatment can effectively control the disease. Importantly, proton CSI may help patients live longer compared to other radiation methods.

One study found that patients tolerated proton CSI well, with few severe side effects. Another study highlighted that proton therapy could improve outcomes without causing significant harm. This is promising because it suggests the treatment is both effective and safe for many people.

Overall, proton CSI with hippocampal avoidance (HA) may lower the risk of neurological side effects. HA is a technique to protect the hippocampus, a part of the brain important for memory. This approach helps keep the brain safe while treating cancer. Thus, the treatment aims to be strong against cancer while being gentle on the rest of the body. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard care options for breast and lung cancer, which often include traditional radiation therapy, Proton Beam Craniospinal Irradiation offers a unique approach. This treatment uses proton beams to deliver precise radiation doses to the craniospinal area, minimizing damage to surrounding healthy tissues. Researchers are excited about this treatment because it has the potential to reduce side effects while maintaining or even improving the effectiveness of cancer control. Additionally, the use of advanced imaging techniques like CT and MRI enhances the precision of radiation delivery, further protecting healthy tissue.

What evidence suggests that craniospinal irradiation with hippocampal avoidance might be an effective treatment for leptomeningeal metastases from breast cancer and NSCLC?

This trial will evaluate proton craniospinal irradiation (pCSI) for patients with breast cancer or non-small cell lung cancer that has spread to the brain and spinal cord. Studies have shown that pCSI can extend patient survival. In one study, patients treated with pCSI lived a median of 11.3 months, compared to 4.9 months for those who received traditional radiation. Another study found that pCSI extended the period before disease progression. Proton therapy targets cancer cells more precisely while protecting healthy tissue, potentially leading to better outcomes. This method might also reduce the risk of damaging the hippocampus, which is crucial for memory. ^{2 6 7 8 9}

Who Is on the Research Team?

Lia M. Halasz

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for patients with breast cancer or non-small cell lung cancer (NSCLC) that has spread to the cerebrospinal fluid and meninges. Participants must have a life expectancy of more than 8 weeks, be able to undergo radiation therapy, and provide tissue samples from previous biopsies.

Inclusion Criteria

The patient/legally authorized representative is able to provide informed consent

Hemoglobin level greater than 8 g/dL

Absolute neutrophil count greater than 1,000/mm

Exclusion Criteria

I've had radiation before where they now want to treat me, and can't have more without risking harm.

I have a visible heart disease.

Patients with multiple, serious major neurologic deficits per physician/investigator assessment including encephalopathy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Radiation Treatment

Participants undergo proton or photon VMAT craniospinal irradiation with hippocampal avoidance over approximately 45 minutes once daily for 10 days

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits at 3, 6, 9, and 12 months, and at the time of CNS disease progression

12 months

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Proton Beam Craniospinal Irradiation

Trial Overview The study tests craniospinal irradiation (CSI) with hippocampal avoidance using proton therapy or volumetric modulated arc therapy (VMAT). It aims to treat leptomeningeal metastases effectively while minimizing neurological side effects by sparing the hippocampus during radiation.

How Is the Trial Designed?

Group I: Treatment (Proton or Photon VMAT CSI) Experimental Treatment 10 Interventions

Patients undergo proton or photon VMAT CSI with HA over approximately 45 minutes once daily (QD) for 10 days (Monday-Friday) in the absence of unacceptable toxicity. Patients also undergo computed tomography (CT) or positron emission tomography (PET)/CT during screening. Additionally, patients undergo additional CT for radiation planning during screening and magnetic resonance imaging (MRI) throughout the trial. Patients may also undergo lumbar puncture (LP) or alternative methods for cerebral spinal fluid (CSF) collection at the discretion of the treating physician and principal investigator throughout the study.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Published Research Related to This Trial

Proton pencil beam scanning (PBS) for craniospinal irradiation in 12 pediatric patients achieved excellent target coverage (mean D98% > 98%) while minimizing radiation exposure to critical organs, such as the lens and kidneys.

