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Background: Adolescents and young adults (AYAs) are diagnosed with cancer during a challenging period of life. We aimed to (1) describe positive changes (posttraumatic growth; PTG) and illness perception, and (2) determine associations between PTG and illness perception, sociodemographic, and cancer-related characteristics in Swiss AYA cancer survivors., Methods: We conducted a population-based survey among AYA cancer survivors diagnosed 1990-2005 at age 16-25 years, who had survived ≥ 5 years. We used the Posttraumatic Growth Inventory (PTGI) and the Brief Illness Perception Questionnaire (BIPQ). Data were analyzed using descriptive statistics and linear regressions., Results: Among 389 contacted survivors, 160 responded (61.3% male; mean age = 34 years, SD = 5.8). The mean PTG sum score was 54.63 (SD = 20.24; range: 8-101). Survivors reported high PTG especially in the domains Appreciation of life (mean = 3.23; 95% confidence interval, 3.05-3.40), Personal strength (2.94; 2.77-3.12), and Relating to others (2.57; 2.40-2.74). Neither sociodemographic nor cancer-related characteristics were associated with PTG. Survivors who perceived follow-up care as helpful (p < 0.001) and those with high concerns about the consequences of the illness (p < 0.001) reported higher PTG., Conclusions: Finding ways to promote PTG and to identify and address maladaptive illness perceptions may help survivors transform their experience into something meaningful for their future life., (© 2023. The Author(s).)

Background: Colorectal cancer (CRC) is among the three most common incident cancers and causes of cancer death in Switzerland for both men and women. To promote aspects of gender medicine, we examined differences in treatment decision and survival by sex in CRC patients diagnosed 2000 and 2001 in the canton of Zurich, Switzerland., Methods: Characteristics assessed of 1076 CRC patients were sex, tumor subsite, age at diagnosis, tumor stage, primary treatment option and comorbidity rated by the Charlson Comorbidity Index (CCI). Missing data for stage and comorbidities were completed using multivariate imputation by chained equations. We estimated the probability of receiving surgery versus another primary treatment using multivariable binomial logistic regression models. Univariable and multivariable Cox proportional hazards regression models were used for survival analysis., Results: Females were older at diagnosis and had less comorbidities than men. There was no difference with respect to treatment decisions between men and women. The probability of receiving a primary treatment other than surgery was nearly twice as high in patients with the highest comorbidity index, CCI 2+, compared with patients without comorbidities. This effect was significantly stronger in women than in men (p-interaction = 0.010). Survival decreased with higher CCI, tumor stage and age in all CRC patients. Sex had no impact on survival., Conclusion: The probability of receiving any primary treatment and survival were independent of sex. However, female CRC patients with the highest CCI appeared more likely to receive other therapy than surgery compared to their male counterparts.

With regard to HCV elimination in opioid agonist therapy patients by 2030, case finding and regular screening for new and re-infections remain a challenge, especially for non-cohort patients in a decentralised setting. Documentation of the HCV sero- and RNA status of each opioid agonist therapy&nbsp; patient by the cantonal physician and a yearly HCV screening reminder sent to the opioid agonist therapy prescriber combined with capillary HCV antibody and HCV RNA testing might facilitate the implementation of the FOPH guidelines. Prescription of direct-acting antivirals directly by the opioid agonist therapy prescriber could increase awareness and improve linkage to care.

Objectives: Adolescents and young adults (AYAs) are diagnosed with cancer during a critical life period full of psychosocial challenges. They may experience a significant impact of the cancer diagnosis on their psychological health, also in the long term. We aimed to (a) evaluate psychological distress in AYA cancer survivors and compare levels of distress with controls and (b) describe socio-demographic and cancer-related characteristics associated with psychological distress., Methods: We sent a questionnaire to AYA cancer survivors (aged 16-25 y at diagnosis, survived ≥5 y) registered in the Cancer Registry Zurich and Zug, Switzerland. Psychological distress was measured using the Brief Symptom Inventory-18 (BSI-18) assessing anxiety, depression, and somatization and a global severity index (GSI) (cutoff score indicating psychological distress: T ≥ 57). Distress levels were compared between survivors and controls. We used logistic regression to determine associations of socio-demographic and cancer-related characteristics with distress., Results: Of 160 AYA cancer survivors, 34 (21%) reported being distressed (27% in women, 17% in men; P = 0.129). Compared with controls, survivors did not report higher levels of distress (all P values > 0.05). Survivors with migration background and survivors with late effects reported higher levels on GSI, somatization, and anxiety. Higher levels of depression were associated with being female, not being in a partnership, and having late effects., Conclusions: A substantial subgroup of AYA cancer survivors reported psychological distress. Systematically screening for distress and providing psychological follow-up for survivors at risk may help to provide adequate psychological support., (© 2019 John Wiley & Sons, Ltd.)

