Stephen C.K. Law

Cancer survival in Africa, Asia, and Central America: a population-based study

BACKGROUNDnPopulation-based cancer survival data, a key indicator for monitoring progress against cancer, are not widely available from countries in Africa, Asia, and Central America. The aim of this study is to describe and discuss cancer survival in these regions.nnnMETHODSnSurvival analysis was done for 341 658 patients diagnosed with various cancers from 1990 to 2001 and followed up to 2003, from 25 population-based cancer registries in 12 countries in sub-Saharan Africa (The Gambia, Uganda), Central America (Costa Rica), and Asia (China, India, Pakistan, Philippines, Saudi Arabia, Singapore, South Korea, Thailand, Turkey). 5-year age-standardised relative survival (ASRS) and observed survival by clinical extent of disease were determined.nnnFINDINGSnFor cancers in which prognosis depends on stage at diagnosis, survival was highest in China, South Korea, Singapore, and Turkey and lowest in Uganda and The Gambia. 5-year ASRS ranged from 76-82% for breast cancer, 63-79% for cervical cancer, 71-78% for bladder cancer, and 44-60% for large-bowel cancers in China, Singapore, South Korea, and Turkey. Survival did not exceed 22% for any cancer site in The Gambia; in Uganda, survival did not exceed 13% for any cancer site except breast (46%). Variations in survival correlated with early detection initiatives and level of development of health services.nnnINTERPRETATIONnThe wide variation in cancer survival between regions emphasises the need for urgent investments in improving awareness, population-based cancer registration, early detection programmes, health-services infrastructure, and human resources.nnnFUNDINGnAssociation for International Cancer Research (AICR; St Andrews, UK), Association pour la Recherche sur le Cancer (ARC, Villejuif, France), and the Bill & Melinda Gates Foundation (Seattle, USA).

Identification of serum amyloid A protein as a potentially useful biomarker to monitor relapse of nasopharyngeal cancer by serum proteomic Profiling

Purpose: Nasopharyngeal cancer (NPC) is a common cancer in Hong Kong, and relapse can occur frequently. Using protein chip profiling analysis, we aimed to identify serum biomarkers that were useful in the diagnosis of relapse in NPC. Experimental Design: Profiling analysis was performed on 704 sera collected from 42 NPC patients, 39 lung cancer patients, 30 patients with the benign metabolic disorder thyrotoxicosis (TX), and 35 normal individuals (NM). Protein profile in each NPC patient during clinical follow up was correlated with the relapse status. Results: Profiling analysis identified two biomarkers with molecular masses of 11.6 and 11.8 kDa, which were significantly elevated in 22 of 31 (71%) and 21 of 31 (68%) NPC patients, respectively, at the time of relapse (RP) as compared with 11 patients in complete remission (CR; RP versus CR, P = 0.009), 30 TX (RP versus TX, P < 0.001), or 35 NM (RP versus NM, P < 0.001). The markers were also elevated in 16 of 39 (41%) lung cancer patients at initial diagnosis. By tryptic digestion, followed by tandem mass spectrometry fragmentation, the markers were identified as two isoforms of serum amyloid A (SAA) protein. Monitoring the patients longitudinally for SAA level both by protein chip and immunoassay showed a dramatic SAA increase, which correlated with relapse and a drastic fall correlated with response to salvage chemotherapy. Serum SAA findings were compared with those of serum Epstein-Barr virus DNA in three relapsed patients showing a similar correlation with relapse and chemo-response. Conclusions: SAA could be a useful biomarker to monitor relapse of NPC.

Clinical Features and Outcome of the Tall Cell Variant of Papillary Thyroid Carcinoma

Objectives: To study the clinical features and outcome of the tall cell variant (TCV) of papillary thyroid carcinoma (PTC).

