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Winnie Yeo,1 Nicole TY Ngai,1 Christopher CH Yip,1 Frankie KF Mo,1 Victoria A Yeo,1 Jonathan WH Ko,1 Leung V Li,1 Thomas KH Lau,1 Kwai Tung Lai,1 Elizabeth Pang,1 Claudia HW Yip,1 Horatio L Yeo,1 Carol Chi Hei Kwok,2 Stephanie WY Ko,1 Alex Molassiotis3 1Department of Clinical Oncology, Prince of Wales Hospital, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, People’s Republic of China; 2Department of Clinical Oncology, Princess Margaret Hospital, Kowloon, Hong Kong, People’s Republic of China; 3School of Nursing, The Hong Kong Polytechnic University, Hong KongCorrespondence: Winnie Yeo, Department of Clinical Oncology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, People’s Republic of China, Email winnieyeo@cuhk.edu.hkPurpose: Although risk factors related to chemotherapy-induced nausea and vomiting (CINV) have been identified in previous studies, only a few studies have evaluated the risk factors associated with contemporary antiemetic prophylaxis, including olanzapine/aprepitant- or NEPA-containing regimens. This study aimed to identify the risk factors associated with CINV development in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide chemotherapy.Methods: Data from 304 patients enrolled in 3 previously reported prospective antiemetic studies were included. Multivariate logistic regression models were used to predict risk factors associated with CINV occurrence. Additionally, the likelihood of treatment failure in relation to the number of risk factors in individual patients was evaluated.Results: Multivariate analysis of the entire study group revealed that obesity status (defined as body mass index/= 25.0 kg/m2) and the use of olanzapine/aprepitant- or NEPA-containing anti-emetic regimens were associated with a high likelihood, while a history of motion sickness was associated with a lower likelihood, complete response (CR), and “no nausea” in the overall phase. A history of vomiting during pregnancy was also associated with a lower likelihood of an overall CR. Patients with an increasing number of risk factors had a higher likelihood of treatment failure and shorter time to first vomiting. Those who did not achieve CR and “no nausea” in the first cycle were less likely to achieve these parameters in the subsequent cycle of chemotherapy.Conclusion: The present study confirmed previously reported risk factors for CINV in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide. Further optimization of CINV control is required for patients with identifiable risk factors; olanzapine/aprepitant- or NEPA- containing prophylaxis are the preferred contemporary anti-emetics regimens for Chinese breast cancer patients undergoing doxorubicin and cyclophosphamide chemotherapy.Keywords: cytotoxic, nausea and vomiting, olanzapine, aprepitant, NEPA

Objective: To investigate the role of diffusion-weighted imaging (DWI) in predicting and monitoring chemoradiotherapy response in head and neck squamous cell carcinoma (HNSCC).Methods: Diffusion-weighted imaging was performed pre-treatment (n = 50), intra-treatment (n = 41) and post-treatment (n = 20). Apparent diffusion coefficient (ADC) values were correlated with locoregional failure (LF).Results: Locoregional failure occurred in 20/50 (40%) patients. A significant correlation was found between LF and post-treatment ADC (p = 0.02) but not pre- or intra-treatment ADC. Serial change in ADC was even more significant (p = 0.00001), using a fall in ADC early (pre- to intra-treatment) or late (intra- to post-treatment) to indicate LF, achieved 100% specificity, 80% sensitivity and 90% accuracy.Conclusions: Single ADC measurements pre- or intra-treatment did not predict response, but ADC post-treatment was a marker for LF. Serial change in ADC was an even stronger marker, when using an early or late treatment fall in ADC to identify LF. [ABSTRACT FROM AUTHOR]

Elevated choline (Cho) level has been documented on proton magnetic resonance spectroscopy ((1)H MRS) in head and neck squamous cell carcinoma and therefore percentage changes in Cho levels after chemoradiotherapy may serve as a marker of residual cancer in a post-treatment mass (PTM). Forty-six patients underwent (1)H MRS before treatment and the 30 patients with a PTM underwent repeat (1)H MRS at 6 weeks post-treatment. The percentage change in Cho/creatine and Cho/water ratios were correlated with residual cancer. The mean pretreatment Cho/creatine and Cho/water ratios were 2.24 and 1.20 x 10(-3), respectively. Cho persisted in four out of nine PTMs with residual cancer. Cho was absent in five out of nine PTMs with residual cancer and 21/21 PTMs without cancer. The number of PTMs with persistent Cho was too small to allow analysis of percentage change in ratios but the presence of Cho in a PTM showed significant correlation with residual cancer (p = 0.0046), producing a sensitivity, specificity, positive predictive value and negative predictive value of 44%, 100%, 100% and 81%, respectively. Therefore, the presence of Cho in a PTM may serve as a marker of residual cancer. Furthermore since so few PTMs contain Cho, a percentage change in Cho ratios may not be a useful method for monitoring treatment response. [ABSTRACT FROM AUTHOR]

Winnie Yeo,1,2 Frankie KF Mo,1,2 Elizabeth Pang,1,2 Joyce JS Suen,1 Jane Koh,1,2 Claudia HW Yip,1 Christopher CH Yip,1 Leung Li,1 Herbert HF Loong,1,2 Giok S Liem1 1Department of Clinical Oncology, Sir YK Pao Centre for Cancer, Prince of Wales Hospital, 2Hong Kong Cancer Institute, State Key Laboratory of Oncology in South China, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong Introduction: Understanding of quality of life (QoL) of young Chinese breast cancer patients after adjuvant cytotoxic chemotherapy is limited. This study aims to assess the QoL of premenopausal Chinese breast cancer women after receiving adjuvant chemotherapy.Patients and methods: Eligibility criteria included stage I–III breast cancer, premenopausal and age ≤45 years at cancer diagnosis and having received adjuvant chemotherapy within 3–10 years before entry to the present study. Patients’ background demographics at the time of breast cancer diagnosis, together with tumor characteristics and anticancer treatments, were collected. At the time of study entry, the menopausal status based on menstrual history, body mass index, and QoL (assessed using Functional Assessment of Cancer Therapy-Breast +4) were recorded.Results: Two hundred and eighty patients were recruited. Ninety-five patients (33.9%) underwent breast-conserving surgery, and nearly all (98.6%) underwent axillary dissection. For adjuvant therapies, 249 patients (88.9%) received anthracycline-containing chemotherapy and 79 (28.2%) received taxane-containing chemotherapy, while 68 (24.3%) received both. One hundred and eighty six patients (66.4%) received adjuvant radiotherapy, and 214 (76.4%) received adjuvant tamoxifen. The median time from breast cancer diagnosis to study entry was 5.01 years. QoL assessment at study entry revealed that older patients had worse social well-being (SWB; mean scores for age ≤40, 41–45, 46–50 and >50 years were 22.0, 19.3, 19.1 and 18.1, respectively, P=0.0442). Patients who underwent axillary dissection had worse scores for breast cancer subscale (BCS; mean score 22.2 vs. 28.3, P=0.0212). Patients who underwent taxane-containing chemotherapy had worse scores for arm subscale (mean score 13.8 vs. 15.3, P=0.0053).Conclusion: At a median follow-up of 5 years post-diagnosis, patients who were younger had fewer disturbances in their SWB. Patients who had axillary dissection had worse BCS scores, while those who received taxane had worse scores for arm subscale. Further studies are warranted for breast-specific QoL to address the specific issues encountered by breast cancer patients. Keywords: cytotoxic, QoL, FACT-B+4, cancer survivors breast, premenopausal

