This phase III trial studies how well radiation therapy with protons works compared with photons in treating patients with liver cancer. Radiation therapy, such as photon therapy, uses high energy x-rays to send the radiation inside the body to the tumor while proton therapy uses a beam of proton particles. Proton therapy can stop shortly after penetrating through the tumor and may cause less damage to the surrounding healthy organs and result in better survival in patients with liver cancer.
PRIMARY OBJECTIVE: I. To determine if overall survival (OS) is different for hepatocellular carcinoma patients treated with protons compared to photons. SECONDARY OBJECTIVES: I. To determine the difference in progression-free-survival (PFS) in patients with hepatocellular carcinoma (HCC) treated with protons compared to patients with HCC treated with photons. II. To determine the difference in local progression (LP) in patients with HCC treated with protons compared to patients with HCC treated with photons. III. To determine differences in toxicity in patients with HCC treated with protons versus photons. IV. To determine differences in fatigue, as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue in patients with HCC treated with protons, versus photons; as well as quality-adjusted survival, if the primary endpoint is met. V. To determine if there are correlations between the baseline values of hepatocyte growth factor (HGF) and outcomes (OS/PFS/fatigue). EXPLORATORY OBJECTIVES: I. To determine differences in overall quality of life, measured by Functional Assessment of Cancer Therapy-Hepatobiliary Cancer (FACT-Hep) in patients with HCC treated with protons. II. Biospecimen collection for future correlative science projects. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo proton therapy over 15-24 days for 5 or 15 fractions. ARM II: Patients undergo photon therapy over 15-24 days for 5 or 15 fractions. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI) and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
186
Undergo blood sample collection
Undergo CT scan
Correlative studies
Undergo MRI
Ancillary studies
Undergo proton therapy
Undergo photon therapy
Emory Proton Therapy Center
Atlanta, Georgia, United States
Emory University Hospital Midtown
Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, United States
Overall survival (OS)
Will be estimated by the Kaplan-Meier method. The distributions of OS between treatment arms will be compared using the log rank test. The final analysis will occur after at least 125 deaths have occurred and will include: tabulation of all cases entered and those excluded from the analyses with the reasons for exclusion, distributions of important prognostic baseline variables, the frequencies and severity of adverse events by treatment arm, treatment delivery compliance, observed results with respect to the primary endpoint of OS. Will be tested with a 2-sided significance level of 0.049.
Time frame: From the date of randomization to the date of death due to any cause assessed up to 4 years
Treatment effect
Will be performed using the Cox proportional hazard regression model.
Time frame: Up to 4 years
Progression-free survival (PFS)
Will be estimated by the Kaplan-Meier method and compared using the log rank test. The Cox proportional hazard regression model will be used.
Time frame: From the date of randomization to the date of first PFS failure or last follow-up for patients without a reported PFS event assessed up to 4 years
Local progression (LP)
Will be estimated by the cumulative incidence method and compared using Gray's test. The Fine-Gray regression model will be used to analyze.
Time frame: From the date of randomization to the date of first LP or date of last follow-up for patients without an LP event reported assessed up to 4 years
Incidence of adverse events
Will be assessed by Common Terminology Criteria for Adverse Events version 4. A Chi-square test will be used to compare the number of patients with at least 1 grade 3 or higher adverse events between the treatment arms.
Time frame: Up to 4 years
Fatigue
Will be measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue short form version 1.0 8a.
Time frame: Baseline up to 6 months
Change in fatigue
Will be compared between treatment arms using a t-test. If the data do not satisfy the normality assumption, a Wilcoxon test may be used instead.
Time frame: Baseline up to 1 month
Quality-adjusted survival
Will be evaluated and compared using European Quality of Life Five Dimension Three Level Questionnaire (EuroQol 5D).
Time frame: Baseline up to 12 months
Plasma hepatocyte growth factor (HGF) levels
Will be dichotomized at the median value and evaluated for prognostic significance using Cox regression model at a 2-sided significance level of 0.05. Additionally, predictive analyses will be done by treatment arm and an exploratory test of HGF by treatment interaction, with the understanding that there will be reduced power for the predictive analyses under the same effect size assumptions. However, there may be sufficient power if there is large interaction.
Time frame: At baseline
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Maryland Proton Treatment Center
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...and 17 more locations