Standard vs Targeted Radiation Therapy for Liver Cancer

(SAVIOR Trial)

Overseen By Morgan Black

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Disqualifiers: Severe cirrhosis, Prior radiotherapy, Active hepatitis, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 2 weeks

110 Participants Needed

Trial Summary

What is the purpose of this trial?

Radiation is a standard treatment option for patients with liver cancer. Unfortunately, the tumour grows after radiation in many patients and radiation can harm normal tissues. A new treatment using a specialized radiation procedure called Stereotactic body radiotherapy (SBRT) may increase the chance to control liver cancer and reduce the chance of harm to normal tissues. SBRT allows radiation treatments to be focused more precisely, and be delivered more accurately than with older treatments. SBRT has become a routine treatment. Further research has found that specialized computer programs can possibly guide the selection of an appropriate SBRT dose. This is called radiobiological guidance. However, this has not yet been proven to improve outcomes and/or reduce toxicity. Therefore, the purpose of this study is to find out if SBRT at standard dose versus SBRT guided by radiobiological techniques is better for you and your liver cancer.

Will I have to stop taking my current medications?

The trial requires that multikinase inhibitors be stopped 2 weeks before radiation and can be restarted 1 week after. Chemotherapy must be completed at least 2 weeks before radiation and not planned for at least 1 week after treatment (4 weeks for anthracyclines).

What data supports the effectiveness of this treatment for liver cancer?

Research shows that modern radiation therapy techniques, like stereotactic body radiotherapy (SBRT) and proton beam therapy (PBT), are effective in treating liver cancer, with response rates between 50% to 97%. These methods allow precise targeting of tumors while sparing healthy liver tissue, making them a promising option for liver cancer treatment. ^{1 2 3 4 5}

Is radiation therapy generally safe for treating liver cancer?

Radiation therapy for liver cancer is generally considered safe, with serious complications being rare. Most side effects are mild, and modern techniques allow precise targeting of tumors while sparing healthy liver tissue. ^{1 6 7 8 9}

How does radiation therapy for liver cancer differ from other treatments?

Radiation therapy for liver cancer is unique because it uses advanced techniques like stereotactic body radiotherapy (SBRT) and proton beam therapy (PBT) to precisely target tumors while sparing healthy liver tissue. These methods allow for effective treatment of liver tumors that were previously difficult to reach, with fewer side effects compared to traditional radiation methods. ^{1 2 3 8 10}

Research Team

Michael Lock, MD

Principal Investigator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Eligibility Criteria

This trial is for adults with liver cancer that can't be removed by surgery. It's open to those with primary liver cancer or certain types of liver metastases, up to 5 measurable lesions, and a life expectancy over 6 months. Patients must not have severe illnesses limiting life span under 6 months, active hepatitis, severe cirrhosis (Child Pugh >B7), or prior overlapping radiation therapy.

Inclusion Criteria

My condition cannot be treated with surgery.

I stopped taking multikinase inhibitors 2 weeks before radiation and can restart 1 week after.

I am older than 18 years.

Exclusion Criteria

My liver condition is not severe (Child Pugh ≤B7).

My life expectancy is more than 6 months despite my other health issues.

I've had radiation in the same area where my current cancer is located.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either standard dose or personalized dose SBRT, delivered in 5 fractions every other day excluding weekends and holidays

2 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and progression of disease

6 months

1 month post-treatment, 3 months post-treatment, every 3 months up to 5 years

Long-term follow-up

Participants' overall survival and quality of life are assessed

Up to 5 years

Treatment Details

Interventions

• Radiation therapy

Trial Overview The study compares standard dose SBRT versus radiobiologically-guided SBRT in treating liver cancer. The goal is to see if the guided approach better controls the cancer while reducing harm to healthy tissues compared to the standard treatment.

Participant Groups

Group I: Personalized Dose Selection Radiation Experimental Treatment 1 Intervention

Patients in the experimental arm will receive individually selected prescription dose guided by radiobiological parameters described below, preferably delivered in 5 fractions every other day, excluding weekends and holidays. Volumetric-modulated arc therapy (VMAT) is the preferred planning technique. Typical planning uses 2 arcs, \<=10MV and FFF mode where possible as almost all liver treatments are gated). In the event of multiple lesions, multiple isocentres are allowed. Often lateral isocentre shifts are significant and therefore arc ranges should be chosen to minimize collision risk. Treatment will be every second day excluding weekends and holidays.

Group II: Standard Dose Radiation Active Control 1 Intervention

Patients in the standard arm will receive a standard dose of 2000cGy in 5 fractions using simple CT planning. IMRT is allowed. Treatment will be every second day excluding weekends and holidays.

Radiation therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiotherapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer

Approved in United States as Radiation therapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer
• Cervical cancer
• Uterine cancer

Approved in Canada as Radiotherapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer

Approved in Japan as Radiation therapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer
• Esophageal cancer

Approved in China as Radiotherapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer
• Nasopharyngeal cancer

Approved in Switzerland as Radiation therapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer

Who Is Running the Clinical Trial?

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Findings from Research

Radiation therapy, including techniques like brachytherapy and stereotactic body radiotherapy (SBRT), is safe and effective for treating liver cancers, with response rates ranging from 50% to 97% in recent studies.

