First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis.

BACKGROUND: Guidelines recommend atezolizumab plus nab-paclitaxel (A + nP) for first-line treatment of unresectable, locally advanced, or metastatic triple-negative breast cancer expressing programmed death-ligand 1 (PD-L1) on tumor-infiltrating immune cells (IC), based on IMpassion130. We report the final overall survival (OS) and safety of that study as per the prespecified analysis plan. PATIENTS AND METHODS: Patients were randomized to nP 100 mg/m2 (days 1, 8, and 15 of a 28-day cycle) with atezolizumab 840 mg (A + nP) or placebo (P + nP; days 1 and 15), until progression or unacceptable toxicity. Coprimary endpoints were progression-free survival [intention-to-treat (ITT) and PD-L1 IC-positive populations] and OS (tested hierarchically in the ITT population and, if significant, in the PD-L1 IC-positive population). RESULTS: Each arm comprised 451 patients; 666 (73.8%) had died by the final OS analysis cut-off (median follow-up, 18.8 months; interquartile range, 8.9-34.7 months). Median OS in the ITT population was 21.0 months [95% confidence interval (CI), 19.0-23.4 months] with A + nP, and 18.7 months (95% CI, 16.9-20.8 months) with P + nP [stratified hazard ratio (HR), 0.87; 95% CI, 0.75-1.02; P = 0.077]. Exploratory analysis in the PD-L1 IC-positive population showed a median OS of 25.4 months (95% CI, 19.6-30.7 months) with A + nP (n = 185) and 17.9 months (95% CI, 13.6-20.3 months) with P + nP (n = 184; stratified HR, 0.67; 95% CI, 0.53-0.86). Safety outcomes were consistent with previous analyses and the known toxicity profiles of each agent. Immune-mediated adverse events of special interest were reported in 58.7% and 41.6% of patients treated with A + nP and P + nP, respectively. CONCLUSION: Although the OS benefit in the ITT population was not statistically significant, precluding formal testing, clinically meaningful OS benefit was observed with A + nP in PD-L1 IC-positive patients, consistent with prior interim analyses. This combination remained safe and tolerable with longer follow-up.

Machine learning and treatment outcome prediction for oral cancer.

BACKGROUND: The natural history of oral squamous cell carcinoma (OSCC) is complicated by progressive disease including loco-regional tumour recurrence and development of distant metastases. Accurate prediction of tumour behaviour is crucial in delivering individualized treatment plans and developing optimal patient follow-up and surveillance strategies. Machine learning algorithms may be employed in oncology research to improve clinical outcome prediction. METHODS: Retrospective review of 467 OSCC patients treated over a 19-year period facilitated construction of a detailed clinicopathological database. 34 prognostic features from the database were used to populate 4 machine learning algorithms, linear regression (LR), decision tree (DT), support vector machine (SVM) and k-nearest neighbours (KNN) models, to attempt progressive disease outcome prediction. Principal component analysis (PCA) and bivariate analysis were used to reduce data dimensionality and highlight correlated variables. Models were validated for accuracy, sensitivity and specificity, with predictive ability assessed by receiver operating characteristic (ROC) and area under the curve (AUC) calculation. RESULTS: Out of 408 fully characterized OSCC patients, 151 (37%) had died and 131 (32%) exhibited progressive disease at the time of data retrieval. The DT model with 34 prognostic features was most successful in identifying "true positive" progressive disease, achieving 70.59% accuracy (AUC 0.67), 41.98% sensitivity and a high specificity of 84.12%. CONCLUSION: Machine learning models assist clinicians in accessing digitized health information and appear promising in predicting progressive disease outcomes. The future will see increasing emphasis on the use of artificial intelligence to enhance understanding of aggressive tumour behaviour, recurrence and disease progression.

Patient-reported outcomes from the phase III IMpassion130 trial of atezolizumab plus nab-paclitaxel in metastatic triple-negative breast cancer.