The innovative techniques used, including patient positioning and beam-splitting, resulted in effective lens sparing (mean D1 ∼ 730 cGyE) and reduced lateral penumbra, demonstrating the safety and efficacy of proton therapy in this sensitive patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supine craniospinal irradiation in pediatric patients by proton pencil beam scanning. Farace, P., Bizzocchi, N., Righetto, R., et al.[2022]

In a study comparing proton beam craniospinal irradiation (PrBCSI) to conventional photon beam CSI (PhBCSI) in children with brain tumors, PrBCSI resulted in significantly less severe thrombocytopenia and no reported cases of diarrhea, indicating a better safety profile.

Patients receiving PrBCSI showed improved recovery rates for leukocyte and platelet counts one month after treatment compared to those receiving PhBCSI, suggesting enhanced efficacy in managing treatment-related blood cell reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy reduces the incidence of acute haematological and gastrointestinal toxicities associated with craniospinal irradiation in pediatric brain tumors. Song, S., Park, HJ., Yoon, JH., et al.[2022]

In a study of six female pediatric patients, craniospinal irradiation (CSI) using proton beam therapy resulted in minimal radiation exposure to breast tissue, with average doses near zero, suggesting a lower risk for secondary breast cancer.

In contrast, CSI using x-ray therapy delivered significant radiation doses to the breast, with average maximum doses of 23 Gy, indicating that early breast cancer screening may be necessary for patients treated with x-ray therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast cancer screening for childhood cancer survivors after craniospinal irradiation with protons versus x-rays: a dosimetric analysis and review of the literature. Kumar, RJ., Zhai, H., Both, S., et al.[2022]

A review of 450 pediatric patients receiving proton craniospinal irradiation (CSI) revealed significant variability in treatment practices across institutions, particularly in the coverage of critical areas like optic nerves and sacral nerves.

Only 48.2% of optic nerves were fully covered, while spinal nerves had a high coverage rate of 95.6%, indicating a need for standardization in treatment protocols to ensure optimal safety and efficacy in radiation therapy for pediatric brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variation in Proton Craniospinal Irradiation Practice Patterns in the United States: A Pediatric Proton Consortium Registry (PPCR) Study. Connor, M., Paulino, AC., Ermoian, RP., et al.[2022]

Proton craniospinal irradiation (p-CSI) demonstrated low rates of acute toxicity in a study of 50 adult patients, with only mild nausea and minimal weight loss reported, suggesting it is a safer alternative to conventional craniospinal irradiation.

The study showed promising clinical outcomes, with 2-year overall and progression-free survival rates of 96% and 82%, respectively, indicating that p-CSI is not only feasible but also effective for treating malignancies while minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technique, outcomes, and acute toxicities in adults treated with proton beam craniospinal irradiation. Barney, CL., Brown, AP., Grosshans, DR., et al.[2021]

The proposed proton pencil beam scanning technique for craniospinal irradiation provides uniform dose coverage and is more robust to setup errors compared to traditional methods, achieving an average conformity number of 0.78 and a homogeneity index of 1.09 across 10 patients.

Setup errors of up to 6 mm can significantly affect dosimetric accuracy, but the gradient optimization approach minimizes these effects, making it a safer and more effective option for delivering precise radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supine craniospinal irradiation using a proton pencil beam scanning technique without match line changes for field junctions. Lin, H., Ding, X., Kirk, M., et al.[2019]

In a study of 24 pediatric patients receiving proton craniospinal irradiation, intensity modulated proton therapy (IMPT) was found to significantly reduce radiation exposure to the lens compared to passive scattered proton therapy (PSPT).

