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BACKGROUND A surge of vascular endothelial growth factor (VEGF) after transarterial chemoembolization (TACE) may contribute to tumor progression. Axitinib is a potent antiangiogenic agent with main activity against VEGF receptors 1 to 3. To the authors' knowledge, its role in combination with TACE for the treatment of patients with inoperable hepatocellular carcinoma (HCC) is unclear. METHODS A phase 2 clinical trial (ClinicalTrials.gov identifier NCT01352728) was conducted to evaluate the combination treatment. Patients with inoperable HCC who were potential candidates for TACE initiated treatment with axitinib at a dose of 5 mg twice daily and were evaluated for the need for TACE every 8 weeks. Axitinib was withheld 24 hours before TACE, and resumed 24 hours afterward when fulfilling predefined criteria. Radiologic assessment was conducted every 8 weeks. The primary endpoint was the 2-year overall survival (OS) rate. RESULTS A total of 50 patients were recruited from March 2011 to April 2014. The mean age of the patients was 61.8 years, and 46 patients (92%) had hepatitis B infection. The Barcelona Clinic Liver Cancer stage B/C percentage was 76% (38 cases)/24% (12 cases). The 2-year OS rate was 43.7%, and the median OS was 18.8 months in the intention-to-treat population. Among the evaluable population (44 patients), 40.9% (18 patients) and 27.3% (12 patients) achieved complete and partial responses, respectively. Common grade 3 or above axitinib-related complications included hand-foot skin reaction (14%) and hypertension (24%). The presence of hypertension during treatment was found to be an independent prognosticator (hazard ratio, 0.563; P = .0073) suggestive of a contributory role of axitinib to efficacy. CONCLUSIONS The combination of axitinib and TACE was potentially efficacious for patients with inoperable HCC with a high radiologic response rate. Cancer 2017. © 2017 American Cancer Society.

Background and Aims The albumin–bilirubin (ALBI) grade is a recently emerging alternative of the Child–Pugh (CP) grade. The Cancer of the Liver Italian Program (CLIP) was demonstrated to be a useful prognostic model for hepatocellular carcinoma (HCC) in large prospective cohorts. We aimed to investigate the feasibility of substituting the CP grade by the ALBI grade in the CLIP system and compare the prognostic performance with other existing staging systems. Methods A large cohort of 1973 Chinese patients with HCC was recruited to evaluate the prognostic performance of CP-based CLIP (CP-CLIP) and ALBI-based CLIP (ALBI-CLIP) systems and nine other staging systems by homogeneity likelihood chi-square, c-index, and corrected Akaike information criterion. Results The ALBI-CLIP system provided comparable prognostic performance than the CP-CLIP system, which was indicated by homogeneity likelihood chi-squares (ALBI-CLIP 1186.35 vs CP-CLIP 1145.54), c-indices (ALBI-CLIP 0.789 vs CP-CLIP 0.785) and AICs (ALBI-CLIP 15 493.47 vs CP-CLIP 15 534.28). Among 11 staging systems, ALBI-CLIP and CP-CLIP systems were associated with the highest homogeneity chi-squares and c-indices, and the lowest corrected Akaike information criterion. Patients in ALBI-CLIP score 0–4 had better median survival than those in corresponding CP-CLIP score. Conclusions The ALBI grade performs as well as the CP grade when integrating into the CLIP system. ALBI-CLIP and CP-CLIP systems are the most accurate prognostic models among 11 existing staging systems.

Background and aim The Japan Integrated Staging (JIS) for hepatocellular carcinoma (HCC) has been extensively studied in hepatitis virus C-endemic Japanese population but seldom evaluated outside Japan, while albumin-bilirubin (ALBI)-based JIS (ALBI-T) has never been externally validated. We evaluate the prognostic significance of the ALBI-T score among Chinese patients with hepatitis virus B (HBV)-related HCC, and to explore its potential therapeutic application in selecting patients for appropriate treatments in addition to the Barcelona Clinic Liver Cancer (BCLC) recommendation. Methods A cohort of 1222 HBV-associated HCC patients was evaluated to compare the prognostic performance of JIS and ALBI-T scores by homogeneity likelihood chi-square and corrected Akaike information criterion. In the subgroup analysis of each BCLC stage, Kaplan-Meier method and log-rank statistics were used to compare overall survival of patients undergoing different treatment options. Results The ALBI-T score showed better prognostic performance than the JIS score, which were indicated by homogeneity likelihood chi-squares (ALBI-T 580.12 vs JIS 536.35) and Akaike information criteria (ALBI-T 9836.57 vs JIS 9880.23). Treatment options significantly influenced prognosis among patients of the same BCLC stage. With the use of ALBI-T score 4 as the cutoff, the current study identified that a portion of patients (14.7%, 25.2% and 28.6% of BCLC stage B, C and D, respectively) undergoing unnecessary therapy without survival advantage. Conclusions The ALBI-T score is applicable to Chinese patients with HBV-related HCC to provide reasonable prognostic information as well as potentially helping clinicians to avoid offering non-beneficial aggressive treatments.

