The Hong Kong consensus statements on unresectable hepatocellular carcinoma: narrative review and update for 2021.

Background and Objective: Hong Kong, like many parts of Asia, faces a high burden of hepatocellular carcinoma (HCC) caused by high endemic rates of hepatitis B virus infection. Hong Kong clinicians have developed a high level of expertise in HCC treatment across surgical, transarterial, ablative, radiotherapeutic and systemic modalities. This publication summarizes the latest evidence-based recommendations on how these modalities should be used. Methods: In two meetings held in 2020, a multidisciplinary panel of surgeons, oncologists and interventional radiologists performed a narrative review of evidence on the management of HCC, with an emphasis on treatment of HCC not amenable to surgical resection. Close attention was paid to new evidence published since the previous version of these statements in 2018. Key Content and Findings: The expert panel has formulated 60 consensus statements to guide the staging and treatment of unresectable HCC. Since the previous version of these statements, considerable additions have been made to the recommendations on use of targeted therapies and immunotherapies because of the large volume of new evidence. Conclusions: Our consensus statements offer guidance on how to select HCC patients for surgical or non-surgical treatment and for choosing among non-surgical modalities for patients who are not candidates for resection. In particular, there is a need for more evidence to aid physicians in the selection of second-line systemic therapies, as currently most data are limited to patients with disease progression on first-line sorafenib.

Presence of tumour capsule on contrast-enhanced CT is associated with improved outcomes of stereotactic body radiation therapy in hepatocellular carcinoma patients.

PURPOSE: Stereotactic body radiation therapy (SBRT) is a novel local therapy for the treatment of hepatocellular carcinoma (HCC). While effective, there is currently no reliable radiological marker to guide patient selection. In this study, we investigated the prognostic value of capsule appearance on contrast-enhanced computed tomography (CT) for patients undergoing SBRT. MATERIALS AND METHODS: Between 2006 and 2017, 156 consecutive patients with Child-Pugh score class A/B and HCC ≥ 5 cm who underwent SBRT were retrospectively analysed. Baseline triple-phase CTs of the abdomen were reviewed for the presence of capsule appearances and correlated with objective response rate (ORR), overall survival (OS) and pattern of treatment failure. RESULTS: Capsule appearance on CT was present in 83 (53.2%) patients. It was associated with improved ORR by Response Evaluation Criteria in Solid Tumours (RECIST) (60.2 vs. 24.7%, p < 0.001) and Modified Response Evaluation Criteria in Solid Tumours (mRECIST) (78.3 vs. 34.2%, p < 0.001). The presence of a capsule was also associated with superior 2­year local control (89.1 vs. 51.4%, p < 0.001) and 2­year OS (34.1 vs. 14.8%, p < 0.01). Hepatic out-field failure was the dominant mode of progression, which was less common in patients with intact capsule (54.2 vs. 60.3%, p = 0.01). CONCLUSION: Capsule appearance on CT could potentially be a non-invasive prognostic marker for selecting HCC patients to undergo SBRT. A larger cohort is warranted to validate our findings.

Better survival after stereotactic body radiation therapy following transarterial chemoembolization in nonresectable hepatocellular carcinoma: A propensity score matched analysis.

BACKGROUND: This study compared outcomes of nonresectable hepatocellular carcinoma (HCC) who had transarterial chemoembolization (TACE) vs. stereotactic body radiation therapy (SBRT) after TACE (TACE + SBRT). METHODS: This was a retrospective study of 2 centers in Hong Kong. There were 49 patients who had TACE + SBRT and 202 patients who had TACE alone. Propensity score matching was used to adjust for differences in patients' demographics and tumor characteristics between the 2 groups. The primary outcome was overall survival (OS) and secondary outcomes were progression-free survival (PFS) and treatment-related toxicity. RESULTS: After matching, 49 patients were in the TACE + SBRT group and 98 patients in the TACE group with similar baseline characteristics. The 1-&3-year OS were better in TACE + SBRT group (67.2 vs. 43.9% and 36.5 vs. 13.3%, p = 0.003). The 1-&3-year PFS was also better in TACE + SBRT group (32.5 vs. 21.4% and 15.1 vs. 5.1%, p = 0.012). Radiological disease control was better in the TACE + SBRT group (98 vs. 56.7%). Risk of severe toxicity was uncommon in both treatment arms. TACE + SBRT was an independent good prognostic factor for OS and PFS in multivariate analysis, whereas AFP>200 ng/ml, large tumor and multiple tumors predicted worse OS. CONCLUSION: TACE + SBRT is safe and results in better survivals in nonresectable HCC patients.

Hong Kong Consensus Statements for the Management of Unresectable Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is highly prevalent in Hong Kong due to the high prevalence of chronic hepatitis B infection. Liver cancer is the fourth most common cancer and the third most common cause of cancer death. Due to the high case load, there is a high level of local expertise in treating HCC, and the full spectrum of treatment modalities is available. This document summarizes how these modalities should be used based on the latest evidence. SUMMARY: In 2 meetings held in early 2017, a multidisciplinary group of Hong Kong clinicians, including liver surgeons, interventional radiologists, clinical oncologists, and medical oncologists, met to update local consensus statements for management of HCC. These statements are based on the latest evidence and give detailed guidance on how to deploy these modalities, in particular for cases of HCC which are not suited to surgical resection. KEY MESSAGES: These statements give detailed information on how to decide if a patient is a candidate for resection, methods to improve candidacy for resection, and guidance for use of various nonsurgical interventions to manage patients ineligible for resection.

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.

