2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology, and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.ope

The Role of Adjuvant Postoperative Radiotherapy in Curative Resectable Sigmoid Colon Carcinoma

PURPOSE: To evaluate the role of postoperative radiation therapy after curative resection of sigmoid colon cancer MATERIALS AND METHODS: From 1988 to 1993, a total of 93 patients with curative resectable sigmoid colon cancer of modified Astler-Coller (MAC) stage B2, B3, C2, C3 was divided into two groups on the basis of those who received radiation treatment and those who did not. Forty-three patients who treated by surgery alone were classified as postop RT ( group. The remaining 50 patients who underwent postoperative radiotherapy were classified as postop RT (+) group. In all patients in postop RT (+) group, radiation therapy was delivered using 4 or 10 MV linear accelerators to treat the tumor bed with approximately 5cm margin to a total dose 50.4-61Gy (median 54Gy) in 1.8Gy per fraction. Thirty-two patients were treated with 5- Fluorouracil based adjuvant chemotherapy at least 3 cycles, but these was no significant difference between two groups. Treatment failure pattern, 5-year local failure-free survival rates (LFFS), and 5-year disease-free survival rates (DFS) were compared between two groups. RESULTS: Five year LFFS and DFS were 85.1%, 68.5%, respectively. In postop RT (-) group, LFFS was 76.2%, compared with 91.7% in postop RT (+) group. Improved LFFS and DFS were seen for patients with stage C3 sigmoid colon carcinoma with postoperative radiation therapy compared with postop RT (-) group (P=0.01, P=0.06 respectively). In stage B3, LFFS washigher in postop RT (+) group than that in postop RT (-) group, although it was not significant. Especially, local control was higher in stage T4 in postop RT (+) group than that in postop RT (-) group. CONCLUSION: This study showed significantly improved LFFS and DFS in MAC Stage C3 and improved tendency of LFFS and DFS in MAC Stage B3 disease. Large scale prospective study is required to verify the role of adjuvant radiation therapy in resectable sigmoid colon cancer.ope

Combined Transcatheter Arterial Chemoembolization and Local Radiotherapy for Unresectable Hepatocellular Carcinoma

Purpose: The best prognosis for hepatocellular carcinoma can be achieved with surgical resection. However, the number of resected cases is limited due to the advanced lesion or associated liver disease. A trial of combined transcatheter arterial chemoembolization(TACE) and local radiotherapy(RT) for unresectable hepatocellular carcinoma(HCC) was prospectively conducted and its efficacy and toxicity were investigated. Materials and Methods: From 1992 to 1994, 30 patients with unresectable HCC due either to advanced lesion or to associated cirrhosis were entered in the study.Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child’s class C, tumors occupying more than two- thirds of the whole liver, and an ECOG scale of more than 3. Patient characteristics were:mean tumor size 8.95 ±3.4cm, serum AFP ＋in all patients, portal vein thrombosis in 11 patients, liver cirrhosis in 22 patients, and UICC stage III and IVA in 10 and 20 patients, respectively. TACE was performed with the mixture of Lipiodol(5ml) and Adriamycin(50mg) and Gelfoam embolization. RT(mean dose 44.0 ±9.3Gy) was followed within 7- 10 days with conventional fractionation. Results:An objective response was observed in 19 patients(63.3%). Survival rates at 1,2, and 3 years were 67%, 33.3% and 22.2%, respectively. Median survival was 17 months. There were 6 patients surviving more than 3 years. Distant metastasis occurred in 10 patients, with 8 in the lung only and 2in both lung and bone. Toxicity included transient elevation of liver function test in all patients, fever in 20, thrombocytopenia in 4, and nausea and vomiting in 1. There was no treatment-related death. Conclusion:Combined TACE and RT appear to produce a favorable response and survival results with minimal toxicity.ope

Consensus on Stereotactic Body Radiation Therapy for Small-Sized Hepatocellular Carcinoma at the 7th Asia-Pacific Primary Liver Cancer Expert Meeting