Background and Aims The albumin–bilirubin (ALBI) grade is a recently reported, simpler, more objective, and evidence-based alternative to the Child–Pugh (CP) score for hepatocellular carcinoma (HCC). We aimed to study whether ALBI grade could substitute for CP score in Barcelona Clinic Liver Cancer (BCLC) for HCC. Methods An international multicentre cohort (n = 3696) was accrued to compare the prognostic performance of the CP-based and ALBI-based BCLC system, in terms of homogeneity, discriminatory ability, and monotonicity of gradients that were numerically reflected by homogeneity likelihood, linear trend chi-squares, and c-indices, respectively. Results The ALBI grade performed as well as CP score when integrated into the BCLC staging system in terms of predicting clinical outcome of HCC regardless of regions, etiology, and treatment options. CP-based and ALBI-based BCLC systems were highly concordant with weighted kappa value of 0.917. All restaged patients showed significantly different clinical outcomes compared with their original stage classification. In particular, ALBI-based BCLC upstaged 83 (2.2%) patients from lower CP-based BC LC stages to ALBI-based BCLC stage D, whose median overall survival was only 3 months. Conclusions The overall prognostic performance of ALBI-based and CP-based BCLC systems was similar. It also potentially allows more precise patient selection for clinical trials on systemic agents.

Background Most women with advanced breast cancer (ABC) show little distress, but about one in ten show persistent distress over time. It remains unclear if meanings ascribed by patients to ABC differentiate these distress trajectories. Study aims This qualitative study (a) compared illness meanings of ABC between women with persistent psychological distress and those with low/transient distress, and (b) examined how illness meanings might influence coping strategies. Methods The sample was drawn from a prior quantitative study exploring psychological distress trajectories following ABC diagnosis. Overall, 42 Cantonese- or Mandarin-speaking Chinese women diagnosed with locally advanced or metastatic ABC were recruited based on their distress trajectory status (low-stable, transient, or persistent distress). Interviews were recorded, transcribed, and analyzed following grounded theory approach using simultaneous analysis. Results Women with persistent distress viewed their diagnosis as another blow in life, the illness was global, permeating every aspect of their life. Maladaptive rumination and thought suppression were common responses to illness demands. These women had poor social support. A sense of demoralization stood out in their narratives. In contrast, women with transient/low-stable distress encapsulated the illness, with minimum impacts of their life. They did not evidence dysfunctional repetitive thoughts. Living in a supportive environment, they were able to accept and/or live in the present-moment. Conclusions Rumination, thought suppression, social constraints, and pre-existing exposure to life stress may be potential risks for chronic distress in response to advanced breast cancer. Persistent and transient distress responses to cancer may have different underpinnings. Copyright © 2016 John Wiley & Sons, Ltd.

Background and Aims The BALAD score is developed to provide an objective determination of prognosis for hepatocellular carcinoma (HCC) by incorporating five serum markers, namely albumin, bilirubin, alpha-fetoprotein (AFP), agglutinin-reactive alpha-fetoprotein (AFP-L3), and des-γ-carboxy prothrombin. We aim to study the applicability of BALAD score and prognostication of the three tumor markers in hepatitis B virus-related HCC. Methods Patients with newly diagnosed HCC were prospectively enrolled. All of the baseline characteristics and serum albumin and bilirubin level were documented at baseline. The levels of the three tumor markers (AFP, AFP-L3, and des-γ-carboxy prothrombin) were determined in archival serum samples. Patients were followed up for survivals according to local practice. The prognostic performances of the three markers and BALAD score were studied in association with overall survival (OS). Results A total of 198 patients with hepatitis B-related HCC were recruited. AFP and AFP-L3 levels were independent prognostic factors. The number of elevated tumor markers was also predictive of worse OS. BALAD score could stratify the cohort into different patient groups with distinct median OS. The median OS of BALAD score of 0, 1, 2, 3, and 4 was not reached, 26.6, 8.3, 2.6, and 1.9 months, respectively (P

