Hepatocellular Carcinoma, Intrahepatic Cholangiocarcinoma, Stage IV Liver Cancer, Stage IVA Liver Cancer, Stage IVB Liver Cancer, Vascular Thrombosis
Conditions
Brief summary
This pilot trial studies how well single photon emission computed tomography (SPECT)/computed tomography (CT) with technetium Tc-99m sulfur colloid works in measuring liver function in patients with liver cancer that has or has not spread to other place in the body who are undergoing radiation therapy or surgery. Diagnostic procedures, such as sulfur colloid SPECT/CT scans, may measure normal liver tissue before, during and after treatment and help doctors plan better treatment for liver cancer patients.
Detailed description
OUTLINE: Patients are assigned to 1 of 2 cohorts depending on which standard of care they are receiving outside of this study, as part of their cancer treatment: radiation treatment (RT) or surgery. All patients have a total of 3 SPECT/CT imaging with 99mTc-SC. The first scan in both cohorts is routine medical care (not experimental) and takes place prior to initiation of RT or surgery. Two follow up scans are part of the protocol. COHORT A (patients receiving radiation therapy per standard cancer treatment): The first follow up scan occurs at mid-RT, and the second one at 1 month post-RT. COHORT B (patients undergoing surgery per standard cancer treatment): The first follow-up scan occurs 3-5 days postoperatively, and the second one at 1 month post-operatively. An additional intravenous (IV) contrast enhanced CT scan (70 second delay) will be obtained immediately following the SPECT/CT scan for all 3 SPECT/CT scans. After completion of study, patients are followed up at 6 months.
Interventions
PROCEDUREComputed Tomography
Undergo SC SPECT/CT
PROCEDURESingle Photon Emission Computed Tomography
Undergo SC SPECT/CT
Given IV
Sponsors
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a diagnosis of hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, or metastatic liver cancer planned to receive definitive doses of radiation or surgical resection are eligible * Measurable hepatic disease and/or presence of vascular tumor thrombosis * Diagnostic CT or magnetic resonance imaging (MRI) scan within 2 months of study entry * There are no limits on prior therapy; patients are allowed to have prior systemic therapy, radiation therapy, radiofrequency ablation, catheter-based therapies, and surgery; patients are allowed to have concurrent chemotherapy with radiation treatment * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Patients unable to tolerate a SPECT/CT 99mTc-SC scan * Patients who are not planning to adhere to the required follow up schedule as outlined in this protocol * Pregnant women * Women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception * Patients unable to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Functional Liver Volume: Cohort A - Radiation | Baseline, mid-treatment at 2 weeks, and post-treatment at 1 month | Functional liver volume ratio (FLV): represents the percent of the anatomic liver which is functioning and is defined as the ratio of liver functional volume (in cc of volume) to the anatomic liver volume (in cc of volume). Since this outcome measure is a ratio, it is unitless. A higher FLV ratio reflects a higher volume of functional liver. |
| Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Liver-to-Spleen Mean: Cohort A - Radiation | Baseline, mid-treatment at 2 weeks, and post-treatment at 1 month | Liver-to-spleen ratio (L/S mean): represents the magnitude of the global liver function and is defined as the ratio of the mean SC counts in the functional liver to the mean SC counts in the spleen. Since this outcome measure is a ratio, it is unitless. A higher L/S mean ratio reflects higher magnitude of liver function. |
| Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Total Liver Function: Cohort A - Radiation | Baseline, mid-treatment at 2 weeks, and post-treatment at 1 month | Total liver function (TLF): represents the integral liver function and is defined by the product of the functional liver volume (FLV) ratio and liver-to-spleen (L/S) mean ratio. Since this outcome measure is a product of ratios, it is unitless. A higher TLF ratio reflects higher liver function. Median differences were estimated using Wilcoxon (Mann-Whitney) tests. |
| Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Spatial Heterogeneity: Cohort A - Radiation | Baseline, mid-treatment at 2 weeks, and post-treatment at 1 month | To characterize spatial distribution of functional liver, the coefficient of variation (CV) within the FLV will be measured (unitless). A higher CV means more variability or heterogeneity in liver function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Liver-to-Spleen Mean: Cohort B - Surgery | Baseline, perioperative (2-3 days post surgery), and postoperative (1 month post surgery) | Liver-to-spleen ratio (L/S mean): represents the magnitude of the global liver function and is defined as the ratio of the mean SC counts in the functional liver to the mean SC counts in the spleen. Since this outcome measure is a ratio, it is unitless. A higher L/S mean ratio reflects higher magnitude of liver function. |
| Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Total Liver Function: Cohort B - Surgery | Baseline, perioperative (2-3 days post surgery), and postoperative (1 month post surgery) | Total liver function (TLF): represents the integral liver function and is defined by the product of the functional liver volume (FLV) ratio and liver-to-spleen (L/S) mean ratio. Since this outcome measure is a product of ratios, it is unitless. A higher TLF ratio reflects higher liver function. Median differences were estimated using Wilcoxon (Mann-Whitney) tests. |
| Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Functional Liver Volume: Cohort B - Surgery | Baseline, perioperative (2-3 days post surgery), and postoperative (1 month post surgery) | Functional liver volume ratio (FLV): represents the percent of the anatomic liver which is functioning and is defined as the ratio of liver functional volume (in cc of volume) to the anatomic liver volume (in cc of volume). Since this outcome measure is a ratio, it is unitless. A higher FLV ratio reflects a higher volume of functional liver. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SC SPECT/CT: Cohort A - Radiation Cohort A includes all subjects receiving radiation therapy per standard of care. Patients have a total of 3 SPECT/CT imaging with 99mTc-SC. The first scan in both cohorts is routine medical care (not experimental) and takes place prior to initiation of RT or surgery. Two follow up scans are part of the protocol.
The first follow up scan occurs at mid-RT, and the second one at 1-month post-RT.
Computed Tomography: Undergo SC SPECT/CT
Single Photon Emission Computed Tomography: Undergo SC SPECT/CT
Technetium Tc-99m Sulfur Colloid: Given IV | 38 |
| SC SPECT/CT: Cohort B - Surgery Cohort B includes all subjects undergoing surgery per standard of care. Patients have a total of 3 SPECT/CT imaging with 99mTc-SC. The first scan in both cohorts is routine medical care (not experimental) and takes place prior to initiation of RT or surgery. Two follow up scans are part of the protocol.
The first follow-up scan occurs 3-5 days postoperatively, and the second one at 1 month post-operatively. An additional IV contrast enhanced CT scan (70 second delay) will be obtained immediately following the SPECT/CT scan for all 3 SPECT/CT scans.
Computed Tomography: Undergo SC SPECT/CT
Single Photon Emission Computed Tomography: Undergo SC SPECT/CT
Technetium Tc-99m Sulfur Colloid: Given IV | 3 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | SC SPECT/CT: Cohort A - Radiation | SC SPECT/CT: Cohort B - Surgery | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 31 Participants | 2 Participants | 33 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 1 Participants | 8 Participants |
| Age, Continuous | 71.87 years | 74.67 years | 72.07 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 3 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 38 participants | 3 participants | 41 participants |
| Sex: Female, Male Female | 15 Participants | 1 Participants | 16 Participants |
| Sex: Female, Male Male | 23 Participants | 2 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 22 / 36 | 1 / 3 |
| other Total, other adverse events | 0 / 36 | 0 / 3 |
| serious Total, serious adverse events | 0 / 36 | 0 / 3 |
Outcome results
Primary
Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Functional Liver Volume: Cohort A - Radiation
Functional liver volume ratio (FLV): represents the percent of the anatomic liver which is functioning and is defined as the ratio of liver functional volume (in cc of volume) to the anatomic liver volume (in cc of volume). Since this outcome measure is a ratio, it is unitless. A higher FLV ratio reflects a higher volume of functional liver.