BACKGROUND: Metastatic triple-negative breast cancer (mTNBC) is incurable. A key treatment goal is providing palliation while maintaining patients' health-related quality of life (HRQoL). IMpassion130 demonstrated progression-free survival benefit with atezolizumab + nab-paclitaxel (A + nP) versus placebo + nab-paclitaxel (Pl + nP) in first-line treatment of mTNBC patients with programmed death-ligand 1 positive (PD-L1+) tumors. We report data on patient-reported outcomes (PROs), which capture patient perspectives of treatment. PATIENTS AND METHODS: Patients with untreated advanced or mTNBC received atezolizumab (840 mg) or placebo every 2 weeks in combination with nab-paclitaxel (100 mg/m2) on days 1, 8, and 15 of each 28-day cycle until progression or intolerance. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and its Breast Cancer Module (QLQ-BR23) on day 1 of each cycle, at end of treatment, and every 4 weeks during 1 year of follow-up. Time-to-deterioration (TTD) in HRQoL (first ≥10-point decrease from baseline lasting two cycles) was a secondary end point. Exploratory end points included TTD in functioning and mean and mean change from baseline scores in HRQoL, functioning, and disease- and treatment-related symptoms. RESULTS: Baseline completion of PROs was 92% (QLQ-C30) and 89% (QLQ-BR23) and remained >80% through cycle 20 in intent-to-treat (ITT) and PD-L1+ patients. No differences between arms in median TTD in PD-L1+ patients were observed for HRQoL {hazard ratio (HR) 0.94 [95% confidence interval (CI) 0.69-1.28]} or physical [HR 1.02 (95% CI 0.76-1.37)] or role [HR 0.77 (95% CI 0.57-1.04)] functioning. Mean baseline scores for A + nP versus Pl + nP for HRQoL (67.5 versus 65.0) and physical (82.8 versus 79.4) and role (73.7 versus 71.7) functioning were comparable between arms and throughout the course of treatment, with no clinically meaningful (≥10 point) changes from baseline until patients discontinued treatment. No differences in clinically meaningful worsening in treatment symptoms (fatigue, diarrhea, or nausea/vomiting) were observed between arms. Results in ITT patients were similar. CONCLUSIONS: A + nP as first-line treatment for mTNBC delayed progression without compromising patients' day-to-day functioning or HRQoL or worsening treatment symptoms. CLINICALTRIAL. GOV IDENTIFIER: NCT02425891.

Photo-induced charge density distribution in metal surfaces and its extraction with apertureless near-field optics.

Electromagnetic (EM) waves impinging on finite metallic structures can induce non-uniform electrical currents and create oscillating charge densities. These local charges govern the important physical processes such as plasmonic behavior or enhanced Raman scattering. Yet the quantitative calculation and probing of the spatial distribution of the charge density still remain challenging at the subwavelength scale. This is especially the case if one considers the boundary effect, where the charge density can become divergent and conventional finite element methods fail to obtain accurate information. With an approach we recently developed, we calculate this charge density for subwavelength structures with and without sharp corners: gold disks and equilateral triangles. We also devise an independent way to extract the surface charge density distributions from experiments using scattering-type scanning near-field optical microscope (s-SNOM). We found that the charge density [Formula: see text] is related to the near field signal S n by [Formula: see text] With no adjustable parameters, the extracted surface charge distribution from the experiments matches well with that from the theoretical prediction, both in magnitude and phase. Our work provides a quantitative study of the surface charge distributions and a systematic and rigorous treatment to extract surface charge distributions at the nanoscale, opening opportunities for mining the near-field data from s-SNOM.

Adventure-based training to promote physical activity and reduce fatigue among childhood cancer survivors: A randomized controlled trial.