Knowledge on former diagnosis, treatment and survivorship is important for adolescent and young adult cancer survivors (AYACS) to make informed healthcare decisions. We aimed to (a) describe the information AYACS reported to have received, (b) identify current information needs and survivors' preferred format of communication, and (c) examine associations between information needs and cancer-related/socio-demographic characteristics, psychological distress and health-related quality of life (HRQoL). We identified AYACS (16-25 years at diagnosis; ≥5 years since diagnosis) through the Cancer Registry Zurich and Zug. Survivors received a questionnaire on information received and current information needs, socio-demographic information, psychological distress (Brief Symptom Inventory-18) and HRQoL (SF-12). Clinical characteristics were available from the cancer registry. We used descriptive statistics and univariable regression models. Of 160 responders, most reported to have received information on disease (96.3%), treatment (96.3%) and follow-up (89.4%), fewer on late effects (63.1%). Survivors reported information needs on late effects (78.7%), follow-up (71.3%), disease (58.1%) and treatment (55.6%). Information needs were associated with experiencing psychological distress and lower mental HRQoL. Most Swiss AYACS have information needs, especially on follow-up and late effects. Therefore, AYACS should be personally, continuously and proactively informed about their disease, treatment, follow-up care and late effects., (© 2018 John Wiley & Sons Ltd.)

Purpose: The aim was to study follow-up care attendance in adolescent and young adult (AYA) cancer survivors to investigate: (1) correlates of the intention to attend follow-up care and (2) whether the intention is associated with the actual attendance, applying the theory of planned behavior (TPB)., Methods: We conducted a questionnaire survey in AYA cancer survivors diagnosed 1990-2005 at age 16-25 years, registered in the Cancer Registry Zurich and Zug, Switzerland, who had survived at least 5 years. Structural equation modeling was applied to investigate TPB-related correlates (attitudes, subjective norms, and perceived behavioral control) of intention to attend follow-up care. Logistic regression analysis was used to study the association between intention and actual attendance., Results: We included 160 AYA cancer survivors in the study (mean age at study: 34.0 years, mean age at diagnosis: 21.6 years, 98 [61.3%] male). Positive attitudes toward follow-up care (coefficient = 0.32, 95% confidence interval [CI]: 0.05 to 0.60) and supportive subjective norms (coefficient = 0.59, 95% CI: 0.41 to 0.78) were associated with higher intention to attend follow-up care. Perceived behavioral control was not associated with intention to attend (coefficient = -0.13, 95% CI: -0.36 to 0.10), but with actual attendance (odds ratio [OR] = 4.55, 95% CI: 1.83 to 11.31). Higher intention was associated with actual follow-up care attendance (OR = 14.29, 95% CI: 5.80 to 35.21)., Conclusion: Positive attitudes and supportive social norms were associated with higher intention to attend follow-up care, and higher intention was associated with actual follow-up care attendance. Increasing awareness of the importance and benefits of follow-up care not only among survivors but also family, friends and healthcare professionals may help increase follow-up care attendance among AYA cancer survivors.

Purpose: Today, survival rates for adolescent and young adult (AYA) cancer patients exceed 80%. However, cancer and treatment leave many patients suffering from chronic conditions. These late effects may impair their health-related quality of life (HRQoL). We aimed to (1) compare HRQoL of AYA cancer survivors with the Swiss general population and (2) investigate socio-demographic and cancer-related characteristics associated with poor HRQoL., Methods: AYA cancer survivors (age 16-25 at diagnosis; ≥5 years survival) who had been identified through the Cancer Registry Zurich and Zug, Switzerland, filled out a questionnaire. We assessed HRQoL using the Short-Form 12 (SF-12), producing two scores: Physical Component Summary score (PCS, physical health) and Mental Component Summary score (MCS, mental health). We used multivariable logistic regression analyses to investigate associated characteristics., Results: We compared 155 survivors with 350 controls. Survivors had significantly lower physical health than controls (mean = 52.5 vs. mean = 54.7, p < 0.001). Male survivors reported better mental health than controls (55.2 vs.53.3, p = 0.078) and females slightly worse (49.8 vs. 51.8, p = 0.285). Poor physical health was strongly associated with having a migration background (OR = 4.63, p = 0.008) and unemployment (OR = 7.66, p = 0.005). Poor mental health was associated with female sex (OR = 2.69, p = 0.057), suffering from late effects (OR = 5.91, p < 0.001) and a migration background (OR = 5.82, p = 0.004)., Conclusions: Results emphasize the need for individualized support services to improve survivors' HRQoL in vulnerable subgroups. We recommend adapted care for women and migrants, in addition to educational and employment support systems.

Data quality is an important issue in cancer registration. This paper provides a comprehensive overview of the four main data quality indicators (comparability, validity, timeliness, and completeness) for the Cancer Registry Zurich and Zug (Switzerland). We extracted all malignant cancer cases (excluding non-melanoma skin cancer) diagnosed between 1980 and 2014 in the canton of Zurich. Methods included the proportion of morphologically verified cases (MV%), the proportion of DCN and DCO cases (2009-2014), cases with primary site uncertain (PSU%), the stability of incidence rates over time, age-specific incidence rates for childhood cancer, and mortality:incidence (MI) ratios. The DCO rate decreased from 6.4% in 1997 to 0.8% in 2014 and was <5% since 2000. MV% was 95.5% in 2014. PSU% was <3% over the whole period. The incidence rate of all tumours increased over time with site-specific fluctuations. The overall M:I ratio decreased from 0.58 in 1980 to 0.37 in 2014. Overall, data quality of the Cancer Registry Zurich and Zug was acceptable according to the methods presented in this review. Most indicators improved over time with low DCO rates, high MV%, low PSU%, relatively low M:I ratios and age-specific incidence of childhood cancer within reference ranges.