Objective A diagnosis of advanced breast cancer (ABC) challenges a woman's ambitions. This longitudinal study explored (1) if goal adjustment disposition influenced psychological adjustment patterns among women with ABC and (2) if dispositional hope and optimism moderate effects of goal adjustment on psychological adjustment. Methods One hundred ninety three out of 225 women with ABC were assessed while they were awaiting/receiving initial chemotherapy, then again at 6 weeks, 3 months, 6 months, and 12 months post-baseline. Goal disengagement, goal reengagement, optimism, hope, and psychological adjustment (anxiety, depression, and positive affect) were assessed at baseline; psychological adjustment was reassessed at each follow-up. Latent growth curve modeling was used to examine the change of psychological adjustment and test the study objectives. Results High goal disengagement, low reengagement, and high optimism were associated with lower initial anxiety, while high goal disengagement and optimism predicted a slower rate of change in anxiety. High goal disengagement, reengagement, and optimism were associated with lower initial depression. High goal reengagement, optimism, and hope were associated with initial positive affect scores, while optimism predicted its rate of change. Optimism moderated the effect of goal disengagement on anxiety and depression, whereas hope moderated the effect of goal reengagement on positive affect. Conclusion Goal disengagement and reengagement are two relatively independent processes influencing psychological well-being. These findings will help clinicians to tailor specific interventions to help women coping with the diagnosis of ABC.

Background Anxiety and depression (distress) over the first year following the initial adjuvant therapy for advanced breast cancer (ABC) remain poorly documented in non-Caucasian populations. This study describes trajectories of distress and their determinants in Chinese women with ABC. Methods Of the 228 Chinese women newly diagnosed with ABC recruited from six oncology units, 192 completed an interview before their first course of chemotherapy (baseline) and follow-up interviews at 1.5, 3, 6, and 12 months thereafter. At baseline, participants were assessed for supportive care needs, psychological distress, physical symptom distress, optimism, and cancer-related rumination. At follow-up, participants completed the measure of psychological distress. Latent growth mixture modeling was used to identify trajectory patterns of distress. Multinominal logistic regression was used to identify predictors of trajectory patterns adjusted for demographic and medical characteristics. Results Four distinct trajectories of anxiety and depression were identified. Most women showed low-stable levels of anxiety (68%) and depression (68%), but one in 11 women were chronically anxious (9%) and depressed (9%). Optimism, negative cancer-related rumination, and physical symptom distress predicted both anxiety and depression trajectories. Psychological needs predicted anxiety trajectories. Women in the low-stable distress group reported high optimism, low psychological supportive care needs, low physical symptom distress, and low negative cancer-related rumination. Conclusion Most women with ABC did not experience psychological distress over 12 months following diagnosis of ABC. Preventive interventions should focus on women at risk of high persistent distress and reducing rumination, providing emotional support, and managing physical symptoms. Copyright © 2013 John Wiley & Sons, Ltd.

Reactivation of hepatitis B virus (HBV) infection is a known complication during and after anti-cancer therapy. This condition can affect two patient populations: it is most commonly seen in patients who are seropositive for hepatitis B surface antigen (HBsAg), but it is also being increasingly reported among patients who are HBsAg-negative but who have prior infection, as evident by seropositive status for antibody to hepatitis B core antigen (anti-HBc), irrespective of their anti-HBs (antibody to HBsAg) status. The clinical course can vary from asymptomatic hepatitis to fulminant hepatic failure that can be potentially fatal. With the increasing use of biological agents in addition to potent cytotoxic chemotherapy in the armamentarium of anti-cancer treatments, reactivation of hepatitis B has become a common clinical situation that is faced by both oncologists and hepatologists especially in HBV endemic areas. In this review, we discuss the clinical course of reactivation in the two HBV-infected sub-populations, and the role of anti-virals in the prevention and management of HBV reactivation in association with cytotoxic chemotherapy and biological therapies.

Background Women with advanced breast cancer (ABC) are living longer, so understanding their needs becomes important. This cross-sectional study investigated the type and extent of unmet supportive care needs in Hong Kong Chinese women with advanced breast cancer. Methods Face-to-face interviews were conducted among women with stage III or stage IV disease mostly awaiting chemotherapy (76%) to identify unmet needs using the Supportive Care Needs Survey Short Form, psychological morbidity using the Hospital Anxiety and Depression Scale, symptom distress using the Memorial Symptom Assessment Scale, and satisfaction with care using the Patient satisfaction questionnaire (PSQ-9). Results About 27–72% of 198/220 (90%) women (mean age = 53.4 ± 9.74 (standard deviation) years) identified needs from the health system, information, and patient support (HSIPS) domain as the top 15 most prevalent unmet needs. ‘having one member of hospital staff with whom you can talk to about all aspect of your condition, treatment, and follow-up’ was most cited by 72% of the patients, with remaining unmet needs addressing mostly desire for information. Unmet need strength did not differ between women with stage III and stage IV disease, whereas women with first time diagnosis reported greater health system and information unmet needs compared with women with recurrent disease. Stepwise multiple regression analyses revealed that symptom distress was consistently positively associated with all but sexuality need domains, whereas low satisfaction with care was associated with HSIPS (β = 3.270, p

