Background Ionizing Radiation and the Risk of Childhood Cancer: A Census-Based Nationwide Cohort Study

BACKGROUND Exposure to medium or high doses of ionizing radiation is a known risk factor for cancer in children. The extent to which low dose radiation from natural sources contributes to the risk of childhood cancer remains unclear. OBJECTIVES In a nationwide census-based cohort study, we investigated whether the incidence of childhood cancer was associated with background radiation from terrestrial gamma and cosmic rays. METHODS Children aged <16 years in the Swiss National Censuses in 1990 and 2000 were included. The follow-up period lasted until 2008 and incident cancer cases were identified from the Swiss Childhood Cancer Registry. A radiation model was used to predict dose rates from terrestrial and cosmic radiation at locations of residence. Cox regression models were used to assess associations between cancer risk and dose rates and cumulative dose since birth. RESULTS Among 2,093,660 children included at census, 1,782 incident cases of cancer were identified including 530 with leukemia, 328 with lymphoma, and 423 with a tumor of the central nervous system (CNS). Hazard ratios for each mSv increase in cumulative dose of external radiation were 1.03 (95% CI: 1.01, 1.05) for any cancer, 1.04 (1.00, 1.08) for leukemia, 1.01 (0.96, 1.05) for lymphoma, and 1.04 (1.00, 1.08) for CNS tumors. Adjustment for a range of potential confounders had little effect on the results. CONCLUSIONS Our study suggests that background radiation may contribute to the risk of cancer in children including leukemia and CNS tumors.

Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: the d: a: d study.

BACKGROUND The association between combination antiretroviral therapy (cART) and cancer risk, especially regimens containing protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear. METHODS Participants were followed from the latest of D:A:D study entry or January 1, 2004, until the earliest of a first cancer diagnosis, February 1, 2012, death, or 6 months after the last visit. Multivariable Poisson regression models assessed associations between cumulative (per year) use of either any cART or PI/NNRTI, and the incidence of any cancer, non-AIDS-defining cancers (NADC), AIDS-defining cancers (ADC), and the most frequently occurring ADC (Kaposi sarcoma, non-Hodgkin lymphoma) and NADC (lung, invasive anal, head/neck cancers, and Hodgkin lymphoma). RESULTS A total of 41,762 persons contributed 241,556 person-years (PY). A total of 1832 cancers were diagnosed [incidence rate: 0.76/100 PY (95% confidence interval: 0.72 to 0.79)], 718 ADC [0.30/100 PY (0.28-0.32)], and 1114 NADC [0.46/100 PY (0.43-0.49)]. Longer exposure to cART was associated with a lower ADC risk [adjusted rate ratio: 0.88/year (0.85-0.92)] but a higher NADC risk [1.02/year (1.00-1.03)]. Both PI and NNRTI use were associated with a lower ADC risk [PI: 0.96/year (0.92-1.00); NNRTI: 0.86/year (0.81-0.91)]. PI use was associated with a higher NADC risk [1.03/year (1.01-1.05)]. Although this was largely driven by an association with anal cancer [1.08/year (1.04-1.13)], the association remained after excluding anal cancers from the end point [1.02/year (1.01-1.04)]. No association was seen between NNRTI use and NADC [1.00/year (0.98-1.02)]. CONCLUSIONS Cumulative use of PIs may be associated with a higher risk of anal cancer and possibly other NADC. Further investigation of biological mechanisms is warranted.

Cancer-related therapies at the end of life in hospitalized cancer patients from four Swiss cantons: SAKK 89/09.

The use of cancer-related therapies in cancer patients hospitalized at the end of life has increased in many countries over time. Given the scarcity of published Swiss data, the objective of this study was to evaluate the influence of hospital type and other factors on the delivery of health care during the last month before death. Claims data were used to assess health care utilization of cancer patients (identified by cancer registry data of four participating Swiss cantons) who deceased between 2006 and 2008. Primary endpoints were delivery of cancer-related therapies during the last 30 days before death. Multivariate logistic regression assessed the explanatory value of hospital type, patient and geographic characteristics. Of 3,809 identified cancer patients in the claims database, 2,086 patients dying from cancer were hospitalized during the last 30 days before death, generating 2,262 inpatient episodes. Anticancer drug therapy was given in 22.2% and radiotherapy in 11.7% of episodes. Besides age and cancer type, the canton of residence and hospital type showed independent, statistically significant associations with intensity of care, which was highest in university hospitals. These results should initiate a discussion among oncologists in Switzerland and may question the compliance with standard of care guidelines for terminal cancer patients.