Parapharyngeal tumor invasion is a known predictor of distant recurrence in stage II-III nasopharyngeal carcinoma (NPC). This study evaluated the prognostic significance of parapharyngeal and cavernous sinus vascular invasion in stage III-IV NPC, and its association with plasma Epstein-Barr virus (pEBV) DNA, disease stage, tumor volume and metabolic activity. Eligible patients underwent magnetic resonance imaging (MRI), 18F-fluorodeoxyglucose (FDG)-positron-emission tomography (PET) and blood sampling for pEBV DNA before undergoing concurrent chemoradiotherapy. Relationship between treatment outcome and tumor vascular invasion was analyzed using Cox regression. Logistic regression was used to analyze the association between vascular invasion and other cofactors. Fifty seven patients with predominantly T3-T4 or N2-N3 stage disease were enrolled. Parapharyngeal invasion was present in 56% and cavernous sinus invasion in 19% of tumors. Multivariate analysis showed that tumor vascular invasion did not predict treatment outcome, while tumor FDG-uptake was the only significant factor that predicted survival and recurrence. Tumor vascular invasion was associated with T-stage, but not pEBV DNA or tumor volume. Parapharyngeal and cavernous sinus invasion were not significant predictors of distant recurrence following chemoradiotherapy in our cohort with locoregionally advanced NPC. [ABSTRACT FROM AUTHOR]

Objectives: This is a prospective study evaluating NEPA in patients with breast cancer (the NEPA group), who received (neo)adjuvant AC chemotherapy (consisting of doxorubicin 60 mg/m 2 and cyclophosphamide 600 mg/m 2 ). The primary objectives were to assess the efficacy and safety of NEPA in controlling chemotherapy-induced nausea and vomiting (CINV). The secondary objectives were to compare CINV between the NEPA group and historical controls (the APR group) who received aprepitant in an earlier prospective randomised study., Patients and Methods: 60 patients participated in the NEPA group; 62 were in the APR group. Eligibility criteria of both groups were similar, that is, Chinese patients with breast cancer who were treated with (neo)adjuvant AC. NEPA group received NEPA and dexamethasone; APR group received aprepitant, ondansetron and dexamethasone. Individuals filled in self-reported diary, visual analogue scale for nausea and Functional Living Index-Emesis questionnaire., Results: Within the NEPA group, 70.0%, 85.7% and 60.0%, respectively reported complete response in the acute, delayed and overall phases in cycle 1 AC. When compared with the historical APR group during cycle 1 AC, NEPA group achieved significantly higher rates of complete response, complete protection, total control, 'no significant nausea' and 'no nausea' in the delayed phase; similar findings were noted in the overall phase with significantly better quality of life. Superior efficacy of NEPA was maintained over multiple cycles. Both antiemetic regimens were well tolerated., Conclusion: In this study on Chinese patients with breast cancer who were uniformly receiving AC, NEPA was effective in controlling CINV., Trial Registration Number: NCT03386617., Competing Interests: Competing interests: WY has been involved in CINV Network in Asia and has been a speaker on CINV, organised by Mundipharma., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Chemotherapy-induced nausea and vomiting (CINV) are common with doxorubicin-cyclophosphamide (AC) chemotherapy. Recommended antiemetic regimens incorporate neurokinin-1 receptor antagonist (NK1RA), 5-hydroxytryptamine type-3 receptor antagonist (5HT3RA), corticosteroid, and dopamine antagonists. This post-hoc analysis compared results of 3 prospective antiemetic studies conducted among Chinese breast cancer patients who received (neo)adjuvant AC, in order to identify optimal antiemetic prophylaxis., Methods: A total of 304 patients were included: Group 1, ondansetron/dexamethasone (D1); Group 2, aprepitant/ondansetron/dexamethasone (D1); Group 3, aprepitant/ondansetron/dexamethasone (D1-3); Group 4, aprepitant/ondansetron/dexamethasone (D1-3)/olanzapine; and Group 5, netupitant/palonosetron/dexamethasone (D1-3). Antiemetic efficacies of Groups 3, 4, and 5 during cycle 1 of AC were individually compared with Group 1. In addition, emesis outcomes of patients in Groups 3 and 5, and those of Groups 2 and 3, were compared., Results: When comparing efficacies of a historical doublet (5HT3RA/dexamethasone) with triplet antiemetic regimens (NK1RA/5HT3RA/dexamethasone) with/without olanzapine, complete response (CR) percentages and quality of life (QOL) in overall phase of cycle 1 AC were compared between Group 1 and the other groups: Group 1 vs. 3, 41.9% vs. 38.3% ( P = 0.6849); Group 1 vs. 4, 41.9% vs. 65.0% ( P = 0.0107); and Group 1 vs. 5, 41.9% vs. 60.0% ( P = 0.0460). Groups 4 and 5 achieved a better QOL. When comparing netupitant-based (Group 3) with aprepitant-based (Group 5) triplet antiemetics, CR percentages were 38.3% vs. 60.0%, respectively ( P = 0.0176); Group 5 achieved a better QOL. When comparing 1 day (Group 2) vs. 3 day (Group 3) dexamethasone, CR percentages were 46.8% and 38.3%, respectively ( P = 0.3459); Group 3 had a worse QOL., Conclusions: Aprepitant-containing triplets were non-superior to doublet antiemetics. Netupitant-containing triplets and adding olanzapine to aprepitant-containing triplets were superior to doublets. Netupitant/palonosetron/dexamethasone was superior to aprepitant/ondansetron/dexamethasone. Protracted administration of dexamethasone provided limited additional benefit., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2021 Cancer Biology & Medicine.)