This is the first comprehensive evaluation of completeness of case ascertainment in Swiss cancer registration. There is currently no method available that is considered to be the gold standard. Apart from simple measures such as the proportion of cases where registration was initiated by a death certificate and the proportion of diagnoses on the basis of histology or cytology/haematology, we applied two dedicated approaches: (i) the semiquantitative method of comparing the mortality to incidence rate ratio with relative survival (MI-Surv method) and (ii) the Flow method, which provides a quantitative estimate for the completeness depending on time since diagnosis. All 10 Swiss cancer registries in operation since at least 2006 and providing the required parameters were included. Simple and dedicated methods showed high completeness across all cancer registries and for most cancer types tested, with the notable exception of lymphoid leukaemia.

The aims of this paper are to describe the incidence trends of invasive cutaneous melanoma in the Canton of Zurich and to evaluate clinical and pathological factors such as cancer subtype, localization, age and Breslow thickness. A retrospective analysis was carried out with data from the population-based Cancer Registry of Zurich and Zug located in Zurich. A total of 8469 cases in 8034 different patients of invasive cutaneous melanoma were registered for the period 1980-2010 in the Canton of Zurich. Incidence trends were age standardized to the European standard population. Joinpoint regression was used to compute changes in incidence and mortality rates, measured as the annual percent change (APC). The most common subtypes of cutaneous melanoma were superficial spreading melanoma (SSM, 41.1%), followed by nodular melanoma (16.5%), lentigo maligna melanoma (13.5%), acral-lentiginous melanoma (5.0%) and other types of melanoma (2.8%); 21.1% were melanoma not otherwise specified. The trunk was the most frequent location (30.8%), followed by the lower limb and hip (26.4%) and the upper limb and shoulder (22.8%). Statistically significantly increasing incidence trends were observed for both men (APC=3.0%) and women (APC=2.1%). Incidences of SSM and melanoma not otherwise specified were the histological subtypes for which a significant increase in incidence was observed (APC for the period 1980-2010=3.2% for both). In terms of Breslow thickness, thin melanomas (0.01-1.00 mm) showed an increasing incidence. The incidence of melanoma increased in both men and women between 1980 and 2010. In terms of the different subtypes and Breslow thickness, increasing incidences of the SSM and of thin melanomas (0.01-1.00 mm) were observed. These observations are in agreement with other studies from Southern and Western Switzerland as well as other European countries and the USA.

Questions Under Study: Teenage and young adult (TYA) cancer patients are faced with the diagnosis during a challenging period of psychosocial development that may affect social outcomes in the long term. Therefore, we aimed to: (1) determine differences in social outcomes between long-term TYA cancer survivors and healthy controls and (2) identify factors associated with adverse social outcomes., Methods: We sent a questionnaire to TYA cancer survivors (aged 16-25 years at diagnosis, 5 years after diagnosis) registered in the Cancer Registry Zurich and Zug. Information on controls was obtained from the Swiss Health Survey 2012. We assessed educational achievement, employment status, marital status and life partnership (survivors only), and compared these outcomes between survivors and controls. We used logistic regression to identify sociodemographic and cancer-related factors associated with social outcomes., Results: We included 160 TYA cancer survivors and 999 controls. Educational achievement of survivors differed significantly from controls (p = 0.012): more survivors than controls reported upper secondary education (33 vs 27%) and fewer survivors reported university education (12 vs 21%). No significant differences were found for employment (p = 0.515) and marital status (p = 0.357). The majority of survivors (91%) and controls (90%) were employed, and 37% of survivors were married, compared with 41% of controls. There were no cancer-related factors associated with having only basic education. Unemployment was associated with younger age at diagnosis (odds ratio [OR] 5.3, 95% confidence interval [CI] 1.3-30.8) and self-reported late effects (OR 4.7, 95% CI 1.3-19.5). Survivors of younger age at diagnosis were more likely not to be married (OR 2.7, 95% CI 1.3-5.7) and not to have a life partner (OR 2.3, 95% CI 1.0-5.2)., Conclusions: Our findings indicate that TYA cancer survivors completed applied higher education rather than a university education. Future studies including larger samples of TYA cancer survivors are needed to validate our findings and to explore the reasons for and satisfaction with the observed educational pathway.

Background: The aim of this study was to assess associations of stage, grade, and age with the primary treatment of prostate cancer (PCa) patients comparing the incidence years 2000/2001 and 2012/2013, and to estimate the relative survival (RS) for patients diagnosed in 2000/2001., Methods: We included 1,541 men diagnosed in 2000/2001 and 1,605 men diagnosed in 2012/2013. Multiple imputation methods were applied to missing data for stage and grade. Multinomial logistic regression analyses were used to explore the associations of stage, grade, and age with treatment. RS was estimated using the Ederer II approach., Results: In 2000/2001, older patients were more likely to choose active surveillance (AS)/watchful waiting (WW) or to receive androgen deprivation therapy (ADT) compared to surgery; in 2012/2013, this association was only observed for ADT but not for AS/WW. In 2000/2001, the overall 1-, 5-, and 10-year RS was approximately 99, 94, and 92%, respectively. RS was highest for patients who underwent surgical procedures or radiotherapy and considerably lower for patients with ADT., Conclusion: Our data show that today AS/WW is an option not only for patients with a life expectancy of < 10 years but also for younger men with localized PCa. PCa patients have a good RS if the cancer is diagnosed at an early stage., (© 2017 S. Karger GmbH, Freiburg.)

