Weng Ng

Psychological morbidity and quality of life of ethnic minority patients with cancer: a systematic review and meta-analysis

BACKGROUND Ethnic minority is associated with higher cancer incidence and poorer survival than is being in the majority group. We did a systematic review and meta-analysis to assess whether psychological morbidity and health-related quality of life (HRQoL) were affected by minority status. METHODS We searched Medline, AMED, PsycINFO, Embase, CENTRAL, CINAHL, PubMed, Sociological Abstracts, and Web of Science for English-language articles published between Jan 1, 1995, and October, 2009. Articles were eligible if they reported original data on anxiety, depression, distress (for psychological morbidity), or HRQoL in minority and majority cancer patients or survivors. Minority status was defined as being an immigrant or having an ethnic, linguistic, or religious background different to the majority of the population in the country where the research was done. We excluded African Americans and indigenous groups. Eligible articles were rated for quality of reporting, external validity, internal validity, sample size, and power. Each quality criterion was rated independently by two reviewers until inter-rater reliability was achieved. In a meta-analysis we compared mean scores adjusted for socioeconomic status and other sociodemographic and clinical variables, where available. Effect sizes greater than 0·5 and 95% CI that included 0·5 or -0·5 were deemed clinically important, with negative values indicating worse outcomes in minority patients. We assessed publication bias by estimating the number of potential unpublished studies and the number of non-signficant studies with p=0·05 required to produce a non-significant overall result. FINDINGS We identified 21 eligible articles that included 18 datasets collected in the USA and one in each of Canada, Romania, and the UK. Ethnic minority groups were Hispanic, Asian or Pacific Islander, or Hungarian (one dataset). Overall, we found minority versus majority groups to have significantly worse distress (mean difference -0·37, 95% CI -0·46 to -0·28; p<0·0001), depression (-0·23, -0·36 to -0·11; p=0·0003), and overall HRQoL (-0·33, -0·58 to -0·07; p=0·013). Further analyses found disparities to be specific to Hispanic patients in the USA, in whom poorer outcomes were consistent with potentially clinically important differences for distress (effect size -0·37, 95% CI -0·54 to -0·20; p<0·0001), social HRQoL (-0·45, -0·87 to -0·03; p=0·035), and overall HRQoL (-0·49, -0·78 to -0.20; p=0·0008). Results were significantly heterogeneous for overall HRQoL and all domains. Tests for interaction, for adjusted versus unadjusted and comparisons of high-quality, medium-quality, and low-quality articles, were generally non-significant, which suggests no bias. We found no evidence of any substantive publication bias. INTERPRETATION Hispanic cancer patients in the USA, but not other ethnic minority groups, report significantly worse distress, depression, social HRQoL, and overall HRQoL than do majority patients, of which all but depression might be clinically important. Heterogeneous results might, however, have limited the interpretation. Data for other minority groups and for anxiety are scarce. More studies are needed from outside the USA. Future reports should more clearly describe their minority group samples and analyses should control for clinical and sociodemographic variables known to predict outcomes. Understanding of why outcomes are poor in US Hispanic patients is needed to inform the targeting of interventions. FUNDING Prince of Wales Hospital, Sydney, Australia.

Predictive and prognostic biomarkers for neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Locally advanced rectal cancer is regularly treated with trimodality therapy consisting of neoadjuvant chemoradiation, surgery and adjuvant chemotherapy. There is a need for biomarkers to assess treatment response, and aid in stratification of patient risk to adapt and personalise components of the therapy. Currently, pathological stage and tumour regression grade are used to assess response. Experimental markers include proteins involved in cell proliferation, apoptosis, angiogenesis, the epithelial to mesenchymal transition and microsatellite instability. As yet, no single marker is sufficiently robust to have clinical utility. Microarrays that screen a tumour for multiple promising candidate markers, gene expression and microRNA profiling will likely have higher yield and it is expected that a combination or panel of markers would prove most useful. Moving forward, utilising serial samples of circulating tumour cells or circulating nucleic acids can potentially allow us to demonstrate tumour heterogeneity, document mutational changes and subsequently measure treatment response.

Circulating tumour cells and the epithelial mesenchymal transition in colorectal cancer

Circulating tumour cells (CTCs) hold great potential as liquid biopsies to prognosticate disease and guide treatment in colorectal cancer. However, their emerging role in determining the molecular phenotype of tumour metastasis carries even more promising clinical use in the provision of comprehensive biomarker detection for targeted therapies and determination of drug resistance. The isolation of CTCs is technology dependent, and in the case of epithelial cell adhesion molecule-based platforms, the ability to detect cells that have undergone the epithelial to mesenchymal transition (EMT) is ineffective. CTCs displaying a mesenchymal phenotype are believed to have an increased metastatic potential. The rarity of CTCs provides another challenge in the enumeration of these cells. The future will likely involve the analysis of individual CTCs at any stage of the EMT in order to provide real-time phenotypic and molecular snapshots capable of tracking the dynamic evolution of tumour progression over time.

