• Radiation Oncology Journal
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• v.36 no.1
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• pp.25-34
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• 2018

Purpose: This study aimed to evaluate the initial outcomes of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety. Materials and Methods: HCC patients who were not indicated for standard curative local modalities and who were treated with PBT at Samsung Medical Center from January 2016 to February 2017 were enrolled. Toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results: A total of 101 HCC patients treated with PBT were included. Patients were treated with an equivalent dose of $62-92GyE_{10}$. Liver function status was not significantly affected after PBT. Greater than 80% of patients had Child-Pugh class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78 patients followed for three months after PBT, infield complete and partial responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively. Conclusion: PBT treatment of HCC patients showed a favorable infield complete response rate of 69.2% with acceptable acute toxicity. An additional follow-up study of these patients will be conducted.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10209-10215
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• 2015

To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.

• Radiation Oncology Journal
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• v.32 no.1
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• pp.14-22
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• 2014

Purpose: To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) followed by radiotherapy (RT) in treatment-na$\ddot{i}$ve patients with locally advanced hepatocellular carcinoma (HCC). Materials and Methods: Eligibility criteria were as follows: newly diagnosed with HCC, the Barcelona Clinic Liver Cancer stage C, Child-Pugh class A or B, and no prior treatment for HCC. Patients with extrahepatic spread were excluded. A total of 59 patients were retrospectively enrolled. All patients were treated with TACE followed by RT. The time interval between TACE and RT was 2 weeks as per protocol. A median RT dose was 47.25 $Gy_{10}$ as the biologically effective dose using the ${\alpha}/{\beta}$ = 10 (range, 39 to 65.25 $Gy_{10}$). Results: At 1 month, complete response was obtained in 3 patients (5%), partial response in 27 patients (46%), stable disease in 13 patients (22%), and progressive disease in 16 patients (27%). The actuarial one- and two-year OS rates were 60.1% and 47.2%, respectively. The median OS was 17 months (95% confidence interval, 5.6 to 28.4 months). The median time to progression was 4 months (range, 1 to 35 months). Grade 3 or greater liver enzyme elevation occurred in only two patients (3%) after RT. Grade 3 gastroduodenal toxicity developed in two patients (3%). Conclusion: The combination treatment of TACE followed by RT with two-week interval was safe and it showed favorable outcomes in treatment-na$\ddot{i}$ve patients with locally advanced HCC. A prospective randomized trial is needed to validate these results.

• Radiation Oncology Journal
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• v.32 no.3
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• pp.170-178
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• 2014

Purpose: We sought to evaluate the clinical outcomes of 3-dimensional conformal radiation therapy (3D-CRT) for portal vein tumor thrombosis (PVTT) alone in patients with advanced hepatocellular carcinoma. Materials and Methods: We retrospectively analyzed data on 46 patients who received 3D-CRT for PVTT alone between June 2002 and December 2011. Response was evaluated following the Response Evaluation Criteria in Solid Tumors. Prognostic factors and 1-year survival rates were compared between responders and non-responders. Results: Thirty-seven patients (80.4%) had category B Child-Pugh scores. The Eastern Cooperative Oncology Group performance status score was 2 in 20 patients. Thirty patients (65.2%) had main or bilateral PVTT. The median irradiation dose was 50 Gy (range, 35 to 60 Gy) and the daily median dose was 2 Gy (range, 2.0 to 2.5 Gy). PVTT response was classified as complete response in 3 patients (6.5%), partial response in 12 (26.1%), stable disease in 19 (41.3%), and progressive disease in 12 (26.1%). There were 2 cases of grade 3 toxicities during or 3 months after radiotherapy. Twelve patients in the responder group (15 patients) received at least 50 Gy irradiation, but about 84% of patients in the non-responder group received less than 50 Gy. The 1-year survival rate was 66.8% in responders and 27.4% in non-responders constituting a statistically significant difference (p = 0.008). Conclusion: Conformal radiotherapy for PVTT alone could be chosen as a palliative treatment modality in patients with unfavorable conditions (liver, patient, or tumor factors). However, more than 50 Gy of radiation may be required.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7213-7218
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• 2014

