Malignant pleural mesothelioma incidence and survival in the Republic of Ireland 1994–2009

ObjectiveMalignant pleural mesothelioma (MPM) is a rare malignancy associated with exposure to asbestos. The protracted latent period of MPM means that its incidence has continued to rise across Europe after the introduction of restrictions on asbestos use. In order to obtain a clearer indication of trends in the Republic of Ireland (ROI), incidence and survival were assessed based on all MPM cases reported since the establishment of the National Cancer Registry of Ireland (NCR).MethodsNCR recorded 337 MPM diagnoses in the ROI during 1994–2009. Survival was assessed for all cases diagnosed with adequate follow-up (n = 330). Crude and European age-standardized incidence rates were calculated for all cases and for 4-year periods. A Cox model of observed (all-cause) survival was used to generate hazard ratios for the effect of: gender; age at diagnosis; diagnosis cohort; region of residence; histological type; and tumour stage. Single P-values for the variables indicated were calculated using either a stratified log-rank test or stratified trend test.ResultsOver the study period the age-standardized MPM incidence in the ROI rose from 4.98 cases per million (cpm) to 7.24 cpm. The 1-year survival rate for all MPM cases was 29.6% (CI 24.7–34.6%). Excess mortality risk was associated with age at diagnosis (75–89 yrs vs. 55–64 yrs, HR 1.88, 95% CI 1.35–2.63, P < 0.001) and tumour stage (III vs. I HR 1.57, 95% CI 1.00–2.48, P < 0.05; IV vs. I HR 1.55, 95% CI 1.08–2.21, P < 0.05). Age showed a significant survival trend (P < 0.001) but tumour stage did not (P = 0.150). There was significant heterogeneity between the survival of patients resident in different regions (P = 0.027).ConclusionMPM incidence and mortality continued to rise in the ROI after the restrictions on asbestos use and the predictors of survival detected in this study are broadly consistent with those identified for other countries.     

Characteristics and outcomes of patients with Ewing sarcoma over 40 years of age at diagnosis

Background: The peak incidence of Ewing sarcoma (EWS) is in adolescence, with little known about patients who are ≥40 years at diagnosis. We describe the clinical characteristics and survival of this rare group. Methods: This retrospective cohort study utilized the Surveillance Epidemiology and End Results database. 2780 patients were identified; including 383 patients diagnosed ≥40 years. Patient characteristics between age groups were compared using chi-squared tests. Survival from diagnosis to death was estimated via Kaplan–Meier methods, compared with log-rank tests, and modeled using multivariable Cox methods. A competing risks analysis was performed to evaluate death due to cancer. Results: Patients ≥40 years of age were more likely to have extra-skeletal tumors (66.1% vs. 31.7%; p < 0.001), axial tumors (64.0% vs. 57.2%; p = 0.01), and metastatic disease at diagnosis (35.5% vs. 30.0%; p = 0.04) compared to younger patients. Five-year survival for those age ≥40 and age <40 were 40.6% and 54.3%, respectively (p < 0.0001). A Cox multivariable model controlling for differences between groups confirmed inferior survival for older patients (hazard ratio for death of 2.04; 95% CI 1.63–2.54; p < 0.0001); though treatment data were unavailable and not controlled for in the model. A competing risks analysis confirmed increased risk of cancer-related death in older patients. Conclusion: Patients ≥40 years at diagnosis with EWS are more likely to have extra-skeletal tumors, metastatic disease, and axial primary tumors suggesting a difference in tumor biology. Independent of differences in these characteristics, older patients also have a lower survival rate.     

Incidence,survival and mortality rates of stage-specific bladder cancer in United States: A trend analysis