Comparison of clinical efficacy and renal safety of telbivudine and entecavir in chronic hepatitis B patients receiving cytotoxic chemotherapy.

OBJECTIVE: Limited data is available on the clinical outcomes of telbivudine (LdT) and entecavir (ETV) in pre-emptive antiviral chemoprophylaxis. This study aimed to evaluate the clinical efficacy and renal safety of LdT and ETV in patients with chronic hepatitis B (CHB) who received cytotoxic chemotherapy. METHODS: Altogether 290 treatment-naïve CHB patients undergoing intense chemotherapy were enrolled to receive daily 600 mg of LdT or 0.5 mg of ETV as pre-emptive antiviral chemoprophylaxis. RESULTS: The ETV group had significantly higher proportion of patients with undetectable hepatitis B viral (HBV) DNA load compared with LdT at week 24 (73.0% vs 50.3%, P = 0.000). The cumulative rates of virological breakthrough in the LdT and ETV groups were 9.15% and 3.65% at the second year of therapy, respectively (P = 0.059), which was associated with detectable HBV DNA at week 24 (P = 0.000). The MELD score of the LdT group was significantly lower than that of the ETV group after the first year (4.53 vs 7.53, P = 0.002) and the second year (1.96 vs 7.09, P = 0.000) of antiviral therapy. Moreover, the estimated glomerular filtration rate (eGFR) was significantly improved in the LdT group than in the ETV group after two years of antiviral therapy. CONCLUSION: LdT has a lower clinical efficacy in viral suppression than ETV, but LdT is associated with greater extent of improvement in liver and renal functions of patients in pre-emptive prophylaxis for cytotoxic chemotherapy.

Hong Kong consensus recommendations on the management of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is particularly prevalent in Hong Kong because of the high prevalence of chronic hepatitis B (CHB) infection; HCC is the fourth commonest cancer in men and the seventh commonest in women, and it is the third leading cause of cancer death in Hong Kong. The full spectrum of treatment modalities for HCC is available locally; however, there is currently no local consensus document detailing how these modalities should be used. SUMMARY: In a series of meetings held between May and October 2013, a multidisciplinary group of Hong Kong clinicians - liver surgeons, medical oncologists, clinical oncologists, hepatologists, and interventional radiologists - convened to formulate local recommendations on HCC management. These recommendations consolidate the most current evidence pertaining to HCC treatment modalities, together with the latest thinking of practicing clinicians engaged in HCC management, and give detailed guidance on how to deploy these modalities effectively for patients in various disease stages. KEY MESSAGES: Distinct from other regional guidelines, these recommendations provide guidance on the use of antiviral therapy to reduce the incidence of HCC in CHB patients with cirrhosis and to reduce recurrence of CHB-related HCC.

Severe ileitis associated with capecitabine: Two case reports and review of the literature.

Capecitabine is a commonly used anticancer drug, which has been associated with adverse events, including skin and gastrointestinal symptoms, such as vomiting and diarrhea. We herein present treated two rare cases of capecitabine-associated ileitis. In one of the patients, ileitis occurred during combination chemotherapy for metastatic colon cancer, despite previous good tolerance to this drug; the other patient developed ileitis following adjuvant single-agent treatment. The first case is unlike previously reported cases, in which patients had no past exposure to capecitabine. Ileitis may be severe but reversible with early diagnosis and proper supportive treatment, and patients may resume chemotherapy following capecitabine discontinuation.

Nasopharyngeal intracavitary brachytherapy: the controversy of T2b disease.

BACKGROUND: Locally persistent nasopharyngeal carcinoma (NPC) carries an increased risk of local failure if additional treatment is not given. It has been shown that intracavitary brachytherapy is effective in the treatment of patients with T1 and T2a NPC, although its role in the treatment of T2b disease had remained uncertain. The objectives of the current study were to evaluate the outcomes of patients with T2b, locally persistent NPC who were treated with high-dose-rate (HDR) intracavitary brachytherapy and to explore whether routine brachytherapy boost could improve the local control of patients who had T2b NPC at initial diagnosis. METHODS: Thirty-four patients with locally persistent NPC who were treated during 1992-2000 with HDR intracavitary brachytherapy were analyzed retrospectively. All patients had T2b disease at initial diagnosis. They were treated with HDR intracavitary brachytherapy at doses of 22.5-24.0 grays (Gy) in 3 weekly sessions. To compare the efficacy of brachytherapy, another 403 consecutive patients with nonmetastatic T2b NPC who were treated with curative intent by external radiotherapy (ERT) during the same period were evaluated. RESULTS: An improvement in the 5-year actuarial local failure-free survival rate (brachytherapy group vs. ERT group: 96.9% vs. 81.5%; P = 0.024), the disease-specific survival rate (84.5% vs. 68.1%; P = 0.021), and the overall survival rate (78.3% vs. 63.1%; P = 0.034) was demonstrated in the group that had locally persistent NPC who were salvaged with brachytherapy. In assessing local control, the addition of brachytherapy was just short of statistical significance on multivariate analysis (P = 0.054). The complication rates were comparable between the brachytherapy group and the ERT group. CONCLUSIONS: The results suggested that patients with T2b NPC who have locally persistent disease can be salvaged effectively with brachytherapy. Their local control was even better than that achieved by patients who had clinical remission of local disease at the completion of ERT. Furthermore, it is possible that routine brachytherapy boost, after the completion of ERT, may improve local control in patients who have T2b disease at initial diagnosis. However, its exact benefit can be elucidated only by prospective, randomized studies.