Explaining the effects of socio-economic deprivation on survival in a national prospective cohort study of 1909 patients with head and neck cancers

Background: Socio-economic differences in survival from head and neck cancers are among the largest of any malignancies. Population-based data have been unable to explain these differences. Aims: To describe survival from head and neck cancers in a large cohort of patients for whom a range of socio-economic, demographic, behavioural and casemix data was available. Methods: Prospective cohort study using data from the Scottish Head and Neck Audit on all patients diagnosed with a head and neck cancer in Scotland between 1st September 1999 and 31st August 2001 linked to General Register Office for Scotland death records to 30th June 2006. Cox proportional hazards models were produced to describe adjusted hazards of death according to socio-economic circumstances, using validated area-based DEPCAT scores. Results: Data on 1909 patients were analysed. 71.0% were male and mean age was 64.3 (SD 12.2) years. Overall 5-year survival was 45.6% (95% CI: 43.4–47.8%). In order of strength of association in univariate regression, World Health Organisation Performance Status, disease stage, patient age, tumour site, smoking status, alcohol use, tumour differentiation, and deprivation were significant predictors of all-cause mortality but after multiple adjustment, deprivation was no longer an independent predictor of survival. Conclusions: Socio-economic differentials in survival from head and neck cancers are determined by a mixture of risk factors, some of which may be amenable to targeted earlier detection methods and lifestyle interventions. However, further research is needed to understand the impacts of performance status in more deprived patients.     

Factors Driving Inequality in Prostate Cancer Survival: A Population Based Study

Purpose

As cancer control strategies have become more successful, issues around survival have become increasingly important to researchers and policy makers. The aim of this study was to examine the role of a range of clinical and socio-demographic variables in explaining variations in survival after a prostate cancer diagnosis, paying particular attention to the role of healthcare provider(s) i.e. private versus public status.

Methods

Data were extracted from the National Cancer Registry Ireland, for patients diagnosed with prostate cancer from 1998–2009 (N = 26,183). A series of multivariate Cox and logistic regression models were used to examine the role of healthcare provider and socio-economic status (area-based deprivation) on survival, controlling for age, stage, Gleason grade, marital status and region of residence. Survival was based on all-cause mortality.

Results

Older individuals who were treated in a private care setting were more likely to have survived than those who had not, when other factors were controlled for. Differences were evident with respect to marital status, region of residence, clinical stage and Gleason grade. The effect of socio-economic status was modified by healthcare provider, such that risk of death was higher in those men of lower socio-economic status treated by public, but not private providers in the Cox models. The logistic models revealed a socio-economic gradient in risk of death overall; the gradient was larger for those treated by public providers compared to those treated by private providers when controlling for a range of other confounding factors.

Conclusion

The role of healthcare provider and socio-economic status in survival of men with prostate cancer may give rise to concerns that warrant further investigation.     

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.     

Socioeconomic inequalities in breast cancer survival in Reunion Island: The contribution of stage at diagnosis as a mediator

IntroductionAlthough breast cancer survival has improved in France, it appears that women living in deprived areas are more likely to die from breast cancer. However, no study has yet examined socioeconomic inequalities in breast cancer survival in La Réunion. Our objective was to examine whether socioeconomic inequalities in breast cancer survival exist in Reunion Island and whether stage at diagnosis could partly explain these differences.MethodsA population-based cohort study of all women on Reunion Island with primary breast cancer diagnosed between 2008 and 2016 was conducted. Each woman was assigned a deprivation index based on her area of residence at diagnosis. Net survival by deprivation group and stage at diagnosis was estimated by the non parametric Pohar Perme method. The role of stage (indirect effect) was assessed using a mediation analysis extended to the relative survival framework.ResultsAt five years, net survival was significantly lower in women living in the most deprived areas than in women living in the least deprived areas (81 % (95 % CI 77–86) and 91 % (95 % CI 89–94), respectively, p < 0.0001), and mediation analysis showed that the contribution of stage at diagnosis to these survival differences was 43 %.DiscussionOur result shows that although measures to promote earlier diagnosis are important, they would only reduce socioeconomic inequalities in breast cancer survival by 43 %. To further investigate these inequalities, future research should explore the role of unmeasured mediators, such as comorbidities and treatment received, as well as the impact of specific interventions that might address the differences in mediator distribution.     