PurposeTo examine the overall and stage-specific age-adjusted incidence, 5-year survival and mortality rates of bladder cancer (BCa) in the United States, between 1973 and 2009.Materials and methodsA total of 148,315 BCa patients were identified in the Surveillance, Epidemiology and End Results database, between years 1973 and 2009. Incidence, mortality, and 5-year cancer-specific survival rates were calculated. Temporal trends were quantified using the estimated annual percentage change (EAPC) and linear regression models. All analyses were stratified according to disease stage, and further examined according to sex, race, and age groups.ResultsIncidence rate of BCa increased from 21.0 to 25.5/100,000 person-years between 1973 and 2009. Stage-specific analyses revealed an increase incidence for localized stage: 15.4–20.2 (EAPC: +0.5%, p < 0.001) and distant stage: 0.5–0.8 (EAPC: +0.7%, p = 0.001). Stage-specific 5-year survival rates increased for all stages, except for distant disease. No significant changes in mortality were recorded among localized (EAPC: ?0.2%, p = 0.1) and regional stage (EAPC: ?0.1%, p = 0.5). An increase in mortality rates was observed among distant stage (EAPC: +1.0%, p = 0.005). Significant variations in incidence and mortality were recorded when estimates were stratified according to sex, race, and age groups.DiscussionAlbeit statistically significant, virtually all changes in incidence and mortality were minor, and hardly of any clinical importance. Little or no change in BCa cancer control outcomes has been achieved during the study period.     

Recent changes in endometrial cancer trends among menopausal-age US women

BackgroundChanges in endometrial cancer incidence rates after the precipitous decline in menopausal hormone therapy (MHT) use in 2002 have not been evaluated.MethodsUsing data from the Surveillance, Epidemiology, and End Results Program from 1992 to 2009 (SEER 13), we identified 63 428 incident endometrial cancer cases among women ages 20–74. We compared annual percent change (APC) in endometrial cancer incidence rates from 1992 to 2002 to rates from 2003 to 2009.ResultsIn contrast to the constant endometrial cancer rate pattern observed from 1992 to 2002 (APC 0.0%), rates increased after 2002 in women 50–74 years old (2.5%; P_{APC comparison} < 0.01). Endometrial cancer incidence increased over the entire time period among women ages 20–49 (1992–2002: 1.1%; 2003–2009: 2.1%; P_{APC comparison} = 0.21). Post-2002 increases in incidence among women ages 50–74 were specific to Type I endometrial tumors (1992–2002: ?0.6%; 2003–2009: 1.6%; P_{APC comparison} < 0.01).DiscussionThe increase in endometrial cancer incidence rates after 2002 may be related to the widespread decrease in estrogen plus progestin MHT use, which has been reported to lower endometrial cancer risk in overweight and obese women.     

Antihypertensive medications and survival in patients with cancer: A population-based retrospective cohort study

Background: The association between antihypertensive medications and survival in cancer patients remains unclear. Objectives: To explore the association between classes of antihypertensive drugs and survival in cancer patients. Methods: Provincial Cancer Registry data was linked with a Provincial Drug Program Information Network (DPIN) for patients with lung (n = 4241), colorectal (n = 3967), breast (n = 4019) or prostate (n = 3355) cancer between the years of 2004 and 2008. Cox regression analyses were used to compare survival of patients using beta blockers (BBs), angiotensin-converting enzyme inhibitors/receptor blockers (ACEi/ARB), calcium channel blockers (CCBs) or thiazide diuretics (TDs) to survival of patients who did not use any of these antihypertensive drugs. Survival of patients using only one class of antihypertensive drugs were compared to each other, with BBs as the reference class. Results: Compared to the antihypertensive drug non-user cohort, BBs had no effect on survival for any of the cancers. ACEi/ARBs use was weakly associated with increased deaths for breast cancer (HR: 1.22, 95% CI: 1.04–1.44) and lung cancer (HR: 1.11, 95% CI: 1.03–1.21) patients. Deaths were also increased with CCB use in patients with breast cancer (HR: 1.22, 95% CI: 1.02–1.47) and with TD use in lung cancer patients (HR: 1.1, 95% CI: 1.01–1.19). There was strong evidence (p-value <0.0001) of an increase in deaths with TD use for colorectal (HR: 1.28, 95% CI: 1.15–1.42), and prostate (HR 1.41, 1.2–1.65) cancer patients. When including only antihypertensive drug users prescribed one drug class, lung cancer patients receiving CCBs had improved survival compared to BBs (HR 0.79, 95% CI: 0.64–0.98). Conclusions: Some classes of antihypertensive agents are associated with a decreased survival in certain cancers. The decrease could be due to more comorbidities in antihypertensive drug users. However, CCB use was associated with improved survival in lung cancer patients.     