Background: Stereotactic body radiation therapy (SBRT) is an advanced technique of external beam radiation therapy that delivers large ablative doses of radiation. In the past decade, many cancer centers have adopted SBRT as one mode of radically treating small-sized hepatocellular carcinoma (HCC), based on encouraging clinical outcomes. SBRT thus seems reasonable as first-line treatment of inoperable HCC confined to the liver. However, most of the clinical studies to date have been retrospective in nature, with key issues still under investigation. Summary: The above-mentioned publications were subjected to scrutiny, fueling discussions at the 7th Asia-Pacific Primary Liver Cancer Expert (APPLE 2016) Meeting on various clinical variables, such as indications for SBRT, therapeutic outcomes, treatment-related toxicities, doses prescribed, and specific techniques. The consensus reached should be of interest to all professionals active in the treatment of HCC, especially radiation oncologists. Key Messages: SBRT is a safe and effective therapeutic option for patients with small-sized HCC, offering substantial local control, improved overall survival, and low toxicity.ope

High Precision Radiotherapy of Hepatocellular Carcinoma

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담낭암의 방사선 치료

담낭암은 초기 증상이 비특이적이고 진단적 기준도 애매하여, 대부분의 환자가 진행성 종양으로 발견되는 경우가 많다. 외과적 절제술이라는 근치적 치료법이 있음에도 불구하고 실제적으로 만족스러운 수준의 절제술이 적용되는 것이 지극히 제한적인, 매우 도전적인 암종이다. 항암 화학 요법 또한, 그간의 치료성적이 매우 실망스러운 현실이다.외과적 절제술 및 항암 화학요법의 한계점으로 인하여, 방사선치료는 상대적으로 그 역할이 주목을 받게 되었다. 그러나 진행성 담낭암의 방사선치료를 의뢰하는 대부분의 의료진들은 이 치료법의 효과에 대하여 그다지 신뢰를 보이고 있지는 않은 것으로 보이며, 여타 방법이 여의치 않을 때, 마지막으로 한번쯤 해보는 “위안적” 치료로 보는 시각이 있는 것도 사실이다. 그러나,최근 치료기기의 눈부신 발전으로 방사선 치료의 내용 및 기술이 빠른 속도로 향상되고 있으며, 이는 담낭암의 치료에도 예외가 아닌 것은 물론이다.ope

Biomarkers for Locally Advanced Hepatocellular Carcinoma Patients Treated with Liver-Directed Combined Radiotherapy

Introduction: In the era of biomarker-driven cancer therapy, robust biomarkers for hepatocellular carcinoma (HCC) have not been well-defined. In this hypothesis-generating study, we investigated biomarkers that can be incorporated to predict treatment outcomes in patients with locally advanced HCC who are administered liver-directed combined radiotherapy (LDCRT). Methods: Ninety-nine patients with HCC who were treated with conventional fractionation LDCRT between July 2016 and October 2018 were enrolled in this prospective single-arm study. Clinical outcomes and possible serum biomarkers, including soluble programmed cell death ligand-1 (sPD-L1), interleukin (IL)-10, IL-6, cell-free DNA (cfDNA), inter-alpha inhibitor H4, and interferon-gamma, were analyzed. The primary endpoint was disease progression, and additional endpoints were local failure-free rate, intrahepatic failure-free rate, and lung metastasis-free rate. Results: The median follow-up period was 18.7 months. The 1-year progression-free rate was 38.2%. Increasing baseline sPD-L1 per pg/mL, previous treatment history, protein induced by vitamin K absence-II >1,629 mAU/mL, and multiple tumors were the adverse factors for progression based on multivariate analysis. Survival tree analysis revealed three prognostic groups for progression, in which patients with multiple lesions and baseline sPD-L1 ≥41.07 pg/mL showed the worst outcomes. For dynamic changes in biomarker levels, sPD-L1 fold change and cfDNA fold-change values were unfavorable factors for progression. Conclusion: Baseline sPD-L1, sPD-L1 fold change, and cfDNA fold-change values showed the highest potential as biomarkers for predicting post-treatment progression after LDCRT in HCC patients. By incorporating clinical factors, these biomarkers may be useful for devising a biomarker-driven treatment paradigm in locally advanced HCC.ope