Primary liver cancer incidence and survival in ethnic groups in England, 2001–2007

Background: The patterns of primary liver cancer incidence and survival are not known for detailed ethnic groups within the UK. Methods: Data on patients resident in England diagnosed with primary liver cancer (ICD-10 C22) between 2001 and 2007 were extracted from the National Cancer Data Repository. Age-standardised incidence rate ratios (IRRs) were calculated for different ethnic groups separately for males and females, using the White ethnic groups as baselines. Overall survival was analysed using Cox regression, adjusting sequentially for age, socioeconomic deprivation and co-morbidity. Results: Ethnicity data were available for 75% (13,139/17,458) of primary liver cancer patients. Compared with the White male baseline, Chinese males had the highest IRR. Black African, Bangladeshi, Pakistani and Indian men also had statistically significant high IRRs. Black Caribbean men had a marginally elevated incidence rate compared with White men. In comparison with White women, Pakistani women had the highest IRR. Bangladeshi, Chinese, Black African and Indian women also had high IRRs. As observed in men, Black Caribbean women had an incidence rate closer to that of White women. Pakistani men and women, Black African women and Chinese men had statistically significantly better survival compared with their White counterparts. Conclusion: The variation found in the incidence of primary liver cancer, could be due to established risk factors such as hepatitis B and C infection being more prevalent among certain ethnic groups. Country of birth, age at migration and length of stay in England are likely to be important factors in this disease, and future research should examine these where possible.     

A comparison of prostate cancer survival in England, Norway and Sweden: a population-based study

Purpose The objective of the study was to compare patterns of survival 2001–2004 in prostate cancer patients from England, Norway and Sweden in relation to age and period of follow-up. Subjects and methods Excess mortality in men with prostate cancer was estimated using nation-wide cancer register data using a period approach for relative survival. 179,112 men in England, 23,192 in Norway and 59,697 in Sweden were included. Results In all age groups, England had the lowest survival, particularly so among men aged 80+. Overall age-standardised five-year survival was 76.4%, 80.3% and 83.0% for England, Norway and Sweden, respectively. The majority of the excess deaths in England were confined to the first year of follow-up. Conclusion The results indicate that a small but important group of older patients present at a late stage and succumb early to their cancers, possibly in combination with severe comorbidity, and this situation is more common in England than in Norway or Sweden.     

Investigating reasons for socioeconomic inequalities in breast cancer survival in New Zealand

Background: This study investigated the role that demographic and tumour factors play in explaining socioeconomic inequalities in breast cancer survival. Methods: Breast cancer cases notified to the New Zealand Cancer Registry (NZCR) from April 2005 to April 2007 were followed up to April 2009. The New Zealand area-based deprivation index (NZDep) was used as a measure of socioeconomic position. Relative survival rates were estimated using sex-, deprivation- and ethnic-specific life tables. Multiple imputation was used to impute missing data. Excess mortality modelling was used to estimate the contribution of demographic and tumour factors to inequalities in survival. Results: There were 2968 breast cancer cases included and 433 recorded deaths. Relative survival rates at 4 years varied across deprivation groups. Using NZDep deciles 1–4 (least deprived) as the reference group, the age- and ethnicity-adjusted hazard ratio (HR) for NZDep deciles 7–8 was 2.03 (CI 1.36–3.04) and for NZDep deciles 9–10 was 1.93 (CI 1.28–2.92). In the fully adjusted model there remained 50% excess mortality for the two most deprived groups compared to the most affluent. Variables which measured timely access to care (extent/size) accounted for more of the survival disparity than breast cancer subtype variables (ER/PR/HER2). Conclusion: Women from deprived areas in New Zealand who are diagnosed with breast cancer are less likely to survive as long as those from affluent areas. A substantial proportion of these socioeconomic disparities can be attributed to differential access to health care although other factors, currently unknown, are also likely to play an important role.     