Cancer survival in patients with HIV/AIDS in the era of highly active antiretroviral therapy in Taiwan: A population-based cohort study

Objectives: HIV-related immunosuppression has been associated with the development of AIDS-defining malignancies. We examined the overall survival of HIV-infected patients who developed cancer. Design: A retrospective cohort study. Methods: Using the Taiwan Longitudinal Health Insurance Database, we compared patients diagnosed with HIV (n = 9918) between January 1, 2002, and December 31, 2007 with age-matched controls (n = 99,180). Each patient was followed until the end of 2009 (least 2 years after the initial HIV diagnosis) to evaluate the incidence of malignancies. Results: The risk of overall malignancies in the HIV-infected cohort was 1.88 times higher than the risk of a first malignancy in the age-matched non-HIV infected cohort (incidence rate ratio [IRR]) = 2.05, p < 0.0001). The diagnosis of a malignancy was negatively correlated with survival in the HIV-infected cohort (p < 0.0011), and HIV infection had a synergistic effect on the survival of patients with malignancies compared with the non-HIV infected cohort, all of who had been newly diagnosed with cancer (p < 0.0001). However, the difference in the risk of developing nasopharyngeal carcinoma (NPC), a highly prevalent malignancy in Taiwan, between the two cohorts was not significant (IRR = 0.22, 95% CI = 0.03–1.65). Conclusions: The risk of cancer in HIV-infected patients in Taiwan has increased significantly in the era of highly active antiretroviral therapy. A history of HIV significantly affected the survival of the patients in our study cohort after they developed cancer.Evidence level: 2B.     

Pre-diagnostic smoking behaviour and poorer prognosis in a German breast cancer patient cohort – Differential effects by tumour subtype,NAT2 status,BMI and alcohol intake

BackgroundInconsistent associations of smoking and breast cancer-specific mortality might be explained by subgroups of patients with different susceptibility to harmful effects of smoking.MethodsWe used a prospective cohort of 3340 postmenopausal breast cancer patients aged 50–74 and diagnosed with invasive tumours 2001–2005 in Germany, with a median follow-up time of 6 years. The effect of pre-diagnostic smoking behaviour on mortality outcomes and risk of recurrence was investigated using delayed entry Cox regression analysis. Differential effects according to N-acetyltransferase (NAT2) status, BMI, alcohol consumption, and tumour subtypes were assessed.ResultsOverall, smoking at time of breast cancer diagnosis versus never/former smoking was non-significantly associated with increased breast cancer-specific mortality and risk of recurrence (HR 1.23, 95% CI 0.93–1.64, and HR 1.29, 95% CI 0.95–1.75, respectively). Associations were consistently stronger in NAT2 slow than in fast acetylators for all mortality outcomes. Breast cancer-specific mortality was significantly increased in smokers with NAT2 slow acetylating status (HR 1.77, 95% CI 1.13–2.79) but not in those with fast acetylating status (HR 1.09, 95% CI 0.60–1.98; P_{heterogeneity} = 0.19). Smoking was associated with significantly poorer outcomes for triple negative and luminal A-like tumours (e.g. all-cause mortality: HR 1.93, 95% CI 1.02–3.65, and HR 2.08, 95% CI 1.40–3.10, respectively). Risk of recurrence was significantly increased for women with HER2 positive tumours (HR 3.64, 95% CI 1.22–10.8). There was significant heterogeneity by BMI for non-breast cancer-specific mortality (<25 kg/m²: HR 2.52, 95% CI 1.52–4.15 vs. ≥25 kg/m²: HR 0.94, 95% CI 0.38–2.36; P_{heterogeneity} = 0.04).ConclusionThe harmful effects of smoking may be particularly relevant for certain subgroups of breast cancer patients. This may include patients with NAT2 slow acetylation status or with tumour subtypes other than luminal B, such as luminal A tumours who usually have a rather good prognosis. Emphasis on smoking cessation programmes for all cancer patients should be strengthened.     