Time frame: Baseline, mid-treatment at 2 weeks, and post-treatment at 1 month
Population: Only participants in Cohort A with evaluable treatment scans were assessed for this outcome.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Functional Liver Volume: Cohort A - Radiation | Baseline FLV Ratio | 0.36 ratio |
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Functional Liver Volume: Cohort A - Radiation | Mid-Treatment FLV Ratio | 0.34 ratio |
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Functional Liver Volume: Cohort A - Radiation | Post-Treatment FLV Ratio | 0.25 ratio |
Primary
Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Liver-to-Spleen Mean: Cohort A - Radiation
Liver-to-spleen ratio (L/S mean): represents the magnitude of the global liver function and is defined as the ratio of the mean SC counts in the functional liver to the mean SC counts in the spleen. Since this outcome measure is a ratio, it is unitless. A higher L/S mean ratio reflects higher magnitude of liver function.
Time frame: Baseline, mid-treatment at 2 weeks, and post-treatment at 1 month
Population: Only participants in Cohort A with evaluable treatment scans were assessed for this outcome.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Liver-to-Spleen Mean: Cohort A - Radiation | Baseline L/S Ratio | 1.11 ratio |
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Liver-to-Spleen Mean: Cohort A - Radiation | Mid-Treatment L/S Ratio | 0.96 ratio |
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Liver-to-Spleen Mean: Cohort A - Radiation | Post-Treatment L/S Ratio | 0.71 ratio |
Primary
Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Spatial Heterogeneity: Cohort A - Radiation
To characterize spatial distribution of functional liver, the coefficient of variation (CV) within the FLV will be measured (unitless). A higher CV means more variability or heterogeneity in liver function.
Time frame: Baseline, mid-treatment at 2 weeks, and post-treatment at 1 month
Population: Only participants in Cohort A with evaluable treatment scans were assessed for this outcome.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Spatial Heterogeneity: Cohort A - Radiation | Baseline CV Ratio | 0.38 ratio |
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Spatial Heterogeneity: Cohort A - Radiation | Mid-Treatment CV Ratio | 0.40 ratio |
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Spatial Heterogeneity: Cohort A - Radiation | Post-Treatment CV Ratio | 0.54 ratio |
Primary
Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Total Liver Function: Cohort A - Radiation
Total liver function (TLF): represents the integral liver function and is defined by the product of the functional liver volume (FLV) ratio and liver-to-spleen (L/S) mean ratio. Since this outcome measure is a product of ratios, it is unitless. A higher TLF ratio reflects higher liver function. Median differences were estimated using Wilcoxon (Mann-Whitney) tests.
Time frame: Baseline, mid-treatment at 2 weeks, and post-treatment at 1 month
Population: Only participants in Cohort A with evaluable treatment scans were assessed for this outcome.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Total Liver Function: Cohort A - Radiation | Mid-Treatment TLF Ratio | 0.29 ratio |
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Total Liver Function: Cohort A - Radiation | Baseline TLF Ratio | 0.41 ratio |
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Total Liver Function: Cohort A - Radiation | Post-Treatment TLF Ratio | 0.18 ratio |
| Child-Pugh A Patients | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Total Liver Function: Cohort A - Radiation | Mid-Treatment TLF Ratio | 0.39 ratio |
| Child-Pugh A Patients | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Total Liver Function: Cohort A - Radiation | Baseline TLF Ratio | 0.44 ratio |
| Child-Pugh A Patients | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Total Liver Function: Cohort A - Radiation | Post-Treatment TLF Ratio | 0.29 ratio |
| Child-Pugh B/C Patients | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Total Liver Function: Cohort A - Radiation | Baseline TLF Ratio | 0.18 ratio |
| Child-Pugh B/C Patients | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Total Liver Function: Cohort A - Radiation | Post-Treatment TLF Ratio | 0.09 ratio |
| Child-Pugh B/C Patients | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Total Liver Function: Cohort A - Radiation | Mid-Treatment TLF Ratio | 0.15 ratio |
