Proton Therapy for Liver Metastases

Overseen By Proton Referral Office First Call: Referral Office intake personnel

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Loma Linda University

Disqualifiers: CNS metastases, Active liver infection, 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: Unknown

35 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that any chemotherapy or targeted therapy be stopped at least 2 weeks before starting radiation and not resumed until at least 14 days after completing the proton therapy. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the treatment Proton Therapy for Liver Metastases?

Proton therapy has been shown to deliver less radiation to nearby healthy organs compared to traditional X-ray therapy, which is important for liver cancers to reduce the risk of liver damage. Studies have shown that high-dose proton therapy can effectively control tumors with minimal side effects in liver cancer patients, including those with liver metastases. ^{1 2 3 4 5}

Is proton therapy safe for treating liver metastases?

Proton therapy has been studied for safety in treating various cancers, including liver tumors and hepatocellular carcinoma (a type of liver cancer). Research suggests it can reduce damage to healthy tissues, which may lower the risk of side effects compared to traditional radiation therapy. ^{4 6 7 8 9}

How is proton therapy different from other treatments for liver metastases?

Proton therapy is unique because it delivers radiation with a near-zero exit dose, meaning it spares more of the healthy liver tissue compared to traditional X-ray therapy. This can reduce the risk of radiation-induced liver disease and improve outcomes for patients with liver metastases. ^{1 2 3 10 11}

What is the purpose of this trial?

Local control of hepatic metastases appears to be a major determinant of overall survival. However, many patients are not suitable for resection due to medical or surgical reasons. Therefore, there is an important role for a treatment that can provide the equivalent of tumor resection with minimal morbidity. Stereotactic body radiotherapy (SBRT) delivers an ablative regimen of highly focused external beam radiotherapy that targets one or more discrete extracranial lesions. Published reports using SBRT to treat liver metastases have shown actuarial local control rates ranging from 50-100% with higher doses associated with better local control. In patients with metastatic liver disease, aggressive local therapy using modern radiotherapy techniques are promising and project to have a substantial role in the treatment of metastatic liver cancer to treat unresectable disease. The dosimetric advantage of proton therapy may lead to improved clinical outcomes with less morbidity, however, there is no clinical data to confirm this assertion. We thus propose a phase I study to determine the feasibility and safety of stereotactic body proton therapy in patients with liver metastases followed by a phase II study to determine the efficacy of such treatment on local control.

Research Team

Gary Yang, MD

Principal Investigator

[e-mail]

Eligibility Criteria

Adults with liver metastases from non-lymphoma cancers, who have good liver, kidney, and bone marrow function. They should not have had prior radiation that overlaps with the treatment area or active infections in the liver. Participants must be able to practice contraception and sign informed consent.

Inclusion Criteria

I am fully active or can carry out light work.

My blood tests show I have enough white blood cells, platelets, and hemoglobin.

My kidney function is good (creatinine level is below 2mg/dL).

Exclusion Criteria

I have had radiation therapy to my liver before.

Severe, active co-morbidity that may impact survival

I need frequent procedures to remove fluid from my abdomen.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Determine the feasibility and safety of stereotactic body proton therapy in patients with liver metastases

6-8 weeks

Phase II Treatment

Determine the efficacy of stereotactic body proton therapy on local control of liver metastases

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Proton

Trial Overview The trial is testing stereotactic body proton therapy for patients with up to three liver lesions smaller than 5cm each. It's a two-phase study: Phase I checks if it's safe and doable; Phase II tests how well it controls cancer spread in the liver.

Participant Groups

Group I: Proton Radiation Experimental Treatment 2 Interventions

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

Approved in United States as Proton Therapy for:

• Liver metastases
• Hepatocellular carcinoma
• Cholangiocarcinoma

Approved in European Union as Proton Therapy for:

• Liver metastases
• Hepatocellular carcinoma
• Cholangiocarcinoma

Approved in Japan as Proton Therapy for:

• Liver metastases
• Hepatocellular carcinoma
• Cholangiocarcinoma

Who Is Running the Clinical Trial?

Loma Linda University

Lead Sponsor

Trials

322

Recruited

267,000+

Findings from Research

Proton therapy (PT) for primary liver cancer showed promising results in a study of 18 patients, with a one-year overall survival rate of 63% and a high local control rate of 90%.

The treatment demonstrated low toxicity, with only one patient experiencing a significant decrease in liver function, indicating that PT is a safe and effective option for patients with primary liver cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical results of active scanning proton therapy for primary liver tumors. Dionisi, F., Brolese, A., Siniscalchi, B., et al.[2022]

Proton beam therapy (PBT) is safer than X-ray therapy (XRT) for liver cancer treatment because it delivers a lower dose of radiation to surrounding healthy organs, which is crucial in reducing the risk of radiation-induced liver disease (RILD).

PBT has demonstrated excellent long-term tumor control with minimal toxicity in patients with hepatocellular carcinoma (HCC) and is increasingly being used effectively for unresectable cholangiocarcinoma and liver metastases, particularly for larger tumors that are not suitable for XRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy for liver cancers. Chuong, M., Kaiser, A., Molitoris, J., et al.[2020]

In a study of 60 patients with unresectable hepatocellular carcinoma treated with proton beam radiotherapy, the 3-year local progression-free survival rate was 90%, indicating high efficacy of this treatment.

The study identified indocyanine-green retention rate (ICG R15) and the volume of noncancerous liver receiving radiation (V30) as important predictors for the risk of developing proton-induced hepatic insufficiency, helping to guide treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-volume histogram analysis of the safety of proton beam therapy for unresectable hepatocellular carcinoma. Kawashima, M., Kohno, R., Nakachi, K., et al.[2018]

Proton beam radiotherapy (PRT) demonstrated excellent control of hepatocellular carcinoma (HCC) with a 2-year local progression-free rate of 96% among 30 patients, indicating its efficacy as a treatment option.

