Extended PET scanning in patients with incurable hepatocellular carcinoma (HCC) treated with sorafenib.

Hepatocellular carcinoma (HCC) is a primary tumor of the liver, which usually
develops in the setting of chronic liver disease, particularly viral hepatitis.
The diagnosis of HCC can be difficult, and often requires the use of serum
markers, one or more imaging modalities, and histologic confirmation. Ideally,
tumors should be detected when they are small in patients who are able to
withstand therapy. However, HCC is frequently diagnosed late in its course
because of the absence of pathognomonic symptoms and the liver's large
functional reserve. As a result, many patients have untreatable disease when
first diagnosed. The median survival following diagnosis is approximately 6 to
20 months. Large tumor size, vascular invasion, poor functional status, and
nodal metastases are all associated with a poor outcome.
A member of the group of protein tyrosine kinases, Sorafenib, has recently been
found to improve survival in modest terms, however as this is sofar the only
systemic approach with activity, this finding has generated much interest.The
manufacturer of the drug (Bayer) has activated a compassionate need program for
Sorafenib, in addition to its registered indication for renal cell cancer. The
nature of this group of drugs is that response evaluation is cumbersome in the
classical way using the serum tumor marker AFP, CT or other dimensional
orientated techniques. The tumor marker AFP can often not be used as an
surrogate marker of response as not all tumors have an increased marker and on
the otherhand many other factors as hepatitis C activity can influence the AFP
level. The dimensional oriental techniques do have problems as usually
responses involve central necrosis that do not involve the outside borders for
some period of time. In addition HCC often has no outside borders but grows
infiltrating in the normal liver parenchyma. Because of these consideration
evaluation of response to tyrosinase inhibitors is best done using PET
scanning, as is the case in Gastro intestinal stroma tumors and kidney cancer.
In contrast with these tumors, liver cell cancer is PET positive in only appr.
60% of cases, this may related to the more aggressive feature of the tumor. In
these patients a diagnosis of response has to rely on scanning with the
addition of markers. Often clinical parameters will have to be used. The
subject of this study is the question if this group of patients has a survival
that is different from those with a positive scan, because of inherent
differences in tumor biology. On the other hand a negative PET scan could be
merely a stage of the tumor in time. In addition to registration of clinical
data in the follow up we will test the hypothesis that a stage difference is
involved by proposing a second PET scan in initially PET negative patients 4
months after start of treatment

Primary objective:
- to test the hypothesis that an initial negative PET scan can be change in 4
months in a positive PET scan.

Secondary objective:
- to test the hypothesis that a negative PET scan is related to a less
aggressive tumor with an increased median overall survival.

Type: observationeel onderzoek

Design: pilot study

The burden or risk associated with this study is considered to be low, there
is no benefit for the patient