3D T1-weighted turbo spin echo contrast-enhanced MRI at 1.5 T for frameless brain metastases radiotherapy.

PURPOSE: Performance of 3D-T1W-TSE has been proven superior to 3D-MP-GRE at 3 T on brain metastases (BM) contrast-enhanced (CE) MRI. However, its performance at 1.5 T is largely unknown and sparsely reported. This study aims to assess image quality, lesion detectability and conspicuity of 1.5 T 3D-T1W-TSE on planning MRI of frameless BM radiotherapy. METHODS: 94 BM patients to be treated by frameless brain radiotherapy were scanned using 3D-T1W-TSE with immobilization on multi-vendor 1.5 T MRI-simulators. BMs were jointly diagnosed by 4 reviewers. Enhanced lesion conspicuity was quantitatively assessed by calculating contrast ratio (CR) and contrast-to-noise ratio (CNR). Signal-to-noise ratio (SNR) reduction of white matter due to the use of flexible coil was assessed. Lesion detectability and conspicuity were compared between 1.5 T planning MRI and 3 T diagnostic MRI by an oncologist and a radiologist in 10 patients. RESULTS: 497 BMs were jointly diagnosed. The CR and CNR were 75.2 ± 39.9% and 14.2 ± 8.1, respectively. SNR reduced considerably from 31.7 ± 8.3 to 21.9 ± 5.4 with the longer distance to coils. 3 T diagnostic MRI and 1.5 T planning MRI yielded exactly the same detection of 84 BMs. Qualitatively, lesion conspicuity at 1.5 T was not inferior to that at 3 T. Quantitatively, lower brain SNR and lesion CNR were found at 1.5 T, while lesion CR at 1.5 T was highly comparable to that at 3 T. CONCLUSION: 1.5 T 3D-T1W-TSE planning MRI of frameless BM radiotherapy was comprehensively assessed. Highly comparable BM detectability and conspicuity were achieved by 1.5 T planning MRI compared to 3 T diagnostic MRI. 1.5 T 3D-T1W-TSE should be valuable for frameless brain radiotherapy planning.

Prognostic and therapeutic evaluation of nasopharyngeal carcinoma by dynamic contrast-enhanced (DCE), diffusion-weighted (DW) magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS).

Nasopharyngeal carcinoma (NPC) is an aggressive head and neck malignancy, and radiotherapy (with or without chemotherapy) is the primary treatment modality. Reliable tumour assessment during the treatment phase, which can portend the efficacy of radiotherapy and early identification of potential treatment failure in radioresistant disease, has been implicit for better cancer management. Technological advancement in the last decade has fostered the development of functional magnetic resonance imaging (fMRI) techniques into a promising tool for diagnostic and therapeutic assessments in head and neck cancer. Apart from conventional morphological assessment, early detection of the physiological environment by fMRI allows a more thorough investigation in monitoring tumour response. This article discusses the relevant fMRI utilities in NPC as an early prognostic and monitoring tool for treatment. Challenges and future developments of fMRI in radiation oncology are also discussed.

Application of circulating plasma/serum EBV DNA in the clinical management of nasopharyngeal carcinoma.

Elevated levels of circulating cell-free Epstein-Barr virus (EBV) DNA have been detected in plasma and serum samples from nasopharyngeal cancer (NPC) patients by quantitative real time PCR (qPCR) test. This qPCR test for circulating EBV DNA was found to be useful in the clinical management of NPC patients. For instance, EBV DNA qPCR test has good sensitivity and specificity in the detection of NPC at disease onset. Increase of the viral DNA load was found in NPC patients at late stages of disease. High EBV DNA load at disease onset or detectable viral load post-treatment was associated with poor survival or frequent relapse in NPC patients. Residual EBV DNA load after primary treatment could be a useful indicator to justify adjuvant chemotherapy. The qPCR test might also be applied to define a poor prognostic group in patients at early stage (I/II) for implementing concurrent chemo-radiotherapy (chemo-RT) to improve patients' outcome. The test is also useful to monitor distant metastases or response to radiotherapy, chemo-RT or surgery. Supplementary tests, however, are needed to pick up EBV negative WHO type I NPC and test improvement is needed to increase sensitivity in detecting stage I disease and local recurrence.

Male breast cancer: a population-based comparison with female breast cancer in Hong Kong, Southern China: 1997-2006.

