Liver Malignacies Treated with Stereotactic Radiosurgery

Dose Escalation Study Evaluating Stereotactic Radiosurgery for Liver Malignancies

The following is a brief summary of the protocol:

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC) are primarily treated with surgery. Unfortunately, this can be performed in less than 30% of cases. The majority of tumors are unresectable because the surgeons are unable to resect the whole tumor completely while leaving enough functioning liver to allow the patient to survive.

Mortality rates from removing part of the liver are approximately 10%, ranging from less that 3% for patients without cirrhosis to 25% for patients with cirrhosis. Five-year survival rates for patients with HCC treated with partial liver resection are approximately 15-49%, with a median survival of 2 years. The overall estimated mean 5-year survival, regardless of extent of surgery, is 31%. Single small tumors (diameter less than 2 cm) have improved survival, with 5-year survival rates of approximately 60%.

Despite aggressive surgery, up to two thirds of patients HCC will have tumor recurrence within the liver, either at the edge of the previous resection cavity, or elsewhere in the liver. To date, no studies evaluating the role of radiation therapy to the liver after surgery have been published.

This phase I toxicity study will explore the practicality and safety of using the Cyberknife Radiosurgical System to treat single liver tumor with large dose of radiation.

The prescribed radiation dose will be escalated gradually throughout the course of this study. Three patients will be accrued at each dose level. A minimum of 60 days will be required between the treatment of the 3rd patient and the 1st patient at the next dose level to permit sufficient time to observe all acute and subacute toxicity. If Grade III toxicity is encountered, an additional 3 patients will be accrued at that dose level. Maximum tolerated dose (MTD) will have been reached if > 50% of patients at a given dose level experience Grade III toxicity (Common Terminology Criteria for Adverse Events (CTCAE), v3. Four dose levels are planned, 1800 cGy, 2200 cGy, 2600 cGy, and 3000 cGy.

The major potential benefit of radiosurgical ablation of liver tumors is better local control of the primary cancer. Such an outcome could translate into both palliation of symptoms and longer survival. The dose escalation used in this investigation will assist in better defining dose selection in future patients.

All the following criteria must be met:
a. Liver tumors not to exceed 5 cm in diameter. If this size can be increased at all, that would be beneficial as many liver lesions present at a larger size given the lack of symptoms until they are larger and adequate hepatic function with albumin >3.0, total bilirubin <3, INR 1.8. In the case of patients with known or suspected cirrhosis, patients must have creatinine <1.5 and cannot have uncontrolled ascites, encephalopathy, active or recent GIB.

b. Age > 18 years old

c. Histologically confirmed HCC, IHCC, or metastatic adenocarcinoma of the breast/colon. In the case of suspected HCC in patients with known cirrhosis, noninvasive criteria recommended by the European Association for the Study of Liver Diseases may be used. Hypervascular lesions > 2cm with AFP > 400ng/mL or hypervascular lesions >2cm on at least 2 imaging studies.

d. Unresectable disease as determined by a surgeon

e. Eastern Clinical Oncology Group performance status 0, 1 or 2

f. No chemotherapy within 1 month of registration

g. No prior radiotherapy to the liver or upper abdominal area

h. Life expectancy > 3 months

i. Patients with IHCC or HCC with distant metastasis are not eligible for this study.

j. For colon cancer patients with metastatic tumor of the liver who are not amenable to surgical resection due to the efficacy of removal of simultaneous lung and liver metastasis.

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