Prognostic factors and outcomes in primary urethral cancer: results from the international collaboration on primary urethral carcinoma.

PURPOSE To evaluate risk factors for survival in a large international cohort of patients with primary urethral cancer (PUC). METHODS A series of 154 patients (109 men, 45 women) were diagnosed with PUC in ten referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank test was used to investigate various potential prognostic factors for recurrence-free (RFS) and overall survival (OS). Multivariate models were constructed to evaluate independent risk factors for recurrence and death. RESULTS Median age at definitive treatment was 66 years (IQR 58-76). Histology was urothelial carcinoma in 72 (47 %), squamous cell carcinoma in 46 (30 %), adenocarcinoma in 17 (11 %), and mixed and other histology in 11 (7 %) and nine (6 %), respectively. A high degree of concordance between clinical and pathologic nodal staging (cN+/cN0 vs. pN+/pN0; p < 0.001) was noted. For clinical nodal staging, the corresponding sensitivity, specificity, and overall accuracy for predicting pathologic nodal stage were 92.8, 92.3, and 92.4 %, respectively. In multivariable Cox-regression analysis for patients staged cM0 at initial diagnosis, RFS was significantly associated with clinical nodal stage (p < 0.001), tumor location (p < 0.001), and age (p = 0.001), whereas clinical nodal stage was the only independent predictor for OS (p = 0.026). CONCLUSIONS These data suggest that clinical nodal stage is a critical parameter for outcomes in PUC.

HIV testing and burden of HIV infection in black cancer patients in Johannesburg, South Africa: a cross-sectional study.

BACKGROUND HIV infection is a known risk factor for cancer but little is known about HIV testing patterns and the burden of HIV infection in cancer patients. We did a cross-sectional analysis to identify predictors of prior HIV testing and to quantify the burden of HIV in black cancer patients in Johannesburg, South Africa. METHODS The Johannesburg Cancer Case-control Study (JCCCS) recruits newly-diagnosed black cancer patients attending public referral hospitals for oncology and radiation therapy in Johannesburg . All adult cancer patients enrolled into the JCCCS from November 2004 to December 2009 and interviewed on previous HIV testing were included in the analysis. Patients were independently tested for HIV-1 using a single ELISA test . The prevalence of prior HIV testing, of HIV infection and of undiagnosed HIV infection was calculated. Multivariate logistic regression models were fitted to identify factors associated with prior HIV testing. RESULTS A total of 5436 cancer patients were tested for HIV of whom 1833[33.7% (95% CI=32.5-35.0)] were HIV-positive. Three-quarters of patients (4092 patients) had ever been tested for HIV. The total prevalence of undiagnosed HIV infection was 11.5% (10.7-12.4) with 34% (32.0-36.3) of the 1833 patients who tested HIV-positive unaware of their infection. Men >49 years [OR 0.49(0.39-0.63)] and those residing in rural areas [OR 0.61(0.39-0.97)] were less likely to have been previously tested for HIV. Men with at least a secondary education [OR 1.79(1.11-2.90)] and those interviewed in recent years [OR 4.13(2.62 - 6.52)] were likely to have prior testing. Women >49 years [OR 0.33(0.27-0.41)] were less likely to have been previously tested for HIV. In women, having children <5 years [OR 2.59(2.04-3.29)], hormonal contraceptive use [OR 1.33(1.09-1.62)], having at least a secondary education [OR:2.08(1.45-2.97)] and recent year of interview [OR 6.04(4.45-8.2)] were independently associated with previous HIV testing. CONCLUSIONS In a study of newly diagnosed black cancer patients in Johannesburg, over a third of HIV-positive patients were unaware of their HIV status. In South Africa black cancer patients should be targeted for opt-out HIV testing.