Biomarkers in critically ill patients with systemic inflammatory response syndrome or sepsis supplemented with high-dose selenium

ObjectiveLow levels of selenium (Se) and glutathione peroxidase (GSHPx), a key selenoenzyme, were documented in systemic inflammatory response syndrome (SIRS) and sepsis, both associated with high mortality. Se supplementation had mixed effects on outcome. We hypothesized that Se supplementation could have a different impact on biomarkers and 28-day mortality in patients with SIRS vs. sepsis.MethodsAdult patients with SIRS or sepsis were randomized to either high-dose (Se+, n = 75) or standard-dose (Se−, n = 75) Se supplementation. Plasma Se, whole blood GSHPx activity, C-reactive protein (CRP), procalcitonin (PCT), prealbumin, albumin and cholesterol levels were measured serially up to day 14.ResultsThere was no difference in mortality between Se− (24/75) vs. Se+ group (19/75; p = 0.367) or between SIRS and septic patients (8/26 vs. 35/124; p = 0.794). There was a trend to reduced mortality in SIRS patients in the Se+ vs. Se− group (p = 0.084). Plasma Se levels increased in the Se+ group only in patients with sepsis but not in patients with SIRS. Plasma Se levels correlated with GSHPx. In SIRS/Se+ group, Se correlated only with GSHPx. In SIRS/Se− group, Se correlated with cholesterol but not with other biomarkers. In sepsis patients, Se levels correlated with cholesterol, GSHPx and prealbumin. Cholesterol levels were higher in survivors in the Se− group.ConclusionsSe levels correlated with GSHPx activity and other nutritional biomarkers with significant differences between SIRS and sepsis groups. High-dose Se supplementation did not affect mortality but a strong trend to decreased mortality in SIRS patients warrants further studies in this population.     

Prostate cancer specific survival in the Prostate,Lung, Colorectal,and Ovarian (PLCO) Cancer Screening Trial

Background: The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized screening trial demonstrated no mortality effect of screening. Here we analyze prostate cancer specific survival in PLCO and its relation to screening. Methods: 76,693 men aged 55–74 were randomized to usual care (n = 38,350) or intervention (n = 38,343). Intervention arm men received annual prostate-specific antigen (6 years) and digital rectal exam (4 years). Men were followed for cancer diagnosis and mortality through 13 years. Medical record abstractors confirmed prostate cancer diagnoses, stage and grade. Prostate-specific survival in PLCO cases was analyzed using Kaplan–Meier analysis and proportional hazards modeling. We utilized data from the Surveillance, Epidemiology and End Results (SEER) program to compute expected survival in PLCO and compared this to observed. Results: There was no significant difference in prostate-specific survival rates between arms; 10 year survival rates were 94.7% (intervention, n = 4250 cases) versus 93.5% (usual care, n = 3815 cases). Within the intervention arm, cases never screened in PLCO had lower 10 year survival rates (82%) than screen detected or interval (following a negative screen) cases, both around 95.5%. The ratio of observed to expected 10 year prostate-specific death (1-survival) rates was 0.59 (95% CI: 0.51–0.68) for all PLCO cases, 0.66 (95% CI: 0.51–0.81) for Gleason 5–7 cases and 1.07 (95% CI: 0.87–1.3) for Gleason 8–10 cases. Conclusion: Prostate cancer specific survival in PLCO was comparable across arms and significantly better than expected based on nationwide population data. How much of the better survival is due to a healthy volunteer effect and to lead-time and overdiagnosis biases is not readily determinable.     

Age-specific breast,uterine and ovarian cancer mortality trends in Spain: Changes from 1980 to 2006

Introduction: Cancers of the breast, uterus and ovary are responsible for 30% of the cancer deaths in Spanish women. In recent decades, Spain has experienced important socioeconomic transformations, which may have affected mortality trends. We present the current situation of mortality in Spain due to cancers of the breast, uterus and ovary, as well as trends over 1980–2006. Methods: Data on population and deaths due to cancers of the breast, uterus and ovary were obtained from records of the National Statistics Institute. Overall and age-specific changes in mortality of these tumors were studied using change-point Poisson regression models. Results: Breast cancer was responsible for more than 140,000 deaths of females in 1980–2006. Trend analysis of breast cancer mortality of women of all ages showed that rates increased 2.9% annually until 1992 (95% confidence interval (CI) = 2.5, 3.3). After 1992, mortality declined steadily at a rate of ?2.1% per year (95% CI = ?2.4, ?1.8). The number of deaths due to cancers of the uterus was 49,287 between the years 1980 and 2006. Uterine cancer mortality registered a steady decrease of ?1.9% every year since 1980 (95% CI = ?2.1, ?1.8). Ovarian cancer caused 36,157 deaths during the same period, with rates in women older than 50 years more than ten-fold those of younger women. Trend analysis showed a sharp increase of mortality up to 1998 (4.4% annually; 95% CI = 3.9, 4.8) followed by a stabilization. Conclusion: The downturn observed in mortality for these tumors mainly reflects improved survival as a result of earlier diagnosis and better cancer treatments. Cancer management is moving in the right direction in Spain.     

