Y90 Radiation Segmentectomy vs SBRT for HCC

Study Overview
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Brief Summary
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The proposed study is a single site, prospective, randomized pilot study to assess the feasibility of recruitment of patients into a trial evaluating the efficacy and tolerability of selective transarterial Y90 radioembolization (radiation segmentectomy) versus stereotactic body radiation therapy (SBRT) for solitary early stage (≤ 3cm) hepatocellular carcinoma (HCC).

Official Title
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Yttrium-90 Radiation Segmentectomy Versus Stereotactic Body Radiation Therapy (SBRT) for the Treatment of Early Stage Hepatocellular Carcinoma (HCC): A Pilot Study

Conditions
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Hepatocellular Carcinoma (HCC)

Intervention / Treatment
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* Radiation: Yttrium-90 Radiation Segmentectomy
* Radiation: Stereotactic Body Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to provide written informed consent and HIPAA authorization Stated willingness to comply with all study procedures and availability for the duration of the study Male or female, aged ≥ 18 years at time of informed consent Solitary HCC (≤3 cm) diagnosed by imaging (LI-RADS 4-5) or histology Childs-Pugh score ≤ 7 ECOG performance status 0-1 Tumor location/characteristics eligible for either SBRT or Y90 therapy as deemed by local tumor board Adequate organ function defined as: serum bilirubin < 4.0 mg/dL , albumin > 2 g/dL Exclusion Criteria: Any prior locoregional therapy to the target tumor Any prior radiation therapy to the liver Pregnancy or lactation: Women of childbearing potential must have a negative pregnancy test within 14 days of protocol registration. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) unless they meet one of the following criteria: i. Has undergone a hysterectomy or bilateral oophorectomy; or ii. Has been naturally amenorrheic for at least 24 consecutive months Known severe allergic reaction (anaphylaxis) to iodinated contrast Coagulopathy (platelets < 50 K/mm3 and/or INR > 2) not correctable by transfusion Macrovascular invasion or extrahepatic HCC

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Yttrium-90 Radiation Segmentectomy<br> | Radiation: Yttrium-90 Radiation Segmentectomy<br>* This therapy arm involves two separate steps, a planning/mapping arteriogram and a therapy delivery. The planning arteriogram will be performed to confirm arterial anatomy is acceptable for RS (≤2 segment delivery) and that lung shunting is not too high to preclude treatment with RS. Once confirmed, patients will return for RS (within 45 days of mapping). Dose will be calculated based off the desired treatment volume using pre-treatment cross-sectional imaging. The desired segmental dose will be calculated to be ≥ 200Gy. RS will be performed by one of three separate interventional radiologists with experience in radioembolization. Actual administered activity and location of dose administration will be recorded.<br>|
| Active Comparator: Stereotactic Body Radiation Therapy<br> | Radiation: Stereotactic Body Radiation Therapy<br>* SBRT will be delivered with linear accelerator-based photon beams with either fixed angle non- coplanar fields or dynamic arcs. An internal target volume (ITV) will be generated to account for tumor movement during breathing cycle. Finally, a planning target volume (PTV) will be an expansion of 3- 5mm from the ITV. For Child Pugh A patients, prescription dose will either be 5000cGy in 5 fractions delivered every other day or 4800cGy in 3 fractions delivered twice weekly. For Child Pugh B patients, prescription dose of 4000cGy in 5 fractions delivered every other day. Inverse planning will be used. 95% of the PTV or more will receive at least 100% of the prescription dose. Normal tissue dose constraints for each dose level will be respected with acceptable deviations permitted as outlined in appendix VII. Patients will be seen at least once per week by a clinician to grade toxicities, with on- treatment labs (CBC, CMP, INR) each week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of Recruitment (Recruitment Rate) | Feasibility of recruitment will be measured by evaluating the proportion of patients enrolled versus those approached for the study after they have been determined to be a candidate. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With Any Toxicities | the proportion of patients with any toxicities (≥ grade 4) using CTCAE between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC). | 16 months for the first subject and 4 months for the second | 
| Mean Change in Hepatobiliary Function | the mean change in hepatobiliary function, as measured 3 months after treatment using a functional HIDA scan, between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC). | 16 months for the first subject and 4 months for the second | 
| Mean Change in Functional Assessment of Cancer Therapy- General (FACT-G) Score | the mean change in patient-reported outcomes from baseline, at 1, 3 and 6 months, between RS and SBRT, for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC), using the Functional Assessment of Cancer Therapy- General (FACT-G). scale goes from 0-108 with a higher score being better. | 6 months | 
| Mean Change in Comprehensive Score for Financial Toxicity | the mean change in patient-reported outcomes from baseline, at 1, 3 and 6 months, between RS and SBRT, for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC), using the Comprehensive Score for Financial Toxicity (COST). scale is from 0-44 with higher being bettter | 6 months | 
| Disease-free Survival (DFS) Rates of RS and SBRT | the disease-free survival (DFS) rates of RS and SBRT at 2 years using mRECIST on CT or MR for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC). | 16 months for the first subject and 4 months for the second | 
| Time-to-secondary Treatment (TTST) Between RS and SBRT | time-to-secondary treatment (TTST) between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC) up to 2 years after initial treatment. | 16 months for the first subject and 4 months for the second | 
| Objective Response Rate | the objective response rate (ORR) of radiation segmentectomy (RS) and stereotactic body radiation therapy (SBRT) as measured at 6 months using mRECIST (appendix IV) for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC) to better allow for an appropriately powered trial evaluating the efficacy of these treatments. | 6 months |