A novel approach to estimate the German-wide incidence of testicular cancer

Background: Currently, only 7 out of 16 Federal States of Germany provide testicular cancer incidence rates with an estimated completeness of at least 90% which complicates the regional comparison of incidence rates. The aim of this study was to provide a novel approach to estimate the testicular cancer incidence in Germany by using nationwide hospitalization data. Methods: We used the nationwide hospitalization data (DRG statistics) of the years 2005–2006 including 16,6 million hospitalizations among men. We identified incident testicular cancer cases by the combination of a diagnosis of testicular cancer and an orchiectomy during the same hospitalization and estimated the age-specific and age-standardized (World Standard Population) incidence of testicular cancer across Federal States. We also analyzed available cancer registry data from 2005 to 2006. Results: A total of 8544 hospitalizations indicated incident testicular cancer cases in 2005–2006. The nationwide crude incidence rate of testicular cancer was 10,6 per 100.000 person-years. The ratio of the number of registered cases (cancer registry) to the estimated number of cases based on the hospitalization statistics ranged between 79% and 100%. There was only little variation of the age-standardized DRG-based incidence estimates across Federal States (range: 8,2–10,6 per 100.000 person-years). Discussion: We provided testicular cancer incidence estimates for each of the 16 Federal States of Germany based on hospitalization data for the first time. The low within-population incidence variability in Germany and high between-population incidence variability in Europe may indicate that ecologic factors play a causal role in the European variation of testicular cancer.     

A guide to the investigation and treatment of patients with AIDS and AIDS-related disorders.

In 1977 the rate of death from testicular cancer in Ontario began to decline following a long period of relative stability. This coincided with the addition of cisplatin to the chemotherapeutic regimens used in the treatment of disseminated germ-cell testicular cancer. A study was carried out to determine whether the decline has been similar for the two major histologic subgroups, seminoma and nonseminoma. By means of Ontario Cancer Registry data, histologic type was determined for all testicular cancers causing death in Ontario residents between 1964 and 1982, and death rates were calculated for seminoma and nonseminoma germ-cell testicular cancer. The rates of death from nonseminoma exceeded those from seminoma for the entire study period. Although the death rates for both subgroups declined by about 50% after 1976, the reduction in the overall rate of death from testicular cancer is primarily attributable to the decline in the rate for nonseminoma germ-cell testicular cancer. The increased overall rate of death from testicular cancer (all types) between 1980 and 1984 is cause for concern and indicates the need for continued monitoring of the trends in rates of death from this disease.     

Mortality and incidence of new primary cancers in men with prostate cancer: A Danish population-based cohort study

Background: Prostate cancer (PC) survivors may have an increased risk of new primary cancers (NPCs) due to shared risk factors or PC-directed treatments. Methods: Using Danish registries, we conducted a cohort study of men with (n = 30,220) and without PC (n = 151,100) (comparators), matched 1:5 on age and PC diagnosis/index date. We computed incidence rates of NPCs per 10,000 person years (PY) and associated 95% confidence intervals (CI), and used Cox proportional hazards regression to compute hazard ratios (HRs) and 95%CI, adjusting for comorbidities. In order to obviate any impact of shorter survival among prostate cancer patients, we censored comparator patients when the matched prostate cancer patient died or was censored. Results: Follow-up spanned 113,487 PY and 462,982 PY in the PC and comparison cohorts, respectively. 65% of the cohorts were aged >70 years at diagnosis. Among PC patients, 51% had distant/unspecified stage, and 63% had surgery as primary treatment. The PC cohort had lower incidence of NPCs than their comparators. The adjusted HR of NPC among men with PC versus the comparators was 0.84 (95%CI = 0.80, 0.88). Lowest HRs were among older men, those with distant stage, and were particularly evident for cancers of the brain, liver, pancreas, respiratory, upper gastrointestinal, and urinary systems. Conclusions: We find no evidence of an increased risk of NPCs among men with PC. The deficit of NPCs among men with PC may be a true effect but is more likely due to lower levels of risk factors (e.g., smoking) in PC patients versus comparators, clinical consideration of cancers at new organs as metastases rather than new primaries, or under-recording/under-reporting of NPCs among PC patients.     