BACKGROUND: Cancer-related fatigue is one of the most distressing symptoms reported by childhood cancer survivors. Despite the body of evidence that regular physical activity helps alleviate cancer-related fatigue, insufficient participation in physical activity is frequently observed among childhood cancer survivors. OBJECTIVES: This study examined the effectiveness of an adventure-based training programme in promoting physical activity, reducing fatigue, and enhancing self-efficacy and quality of life among Hong Kong Chinese childhood cancer survivors. DESIGN: A prospective randomised controlled trial. SETTINGS: A paediatric oncology outpatient clinic, a non-governmental organisation, and a non-profit voluntary organisation. PARTICIPANTS: Hong Kong Chinese childhood cancer survivors aged 9-16 years who reported symptoms of fatigue and had not engaged in regular physical exercise in the past 6 months. METHODS: The experimental group underwent a 4-day adventure-based training programme. The control group received a placebo intervention. The primary outcome was fatigue at 12 months. Secondary outcomes were physical activity levels, self-efficacy and quality of life at 12 months. Data collection was conducted at baseline, and 6 and 12 months after the intervention began. We performed intention-to-treat analyses. RESULTS: From 6 January, 2014 to 8 June, 2015, we randomly assigned 222 eligible childhood cancer survivors to either an experimental (n = 117) or a control group (n = 105). The experimental group showed statistically significantly lower levels of cancer-related fatigue (P < 0.001), higher levels of self-efficacy (P < 0.001) and physical activity (P < 0.001), and better quality of life (P < 0.01) than the control group at 12 months. CONCLUSIONS: This study provides evidence that adventure-based training is effective in promoting physical activity, reducing cancer-related fatigue, and enhancing self-efficacy and quality of life among Hong Kong Chinese childhood cancer survivors. These results may help inform parents and healthcare professionals that regular physical activity is crucial for the physical and psychological wellbeing and quality of life of childhood cancer survivors.

Transcatheter aortic valve implantation: initial experience in Hong Kong.

INTRODUCTION: Aortic stenosis is one of the most common valvular heart diseases in the ageing population. Patients with symptomatic severe aortic stenosis are at high risk of sudden death. Surgical aortic-valve replacement is the gold standard of treatment but many patients do not receive surgery because of advanced age or co-morbidities. Recently, transcatheter aortic valve implantation has been developed as an option for these patients. This study aimed to assess efficacy and safety of this procedure in the Hong Kong Chinese population. METHODS: Data for baseline patient characteristics, procedure parameters, and clinical outcomes up to 1-year post-implantation in a regional hospital in Hong Kong were collected and analysed. RESULTS: A total of 56 patients with severe aortic stenosis underwent the procedure from December 2010 to September 2015. Their mean (± standard deviation) age was 81.9 ± 4.8 years; 64.3% of them were male. Their mean logistic EuroSCORE was 22.6% ± 13.4%. After implantation, the mean aortic valve area improved from 0.70 cm2 ± 0.19 cm2 to 1.94 cm2 ± 0.37 cm2. Of the patients, 92% were improved by at least one New York Heart Association functional class. Stroke and major vascular complications occurred in one (1.8%) and five (8.9%) patients, respectively. A permanent pacemaker was implanted in seven (12.5%) patients. Both hospital and 30-day mortalities were 1.8%. The 1-year all-cause and cardiovascular mortality rates were 12.5% and 7.1%, respectively. CONCLUSIONS: Transcatheter aortic valve implantation has been developed as an alternative treatment for patients with symptomatic severe aortic stenosis who are deemed inoperable or high risk for surgery. Our results are very promising and comparable with those of major clinical trials.

Scattering of electromagnetic waves from surfaces with conformal mapping: An example of a triangular plate.

We discuss a way to exploit conformal mapping to study the response of a finite metallic film of arbitrary shape to an external electromagnetic field at finite frequencies. This provides a simple way to understand different physics issues and provides insights that include the issue of vorticity and eddy current and the nature of the divergent electric field at the boundaries and at corners. We study an example of an equilateral triangular plate and find good agreement with results obtained with traditional numerical techniques.

Psychometric properties of the Chinese version of the fatigue scale-adolescent.