BACKGROUND: Male 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. METHODS: A 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. RESULTS: Mean age at diagnosis of male and female patients was 64.5 and 52.7 years 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 81.4 % respectively. Male patients had poorer OS at early overall stage but better breast-cancer-specific mortality rates at any age (p < 0.01). 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. CONCLUSIONS: Chinese male breast cancer patients tend to have poorer OS but better breast-cancer-specific survival compared with their female counterparts.

Incidence, mortality, and survival trends of ovarian cancer in Hong Kong, 1997 to 2006: a population-based study.

OBJECTIVES: To assess the incidence and mortality of ovarian cancer, and the survival patterns of the invasive epithelial ovarian carcinoma in Hong Kong based on population-based cancer registry data. DESIGN: Historical cohort study. SETTING: Hong Kong. PATIENTS: All patients with ovarian cancer diagnosed between 1997 and 2006 were included. Patients eligible for survival analysis were followed up until 31 December 2007. MAIN OUTCOME MEASURES: Age-standardised incidence and mortality rates with their estimated annual percent changes were determined. Cumulative observed and relative survival rates were estimated using a period approach. RESULTS: During the study period, in Hong Kong there was a steadily increasing ovarian cancer incidence rate (1.4% annually) but a steadily decreasing mortality rate (1.9% annually). The improvement in mortality was mainly in the age-group of 50-69 years (4.7% annually). Invasive epithelial ovarian carcinoma accounted for 79.6% of the study cohort. The 2-year and 5-year relative survival rates were 75.8% and 63.1%, respectively. Those diagnosed in the period 2002 to 2006 had significantly better survival than those diagnosed in the period 1997 to 2001 (65.3% vs 60.7%; P=0.008); a significant improvement was evident for patients with stage II disease and in the age-group of 50-69 years. Multivariate analyses confirmed that age, histological subtype, FIGO stage, and the period of diagnosis were independent prognostic indicators of invasive epithelial ovarian carcinoma. CONCLUSION: In Hong Kong, invasive epithelial ovarian carcinoma showed an increasing incidence and an improving survival trend over the period 1997 to 2006. The survival data derived from this study provides a baseline from which to monitor the effectiveness of ovarian cancer treatment in Hong Kong.

Early data from the first population-wide breast cancer-specific registry in Hong Kong.

BACKGROUND: Current measures for breast cancer prevention and options for treatment adopted in Hong Kong are mainly based on research data and clinical evidence from overseas. It is essential to establish a cancer-specific registry to monitor the status of breast cancer in Hong Kong. OBJECTIVES: We summarized the current status of breast cancer in Hong Kong based on the data collected from Hong Kong Breast Cancer Registry (HKBCR). METHODS: Prevalent and newly diagnosed breast cancers (including in situ and invasive breast cancers) were registered in the HKBCR. Information on patient demographics, risk factors, medical information, and survival were analyzed and reported in this study. RESULTS: Data of 2,330 breast cancer patients were analyzed. We observed an earlier median age at diagnosis in Hong Kong than those reported in other countries. Distribution of cancer stage was: stage 0 (11.4%), stage I (31.4%), stage II (41%), stage III (12.5%), stage IV (0.8%), and unclassified (2.9%). The percentages of patients who received surgery, chemotherapy, radiation therapy, and endocrine therapy were 98.7, 67.9, 64.8, and 64.1%, respectively. At a median follow-up of 1.2 years, locoregional recurrence was recorded at 2%, distant recurrence at 2.8%, and breast-cancer-related mortality at 0.3%. CONCLUSIONS: The HKBCR serves as a surveillance program to monitor disease and treatment patterns. It is pivotal to support research for more effective breast cancer prevention and treatment strategies in Hong Kong.

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.

BACKGROUND: Cancer 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. METHODS: A 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 5 years were estimated by the Kaplan-Meier method and stage-specific relative survival rates were calculated. RESULTS: A 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 84 months. A total of 47.4% were diagnosed with breast cancer at age 49 years 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 5 years were 84%, 85.2%, and 81.2%, respectively. DISCUSSION: We 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.

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

BACKGROUND: To evaluate prognostic factors that may influence local control (LC) of T1N0 glottic cancer treated by primary radiotherapy (RT) with 6 MV photons. METHODS: We 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. RESULTS: The 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). CONCLUSIONS: The 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.

A population-based analysis of incidence, mortality, and stage-specific survival of cervical cancer patients in Hong Kong: 1997-2006.

