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Recent studies have shown that in the area of the Kangerlussuaq glacier, a large GPS velocities residual after removing predicted purely elastic deformations caused by present-day ice loss suggests the possibility of a fast rebound to little ice age (LIA) deglaciation. We previously investigated this area with a Maxwell viscoelastic rheology Earth model and compared the model predictions with GPS residual. We found a match for a rather thick lithospheric thickness and a rather low mantle viscosity structure beneath SE-Greenland. In this study we are going to examine the effect of a Burger model: 1) we compare the results with those from the Maxwell model and 2) we estimate if and where the differences can be discriminated with observational data.Maxwell models describe a steady state mantle deformation and they are the most commonly model used in post glacial rebound problems. Burgers models, instead, describe a time-varying mantle deformation, which include an initial fast transient components followed by a steady-state phase of mantle deformation. This kind of transient deformation would allow to reconcile the Earth rebound caused by the Pleistocene deglaciation and the faster rebound caused by the recent LIA deglaciation.We then analyze several scenarios of ice retreat in the last 2000 years in the fiord in front of Kangerlussuaq glacier, in view of the difference between the two rheologies.

PDF file - 69K, Italian GIST case material.

PDF file - 76K, Swiss GIST case material.

Purpose: Gastrointestinal stromal tumors (GIST) are characterized by gain-of-function mutations in KIT/PDGFRA genes leading to a constitutive receptor activation which is well counteracted by imatinib. However, cases in which imatinib as first-line treatment has no effects are reported (primary resistance). Our purpose is to investigate alterations in downstream effectors, not reported so far in mutated GIST, possibly explaining the primary resistance to targeted treatments.Experimental Design: Two independent naive GIST cohorts have been analyzed for KIT, PDGFRA, KRAS, and BRAF mutations by direct sequencing. Cell lines expressing a constitutively activated and imatinib-responding KIT, alone or in combination with activated KRAS and BRAF, were produced and treated with imatinib. KIT receptor and its downstream effectors were analyzed by direct Western blotting.Results: In naive GISTs carrying activating mutations in KIT or PDGFRA a concomitant activating mutation was detected in KRAS (5%) or BRAF (about 2%) genes. In vitro experiments showed that imatinib was able to switch off the mutated receptor KIT but not the downstream signaling triggered by RAS–RAF effectors.Conclusions: These data suggest the activation of mitogen—activated protein kinase pathway as a possible novel mechanism of primary resistance to imatinib in GISTs and could explain the survival curves obtained from several clinical studies where 2% to 4% of patients with GIST treated with imatinib, despite carrying KIT-sensitive mutations, do not respond to the treatment. Clin Cancer Res; 18(6); 1769–76. ©2012 AACR.

Breast cancer survivors often experience recurrence or a second primary cancer. We developed an automated approach to predict the occurrence of any second breast cancer (SBC) using patient-level data and explored the generalizability of the models with an external validation data source. Breast cancer patients from the cancer registry of Zurich, Zug, Schaffhausen, Schwyz (N = 3213; training dataset) and the cancer registry of Ticino (N = 1073; external validation dataset), diagnosed between 2010 and 2018, were used for model training and validation, respectively. Machine learning (ML) methods, namely a feed-forward neural network (ANN), logistic regression, and extreme gradient boosting (XGB) were employed for classification. The best-performing model was selected based on the receiver operating characteristic (ROC) curve. Key characteristics contributing to a high SBC risk were identified. SBC was diagnosed in 6% of all cases. The most important features for SBC prediction were age at incidence, year of birth, stage, and extent of the pathological primary tumor. The ANN model had the highest area under the ROC curve with 0.78 (95% confidence interval [CI] 0.750.82) in the training data and 0.70 (95% CI 0.61-0.79) in the external validation data. Investigating the generalizability of different ML algorithms, we found that the ANN generalized better than the other models on the external validation data. This research is a first step towards the development of an automated tool that could assist clinicians in the identification of women at high risk of developing an SBC and potentially preventing it., International Journal of Cancer, ISSN:0020-7136, ISSN:1097-0215

BACKGROUND Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0-14 years) and adults (aged 15-99 years) diagnosed with a haematological malignancy during 2000-14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0-24 years). METHODS We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0-14 years), adolescents (15-19 years), and young adults (20-24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. FINDINGS 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010-14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000-14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. INTERPRETATION This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group. FUNDING Children with Cancer UK, the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute, and the American Cancer Society.