Unstaged cancer in a population-based registry: Prevalence,predictors and patient prognosis

Purpose: Information on cancer stage at diagnosis is critical for population studies investigating cancer care and outcomes. Few studies have examined the factors which impact (1) staging or (2) outcomes for patients who are registered as having unknown stage. This study investigated (1) the prevalence of unknown stage at diagnosis on the New Zealand Cancer Registry (NZCR); (2) explored factors which predict unknown stage; (3) described receipt of surgery and (4) survival outcomes for patients with unknown stage. Methods: Patients diagnosed with the most prevalent 18 cancers between 2006 and 2008 (N = 41,489) were identified from the NZCR, with additional data obtained from mortality and hospitalisation databases. Logistic and Cox regression were used to investigate predictors of unknown stage and patient outcomes. Results: (1) Three distinct groups of cancers were found based on proportion of patients with unknown stage (low = up to 33% unknown stage; moderate = 33–64%; high = 65%+). (2) Increasing age was a significant predictor of unknown stage (adjusted odds ratios [ORs]: 1.18–1.24 per 5-year increase across groups). Patients with substantive comorbidity were more likely to have unknown stage but only for those cancers with a low (OR = 2.65 [2.28–3.09]) or moderate (OR = 1.17 [1.03–1.33]) proportion of patients with unknown stage. (3) Patients with unknown stage were significantly less likely to have received definitive surgery than those with local or regional disease across investigated cancers. (4) Patients with unknown stage had 28-day and 1-year survival which was intermediate between regional and distant disease. Discussion: We found that stage completeness differs widely by cancer site. In many cases, the proportion of unknown stage on a population-based register can be explained by patient, service and/or cancer related factors.     

Diabetes,metformin use,and colorectal cancer survival in postmenopausal women

Background: Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study. Methods: 2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n = 84); women with diabetes with no metformin use (n = 128); and women without diabetes (n = 1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results: After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40–1.38, p = 0.67) and to women without diabetes (HR 1.00; 95% CI 0.61–1.66, p = 0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38–1.55, p = 0.47) and for overall survival was 0.86 (95% CI 0.49–1.52; p = 0.60). Conclusions: In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.     

Neutrophil CD64 expression and serum IL-8: Sensitive early markers of severity and outcome in sepsis

The aim of the present study was to investigate which biomarker/s reliably assess severity and mortality early in the sepsis process. In 47 critically-ill patients within the 24 h of septic onset, Interleukins (IL)-8, -1β, -6, -10, and -12p70, tumor necrosis factor-α (TNF-α), procalcitonin (PCT) and C-reactive protein (CRP) were measured in serum. Additionally, CD64 expression was measured in neutrophils. In early sepsis, neutrophil CD64 expression and IL-8 levels are the only biomarkers that increased with sepsis severity, differentiating disease stages: sepsis, severe sepsis and septic shock (p < 0.001). The biomarkers that best evaluate the severity of sepsis (via APACHE II) were CD64, IL-8 and IL-6 (p < 0.01), and the severity of organ failure (via SOFA) were CD64 and IL-8 (p < 0.01). CD64 expression and IL-8 levels were associated with mortality within 28-days (OR = 1.3, p = 0.01 for CD64 and OR = 1.26, p = 0.024 for IL-8 by logistic regression analysis) and ROC curve analysis showed high sensitivity and specificity for predicting sepsis stages and the 28 day mortality. We conclude that there is an early increase of neutrophil CD64 expression and IL-8 levels during sepsis. Based on this single measurement it is possible to reliably assess the stage, detect the severity and predict the 28-day mortality of sepsis.     