Background: Egypt has one of the highest prevalences of hepatitis C virus (HCV) infection worldwide. Although the IL28B gene polymorphism has been shown to modify the course of chronic HCV infection, this has not been properly assessed in the Egyptian population. Materials and Methods: The IL28B rs12979860 single nucleotide polymorphism (SNP) was therefore examined in 256 HCV-infected Egyptian patients (group II) at different stages of disease progression and in 48 healthy volunteers (group I). Group II was subdivided into GII-A (chronic hepatitis patients, n=119), GII-B (post hepatitis cirrhosis, n=66) and GII-C (HCC on top of cirrhosis, n=71). Results: The C/T genotype was the commonest in all groups. It was more frequent in GI (52%) than in GII (48%). There was no significant difference in the frequency of C/T and C/C or T/T genotypes between groups and subgroups (p=0.82). Within the subgroups; the C/C genotype was more common in GII-B while C/T and T/T genotypes were more common in GII-C, though with no significant difference (p=0.59 and p=0.80). There was no significant association between IL28B rs12979860 SNP and viral load, ALT, AFP level, METAVIR scores for necro-inflammation and fibrosis, and Child-Pugh classification. Conclusions: 1) IL28Brs12979860 C/T genotype is the commonest genotype in HCV-associated CH and HCC in Egypt. 2) IL28Brs12979860 polymorphisms are not associated with disease progression or aggression (histological staging, severity of fibrosis in CH or the incidence of post-HCV HCC). 3) Differences in IL28Brs12979860 genotypes could be a consequence of environmental or ethnic variation.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6293-6299
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• 2013

Background: A number of clinicopathologic factors have been found to be associated with pathological lymph node metastasis (pLNM) in rectal cancer; however, most of them can only be identified by expensive high resolution imaging or obtained after surgical treatment. Just like the Child-Turcotte-Pugh (CTP) and the model for end-stage liver disease (MELD) scores which have been widely used in clinical practice, our study was designed to assess the pre-operative factors which could be obtained easily to predict intra-operative pLNM in rectal cancer. Methods: A cohort of 469 patients who were treated at our hospital in the period from January 2003 to June 2011, and with a pathologically hospital discharge diagnosis of rectal cancer, were included. Clinical, laboratory and pathologic parameters were analyzed. A multivariate unconditional logistic regression model, areas under the curve (AUC), the Kaplan-Meier method (log-rank test) and the Cox regression model were used. Results: Of the 469 patients, 231 were diagnosed with pLNM (49.3%). Four variables were associated with pLNM by multivariate logistic analysis, age<60 yr (OR=1.819; 95% CI, 1.231-2.687; P=0.003), presence of abdominal pain or discomfort (OR=1.637; 95% CI, 1.052-2.547; P=0.029), absence of allergic history (OR=1.879; 95% CI, 1.041-3.392; P=0.036), and direct $bilirubin{\geq}2.60{\mu}mol/L$ (OR=1.540; 95% CI, 1.054-2.250; P=0.026). The combination of all 4 variables had the highest sensitivity (98.7%) for diagnostic performance. In addition, age<60 yr and direct $bilirubin{\geq}2.60{\mu}mol/L$ were found to be associated with prognosis. Conclusion: Age, abdominal pain or discomfort, allergic history and direct bilirubin were associated with pLNM, which may be helpful for preoperative selection.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5541-5547
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• 2015

Background: The role of surgical resection for patients with single large (${\geq}5cm$) and/or multinodular (${\geq}2$) hepatocellular carcinoma (HCC) is still controversial. This systematic review was performed to evaluate the safety and efficacy of resection for patients with single large and/or multinodular HCC. Materials and Methods: Databases (the PubMed, Web of Science, Embase, and Cochrane databases) were systematically searched to identify relevant studies exploring the safety and efficacy of resection for single large and/or multinodular HCC, published between January 2000 and December 2014. Perioperative morbidity and mortality, overall survival, and disease-free survival of the resection group were calculated. In addition, these outcome variables were also calculated for the control group in the included studies. Results: One randomized controlled trial and 42 nonrandomized studies involving 9,580 patients were eligible for analysis. Eight (1,594 patients) of the 43 studies also reported the outcomes of transarterial chemoembolization (TACE). Although 51.4% of patients featured cirrhosis, 90.7% of them demonstrated Child-Pugh A liver function in the resection group. The median rates of morbidity (24.5%) and mortality (2.5%) after resection were significantly higher than that of TACE (11.0%, P<0.001; 1.9%, P<0.001). However, patients who underwent resection had significantly higher median one-, three-, and five-year overall survival (76.1%, 51.7%, and 37.4%) than those who underwent TACE (68.3%, 31.5%, and 17.5%, all P<0.001). The median 1-, 3-, and 5-year DFS rates after resection were 58.3%, 34.6%, and 24.0%, respectively. Conclusions: Although tumor recurrence after resection for patients with single large and/ or multinodular HCC continues to be a major problem, resection should be considered as a strategy to achieve long-term survival.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.637-642
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• 2014