Following the encouraging results of sorafenib in advanced hepatocellular carcinoma (HCC), targeted therapy has become a new direction of research in the treatment of HCC. Emerging data provide evidence that the pathogenesis and progression of HCC are mediated by a number of molecular defects and dysregulated pathways. Novel targeted therapies are designed to inhibit the aberrant pathways at a molecular level with an aim to improve the clinical outcome. For the past few years, an increasing number of targeted agents have been tested in HCC in the clinical setting. This review aims to summarize the current status of clinical development of targeted therapy in HCC, with focus on novel agents targeting angiogenesis, signal transduction and epigenetic dysregulation of tumors. The review also discusses the lessons learned from outcomes of completed clinical trials and provides perspectives on future clinical trials in HCC.

Background Antiviral therapy for hepatitis B virus (HBV) infection is frequently prescribed for patients with chronic HBV infection during surveillance for hepatocellular carcinoma (HCC). In patients who subsequently develop HCC, the impact of antiviral therapy on the outcome of HCC remains unclear. Aims We aimed to study the impact of antiviral therapy on the survival of patients who developed HCC. Methods From two prospective surveillance cohorts, the use of antiviral therapy for patients with HCC was retrospectively reviewed. We compared the overall survival, liver function and tumour characteristics between patients with and without antiviral therapy during surveillance. Multivariate analysis was conducted to determine the independent prognostication of antiviral therapy. Results During a median follow-up of 10.1 years of 1429 patients, 148 cases of HCC were diagnosed and followed up for a median of 5.7 years. Twenty-nine patients were given antiviral therapy during surveillance and continued treatment after diagnosis of HCC. The median survival of this group of patients was better than the rest of cohorts (hazard ratio: 0.472; 95% CI: 0.25–0.89; P = 0.0191). Use of antiviral therapy remained an independent prognostic factor after adjustment for demographic factors and tumour staging on multivariate analysis. Exploratory analysis revealed that patients who commenced antiviral therapy during surveillance had lower HBVDNA, lower serum alanine transaminase, better hepatic reserves and higher rate of local treatment at diagnosis of HCC. Conclusion This study provides evidence that commencement of antiviral therapy during the surveillance period is associated with improvement in overall survival in HBV-related HCC.

The E6 and E7 proteins encoded by human papillomaviruses (HPV) are prime targets for therapeutic vaccine development. Ninety-five women with HPV 52 infection (33 transient infections, 17 cervical intraepithelial neoplasia grade II, 15 cervical intraepithelial neoplasia grade III, and 30 invasive cervical cancers) were examined for T-cell responses using interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT) assay. Of the 29 peptides (13 L1, 10 E6, and 6 E7) screened positive by an in vitro peptide-binding assay, 14 were positive by the IFN-γ ELISPOT assay. Positive epitopes for HLA A11 were located at amino acid positions 103-111, 332-340, 342-350, and 373-381 of the L1 protein; and at 27-35 and 86-94 of the E6 protein; and at 1-9 and 27-35 of the E7 protein. A24-specific epitopes included 60-68 and 98-106 of the L1 protein, 42-50 and 59-67 of the E6 protein, and 24-32 of the E7 protein. Only one epitope (99-107) of the E6 protein showed positive responses for HLA A2 subjects. Overall, T-cell responses against L1 were observed mainly in subjects who had cleared infection; whereas responses against E6 and E7 were confined mainly to subjects who had developed cervical neoplasia. The proportion of subjects showing detectable T-cell responses was low across all grades of cervical neoplasia suggesting that immune evasion mechanisms had set on early in the course of disease progression. This study provides the first set of T-cell epitopes mapped for HPV 52, which can be considered for further evaluation as targets for immunotherapy.

Background and Aim: Hepatitis B viral (HBV) infection is the predominant etiology of hepatocellular carcinoma (HCC) in Asia. Our group previously reported a staging system known as the Chinese University Prognostic Index (CUPI) for HCC populations of which HBV infection is the predominant etiology. This study aims to validate CUPI and compare with other published staging systems. Methods: We analyzed a prospective cohort of patients with newly diagnosed HCC from 2003 to 2005. All patients were staged with CUPI, Barcelona Clinic Liver Cancer Classification (BCLC), Cancer of the Liver Italian Program score (CLIP), tumor-node-metastasis (TNM) and Okuda systems at diagnosis. They were followed with survival data and the performance of each staging system (in terms of homogeneity, discriminatory ability and monotonicity of gradient) were analyzed and compared. Results: A total of 595 patients (80.2% with chronic HBV infection) were analyzed. The median follow-up was 41.4 months and the median survival was 6.6 months. Multivariate analyses identified symptomatic disease, ascites, vascular involvement, Child-Pugh-stage, alpha-fetoprotein and treatment to be the independent prognostic factors. CUPI could identify three groups with statistically significant survival difference (P