OBJECTIVES: To determine the trends in incidence and mortality of cervical cancer patients diagnosed during 1997 to 2006, and to describe stage-specific survival using population-based cancer registry data. DESIGN: Retrospective, population-based study. SETTING: Hong Kong. PATIENTS: All patients diagnosed with cervical cancer between 1997 and 2006. Patients eligible for survival analysis were followed up till 31 December 2007. MAIN OUTCOME MEASURES: Age-standardised incidence and mortality rates and average annual percent changes in these parameters were calculated using the Poisson regression model. Survival was expressed as relative survival rate using a period approach. Hazard ratios of mortality including 95% confidence intervals for certain variables were estimated using the Cox proportional hazards model. RESULTS: During the 10-year period of the study, overall annual incidence and mortality rates decreased by 4.2% and 6.0%, respectively. Significant rates of reduction were observed in all age-groups except those younger than 45 years. The reduction in incidence of squamous cell carcinoma (3.6% annually) was less than that of adenocarcinoma (5.2%) and other histological types (6.8%). In all, 3807 (86.4%) of the patients were included in survival analysis. The overall 5-year relative survival rate was 71.3% (95% confidence interval, 69.5-73.1%), while the values for stages I, II, III, and IV were 90.9%, 71.0%, 41.7%, and 7.8%, respectively. Age, stage, and histology were independent prognostic factors. Survival of stage IA patients was as good as that of the general population. CONCLUSIONS: As in other industrialised countries, the incidence and mortality rate of cervical cancer were decreasing. Stage-specific population-based cancer survival was available for the first time, and was useful as an indicator of cancer control. Collaboration between public and private sectors to further improve the follow-up data could provide more comprehensive surveillance information.

Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma.

BACKGROUND: Current practice of adding concurrent-adjuvant chemotherapy to radiotherapy (CRT) for treating advanced nasopharyngeal carcinoma is based on the Intergroup-0099 Study published in 1998. However, the outcome for the radiotherapy-alone (RT) group in that trial was substantially poorer than those in other trials, and there were no data on late toxicities. Verification of the long-term therapeutic index of this regimen is needed. METHODS: Patients with nonkeratinizing nasopharyngeal carcinoma staged T1-4N2-3M0 were randomly assigned to RT (176 patients) or to CRT (172 patients) using cisplatin (100 mg/m(2)) every 3 weeks for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m(2)) plus fluorouracil (1000 mg per m(2) per day for 4 days) every 4 weeks for three cycles. Primary endpoints included overall failure-free rate (FFR) (the time to first failure at any site) and progression-free survival. Secondary endpoints included overall survival, locoregional FFR, distant FFR, and acute and late toxicity rates. All statistical tests were two-sided. RESULTS: The two treatment groups were well balanced in all patient characteristics, tumor factors, and radiotherapy parameters. Adding chemotherapy statistically significantly improved the 5-year FFR (CRT vs RT: 67% vs 55%; P = .014) and 5-year progression-free survival (CRT vs RT: 62% vs 53%; P = .035). Cumulative incidence of acute toxicity increased with chemotherapy by 30% (CRT vs RT: 83% vs 53%; P < .001), but the 5-year late toxicity rate did not increase statistically significantly (CRT vs RT: 30% vs 24%; P = .30). Deaths because of disease progression were reduced statistically significantly by 14% (CRT vs RT: 38% vs 24%; P = .008), but 5-year overall survival was similar (CRT vs RT: 68% vs 64%; P = .22; hazard ratio of CRT = 0.81, 95% confidence interval = 0.58 to 1.13) because deaths due to toxicity or incidental causes increased by 7% (CRT vs RT: 1.7% vs 0, and 8.1% vs 3.4%, respectively; P = .015). CONCLUSIONS: Adding concurrent-adjuvant chemotherapy statistically significantly reduced failure and cancer-specific deaths when compared with radiotherapy alone. Although there was no statistically significant increase in major late toxicity, increase in noncancer deaths narrowed the resultant gain in overall survival.

Method of regulatory network that can explore protein regulations for disease classification.

