Proposal for the 8th edition of the AJCC/UICC staging system for nasopharyngeal cancer in the era of intensity-modulated radiotherapy

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Global Pattern of Nasopharyngeal Cancer: Correlation of Outcome With Access to Radiation Therapy

Purpose: This study aimed to estimate the treatment outcome of nasopharyngeal cancer (NPC) across the world and its correlation with access to radiation therapy (RT). Methods and Materials: The age-standardized mortality (ASM) and age-standardized incidence (ASI) rates of NPC from GLOBOCAN (2012) were summarized, and [1−(ASM/ASI)] was computed to give the proxy relative survival (RS). Data from the International Atomic Energy Agency (IAEA) and the World Bank were used to assess the availability of RT in surrogate terms: the number of RT equipment units and radiation oncologists per million population. Results: A total of 112 countries with complete valid data were analyzed, and the proxy RS varied widely from 0% to 83% (median, 50%). Countries were categorized into Good, Median, and Poor outcome groups on the basis of their proxy RS (55%). Eighty percent of new cases occurred in the Poor outcome group. Univariable linear regression showed a significant correlation between outcome and the availability of RT: proxy RS increased at 3.4% (P<.001) and 1.5% (P=.001) per unit increase in RT equipment and oncologist per million population, respectively. The median number of RT equipment units per million population increased significantly from 0.5 in the Poor, to 1.5 in the Median, to 4.6 in the Good outcome groups, and the corresponding number of oncologists increased from 1.1 to 3.3 to 7.1 (P<.001). Conclusions: Nasopharyngeal cancer is a highly treatable disease, but the outcome varies widely across the world. The current study shows a significant correlation between survival and access to RT based on available surrogate indicators. However, the possible reasons for poor outcome are likely to be multifactorial and complex. Concerted international efforts are needed not only to address the fundamental requirement for adequate RT access but also to obtain more comprehensive and accurate data for research to improve cancer outcome.postprin

The International Atomic Energy Agency global initiatives on nasopharyngeal cancer treatment

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Should young age be a contra-indication to breast conservation treatment in Chinese women? Twelve-year experience from a public cancer centre in Hong Kong

Objective: It has been proposed that young women should not be treated by breast conservation treatment because of a higher risk of local recurrences and worse survival. We therefore examined whether breast conservation treatment in young Chinese women yielded inferior clinical outcomes compared to modified radical mastectomy. Design: Retrospective study. Setting: Clinical oncology department in a public hospital in Hong Kong. Patients: A total of 258 Chinese women with invasive breast cancer, aged below 40 years, and referred between January 1994 and July 2006. Results: A total of 124 (48%) and 134 (52%) patients were treated by breast conservation treatment and modified radical mastectomy, respectively. Mastectomy patients tended to have larger primary tumours (P<0.001) and more nodal involvement (P<0.001). At a median follow-up of 6.5 years, there was no significant difference in the local failure-free survival rate (92% vs 93%, P=0.324) and loco-regional failure-free survival rate (89% vs 88%, P=0.721) in patients having breast conservation treatment and mastectomy. Probably due to their earlier presentation with disease, the former actually had better 6-year distant failure-free survival (88% vs 71%, P=0.002) and overall survival (92% vs 81%, P=0.173) rates. Multivariate analyses showed that both the resection margin status (hazard ratio=2.77, P=0.050) and the presence of peritumoural vascular invasion (hazard ratio=3.01, P=0.038) were independent predictors of local recurrence; the nodal status (hazard ratio=3.91, P<0.001) was the only predictive factor for overall survival. The choice of breast conservation treatment (vs modified radical mastectomy) had no apparent adverse impact on all the clinical outcome parameters analysed. Conclusion: Breast conservation treatment is a reasonable option for many suitably selected young Chinese women.published_or_final_versio

Authors' reply

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Hong Kong domestic health spending: Financial years 1989/90 to 2009/10

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HER2 overexpression of breast cancers in Hong Kong: Prevalence and concordance between immunohistochemistry and in-situ hybridisation assays