Objectives: Chemotherapy-induced nausea and vomiting (CINV) are distressing symptoms. This randomized study evaluated the antiemetic efficacies of standard antiemetic regimen with/without olanzapine., Patients and Methods: Eligible patients were chemotherapy-naive Chinese breast cancer patients who were planned for (neo)adjuvant doxorubicin/cyclophosphamide. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomized to Olanzapine (with olanzapine) or Standard arms (without olanzapine). Patients filled in self-reported diaries and completed visual analogue scales for nausea, as well as Functional Living Index-Emesis questionnaires. Blood profiles including fasting glucose and lipids were monitored., Results: 120 patients were randomized. In Cycle 1 doxorubicin/cyclophosphamide, the Olanzapine arm had significantly higher rates of "Complete Response" than the Standard arm: 65.0% vs 38.3% in the overall period (p = 0.0035), 70.0% vs 51.7% in the acute period (p = 0.0397) and 92.9% vs 74.2% in the delayed period (p = 0.0254). Olanzapine arm also had significantly higher rates of "No significant nausea" and "No nausea" during all 3 time-frames and better QOL. Similar findings were also revealed throughout multiple cycles. Pre-study abnormalities in glucose and lipids occurred in 39.7% and 34.2% of the studied population respectively; there were no differences in these parameters between the two arms at end-of-study assessment., Conclusion: The addition of olanzapine to standard aprepitant-based antiemetic regimen provides clinically meaningful improvement in controlling CINV. This was associated with a positive impact on QOL and tolerable toxicity profiles among Chinese breast cancer patients receiving doxorubicin/cyclophosphamide chemotherapy. Further studies on metabolic profiles of breast cancer patients are warranted., Competing Interests: Declaration of competing interest WY reports consultancy/advisory roles and receipt of personal fees for Novartis, Pfizer, AstraZeneca, Eli Lilly, Roche, Mundipharma and Amgen., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose To evaluate the utility of amide proton transfer (APT) imaging in the characterization of head and neck tumors. Materials and Methods This retrospective study of APT imaging included 117 patients with 70 nasopharyngeal undifferentiated carcinomas (NUCs), 26 squamous cell carcinomas (SCCs), eight non-Hodgkin lymphomas (NHLs), and 13 benign salivary gland tumors (BSGTs). Normal tissues were examined in 25 patients. The APT means of malignant tumors, normal tissues, and benign tumors were calculated and compared with the Student t test and analysis of variance. The added value of the mean APT to the mean apparent diffusion coefficient (ADC) for differentiating malignant and benign tumors was evaluated by using receiver operating characteristic analysis and integrated discrimination index. Results The mean APT of malignant tumors (2.40% ± 0.97 [standard deviation]) was significantly higher than that of brain tissue (1.13% ± 0.43), muscle tissue (0.23% ± 0.73), and benign tumors (1.32% ± 1.20) (P < .001). There were no differences between malignant groups (NUC, 2.37% ± 0.90; SCC, 2.41% ± 1.16; NHL, 2.65% ± 0.89; P = .45 to P = .86). The mean ADC of malignant tumors ([0.85 ± 0.17] × 10 -3 mm 2 /sec) was significantly lower than that of benign tumors ([1.46 ± 0.47] × 10 -3 mm 2 /sec) (P = .001). Adding APT to ADC increased the area under the curve from 0.87 to 0.96, with an integrated discrimination index of 7.6% (P = .13). Conclusion These preliminary data demonstrate differences in amide proton transfer (APT) mean of malignant tumors, normal tissues, and benign tumors, although APT mean could not be used to differentiate between malignant tumor groups. APT imaging has the potential to be of added value to apparent diffusion coefficient in differentiating malignant from benign tumors., (© RSNA, 2018 Online supplemental material is available for this article.)

Introduction: The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has changed dramatically with the introduction and widespread use of HER2-targeted therapies. There is, however, relatively limited real-world information about the effectiveness and safety of trastuzumab emtansine (T-DM1) in Hong Kong Chinese patients. We assessed the efficacy and toxicity profiles among local patients with HER2-positive advanced breast cancer who had received T-DM1 therapy in the second-line setting and beyond., Methods: This retrospective study involved five local centres that provide service for over 80% of the breast cancer population in Hong Kong. The study period was from December 2013 to December 2015. Patients were included if they had recurrent or metastatic histologically confirmed HER2+ breast cancer who had progressed after at least one line of anti-HER2 therapy including trastuzumab. Patients were excluded if they received T-DM1 as first-line treatment for recurrent or metastatic HER2+ breast cancer. Patient charts including biochemical and haematological profiles were reviewed for background information, T-DM1 response, and toxicity data. Adverse events were documented during chemotherapy and 28 days after the last dose of medication., Results: Among 37 patients being included in this study, 28 (75.7%) had two or more lines of anti-HER2 agents and 26 (70.3%) had received two or more lines of palliative chemotherapy. Response assessment revealed that three (8.1%) patients had a complete response, eight (21.6%) a partial response, 11 (29.7%) a stable disease, and 12 (32.4%) a progressive disease; three patients could not be assessed. The median duration of response was 17.3 (95% confidence interval, 8.4-24.8) months. The clinical benefit rate (complete response + partial response + stable disease, ≥12 weeks) was 37.8% (95% confidence interval, 22.2%-53.5%). The median progression-free survival was 6.0 (95% confidence interval, 3.3- 9.8) months and the median overall survival had not been reached by the data cut-off date. Grade 3 or 4 toxicities included thrombocytopaenia (13.5%), raised alanine transaminase (8.1%), anaemia (5.4%), and hypokalaemia (2.7%). No patient died as a result of toxicities., Conclusions: In patients with HER2-positive advanced breast cancer who have been heavily pretreated with anti-HER2 agents and cytotoxic chemotherapy, T-DM1 is well tolerated and provided a meaningful progression-free survival of 6 months and an overall survival that has not been reached. Further studies to identify appropriate patient subgroups are warranted.

Our study aimed to identify diffusion-weighted imaging (DWI) parameters obtained from primary nasopharyngeal carcinoma (NPC) at initial presentation, that can predict patients at risk of distant metastases. One hundred and sixty-four patients underwent pretreatment magnetic resonance imaging and DWI. The apparent diffusion coefficient (ADC) mean , ADC skewness , and ADC kurtosis were obtained by histogram analysis. Univariate and multivariate analyses of these ADC parameters together with primary volume (PV), nodal volume (NV), T stage, N stage and presence of locoregional relapse (LRR) were compared between patients with distant metastases (DM+) and patients without distant metastases (DM-) at 5 years using logistic regression. Twenty-eight out of 164 patients (17.1 %) were DM+ (2.5-60 months) and 136/164 patients were DM- (61.2-119.4 months). Compared to DM- patients, the primary tumour of DM+ patients showed significantly lower ADC skewness (ADC values with the greatest frequency were higher) (p = 0.041), and higher PV (p = 0.022), NV (p < 0.01), T stage (p = 0.023), N stage (p < 0.01) and LRR (p < 0.01). On multivariate analysis the ADC skewness was no longer significant (p = 0.120) and only NV and LRR were independent predictors for DM+ (p = 0.023 and 0.021, respectively). DWI showed that compared to DM- patients, DM+ patients had a significantly lower primary tumour ADC skewness , but at initial presentation NV was the only independent predictor of DM.

Introduction: The use of adjuvant chemotherapy with S-1 (tegafur, gimeracil, and oteracil potassium) has been shown to improve the outcome of patients with gastric cancer. There are limited data on the tolerability of S-1 in Chinese patients. In this multicentre retrospective study, we assessed the toxicity profile in local patients., Methods: Patients with stage II-IIIC gastric adenocarcinoma who had undergone curative resection and who had received S-1 adjuvant chemotherapy were included in the study. Patient demographics, tumour characteristics, chemotherapy records, as well as biochemical, haematological, and other toxicity profiles were extracted from medical charts. Potential factors associated with grade 2-4 toxicities were identified., Results: Adjuvant S-1 was administered to 30 patients. Overall, 19 (63%) patients completed eight cycles. The most common grade 3-4 adverse events included neutropaenia (10%), anaemia (6.7%), septic episode (16.7%), diarrhoea (6.7%), hyperbilirubinaemia (6.7%), and syncope (6.7%). Dose reductions were made in 22 (73.3%) patients and 12 (40.0%) patients had dose delays. Univariate analyses showed that patients who underwent total gastrectomy were more likely to experience adverse haematological events (P=0.034). Patients with nodal involvement were more likely to report adverse non-haematological events (P=0.031). Patients with a history of regular alcohol intake were more likely to have earlier treatment withdrawal (P=0.044). Lower body weight (P=0.007) and lower body surface area (P=0.017) were associated with dose interruptions., Conclusions: The tolerability of adjuvant S-1 in our patient population was similar to that in other Asian patient populations. The awareness of S-1-related toxicities and increasing knowledge of potential associated factors may enable optimisation of S-1 therapy.