Survival after a diagnosis of testicular germ cell cancers in Germany and the United States, 2002–2006: A high resolution study by histology and age

Introduction: The aim of this study was to provide detailed age-specific (5-year age groups) and histology-specific (histologic subtypes of seminoma and nonseminoma) relative survival estimates of testicular germ cell cancer patients in Germany and the United States (U.S.) for the years 2002–2006 and to compare these estimates between countries. Methods: We pooled data from 11 cancer registries of Germany and used data from the U.S. (SEER-13 database) including 11,508 and 10,774 newly diagnosed cases (1997–2006) in Germany and the U.S., respectively. We estimated 5-year relative survival (5-year-RS) by histology and age based on period analysis. Results: 5-year-RS for testicular germ cell tumors was 96.7% and 96.3% in Germany and the U.S., respectively. 5-Year-RS for spermatocytic seminoma was close to 100% in both countries. 5-Year-RS for nonseminoma was lower than for classical seminoma in Germany (93.3% versus 97.6%) and the U.S. (91.0% versus 98.2%). Among nonseminomas, choriocarcinomas provided the lowest 5-year-RS in both countries (Germany 80.1%, U.S. 79.6%). Age-specific 5-year-RS for seminoma showed only little variation by age. 5-Year-RS for nonseminomas tended to be lower at higher ages, especially for malignant teratoma. Discussion: This is the first study that provides up-to-date survival estimates for testicular cancer by histology and age in Germany and the U.S. Survival after a diagnosis of testicular cancer is very comparable between Germany and the U.S. 5-Year-RS for spermatocytic seminoma was close to 100% and the lowest 5-year-RS occurred among choriocarcinoma. Higher age at diagnosis is associated with a poorer prognosis among nonseminoma patients.     

Trends in incidence and survival from anal cancer and incidence of high-grade anal intraepithelial neoplasia in Denmark

ObjectiveThe aim of the current study was to assess temporal trends in incidence of anal squamous cell carcinomas (SCC) and high-grade anal intraepithelial lesions (AIN2/3), and estimate survival from anal cancer and factors related to 5-year mortality in Denmark.MethodsWe analyzed anal SCC and AIN2/3 cases in the period of 1998–2018 from the Danish Cancer Register and the Danish Registry of Pathology, respectively. Overall, period, gender, and histology specific age-standardized incidence rates, average annual percentage change (AAPC), and 5-year relative survival were estimated. Cox proportional hazards models were applied to evaluate the effect on 5-year mortality of period, age, gender, and stage of disease.ResultsAltogether 2580 anal cancers and 871 AIN2/3 were identified. The AIN2/3 incidence increased for women 1998–2007 (AAPC: 3.5% (95% CI −0.7, 8.0)) and then tended to decrease during 2008–2018(AAPC: −5.2% (95% CI −9.6, −0.6)). A similar pattern was observed for men, although at a lower incidence with the decrease starting later (2008–2012) and the trend not reaching statistical significance. The anal SCC incidence increased over the whole study period for both women and men (women AAPC: 4.0% (95% CI 3.2%, 4.9%) and men AAPC: 3.6% (95% CI 2.3%, 4.9%)). The relative survival improved over time (from 61% to 72%). Being older and male was associated with a higher risk of dying within 5 years.ConclusionsThere is a need to focus attention on anal cancer and its precursor lesions, as the cancer incidence continues to increase. Actions could include screening and gender-neutral HPV vaccination.     

Maternal body mass index and risk of testicular cancer in male offspring: A systematic review and meta-analysis

Objectives: To date a number of studies have examined the association between maternal weight and testicular cancer risk although results have been largely inconsistent. This systematic review and meta-analysis investigated the nature of this association. Methods: Search strategies were conducted in Ovid Medline (1950–2009), Embase (1980–2009), Web of Science (1970–2009), and CINAHL (1937–2009) using keywords for maternal weight (BMI) and testicular cancer. Results: The literature search produced 1689 hits from which 63 papers were extracted. Only 7 studies met the pre-defined criteria. Random effects meta-analyses were conducted. The combined unadjusted OR (95% CI) of testicular cancer in the highest reported category of maternal BMI compared with the moderate maternal BMI was 0.82 (0.65–1.02). The Cochran's Q P value was 0.82 and the corresponding I² was 0%, both indicating very little variability among studies. The combined unadjusted OR (95% CI) for testicular cancer risk in the lowest reported category of maternal BMI compared to a moderate maternal BMI category was 0.88 (0.65–1.20). The Cochran's Q P value was 0.05 and the corresponding I² was 54%, indicating evidence of statistical heterogeneity. The combined unadjusted OR (95% CI) of testicular cancer risk per unit increase in maternal BMI was 1.01 (0.97–1.06). The Cochran's Q test had a P value of 0.05 and the corresponding I² was 55% indicating evidence of statistical heterogeneity. Conclusion: This meta-analysis, which included a small number of studies, showed that a higher maternal weight does not increase the risk of testicular cancer in male offspring. Though an inverse association between high maternal BMI and testicular cancer risk was detected, it was not statistically significant. Further primary studies with adjustment for appropriate confounders are required.     