Follow-up care of adolescent survivors of childhood cancer: The role of health beliefs

BACKGROUND Little is known about follow-up care attendance of adolescent survivors of childhood cancer, and which factors foster or hinder attendance. Attending follow-up care is especially important for adolescent survivors to allow for a successful transition into adult care. We aimed to (i) describe the proportion of adolescent survivors attending follow-up care; (ii) describe adolescents' health beliefs; and (iii) identify the association of health beliefs, demographic, and medical factors with follow-up care attendance. PROCEDURE Of 696 contacted adolescent survivors diagnosed with cancer at ≤16 years of age, ≥5 years after diagnosis, and aged 16-21 years at study, 465 (66.8%) completed the Swiss Childhood Cancer Survivor Study questionnaire. We assessed follow-up care attendance and health beliefs, and extracted demographic and medical information from the Swiss Childhood Cancer Registry. Cross-sectional data were analyzed using descriptive statistics and logistic regression models. RESULTS Overall, 56% of survivors reported attending follow-up care. Most survivors (80%) rated their susceptibility for late effects as low and believed that follow-up care may detect and prevent late effects (92%). Few (13%) believed that follow-up care is not necessary. Two health beliefs were associated with follow-up care attendance (perceived benefits: odds ratio [OR]: 1.56; 95% confidence interval [CI]: 1.07-2.27; perceived barriers: OR: 0.70; 95%CI: 0.50-1.00). CONCLUSIONS We show that health beliefs are associated with actual follow-up care attendance of adolescent survivors of childhood cancer. A successful model of health promotion in adolescent survivors should, therefore, highlight the benefits and address the barriers to keep adolescent survivors in follow-up care. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.

Childhood cancer and residential exposure to highways: a nationwide cohort study.

Children living near highways are exposed to higher concentrations of traffic-related carcinogenic pollutants. Several studies reported an increased risk of childhood cancer associated with traffic exposure, but the published evidence is inconclusive. We investigated whether cancer risk is associated with proximity of residence to highways in a nation-wide cohort study including all children aged <16 years from Swiss national censuses in 1990 and 2000. Cancer incidence was investigated in time to event analyses (1990-2008) using Cox proportional hazards models and incidence density analyses (1985-2008) using Poisson regression. Adjustments were made for socio-economic factors, ionising background radiation and electromagnetic fields. In time to event analysis based on 532 cases the adjusted hazard ratio for leukaemia comparing children living <100 m from a highway with unexposed children (≥500 m) was 1.43 (95 % CI 0.79, 2.61). Results were similar in incidence density analysis including 1367 leukaemia cases (incidence rate ratio (IRR) 1.57; 95 % CI 1.09, 2.25). Associations were similar for acute lymphoblastic leukaemia (IRR 1.64; 95 % CI 1.10, 2.43) and stronger for leukaemia in children aged <5 years (IRR 1.92; 95 % CI 1.22, 3.04). Little evidence of association was found for other tumours. Our study suggests that young children living close to highways are at increased risk of developing leukaemia.

Very long-term survival patterns of young patients treated with radical prostatectomy for high-risk prostate cancer