To document the magnetic resonance imaging (MRI) features of diffuse large B-cell lymphoma (DLBCL) in Waldeyer's ring (WR) and the sinonasal (SN) region, and to identify any differences between lymphatic and extra-lymphatic DLBCLs, and predictors of disease beyond the neck. Primary, nodal, and multifocal sites on head and neck MRI were compared between 31 WR and 15 SN DLBCL, and between 27 patients with disease confined to the head and neck and 16 patients with disease beyond the neck, using logistic regression. Compared to SN, WR DLBCLs had significantly smaller primary tumour volumes (p = 0.009), less deep invasion (p = 0.001), and more nodal disease (p = 0.016). Tumour site (WR vs. SN) was an independent predictor of deep invasion (p = 0.007). Nodal and multifocal diseases were predictors of disease beyond the neck (p = 0.027 and 0.011, respectively). Lymphatic WR DLBCLs were less locally aggressive but had greater propensity to nodal spread than extra-lymphatic SN DLBCLs. Nodal and multifocal diseases predicted disease beyond the neck.

Background: Health-related quality-of-life (HRQOL) assessment with EORTC QLQ-C30 was prognostic for overall survival (OS) in patients with advance-stage hepatocellular carcinoma (HCC), but no data existed for early-stage patients. The HCC-specific QLQ-HCC18 has not been evaluated for prognostic value in HCC patients. Utilization of raw HRQOL data in clinical setting has been impractical and non-meaningful. Therefore we developed index scores of QLQ-C30 and QLQ-HCC18 in an attempt to enable clinical utilization of these HRQOL measurements. This study investigates the prognostic significance of QLQ-C30, QLQ-HCC18 and C30/HCC18 index-scores in patients with newly diagnosed HCC which encompasses all stages., Methods: From 2007-2011, 517 patients were prospectively recruited. HRQOL was assessed at diagnosis using QLQ-C30 and QLQ-HCC18; C30 and HCC18 index-scores were calculated from raw HRQOL data. Cox regression was performed using continuous, dichotomized QLQ-C30 and QLQ-HCC18 variables, or index-scores, together with clinical factors to identify independent factors for OS. Various multivariate models were validated with c-index and bootstrapping for 1000 replications., Results: Four hundred and seventy two patients had complete HRQOL data. Their median OS was 8.6 months. In multivariate analysis, independent prognostic HRQOL variables for OS were QLQ-C30 pain (HR 1.346 [1.092-1.661], p = 0.0055), QLQ-C30 physical functioning (HR 0.652 [0.495-0.860], p = 0.0024); QLQ-HCC18 pain (HR 1.382 [1.089-1.754], p = 0.0077) and QLQ-HCC18 fatigue (HR 1.441 [1.132-1.833], p = 0.0030). C30 index-score (HR 2.143 [1.616-2.841], p < 0.0001) and HCC18 index-score (HR 1.957 [1.411-2.715], p < 0.0001) were highly significant factors for OS. The median OS of patients with C30 index-score of 0-20, 21-40, 41-60, 61-100 were 16.4, 7.3, 3.1, 1.8 months respectively (p < 0.0001); while for HCC18 index-score: 16.4, 6.0, 2.8, 1.8 months respectively (p < 0.0001). All the multivariate models were validated, with mean optimism <0.01. The bootstrap validated c-index was 0.78., Conclusions: QLQ-C30 and QLQ-HCC18 were prognostic for OS in patients with newly diagnosed HCC irrespective of stage. Both C30 and HCC18 index-scores were highly significant prognostic factors for OS in newly diagnosed HCC patients. Index-scoring provides an effective way to summarize, analyze and interpret raw HRQOL data, and renders QLQ-C30 and QLQ-HCC18 meaningful and communicable in clinical practice. Index-scores could potentially serve as a standardized tool for future HRQOL research.

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., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objectives: To review the clinical outcome of locally advanced rectal cancer treated with neoadjuvant chemoradiation followed by definitive surgery with or without adjuvant chemotherapy and to elucidate the prognostic factors for treatment outcome., Methods: This historical cohort study was conducted at a tertiary public hospital in Hong Kong. All patients who had undergone neoadjuvant chemoradiation for locally advanced rectal cancer in our department from November 2005 to October 2014 were recruited. Local recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival of patients were documented., Results: A total of 135 patients who had received neoadjuvant chemoradiation during the study period were reviewed. There were 130 patients who had completed neoadjuvant chemoradiation and surgery. The median follow-up time was 35.1 months. The 3- and 5-year local recurrence-free survival, distant metastasis-free survival, disease-free survival, as well as overall survival rates were 91.8% and 86.7%, 73.9% and 72.1%, 70.1% and 64.6%, as well as 86.5% and 68.4%, respectively. The rate of pathological complete response was 13.8%. The T and N downstaging rate was 49.2% and 63.1%, respectively. The rate of conversion from threatened circumferential resection margin to clearance of margin was 90.6%. Of the 42 cases that were initially deemed to require abdominal perineal resection, 15 (35.7%) were converted to sphincter-sparing surgery., Conclusions: The treatment outcome of neoadjuvant chemoradiation for locally advanced rectal cancer was comparable with overseas data in terms of local control rate and overall survival. This strategy may increase the chance of achieving a clear surgical margin by downstaging the tumour, especially in patients who presented with threatened circumferential margin.

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., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Purpose: Pretreatment prediction of patients with nasopharyngeal carcinoma who will fail conventional treatment would potentially allow these patients to undergo more intensive treatment or closer posttreatment monitoring. The aim of the study was to determine the ability of pretreatment DWI to predict local failure in patients with nasopharyngeal carcinoma based on long-term clinical outcome., Materials and Methods: One hundred fifty-eight patients with pretreatment DWI underwent analysis of the primary tumor to obtain the ADC mean, ADC skewness, ADC kurtosis, volume, and T-stage. Univariate and multivariate analyses using logistic regression were performed to compare the ADC parameters, volume, T-stage, and patient age in primary tumors with local failure and those with local control, by using a minimum of 5-year follow-up to confirm local control., Results: Local control was achieved in 131/158 (83%) patients (range, 60.3-117.7 months) and local failure occurred in 27/158 (17%) patients (range, 5.2-79.8 months). Compared with tumors with local control, those with local failure showed a significantly lower ADC skewness (ADC values with the greatest frequencies were shifted away from the lower ADC range) (P = .006) and lower ADC kurtosis (curve peak broader) (P = .024). The ADC skewness remained significant on multivariate analysis (P = .044). There was a trend toward higher tumor volumes in local failure, but the volume, together with T-stage and ADC mean, were not significantly different between the 2 groups., Conclusions: Pretreatment DWI of primary tumors found that the skewness of the ADC distribution curve was a predictor of local failure in patients with nasopharyngeal carcinoma, based on long-term clinical outcome., (© 2016 by American Journal of Neuroradiology.)