Nasopharyngeal carcinoma in Slovenia, 1990–2003 (results of treatment with conventional two-dimensional radiotherapy)

AimTo review the treatment results and identify prognostic factors for disease control and survival in a cohort of nasopharyngeal carcinoma (NPC) patients from a non-endemic population in Slovenia, diagnosed between 1990 and 2003.BackgroundIn Caucasians, nasopharyngeal carcinoma is a rare malignant tumor. Its diagnosis and treatment are complex and have been dramatically impacted by recent technological advances.Materials and methodsIn the Cancer Registry of Slovenia database, a total of 126 patients with NPC were identified, 93 of whom were available for analysis. All patients were treated with conventional two-dimensional radiotherapy (RT) and 29.3% underwent chemotherapy (ChT).ResultsThe median follow-up time for those alive at the last follow-up examination was 74.5 months. Disease recurred locally in 17 patients, regionally in 4 patients and at distant sites in 18 patients, resulting in 5-year locoregional control (LRC), distant failure-free survival (DFFS) and disease-free survival (DFS) of 73.7%, 78.6% and 59.3%, respectively. Disease-specific survival at 5 years was 59% and overall survival (OS) was 49.7%. In a multivariate analysis, LRC was favorably affected (P < 0.05) by an undifferentiated histology (hazard ratio [HR] = 2.86), DFFS through the absence of neck metastases (HR = 0.28), DFS by younger age (HR = 0.46), and more intensive RT (expressed as the isoeffective dose, EQD_2,T; HR = 2.08). The independent prognosticator for OS was age (≤55 years vs. >55 years, HR = 0.39); in the ≤55 years subgroup, an improved OS was connected to a more intensive RT regimen of EQD_2,T ≥ 66 Gy (HR = 4.17).ConclusionsOur results confirm an independent and favorable effect from an undifferentiated histology, the absence of neck metastases, a younger patient age at diagnosis, and more intensive RT regimens for disease control and survival.     

The impact of chemokine receptor CXCR4 on breast cancer prognosis: A meta-analysis

Background: C-X-C chemokine receptor type 4 (CXCR4) has been implicated in the invasiveness and metastasis of diverse cancers. However, the published data remain controversial on the correlation between CXCR4 expression level, as well as its subcellular distribution in tumor cells, and the clinical outcome of patients with breast cancer. Methods: To identify the precise role of CXCR4 in the clinical outcome of breast cancer, we performed a meta-analysis including 15 published studies. Original data included the hazard ratios (HRs) of overall survival (OS) and disease-free survival (DFS) in breast cancer with high CXCR4 expression versus low expression. We pooled hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate the hazard. Results: A total of 15 published studies (including 3104 patients) were eligible. Overall survival (OS) and disease-free survival (DFS) of breast cancer were found to be significantly related to CXCR4 expression level, with the HR being 1.65 (95%CI: 1.34–2.03; P < 0.00001) and 1.94 (95%CI: 1.42–2.65; P < 0.00001) respectively. Stratified analysis according to subcellular distribution of CXCR4 showed that high expression in whole cells, cytoplasm and nucleus could predict unfavorable OS, with the HR of 2.02 (95%CI: 1.43–2.85; P < 0.0001), 1.57 (95%CI: 1.13–2.18; P = 0.007), and 1.47 (95%CI: 1.19–1.81; P = 0.0004) respectively. As for DFS, elevated expression level of CXCR4 both in whole cells and cytoplasm predicted a poor outcome, with the HR being 2.23 (95%CI: 1.48–3.37; P = 0.0001) and 1.76 (95%CI: 1.11–2.80; P = 0.02), while high expression in the nucleus had no statistical significance, with HR 1.15 (95%CI: 0.52–2.55; P = 0.73). Conclusions: Increased CXCR4 expression, especially in whole cells and cytoplasm, may serve as a poor prognostic indicator in patients with breast cancer. Future studies are warranted to investigate the relationship between CXCR4 expression and survival of patients with breast carcinoma, which could help predict the clinical outcome and guide clinical decision-making for therapy.     