Breast Cancer in Hong Kong, Southern China: The First Population-Based Analysis of Epidemiological Characteristics, Stage-Specific, Cancer-Specific, and Disease-Free Survival in Breast Cancer Patients: 1997–2001

BackgroundCancer registries have been set up worldwide to provide information for cancer health planning. There are known variations in breast cancer incidence and mortality worldwide. However, breast cancer incidence, pathological characteristics, and survival data is still under-reported in Asian countries. This is the first comprehensive population-based breast cancer study performed using population database of the Hong Kong Cancer Registry.MethodsA retrospective review of medical records of 8,961 subjects who were diagnosed with breast cancer between January 1, 1997 to December 31, 2001 and followed up to December 31, 2007. Descriptive statistics were employed to analyze the epidemiological and clinical data. Estimates of overall, disease-free, and cancer-specific survival at 5xa0years were estimated by the Kaplan–Meier method and stage-specific relative survival rates were calculated.ResultsA total of 7,630 breast cancer patients’ medical records and dataset were available during this period, and 7,449 subjects were eligible for the final analysis. Median follow-up was 84xa0months. A total of 47.4% were diagnosed with breast cancer at age 49xa0years and younger; 22.2%, 46.9%, 10.8%, and 4.1% presented at stages I, II, III, and IV, respectively. A total of 53.5% had ER-positive cancer, and 20.3% had HER2-positive cancers; 13.4% had triple-negative cancers. The relative, cancer-specific, and disease-free survival rates at 5xa0years were 84%, 85.2%, and 81.2%, respectively.DiscussionWe performed the first comprehensive population-based breast cancer epidemiology study in Southern China using the Hong Kong Cancer Registry database. This provides a baseline study cohort for comparative studies with other Asian countries and Chinese who have migrated to the West.

Health-related quality-of-life study in patients with carcinoma of the thyroid after thyroxine withdrawal for whole body scanning.

Objectives/Hypothesis: The authors studied the change of health‐related quality of life (HR‐QOL) in patients with differentiated thyroid carcinoma (DTC) with thyroxine (T4) withdrawal in preparation for whole body radioactive iodine scanning.

Proteomic Approach to Biomarker Discovery in Cancer Tissue from Lung Adenocarcinoma Among Nonsmoking Chinese Women in Hong Kong

Half of the female patients with adenocarcinoma in East Asia are never-smokers. Proteomic analysis of tumor tissue may throw important light on the pathogenesis of this interesting subgroup of lung cancer. The cancer and adjacent normal lung tissue were taken from 21 never-smoked adenocarcinoma and profiled using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Fifty-two proteins were significantly discriminatory between tumor and normal lung tissues. Ninety-three proteins were found to have high accuracy in discriminating between adenocarcinoma with or without smoking history. These proteins may yield new insights about the altered pathogenetic pathways of never-smoked lung cancers.

Impact and relationship of anterior commissure and time-dose factor on the local control of T1N0 glottic cancer treated by 6 MV photons

BackgroundTo evaluate prognostic factors that may influence local control (LC) of T1N0 glottic cancer treated by primary radiotherapy (RT) with 6 MV photons.MethodsWe retrospectively reviewed the medical records of 433 consecutive patients with T1N0 glottic cancer treated between 1983 and 2005 by RT in our institution. All patients were treated with 6 MV photons. One hundred and seventy seven (41%) patients received 52.5 Gy in 23 fractions with 2.5 Gy/fraction, and 256 (59%) patients received 66 Gy in 33 fractions with 2 Gy/fraction.ResultsThe median follow-up time was 10.5 years. The 10-year LC rates were 91% and 87% for T1a and T1b respectively. Multivariate analysis showed LC rate was adversely affected by poorly differentiated histology (Hazard Ratio [HR]: 7.5, p = 0.035); involvement of anterior commissure (HR: 2.34, p = 0.011); fraction size of 2.0 Gy (HR: 2.17, p = 0.035) and tumor biologically effective dose (BED) < 65 Gy15 (HR: 3.38, p = 0.017).ConclusionsThe negative impact of anterior commissure involvement could be overcome by delivering a higher tumor BED through using fraction size of > 2.0 Gy. We recommend that fraction size > 2.0 Gy should be utilized, for radiation schedules with five daily fractions each week.

Male Breast Cancer: A Population-Based Comparison with Female Breast Cancer in Hong Kong, Southern China: 1997–2006

