Fusion Guided Thermal Ablation Combined With External Beam Radiation for Hepatic Neoplasms

Background:

Pilot study to assess feasibility for combining treatment modalities that should be
synergistic (radiation and thermal ablation).

Thermal ablation with Radiofrequency Ablation (RFA) and microwave ablation (MWA) are standard
treatments for focal neoplasms in the liver.

High volume or scattered locations of tumor burden results in inability to successfully use
this technology for a large proportion of patients with hepatic neoplasms.

Methods to enhance treatment volumes could be advantageous in potentially increasing the
indications for thermal ablation or the number of patients benefitting from local ablation.

Primary objective:

To determine the safety of combining 2 standard therapies (thermal ablation and external beam
radiation therapy) for liver neoplasms up to 10 cm diameter.

Eligibility:

Patients greater than 18 years of age with pathologically proven unresectable primary or
metastatic hepatic neoplasms

Patients whose extent of hepatic neoplasms represents approximately less than 60% of total
liver volume AND whose extrahepatic metastatic disease is determined to be minimal

ECOG performance status of less than or equal to 2 and a life expectancy of more than 3
months

Patients with a history of chemotherapy, radiation therapy to liver, or biological therapy
must have had last dose/ treatment for at least 14 days prior to starting study treatments.

Patients must not have an acute, critical illness

Design:

Patients will undergo external beam radiation as well as thermal ablation according to
standard operating procedures of the NCI and NIH CC.

Patients will be monitored using the standard imaging studies when clinically warranted.

Patients may be treated with a second (or more) thermal ablation procedure ALONE if it is
deemed beneficial for the patient by the investigator.

The sample size will be 10 evaluable patients

- INCLUSION CRITERIA:

Patients with hepatic-dominant neoplasms where the life limiting component of the disease
is hepatic neoplasms

Patients hepatic lesions must be considered technically unresectable or that their overall
health makes surgery inadvisable

Have 5 or fewer lesions and with no single lesion greater than 10 cm in maximum diameter

Patients with extrahepatic neoplasms or an unresected primary lesion will be considered
eligible if the extrahepatic disease is minimal and stable

Serum Creatinine less than 2.0 mg/dl unless the measured creatinine clearance is greater
than 60 ml/min.

Absolute neutrophil count (ANC) greater than or equal to1500/m3 without help of Filgastim,
hemoglobin greater than 8 g/dL, and platelet count greater than or equal to 75,000 m3

Bilirubin less than 3 mg/dl, and AST and ALT less than 5 X upper limit of normal except in
the presence of obstructive liver neoplasms where ALT/AST may be up to 10 X the upper limit
of normal.

Prothrombin Time (PT) within 2 seconds of the upper limit normal (INR less than or equal to
1.5)

Patient on oral, SQ or IV anticoagulants will be expected to have an abnormal PT and will
be considered eligible if they can safely dicontinue the anticoagulant before ablation. A
repeat PT will be obtained at least 24 hours prior to the radiofrequency ablation (only)
and should be within practice safety guidelines of an INR less than 1.5 or if greater than
1.5 have clinical reversal agent as appropriate to the anticoagulant administered.

Extent of hepatic neoplasms is approximately less than 60% of total hepatic volume

Patients must have pathology proof of neoplasm. If proof of pathology is unavailable,
histopathological confirmation of liver neoplasm may not be requisite in the setting of
clinical or radiological characteristics that are highly suggestive of a neoplastic
diagnosis, with such designation determined by PI and a medical or surgical oncologist,
with the NCI multidisciplinary gastrointestinal tumor board review, in the event of absence
of such consensus.

Patients referred for ablation or radiation of liver neoplasm

ECOG performance status less than or equal to 2

Life expectancy greater than 3 months

At least 18 years of age

Age less than 85 years

Patients must have had no chemotherapy, radiotherapy, or biologic therapy for their
malignancy for at least 28 days prior to treatment and must have recovered from all
clinically significant side effects of therapeutic and diagnostic interventions.

EXCLUSION CRITERIA:

Portal Vein Occlusion or other contraindications to thermal ablation or radiation Prior
selective internal radiation therapy (SIRT) with Yttrium-90 or prior radiation to the liver

Prior biliary diversion surgery

Patients with active bacterial infections with systemic manifestations (malaise, fever,
leukocytosis) are not eligible until completion of appropriate therapy.

Any exclusion criteria for radiation or for ablation, such as ataxia telangiectasia, active
connective tissue disease, or inflammatory bowel disease, or other known conditions which
predispose to radiation toxicities

Patients with an acute, critical illness

Pregnant women are excluded from the study. Patients are excluded from pregnancy testing if
they are above the childbearing age of 55 years old, or if they have documented history of
infertility or acquired or congenital disorders incompatible with pregnancy or if the
patient has had a hysterectomy or bilateral oophorectomy. Patients are also excluded from
pregnancy testing if they are at least 50 years of age AND have not menstruated for at
least 12 months OR have a documented Follicle Stimulating Hormone (FSH) level of greater
than 40 mIU/mL.