Despite the individually different molecular alterations in tumors, the malignancy associated biological traits are strikingly similar. Results of a previous study using renal cell carcinoma (RCC) as a model pointed towards cancer-related features, which could be visualized as three groups by microarray based gene expression analysis. In this study, we used a mathematic model to verify the presence of these groups in RCC as well as in other cancer types. We developed an algorithm for gene-expression deviation profiling for analyzing gene expression data of a total of 8397 patients with 13 different cancer types and normal tissues. We revealed three common Cancer Transcriptomic Profiles (CTPs) which recurred in all investigated tumors. Additionally, CTPs remained robust regardless of the functions or numbers of genes analyzed. CTPs may represent common genetic fingerprints, which potentially reflect the closely related biological traits of human cancers.

The cytokine interleukin-33 (IL-33) is abundantly expressed in epithelial barrier tissues such as salivary glands. Here, we characterized nuclear IL-33 protein expression by immunohistochemistry in benign and malignant salivary gland tumors and associated it with disease outcome. Most benign salivary gland tumors expressed IL-33, and all Warthin's tumors showed strong and consistent IL-33 expression in the basally oriented cells of their bilayered epithelium. In the malignant group of neoplasms, nuclear IL-33 expression was limited to specific tumor entities-for example, to epithelial-myopepithelial carcinomas (n = 9/11), acinic cell carcinomas (n = 13/27), and oncocytic carcinomas (n = 2/2). IL-33 expression in the combined group of malignant salivary gland neoplasms was significantly associated with favorable histological parameters, lack of metastasis, and longer overall survival, compared with IL-33-negative tumors. We conclude that IL-33 expression is a novel prognostic marker for malignant salivary gland tumors with potential use in clinical diagnostics., (© The Author(s) 2016.)

Purpose: As survival rates of adolescent and young adult (AYA) cancer patients increase, a growing number of AYA cancer survivors need follow-up care. However, there is little research on their preferences for follow-up care. We aimed to (1) describe AYA cancer survivors' preferences for the organization and content of follow-up care, (2) describe their preferences for different models of follow-up, and (3) investigate clinical and sociodemographic characteristics associated with preferences for the different models., Methods: AYA cancer survivors (diagnosed with cancer at age 16-25 years; ≥5 years after diagnosis) were identified through the Cancer Registry Zurich and Zug. Survivors completed a questionnaire on follow-up attendance, preferences for organizational aspects of follow-up care (what is important during follow-up, what should be included during appointments, what specialists should be involved, location), models of follow-up (telephone/questionnaire, general practitioner (GP), pediatric oncologist, medical oncologist, multidisciplinary team), and sociodemographic characteristics. Information on tumor and treatment was available through the Cancer Registry Zurich and Zug., Results: Of 389 contacted survivors, 160 (41.1 %) participated and 92 (57.5 %) reported still attending follow-up. Medical aspects of follow-up care were more important than general aspects (p < 0.001). Among different organizational models, follow-up by a medical oncologist was rated higher than all other models (p = 0.002). Non-attenders of follow-up rated GP-led follow-up significantly higher than attenders (p = 0.001)., Conclusion: Swiss AYA cancer survivors valued medical content of follow-up and showed a preference for medical oncologist-led follow-up. Implementation of different models of follow-up care might improve accessibility and attendance among AYA cancer survivors.