The treatment was well tolerated with minimal acute toxicity, and despite some patients experiencing hepatic insufficiency, PRT was completed as planned, suggesting it is a safe intervention for patients with liver cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of radiotherapy employing proton beam for hepatocellular carcinoma. Kawashima, M., Furuse, J., Nishio, T., et al.[2022]

Proton beam therapy (PBT) is a safe and effective treatment for hepatocellular carcinoma (HCC) in patients with cirrhosis, with minimal acute toxicity and no significant liver function changes observed six months post-treatment.

In a study of 76 patients, the median progression-free survival was 36 months, and 60% of patients within the Milan criteria achieved a 3-year progression-free survival rate, indicating promising long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of high-dose proton beam radiotherapy for hepatocellular carcinoma: a phase 2 prospective trial. Bush, DA., Kayali, Z., Grove, R., et al.[2022]

Proton beam therapy (PBT) for hepatocellular carcinoma (HCC) demonstrated a median overall survival of 48.8 months and a 3-year local control rate of 90%, indicating its efficacy in treating this type of cancer.

The treatment had a low incidence of severe late adverse events, with only 4.7% of patients experiencing grade 3 or higher complications, suggesting that PBT is a safe option for patients with HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Beam Therapy for Hepatocellular Carcinoma: Multicenter Prospective Registry Study in Japan. Mizumoto, M., Ogino, H., Okumura, T., et al.[2023]

Proton beam therapy may lead to fewer side effects compared to conventional photon therapy, particularly in children with brain tumors and certain adult cancers, while showing similar overall survival rates.

The estimated cost of establishing a proton beam therapy center in Ontario is $124.8 million over five years, but it could significantly reduce per-patient costs compared to current out-of-country treatments, making it a potentially cost-effective option for specific pediatric cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Beam Therapy for Cancer in Children and Adults: A Health Technology Assessment. [2022]

Proton beam therapy (PBT) was found to be a potentially safe and effective treatment for metastatic liver tumors, with a 5-year overall survival rate of 24% among 140 patients studied.

Patients with lesions confined to the liver had a higher 5-year overall survival rate of 28%, especially those receiving curative treatment (30%), compared to those receiving palliative care (23%), indicating that treatment strategy significantly impacts survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy for metastatic liver tumors. Fukumitsu, N., Okumura, T., Takizawa, D., et al.[2018]

In a study of 192 prostate cancer patients treated with proton beam therapy (PBT) over a median follow-up of 1.7 years, only 5 patients experienced grade 3 toxicity, with no occurrences of grade 4 or 5 toxicity, indicating a high safety profile for this treatment.

Patient-reported outcomes showed stable urinary function post-treatment, while sexual health scores declined slightly at 1 year but did not worsen thereafter; bowel function scores also decreased but stabilized, suggesting manageable side effects associated with PBT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early toxicity and patient reported quality-of-life in patients receiving proton therapy for localized prostate cancer: a single institutional review of prospectively recorded outcomes. Lee, HJ., Macomber, MW., Spraker, MB., et al.[2019]

In a study of 17 patients with liver metastasis from breast cancer treated with proton beam therapy (PBT), the treatment demonstrated a very high freedom from local progression rate of 94.1% over three years, indicating its effectiveness in controlling local disease.

The treatment was well-tolerated, with no grade 3 or higher adverse events reported, suggesting that PBT is a safe option for patients with liver metastasis from breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness of Hypofractionated Proton Beam Therapy for Liver Metastasis From Breast Cancer. Kim, TH., Lee, KS., Sim, SH., et al.[2022]

Proton radiation therapy is effective in treating hepatocellular carcinoma (HCC), especially in complex cases like larger tumors or those with vascular involvement, due to its near-zero exit dose and ability to spare healthy liver tissue.

Emerging evidence indicates that proton therapy may lead to better survival rates and lower toxicity, particularly in reducing the risk of liver failure, compared to traditional photon therapy, with a randomized controlled trial currently in progress to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Therapy in the Management of Hepatocellular Carcinoma. Kobeissi, JM., Hilal, L., Simone, CB., et al.[2022]

References

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

Clinical results of active scanning proton therapy for primary liver tumors. [2022]

2. China pubmed.ncbi.nlm.nih.gov

Proton beam therapy for liver cancers. [2020]

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

Dose-volume histogram analysis of the safety of proton beam therapy for unresectable hepatocellular carcinoma. [2018]

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

Phase II study of radiotherapy employing proton beam for hepatocellular carcinoma. [2022]

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

The safety and efficacy of high-dose proton beam radiotherapy for hepatocellular carcinoma: a phase 2 prospective trial. [2022]

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

Proton Beam Therapy for Hepatocellular Carcinoma: Multicenter Prospective Registry Study in Japan. [2023]

7. Canada pubmed.ncbi.nlm.nih.gov

Proton Beam Therapy for Cancer in Children and Adults: A Health Technology Assessment. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

Proton beam therapy for metastatic liver tumors. [2018]

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

Early toxicity and patient reported quality-of-life in patients receiving proton therapy for localized prostate cancer: a single institutional review of prospectively recorded outcomes. [2019]

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

Clinical Effectiveness of Hypofractionated Proton Beam Therapy for Liver Metastasis From Breast Cancer. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Proton Therapy in the Management of Hepatocellular Carcinoma. [2022]