Neoplasms

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Carcinoma

Neoplasm Metastasis

Carcinoma, Hepatocellular

Colonic Neoplasms

Liver Neoplasms

Neoplastic Processes

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Hematinics

All Drugs and Chemicals

Herbal and Botanical

Liver Extracts

Cola

Patients with good liver function as defined by no more than Child-Pugh Class A.

Patients with compromised liver function as defined by patients with Child-Pugh Class B.

Radiation: Stereotactic Radiosurgery using the CyberKnife System. The CyberKnife system has been cleared by the U.S. Food and Drug Administration (FDA) to treat lesions, tumors and conditions, anywhere in the body when radiation treatment is indicated. To address movement of target lesion during the respiratory cycle, the Synchrony™ option will be used.

The Synchrony option precisely tracks tumors in or near the target organ as they move, enabling the highly focused beams of radiation to destroy the tumors with minimal injury to adjacent normal tissue. The Synchrony option records the breathing movements of a patient's chest and combines that information with sequential x-ray pictures of tiny markers inserted inside or in the proximity of the tumor to enable precise delivery of radiation during any point in the respiration cycle. The CyberKnife system with the Synchrony option enables reduced normal tissue exposure by using smaller treatment margins and increased accuracy.

Stereotactic Radiosurgery using the CyberKnife System.

Joel Tepper, MD

The purpose of this study is to determine a tolerable dose of radiation delivered by the CyberKnife system in two groups of patients with hepatocellular carcinoma (HCC).

The CyberKnife system has been cleared by the U.S. Food and Drug Administration (FDA) to treat lesions, tumors and conditions anywhere in the body when radiation treatment is indicated. In order to treat tumors during the respiratory cycle (vs. increasing the margin of treatment around the tumor to compensate for movement or requiring the patient to breath hold during the delivery of each beam), the Synchrony™ option, a system option that enables dynamic radiosurgery during respiration, will be used. The purpose of this study is to determine a tolerable dose of radiation delivered by the CyberKnife in two groups of patients with hepatocellular carcinoma (HCC).Group 1: Patients with HCC and Childs A cirrhosis, and patients with colorectal liver metastases. Group 2: Patients with Childs B cirrhosis. Patients will be irradiated with radiation doses using the CyberKnife system in 3-5 radiation fractions using guidance from fiducials placed by interventional radiology. Treatments will be delivered with standard CyberKnife procedures to account for respiratory motion and set up variations. The fiducial location will be the prime determinant of the delivery site and respiratory motion and fiducial markers will be placed via percutaneous approach by interventional radiology.

Safety, Efficacy, and Dosing of Stereotactic Radiosurgery for Hepato-cellular Carc/Colo-rectal Liver Metastases

A Dose-finding, Safety and Preliminary Efficacy Study of Stereotactic Radiosurgery for Hepato-cellular Carcinoma and Metastatic Disease to the Liver.

To determine a tolerable dose, cumulative acute toxicity was collected (defined as toxicity occurring within 90 days of treatment initiation). Adverse events were graded by the Common Terminology Criteria for Adverse Events version 3.0. Tolerability was based on hepatic toxicity. A grading (severity) scale is provided for each adverse event (AE) term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

1 year local control defined as percentage of patients with freedom from local progression at a median follow-up time of 12.7 months. Progressive disease is defined as increase by \>= 50% of product of the two perpendicular diameters of an irradiated lesion.

Complete response (CR) is defined as disappearance of the target lesion, partial response (PR) as regression of measureable disease, progressive disease (PD) as increase by \>= 50% in product of the two perpendicular diameters of an irradiated lesion, and stable disease (SD) as all others not meeting criteria for CR, PR, or PD.

Overall survival is defined as percentage of patients remaining alive from start of study treatment to 1 year.

UNC Lineberger Comprehensive Cancer Center

Patients with hepatocellular carcinoma (HCC) who are not appropriate for surgical resection or radiofrequency ablation (RFA) as a bridge to transplant. The original cohort was not analyzed between good vs compromised liver function because there were only 2 patients with Child-Pugh Class B and secondary outcomes measured are thought to be more influenced by disease rather than liver function (which may be more relevant for toxicity).

Single Arm Patients With HCC or Liver Metastases

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Measure Description: A scale from 0-5 to describe a patient's level of functioning in terms of selfcare ability and activity level.

0, Fully active

1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature
2. Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
3. Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
4. Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
5. Dead

Eastern Cooperative Oncology Group (ECOG) Performance Status

The Child-Pugh score consists of five clinical features and is used to assess the prognosis of chronic liver disease and cirrhosis. The score employs five clinical measures of liver disease. Each measure is scored 1-3, with 3 indicating most severe derangement.

Child- Pugh Class:

A 5-6 points B 7-9 points C \>9 points

Child Pugh Score

Primary Disease

Any local therapy

Liver resection

Trans-arterial chemoembolization (TACE)

Radiofrequency ablation (RFA)

> 1 prior local therapy

Resection + RFA

Resection + TACE

Resection x2 + RFA

TACE + RFA x3

TACE x 2 + RFA

TACE x 2

Prior liver-directed therapies

Prior systemic therapy

Number of lesions treated

Lesion size (cm)

Lesion size (cm) median (range)

The demonstrable extent of a tumor seen or felt with standard examination techniques. The gross tumor volume is used in radiation oncology as the basis for initial estimates of the extent of a tumor that will undergo treatment with external beam radiation or brachytherapy

Gross tumor volume (cc) median (range)

Planning target volume (PTV) is created by expanding gross tumor volume (GTV) by 0.5-0.8 cm in all directions

Planning target volume (cc) median (range)

When the total dose of radiation is divided into several, smaller doses over a period of several days, there are fewer toxic effects on healthy cells

Fractionation

Dose of Radiation Therapy (Gy)

Mean liver dose (Gy) )

Volume of liver receiving <15 Gy (cc)

The original cohort was not analyzed between good vs compromised liver function because there were only 2 patients with Child-Pugh Class B and secondary outcomes measured are thought to be more influenced by disease rather than liver function (which may be more relevant for toxicity).

Robin Johnson

Elevated Aspartate Aminotransferase

Elevated Bilirubin

Low Hemoglobin

Fatigue

Increased Alanine Aminotransferase

Decreased Leukocyte

Nausea

Abdominal pain

Increased alkaline phosphatase

international normalized ratio increased

Decreased Platelets

Dyspnea

Acute total

Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL)

Grade 2 Adverse Events

Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.

Grade 3 Adverse Events

Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT.

Local Tumor Control to Doses of Radiation in Patients With Liver Cancer or Metastases to the Liver

Complete Response

Partial Response

Stable Disease

Percentage of Local Response to Doses of Radiation in Patients With Liver Cancer or Metastases to the Liver

Overall Survival of Patients With Liver Cancer or Metastases to the Liver

Overall Study

Spots Global Cancer Trial Database for stereotactic radiosurgery using the cyberknife system.