Effects of deprivation on the geographical variability of larynx cancer incidence in men,Girona (Spain) 1994–2004

Objective: To assess the association between the incidence of larynx cancer and socioeconomic conditions in the province of Girona from a spatial viewpoint. Materials and methods: Incidence cases of larynx cancer (CL) in 1994–2004 were provided by the Girona Cancer Registry. A census tract (CT) was assigned to all patients. Socioeconomic data were extracted from the 2001 Census. A deprivation index for each CT was obtained by principal component analysis, using four socioeconomic indicators. The standardised incidence ratio (SIR) was calculated using the CL incidence rates in the men of the province of Girona assuming a Poisson distribution. Relative risk was obtained applying the Besag, York and Mollié model. The deprivation index was introduced into the model and was categorised in quartiles. Results: Four hundred and seventy-six incident cases in men were registered. CTs in the lowest deprivation index had a lower risk of larynx cancer, with a risk increase in the higher quartiles. In the highest quartile it was 1.91 times greater than in the lowest. This association was significant when the whole province was considered. Discussion: The deprivation index explains only part of the geographical variability of CL incidence. Other risk factors without spatial structure may contribute to this explaination.     

Marital status and colon cancer outcomes in US Surveillance, Epidemiology and End Results registries: does marriage affect cancer survival by gender and stage?

Background: Marital status has been associated with outcomes in several cancer sites including breast cancer in the literature, but little is known about colon cancer, the fourth most common cancer in the US. Methods: A total of 127,753 patients with colon cancer were identified who were diagnosed between 1992 and 2006 in the US Surveillance, Epidemiology and End Results (SEER) Program. Marital status consisted of married, single, separated/divorced and widowed. Chi-square tests were used to examine the association between marital status and other variables. The Kaplan–Meier method was used to estimate survival curves. Cox proportional hazards models were fit to estimate the effect of marital status on survival. Results: Married patients were more likely to be diagnosed at an earlier stage (and for men also at an older age) compared with single and separated/divorced patients, and more likely to receive surgical treatment than all other marital groups (all p < 0.0001). The five-year survival rate for the single was six percentage points lower than the married for both men and women. After controlling for age, race, cancer stage and surgery receipt, married patients had a significantly lower risk of death from cancer (for men, HR: 0.86, CI: 0.82–0.90; for women, HR: 0.87, CI: 0.83–0.91) compared with the single. Within the same cancer stage, the survival differences between the single and the married were strongest for localized and regional stages, which had overall middle-range survival rates compared to in situ or distant stage so that support from marriage could make a big difference. Conclusions: Marriage was associated with better outcomes of colon cancer for both men and women, and being single was associated with lower survival rate from colon cancer.     

Socio-Economic Inequalities in Survival of Patients with Prostate Cancer: Role of Age and Gleason Grade at Diagnosis