Comparison: Null hypothesis = no difference in TLF between mid-treatment and baseline. Wilcoxon (Mann-Whitney) tests were performed assessing the longitudinal difference between mid-treatment TLF from baseline TLF.p-value: <0.05Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis = no difference in TLF between mid-treatment and baseline. Wilcoxon (Mann-Whitney) tests were performed assessing the longitudinal difference between post-treatment TLF from baseline TLF.p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis = no difference in TLF between mid-treatment and baseline. Wilcoxon (Mann-Whitney) tests were performed assessing the longitudinal difference between mid-treatment TLF from baseline TLF.p-value: <0.05Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis = no difference in TLF between mid-treatment and baseline. Wilcoxon (Mann-Whitney) tests were performed assessing the longitudinal difference between post-treatment TLF from baseline TLF.p-value: <0.01Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis = no difference in TLF between mid-treatment and baseline. Wilcoxon (Mann-Whitney) tests were performed assessing the longitudinal difference between mid-treatment TLF from baseline TLF.p-value: 0.13Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis = no difference in TLF between mid-treatment and baseline. Wilcoxon (Mann-Whitney) tests were performed assessing the longitudinal difference between post-treatment TLF from baseline TLF.p-value: <0.05Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis = no monotonic association between the baseline TLF and Child-Pugh scores. Spearman rank correlation was performed to assess association between baseline TLF and Child-Pugh scores.p-value: 0.002Spearman rank correlation
Secondary
Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Functional Liver Volume: Cohort B - Surgery
Functional liver volume ratio (FLV): represents the percent of the anatomic liver which is functioning and is defined as the ratio of liver functional volume (in cc of volume) to the anatomic liver volume (in cc of volume). Since this outcome measure is a ratio, it is unitless. A higher FLV ratio reflects a higher volume of functional liver.
Time frame: Baseline, perioperative (2-3 days post surgery), and postoperative (1 month post surgery)
Population: Cohort B - Only patients undergoing surgery
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Functional Liver Volume: Cohort B - Surgery | Preoperative FLV Ratio | 0.52 ratio |
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Functional Liver Volume: Cohort B - Surgery | Perioperative FLV Ratio | 0.59 ratio |
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Functional Liver Volume: Cohort B - Surgery | Postoperative FLV Ratio | 0.54 ratio |
Secondary
Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Liver-to-Spleen Mean: Cohort B - Surgery
Liver-to-spleen ratio (L/S mean): represents the magnitude of the global liver function and is defined as the ratio of the mean SC counts in the functional liver to the mean SC counts in the spleen. Since this outcome measure is a ratio, it is unitless. A higher L/S mean ratio reflects higher magnitude of liver function.
Time frame: Baseline, perioperative (2-3 days post surgery), and postoperative (1 month post surgery)
Population: Cohort B - Only patients undergoing surgery
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Liver-to-Spleen Mean: Cohort B - Surgery | Preoperative L/S Ratio | 1.53 ratio |
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Liver-to-Spleen Mean: Cohort B - Surgery | Perioperative L/S Ratio | 1.23 ratio |
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Liver-to-Spleen Mean: Cohort B - Surgery | Postoperative L/S Ratio | 1.71 ratio |
Secondary
Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Total Liver Function: Cohort B - Surgery
Total liver function (TLF): represents the integral liver function and is defined by the product of the functional liver volume (FLV) ratio and liver-to-spleen (L/S) mean ratio. Since this outcome measure is a product of ratios, it is unitless. A higher TLF ratio reflects higher liver function. Median differences were estimated using Wilcoxon (Mann-Whitney) tests.
Time frame: Baseline, perioperative (2-3 days post surgery), and postoperative (1 month post surgery)
Population: Cohort B - Only patients undergoing surgery
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Total Liver Function: Cohort B - Surgery | Preoperative TLF Ratio | 0.89 ratio |
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Total Liver Function: Cohort B - Surgery | Perioperative TLF Ratio | 0.73 ratio |
| SC SPECT/CT: Cohort A - Radiation | Longitudinal Changes in Liver Function as Measured by SC SPECT/CT Total Liver Function: Cohort B - Surgery | Postoperative TLF Ratio | 1.1 ratio |