Pancreatic Atrophy in Hepatocellular Carcinoma Patients Receiving Long-Term Treatment with Sorafenib

OBJECTIVE: To date, sorafenib is the only approved systemic therapy for advanced hepatocellular carcinoma (HCC). Pancreatic atrophy has recently been reported in 2 patients as a novel side effect after long-term sorafenib treatment. METHODS: We retrospectively analyzed clinical and radiological data of patients with advanced HCC with long-term treatment of sorafenib (median 279 days, range 153-826 days). Pancreata were semi-manually segmented section by section to calculate the pancreas volumes before and under sorafenib treatment. RESULTS: Sorafenib reduced pancreatic volume in 18/19 (95%) HCC patients with a mean pancreatic volume loss of 25% (p = 0.002). Pancreatic volume loss depended on the dose (r = 0.36) and exposure time of sorafenib (r = 0.35) and was detectable as early as after 3 months of sorafenib treatment and already after a cumulative sorafenib dose of <100 g. Median overall survival was 13.2 months (range 7.8-31.3 months) but did not correlate with sorafenib-induced pancreatic volume reduction (hazard ratio 1.002, 95% confidence interval 0.981-1.060, p = 0.24). CONCLUSION: We could confirm pancreatic atrophy as a novel adverse event of sorafenib therapy in HCC patients, correlating with sorafenib dose and exposure time.