Upregulated Polo-Like Kinase 1 Expression Correlates with Inferior Survival Outcomes in Rectal Cancer.

Background Human polo-like kinase 1 (PLK1) expression has been associated with inferior outcomes in colorectal cancer. Our aims were to analyse PLK1 in rectal cancer, and its association with clinicopathological variables, overall survival as well as tumour regression to neoadjuvant treatment. Methods PLK1 expression was quantified with immunohistochemistry in the centre and periphery (invasive front) of rectal cancers, as well as in the involved regional lymph nodes from 286 patients. Scores were based on staining intensity and percentage of positive cells, multiplied to give weighted scores from 1–12, dichotomised into low (0–5) or high (6–12). Results PLK1 scores in the tumour periphery were significantly different to adjacent normal mucosa. Survival analysis revealed that low PLK1 score in the tumour periphery had a hazard ratio of death of 0.59 in multivariate analysis. Other predictors of survival included age, tumour depth, metastatic status, vascular and perineural invasion and adjuvant chemotherapy. There was no statistically significant correlation between PLK1 score and histological tumour regression in the neoadjuvant cohort. Conclusion Low PLK1 score was an independent predictor of superior overall survival, adjusting for multiple clinicopathological variables including treatment.

Migrant Health in Cancer: Outcome Disparities and the Determinant Role of Migrant-Specific Variables

BACKGROUND Multiethnic societies face challenges in delivering evidence-based culturally competent health care. This study compared health-related quality of life and psychological morbidity in a hospital-based sample of first-generation migrants and Australian-born Anglo cancer patients, controlling for potential confounders related to migrant status. Further, it explored the relative contribution of ethnicity versus migrant-related variables. METHODS Eligible participants, recruited via 16 oncology clinics in Australia, included those over the age of 18, diagnosed with cancer (any type or stage) within the previous 12 months and having commenced treatment at least 1 month previously. RESULTS In total, 571 migrant patients (comprising 145 Arabic, 248 Chinese, and 178 Greek) and a control group of 274 Anglo-Australian patients participated. In multiple linear regression models adjusted for age, sex, education, marital status, socioeconomic status, time since diagnosis, and type of cancer, migrants had clinically significantly worse health-related quality of life (HRQL; 3.6-7.3 points on FACT-G, p < .0001), higher depression and anxiety (both p < .0001), and higher incidence of clinical depression (p < .0001) and anxiety (p = .003) than Anglo-Australians. Understanding the health system (p < .0001 for each outcome) and difficulty communicating with the doctor (p = .04 to .0001) partially mediated the impact of migrancy. In migrant-only analyses, migrant-related variables (language difficulty and poor understanding of the health system), not ethnicity, predicted outcomes. CONCLUSION Migrants who develop cancer have worse psychological and HRQL outcomes than Anglo-Australians. Potential targets for intervention include assistance in navigating the health system, translated information, and cultural competency training for health professionals.

Estimation of an optimal chemotherapy utilisation rate for lung cancer: An evidence-based benchmark for cancer care

BACKGROUND Optimal chemotherapy utilisation rates can serve as benchmarks to assess the quality of cancer service delivery. This study aims to determine the optimal proportion of patients with lung cancer that should receive chemotherapy at least once during the course of their illness, based on the best available evidence. METHODS An optimal chemotherapy utilisation tree was constructed using indications for chemotherapy identified from evidence-based treatment guidelines. Data on the proportion of patient and tumour-related attributes for which chemotherapy was indicated were obtained and merged with the treatment indications to calculate an optimal chemotherapy utilisation rate. This optimal rate was compared with reported actual rates of chemotherapy utilisation. RESULTS Chemotherapy is recommended at least once in 73% of all patients with lung cancer (93% of small cell lung cancer (SCLC) patients and 69% of non-small cell lung cancer (NSCLC) patients). Comparison of these benchmark rates with international reported actual chemotherapy utilisation rates reveals under-utilisation of chemotherapy in all newly diagnosed lung cancer patients, regardless of histological type and stage, with the exception of stage I NSCLC. CONCLUSION The optimal chemotherapy utilisation rate can serve as a feasible, evidence-based measure of the quality of cancer care. Chemotherapy may be under-utilised in the initial management of lung cancer.

A comparison of surgical and radiotherapy breast cancer therapy utilization in Canada (British Columbia), Scotland (Dundee), and Australia (Western Australia) with models of “optimal” therapy

BACKGROUND Different jurisdictions report different breast cancer treatment rates. Evidence-based utilization models may be specific to derived populations. We compared predicted optimal with actual radiotherapy utilization in British Columbia, Canada; Dundee, Scotland; and Perth, Western Australia. DESIGN Data were analyzed for differences in demography, tumor, and treatment. Epidemiological data were fitted to published Australian optimal radiotherapy utilization trees and region-specific optimal treatment rates were calculated. Optimal and actual surgery/radiotherapy rates from 2 population-based and 1 institution-based registries were compared for patients diagnosed with breast cancer between 2000 and 2004, and 2002 for British Columbia. RESULTS Mastectomy rates differed between British Columbia (40%), Western Australia (44%), and Dundee (47%, p<0.01). Radiotherapy rates differed between British Columbia (60%), Western Australia (52%), and Dundee (49%, p<0.01). Actual radiotherapy utilization rates were lower than optimal estimates. Region-specific optimal utilization rates at diagnosis varied from 57% to 71% for radiotherapy and 62% to 64% when taking into account patient preference. Variation was attributed to local differences in demography and tumor stage. CONCLUSIONS Actual treatment rates varied, and were associated with patterns of care and guideline differences. Actual radiotherapy rates were lower than optimal rates. Differences between optimal and actual utilization may be due to access shortfalls, and patient preference.