The pathogenesis of hepatocellular carcinoma (HCC) related to habitual betel quid (BQ) chewing is unclear. Risk of HCCis increased with adverse hepatic fibrosis. This study aimed to assess the impact of chronic viral hepatitis on adverse hepatic fibrosis in HCC related to BQ chewing. This hospital-based case-control study enrolled 200 pairs of age- and gender-matched patients with HCC and unrelated healthy controls. Serologic hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), ${\alpha}$-fetoprotein (AFP), and surrogate markers for significant hepatic fibrosis were measured. Information on substance-use habits was obtained with a questionnaire. By analysis of surrogate markers for hepatic fibrosis, the prevalence of significant hepatic fibrosis in patients chewing BQ was between 45.8% and 91.7%, whereas that for patients without BQ chewing was between 18.4% and 57.9%. The difference was significant (P <0.05 for each surrogate marker). Multivariate analysis indicated that cirrhosis with Child-Pugh C (odds ratio (OR) = 3.28; 95% confidence interval (CI), 1.29-8.37), thrombocytopenia (OR = 3.92, 95% CI, 1.77-8.68), AFP >400 mg/L (OR = 2.21, 95% CI, 1.05-4.66) and male gender (OR = 4.06, 95% CI, 1.29-12.77) were independent factors associated with habitual BQ chewing. In conclusion, adverse hepatic fibrosis and severe liver damage play important roles in the pathogenesis of BQ-related HCC, which could be aggravated by chronic hepatitis B and hepatitis C. BQ-cessation programs and prevention of chronic HBV/HCV infection are needed to prevent HCC related to BQ chewing.

• Radiation Oncology Journal
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• v.36 no.2
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• pp.129-138
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• 2018

Purpose: This study was conducted to compare clinical outcomes and treatment-related toxicities after stereotactic body radiation therapy (SBRT) with two different dose regimens for small hepatocellular carcinomas (HCC) ${\leq}3cm$ in size. Materials and Methods: We retrospectively reviewed 44 patients with liver-confined HCC treated between 2009 and 2014 with SBRT. Total doses of 45 Gy (n = 10) or 60 Gy (n = 34) in 3 fractions were prescribed to the 95% isodose line covering 95% of the planning target volume. Rates of local control (LC), intrahepatic failure-free survival (IHFFS), distant metastasis-free survival (DMFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Results: Median follow-up was 29 months (range, 8 to 64 months). Rates at 1 and 3 years were 97.7% and 95.0% for LC, 97.7% and 80.7% for OS, 76% and 40.5% for IHFFS, and 87.3% and 79.5% for DMFS. Five patients (11.4%) experienced degradation of albumin-bilirubin grade, 2 (4.5%) degradation of Child-Pugh score, and 4 (9.1%) grade 3 or greater laboratory abnormalities within 3 months after SBRT. No significant difference was seen in any oncological outcomes or treatment-related toxicities between the two dose regimens. Conclusions: SBRT was highly effective for local control without severe toxicities in patients with HCC smaller than 3 cm. The regimen of a total dose of 45 Gy in 3 fractions was comparable to 60 Gy in efficacy and safety of SBRT for small HCC.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.28 no.1
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• pp.25-33
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• 2024

Backgrounds/Aims: Parenchymal-sparing anatomical hepatectomy (Ps-AH) based on portal ramification of the right anterior section (RAS) is a new technique to avoid unnecessarily transecting too much liver parenchyma, especially in cases of major anatomical hepatectomy. Methods: We prospectively assessed 26 patients with primary hepatic malignancies having undergone major Ps-AH based on portal ramification of the RAS from August 2018 to August 2022 (48 months). The perioperative indications, clinical data, intra-operative index, pathological postoperative specimens, postoperative complications, and follow-up results were retrospectively evaluated. Results: Among the 26 patients analyzed, there was just one case that had intrahepatic cholangiocarcinoma The preoperative level of α-Fetoprotein was 25.2 ng/mL. All cases (100%) had Child-Pugh A liver function preoperatively. The ventral/dorsal RAS was preserved in 19 and 7 patients, respectively. The mean surgical margin was 6.2 mm. The mean surgical time was 228.5 minutes, while the mean blood loss was 255 mL. In pathology, 5 cases (19.2%) had microvascular invasion, and in the group of HCC patients, 92% of all cases had moderate or poor tumor differentiation. Six cases (23.1%) of postoperative complications were graded over III according to the Clavien-Dindo system, including in three patients resistant ascites or intra-abdominal abscess that required intervention. Conclusions: Parenchymal-sparing anatomical hepatectomy based on portal ramification of the RAS to achieve R0-resection was safe and effective, with favorable short-term outcomes. This technique can be used widely in clinical practice.