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., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The purpose of this study was to assess MRI criteria for detecting residual malignant head and neck squamous cell carcinoma (HNSCC) nodes after chemoradiotherapy (CRT)., Methods: One hundred and six metastatic nodes were assessed 6 weeks posttreatment by MRI for necrosis, extranodal neoplastic spread (ENS), size, and percentage of size change. Size measurements were reanalyzed after dividing posttreatment nodes into "discrete solid," "discrete necrotic," and "indiscrete" groups. Results were correlated with nodal response at 2 years., Results: Eighty-three residual nodes were benign and 23 were malignant. Significant predictors of outcome were percentage of change in solid volume (total-necrotic volume; p = .0002) for all posttreatment nodes and percentage of change in total volume for "discrete solid" posttreatment nodes (p = .0003), the latter showing a ≤78% reduction of predicted residual malignant nodes with a negative predictive value (NPV) of 98.2% and positive predictive value (PPV) of 60%. Necrosis, ENS, and size of "discrete necrotic" and "indiscrete" nodes were not significant criteria., Conclusion: Necrosis and ENS were inaccurate criteria for residual malignant nodes and hindered the accuracy of size measurements. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1598-E1604, 2016., (© 2016 Wiley Periodicals, Inc.)

Background and Purpose: It is important to identify patients with head and neck squamous cell carcinoma (SCC) who fail to respond to chemoradiotherapy so that they can undergo post-treatment salvage surgery while the disease is still operable. This study aimed to determine the diagnostic performance of dynamic contrast enhanced (DCE)-MRI using a pharmacokinetic model for pre-treatment predictive imaging, as well as post-treatment diagnosis, of residual SCC at primary and nodal sites in the head and neck., Material and Methods: Forty-nine patients with 83 SCC sites (primary and/or nodal) underwent pre-treatment DCE-MRI, and 43 patients underwent post-treatment DCE-MRI, of which 33 SCC sites had a residual mass amenable to analysis. Pre-treatment, post-treatment and % change in the mean Ktrans, kep, ve and AUGC were obtained from SCC sites. Logistic regression was used to correlate DCE parameters at each SCC site with treatment response at the same site, based on clinical outcome at that site at a minimum of two years., Results: None of the pre-treatment DCE-MRI parameters showed significant correlations with SCC site failure (SF) (29/83 sites) or site control (SC) (54/83 sites). Post-treatment residual masses with SF (14/33) had significantly higher kep (p = 0.05), higher AUGC (p = 0.02), and lower % reduction in AUGC (p = 0.02), than residual masses with SC (19/33), with the % change in AUGC remaining significant on multivariate analysis., Conclusion: Pre-treatment DCE-MRI did not predict which SCC sites would fail treatment, but post-treatment DCE-MRI showed potential for identifying residual masses that had failed treatment.

Purpose: In this prospective cross-sectional study on young premenopausal breast cancer patients, the objectives were to: determine the incidences of chemotherapy-related amenorrhea (CRA) and menopause (CRM); identify associated factors; and assess plasma levels of estradiol (E2) and follicular stimulating hormone (FSH) among patients who developed menopause., Methods: Eligibility criteria include Chinese stage I-III breast cancer patients, premenopausal, age ≤45 at breast cancer diagnosis, having received adjuvant chemotherapy, within 3-10 years after breast cancer diagnosis. Detailed menstrual history prior to and after adjuvant treatment was taken at study entry. Patients' background demographics, tumor characteristics and anti-cancer treatments were collected. The rates of CRA and CRM were determined. Analysis was conducted to identify factors associated with CRM. For postmenopausal patients, levels of E2 and FSH were analyzed., Results: 286 patients were recruited; the median time from breast cancer diagnosis to study entry was 5.0 years. 255 patients (91.1%) developed CRA. Of these, 66.7% regained menstruation. At the time of study entry, 137 (48.9%) had developed CRM, amongst whom 84 were age ≤45. On multivariate analysis, age was the only associated factor. Among patients with CRM, the median FSH was 41.0 IU/L; this was significantly lower in those who were taking tamoxifen compared to those who were not (20.1 vs. 59.7 IU/L, p<0.0001). The E2 level was <40 pmol/L; there was no difference between those who were still on tamoxifen or not., Conclusion: After adjuvant chemotherapy, the majority of young Chinese breast cancer patients developed CRA; ~50% developed CRM, with 61% at age ≤45. Age at diagnosis is the only factor associated with CRM. FSH level may be affected by tamoxifen intake.

Background: The oncogenic PI3K/Akt/mTOR pathway is frequently activated in HCC. Data on the mTOR inhibitor, temsirolimus, is limited in HCC patients with concomitant chronic liver disease. The objectives of this study were: (1) In phase I, to determine DLTs and MTD of temsirolimus in HCC patients with chronic liver disease; (2) In phase II, to assess activity of temsirolimus in HCC, and (3) to explore potential biomarkers for response., Methods: Major eligibility criteria included histologically confirmed advanced HCC and adequate organ function. In Phase I part of the study, temsirolimus was given weekly in 3-weekly cycle; dose levels were 20 mg (level 1), 25 mg (level 2) and 30 mg (level 3). The MTD was used in the subsequent phase II part; the primary endpoint was PFS and secondary endpoints were response and OS. In addition, exploratory analysis was conducted on pre-treatment tumour tissues to determine stathmin, pS6, pMTOR or p-AKT expressions as potential biomarkers for response. Overall survival and PFS were calculated using the Kaplan-Meier method. Reassessment CT scans were done every 6 weeks. All adverse events were reported using CTCAE v3., Results: The Phase I part consisted of 19 patients, 2 of 6 patients at level 3 experienced DLT; dose level 2 was determined to be the MTD. The phase II part consisted of 36 patients. Amongst 35 assessable patients, there were 1 PR, 20 SD and 14 PD. Overall, the median PFS was 2.83 months (95% C.I. 1.63-5.24). The median OS was 8.89 months (95% C.I. 5.89-13.30). Grade ≥ 3 that occurred in > 10% of patients included thrombocytopenia (4) and hyponatraemia (4). Exploratory analysis revealed that disease stabilization (defined as CR + PR + SD > 12 weeks) in tumours having high and low pMTOR H-scores to be 70% and 29% respectively (OR 5.667, 95% CI 1.129-28.454, p = 0.035)., Conclusions: In HCC patients with chronic liver disease, the MTD of temsirolimus was 25 mg weekly in a 3-week cycle. The targeted PFS endpoint was not reached. However, further studies to identify appropriate patient subgroup are warranted., Trial Registration: This study has been registered in ClinicalTrials.gov (Id: NCT00321594) on 1 December 2010.

Prognosis of patients with hepatocellular carcinoma (HCC) depends on both tumour extent and hepatic function reserve. Liver function test (LFT) is a basic routine blood test to evaluate hepatic function. We first analysed LFT components and their associated scores in a training cohort of 217 patients who underwent curative surgery to identify LFT parameters with high performance (discriminatory capacity, homogeneity, and monotonicity of gradient). We derived a novel index, albumin-to-alkaline phosphatase ratio (AAPR), which had the highest c-index (0.646) and χ(2) (24.774) among other liver biochemical parameters. The AAPR was an independent prognostic factor for overall and disease-free survival. The adjusted hazard ratio of death and tumour relapse was 2.36 (P = 0.002) and 1.85 (P = 0.010), respectively. The independent prognostic significance of AAPR on top of 5 commonly used and well established staging systems was further confirmed in 2 independent cohorts of patients receiving surgical resection (n = 256) and palliative therapy (n = 425). In summary, the AAPR is a novel index readily derived from a simple low-cost routine blood test and is an independent prognostic indicator for patients with HCC regardless of treatment options.

