Cholangiocarcinoma, Hepatocellular Carcinoma, Liver Cancer
Conditions
Keywords
Radiation Treatment
Brief summary
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.
Interventions
DIAGNOSTIC_TESTHepatobiliary Iminodiacetic Acid (HIDA) scan
HIDA scan was used as the planning scan for SBRT.
Sponsors
Indiana University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. History of liver resection (at any time) 2. History of cirrhosis (any cause), fatty liver disease, or hepatic insufficiency due to any cause 3. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Functional Reserve of Liver Between Theragnostic SBRT Planning and Standard SBRT Planning | Day -1 of Radiation Treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Local Control | Up to 15 months | 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. |
| Progression Free Survival | Up to 15 months | 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. |
| Overall Survival | Up to 3 years | 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. |
| Time to Transplant | Up to 15 months | 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. |
| Percentage of Participants for Whom Theragnostically Planned Radiation is Chosen for the Radiation Treatment Plan | Day -1 of Radiation Treatment | 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. |
| Time Until Salvage Treatment | Up to 15 months | 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. |
| Number of Patients With Treatment-Related Adverse Events Grade 3 or Above | Every 15 days for approximately 6 months | 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. |
| Change in MELD Score | Up to 1 year | 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. |
| Time to Distant Liver Failure | Up to 15 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Theragnostic SBRT Planning 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. | 10 |
| Standard SBRT Planning 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. | 5 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Alternative Therapy | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Theragnostic SBRT Planning | Standard SBRT Planning |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 4 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 6 Participants | 3 Participants |
| Age, Continuous | 64.1 years STANDARD_DEVIATION 8.46 | 63.8 years STANDARD_DEVIATION 9.65 | 64.6 years STANDARD_DEVIATION 6.36 |
| Baseline MELD Score | 10.4 units on a scale STANDARD_DEVIATION 4.4 | 10.2 units on a scale STANDARD_DEVIATION 4.8 | 10.8 units on a scale STANDARD_DEVIATION 3.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 9 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Karnofsky Performance Status KPS 100 | 1 Participants | 1 Participants | 0 Participants |
| Karnofsky Performance Status KPS 80 | 5 Participants | 3 Participants | 2 Participants |
| Karnofsky Performance Status KPS 90 | 9 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 10 Participants | 4 Participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 10 Participants | 7 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 9 | 2 / 5 |
| other Total, other adverse events | 9 / 9 | 4 / 5 |
| serious Total, serious adverse events | 3 / 9 | 1 / 5 |
Outcome results
Primary
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.
Time frame: Day -1 of Radiation Treatment
Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Theragnostic SBRT Planning | Difference in Functional Reserve of Liver Between Theragnostic SBRT Planning and Standard SBRT Planning | 0.22 %/min/m^2 | Standard Deviation 0.25 |
| Standard SBRT Planning | Difference in Functional Reserve of Liver Between Theragnostic SBRT Planning and Standard SBRT Planning | 0.02 %/min/m^2 | Standard Deviation 0.07 |
Secondary
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.
Time frame: Up to 1 year
Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes. Patient numbers differ due to missed visits and/or patients no longer being on study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Theragnostic SBRT Planning | Change in MELD Score | Change from Baseline to 3 Month | 0.8 units on a scale | Standard Deviation 3.9 |
| Theragnostic SBRT Planning | Change in MELD Score | Baseline MELD Score | 8.8 units on a scale | Standard Deviation 1.9 |
| Theragnostic SBRT Planning | Change in MELD Score | Change from Baseline to 6 Month | 1.0 units on a scale | Standard Deviation 1.9 |
| Theragnostic SBRT Planning | Change in MELD Score | Change from Baseline to 1 Month | 0.2 units on a scale | Standard Deviation 1.2 |
| Theragnostic SBRT Planning | Change in MELD Score | Change from Baseline 12 Month | 1.4 units on a scale | Standard Deviation 1.8 |
| Theragnostic SBRT Planning | Change in MELD Score | Change from Baseline to Mid-Treatment | 0.4 units on a scale | Standard Deviation 1.7 |
| Standard SBRT Planning | Change in MELD Score | Change from Baseline 12 Month | -1.8 units on a scale | Standard Deviation 2.1 |
| Standard SBRT Planning | Change in MELD Score | Change from Baseline to Mid-Treatment | -0.4 units on a scale | Standard Deviation 0.5 |
| Standard SBRT Planning | Change in MELD Score | Change from Baseline to 1 Month | 1.8 units on a scale | Standard Deviation 8.6 |
| Standard SBRT Planning | Change in MELD Score | Change from Baseline to 3 Month | -2.0 units on a scale | Standard Deviation 2.8 |
| Standard SBRT Planning | Change in MELD Score | Change from Baseline to 6 Month | -2.0 units on a scale | Standard Deviation 3.7 |
| Standard SBRT Planning | Change in MELD Score | Baseline MELD Score | 10.8 units on a scale | Standard Deviation 3.7 |
Secondary
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.
Time frame: Up to 15 months
Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Theragnostic SBRT Planning | Duration of Local Control | NA months |
| Standard SBRT Planning | Duration of Local Control | NA months |
Secondary
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.
Time frame: Every 15 days for approximately 6 months
Population: Patients who received at least one dose of radiation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Theragnostic SBRT Planning | Number of Patients With Treatment-Related Adverse Events Grade 3 or Above | 0 Participants |
| Standard SBRT Planning | Number of Patients With Treatment-Related Adverse Events Grade 3 or Above | 0 Participants |
Secondary
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.
Time frame: Up to 3 years
Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Theragnostic SBRT Planning | Overall Survival | 23.9 months |
| Standard SBRT Planning | Overall Survival | 27.5 months |
Secondary
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.
Time frame: Day -1 of Radiation Treatment
Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes. The two study arms are combined for this analysis because the arm was assigned based on the SBRT planning scheme that was ultimately chosen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Theragnostic SBRT Planning | Percentage of Participants for Whom Theragnostically Planned Radiation is Chosen for the Radiation Treatment Plan | 64.3 percentage of participants |
Secondary
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.
Time frame: Up to 15 months
Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Theragnostic SBRT Planning | Progression Free Survival | NA months |
| Standard SBRT Planning | Progression Free Survival | NA months |
Secondary
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.
Time frame: Up to 15 months
Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Theragnostic SBRT Planning | Time to Distant Liver Failure | NA months |
| Standard SBRT Planning | Time to Distant Liver Failure | NA months |
Secondary
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.
Time frame: Up to 15 months
Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Theragnostic SBRT Planning | Time to Transplant | NA months |
| Standard SBRT Planning | Time to Transplant | NA months |
Secondary
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.
Time frame: Up to 15 months
Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Theragnostic SBRT Planning | Time Until Salvage Treatment | NA months |
| Standard SBRT Planning | Time Until Salvage Treatment | NA months |