Objectives: To evaluate the prevalence of human epidermal growth factor receptor 2 (HER2) gene overexpression in breast cancer patients encountered in Hong Kong and the concordance of HER2 findings from primary immunohistochemistry assays and confirmatory in-situ hybridisation assays. Design: Retrospective study. Setting: Department of Clinical Oncology in a public hospital in Hong Kong. Patients: All patient referrals between July 2006 and June 2007 with newly diagnosed invasive breast cancer (for prevalence evaluation), and all patients treated at our unit with confirmatory in-situ hybridisation tests performed within the study period (for concordance evaluation). Results: There were 272 consecutive breast cancer patients eligible for prevalence evaluation. The distribution for immunohistochemistry staining in 249 cases for scores 0, 1+, 2+, and 3+ were 99 (40%), 40 (16%), 58 (23%), and 52 (21%) respectively. In the remaining 23 patients, four and 19 breast cancers were unscored and reported by immunohistochemistry to be HER2-positive and -negative, respectively. The overall HER2 overexpression rate (3+ or reported as positive) was 21%. HER2 overexpression was associated with grade 3 histology (P<0.001) and negative hormonal receptor status (P<0.001). However, it was not associated with age (P=0.525), T-classification (P=0.740), N-classification (P=0.691), nor group stages (P=0.433). Of the 37 patients with confirmatory in-situ hybridisation tests performed, 10 (71%) of 14 with immunohistochemistry staining of 3+ and 1 (4%) of 23 with immunohistochemistry staining of 2+ were found to have HER2 gene amplification. Conclusions: More than 25% of HER2 overexpression identified by immunohistochemistry assays in this Hong Kong cohort could not be verified by confirmatory in-situ hybridisation assays. Compliance with the latest guidelines for HER2 testing should improve the future accuracy and concordance.published_or_final_versio

Hong Kong domestic health spending: Financial years 1989/90 to 2008/09

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Secular trends of salted fish consumption and nasopharyngeal carcinoma: a multi-jurisdiction ecological study in 8 regions from 3 continents

Background: Despite salted fish being a classical risk factor of Nasopharyngeal Carcinoma (NPC), whether secular trends in salted fish consumption worldwide accounted for changes in NPC rates were unknown. The relationship between vegetable and cigarette consumption to NPC risk worldwide were also largely uncertain. We investigated the longitudinal trends in standardised NPC incidence/mortality rates across 8 regions and their associations with secular trends in salted fish, vegetable and tobacco consumptions. Methods: Age standardised mortality rate (ASMR) and age standardised incidence rate (ASIR) of NPC were obtained from the WHO cancer mortality database and Hong Kong Cancer Registry. Per capita consumption of salted fish, tobacco and vegetables in Hong Kong and 7 countries (China, Finland, Japan, Portugal, Singapore, United Kingdom and United States) were obtained from the Food and Agriculture Organization of the United Nation (FAO) and Hong Kong Trade and Census Statistics. Pearson correlation and multivariate analysis were performed to examine both crude and adjusted associations. Results: There were markedly decreasing trends of NPC ASIR and ASMR in Hong Kong over the past three decades, which were correlated with corresponding secular changes in salted fish consumption per capita (Pearson r for 10 cumulative years : ASIR = 0.729 (male), 0.674 (female); ASMR = 0.943 (male), 0.622 (female), all p 0.05). However, there were no clear or consistent patterns in relations between NPC ASIR and ASMR with salted fish consumption across 7 regions in 3 continents. Conclusions: Our results do not support the notion that changes in salted fish consumption had played an important role in explaining secular trends of NPC rates in Hong Kong and worldwide. Further studies should explore other lifestyle and genetic factors. However, our findings do support the potentially protective effects of vegetable consumption against NPC.published_or_final_versio

Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma

© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10 -9 ), but was less obvious in other types of solid tumors except for prostate and Epstein-Barr virus (EBV)-positive gastric cancer (FDR < 10 -3 ). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection.published_or_final_versio