Background and Purpose: T2-weighted MRI shows potential in early posttreatment assessment of the primary tumor. Residual masses composed entirely of low T2-signal scar tissue suggest local control and those ≥1 cm of similar signal to untreated tumor suggest local failure. The purpose of this study was to investigate the diagnostic accuracy of T2-weighted MR imaging early after chemoradiotherapy for identifying primary tumor treatment failure in squamous cell carcinoma of the head and neck., Materials and Methods: At 6 weeks after treatment, T2-weighted MR images of 37 primary tumors in 37 patients were assessed. Residual masses were divided into 3 patterns: pattern 1 = scar tissue only (flat-edged/retracted mass of low T2 signal intensity); pattern 2 = mass without features described in pattern 1 or 3; and pattern 3 = any pattern that included an expansile mass ≥1 cm of intermediate T2 signal intensity (similar grade of signal intensity to the untreated tumor). T2 patterns were analyzed for local outcome (Fisher exact test) and time to local failure (univariate and multivariate analysis of T2 pattern, age, T stage, and tumor size by use of the Cox regression model)., Results: Residual masses after treatment were present in 34 (92%) of 37 patients. Local failures occurred in residual masses with pattern 1 in 0 (0%) of 14 patients; pattern 2 in 6 (55%) of 11 patients; and pattern 3 in 9 (100%) of 9 patients. Significant associations were found between local control and pattern 1 (P = <.0001; sensitivity, 74%; specificity, 100%; PPV, 100%; NPV, 75%; accuracy, 85%), and between local failure and pattern 3 (P = <.0001; sensitivity, 60%; specificity, 100%; PPV, 100%; NPV, 76%; accuracy, 82%). Pattern 2 showed no significant associations with local outcome. Univariate analysis of time to local failure showed that the T2 pattern was significant (P < .0001) and remained significant on multivariate analysis., Conclusions: T2-weighted MR imaging is a potential tool for early posttreatment assessment of primary HNSCC treatment response. Awareness of correlation of the T2 pattern of any residual mass with treatment outcome at the primary site may contribute to patient treatment.

Background: Breast cancer patients regularly undergo adjuvant chemotherapies following surgery. However, these treatments are largely associated with chemotherapeutic toxicities ranging from nausea to severe myelosuppression. In this investigation, we examined the effects of four SNPs in NR1I2, CYP3A4 and CYP3A5 genes on chemotherapy-induced severe neutropenia in 311 female Chinese breast cancer patients undergoing a standard adjuvant chemotherapy regimen., Methods: Patients were monitored for adverse reactions throughout the treatment, then divided into "none or mild" (80 %) or "severe" (20 %) toxicity groups according to whether they suffered grade 4 neutropenia defined as having an absolute neutrophil counts (ANC) of less than 0.5 × 10(9)/L anytime during the treatment. DNA was extracted from patients' peripheral blood samples, then genotyped using allele-specific Tm-shift PCR and melting analysis., Results: Logistic regression revealed that rs776746 or CYP3A5*3 strongly associated with grade 4 neutropenia (OR = 2.56, P = 0.023) after adjustment for covariates, one of which more significant factor was baseline ANC (OR = 0.68, P = 0.020). Although univariate analysis in all patients did not reveal any association at first, further analysis indicated that rs776746 is significantly associated with severe neutropenia in subgroup of breast cancer patients with normal baseline ANC (≥2.0 × 10(9)/L). These carriers of A-allele have 3.14-fold increased risk of developing severe neutropenia (P = 0.004)., Conclusion: Our results suggested that polymorphisms in CYP3A5 might be useful pharmacogenetic markers for the prediction of severe neutropenia during chemotherapy, however, only after screening patients by their baseline ANC in the presence of gene-environmental interaction. We demonstrate an approach of pharmacogenetic analysis, in which the genetic data should be analyzed in the perspective of other clinical parameters.

Purpose: To determine the diagnostic performance of diffusion-weighted (DW) imaging for the prediction of treatment failure in primary head and neck squamous cell carcinoma (HNSCC)., Materials and Methods: The study was approved by the local institutional ethics committee and conducted with informed written consent in patients with primary HNSCC treated with radiation therapy and chemotherapy. DW imaging of the primary tumor was performed before treatment in 37 patients and was repeated within 2 weeks of treatment in 30 patients. Histograms of apparent diffusion coefficients (ADCs) were analyzed, and mean ADC, kurtosis, skewness, and their respective percentage change were correlated for local failure and local control at 2 years by using the Student t test. Univariate and multivariate analyses of the ADC parameters, T stage, and tumor volume were performed by using logistic regression for prediction of local failure., Results: Local failure occurred in 16 of 37 (43%) patients and local control occurred in 21 of 37 (57%) patients. Pretreatment ADC parameters showed no correlation with local failure. There was significant intratreatment increase in mean ADC and a decrease in skewness and kurtosis (P < .001, P < .001, P = .024, respectively) for the whole group of patients when compared with those before treatment. During treatment, primary tumors showed a significantly lower increase in percentage change of mean ADC, higher skewness, and higher kurtosis for local failure than for local control (P = .016, .015, and .040, respectively). These ADC parameters also were significant for predicting local failure with use of univariate but not multivariate analysis., Conclusion: Early intratreatment DW imaging has the potential to allow prediction of treatment response at the primary site in patients with HNSCC.

Background: The level of circulating interleukin 10 (IL-10) is elevated in a proportion of patients with hepatocellular carcinoma (HCC). The objective of the current study was to evaluate the prognostic significance of serum the IL-10 level in patients with unresectable HCC., Methods: Patients with unresectable HCC who provided serum at the time of diagnosis were enrolled prospectively in the study. The level of circulating IL-10 in serum samples was determined by enzyme-linked immunosorbent assay. The association of the IL-10 level with overall survival was evaluated in relation to sociodemographics, liver function, hepatitis B viral load, and tumor staging., Results: In total, 222 patients were recruited; of these, 82.4% were positive for hepatitis B virus surface antigen, and 65.8% had Barcelona Clinic Liver Cancer stage C disease. The mean log IL-10 level was 1.1 pg/mL, and 146 patients had an IL-10 level >1 pg/mL (high IL-10 group). The high IL-10 group had worse overall survival than the low IL-10 group (5.0 months vs 14.9 months; hazard ratio, 2.192; P < .0001). The IL-10 level was associated with worse hepatic function and with a high alanine transaminase (ALT) level. The IL-10 level remained an independent prognostic factor (hazard ratio, 1.824; P = .0005) after adjustment for sociodemographics, tumor staging, treatment, Child-Pugh stage, and ALT level. The IL-10 level also subdivided patients into 2 populations with distinct survival (10.2 months vs 3.5 months; P = .0027)., Conclusions: The serum IL-10 level was identified as an independent prognostic factor for unresectable HCC. The current findings suggested that an elevated IL-10 level may be related to hepatic injury caused by cirrhotic processes rather than tumor load. The authors concluded that the IL-10 level offers additional prognostic value to the existing tumor staging systems., (Copyright © 2011 American Cancer Society.)