Background: There is no instrument available in Chinese for assessing psychosocial needs. This study aimed to assess the validity and reliability of the Chinese version of the Supportive Care Needs Survey short form (SCNS-SF34-C) in Chinese women with breast cancer (BC). Methods: The Chinese version of the 34-item SCNS-SF34-C, a self-report measure for assessing psychosocial unmet needs, was administered to 348 Chinese women with BC at the outpatient oncology unit. Exploratory factor analysis (EFA) tested the factor structure. The internal consistency, convergent, divergent, and discriminant validity of the identified factor structure were assessed. Results: In contrast to the five-factor structure identified in the original 34-item SCNS-SF34, our EFA produced a 33-item solution accounting for 54% of score variance comprising four-factors: (1) Health system, information, and patient support, (2) Psychological needs, (3) Physical and daily living, and (4) Sexuality needs. Separate dimensions for Health system and information, and the Patient care and support domains were not supported. Cronbach alphas ranged from 0.75 to 0.92. Correlations of psychological and physical symptom distress measures indicated acceptable convergent validity. No correlation with optimism and positive affect measures indicated divergent validity. Discriminant validity was demonstrated by effective differentiation between clinically distinct patient groups (no active treatment versus active treatment; advanced BC versus localized BC). Discussion: The Chinese version of the Supportive Care Needs Survey has suitable factor structure and psychometric properties for use in assessing psychosocial needs among Chinese women with BC. Further validation is needed for other cancer types. Copyright © 2010 John Wiley & Sons, Ltd.

Asia has a disproportionate share of the world's burden of hepatocellular carcinoma (HCC). However, the highly regarded clinical practice guidelines and recommendations for the design and conduct of clinical trials for HCC largely reflect Western practice. In order to design mutually beneficial international clinical trials of promising targeted therapies, it is imperative to understand how the aetiology, staging and treatment of HCC differ between Asian and Western countries. Our group, comprising experts in oncology and hepatology from countries that constitute the Eastern Asian region, convened to compare and contrast our current practices, evaluate potential compliance with the clinical trial recommendations, and offer suggestions for modifications that would enhance international collaboration. Here, we describe the results of our discussions, including recommendations for appropriate patient stratification based on potentially important differences in HCC aetiology, identification of practices that may confound interpretation of clinical trial outcomes (traditional Chinese medicine; antivirals that target hepatitis B virus; heterogeneous embolization procedures), suggestions for utilizing a common staging system in study protocols, recognition that sorafenib usage is limited by financial constraints and potentially increased toxicity in Asian patients, and expansion of patient populations that should be eligible for initial clinical trials with new agents.

Aim: To examine the association between a broad array of characteristics and sexuality in breast cancer patients in Hong Kong. Method: We collected data on demographic and clinical factors, psychosocial well-being, quality of life (QOL), body image and sexual health of breast cancer patients presented to the Department of Clinical Oncology, Prince of Wales Hospital from November 2005 to February 2006. Results: More than 40% of Chinese breast cancer patients experienced moderate problems in sexual health. Their medical treatment had a greater influence on their sexual functioning in a change in their social activities, whereas more support from their partner predicted less influence. The presence of a child and more support from their partner predicted greater sexual satisfaction. Undergoing the menopause related to a longer time to resume sexual activity after cancer treatment. A change of relationship with their partner and a loss of self-confidence were strong predictors of sexual problems influencing their QOL. Patients who had experienced a change in their relationship with their partner or had greater sexual problems were more likely to perceive greater benefit from professional intervention on sexual problem. Conclusion: An improvement in their intimate relationships and enhanced psychosocial functioning should improve the sexual health of Chinese women with breast cancer.

Purpose: To determine the presence of ras association domain family 1A (RASSF1A) promoter methylation in the tumor tissues and plasma of patients with hepatocellular carcinoma (HCC). Experimental Design: Methylation-specific polymerase chain reaction was used to detect RASSF1A methylation in DNA extracted from HCC tumors and paired plasma samples of 40 patients. The association of RASSF1A hypermethylation in tumor and plasma DNA of HCC patients with clinicopathological characteristics was also analyzed. Results: RASSF1A promoter hypermethylation was detected in 37 of the 40 HCC tissues (92.5%). Of the paired plasma from the 40 HCC patients, aberrant methylation was detected in 17 (42.5%). No RASSF1A methylation was detected in the plasma in the absence of methylation in the corresponding tumor. The presence of RASSF1A promoter hypermethylation in plasma DNA was found to associate with HCC size of ≥4 cm (P=0.035). Conclusion: RASSF1A promoter hypermethylation occurred at a high frequency in HCC. The aberrant methylation was also detectable in over 40% of matched plasma. The latter should be evaluated as a screening tool and/or prognosticator of HCC patients.