The vertebral body sparing (VBS) technique resulted in lower radiation doses to critical organs such as the thyroid, lungs, esophagus, and kidneys compared to the whole vertebral body technique, indicating a safer approach for younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Craniospinal Irradiation Using Proton Beams According to Irradiation Method and Initial Experience Treating Pediatric Patients. Fukumitsu, N., Kubota, H., Mima, M., et al.[2023]

In a study of 38 pediatric patients treated with either vertebral body-sparing proton craniospinal irradiation (VBSpCSI) or traditional photon-based craniospinal radiotherapy (3DCRT), VBSpCSI was associated with significantly lower rates of acute gastrointestinal toxicity and nausea, indicating a safer profile for young patients.

Patients receiving VBSpCSI also experienced fewer severe hematologic toxicities, such as lower rates of red blood cell transfusions and lymphopenia, suggesting that this technique may reduce treatment-related side effects compared to conventional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Volumetric de-escalation and improved acute toxicity with proton craniospinal irradiation using a vertebral body-sparing technique. Chou, B., Hopper, A., Elster, J., et al.[2022]

Proton beam radiotherapy (PBT) for breast cancer shows promising results, with skin toxicity rates (grade 1 dermatitis at ~25% and grade 2 dermatitis at 71-75%) comparable or better than traditional photon therapy.

PBT has the potential to significantly reduce cardiac risks by keeping the mean heart dose at ≤ 1 Gy, although more definitive clinical data is needed, and ongoing randomized trials will help clarify its efficacy compared to photon therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes and Toxicity of Proton Radiotherapy for Breast Cancer. Verma, V., Shah, C., Mehta, MP.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1879850025001122

Real-World Experience Using Proton Versus Photon ... Data demonstrate improved survival with proton craniospinal irradiation (CSI) over involved field radiation therapy for leptomeningeal disease (LMD). It is ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9671756/

Randomized Phase II Trial of Proton Craniospinal Irradiation ... CNS PFS was significantly longer for patients with NSCLC and breast cancer LM who underwent pCSI compared with standard-of-care photon IFRT, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06500481?term=NCT06500481&rank=1

NCT06500481 | Testing Proton Craniospinal Radiation ... Giving pCSI may be better than IFRT in treating LM in patients with breast or non-small cell lung cancer. Detailed Description. PRIMARY OBJECTIVE: I. To compare ...

4. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-025-02618-7

Early experience with proton craniospinal irradiation in adult ... Recent data suggest proton craniospinal irradiation (pCSI) to be a promising treatment option, potentially prolonging progression-free survival (PFS) and ...

5. ascopost.com ascopost.com/news/september-2025/proton-craniospinal-irradiation-for-leptomeningeal-metastasis-in-lung-or-breast-cancer/

Proton Craniospinal Irradiation for Leptomeningeal ... Median overall survival was 11.3 months (95% CI = 7.5–18.3 months) in the pCSI group vs 4.9 months (95% CI = 3.9–15.0 months) in the IFRT group ...

6. nrgoncology.org nrgoncology.org/Home/News/Post/testing-proton-craniospinal-radiation-therapy-for-patients-with-breast-or-non-small-cell-lung-cancer-leptomeningeal-metastasis-nrg-bn014

Testing Proton Craniospinal Radiation Therapy for Patients ... “Proton craniospinal radiation therapy has showed potential promise in improving survival outcomes for this population as well as limited high- ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7850116/

Clinical trial of proton craniospinal irradiation for ... Hypofractionated proton CSI using proton therapy is a safe treatment for patients with LM from solid tumors. We saw durable disease control in ...

8. practicalradonc.org practicalradonc.org/article/S1879-8500(25)00112-2/fulltext

Real-World Experience Using Proton Versus Photon ... Data demonstrate improved survival with proton craniospinal irradiation (CSI) over involved field radiation therapy for leptomeningeal disease (LMD).

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301625059012

1067 Toxicity and Clinical Outcomes of Proton vs. Photon ... Craniospinal irradiation (CSI) is an effective treatment for solid tumor leptomeningeal carcinomatosis (LMC). Although proton CSI (pCSI) improves survival vs ...