Background: A population-based analysis of patients with glioma diagnosed between 1980 and 1994 in the Canton of Zurich in Switzerland confirmed the overall poor prognosis of glioblastoma. To explore changes in outcome, registry data were reevaluated for patients diagnosed between 2005 and 2009., Methods: Patients with glioblastoma who were diagnosed between 2005 and 2009 were identified by the Zurich and Zug Cancer Registry. The prognostic significance of epidemiological and clinical data, isocitrate dehydrogenase 1 (IDH1)(R132H) mutation status, and O6 methylguanine DNA methyltransferase (MGMT) promoter methylation status was analyzed using the Kaplan-Meier method and the Cox proportional hazards model., Results: A total of 264 patients with glioblastoma were identified, for an annual incidence of 3.9 compared with the previous incidence of 3.7. The mean age of the patients at the time of diagnosis was 59.5 years in the current cohort compared with 61.3 years previously. The overall survival (OS) rate was 46.4% at 1 year, 22.5% at 2 years, and 14.4% at 3 years in the current study compared with 17.7% at 1 year, 3.3% at 2 years, and 1.2% at 3 years as reported previously. The median OS for all patients with glioblastoma was 11.5 months compared with 4.9 months in the former patient population. The median OS was 1.9 months for best supportive care, 6.2 months for radiotherapy alone, 6.7 months for temozolomide alone, and 17.0 months for radiotherapy plus temozolomide. Multivariate analysis revealed age, Karnofsky performance score, extent of tumor resection, first-line treatment, year of diagnosis, and MGMT promoter methylation status were associated with survival in patients with IDH1(R132H) -nonmutant glioblastoma., Conclusions: The OS of patients newly diagnosed with glioblastoma in the Canton of Zurich in Switzerland markedly improved from 1980 through 1994 to 2005 through 2009. Cancer 2016;122:2206-15. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Questions Under Study: Lung cancer belongs to the most common cancers in Switzerland. We examined trends in lung cancer incidence, with focus on sex, histology and laterality, in the Canton of Zurich since 1980., Material and Methods: Registry data consisting of 16 798 lung cancer cases from 1980 to 2010 were analysed. Cases were classified into adenocarcinoma (ADC), squamous cell carcinoma (SCC), small-cell carcinoma (SCLC), large cell tumour and carcinoid tumour. Age-standardised (European standard) incidence rates (IR) per 100 000 person-years, male-to-female incidence-rate ratio (M/F-IRR), and left-to-right lung incidence-rate ratio (L/R-IRR) were calculated., Results: Over the study period, ADC occurred most frequently (31.9%), followed by SCC (29.1%), SCLC (15.4%), large cell carcinoma (6.3%), and carcinoid tumour (1.5%). Other/unspecified subtypes accounted for 15.7%. In men, the IR of SCC decreased from 34.2/100 000 (95% confidence interval [CI] 32.5-35.9) in 1980 to 12.8/100 000 (12.0-13.6) in 2010, but increased in women from 3.4/100 000 (2.7-4.0) to 4.0/100 000 (3.4-4.5). The IR of ADC increased in women from 5.1/100 000 (4.1-5.8) to 12.6/100 000 (11.8-13.4) and in men from 15.1/100 000 (14.0-16.3) to 19.4/100 000 (18.4-20.4). Overall M/F-IRR was 2.61; the highest ratio (5.8) was seen for SCC and the lowest (0.77) for carcinoid tumour. All histological subtypes showed a higher susceptibility of the right lung., Conclusion: Our data reflect the global increase of lung cancer in women. ADC increased over time in women and men, whereas SCC decreased markedly among men. These trends may have occurred owing to changes in smoking behaviour and cigarette composition.

Background: Brain metastasis is a common endpoint in patients suffering from malignant melanoma. However, little is known about factors that predispose to brain metastases., Objective: We performed a retrospective clinical and pathological investigation of melanoma patients with brain metastases in order to better characterise this patient population., Methods: 193 melanoma patients with brain metastasis histologically diagnosed between 1990 and 2015 at the University Hospital Zurich were retrospectively identified and further specified for sex, age at diagnosis and detection of brain metastasis, and localisation. In addition, data were extracted regarding the subtype of primary melanoma, Breslow tumour thickness, Clark Level, mutation status, extent of metastatic spread and history of a second melanoma., Results: We found a significant male predominance (n = 126/193; 65%; p < 0.001). Breslow tumour thickness showed a wide range from 0.2 to 12.0 mm (n = 99; median 2.3 mm). 14 of 101 melanomas (14%) were classified as T1, thereof 11 (79%) were found in men. In 32 of 193 patients (17%), the primary melanoma was unknown., Conclusions: Of special interest in our series is the high incidence of male predominance (79%) in cases of thin metastasing melanoma (14%), implicating genetic or epigenetic (hormonal) gender differences underlying tumour progression. Additionally, the high percentage of unknown primary melanoma (17%), at least partly representing completely regressed melanomas, indicates the importance of immune surveillance in melanoma progression.

HIV-infected women are at increased risk of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir [odds ratio (OR) per 100-cell/μL decrease = 1.15, 95% CI: 1.08, 1.22], or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/μL (OR = 1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use = 0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 vs. >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts, is a significant risk factor for CIN2/3 and cervical cancer., (© 2015 UICC.)

Purpose: To examine the incidence and characteristics of metachronous contralateral breast cancer (CBC) among women in the Canton of Zurich, Switzerland., Methods: For 1980-2006, patients with unilateral invasive breast cancer (UBC) were analysed for metachronous CBC. Poisson's regression was used to estimate incidence rates of metachronous CBC according to age, year of diagnosis, follow-up period since first breast cancer and morphology., Results: Of 16,323 patients with UBC, 700 (4.3%) developed a second malignant tumour of the opposite breast. Median age at first breast cancer was lower in the CBC group than in the full cohort. Median interval time between first and second breast cancer was 5.5 (interquartile range 2.6-10.1) years. Incidence rate at age 20-29 was 1006 (95% confidence interval, CI, 452-2238) cases per 100,000 person-years and decreased to 299 (199-450) at 80-84. Age-adjusted incidence rates according to period of diagnosis decreased from 618 (530-721) for 1980-1984 to 329 (217-500) cases per 100,000 person-years for 2005-2006. Incidence rate ratio of CBC for lobular carcinoma was 1.28 (95% CI 0.99-1.67) adjusted by age group and period of diagnosis compared to ductal carcinoma., Conclusions: In our study, incidence rates for CBC are comparable with findings from the literature. A reduction in the incidence of metachronous CBC, thought to be due to adjuvant therapies, is seen in our data. In our cohort, younger age and lobular carcinoma were associated with an increased risk of CBC.