In the United Kingdom, survival of prostate cancer patients has improved since the 1990s. A deprivation gap in survival (better survival for the least deprived compared with the most deprived) has been reported but it is not known if differential distribution of earlier age or lower grade disease at diagnosis might explain such patterns. We therefore investigated the impact of age and Gleason grade at diagnosis on the deprivation gap in survival of prostate cancer patients over time. Incident cases of prostate cancer (ICD-10 C61) from the West of Scotland were extracted from the Scottish Cancer Registry from 1991 to 2007. Socio-economic circumstances were measured using the Scottish Index for Multiple Deprivation 2004 (SIMD). Age and deprivation specific mortality rates were obtained from the General Registrar Office for Scotland (GRO(S)). The survival gradient across the five deprivation categories was estimated with linear regression, weighted by the variance of the relative survival estimate. We examined the data for 15,292 adults diagnosed with prostate cancer between 1991 and 2007. Despite substantial improvements in survival of prostate cancer patients, a deprivation gap persists throughout the three periods of diagnoses. The deprivation gap in five year relative survival widened from −4.76 in 1991–1996 to −10.08 in 2003–2007. On age and grade-specific analyses, a significant deprivation gap in five year survival existed between all age groups except among patients'' age ≥75 and both low and high grade disease. On multivariate analyses, deprivation was significantly associated with increased excess risk of death (RER 1.48, 95% CI 1.31–1.68, p-value<0.001) independent of age, Gleason grade and period of diagnosis. The deprivation gap in survival from prostate cancer cannot be wholly explained by socio-economic differentials in early detection of disease. Further research is needed to understand whether differences in comorbidities or treatment explain inequalities in prostate cancer outcomes.     

Occupational disparities in survival from common cancers in Japan: Analysis of Kanagawa cancer registry

BackgroundLittle is known about occupational disparities in survival for common cancer sites in Japan.MethodsUsing data from a population-based cancer registry, we identified 32,870 cancer patients diagnosed during 1992–2011. We followed the patients for 5 years (median follow-up time 5.0 years). For each individual, we classified their longest-held occupation into 5 classes (upper non-manual, lower non-manual, manual, farmer, and others) following the Erikson-Goldthorpe-Portocarero scheme. Poisson regression models were used to estimate overall and site-specific mortality rate ratios (MRRs) and 95% confidence intervals (CI) for each occupational class, adjusted for sex, age, and diagnosis year. Upper non-manual workers served as the reference group. Additionally, using a binary categorization of occupations (manual workers versus non-manual workers), a causal mediation analysis with 4-way decomposition was performed to investigate the potential mediation of the association between occupation and overall mortality by cancer stage.ResultsOverall prognosis was good in this population (5-year overall survival was 81.7%). Compared with upper non-manual workers, both overall and cancer-specific mortality was higher in lower non-manual workers (MRR=1.14, 95% CI 1.05–1.24) and manual workers (MRR=1.40, 95% CI 1.29–1.53). After adjusting for the mediating influence of prognostic factors (stage and treatment), the observed occupational differences were attenuated but remained significant in manual workers: MRR = 1.23 (95% CI 1.08–1.39). Observed occupational disparities tended to be attributable to common cancers, i.e., stomach and lung among men and female breast cancer. Additionally, manual workers had 1.25 times higher odds for advanced stage. In the mediation analysis, the overall proportion explained by mediating effect of cancer stage was 29% (4% due to mediated interaction and 25% due to pure indirect effect).ConclusionWe documented occupational disparities in survival from commonly-occurring cancers in Japan. Occupational differences in cancer stage may explain one-third of the survival disparities.     

The Prognostic Value of Microsatellite Instability,KRAS, BRAF and PIK3CA Mutations in Stage II Colon Cancer Patients

In the era of personalized cancer medicine, identifying mutations within patient tumors plays an important role in defining high-risk stage II colon cancer patients. The prognostic role of BRAF V600E mutation, microsatellite instability (MSI) status, KRAS mutation and PIK3CA mutation in stage II colon cancer patients is not settled. We retrospectively analyzed 186 patients with stage II colon cancer who underwent an oncological resection but were not treated with adjuvant chemotherapy. KRAS mutations, PIK3CA mutation, V600E BRAF mutation and MSI status were determined. Survival analyses were performed. Mutations were found in the patients with each mutation in the following percentages: 23% (MSI), 35% (KRAS), 19% (BRAF) and 11% (PIK3CA). A trend toward worse overall survival (OS) was seen in patients with an MSI (5-year OS 74% versus 82%, adjusted hazard ratio [HR] 1.8, 95% confidence interval [CI] 0.6–4.9) and a KRAS-mutated tumor (5-year OS 77% versus 82%, adjusted HR 1.7, 95% CI 0.8–3.5). MSI and BRAF-mutated tumors tended to correlate with poorer disease-free survival (DFS) (5-year DFS 60% versus 78%, adjusted HR 1.6, 95% CI 0.5–2.1 and 5-year DFS 57% versus 77%, adjusted HR 1.1, 95% CI 0.4–2.6 respectively). In stage II colon cancer patients not treated with adjuvant chemotherapy, BRAF mutation and MSI status both tended to have a negative prognostic effect on disease-free survival. KRAS and MSI status also tended to be correlated with worse overall survival.     