OBJECTIVE: To develop regulatory network to explore and model the regulatory relationships of protein biomarkers and classify different disease groups. METHODS: Regulatory network is constructed to be a hopfield-like network with nodes representing biomarkers and directional connections to be regulations in between. The input to the network is the measured expression levels of biomarkers, and the output is the summation of regulatory strengths from other biomarkers. The network is optimized towards minimizing the energy function that is defined as the measure of the disagreement between the input and output of the network. To simulate more complicated regulations, a sigmoid kernel function is imposed on each node to construct a non-linear regulatory network. RESULTS: Two datasets have been used as test beds, one dataset includes patients of nasopharyngeal carcinoma with different responses to chemotherapy drug, and the other consists of patients of severe acute respiratory syndrome, influenza, and control normals. The regulatory networks among protein biomarkers were reconstructed for different disease conditions in each dataset. We demonstrated our methods have better classification capability when comparing with conventional methods including Fisher linear discriminant (FLD), K-nearest neighborhood (KNN), linear support vector machines (linSVM) and radial basis function based support vector machines (rbfSVM). CONCLUSION: The derived networks can effectively capture the unique regulatory patterns of protein markers associated with different patient groups and hence can be used for disease classification. The discovered regulation relationships can potentially provide insights to revealing the molecular signaling pathways. In this paper, a novel technique of regulatory network is proposed on purpose of modeling biomarker regulations and classifying different disease groups. The network is composed of a certain number of nodes that are directionally connected in between in which nodes denote predictors and connections to be the regulation relationship. The network is optimized towards minimizing its energy function with biomarker expression data acquired from a specific patient group, thus the optimized network can model the regulatory relationship of biomarkers under the same circumstance. To simulate more complicated regulations, a sigmoid kernel function is imposed on each node to construct a non-linear regulatory network. The regulatory network can extract unique features of each disease condition, thus one immediate application of regulatory network is to classifying different diseases. We demonstrated that regulatory network is capable of performing disease classification through comparing with conventional methods including FLD, KNN, linSVM and rbfSVM on two protein datasets. We believe our method is promising in mining knowledge of protein regulations and be powerful for disease classification.

Understanding sociohistorical imprint on cancer risk by age-period-cohort decomposition in Hong Kong.

BACKGROUND: Research on trends in cancer incidence has usually examined single sites in populations that long ago completed the economic transition. The trends in 11 cancers in three groups in the recently transitioned Hong Kong Chinese population were examined to delineate the effects of economic transition and provide generalised aetiological insights. METHODS: Sex-specific Poisson models were fitted to cancer incidence in Hong Kong (1974-2003) to examine age, period and birth cohort effects. Cancers were grouped as: hormonally modulated (including breast, endometrium, ovary and prostate), infection-related (cervix, liver, nasopharynx, lymphoma and stomach) and lifestyle-related (colorectum and lung). RESULTS: Age-standardised incidence of hormonally modulated female cancers increased for the first generation (women born approximately 1940) to experience puberty in the transitioning environment of Hong Kong. Prostate cancer incidence increased, despite a downturn for the first generation growing up in Hong Kong. Incidence of infection-related cancers decreased, mainly due to birth cohort effects; coinciding with birth for liver cancer and lymphoma, with reaching adulthood for cervical and male nasopharyngeal cancers, and with a generation for stomach cancer. Lifestyle-related cancers had sex-specific declines by birth cohort. CONCLUSION: With economic transition and the associated lifestyle changes, environmentally determined levels of pubertal female hormones may drive intergenerational increases in hormonally related female cancers. Economic development, via improved living conditions, may also reduce infection-related cancers, possibly including prostate cancer; however, the effects depend on transmission dynamics and perhaps specific public health initiatives. In traditional societies, males may benefit from economic development sooner than females.

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

BACKGROUND: Population-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. METHODS: Survival 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. FINDINGS: For 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. INTERPRETATION: The 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. FUNDING: Association 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).

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.