During the last decades, autopsy rates have dramatically decreased in many countries. The Cancer Registry Zurich, which exists since 1980, provides the opportunity to address to what extent the number of autopsies in cancer patients has changed over a longer period of time and how often autopsies provide a diagnosis of clinically undetected cancer. Data from the Cancer Registry Zurich consisting of 102,434 cancer cases among 89,933 deceased patients between 1980 and 2010 were analyzed by means of descriptive statistics. The autopsy rate declined from 60 % in 1980 to 7 % in 2010. The total number of autopsies performed decreased from 1179 in 1986 to 220 in 2010. Furthermore, there was also a decline in the rate of newly detected tumours based on autopsy information. In 1980, the rate of newly detected tumours through autopsy was 42 % compared with 2010, when the rate had declined to 17 %. A consequence of the reduced autopsy rate is the reduction of incidental findings at autopsy in cancer registration. However, this reduction has not negatively affected the total incidence of cancer. It seems that the state-of-the-art diagnostic tools used for tumour detection are sufficiently reliable, allowing the scientific community to trust the quality of data provided by cancer registries in spite of decreasing autopsy rates.

Background: Breast cancer (BC) is the most commonly diagnosed cancer and a leading cause of death in younger women., Methods: We analysed incidence, mortality and relative survival (RS) in women with BC aged 20-49 years at diagnosis, between 1996 and 2009 in Switzerland. Trends are reported as estimated annual percentage changes (EAPC)., Results: Our findings confirm a slight increase in the incidence of BC in younger Swiss women during the period 1996-2009. The increase was largest in women aged 20-39 years (EAPC 1.8%). Mortality decreased in both age groups with similar EAPCs. Survival was lowest among women 20-39 years (10-year RS 73.4%). We observed no notable differences in stage of disease at diagnosis that might explain these differences., Conclusions: The increased incidence and lower survival in younger women diagnosed with BC in Switzerland indicates possible differences in risk factors, tumour biology and treatment characteristics that require additional examination., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Chimeric read-through RNAs are transcripts originating from two directly adjacent genes (<10 kb) on the same DNA strand. Although they are found in next-generation whole transcriptome sequencing (RNA-Seq) data on a regular basis, investigating them further has usually been refrained from. Therefore, their expression patterns or functions in general, and in oncogenesis in particular, are poorly understood., Results: We used paired-end RNA-Seq and a specifically designed computational data analysis pipeline (FusionSeq) to nominate read-through events in a small discovery set of renal cell carcinomas (RCC) and confirmed them in a larger validation cohort. 324 read-through events were called overall; 22/27 (81%) selected nominees passed validation with conventional PCR and were sequenced at the junction region. We frequently identified various isoforms of a given read-through event. 2/22 read-throughs were up-regulated: BC039389-GATM was higher expressed in RCC compared to benign adjacent kidney; KLK4-KRSP1 was expressed in 46/169 (27%) RCCs, but rarely in normal tissue. KLK4-KRSP1 expression was associated with worse clinical outcome in the patient cohort. In cell lines, both read-throughs influenced molecular mechanisms (i.e. target gene expression or migration/invasion) in a way that counteracted the effect of the respective parent transcript GATM or KLK4., Conclusions: Our data suggests that the up-regulation of read-through RNA chimeras in tumors is not random but causes regulatory effects on cellular mechanisms and may impact patient survival.

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., (© 2014 S. Karger AG, Basel.)

Introduction: There is a need to assess risk of second primary cancers in prostate cancer (PCa) patients, especially since PCa treatment may be associated with increased risk of second primary tumours., Methods: We calculated standardized incidence ratios (SIRs) for second primary tumours comparing men diagnosed with PCa between 1980 and 2010 in the Canton of Zurich, Switzerland (n = 20,559), and the general male population in the Canton., Results: A total of 1,718 men developed a second primary tumour after PCa diagnosis, with lung and colon cancer being the most common (15 and 13% respectively). The SIR for overall second primary cancer was 1.11 (95%CI: 1.06-1.17). Site-specific SIRs varied from 1.19 (1.05-1.34) to 2.89 (2.62-4.77) for lung and thyroid cancer, respectively. When stratified by treatment, the highest SIR was observed for thyroid cancer (3.57 (1.30-7.76)) when undergoing surgery, whereas liver cancer was common when treated with radiotherapy (3.21 (1.54-5.90)) and kidney bladder was most prevalent for those on hormonal treatment (3.15 (1.93-4.87)). Stratification by time since PCa diagnosis showed a lower risk of cancer for men with PCa compared to the general population for the first four years, but then a steep increase in risk was observed., Conclusion: In the Canton of Zurich, there was an increased risk of second primary cancers among men with PCa compared to the general population. Increased diagnostic activity after PCa diagnosis may partly explain increased risks within the first years of diagnosis, but time-stratified analyses indicated that increased risks remained and even increased over time.