Hepatitis B virus (HBV) reactivation during cytotoxic chemotherapy for cancer may complicate treatment and cause liver damage. The complication has been reported to occur in 10% to over 50% of HBV carriers, but the factors that determine which patients will develop reactivation remain unclear. The objective of the study is to test the hypothesis that the prechemotherapy HBV DNA level is a risk factor for the development of HBV reactivation. We studied 41 women undergoing cytotoxic chemotherapy for breast cancer, 17 of whom developed reactivation and 24 who did not. We developed a novel, ultra-sensitive, real-time polymerase chain reaction assay for the measurement of HBV DNA. The sera of 37 patients (16 who developed reactivation and 21 who did not) were available for measurement of HBV DNA using this technique. The results showed that patients in the reactivation group had a significantly higher median HBV DNA load (1.03 x 10(6) copies/mL; range

The diagnosis of HBV reactivation during cytotoxic chemotherapy is based on an abrupt rise in levels of serum HBV DNA in conjunction with a hepatitic picture and in the absence of other causes of hepatitis. However, several cases of “hepatitis” have been noted during chemotherapy in HBsAg-positive patients, for which no cause could be found and in which HBV DNA levels were negative. One possible explanation is that HBV reactivation may, indeed, have been the cause but that HBV DNA levels became negative by the time ALT levels peaked and the clinical diagnosis of hepatitis was made. During the course of a longitudinal study of HBsAg-seropositive cancer patients who were monitored during standard chemotherapy, the opportunity was available to test this hypothesis. J. Med. Virol. 65:473–477, 2001. © 2001 Wiley-Liss, Inc.

Reactivation of the hepatitis B virus (HBV) is a well-described complication among cancer patients undergoing cytotoxic chemotherapy. Mutations in the preC/C and the preC promoter regions of HBV have been reported in some patients who developed this condition. A G-to-A mutation at nt 1896 in the preC/C region (HBeAg negative/ anti-HBe positive) has been associated with more severe liver disease than that caused by wild type virus. In addition, it has been suggested that patients with these mutations may be more likely to reactivate than those with the wild type virus. Whether or not such mutations were present before the commencement of or developed during the course of cytotoxic chemotherapy is not known. In this study, 28 cancer patients (consisting of 14 consecutive patients who developed HBV reactivation and another 14 who had no reactivation during cytotoxic chemotherapy) are reported. The objectives were firstly, to determine the prechemotherapy HBeAg status and nucleotide sequences of the preC/C and preC promoter regions of HBV in order to determine if these parameters affected the rate of reactivation, and secondly, for those who developed reactivation, to determine whether the mutations were present before chemotherapy or developed during, possibly as a result of, cytotoxic chemotherapy. HBV DNA was amplified by PCR and nucleotide sequencing performed on samples taken prior to chemotherapy and at the time of reactivation. Results revealed that 16 of the 28 patients were HBeAg negative/anti-HBe positive. Of these 16, four (57%) of the seven patients who had nt 1896 mutation, but only one (17%) of the six who had the wild type HBV genome, developed reactivation. Three had no detectable HBV DNA. In the majority of cases, the type of virus, i.e. wild/mutant at preC/C, that was detected during the reactivation was identical to that detected in the pretreatment samples. With respect to the preC promoter region, the two commonest mutations detected were at nt 1762 (A to T) and nt 1764 (G to A). When this region was translated into amino acid sequences, stop codons leading to truncated X protein at carboxyl terminus were found in four patients, three of whom developed HBV reactivation. We conclude that chronic HBV carriers who are HBeAg negative/anti-HBe positive with nt 1896 mutation (G to A) may be more likely to develop HBV reactivation during cytotoxic chemotherapy than those with the wild type virus. Cytotoxic chemotherapy does not appear to select out mutant HBV, or to be consistently mutagenic in patients who develop HBV reactivation. The occurrence of stop codons in the amino acid sequences of the X protein in three patients who developed HBV reactivation, including one who was detected only at the time of reactivation, is of particular interest, as such mutant viruses remain replication competent.

