The impact of an additional extra-hepatic primary malignancy on the outcomes of patients with hepatocellular carcinoma

<div><p>Background</p><p>The impact of additional extra-hepatic primary cancer (EHPC) on the outcomes of patients with hepatocellular carcinoma (HCC) remains uncertain.</p><p>Methods</p><p>We retrospectively analyzed the cancer registration database from a tertiary hospital in Southern Taiwan. Patients who were diagnosed with HCC from 2008 to 2012 were enrolled. Overall survival (OS), HCC-specific survival and recurrence after curative therapy were analyzed and compared between the patients with and the patients without EHPC.</p><p>Results</p><p>EHPC was found in 121/1506 (8.0%) patients. HCC patients with EHPC were older, more likely to be classified as Child-Pugh A, less likely to have viral hepatitis B or C, more likely to be single, had early stage HCC and received curative therapy for HCC. The OS did not significantly differ between the patients with and without EHPC(p = 0.061). However, significantly higher HCC-specific survival was observed in patients with EHPC (p<0.001), and a higher rate of non-HCC mortality was demonstrated in patients with EHPC (54.4% vs 9.3%). The subgroup analysis revealed better OS in patients with EHPC who were older than 65, had viral hepatitis B or C, had non-stage 1 HCC, had non-early stage BCLC and received non-curative therapy. Conversely, patients with HCC stage 1 who received curative therapy exhibited worse OS if they also had EHPC. The analysis of recurrence after curative therapy showed no difference between the two groups.</p><p>Conclusions</p><p>Our results implied that EHPC did not affect OS, but HCC-related survival was better in patients with EHPC. Based on these findings, the management of additional primary cancer is warranted.</p></div

The Cox regression hazard analysis of factors associated with overall survival.

<p>The Cox regression hazard analysis of factors associated with overall survival.</p

Comparison of overall survival and HCC-specific survival between patients with EHPC and patients without EHPC according to different parameters.

<p>Comparison of overall survival and HCC-specific survival between patients with EHPC and patients without EHPC according to different parameters.</p

Mean HBV DNA levels of all (A) and virologic breakthrough (B) patients according to the time points of nucleot(s)ide analogues therapy.

<p>HBV DNA levels detected by <i>RealTime</i> assay were slightly higher than TaqMan assay although these differences were not statistically significant.</p

Comparison of overall and HCC-specific survival between patients with and patients without EHPC before and after HCC diagnosis.

<p>Comparison of overall and HCC-specific survival between patients with and patients without EHPC before and after HCC diagnosis.</p

Comparison of HCC recurrence after curative therapy.

<p>Comparison of HCC recurrence after curative therapy.</p

Sites of extra-hepatic primary cancer.

<p>Sites of extra-hepatic primary cancer.</p

Cox regression hazard analysis of factors associated with HCC-specific survival.

<p>Cox regression hazard analysis of factors associated with HCC-specific survival.</p

The correlation of measurements and limits of agreement between RealT<i>ime</i> and TaqMan assay in the 434 samples of HBV DNA level <3 log₁₀ IU/mL.

<p>The correlation of HBV DNA in the 434 samples between the two assays was not as good as all samples (R² = 0.457; <i>P</i><0.001). (A) The mean difference was 0.40±0.77 log₁₀ IU/ml (limits of agreement, −1.15 to 1.95 log₁₀ IU/ml). (B)</p

Comparison of overall and HCC-specific survival between patients with EHPC and patients without EHPC.

<p>Comparison of overall and HCC-specific survival between patients with EHPC and patients without EHPC.</p