Aims and background. Cancer incidence variations are influenced by different factors including socioeconomic status, risk factors and use of screening. The purpose of this study was to examine trends in cancer incidence in two urban areas in Europe showing differences in influencing factors but also some common characteristics in the context of data quality of the corresponding cancer registries.Methods. Age-standardized incidence rates (world standard - ASRW) for cases diagnosed in 2000-2009 for Sofia (Bulgaria) and the Canton of Zurich (Switzerland) were calculated using data from the corresponding cancer registries. Average annual percent change (AAPC) was estimated with Joinpoint regression analysis. Data quality was estimated in terms of proportions of microscopically verified (MV%) and death-certificate-only (DCO%) cases. Results. ASRWs for all sites were higher in Zurich for men (311 vs 262 per 100,000) and women (241 vs 231 per 100,000) than in Sofia. Colorectal (both sexes), lung (men), cervical and corpus uteri cancer had a higher incidence in Sofia. Prostate, breast and lung (women) cancer were more often diagnosed in Zurich. A significant increase in female lung cancer incidence was observed in both areas. Overall incidence decreased in Zurich, while it did not significantly change in Sofia. MV% was lower in Sofia than in the Canton of Zurich but increased steadily up to 85% in 2009, whereas in the Canton of Zurich MV% was more or less stable around 95%. The DCO% of Sofia was 19% in 2000 and steadily decreased to 8% in 2009. In the Canton of Zurich, the DCO% decreased from 5% in 2000 but increased again from 2006 onwards, up to 3% in 2009. Conclusions. Cancer incidence rates differ between Sofia and Zurich. Differences concerning socioeconomic status, risk factors, use of cancer screening but also data quality may influence these results.

Background: The use of cancer related therapy in cancer patients at the end-of-life has increased over time in many countries. Given a lack of published Swiss data, the objective of this study was to describe delivery of health care during the last month before death of cancer patients., Methods: Claims data were used to assess health care utilization of cancer patients (identified by cancer registry data of four participating cantons), deceased between 2006-2008. Primary endpoints were hospitalization rate and delivery of cancer related therapies during the last 30 days before death. Multivariate logistic regression assessed the explanatory value of patient and geographic characteristics., Results: 3809 identified cancer patients were included. Hospitalization rate (mean 68.5%, 95% CI 67.0-69.9) and percentage of patients receiving anti-cancer drug therapies (ACDT, mean 14.5%, 95% CI 13.4-15.6) and radiotherapy (mean 7.7%, 95% CI 6.7-8.4) decreased with age. Canton of residence and insurance type status most significantly influenced the odds for hospitalization or receiving ACDT., Conclusions: The intensity of cancer specific care showed substantial variation by age, cancer type, place of residence and insurance type status. This may be partially driven by cultural differences within Switzerland and the cantonal organization of the Swiss health care system.

Background: In diffuse large B-cell lymphomas, gene expression profiling studies attributed a major biologic role to non-neoplastic cells of the tumour microenvironment as its composition and characteristics were shown to predict survival. In particular, the expression of selected genes encoding components of the extracellular matrix was reported to be associated with clinical outcome. Nevertheless, the translation of these data into robust, routinely applicable immunohistochemical markers is still warranted. Therefore, in this study, we analysed the combination of the expression of the extracellular matrix components Fibronectin and SPARC on formalin-fixed paraffin embedded tissue derived from 173 patients with DLBCL in order to recapitulate gene expression profiling data., Results: The expression of Fibronectin and SPARC was detected in 77/173 (44.5%) and 125/173 (72.3%) cases, respectively, and 55/173 (31.8%) cases were double positive. Patients with lymphomas expressing Fibronectin showed significantly longer overall survival when compared to negative ones (6.3 versus 3.6 years). Moreover, patients with double positive lymphomas also presented with significantly longer overall survival when compared with the remaining cases (11.6 versus 3.6 years) and this combined expression of both markers results in a better association with overall survival data than the expression of SPARC or Fibronectin taken separately (Hazard ratio 0.41, 95% confidence interval 0.17 to 0.95, p = 0.037). Finally, neither Fibronectin nor SPARC expression was associated with any of the collected clinico-pathological parameters., Conclusions: The combined immunohistochemical assessment of Fibronectin and SPARC, two components of the extracellular matrix, represents an important tool for the prediction of survival in diffuse large B-cell lymphomas. Our study suggests that translation of gene expression profiling data on tumour microenvironment into routinely applicable immunohistochemical markers is a useful approach for a further characterization of this heterogeneous type of lymphoma.

Although persons infected with human immunodeficiency virus (HIV), particularly men who have sex with men, are at excess risk for anal cancer, it has been difficult to disentangle the influences of anal exposure to human papillomavirus (HPV) infection, immunodeficiency, and combined antiretroviral therapy. A case-control study that included 59 anal cancer cases and 295 individually matched controls was nested in the Swiss HIV Cohort Study (1988-2011). In a subset of 41 cases and 114 controls, HPV antibodies were tested. A majority of anal cancer cases (73%) were men who have sex with men. Current smoking was significantly associated with anal cancer (odds ratio (OR) = 2.59, 95% confidence interval (CI): 1.25, 5.34), as were antibodies against L1 (OR = 4.52, 95% CI: 2.00, 10.20) and E6 (OR = ∞, 95% CI: 4.64, ∞) of HPV16, as well as low CD4+ cell counts, whether measured at nadir (OR per 100-cell/μL decrease = 1.53, 95% CI: 1.18, 2.00) or at cancer diagnosis (OR per 100-cell/μL decrease = 1.24, 95% CI: 1.08, 1.42). However, the influence of CD4+ cell counts appeared to be strongest 6-7 years prior to anal cancer diagnosis (OR for <200 vs. ≥500 cells/μL = 14.0, 95% CI: 3.85, 50.9). Smoking cessation and avoidance of even moderate levels of immunosuppression appear to be important in reducing long-term anal cancer risks.