Recent studies suggest the hotspot currently under Iceland was located beneath eastern Greenland at ~40 Ma BP and that the upwelling of hot material from the Iceland plume towards Greenland is ongoing. A warm upper mantle has a low viscosity, which in turn causes the solid Earth to rebound much faster to deglaciation. In the area of the Kangerlussuaq glacier, a large GPS velocities residual after removing predicted purely elastic deformations caused by present-day ice loss suggests the possibility of such fast rebound to little ice age (LIA) deglaciation. Here we investigate the lithospheric thickness and the mantle viscosity structure beneath SE-Greenland by means of model predictions of solid Earth deformation driven by a low viscosity mantle excited by the LIA deglaciation to the present day. From the comparison of such modeled deformations with the GPS residual, we conclude that 1) a rather thick lithosphere is preferred (90-100 km) 2) and the upper mantle most likely has a viscosity that changes with depth. Assuming a two layer upper mantle, it is not well constrained which part of the upper mantle has to be low, with a preference for low viscosity in the deeper upper mantle.To understand such results we implemented forward modelling with more realistic earth models, relying on improvements in seismic models, petrology and gravity data. This yields 3D viscosity maps that can be compared to inferences based on the 1D model and forms the basis for 3D GIA models. The conclusion based on the 1D model can be explained with 3D Earth models. In the area of the Kangerlussuaq glacier the seismic derived viscosities prefer a higher viscosity layer above a lower viscosity one. This stems from the slow decrease in viscosity with depth. The layer that is characterized as shallow upper mantle still contains shallow regions with low temperatures, while the deeper upper mantle reaches low viscosities. Generally, for GIA earth models the “higher above lower” viscosity layering is unusual. However, the analysis of the 1D model clearly shows this to be one of the preferred model regions, in combination with a large lithosphere thickness of 100 km. This is a notable result that draws attention to the importance of shallow layering in GIA models.

Background: An increase in breast cancer (BC) incidence in young women (YW) as well as disparities in BC outcomes have been reported in Switzerland. We sought to evaluate treatment and outcome differences among YW with BC (YWBC).Methods: YW diagnosed with stage I-III BC between 2000-2014 were identified through nine cancer registries. Concordance with international guidelines was assessed for 12 items covering clinical/surgical management, combined in a quality-of-care score. We compared score and survival outcome between the two linguistic-geographic regions of Switzerland (Swiss-Latin and Swiss-German) and evaluated the impact of quality-of-care on survival.Results: A total of 2477 women were included. The median age was 37.3 years (IQR 34.0-39.4 years), with 50.3% having stage II BC and 70.3% having estrogen receptor positive tumors. The mean quality-of-care score was higher in the Latin region compared to the German region (86.0% vs. 83.2%, p < 0.0005). Similarly, 5- and 10-year overall survival rates were higher in the Latin compared to the German region (92.3% vs. 90.2%, p = 0.0593, and 84.3% vs. 81.5%, p = 0.0025, respectively). There was no difference in survival according to the score. In the univariate analysis, women in the Latin region had a 28% lower mortality risk compared to women in the German region (hazard ratio 0.72; 95% CI 0.59-0.89). In the multivariable analysis, only stage, differentiation, tumor subtype and treatment period remained independently associated with survival.Conclusions: We identified geographic disparities in the treatment and outcome of YWBC in Switzerland. National guidelines for YWBC should be implemented to standardize treatment. Awareness should be raised among YW and clinicians that BC does not discriminate by age.