OBJECTIVE In patients with a long life expectancy with high-risk (HR) prostate cancer (PCa), the chance to die from PCa is not negligible and may change significantly according to the time elapsed from surgery. The aim of this study was to evaluate long-term survival patterns in young patients treated with radical prostatectomy (RP) for HRPCa. MATERIALS AND METHODS Within a multiinstitutional cohort, 600 young patients (≤59 years) treated with RP between 1987 and 2012 for HRPCa (defined as at least one of the following adverse characteristics: prostate specific antigen>20, cT3 or higher, biopsy Gleason sum 8-10) were identified. Smoothed cumulative incidence plot was performed to assess cancer-specific mortality (CSM) and other cause mortality (OCM) rates at 10, 15, and 20 years after RP. The same analyses were performed to assess the 5-year probability of CSM and OCM in patients who survived 5, 10, and 15 years after RP. A multivariable competing risk regression model was fitted to identify predictors of CSM and OCM. RESULTS The 10-, 15- and 20-year CSM and OCM rates were 11.6% and 5.5% vs. 15.5% and 13.5% vs. 18.4% and 19.3%, respectively. The 5-year probability of CSM and OCM rates among patients who survived at 5, 10, and 15 years after RP, were 6.4% and 2.7% vs. 4.6% and 9.6% vs. 4.2% and 8.2%, respectively. Year of surgery, pathological stage and Gleason score, surgical margin status and lymph node invasion were the major determinants of CSM (all P≤0.03). Conversely, none of the covariates was significantly associated with OCM (all P≥ 0.09). CONCLUSIONS Very long-term cancer control in young high-risk patients after RP is highly satisfactory. The probability of dying from PCa in young patients is the leading cause of death during the first 10 years of survivorship after RP. Thereafter, mortality not related to PCa became the main cause of death. Consequently, surgery should be consider among young patients with high-risk disease and strict PCa follow-up should enforce during the first 10 years of survivorship after RP.

Swiss Feline Cancer Registry: A Retrospective Study of the Occurrence of Tumours in Cats in Switzerland from 1965 to 2008

Cancer is one of the leading causes of death in companion animals. Information on the epidemiology of cancer is instrumental for veterinary practitioners in patient management; however, spontaneously arising tumours in companion animals also resemble those in man and can provide useful data in combating cancer. Veterinary cancer registries for cats are few in number and have often remained short-lived. This paper presents a retrospective study of tumours in cats in Switzerland from 1965 to 2008. Tumour diagnoses were coded according to topographical and morphological keys of the International Classification of Oncology for Humans (ICD-O-3). Correlations between breed, sex and age were then examined using a multiple logistic regression model. A total of 18,375 tumours were diagnosed in 51,322 cats. Of these, 14,759 (80.3%) tumours were malignant. Several breeds had significantly lower odds ratios for developing a tumour compared with European shorthair cats. The odds of a cat developing a tumour increased with age, up to the age of 16 years, and female cats had higher risk of developing a tumour compared with male cats. Skin (4,970; 27.05%) was the most frequent location for tumours, followed by connective tissue (3,498; 19.04%), unknown location (2,532; 13.78%) and female sexual organs (1,564; 8.51%). The most common tumour types were epithelial tumours (7,913; 43.06%), mesenchymal tumours (5,142; 27.98%) and lymphoid tumours (3,911; 21.28%).

Prognostic Relevance of Palliative Primary Tumor Removal in 37,793 Metastatic Colorectal Cancer Patients: A Population-Based, Propensity Score-Adjusted Trend Analysis

OBJECTIVE To assess whether palliative primary tumor resection in colorectal cancer patients with incurable stage IV disease is associated with improved survival. BACKGROUND There is a heated debate regarding whether or not an asymptomatic primary tumor should be removed in patients with incurable stage IV colorectal disease. METHODS Stage IV colorectal cancer patients were identified in the Surveillance, Epidemiology, and End Results database between 1998 and 2009. Patients undergoing surgery to metastatic sites were excluded. Overall survival and cancer-specific survival were compared between patients with and without palliative primary tumor resection using risk-adjusted Cox proportional hazard regression models and stratified propensity score methods. RESULTS Overall, 37,793 stage IV colorectal cancer patients were identified. Of those, 23,004 (60.9%) underwent palliative primary tumor resection. The rate of patients undergoing palliative primary cancer resection decreased from 68.4% in 1998 to 50.7% in 2009 (P < 0.001). In Cox regression analysis after propensity score matching primary cancer resection was associated with a significantly improved overall survival [hazard ratio (HR) of death = 0.40, 95% confidence interval (CI) = 0.39-0.42, P < 0.001] and cancer-specific survival (HR of death = 0.39, 95% CI = 0.38-0.40, P < 0.001). The benefit of palliative primary cancer resection persisted during the time period 1998 to 2009 with HRs equal to or less than 0.47 for both overall and cancer-specific survival. CONCLUSIONS On the basis of this population-based cohort of stage IV colorectal cancer patients, palliative primary tumor resection was associated with improved overall and cancer-specific survival. Therefore, the dogma that an asymptomatic primary tumor never should be resected in patients with unresectable colorectal cancer metastases must be questioned.