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 HBV DNA, 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., (© 2011 John Wiley & Sons A/S.)

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 < 0.0001). Both CUPI and CLIP had the most favorable performance in terms of discriminatory ability, homogeneity and monotonicity. CUPI performed the best in predicting 3-month survival while CLIP performed better in predicting the outcome of 6- and 12-month survival rate. BCLC was inferior to CLIP and CUPI in the overall performance., Conclusion: We have validated CUPI in a population composed of predominant HBV-related HCC. CUPI is an appropriate staging system for HBV-related HCC. In patients with advanced HCC, both CUPI and CLIP offer good risk stratification., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Although previous studies have documented correlations between pre-treatment or post-treatment primary tumour volumes and local outcome following definitive concomitant chemoradiotherapy (CCRT) in head and neck squamous cell carcinoma (HNSCC), no study has included and compared tumour volumes during CCRT. We reviewed the MRIs of 69 HNSCC patients treated with a 6 weeks course of CCRT and who underwent successful MRI pre-treatment (n = 69), 2 weeks intra-treatment (n = 48) and 6 weeks post-treatment (n = 61). Primary tumour volumes on MRI at the three time points were calculated and compared for their predictive value for primary site outcome. Volume thresholds optimised to predict failure with the highest accuracy and positive predictive value (PPV) were calculated. The mean pre-treatment volume was 24.6 cm³ (range, 1.1-187.9 cm³) and the mean follow-up interval was 41 months (range, 12-100 months). 23 primary tumours failed treatment (33%). Volumes before, during and after CCRT were positively associated with local failure (p = 0.015, p = 0.009, p<0.0001). Volume reductions during and after CCRT were negatively associated with local failure (p = 0.021, p = 0.001). Pre-treatment and intra-treatment volume thresholds achieved the highest accuracy and produced intermediate PPVs (51-64%) for predicting local failure. Optimised intra-treatment thresholds did not identify any more treatment failures than the pre-treatment thresholds. By comparison, a 6 weeks post-treatment volume reduction (<35%) achieved 100% PPV for failure, albeit with 26% sensitivity. In conclusion, primary tumour volumetry performed early in CCRT provides minimal additional information compared with pre-treatment volumetry, with respect to predicting post-treatment local failures. Therefore, volumetry during CCRT is unlikely to be useful for guiding individual response-based therapeutic modifications.

Folfox and Folfiri are active chemotherapy treatments used in advanced colorectal cancer. The total admission for these treatments has been significantly increasing in the study hospital. An ambulatory infusion programme was launched to address the problems of long waiting list and bed shortage. The study objective was to compare the quality of life between patients receiving the chemotherapy treatments in the ambulatory infusion group and the inpatient infusion group. The results showed that some demographic variables of education level, family role and employment status were determinants of the treatment mode. Patients in the ambulatory infusion group of social and global domains performed better than the inpatient group. However, the inpatient group had better quality of life of nauseated symptom at different stages. Some nursing educations should be reinforced to address the symptom management for patients receiving ambulatory infusion at home. The ambulatory infusion programme offered considerable quality of life benefits to colorectal cancer patients receiving chemotherapy., (© 2010 Blackwell Publishing Asia Pty Ltd.)

Objective: To identify clinical markers to predict which patients with advanced colorectal cancers are likely to benefit from cetuximab-chemotherapy., Design: Retrospective review., Setting: Oncology unit in a university teaching hospital in Hong Kong., Patients: A total of 102 patients with metastatic colorectal cancer treated with cetuximab-chemotherapy., Main Outcome Measures: Correlation of multiple potential clinical predictive factors with tumour response to cetuximab-chemotherapy., Results: The objective response rates to cetuximab plus chemotherapy were 53% in patients receiving first-line treatment and 17% in previously treated patients. The univariate analysis indicated that fewer prior lines of chemotherapy (odds ratio=0.36; 95% confidence interval, 0.21-0.63; P<0.01) and development of cetuximab-related grade 3 rash (5.52; 1.62-18.76; P<0.01) were associated with significantly higher response rates. Multivariate analysis confirmed the independent predictive value of the number of prior chemotherapy regimens (odds ratio=0.37; 95% confidence interval, 0.20-0.69; P<0.01) and grade 3 rash (4.65; 1.21-19.29; P=0.03)., Conclusions: In this cohort of Chinese patients with advanced colorectal cancer, the presence of grade 3 rash and the number of prior chemotherapy regimens were independent predictors of response to cetuximab-chemotherapy. The utility of these clinical markers in clinical practice should be further evaluated together with established biomarkers.

Chitosan is a biocompatible, biodegradable and non-toxic polysaccharide polymer. It dissolves in water only if the pH is lower than 6.5. To extend its range of application, many water-soluble derivatives have therefore been prepared. In this research, chitosan-vitamin C complex was synthesized and characterized with Fourier transformed infrared spectroscopy, differential scanning calorimetry and (1)H-NMR. The solubility of chitosan-vitamin C complex in distilled water was greatly improved. The *O(2) (-) scavenging activity of chitosan-vitamin C complex was compared with chitosan and vitamin C by measuring the auto-oxidation rate of pyrogallic acid. Results showed that the scavenging activity on *O(2) (-) by chitosan-vitamin C complex was stronger than that by CS. At low concentrations (< 0.05 mg/ml), the scavenging activity of chitosan-vitamin C complex was stronger than that of vitamin C, but after certain concentrations (>0.1mg/ml), its scavenging activity was lower than that of vitamin C.

Objectives: This is a single center, randomized, double-blind placebo-controlled study to evaluate the NK(1)-receptor antagonist, aprepitant, in Chinese breast cancer patients. The primary objective was to compare the efficacy of aprepitant-based antiemetic regimen and standard antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who received moderately emetogenic chemotherapy. The secondary objective was to compare the patient-reported quality of life in these two groups of patients., Patients and Methods: Eligible breast cancer patients were chemotherapy-naive and treated with adjuvant AC chemotherapy (i.e. doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2)). Patients were randomly assigned to either an aprepitant-based regimen (day 1, aprepitant 125 mg, ondansetron 8 mg, and dexamethasone 12 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, aprepitant 80 qd) or a control arm which consisted of standard regimen (day 1, ondansetron 8 mg and dexamethasone 20 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, ondansetron 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary, patients quality of life were assessed by self-administered Functional Living Index-Emesis (FLIE)., Results: Of 127 patients randomized, 124 were assessable. For CINV in Cycle 1 AC, there was no significant difference in the proportion of patients with reported complete response, complete protection, total control, 'no vomiting', 'no significant nausea' and 'no nausea'. The requirement of rescue medication appears to be lesser in patients treated with the aprepitant-based regimen compared to those with the standard regimen (11% vs. 20%; P = 0.06). Assessment of FLIE revealed that while there was no difference in the nausea domain and the total score between the two groups; however, patients receiving standard antiemetic regimen had significantly worse quality of life in the vomiting domain (mean score [SD] = 23.99 [30.79]) when compared with those who received the aprepitant-based regimen (mean score [SD] = 3.40 [13.18]) (P = 0.0002). Both treatments were generally well tolerated. Patients treated with the aprepitant-based regimen had a significantly lower incidence of neutropenia (53.2% vs. 35.5%, P = 0.0468), grade >or= 3 neutropenia (21.0% vs. 45.2, P = 0.0042) and delay in subsequent cycle of chemotherapy (8.1% vs. 27.4%, P = 0.0048)., Conclusion: The aprepitant regimen appears to reduce the requirement of rescue medication when compared with the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide, and is associated with a better quality of life during adjuvant AC chemotherapy.