Estimation of an optimal chemotherapy utilisation rate for breast cancer: Setting an evidence-based benchmark for the best-quality cancer care

BACKGROUND The proportion of breast cancer patients that received chemotherapy varies widely in high-income countries. An evidence-based estimate of the optimal chemotherapy utilisation rate for a breast cancer population may serve as a useful benchmark for measuring and improving the quality of care. METHODS An optimal chemotherapy utilisation model was constructed using indications for chemotherapy identified from evidence-based guidelines. Data on the proportion of patient (age, performance status and preference) and tumour (stage, size, grade, nodal status, hormone receptor and HER2 status) attributes were obtained and merged with the treatment indications to calculate an optimal utilisation rate. This model was peer-reviewed by a panel of independent experts. RESULTS Chemotherapy was indicated in 17 of the 24 possible clinical scenarios depicted in the optimal utilisation model. The estimated optimal proportion of breast cancer patients who should received chemotherapy at least once was 68%. Sensitivity analyses showed that the range of optimal rate was 60-69%. The optimal rate appears to be substantially higher than the reported actual rates (29-49%). CONCLUSION It is possible to generate an optimal chemotherapy utilisation rate in breast cancer to serve as an evidence-based benchmark. The optimal chemotherapy utilisation rate in breast cancer has remained largely unchanged over the past 15years. The reported actual utilisation rates of chemotherapy in breast cancer populations appear to have remained below the estimated optimal rate, suggesting that potential opportunities for improvement in the compliance to guideline recommended care exist.

A comparison of systemic breast cancer therapy utilization in Canada (British Columbia), Scotland (Dundee), and Australia (Western Australia) with models of “optimal” therapy

BACKGROUND Different jurisdictions report different breast cancer treatment rates. Evidence-based optimal utilization models may be specific to the derived population. We compared predicted optimal with actual endocrine and chemotherapy utilization in British Columbia, Canada; Dundee, Scotland; and Perth, Western Australia. DESIGN Data were analyzed for differences in demography, tumour, and treatment. Epidemiological data were fitted to published Australian optimal radiotherapy utilization trees and region-specific optimal treatment rates were calculated. Optimal and actual systemic therapy rates from 2 population-based and 1 institution-based cancer registries were compared for patients diagnosed with breast cancer between 2000-2004, and 2002 for British Columbia. RESULTS Chemotherapy rates differed between British Columbia (32%), Perth (29%), and Dundee (24%, p = 0.014). Endocrine therapy rates were similar between British Columbia (56%), Perth (59%), and Dundee (64%, p > 0.05). Actual utilization rates were lower than optimal estimates for chemotherapy, but higher for endocrine therapy. Region-specific optimal utilization rates at diagnosis varied between 50-56% for chemotherapy, and 49-54% for endocrine therapy. Variation was attributed to local differences in demographics, and tumour stage. CONCLUSION Actual treatment rates varied. There was lower than estimated optimal chemotherapy use but higher than expected use of endocrine therapy.

Estimation of an optimal chemotherapy utilisation rate for head and neck carcinoma: Setting an evidence-based benchmark for the best-quality cancer care

BACKGROUND We estimated the optimal chemotherapy utilisation rate for head and neck cancer as a benchmark for measuring and improving the quality of cancer care. METHODS An optimal chemotherapy utilisation tree was constructed using indications for chemotherapy that were identified from evidence-based treatment guidelines. Data on the proportion of patient and tumour-related attributes for which chemotherapy was indicated were obtained and merged with the treatment indications to calculate the optimal utilisation rate. The robustness of the model was tested with sensitivity analysis and Monte Carlo simulation. The optimal chemotherapy utilisation rate was compared with actual utilisation rates reported. RESULTS Chemotherapy is indicated at least once in 36% (95% CI, 33-38%) of all patients with head and neck carcinoma. The optimal utilisation rates by subsites were as follows: lip, 8%; oral cavity, 40%; nasopharynx, 69%; oropharynx, 66%; hypopharynx, 74%; larynx, 43%; salivary gland, 48% and paranasal sinus with nasal cavity, 38%. CONCLUSIONS The optimal proportion of patients who should receive chemotherapy in the head and neck carcinoma population has risen significantly over the past 20 years. This temporal rise does not appear to be reflected in the limited actual utilisation rates that are available for comparison. Large population-based studies are recommended to further assess the current practice and compliance to guideline recommended care.