BACKGROUND: The availability of a valid and reliable instrument that accurately assesses the level of fatigue among adolescent cancer survivors is crucial before any appropriate interventions to reduce their fatigue can be appropriately planned and evaluated. The study aimed to test the psychometric properties of the Chinese version of the Fatigue Scale for Adolescents. In particular, confirmatory factor analysis was conducted to examine its factorial structure. METHODS: A cross-sectional study was employed. Adolescents (13- to 18-year-olds) who had survived cancer and attended medical follow-up at the outpatient clinic in Hong Kong were invited to participate. The internal consistency, content validity and construct validity and test-retest reliability of the Chinese version of the Fatigue Scale for Adolescents were assessed. RESULTS: The content validity index was 0.92. There was a strong positive correlation between adolescents' levels of fatigue and depressive symptoms (r = 0.53) and a strong negative correlation between adolescents' levels of fatigue and quality of life (r = -0.58). The mean levels of fatigue of the survivors group was significantly lower than that of those still receiving treatment in hospital, but significantly higher than that of their healthy counterparts. Confirmatory factor analysis indicated that there were 4 factors underlying the Chinese version of the Cancer Module. CONCLUSIONS: The findings of the study add further evidence that the Chinese version of the Fatigue Scale for Adolescents (12-item) can be used as a reliable and valid tool in assessing cancer-related fatigue among Hong Kong Chinese adolescents who have survived cancer.

Resonances and circuit theory for the interaction of metallic disks and annuli with an electromagnetic field.

To understand the nature of the electromagnetic resonances of finite metallic surfaces, we formulate a rigorous and rapidly convergent circuit theory for the interaction of a metallic disk and a metallic annulus with an electromagnetic field. Expressions for the current induced and the resonance condition are derived. A new understanding of the nature of the resonances is obtained. For half of the resonances we find a divergent electric field at the edge of the disk, even though it is smooth in shape. For the disk, we compare with previous results using vector spheroidal wave functions and found good agreement for the resonance condition. Our approach can be generalized to other finite surfaces.

Entangled transverse optical vortex.

We discuss a new kind of optical vortex with the angular momentum perpendicular to the flow direction and entangled in that it is a coherent combination of different orbital angular momentum states of the same sign. This entangled state exhibits many unexpected physical properties. The transverse optical vortex can be generated from the reflection of an electromagnetic wave off an array of ferrite rods. Its vorticity can be reversed by switching the direction of the magnetization of the rods, which usually takes only a nanosecond.

Multiple flat photonic bands with finite Chern numbers.

We show both analytically and numerically that there is an infinite number of flat bands with different Chern numbers in a two-dimensional magnetic photonic crystal at nearly the same frequency determined by the condition that the effective magnetic permeability µ_{eff}≈-1. This opens the door to explore the physics involving higher order topological invariants in this system. The frequency of these states can be flexibly tuned by an external magnetic field.

Nearly total omnidirectional reflection by a single layer of nanorods.

It is shown that a single-layer array of high electric permittivity (high-ε) rods with a radius smaller than λ/10 is capable of reflecting more than 97% of the energy of optical waves with an arbitrary incident angle. Here, λ is the incident wavelength. The occurrence of the phenomenon depends on the construction of two particular grating modes (GMs) in the array which result in two corresponding transmitted wave components that cancel each other. The construction of the dominant GMs in the array benefits from the highly independent manipulability of the angular momenta components with opposite signs in high-ε particles. The effect offers the possibility to improve the optical elements integration level in on-chip optical circuits.

Study of heavy metal poisoning in frequent users of Chinese medicines in Hong Kong and Macau.

This study is a direct assessment of blood heavy metal concentrations of frequent users of Chinese medicines (CM), who had been taking prescribed CM at least 6 days per week for not less than 3 months, to determine whether their intake of CM could cause an increased load of toxic heavy metals in the body. From November 2009 to June 2010, 85 subjects were recruited with informed consent, and their blood samples were collected for measurement of arsenic, cadmium, lead and mercury concentrations. Results showed that blood concentrations of four heavy metals of nearly all 85 subjects were within reference ranges. Only one subject who had consumed plentiful seafood was found to have transiently increased blood arsenic concentration (29% higher than the upper limit of the reference range). However, after refraining from eating seafood for 1 month, his blood arsenic concentration returned to normal. Eighty commonly prescribed CM in both raw medicine and powder concentrate supplied by local distributors were also tested for the four heavy metals. Twelve out of the 80 raw medicines were found to contain one or more of the heavy metals that exceeded the respective maximum permitted content. Cadmium was most frequently found in the contaminated samples. None of the powder concentrates had heavy metal content exceeding their respective maximum permitted level.

Serum small-dense LDL abnormalities in chronic renal disease patients.