BACKGROUND The authors have designed a non-cisplatin-based chemotherapy regimen for the treatment of patients with advanced nonsmall cell lung carcinoma (NSCLC). This regimen capitalizes on the mild toxicity of gemcitabine, a novel nucleoside analog. METHODS A total of 46 chemotherapy-naive patients with histologically confirmed Stage IIIB or IV NSCLC were enrolled. Eligible patients were treated with gemcitabine 1000 mg/m2 on Days 1, 8, and 15, plus oral etoposide 50 mg daily for 14 days, which was increased to 21 days if there was no World Health Organization (WHO) Grade 3 or 4 toxicity in the 1st 2 cycles (each cycle was 28 days long). All patients were included for analysis of response and survival according to an intention-to-treat principle. RESULTS The overall response rate was 43.5% (95% confidence interval [CI], 30.7–60.2%). There was 1 complete response (2.2%) and 19 partial responses (41.3%). The median survival was 48.0 weeks (95% CI, 38.1–75.9 weeks) and the 1-year survival rate was 45% (95% CI, 29–62%). The median time to progression for all patients was 39.2 weeks (95% CI, 35.7–49.7 weeks). World Health Organization (WHO) Grade 3 and 4 anemia, neutropenia, and thrombocytopenia was reported in 29%, 32%, and 18% of patients, respectively. Two patients had reactivation of hepatitis B viral infection that resulted in WHO Grade 4 hepatic dysfunction. Other nonhematologic toxicities were uncommon. CONCLUSIONS This non-cisplatin-based regimen of gemcitabine and oral etoposide achieved a high response and survival rate. Toxicity appeared to be less severe than that associated with existing cisplatin-based regimens. A randomized study of this regimen versus a cisplatin-based regimen is indicated. Cancer 2000;89:543–50. © 2000 American Cancer Society.

Hepatitis B virus (HBV) reactivation is a well-described complication in cancer patients who receive cytotoxic chemotherapy and may result in varying degrees of liver damage. As chemotherapy is used increasingly in cancer patients, HBV reactivation during cytotoxic treatment may become a more common problem. In lymphoma patients, the incidence of chronic HBV infection has been reported to be 26%, of whom 47% developed HBV reactivation during chemotherapy. However, corresponding data for patients with other malignancies undergoing cytotoxic chemotherapy are not known. In this prospective study, hepatitis B surface antigen (HBsAg) was determined in 626 consecutive cancer patients who received cytotoxic chemotherapy over a 12-month period. Seventy-eight patients (12%) were found to be HBsAg positive. Thirty-four (44%) developed raised alanine transaminase during their course of chemotherapy. In these 34 patients, hepatitis was attributed to HBV reactivation in 15 patients (44%), chronic active HBV infection in 1 patient (3%), hepatitis C infection in 1 patient (3%), malignant hepatic infiltration in 2 patients (6%), and the use of hepatotoxic chemotherapeutic agents in 11 patients (32%). The causes of hepatitis were unknown in 4 patients (12%). HBV reactivation was more likely to develop in patients who were male, younger age, HBeAg seropositive, and those with lymphoma. Presence of malignant hepatic infiltration, baseline pre-treatment alanine transaminase, total bilirubin, and HBV DNA levels did not correlate with the development of HBV reactivation. Of the 15 patients who developed HBV reactivation, antiviral therapy with lamivudine was available and used in 9. There was no HBV-related mortality during chemotherapy. It is concluded that in patients with chronic HBV infection under chemotherapy, HBV reactivation occurs in nearly 20% of them and accounts for 44% of hepatitis cases. The risk factors identified include male sex, younger age, HBeAg seropositive, and the diagnosis of lymphoma. In HBV endemic areas, patients with risk factors for HBV reactivation should be identified prior to receiving cytotoxic treatment and monitored closely. The potential benefit of lamivudine requires further confirmation.

Symptomatic metastases in skeletal muscles are rare, and involvement of the masseter muscle is extremely rare, with only 3 reported cases. We report 2 additional cases of masseter-muscle metastases. Sonographically, the masseter-muscle metastases appeared as ill-defined, hypoechoic, heterogeneous lesions aligned with the long axis of the muscle. Fine-needle aspiration was confirmatory. The combination of sonography and fine-needle aspiration is the ideal method for diagnosing masseteric metastases.

Hepatitis B virus (HBV) reactivation has been described in cancer patients who received cytotoxic/immunosuppressive therapy and may result in liver damage of varying degrees of severity. There is no known effective treatment. Lamivudine, a nucleoside analogue, has been found to suppress HBV replication and to improve histology in chronic carriers of hepatitis B virus. The outcome of lamivudine therapy (at doses of 100 or 150 mg/day) in eight patients who developed HBV reactivation while receiving cytotoxic chemotherapy is described. Each of the eight patients had >98% suppression of the pretreatment HBV DNA levels. Three of the five patients who were initially HBeAg positive underwent seroconversion. Five patients had normalization of liver function tests and improvement in clinical condition. However, one patient died of hepatic failure due to HBV-related submassive liver necrosis, and two died of widespread metastases (including liver) from the primary malignancies. It is concluded that early commencement, i.e., at the onset of HBV reactivation before severe hepatic decompensation, of lamivudine may be effective in the control of HBV reactivation during chemotherapy. In Hong Kong, where hepatitis B infection is endemic, we propose to screen all cancer patients for hepatitis B surface antigen before immunosuppressive/cytotoxic therapy, and to closely monitor liver function of those who are found to be HBsAg seropositive. J. Med. Virol. 59:263–269, 1999. © 1999 Wiley-Liss, Inc.