SUMMARY We consider the viscoelastic rheology of the solid Earth under the Antarctic Peninsula due to ice mass loss that commenced after the breakup of the Larsen-B ice shelf. We extend the previous analysis of nearby continuous GPS time-series to include five additional years and the additional consideration of the horizontal components of deformation. They show strong uplift from ∼2002 to 2011 followed by reduced uplift rates to 2018. Modelling the GPS-derived uplift as a viscoelastic response to ongoing regional ice unloading from a new ice model confirms earlier estimates of low upper-mantle viscosities of ∼0.3–3 × 1018 Pa s in this region but allows a wide range of elastic lithosphere thickness. The observed and modelled north coordinate component shows little nonlinear variation due to the location of ice mass change to the east of the GPS sites. However, comparison of the observed and modelled east coordinate component constrains the upper-mantle viscosity to be less than ∼9 × 1018 Pa s, consistent with the viscosity range suggested by the uplift rates alone and providing important, largely independent, confirmation of that result. Our horizontal analysis showed only marginal sensitivity to modelled lithospheric thickness. The results for the horizontal components are sensitive to the adopted plate rotation model, with the estimate based on ITRF2014 suggesting that the sum of residual plate motion and pre-2002 glacial isostatic adjustment is likely less than ∼±0.5 mm yr−1 in the east component.

Background: To examine time intervals between needle/core biopsy, breast cancer diagnosis, surgery and radiotherapy (RT) as quality metrics in the management of stage I-III breast cancer in a representative Swiss population sample. Methods: Based on seven regional cancer registries covering 45% of the Swiss population, we identified 2628 women which underwent surgery for stage I-III breast cancer without receiving (neo)-adjuvant chemotherapy between January 1, 2003 and December 31, 2005. Four different time intervals were defined: a) time between needle/core biopsy and diagnosis of breast cancer, b) time between diagnosis of breast cancer and surgery, c) time between needle/core biopsy and surgery, d) time between surgery and adjuvant RT. These four time intervals were analyzed according to age, nationality, health insurance status, public vs. private hospitals and geography. We also investigated whether case discussion at tumor board delayed patient management. A one-way analysis of variance (ANOVA) and multiple comparison tests were used to assess differences between groups. All tests were performed using STATA v.15. Results: 2628 women were identified, median age was 67 years (IQR: 58-77). Breast-conserving surgery was performed in 1899 cases (72.3%), mastectomy in 539 cases (20.5%), unspecified surgery /missing data in 190 cases (7.2%). Adjuvant RT was delivered in 1546/2628 patients (58.8 %). Time interval between biopsy and surgery was age-dependent, ranging from 22 days (95% CI: 19.6 - 25.2) for women < 60 years to 39 days (95% CI: 27.0-50.3) for women 80+ years old (p Time between surgery and RT did not correlate with age (p=0.83); the interval was 33% longer in tertiary teaching hospitals than in private clinics (61 vs. 46 days, p Conclusions: Major differences in treatment waiting times were observed between patients with stage I-III breast cancer. Elderly and foreign patients were at risk for delayed surgery after biopsy. Data from patients with longer timelines need to be analyzed to identify further reasons for delays. Citation Format: Zwahlen DR, Herrmann C, Mousavi M, Bordoni A, Bouchardy C, Konzelmann I, Staehlin K, Rohrmann S, Oehler C, Zimmermann M. Treatment delivery waiting times for stage I-III breast cancer patients in Switzerland : A pooled analysis of 7 cancer registries over the 2003-2008 period [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-32.

Purpose of the review: More than 50% of all gynaecological cancers can be classified as rare tumours (defined as an annual incidence of

We constrain viscoelastic Earth rheology and recent ice-mass change in the northern Marguerite Bay region of the Antarctic Peninsula. GPS time series from Rothera and San Martin stations show bedrock uplift range of ∼-0.8-1.8 mm/year over 1999-2005 and 2016-2020 but ∼3.5-6.0 mm/year over ∼2005-2016. Digital elevation models reveal substantial surface lowering, but at a lower rate since ∼2009. Using these data, we show that an elastic-only model cannot explain the non-linear uplift of the GPS sites but that a layered viscoelastic model can. We show close agreement between GPS uplift changes and viscoelastic models with effective elastic lithosphere thickness and upper-mantle viscosity ∼10-95 km and ∼0.1-9×1018 Pa s, respectively. Our viscosity estimate is consistent with a north-south gradient in viscosity suggested by previous studies focused on specific regions within the Antarctic Peninsula and adds further evidence of the low viscosity upper mantle in the northern Antarctic Peninsula.

