A Pilot Study to Assess Theragnostically Planned Liver Radiation to Optimize Radiation Therapy

Study Overview
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Brief Summary
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The purpose of this study is to compare radiation treatment plans that are designed for patients with liver cancer. One treatment plan will be created using routine procedures and scans normally performed for radiation treatment planning. The other treatment plan will be created using routine procedures with the addition of two imaging scans; a HIDA (Hepatobiliary Iminodiacetic Acid) scan and an MRI (Magnetic Resonance Imaging) scan. This study will evaluate if adding these imaging scans to treatment planning can reduce the amount of radiation to healthy liver tissue during treatment.

Official Title
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A Pilot Study to Assess Theragnostically Planned Liver Radiation With Functional DVH Analysis to Optimize Individualized Radiation Therapy

Conditions
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Liver Cancer, Hepatocellular Carcinoma, Cholangiocarcinoma

Intervention / Treatment
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* Diagnostic Test: Hepatobiliary Iminodiacetic Acid (HIDA) scan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subjects must be ≥ 18 years of age at the time of signing informed consent Diagnosis of primary liver malignancy (including hepatocellular carcinoma [HCC] or cholangiocarcinoma) or liver metastasis from any primary solid tumor site by characteristic imaging findings on CT or MRI, clinical presentation, and/or pathologic confirmation of diagnosis. Subjects with other current or prior malignancies are eligible for this study. Patients with liver metastases must have at least one of the following clinical factors that may affect liver function: History of liver resection (at any time) History of cirrhosis (any cause), fatty liver disease, or hepatic insufficiency due to any cause Prior radiation to the upper abdomen including radioembolization ECOG (Zubrod) Performance Status 0-2. Subjects must have a Child-Turcotte-Pugh (CTP) score ≤ 7 to be eligible. Patients who have been previously treated with non-SBRT liver directed therapies may be enrolled on study. At least 3 months must have elapsed between the most recent liver-directed therapy and study entry. Ability to provide written informed consent and HIPAA authorization Subjects with an allergy to contrast agents may be enrolled at the treating physician's discretion with appropriate pre-treatment and symptom management. Exclusion Criteria Subjects who are pregnant or planning to become pregnant during the study. Women of child bearing potential must have a negative pregnancy test Subjects must not have received chemotherapy within 2 weeks of planned 1st day of RT. No more than 3 lesions may be treated. The maximum sum of the diameter(s) of the lesion(s) must be ≤6 cm Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (or infections requiring systemic antibiotic treatment), active upper GI ulceration or hemorrhage, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would in the opinion of the investigator limit compliance with study requirements

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Theragnostic SBRT Planning<br>The theragnostic SBRT plan using the HIDA scan was chosen as the plan that reduced the dose of radiation to functional liver without compromising target coverage or tumor control. | Diagnostic Test: Hepatobiliary Iminodiacetic Acid (HIDA) scan<br>* HIDA scan was used as the planning scan for SBRT.<br>|
| No Intervention: Standard SBRT Planning<br>The standard SBRT plan was chosen as the plan that reduced the dose of radiation to functional liver without compromising target coverage or tumor control. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Functional Reserve of Liver Between Theragnostic SBRT Planning and Standard SBRT Planning | The functional reserve of the liver for both standard SBRT planning and theragnostic SBRT planning will be calculated for each patient regardless of which plan was ultimately chosen. Function reserve of the liver = (number of counts outside 15 Gy isodose line / total number of counts within the liver) * global liver function; where global liver function is the rate of liver uptake (%/min) between 150 to 300 seconds normalized to body surface area (m^2) using the Du Bois method. The difference in functional reserve between the theragnostic plan and the standard plan was calculated for each patient. | Day -1 of Radiation Treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants for Whom Theragnostically Planned Radiation is Chosen for the Radiation Treatment Plan | The percentage of participants for whom theragnostically planned radiation is chosen for the radiation treatment plan over the standard plan will be calculated along with the corresponding exact 95% Binomial confidence interval. | Day -1 of Radiation Treatment | 
| Duration of Local Control | Duration of local control was assessed by calculating the time from on study date to date of local failure. Patients who did not experience local failure were censored at their last evaluation date. Local failure (progressive disease at primary diagnosis site) was evaluated using RECIST v1.1 criteria: Complete response: Disappearance of all target lesions; Partial response: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter; Stable Disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Progressive Disease: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. The Kaplan-Meier method was used to determine the median and 95% confidence interval. | Up to 15 months | 
| Progression Free Survival | Progression free survival was defined as the time from on study date to date of recurrence of any type or death from any cause. Patients who did not experience recurrence or death were censored at their last evaluation date. The Kaplan-Meier method was used to determine the median and 95% confidence interval. | Up to 15 months | 
| Overall Survival | Overall survival was defined as the time from on study date to death due to any cause. Patients who remained alive were censored at their last known alive date. The Kaplan-Meier method was used to determine the median and 95% confidence interval. | Up to 3 years | 
| Time to Transplant | Time to transplant was defined as the time from on study date to the date of transplant. Patients who did not receive transplant were censored at their off study date. The Kaplan-Meier method was used to determine the median and 95% confidence interval. | Up to 15 months | 
| Time to Distant Liver Failure | Time to distant liver failure was defined as the time from on study date to the date of distant liver failure. Patients who did not experience distant liver failure were censored at their date of last evaluation. The Kaplan-Meier method was used to determine the median and 95% confidence interval. | Up to 15 months | 
| Time Until Salvage Treatment | Time until salvage treatment was defined as the time from on study date to the start date of salvage treatment. Patients who did not receive salvage treatment were censored at their off study date. The Kaplan-Meier method was used to determine the median and 95% confidence interval. | Up to 15 months | 
| Number of Patients With Treatment-Related Adverse Events Grade 3 or Above | Number of unique patients who had a treatment-related (possible, probable, or definite) adverse event with grade 3 or greater using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. | Every 15 days for approximately 6 months | 
| Change in MELD Score | Model for end-stage liver disease (MELD) score measures the severity of liver dysfunction. MELD scores range from 6 to 40 and are based on lab tests including serum creatinine, total bilirubin, and INR. The higher the number, the worse the liver function. | Up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiation Treatment