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

Trial Summary

What is the purpose of this trial?

This phase II clinical trial studies how well craniospinal irradiation (CSI) with hippocampal avoidance, using proton therapy or volumetric modulated arc therapy (VMAT), works in treating patients with breast cancer or non-small cell lung cancer (NSCLC) that has spread from the original (primary) tumor to the cerebrospinal fluid (CSF) and meninges (thin layers of tissue that cover and protect the brain and spinal cord) (leptomeningeal metastases). Radiation therapy is an effective treatment in relieving localized symptoms caused by leptomeningeal metastases. However, the type of radiation therapy typically used does not prevent the spread of leptomeningeal disease. CSI (radiation therapy directed at the brain and spinal cord to kill tumor cells) may be able to target all of the areas of possible leptomeningeal tumor spread. CSI may however result in significant neurological side effects due to radiation damage to a part of the brain called the hippocampus. Hippocampal avoidance (HA) reduces the amount of radiation to the hippocampus. Proton or VMAT CSI with HA may be an effective treatment while reducing neurological side effects for patients with leptomeningeal metastases from breast cancer and NSCLC.

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 data supports the effectiveness of the treatment Proton Beam Craniospinal Irradiation for breast and lung cancer?

Proton beam craniospinal irradiation (PrBCSI) has been shown to reduce side effects like blood and stomach issues in children with brain tumors compared to traditional methods. While this is not directly about breast and lung cancer, it suggests that PrBCSI might also help reduce side effects in other conditions. ^{1 2 3 4 5}

Is craniospinal irradiation safe for humans?

Proton beam craniospinal irradiation (PrBCSI) has been shown to reduce certain side effects compared to traditional methods, such as lower rates of skin irritation and esophagitis in breast cancer treatment, and reduced acute toxicities in both children and adults. However, more clinical data is needed to fully understand its safety profile. ^{2 5 6 7 8}

How is Proton Beam Craniospinal Irradiation different from other treatments for breast and lung cancer?

Proton Beam Craniospinal Irradiation is unique because it uses proton therapy, which is a type of radiation that can more precisely target tumors, potentially reducing damage to surrounding healthy tissues compared to traditional radiation methods. This approach is particularly novel for breast and lung cancer, as craniospinal irradiation is typically used for pediatric brain tumors. ^{1 2 3 4 9}

Research Team

Lia M. Halasz

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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, as well as additional CT for radiation planning during screening. Additionally, patients undergo magnetic resonance imaging (MRI) throughout the trial. They may also undergo lumbar puncture (LP) or alternative methods for cerebral spinal fluid (CSF) collection.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Findings from Research

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]

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]

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]

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 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 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]

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]

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]

References

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

Supine craniospinal irradiation using a proton pencil beam scanning technique without match line changes for field junctions. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Technique, outcomes, and acute toxicities in adults treated with proton beam craniospinal irradiation. [2021]

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

Variation in Proton Craniospinal Irradiation Practice Patterns in the United States: A Pediatric Proton Consortium Registry (PPCR) Study. [2022]

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

Comparison of Craniospinal Irradiation Using Proton Beams According to Irradiation Method and Initial Experience Treating Pediatric Patients. [2023]

5. England 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. [2022]

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

Volumetric de-escalation and improved acute toxicity with proton craniospinal irradiation using a vertebral body-sparing technique. [2022]

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

Clinical Outcomes and Toxicity of Proton Radiotherapy for Breast Cancer. [2022]

8. United States 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. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

Supine craniospinal irradiation in pediatric patients by proton pencil beam scanning. [2022]