Clinicopathological Characteristics of Gynecological Cancer Associated with Hypoxia-Inducible Factor 1α Expression: A Meta-Analysis Including 6,612 Subjects

BackgroundGynecological cancer is characterized by tumor hypoxia. However, the role of hypoxia-inducible factor 1α (HIF-1α) in gynecological cancer remains unclear.MethodElectronic databases including Cochrane Library, PUBMED, Web of Knowledge and clinical trial registries were searched from inception through October 2014 for published, case-control studies assessing the association between HIF-1α and the clinicopathological characteristics of gynecological cancer. We pooled results from 59 studies using fixed or random-effects models and present results as odds ratios (ORs) following the PRISMA guidelines.ResultsOur meta-analysis, which included 6,612 women, demonstrated that the expression of HIF-1α was associated with the clinicopathological characteristics of gynecological cancer. The expression of HIF-1α in cancer or borderline tissue was significantly higher than that in normal tissue (cancer vs. normal: odds ratio (OR) =9.59, 95% confidence interval (CI): 5.97, 15.39, p<0.00001; borderline vs. normal: OR=4.13, 95% (CI): 2.43, 7.02, p<0.00001; cancer vs. borderline: OR=2.70, 95% (CI): 1.69, 4.31, p<0.0001). The expression of HIF-1α in III‒IV stage or lymph node metastasis was significantly higher than that in I‒II stage or that without lymph node metastasis, respectively (OR=2.66, 95% (CI): 1.87,3.79, p<0.00001; OR= 3.98, 95% (CI): 2.10,12.89, p<0.0001). HIF-1α was associated with histological grade of cancer (Grade 3 vs. Grade 1: OR=3.77, 95% (CI): 2.76,5.16, p<0.00001; Grade 3 vs. Grade 2: OR=1.62, 95% (CI): 1.20,2.19, p=0.002; Grade 2 vs. Grade 1: OR=2.34, 95% (CI): 1.82,3.00, p<0.00001),5-years disease free survival (DFS) rates (OR=2.93, 95% (CI):1.43,6.01, p=0.001) and 5-years overall survival (OS) rates (OR=5.53, 95% (CI): 2.48,12.31, p<0.0001).ConclusionHIF-1α is associated with the malignant degree, FIGO stage, histological grade, lymph node metastasis, 5-years survival rate and recurrence rate of gynecological cancer. It may play an important role in clinical treatment and prognostic evaluation.     

Prognostic impact of definitive local therapy of the primary tumor in men with metastatic prostate cancer at diagnosis: A population-based,propensity score analysis

BackgroundThis study investigated whether definitive local therapy [radical prostatectomy (RP) or brachytherapy (BT)] of the primary tumor improves survival in men with metastatic prostate cancer (PrCA) at diagnosis.MethodsData on newly diagnosed metastatic PrCA cases (stage IV, N = 7858) were obtained from the Surveillance Epidemiology and End Results (SEER) program. Conventional multivariable survival analysis and propensity score analysis were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CI) comparing men who underwent definitive local therapy of the primary tumor to those who did not.ResultsAfter adjusting for sociodemographic and tumor attributes, having RP after diagnosis with metastatic PrCA was associated with 73% (HR = 0.27, 95% CI: 0.20–0.38) lower risk of all-cause mortality and 72% (HR = 0.28, 95% CI: 0.20–0.39) reduced risk of death from PrCA. Having BT also was associated with 57% (HR = 0.43, 95% CI: 0.31–0.59) and 54% (HR = 0.46, 95% CI: 0.33–0.64) lower risk of all-cause and PrCA-specific mortality. Similar results were observed in propensity score-adjusted analysis as well as when stratified by age and extent of tumor metastasis.ConclusionsThese findings suggest that definitive local therapy improves survival in men with metastatic PrCA at diagnosis. Future work should consider comorbidities, diet, physical activity and smoking status.