Childhood cancer survival: A report from the United Kingdom Childhood Cancer Study

Background: Improvements in diagnostic approaches and refinements to treatment protocols have resulted in 5-year survival levels above 70% for children diagnosed with cancer in economically developed parts of the world. For some cancers, including leukaemia and tumours of the central nervous system, age and sex have been identified as important prognostic indicators. Methods: We examined long-term survival, and affects of age and sex, in a population-based case–control study. Children (0–14 years) newly diagnosed with cancer were ascertained between 1991 and 1996 (n = 4433). Follow-up information was obtained from the National Health Service (NHS) Information Centre for Health and Social Care which records all exits from the NHS including deaths. Results: For all cancer diagnoses combined, 5-year survival was 72.7% dropping to 67.9% at 15 years. As expected, survival differed between diagnostic subtypes ranging from 38.1% for intracranial embryonal tumours to 96.2% for Hodgkin lymphoma. Compared to girls, boys diagnosed with acute lymphoblastic leukaemia were at a higher risk of dying (RR = 1.26, 95% CI 1.03–1.53), whereas boys diagnosed with an intracranial embryonal tumour were at a lower risk of death (RR = 0.63, 95% CI 0.43–0.91). Conclusion: Our initial findings are consistent with previous reports, and highlight the importance of considering differences by age and sex. The completeness and population-based nature of the original case–control study is an important feature which will provide the basis for future more detailed investigations linking disease determinants to outcome.     

Prediction of all-cause mortality with copeptin in cardio-cerebrovascular patients: A meta-analysis of prospective studies

BackgroundMeasurement of the biomarker copeptin may help identify disease severity and risk of mortality for a various diseases. This study sought to determine the relationship between copeptin and all-cause mortality of patients with cardio-cerebrovascular disease.MethodsDatabase of Medline and Web of Science were searched for studies with data involving the baseline copeptin levels and subsequent all-cause mortality outcomes. The pooled HRs of all-cause mortality were calculated and presented with 95%CIs. Subgroup analysis and sensitivity analysis were conducted to explore the possible sources of heterogeneity.ResultsData from 14,395 participants were derived from 28 prospective studies. Higher copeptin significantly increased the risk of all-cause mortality (per unit copeptin: HR = 1.020, 95%CI = 1.004–1.036; log unit copeptin: HR = 2.884, 95%CI = 1.844–4.512; categorical copeptin: HR = 3.371, 95%CI = 2.077–5.472). Subgroup analysis indicated that the risk of all-cause death was higher in cerebrovascular patients (per unit copeptin: HR = 2.537, 95%CI = 0.956–6.731; log unit copeptin: HR = 3.419, 95%CI = 2.391–4.888) than cardiovascular patients (per unit copeptin: HR = 1.011, 95%CI = 1.002–1.020; log unit copeptin: HR = 2.009, 95%CI = 1.119–3.608).ConclusionCopeptin is associated with all-cause mortality of patients with cardiovascular and cerebrovascular disease. Our study suggests that copeptin seems to be a promising novel biomarker for prediction of mortality in cardio-cerebrovascular patients, especially for cerebrovascular patients.     

Correlation between VEGFR-2 receptor kinase domain-containing receptor (KDR) mRNA and angiotensin II receptor type 1 (AT1-R) mRNA in endometrial cancer