Noninvasive Biomarker for Predicting Treatment Response to Concurrent Chemoradiotherapy in Patients with Hepatocellular Carcinoma

Purpose: To investigate noninvasive biomarkers for predicting treatment response in patients with locally advanced HCC who underwent concurrent chemoradiotherapy (CCRTx). Materials and Methods: Thirty patients (55.5 ± 10.2 years old, M:F = 24:6) who underwent CCRTx due to advanced HCC were enrolled. Contrast-enhanced US (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) were obtained before and immediately after CCRTx. The third CEUS was obtained at one month after CCRTx was completed. Response was assessed at three months after CCRTx based on RECIST 1.1. Quantitative imaging biomarkers measured with CEUS and MRI were compared between groups. A cutoff value was calculated with ROC analysis. Overall survival (OS) was compared by the Breslow method. Results: Twenty-five patients were categorized into the non-progression group and five patients were categorized into the progression group. Peak enhancement of the first CEUS before CCRTx (PE1) was significantly lower in the non-progression group (median, 18.6%; IQR, 20.9%) than that in the progression group (median, 59.1%; IQR, 13.5%; P = 0.002). There was no significant difference in other quantitative biomarkers between the two groups. On ROC analysis, with a cutoff value of 42.6% in PE1, the non-progression group was diagnosed with a sensitivity of 90.9% and a specificity of 100%. OS was also significantly longer in patients with PE1 < 42.6% (P = 0.014). Conclusion: Early treatment response and OS could be predicted by PE on CEUS before CCRTx in patients with HCC.ope

Comparison of radiofrequency ablation and ablative external radiotherapy for the treatment of intrahepatic malignancies: A hybrid meta-analysis

Background & aims: Radiofrequency ablation (RFA) and ablative external beam radiotherapy (ablative RT) are commonly used to treat small intrahepatic malignancies. We meta-analysed oncologic outcomes and systematically reviewed the clinical consideration of tumour location and size. Methods: PubMed, Medline, Embase, and Cochrane Library databases were searched on February 24, 2022. Studies comparing RFA and ablative RT, providing one of the endpoints (local control or survival), and encompassing ≥5 patients in each arm were included. Results: Twenty-one studies involving 4,638 patients were included. Regarding survival, the odds ratio (OR) was 1.204 (p = 0.194, favouring RFA, not statistically significant) among all studies, 1.253 (p = 0.153) among hepatocellular carcinoma (HCC) studies, and 1.002 (p = 0.996) among colorectal cancer metastasis studies. Regarding local control, the OR was 0.458 (p <0.001, favouring ablative RT) among all studies, 0.452 (p <0.001) among HCC studies, favouring the ablative RT arm, and 0.649 (p = 0.484) among colorectal cancer metastasis studies. Pooled 1- and 2-year survival rates for HCC studies were 91.8% and 77.7% after RFA, and 89.0% and 76.0% after ablative RT, respectively; and for metastasis studies were 88.2% and 66.4% after RFA and 82.7% and 60.6% after RT, respectively. Literature analysis suggests that ablative RT can be more effective than RFA for tumours larger than 2-3 cm or for specific sublocations in the liver (e.g. subphrenic or perivascular sites), with moderate quality of evidence (reference to the grading system of the American Society for Radiation Oncology Primary Liver Cancer Clinical Guidelines). The pooled grade ≥3 complication rates were 2.9% and 2.8% in the RFA and ablative RT arms, respectively (p = 0.952). Conclusions: Our study shows that ablative RT can yield oncologic outcomes similar to RFA, and suggests that it can be more effective for the treatment of tumours in locations where RFA is difficult to perform or for large-sized tumours. Systematic review registration: This study was registered with PROSPERO (Protocol No: CRD42022332997). Impact and implications: Radiofrequency ablation (RFA) and ablative radiotherapy (RT) are non-surgical modalities for the treatment of small intrahepatic malignancies. Ablative RT showed oncologic outcomes at least similar to those of RFA, and was more effective at specific locations (e.g. perivascular or subphrenic locations).ope

2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma

The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.ope