BACKGROUND Chemotherapy containing anthracycline is the standard initial treatment for aggressive non-Hodgkin's lymphoma (NHL), and the International Prognostic Index (IPI) is widely accepted as the standard tool for determining the prognosis of patients with this disease. However, the data on which the IPI was based primarily came from studies conducted in Western countries. It may not be directly applicable to Asian populations, in which the incidence of primary extranodal lymphoma (PENL) is known to be high. METHODS The authors conducted a retrospective study of 218 patients with aggressive NHL who were treated with chemotherapy. They analyzed the distribution of stage and pathology, prognostic factors, toxicity, and treatment outcome. The IPI was then applied and its ability to identify distinct prognostic groups tested. RESULTS Eighty-six patients (39.4%) had lymph node lymphoma (LNL) and 132 (60.6%) had primary extranodal lymphoma (defined as non-Hodgkin's lymphoma with primary presentation, bulk of disease, and histologic confirmation at an extranodal site). The most common primary extranodal sites were the stomach (22%) and Waldeyer's tonsillar ring (18.9%). The complete response rate of PENL patients to chemotherapy containing anthracycline was 52%, as compared with 64% of the LNL group. The 5-year survival rates for patients with LNL and PENL were 57.4% and 52.1%, respectively. The toxicity in the two patient groups was similar. Four of the prognostic factors in the IPI–age, serum LDH, performance status, and disease stage–predicted significantly different survival for PENL and LNL patients. However, the number of extranodal sites involved was not a significant predictive variable in PENL. CONCLUSIONS The IPI was applicable to this Chinese population in which the incidence of PENL was high, although the number of extranodal sites did not achieve statistical significance as a risk factor. A proposal for modification was made. Chemotherapy containing anthracycline was an effective treatment for both PENL and LNL patients. Cancer 1998;82:2439-2448. © 1998 American Cancer Society.

Background Primary nasal lymphoma is a rare disease. Although most patients are initially seen in early Ann Arbor stages, their prognosis is poor. The prognostic significance of local tumor bulk has not been well studied. Methods Twenty-one patients with nasal lymphoma treated between 1985 and 1992 were retrospectively studied. Sixteen patients (76%) below the age of 75 years received combined radiotherapy and chemotherapy. One young patient with early disease and 4 elderly patients had radiotherapy alone. Twelve cases (57%) were diagnosed as pleomorphic T-cell lymphoma based on typical histologic features alone. Immunophenotyping was performed in 10 cases; 8 were T cell and 2 were B cell. Seventeen patients (81%) had Ann Arbor clinical stage IE disease, and 4 had stage IIE disease. The local tumor extent was assessed by endoscopy in all patients and by computerized tomography (CT) in 14 patients. Eleven local tumors (52%) extended to the posterior ethmoids, sphenoid sinus, orbit, or beyond. Using a T-stage system, the prognostic significance of local tumor bulk was evaluated for stage IE patients. Results At a median follow-up time of 16.8 months, the lymphoma recurred in 13 patients; 10 patients had systemic relapse and 10 patients, local relapse. The 5-year actuarial overall survival rate was 24%. Complete response to chemotherapy was achieved in 5 of 16 patients (31%). Four of the 6 patients who remained alive and disease-free were chemotherapy complete responders. Among stage IE patients, those with early and those with advanced local disease did not have significantly different survival. Conclusions In view of the high systemic and local relapse rates, more-effective chemotherapy is needed to improve the survival rates, and the role of combined chemotherapy and radiotherapy should be evaluated. Further studies are required to identify patients at high risk of relapse for clinical trials with investigational treatment. © 1997 John Wiley & Sons, Inc. Head Neck19: 251–259, 1997.

A patient with angiomyelolipoma of the liver, together with radiological evidence of pancreatic, renal and bony lesions characteristic of tuberous sclerosis, is described. Although the patient had no other clinical features of tuberous sclerosis, her daughter was found to suffer from the classical triad of this syndrome and also has had hepatic lipomatous lesions and bony involvement. This is the first histologically proven case of hepatic angiomyelolipoma associated with tuberous sclerosis.