Background: There is considerable heterogeneity in the use of chemotherapy in early breast cancer (BC), despite international recommendations issued from the NCCN, NIH and the St.Gallen bi-annual conference., Methods: We included 1,535 patients from seven Swiss cancer registries between 2003 and 2005 receiving chemotherapy for stage I to III BC. Chemotherapy was categorised into (a) FAC/FEC, anthracyclines followed by CMF or anthracycline-taxane combinations (FAC-T) (781 patients) and (b) other chemotherapy regimens such as CMF/AC (EC) (754 patients). Predictors for choosing FAC-T over non-FAC-T chemotherapy were separately determined in all patients and in ER-negative patients (n = 496) by multivariate logistic regression analysis., Results: The use of FAC-T increased significantly over time, from 44% in 2003 to 55% in 2005. BC stage III (versus stage I-II) and nodal positivity were the predominant predictors for using FAC-T chemotherapy in the adjusted model (odds ratio (OR) 4.1, 95%-confidence intervals (CI) 2.6-6.3 and OR 3.0, 95%-CI 2.0-4.4, respectively). In high-risk ER-negative BC patients, poor histological differentiation was more important to choose FAC-T chemotherapy (OR 3.8, 95%-CI 1.9-7.5) than tumour stage or nodal status. The use of FAC-T chemotherapy varied substantially among the seven geographic regions, from 20% in rural Grisons-Glarus to 73% in Zurich., Conclusions: Tumour biology is a predominant factor for choosing FAC-T over older chemotherapy regimens in patients with ER-negative early BC, but improvements should be made to reduce the substantial regional heterogeneity. Further epidemiological studies should assess how the use of FAC-T chemotherapy is affecting clinical outcome in patients with early BC and different risk profiles.

Objective: Tumor necrosis factor (TNF) inhibitors have revolutionized the treatment of severe rheumatoid arthritis (RA), yet drug discontinuation is common. The aim of this study was to compare treatment retention rates and specific causes of anti-TNF discontinuation in a population-based RA cohort., Methods: All patients treated with etanercept, infliximab, or adalimumab within the Swiss Clinical Quality Management RA cohort between 1997 and 2006 were included in the study. Causes of treatment discontinuation were broadly categorized as adverse events (AEs) or nontoxic causes, and further subdivided into specific categories. Specific causes of treatment interruption were analyzed using a Cox proportional hazards model and adjusted for potential confounders., Results: A total of 2,364 anti-TNF treatment courses met the inclusion criteria. Treatment discontinuation was reported 803 times: 309 with etanercept, 249 with infliximab, and 245 with adalimumab. Drug inefficacy represented the largest single cause of treatment discontinuation (55.8% of cases). The median time of receiving anti-TNF therapy was 37 months, but discontinuation rates differed between the 3 anti-TNF agents (P < 0.001), with shorter retention rates for infliximab (hazard ratio [HR] 1.24, 99% confidence interval [99% CI] 1.01-1.51). The specific causes of treatment discontinuation revealed an increased risk of AEs with infliximab (HR 1.4, 99% CI 1.003-1.96), mostly due to an increased risk of infusion or allergic reactions (HR 2.11, 99% CI 1.23-3.62). Other discontinuation causes were equally distributed between the anti-TNF agents., Conclusion: In this population, infliximab was associated with higher overall discontinuation rates compared with etanercept and adalimumab, which is mainly due to an increased risk of infusion or allergic reactions.

Objective: Patients with rheumatoid arthritis (RA) in whom the response to anti-tumor necrosis factor (anti-TNF) therapy is inadequate have several therapeutic options, such as switching to an alternative anti-TNF agent or initiating B cell-depleting therapy with rituximab (RTX). Although both therapeutic options have been proven effective in trials, no head-to-head comparisons are available. The aim of this study was to compare the effectiveness of RTX with that of an alternative anti-TNF agent in the management of patients with RA who had an inadequate response to anti-TNF therapy., Methods: This prospective cohort study was nested within the Swiss Clinical Quality Management RA cohort and included all patients who had an inadequate response to at least 1 anti-TNF agent and subsequently received either 1 cycle of RTX or an alternative anti-TNF agent. The primary outcome was the evolution of RA disease activity (as measured on the Disease Activity Score in 28 joints [DAS28]), which was analyzed using multivariate regression models for longitudinal data., Results: One hundred sixteen patients with RA were included; 50 patients received 1 cycle of RTX, and 66 patients were treated with a second or a third alternative anti-TNF agent. At baseline, there were no significant differences between the 2 groups in age, sex, disease duration, and disease activity. Evolution of the DAS28 was more favorable in the group that received RTX compared with the group that received an alternative anti-TNF agent (P = 0.01). At 6 months, the mean decrease in the DAS28 was -1.61 (95% confidence interval [95% CI] -1.97, -1.25) among patients receiving RTX and -0.98 (95% CI -1.33, -0.62) among those receiving subsequent anti-TNF therapy., Conclusion: The results of this observational study suggest that treatment with RTX may be more effective than switching to an alternative anti-TNF agent in patients with RA in whom active disease persists despite anti-TNF therapy.