The mass lost from Greenland ice sheet is one of the most important contribution to the global sea level rise, and it is under constant monitoring. However, still little is known about the heat flux at the glacier bedrock, and how it affects dynamics of the major outlet glaciers in Greenland. Recent studies suggest that the hotspot currently under Iceland have been under eastern Greenland at ~40 Ma BP and that the upwelling of hot material from the Iceland plume towards Greenland is ongoing. A warm upper mantle has a low viscosity, which in turn causes the solid Earth to rebound much faster to deglaciation. We have good reasons to believe that mantle beneath SE-Greenland has very low viscosity (Khan, et al. 2016), as also suggested by the discrepancy between the GPS velocities and the predicted purely elastic deformations caused by present-day ice loss. Here we present a preliminary computation of the Earth deformation driven by a low viscosity mantle excited by the deglatiation since the little ice age (LIA) to the present day. We produce the time series of such deformation and compare it with GPS time series, the oldest dating back to 1992.

Wieser and colleagues, in a study published in Swiss Medical Weekly in July 2018, compared incidence rates of ovarian cancer derived from the cantonal cancer registries (CCRs) as published by the National Institute for Cancer Epidemiology and Registration (NICER) with those derived from the hospital discharge data compiled by the Swiss Federal Statistical Office. The authors observed a substantial difference between these two estimates. The average age-adjusted ovarian cancer incidence rate was 14.6 per 100,000 women per year over the period 2004–2012 compared with a rate of 11.3 per 100,000 women per year reported by NICER for the same period [1]. The authors argue that the figure provided by NICER is probably an underestimation of the true figure because cancer registry data are based on voluntary information on new cases from clinicians.With our response, we show that this conclusion is not correct and the observed high rate of ovarian cancer in hospital discharge data is an artefact, probably arising from incorrect coding of non-malignant ovarian tumours. Further, we explain the purpose of epidemiological cancer registries and their difference from routinely collected discharge data.

Background: The aim of this study was to identify factors that influence the delivery of post-mastectomy radiotherapy (PMRT) in Switzerland, and to analyze the adherence to consensus guidelines. Methods: Based on 7 regional cancer registries covering 45% of the Swiss population, we identified 1408 women which underwent mastectomy for stage I-III breast cancer between January 1, 2003 and December 31, 2005. We categorized patients according to ASCO grouping in similar fashion to other comparable studies: low-risk group (T1/T2 N0): PMRT not routinely recommended; intermediate-risk group (T1/T2 N1): PMRT controversial; high risk group (T3-T4 and/or N2-N3): PMRT recommended. We further investigated factors leading to potential overtreatment (PMRT in low-risk group) or undertreatment (absence of PMRT in high-risk group). Data analysis was performed for the entire cohort, and separately for patients Results: A total of 421 patients (29.9%) received adjuvant RT after mastectomy. The rate of PMRT delivery was 67% in the high-risk group, compared to 6% and 18% in the low-risk and intermediate-risk groups, respectively. For patients at high-risk of chest wall recurrence after mastectomy (T3-T4 or N2-N3 disease), the risk of PMRT omission wassignificantly associated to older age (OR 4.25 [95% CI: 2.27-7.95] for patients ≥ 70 years) and to the absence of chemotherapy (OR 4.30 [95% CI: 1.97-9.36]). In patients with T3-T4 disease, PMRT was delivered in 77% of patients < 70 years and in 42% of patients ≥ 70 years (p PMRT was delivered to 28 patients (7%) at low-risk of recurrence after mastectomy (T1-T2 N0, negative margins). It was more frequently offered to patients Positive or close surgical margins (< 1mm) were a strong indicator for PMRT (p=0.001) and chest wall boost (p Conclusions: After mastectomy, one third of patients (33.26%) with high-risk disease did not receive PMRT. Even if we consider only patients < 70 years, a non-trivial proportion of patients with clear indication for treatment delivery did not receive PMRT (T3-T4 disease: 23%; N2-N3 disease: 18%). Further analyses are planned to explain the apparent failure of evidence-based guidelines to impact the adoption of PMRT in women with high-risk breast cancer. Citation Format: Zwahlen DR, Ess S, Zimmermann M, Bordoni A, Bouchardy C, Frick H, Konzelmann I, Mousavi M, Rohrmann S, Oehler C. Disparities in the application of post-mastectomy radiotherapy in Switzerland: A pooled analysis of 7 cancer registries over the 2003-2005 period [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-24.