Follow-up care of young childhood cancer survivors: attendance and parental involvement.

PURPOSE Despite recommendations, only a proportion of long-term childhood cancer survivors attend follow-up care. We aimed to (1) describe the follow-up attendance of young survivors aged 11-17 years; (2) describe the parental involvement in follow-up, and (3) investigate predictors of follow-up attendance and parental involvement. METHODS As part of the Swiss Childhood Cancer Survivor Study, a follow-up questionnaire was sent to parents of childhood cancer survivors aged 11-17 years. We assessed follow-up attendance of the child, parents' involvement in follow-up, illness perception (Brief IPQ), and sociodemographic data. Clinical data was available from the Swiss Childhood Cancer Registry. RESULTS Of 309 eligible parents, 189 responded (67 %; mean time since diagnosis 11.3 years, range 6.8-17.2) and 75 % (n = 141) reported that their child still attended follow-up. Of these, 83 % (n = 117) reported ≥1 visit per year and 17 % (n = 23) reported <1 visit every year. Most survivors saw pediatric oncologists (n = 111; 79 % of 141), followed by endocrinologists (n = 24, 17 %) and general practitioners (n = 22, 16 %). Most parents (92 %) reported being involved in follow-up (n = 130). In multivariable and Cox regression analyses, longer time since diagnosis (p = 0.025) and lower perceived treatment control (assessed by IPQ4: how much parents thought follow-up can help with late effects; p = 0.009) were associated with non-attendance. Parents' overall information needs was significantly associated with parental involvement in the multivariable model (p = 0.041). CONCLUSION Educating survivors and their parents on the importance and effectiveness of follow-up care might increase attendance in the longer term.

Employment Situation of Parents of Long-Term Childhood Cancer Survivors.

BACKGROUND Taking care of children diagnosed with cancer affects parents' professional life. The impact in the long-term however, is not clear. We aimed to compare the employment situation of parents of long-term childhood cancer survivors with control parents of the general population, and to identify clinical and socio-demographic factors associated with parental employment. METHODS As part of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to parents of survivors aged 5-15 years, who survived ≥5 years after diagnosis. Information on control parents of the general population came from the Swiss Health Survey (restricted to men and women with ≥1 child aged 5-15 years). Employment was categorized as not employed, part-time, and full-time employed. We used generalized ordered logistic regression to determine associations with clinical and socio-demographic factors. Clinical data was available from the Swiss Childhood Cancer Registry. RESULTS We included 394 parent-couples of survivors and 3'341 control parents (1'731 mothers; 1'610 fathers). Mothers of survivors were more often not employed (29% versus 22%; ptrend = 0.007). However, no differences between mothers were found in multivariable analysis. Fathers of survivors were more often employed full-time (93% versus 87%; ptrend = 0.002), which remained significant in multivariable analysis. Among parents of survivors, mothers with tertiary education (OR = 2.40, CI:1.14-5.07) were more likely to be employed. Having a migration background (OR = 3.63, CI: 1.71-7.71) increased the likelihood of being full-time employed in mothers of survivors. Less likely to be employed were mothers of survivors diagnosed with lymphoma (OR = 0.31, CI:0.13-0.73) and >2 children (OR = 0.48, CI:0.30-0.75); and fathers of survivors who had had a relapse (OR = 0.13, CI:0.04-0.36). CONCLUSION Employment situation of parents of long-term survivors reflected the more traditional parenting roles. Specific support for parents with low education, additional children, and whose child had a more severe cancer disease could improve their long-term employment situation.

Cause-Specific Long-Term Mortality in Survivors of Childhood Cancer in Switzerland: A Population Based Study.