Genomic gain represents an important mechanism in the activation of proto-oncogenes. In many instances, induced oncogenes hold clinical implications both as prognostic markers and targets for therapeutic design. In hepatocellular carcinoma (HCC), although chromosomal gains are common, information on underlying oncogenes induced remains minimal. Here, we examined 7 causal sites of HCC for overexpressed genes by array-based transcriptional mapping. In 22 HCC cell lines and early passages of cultures studied, clusters of up-regulated genes were indicated, where TOP2A expression ranked the highest. Distinct TOP2A transcriptions were confirmed in an independent series of HCC tumors relative to adjacent non-tumoral liver (p=0.0018). By tissue microarray analysis of 172 HCC, we found TOP2A expressions correlated with advance histological grading (p<0.001), microvascular invasion (p=0.004) and an early age onset of the malignancy (

A simple, reproducible and efficient reverse phase high performance liquid chromatographic method was developed for simultaneous determination of valsartan and hydrochlorothiazide in tablets. A column having 200 x 4.6 mm i.d. in isocratic mode with mobile phase containing methanol:acetonitrile:water:isopropylalcohol (22:18:68:2; adjusted to pH 8.0 using triethylamine; v/v) was used. The flow rate was 1.0 ml/min and effluent was monitored at 270 nm. The retention time (min) and linearity range (mug/ml) for valsartan and hydrochlorothiazide were (3.42, 8.43) and (5-150, 78-234), respectively. The developed method was found to be accurate, precise and selective for simultaneous determination of valsartan and hydrochlorothiazide in tablets.

Unlabelled: HCC is a common cause of morbidity and mortality. For patients who are not candidates for curative surgery, systemic chemotherapy is one of the standard treatments. In parts of China and the Far East, over 80% of HCC patients have chronic HBV infection. In this study, we aimed to assess the relationship between pre-chemotherapy HBV viral load and the survival of HCC patients. HBV infection status was determined prior to chemotherapy in 188 patients, 170 of whom had evidence of HBV chronic infection/exposure (160 hepatitis B surface antigen [HBsAg]-positive, 10 HBsAg-negative/hepatitis B core antibody-positive). Of these, 125 had pretreatment HBV DNA levels determined via real-time PCR. Virological data were analyzed using conventional clinical variables to identify factors that influenced survival. Multivariate analysis revealed that high total bilirubin (P = 0.0016; hazard ratio = 1.040 per 1 muM increase; 95% CI 1.015-1.065), HCV infection (P = 0.0095; hazard ratio = 6.955; 95% CI 1.606-30.129), and high HBV DNA level (P = 0.0217; hazard ratio = 1.650; 95% CI 1.076-2.531) affected survival significantly. Exploratory analysis revealed that high levels of pretreatment HBV DNA had a significantly higher incidence of severe hepatitis during chemotherapy., Conclusion: For HCC patients with HBV chronic infection/exposure, a high viral load prior to treatment is an adverse factor for survival and may be associated with a higher incidence of severe hepatitis during chemotherapy. Future strategies to improve the prognosis of HCC patients undergoing chemotherapy should consider supportive therapy that incorporates antiviral therapies to reduce HBV viral load.

Cycloxygenase-2 (COX-2), hypoxia inducible factor 1-alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) can be induced by the Epstein-Barr virus oncoprotein latent membrane protein-1 (LMP-1) in nasopharyngeal cancer (NPC) cell lines. This study examined the prognostic relevance of COX-2 and its relationship with HIF-1alpha and VEGF expression in NPC biopsies. Primary tumor biopsies were obtained from 78 participants of a randomized trial who received radiotherapy (RT) with or without concurrent chemotherapy for locoregionally advanced NPC. These were analyzed for COX-2 expression and then correlated with age, sex, disease stage, treatment arm, survival and disease recurrence, VEGF and HIF-1alpha expression in a regression model. 83% of tumors expressed COX-2, 47% co-expressed COX-2 and VEGF, 38% co-expressed COX-2 and HIF-1alpha. On univariate analysis, COX-2 expression did not correlate with survival and recurrence, but moderate to high COX-2 expression was associated with advanced nodal stage (p=0.03). Although univariate analysis showed that COX-2-HIF-1alpha co-expression was associated with worse progression-free survival (p=0.046), time to local (p=0.004) and regional recurrence (p=0.007), multivariate analysis failed to confirm any correlation between COX-2-HIF-1alpha or COX-2-VEGF co-expression and survival or disease recurrence. Contrary to previous report, this study failed to demonstrate any prognostic significance of COX-2 expression alone or co-expression with HIF-1alpha or VEGF in advanced NPC.

Background: The purpose of this study was to evaluate the tolerability and efficacy of irofulven, a DNA interacting acylfulvene analog, as first line therapy for patients with recurrent or metastatic gastric cancer., Patients and Methods: Twenty-three patients with recurrent or metastatic gastric cancer received irofulven at a dose of 0.45 mg/kg administered intravenously over 30-min infusion (up to a maximum of 50 mg), on days 1 and 8, every 3 weeks., Results: The median number of cycles delivered per patient was 2 (range 1-6). Two patients (9%) had >or= 1-week delay in administration of subsequent cycle of chemotherapy. For the day 8 chemotherapy, dose reductions were required in seven patients (30%); dose omitting occurred in five patients (22%). Grade 3/4 anemia and neutropenia occurred in 22 and 17% of patients, respectively. There was no grade 4 thrombocytopenia and no neutropenic fever was observed. Of the 20 evaluable patients, there were no responses observed, 3 patients had stable disease after 2 cycles of treatment which was not confirmed by a further assessment. Median overall survival was 6.05 months (95% CI 4.55-9.39)., Conclusions: Irofulven was tolerated at the dose of 0.45 mg/kg on days 1 and 8, every 3 weeks but showed no evidence of antitumor activity in patients with advanced gastric cancer.

A new oil-in-water microemulsion containing 0.375% meloxicam was developed in order to improve the skin permeability of meloxicam. Among various surfactants and cosurfactants investigated in the microemulsion system, polyoxyethylene sorbitan trioleate (Tween 85) showed excellent solubility and ethanol expressed skin permeation enhancing effect for meloxicam. The microemulsion existence ranges were defined through the construction of the pseudo-ternary phase diagram. The effect of the content of isopropyl myristate (IPM) and the effect of the mass ratio of the surfactant/cosurfactant (Km) on skin permeation of meloxicam were evaluated with excised rat skins. The optimum formulation with the highest skin permeation rate (5.40 microg/cm2/h) consisted of 0.375% meloxicam, 5% IPM, 50% Tween 85/ethanol (1:1) and water.