PurposeAngiogenesis, a multistep process that results in new blood vessel formation from preexisting vasculature is essential for both the growth of solid tumour and for metastasis. Stimulation of vascular endothelial growth factor receptor (VEGFR), a transmembrane glycoprotein, results in mitogenesis. Within this family of receptors, VEGFR 2/kinase-insert-domain containing receptor appears to be principally upregulated during tumorigenesis. The aim of this study was to determine the expression of VEGFR-2/kinase-insert-domain containing receptor (KDR) and its correlation with angiotensin receptor type 1 (AT1-R) and clinical factors in endometrial carcinoma.MethodsThe expression of KDR and AT1-R was studied in endometrial carcinoma and normal endometrium by Real-time RT-PCR and Western blot analysis in 136 samples. The expression profile was correlated with the clinicopathological characteristics of endometrial adenocarcinoma.ResultsWe noted a significant correlation between the expression of KDR and AT1-R in tumour grade G1, G2 and G3 (R_s = 0.50; p = 0.002, R_s = 0.69; p = 0.0001, R_s = 0.52; p = 0.005, respectively). In stage I and stage II carcinoma, a significant correlation was also found between the expression of KDR and AT1-R (R_s = 0.70, p = 0.0001, R_s = 0.67; p = 0.001, respectively). Moreover significant correlation was observed between both KDR and AT1-R in tissue with different myometrial invasion (R_s = 0.54, p = 0.0001, R_s = 0.68; p = 0.0001; respectively for tumours with invasion into the inner half and invasion into the outer half).ConclusionsBasing on received correlation between AT1-R and KDR expression and previous results we speculate that angiotensin through AT1-R modulates KDR expression and thus have influence on local VEGF level. However, further studies are required to clarify the biological interaction between KDR, AT1-R and other hormonal regulators in endometrial carcinoma.     

Beta-blocker usage and prostate cancer survival: A nested case–control study in the UK Clinical Practice Research Datalink cohort

BackgroundRecent laboratory and epidemiological evidence suggests that beta-blockers could inhibit prostate cancer progression. Methods: We investigated the effect of beta-blockers on prostate cancer-specific mortality in a cohort of prostate cancer patients. Prostate cancer patients diagnosed between 1998 and 2006 were identified from the UK Clinical Practice Research Database and confirmed by cancer registries. Patients were followed up to 2011 with deaths identified by the Office of National Statistics. A nested case–control analysis compared patients dying from prostate cancer (cases) with up to three controls alive at the time of their death, matched by age and year of diagnosis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression. Results: Post-diagnostic beta-blocker use was identified in 25% of 1184 prostate cancer-specific deaths and 26% of 3531 matched controls. There was little evidence (P = 0.40) of a reduction in the risk of cancer-specific death in beta-blocker users compared with non-users (OR = 0.94 95% CI 0.81, 1.09). Similar results were observed after adjustments for confounders, in analyses by beta-blocker frequency, duration, type and for all-cause mortality. Conclusions: Beta-blocker usage after diagnosis was not associated with cancer-specific or all-cause mortality in prostate cancer patients in this large UK study.     

Cancer with Diabetes: Prevalence,Metabolic Control,and Survival in an Academic Oncology Practice

ObjectiveTo determine the prevalence of diabetes mellitus, glycemic control, and impact of diabetes on over all survival in an academic oncology practice.MethodsData on cancer patients (1999 to 2008) were retrieved from the institutional cancer registry and linked to electronic files to obtain diabetes status and hemoglobin A1c (A1C) values within the first 6 months of cancer diagnosis. Overall survival by cancer type with and without diabetes was compared using Cox regression.ResultsExcluding skin and hematologic malignancies, 15,951 cancer cases were identified. Overall diabe tes prevalence was 6.8% (n = 1,090), declining over time (P < 0.001). Diabetes was common among patients with pancreatic (9.8% [61 of 624]), colorectal (7.7% [89 of 1,151]), or bladder cancers (7.6% [68 of 899]). Patients with diabetes were older (mean age, 70 versus 66 years; P < 0.001) and more likely to be male (66.3% [723 of 1,090] versus 60.2% [8,949 of 14,858]; P < 0.001). The mean A1C among diabetic cancer patients was 6.8% and did not dif fer across cancer types (P = 0.80). Only 58.6% (331 of 565) of diabetic cancer patients had all A1C < 7.0% during the first 6 months following cancer diagnosis. Pancreatic cancer patients with coexisting diabetes had better overall survival than pancreatic cancer patients without diabetes (hazard ratio, 0.60; 95% confidence interval 0.44 to 0.80; P < 0.001). Conversely, diabetic prostate cancer patients had worse overall survival than prostate cancer patients without diabetes (hazard ratio, 1.36; 95% confidence interval 1.05 to 1.76; P = 0.02).ConclusionIn this academic oncology practice, diabetes was common, glycemic control often was subopti mal, and survival varied by cancer type. Additional study is needed to optimize glucose management and investigate mechanisms underlying age, sex, and survival differences. (Endocr Pract. 2012;18:898-905)