Survivors of childhood cancer have a higher mortality than the general population. We describe cause-specific long-term mortality in a population-based cohort of childhood cancer survivors. We included all children diagnosed with cancer in Switzerland (1976-2007) at age 0-14 years, who survived ≥5 years after diagnosis and followed survivors until December 31, 2012. We obtained causes of death (COD) from the Swiss mortality statistics and used data from the Swiss general population to calculate age-, calendar year- and sex-standardized mortality ratios (SMR), and absolute excess risks (AER) for different COD, by Poisson regression. We included 3'965 survivors and 49'704 person years at risk. Of these, 246 (6.2%) died, which was 11 times higher than expected (SMR 11.0). Mortality was particularly high for diseases of the respiratory (SMR 14.8) and circulatory system (SMR 12.7), and for second cancers (SMR 11.6). The pattern of cause-specific mortality differed by primary cancer diagnosis, and changed with time since diagnosis. In the first 10 years after 5-year survival, 78.9% of excess deaths were caused by recurrence of the original cancer (AER 46.1). Twenty-five years after diagnosis, only 36.5% (AER 9.1) were caused by recurrence, 21.3% by second cancers (AER 5.3) and 33.3% by circulatory diseases (AER 8.3). Our study confirms an elevated mortality in survivors of childhood cancer for at least 30 years after diagnosis with an increased proportion of deaths caused by late toxicities of the treatment. The results underline the importance of clinical follow-up continuing years after the end of treatment for childhood cancer. This article is protected by copyright. All rights reserved.

Older patients with low Charlson score and high-risk prostate cancer benefit from radical prostatectomy

INTRODUCTION The aim of the study was to identify the appropriate level of Charlson comorbidity index (CCI) in older patients (>70 years) with high-risk prostate cancer (PCa) to achieve survival benefit following radical prostatectomy (RP). METHODS We retrospectively analyzed 1008 older patients (>70 years) who underwent RP with pelvic lymph node dissection for high-risk prostate cancer (preoperative prostate-specific antigen >20 ng/mL or clinical stage ≥T2c or Gleason ≥8) from 14 tertiary institutions between 1988 and 2014. The study population was further grouped into CCI < 2 and ≥2 for analysis. Survival rate for each group was estimated with Kaplan-Meier method and competitive risk Fine-Gray regression to estimate the best explanatory multivariable model. Area under the curve (AUC) and Akaike information criterion were used to identify ideal 'Cut off' for CCI. RESULTS The clinical and cancer characteristics were similar between the two groups. Comparison of the survival analysis using the Kaplan-Meier curve between two groups for non-cancer death and survival estimations for 5 and 10 years shows significant worst outcomes for patients with CCI ≥ 2. In multivariate model to decide the appropriate CCI cut-off point, we found CCI 2 has better AUC and p value in log rank test. CONCLUSION Older patients with fewer comorbidities harboring high-risk PCa appears to benefit from RP. Sicker patients are more likely to die due to non-prostate cancer-related causes and are less likely to benefit from RP.

Income in Adult Survivors of Childhood Cancer.

INTRODUCTION Little is known about the impact of childhood cancer on the personal income of survivors. We compared income between survivors and siblings, and determined factors associated with income. METHODS As part of the Swiss Childhood Cancer Survivor Study (SCCSS), a questionnaire was sent to survivors, aged ≥18 years, registered in the Swiss Childhood Cancer Registry (SCCR), diagnosed at age <21 years, who had survived ≥5 years after diagnosis of the primary tumor. Siblings were used as a comparison group. We asked questions about education, profession and income and retrieved clinical data from the SCCR. We used multivariable logistic regression to identify characteristics associated with income. RESULTS We analyzed data from 1'506 survivors and 598 siblings. Survivors were less likely than siblings to have a high monthly income (>4'500 CHF), even after we adjusted for socio-demographic and educational factors (OR = 0.46, p<0.001). Older age, male sex, personal and parental education, and number of working hours were associated with high income. Survivors of leukemia (OR = 0.40, p<0.001), lymphoma (OR = 0.63, p = 0.040), CNS tumors (OR = 0.22, p<0.001), bone tumors (OR = 0.24, p = 0.003) had a lower income than siblings. Survivors who had cranial irradiation, had a lower income than survivors who had no cranial irradiation (OR = 0.48, p = 0.006). DISCUSSION Even after adjusting for socio-demographic characteristics, education and working hours, survivors of various diagnostic groups have lower incomes than siblings. Further research needs to identify the underlying causes.