PMC3328781_01
Baseline radiologic assessment of the patient in September 2009 before initiation of sorafenib therapy. A: sonography showing a 10 cm lesion in the liver. B: Magnetic resonance imaging (MRI) of the liver revealing a large lesion in the right liver lobe and several diffuse smaller nodules in the total liver. C: MRI scan of the soft tissue metastasis in the autochthonic spine musculature.
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F2
A) in September 2009. At the time of diagnosis, a moderately differentiated metastasis to the thyroid gland and several metastases to the autochthonic spine musculature and the vertebral bodies with stenoses of the spinal canal (L I) and the neuroforamina (Th XII to L I) were present (Figure 2).
Staging after sorafenib monotherapy and before initiation of additional panobinostat treatment. A: Contrast enhanced (left) and native sonography (right) showing necrosis (> 75%) in the largest lesion. B: MRI scan of the liver showing a mixed radiologic response compared to baseline. C: MRI scan of the soft tissue metastasis.
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F3
September 2009 and showed a mixed response in MRI scan 6 weeks after treatment start with partly necrotic or decreased lesions but also increasing and novel lesions in the liver and stable soft tissue and bone metastases. Sonography revealed a large lesion (11 cm) in the right liver lobe which was more than 75% necrotic but also 8 additional lesions up to 5 cm (Figure 3).
Staging after 8 weeks of sorafenib and panobinostat combination therapy. A: Contrast enhanced (left) and native sonography (right). B: MRI scan of the liver. C: MRI scan of the soft tissue metastasis.
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F4
Staging was performed after three cycles in January 2010 (Figure 4).
Time course of transaminases and AFP under sorafenib and panobinostat treatment. (A) Serum levels of GOT, GPT and gamma-GT remained in the normal range under panobinostat (< 50 U/l for GOT and GPT, < 60 U/l for gamma-GT) but rapidly increased again after cessation of panobinostat intake. (B) The tumor marker alpha-fetoprotein (AFP) decreased under the combination therapy with sorafenib and panobinostat but rised again under sorafenib monotherapy (normal level < 10 ng/ml). Panobinostat treatment period is indicated in the figure.
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F5
Although transaminases and gamma-GT were initially elevated (maximum GOT 130 U/l, GPT 178 U/l, gamma-GT 167 U/l), these parameters rapidly normalized under sorafenib therapy and stayed in the normal range until the end of treatment with panobinostat (Figure 5A). Interestingly, the initially elevated tumor marker alpha-fetoprotein (AFP) returned to normal values already under sorafenib therapy despite a lack of radiologic response at this stage (Figure 5B).