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). STUDY DESIGN AND METHODS: A single-institution retrospective analysis was performed to review patients with TCV and the usual type of PTC diagnosed from 1960 to 2000. RESULTS: Fourteen of 1,108 patients (median follow-up, 8.9 yr) diagnosed with PTC had TCV. Ten were female, and four were male, with a mean age of 53.7 (33-81) years. All were ethnic Chinese. Compared with the usual PTC cohort, TCV patients presented at an older age (mean, 53.7 vs. 45.2 yr; P = .015). They had a higher rate of extrathyroidal extension (78.6% vs. 43.4%, P = .009), tracheal invasion (28.6% vs. 9%, P = .034), and carotid vessel invasion (14.3% vs. 1.5%, P = .021). TCV patients had more frequent gross (42.9% vs. 17.2%) and microscopic (14.3% vs. 6%) postoperative locoregional residual disease (P = .008). They also had a higher percentage of stage III and IV disease (American Joint Committee on Cancer, 6th ed) (74.3% vs. 31.3%, P = .009). Ten-year local failure-free, regional failure-free, and metastasis-free survival were worse in the TCV group (78.6% vs. 88.8%. P = .017; 53.0% vs. 85.9%, P < .0001; 35.7% vs. 92.1%, P < .0001, respectively). The 10-year cause-specific survival was also lower in TCV patients (48.2% vs. 93.4%, P < .0001). CONCLUSION: TCV presents at a higher stage with more advanced local disease. It has a higher risk of locoregional and distant relapse and a worse overall survival rate. Stratification by stage reveals that TCV has significantly higher mortality compared with PTC for stage IV disease. Aggressive treatment and close follow-up of these patients is necessary.

Deep proteome profiling of sera from never-smoked lung cancer patients.

Previous studies on the serum proteome are hampered by the huge dynamic range of concentration of different protein species. The use of Equalizer Beads coupled with a combinatorial library of ligands has been shown to allow access to many low-abundance proteins or polypeptides undetectable by classical analytical methods. This study focused on never-smoked lung cancer, which is considered to be more homogeneous and distinct from smoking-related cases both clinically and biologically. Serum samples obtained from 42 never-smoked lung cancer patients (28 patients with active untreated disease and 14 patients with tumor resected) were compared with those from 30 normal control subjects using the pioneering Equalizer Beads technology followed by subsequent analysis by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Eighty-five biomarkers were significantly different between lung cancer and normal control. The application of classification algorithms based on significant biomarkers achieved good accuracy of 91.7%, 80% and 87.5% in class-prediction with respect to presence or absence of disease, subsequent development of metastasis and length of survival (longer or shorter than median) respectively. Support vector machine (SVM) performed best overall. We have proved the feasibility and convenience of using the Equalizer Beads technology to study the deep proteome of the sera of lung cancer patients in a rapid and high-throughput fashion, and which enables detection of low abundance polypeptides/proteins biomarkers. Coupling with classification algorithms, the technologies will be clinically useful for diagnosis and prediction of prognosis in lung cancer.

Staging systems for papillary thyroid carcinoma: a study of 2 tertiary referral centers.

OBJECTIVE: To find out the most applicable and consistent staging system for papillary thyroid carcinoma (PTC) available in the literature. BACKGROUND: The commonly used staging systems for PTC have predicted cancer-specific survival (CSS) well. However, their applicability and generalizability have not yet been evaluated in different clinical settings. METHODS: A MEDLINE search from 1965 to 2005 was carried out to identify different staging systems available in the literature and 9 systems were applicable to 1634 PTC patients within 2 tertiary-referral centers. The CSS of each staging system within individual centers were calculated using Kaplan-Meier method and the CSS of each tumor stage in one individual center was compared with that of the other by log-rank test. In addition, within each center, the predictability of each staging system relative to the others was ranked based on the proportion of variation explained (PVE) value. RESULTS: Clinicopathologic features, treatment received, and tumor stages were significantly different between the 2 centers. There were also significant differences in CSS within at least one tumor stage between the 2 centers in 8 of the 9 staging systems. The TNM was a highly predictive and consistent staging system within the 2 centers. Although the absolute PVE values differed between the 2 centers, the relative ranking of the 9 staging systems within each center correlated significantly to each other (P < 0.05). CONCLUSIONS: Despite referral, treatment, and data collection biases inherent within each center, the TNM system remained to be the most applicable and consistent staging system for PTC in 2 centers managing the same population group.

ProteinChip array profiling for identification of disease- and chemotherapy-associated biomarkers of nasopharyngeal carcinoma.