Cardiovascular disease (CVD) is the principal cause of mortality in chronic kidney disease (CKD) patients. Dyslipoproteinaemia is a common metabolic derangement in CKD and a traditional risk factor for CVD. This study investigates serum lipoprotein, especially small-dense low-density lipoprotein (sd-LDL), abnormalities in CKD patients. A total of 131 CKD patients (age: 59 +/- 12 years, male = 64) diagnosed according to Kidney Disease: Improving Global Outcomes, 2004 (KDIGO) and 121 age- and gender-matched control subjects (age: 58 +/- 6 years, male = 62) were recruited from Hong Kong and Macau. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and direct LDL-C were assayed enzymatically. In addition, sd-LDL, together with very low density and intermediate-density lipoproteins (VLDL and IDL) were measured by US Food and Drug Administration (FDA)-approved polyacrylamide gradient gel electrophoresis. Compared to controls, CKD patients showed significantly decreased TC, LDL-C, normal-size LDL and HDL-C with increased TG, VLDL, IDL and sd-LDL (all P < 0.01). The increased sd-LDL and decreased normal-size LDL fractions resulted in a significantly elevated sd-LDL:LDL ratio in CKD (P < 0.005). In contrast to the low TC and LDL-C, sd-LDL and sd-LDL:LDL ratio were significantly elevated in CKD. Thus, sd-LDL will be used increasingly for CVD risk assessment in CKD and other diseases that show lipoprotein derangement.

Human papillomavirus infection in Macau women.

OBJECTIVE: To investigate the prevalence and genotypes of human papillomavirus (HPV) infection in Macau women. STUDY DESIGN: Female patients presenting for a medical consultation or medical check-up were recruited with informed consent. METHODS: Cytology and HPV-DNA genotyping were performed on 402 cervical specimens that were collected from Macau women. RESULTS: Of the specimens, 29.9% were found to be HPV-DNA positive; 26.4% were infected with one HPV genotype, while 3.0% and 0.5% were infected with two and three HPV genotypes, respectively. The most prevalent HPV genotype was type 52 (11.1%), followed by type 16 (9.7%). Both types 51 and 62 ranked third (9.0%). CONCLUSIONS: The HPV infection rate in Macau appears to be higher than that in the neighbouring city of Hong Kong. The most prevalent genotypes were similar to those in South-west and Southern China.

Prevalence of hepatitis B genotype and viral basic core promoter and precore mutations among teenagers in Macao: relationship with hepatocellular carcinoma development.

Chronic hepatitis B virus (HBV) infection is a global problem and over 75% of cases are reported in the Asia Pacific region. Infection can lead to progressive liver disease, cirrhosis and hepatocellular carcinoma (HCC). Previous studies suggest the prevalence of HBV carriers in Macau to be approximately 10% of the population. This study aims to investigate the prevalence of HBV genotypes among HBV-positive teenagers in Macao and the prevalence of base core promoter (BCP) and precore (PreC) mutations in the viral genome. In addition, through monitoring aminotransferase and alpha-fetoprotein, it aims to investigate relationships among HBV genotypes, BCP/PreC mutations and HCC development. This study recruited 1991 teenagers in Macau in 2008, and the PreS1/S2, BCP and PreC region of the HBV genome from 34 HBsAg-positive subjects were amplified and sequenced to determine HBV genotype and presence of HCC-associated mutations. Results suggested that the average rate of HBV infection among secondary school teenagers in Macao is low, and HBV genotype B and C viruses were found to predominate in Macao. The BCP/PreC mutations A1762T, G1764A, G1896A and C1766T were identified in 2.9-11.7% of subjects. However, no significant relationship was observed between HBV genotype, BCP/PreC mutations and HCC development.

Optical beam steering based on the symmetry of resonant modes of nanoparticles.

We report a phenomenon that an optical beam transmits in a negative direction when passing through a single array of high-refractive-index dielectric nanorods. The mechanism of the negative directional transmission is believed to be due to the symmetry of resonant modes in the dielectric nanoparticles. It is expected to find applications in designing compact optical components to achieve the on-chip beam steering in photonic circuits.