Technological advancements in imaging and radiation delivery have improved the ability to treat difficult-to-reach tumors while minimizing damage to surrounding healthy tissue, making these therapies increasingly viable for patients with compromised liver function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation oncology approaches in liver malignancies. Kennedy, AS.[2018]

Modern radiation therapy techniques, such as image-guided radiotherapy and stereotactic body radiotherapy, have significantly improved the treatment of liver cancers by allowing for more effective targeting of tumors while protecting healthy tissue.

These advancements in radiation therapy should be considered alongside traditional treatments like surgery and radiofrequency ablation, providing a comprehensive approach to managing various types of liver cancer, including colorectal liver metastases and intrahepatic cholangiocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ablative radiotherapy for colorectal liver metastases and intrahepatic cholangiocarcinoma. Schiff, JP., D'Souza, A., Henke, LE.[2023]

External beam radiation therapy is emerging as a promising treatment option for hepatocellular carcinoma (HCC) due to advancements in planning and delivery techniques.

The review highlights the growing interest in radiation therapy for liver tumors and suggests that ongoing research may further enhance its effectiveness and integration into treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy for hepatocellular carcinoma: History, current status, and opportunities. Meyer, J., Singal, AG.[2018]

High dose rate interstitial irradiation with (192)Ir showed promising results, achieving local control of hepatic metastases for a median of 8 months and complete tumor eradication in 2 patients.

Direct intratumoral injection of 90Y microspheres was highly effective, reducing the size of 90.6% of tumors and completely destroying them in 8 patients, indicating a potential for targeted treatment in liver cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Internal radiation therapy for patients with primary or metastatic hepatic cancer: a review. Ho, S., Lau, WY., Leung, TW., et al.[2005]

In a study of 133 patients with unresectable hepatocellular carcinoma (HCC), proton radiation therapy significantly improved overall survival compared to photon therapy, with median survival times of 31 months for protons versus 14 months for photons.

Proton therapy also reduced the risk of non-classic radiation-induced liver disease, which is linked to worse survival outcomes, suggesting that proton therapy may help prevent liver decompensation after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protons versus Photons for Unresectable Hepatocellular Carcinoma: Liver Decompensation and Overall Survival. Sanford, NN., Pursley, J., Noe, B., et al.[2020]

Selective internal radiation therapy (SIRT) is an effective targeted treatment for both primary and metastatic liver diseases, utilizing brachytherapy to deliver radiation directly to the tumor.

The review emphasizes the importance of thorough pre-treatment workup and safety considerations to optimize patient outcomes and minimize risks associated with this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective internal radiation therapy in the management of primary and metastatic disease in the liver. Preston, E., Shaida, N.[2021]

Stereotactic body radiotherapy and selective internal radiotherapy (radioembolization) are advanced techniques that provide precise and safe radiation delivery for treating hepatocellular carcinoma, showing excellent local control with acceptable toxicity.

Further research is needed to determine the most suitable patient populations and the optimal timing for using these radiation therapies in the treatment of liver cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiation therapy and selective internal radiation therapy for hepatocellular carcinoma. Bujold, A., Dawson, LA.[2011]

Recent advancements in radiation therapy techniques, such as intensity-modulated and stereotactic body radiation therapy, allow for more precise targeting of liver tumors while minimizing damage to surrounding healthy liver tissue.

These innovations could enhance the safety and efficacy of external beam radiotherapy for treating hepatocellular carcinoma, which has historically been limited due to the sensitivity of normal liver tissue to radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External beam radiation therapy for hepatocellular carcinoma: potential of intensity-modulated and image-guided radiation therapy. Fuss, M., Salter, BJ., Herman, TS., et al.[2022]

Recent advancements in 3-dimensional conformal and intensity-modulated radiotherapy allow for higher doses of radiation to be safely delivered to hepatocellular carcinoma (HCC) lesions while minimizing exposure to healthy liver tissue.

These improvements in radiotherapy techniques, along with a better understanding of radiation dose relationships and risks, support the potential for effective treatment of unresectable HCC, warranting further investigation through randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy for hepatocellular carcinoma. Feng, M., Ben-Josef, E.[2022]

An international survey involving 69 radiation therapy professionals revealed a significant increase (36%) in referrals for liver metastases treatment over the past five years, indicating a growing demand for radiation therapy in this area.

The survey highlighted a lack of uniformity in treatment approaches, with various dose regimens and technologies being used, suggesting the need for prospective studies to optimize patient selection and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An international survey on liver metastases radiotherapy. Lock, MI., Hoyer, M., Bydder, SA., et al.[2015]

References

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

Radiation oncology approaches in liver malignancies. [2018]

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

Ablative radiotherapy for colorectal liver metastases and intrahepatic cholangiocarcinoma. [2023]

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

Stereotactic ablative radiotherapy for hepatocellular carcinoma: History, current status, and opportunities. [2018]

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

Internal radiation therapy for patients with primary or metastatic hepatic cancer: a review. [2005]

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

Protons versus Photons for Unresectable Hepatocellular Carcinoma: Liver Decompensation and Overall Survival. [2020]

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

Selective internal radiation therapy in the management of primary and metastatic disease in the liver. [2021]

7. France pubmed.ncbi.nlm.nih.gov

Stereotactic radiation therapy and selective internal radiation therapy for hepatocellular carcinoma. [2011]

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

External beam radiation therapy for hepatocellular carcinoma: potential of intensity-modulated and image-guided radiation therapy. [2022]

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

Radiation therapy for hepatocellular carcinoma. [2022]

10. England pubmed.ncbi.nlm.nih.gov

An international survey on liver metastases radiotherapy. [2015]