BACKGROUND: We previously used ProteinChip array profiling analysis to discover a serum biomarker associated with nasopharyngeal carcinoma (NPC). In this study, we used the same method to examine other biomarkers associated with NPC and response to chemotherapy (CT) in NPC patients. METHODS: We performed ProteinChip array analysis in 209 serum samples from 66 relapsed patients before and after salvage CT with gemcitabine and cisplatin or etoposide and cisplatin combinations, 11 patients in remission, and 35 healthy individuals. Intensities of the biomarker peaks were correlated with CT response of the patients and other clinical parameters. RESULTS: We discovered 13 candidate biomarkers associated with different clinical parameters. Two biomarkers (2803 and 3953 Da) were significantly increased in patients compared with controls at all stages of disease. Analysis of pre- and post-CT paired serum samples revealed 7 biomarkers correlated with impact of CT. Of these 7 biomarkers, 2 (2509 and 2756 Da) were significantly increased and 5 (7588, 7659, 7765, 7843, and 8372 Da) were significantly decreased post-CT in either 1 or both CT cohorts. Four biomarkers from pre-CT sera were correlated with CT response, with 3 (2950, 13 510, and 14 855 Da) being significantly decreased and 1 (6701 Da) significantly increased in patients who did not respond to CT. Tandem mass spectrometric sequencing and/or immunoaffinity capture assay identified the 3953 Da biomarker as a fragment of interalpha-trypsin inhibitor precursor and 7765 Da biomarker as platelet factor-4. CONCLUSIONS: Treatment-associated serum biomarkers found might serve to triage NPC patients for appropriate CT treatment.

Local and regional control in patients with papillary thyroid carcinoma: specific indications of external radiotherapy and radioactive iodine according to T and N categories in AJCC 6th edition.

To identify indications for external radiotherapy (EXT) and radioactive iodine (RAI) in papillary thyroid carcinoma (PTC), we conducted a retrospective study of local and regional control in 1297 patients diagnosed with PTC in a tertiary referral center. Managed by surgery alone, patients with bilateral thyroidectomy had a lower rate of local relapse compared with lobectomy (P=0.02). EXT improved locoregional (LR) failure-free survival (FFS) (P<0.001) and survival (P=0.01) in patients with gross postoperative LR residual disease. EXT also improved local FFS in patients with pathologically confirmed positive resection margins (P<0.001) and reduced local failures in patients with T4 disease (P=0.002). In patients with lymph nodes (LN) metastasis, more extensive surgery by functional or radical neck dissection resulted in less LN relapse compared with excision alone (P<0.001). EXT improved 10-year LN FFS in patients with N1b disease (P=0.005) and patients with LN metastasis of size>2 cm (P=0.02). RAI was effective in improving local control in patients with T2 to T4 diseases and LN control in patients with N0, N1a, and N1b categories. Local or LN relapses were associated with worse survival (P<0.001 and P<0.0001). The survival of patients with PTC could be improved by reducing local or LN relapses. RAI is indicated in patients with T2 to T4 disease. EXT is indicated in patients with gross postoperative disease, positive resection margins or T4 disease, N1b, or a LN size of >2 cm. LN relapse can be reduced by RAI in N0, N1a, and N1b disease.

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. STUDY DESIGN: Seventy-eight patients with DTC and history of radioactive iodine (RAI) ablation were prospectively recruited. They completed the Functional Assessment of Cancer Treatment-General (FACT-G) questionnaire on weeks 0, 2, and 4 after T4 withdrawal with corresponding checking of serum thyroid-stimulating hormone (TSH). RESULTS: Overall, 74.5% (58 of 78) of patients completed all FACT-G. Comparing FACT-G scores at weeks 0 and 4, "physical" (P < .001), "social" (P = .04), and "emotional" (P = .047) aspects were lowered as well as "total" HR-QOL (P = .001). However, the "functional" domain of HR-QOL was not affected (P = .14). Comparing FACT-G scores at week 0 and 2, we found that "physical" (P = .049) and "total" (P = .05) HR-QOL were affected early (in the first 2 weeks) in T4 withdrawal. Comparison of week 2 and 4 showed that in the later half of the withdrawal period, "physical" (P = .001), "emotional" (P = .02), and "total" FACT-G scores (P = .002) were affected. Mean TSH level (in mIU/L) increased gradually: 2.8 (week 0), 42.8 (week 2), 97 (week 3), and 153 (week 4). The percentage of patients attaining TSH level of >30 mIU/L were 55% (week 2), 96.2% (week 3), and 100% (week 4). CONCLUSIONS: HR-QOL declines with time of T4 withdrawal. The impact is more severe in the later period of T4 withdrawal. In 3 weeks, 96.2% of our patients attained TSH level of 30 mIU/L. To minimize the impact on HR-QOL, duration of T4 withdrawal can be decreased to 3 weeks.