Individualized Stereotactic Body Radiotherapy of Liver Metastases

• Toxicity rate [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  To determine the frequency and severity of treatment related toxicities of this treatment program
• Dosimetric differences [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To evaluate the dosimetric differences (prescription dose selected and non-target liver dose) between patients treated with photons and protons.
• 2-year Local Control Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To assess the 2-year local control rate of this treatment program

• Safety and Tolerance [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  To determine safety and tolerance of this treatment program
• Dosimetric differences [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To evaluate the dosimetric differences (prescription dose selected and non-target liver dose) between patients treated with photons and protons.
• Local Control [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To assess the 2-year local control of this treatment program

Stereotactic body radiation therapy (SBRT) is a technique that is used to deliver radiation, whether with protons or photons, to sites in the body. All participants in this study will be treated with SBRT; some will receive proton radiation and some will receive photon radiation. Proton beam radiation uses tiny particles to deliver radiation to tumors. Photon beam radiation uses high-energy x-rays to deliver radiation to tumors. The purpose of this research study is to determine if SBRT will prevent tumor growth and reduce the treatment side effects for liver metastases. We will also be looking to see if there is a difference in the radiation side effects when SBRT is given with protons or photons.

• Participants receiving SBRT with protons, will receive radiation treatment as an outpatient at the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital. Participants receiving SBRT with photons, will receive radiation treatment as an outpatient at Brigham and Women's Hospital.
• Not everyone who participates in this study will be receiving the same dose of radiation. The dose received will be determined by the size and location of the tumor(s).
• Participants will receive 2-3 SBRT treatments per week for two weeks.
• During radiation therapy visits the following tests/procedures will be performed: vital signs, physical examination, routine blood tests, research blood tests, and radiation planning.
• Follow-up assessments will be performed once at 9 weeks after study treatment, then at 6 months, 12 months, 18 months and 24 months after treatment.

• Solid Tumor
• Liver Metastases

• Radiation: stereotactic body radiotherapy-photon
  Dose determined by size and location of tumor; 2-3 treatments per week for two weeks
• Radiation: Stereotactic body radiotherapy-proton
  Dose will be determined by the size and location of the tumor(s); 2-3 treatments per week for two weeks

• Active Comparator: SBRT-Proton
  SBRT by proton radiation
  Intervention: Radiation: Stereotactic body radiotherapy-proton
• Active Comparator: SBRT-Photon
  SBRT with photon radiation
  Intervention: Radiation: stereotactic body radiotherapy-photon

Inclusion Criteria:

• Biopsy-proven cancer diagnosis of a solid tumor with 1-4 liver metastases. There is no upper size limit. Liver metastases may be diagnosed by imaging alone, no liver biopsy is required. Extrahepatic disease is allowed if it have been stable for 3 months prior to study entry, the dominant disease burden is intrahepatic and the patient is referred for definitive radiation therapy to the disease in the liver
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as 10mm or greater with spiral CT scan
• Patients may have had prior chemotherapy, targeted biological therapy, surgery, transarterial chemoembolization (TACE), radiofrequency ablation, or cryosurgery for their disease as long as the prior therapy occured greater than 3 weeks elapsed before the first radiation treatment. Patients may not have had prior liver directed radiation, including radioembolization.
• 18 years of age or older
• Expected survival must be greater than three months
• ECOG performance status of 0, 1 or 2
• Patients must have at least 800mL of uninvolved liver
• Normal organ and marrow function as outlined in the protocol
• If patient has underlying cirrhosis, only Child-Pugh classification Group A patients should be included in this study. Clinical assessment of ascites and encephalopathy is required. Child-Pugh classification must be determined for all study participants at the time of eligibility analysis.
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria:

• Women who are pregnant or lactating
• Patients with gross ascites or encephalopathy
• Local conditions or systemic illnesses which would reduce the local tolerance to radiation treatment, such as serious local injuries, active collagen vascular disease, etc.
• Prior liver directed radiation treatment, including selective internal radiation
• No serious medical illness, which may limit survival to less than 3 months
• No serious psychiatric illness which would limit compliance with treatment
• Participants who have had chemotherapy or radiotherapy within 3 weeks prior to starting study treatment or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier
• Participants may not be receiving any other investigational agents, or any other anti-cancer therapy during treatment
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia.
• Only solid tumors are permitted. Thus, individuals with a liver mass from a diagnosis of lymphoma or leukemia are excluded

• Dana-Farber Cancer Institute
• Brigham and Women's Hospital
• National Cancer Institute (NCI)