BackgroundMale breast cancer (MBC) is uncommon. As a result, there is limited availability of studies and reviews and even fewer reports from Asia. This is the largest population-based study to compare Chinese MBC patients with female patients during a 10-year period in Hong Kong, Southern China.MethodsA retrospective review of medical records of 132 male and 8,118 female breast cancer patients between year 1997 and 2006 in Hong Kong was performed. Each MBC patient was matched with three female breast cancer patients for further analysis. Different characteristics, overall, breast-cancer specific, and disease-free survivals (DFS) were compared.ResultsMean age at diagnosis of male and female patients was 64.5 and 52.7xa0years respectively. Male patients showed lower histological grade, overall stage, smaller tumor size, and more positive sensitivity in hormone receptors. They were more likely to die of causes other than breast cancer. Matched analysis found that the 5-year overall survival (OS), breast-cancer–specific mortality, and DFS for male and female patients were 78.7, 90.5, 90.5, and 77.9, 86.4, and 81.4xa0% respectively. Male patients had poorer OS at early overall stage but better breast-cancer—specific mortality rates at any age (pxa0<xa00.01). Male patients had a significant risk of dying due to any cause in the presence of distant relapse and had less risk of dying when tumor was ER-positive and HER2-positive.ConclusionsChinese male breast cancer patients tend to have poorer OS but better breast-cancer—specific survival compared with their female counterparts.

Application of ProteinChip Array Profiling in Serum Biomarker Discovery for Patients Suffering From Severe Acute Respiratory Syndrome

A new strain of coronavirus has caused an outbreak of severe acute respiratory syndrome (SARS) from 2002 to 2003 resulting in 774 deaths worldwide. By protein chip array profiling technology, a number of serum biomarkers that might be useful in monitoring the clinical course of SARS patients were identified. This book chapter describes how the protein chip array profiling was carried out for this study. Briefly, SARS patients’ serum samples were first fractionated in Q Ceramic HyperD ion exchange sorbent beads by buffers at different pH. Serum protein fractions thus obtained were then bound onto a copper (II) immobilized metal affinity capture (IMAC30 Cu [II]) ProteinChip® Array or a weak cation-exchange (CM10) ProteinChip Array. After washing and addition of sinapinic acid, the chips were read in a Protein Biological System (PBS) IIc mass spectrometer. Ions were generated by laser shots and flied in a time of flight mode to the ion detector according to their mass over charge (m/z) ratio. The serum profiling spectra in SARS patients were acquired, baseline subtracted and analyzed in parallel with those from the control subjects by Ciphergen ProteinChip Software 3.0.2 with their peak intensities compared by a nonparametric two sample Mann-Whitney-U test. More than twelve peaks were differentially expressed in SARS patients with one at m/z of 11,695 (later identified to be serum amyloid A protein), which had increase in peak intensity correlating with the extent of SARS-coronavirus induced pneumonia as defined by a serial chest X-ray opacity score. The remaining biomarkers could also be useful in the study of other clinical parameters in SARS patients.

Risk factors and natural history of breast cancer in younger Chinese women

AIMnTo investigate the age differences in the risk factors, clinicopathological characteristics and patterns of treatment of female breast cancer patients.nnnMETHODSnSeven thousand one hundred and fifty-two women with primary breast cancer from the Hong Kong Breast Cancer Registry were recruited after receiving patients consent, they were asked to complete standardized questionnaires which captured their sociodemographic characteristics and risk factors associated with breast cancer development. Among them, clinicopathological data and patterns of treatment were further collected from medical records of 5523 patients with invasive breast cancers. Patients were divided into two groups according to the age at diagnosis: younger (< 40 years old) vs older patients (≥ 40 years old) for subsequent analyses.nnnRESULTSnAnalysis on the sociodemographic characteristics and exposure to risk factors were performed on 7152 women with primary breast cancer and the results revealed that younger patients were more likely to have unhealthy lifestyles; these include a lack of exercise (85.4% vs 73.2%, P < 0.001), having high stress in life (46.1% vs 35.5%, P < 0.001), having dairy/meat-rich diets (20.2% vs 12.9%, P < 0.001), having alcohol drinking habit (7.7% vs 5.2%, P = 0.002). Younger patients were also more likely to have hormone-related risk factors including nulliparity (43.3% vs 17.8%, P < 0.001) and an early age at menarche (20.7% vs 13.2%, P < 0.001). Analyses on clinicopathological characteristics and patterns of treatment were performed on 5523 women diagnosed with invasive breast cancer. The invasive tumours in younger patients showed more aggressive pathological features such as having a higher percentage of grade 3 histology (45.7% vs 36.5%, P < 0.001), having a higher proportion of tumours with lymphovascular invasion (39.6% vs 33.2%, P = 0.003), and having multifocal disease (15.7% vs 10.3%, P < 0.001); they received different patterns of treatment than their older counterparts.nnnCONCLUSIONnYounger patients in Hong Kong are more likely to encounter risk factors associated with breast cancer development and have more aggressive tumours than their older counterparts.