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.

We explored socioeconomic and demographic disparities in breast cancer (BC) stage at presentation and survival in a Swiss population-based sample of female BC patients linked to the census-based Swiss National Cohort. Tumor stage was classified according to Surveillance, Epidemiology and End Results Program summary stage (in situ/localized/regional/distant). We used highest education level attained to estimate SEP (low/middle/high). Further demographic characteristics of interest were age at presentation (30-49/50-69/70-84 years), living in a canton with organized screening (yes/no), urbanity of residence (urban/peri-urban/rural), civil status (single/married/widowed/divorced) and nationality (Swiss/non-Swiss). We used ordered logistic regression models to analyze factors associated with BC stage at presentation and competing risk regression models for factors associated with survival. Odds of later-stage BC were significantly increased for low SEP women (odds ratio 1.19, 95%CI 1.06-1.34) compared to women of high SEP. Further, women living in a canton without organized screening program, women diagnosed outside the targeted screening age and single/widowed/divorced women were more often diagnosed at later stages. Women of low SEP experienced an increased risk of dying from BC (sub-hazard ratio 1.22, 95%CI 1.05-1.43) compared to women of high SEP. Notably, these survival inequalities could not be explained by socioeconomic differences in stage at presentation and/or other sociodemographic factors. It is concerning that these social gradients have been observed in a country with universal health insurance coverage, high health expenditures and one of the highest life expectancies in the world.

Rare cancers epidemiology is better known compared to the other rare diseases. Thanks to the long history of the European population-based cancer registries and to the EUROCARE huge database, the burden of rare cancers has been estimated the European (EU28) population. A considerable fraction of all cancers is represented by rare cancers (24%). They are a heterogeneous group of diseases, but they share similar problems: uncertainty of diagnosis, lack of therapies, poor research opportunities, difficulties in clinical trials, lack of expertise and of centres of reference. This paper analyses the major epidemiological indicators of frequency (incidence and prevalence) and outcome (5-year survival) of all rare cancers combined and of selected rare cancers that will be in depth treated in this monographic issue. Source of the results is the RARECAREnet search tool, a database publicly available. Disparities both in incidence and survival, and consequently in prevalence of rare cancers were reported across European countries. Major differences were shown in outcome: 5-year relative survival for all rare cancers together, adjusted by age and case-mix, varied from 55% or more (Italy, Germany, Belgium and Iceland) and less than 40% (Bulgaria, Lithuania and Slovakia). Similarly, for all the analyzed rare cancers, a large survival gap was observed between the Eastern and the Nordic and Central European regions. Dramatic geographical variations were assessed for curable cancers like testicular and non epithelial ovarian cancers. Geographical difference in the annual age-adjusted incidence rates for all rare cancers together varied between >140 per 100,000 (Italy, Scotland, France, Germany, and Switzerland) and

Pancreatic Neuroendocrine Neoplasms comprise a group of rare tumours with special biology, an often indolent behaviour and particular diagnostic and therapeutic requirements. The specialized biochemical tests and radiological investigations, the complexity of surgical options and the variety of medical treatments that require individual tailoring, mandate a multidisciplinary approach that can be optimally achieved through an organized network. The present study describes currents concepts in the management of these tumours as well as an insight into the challenges of delivering the pathway in and outside a Network.

Patients with soft tissue sarcoma (STS) experienced better outcomes when treated according to existing clinical practice guidelines either at reference institution or dedicated treatment networks. Despite increasing evidence supporting referral to sarcoma specialised units, up to half of patients are not managed according to guidelines, particularly those in the early stage of their disease requiring surgery. Also, criteria to certify expertise of institutions, such as the treatment volume, are debated and health authorities have only recently started identification of these centres and creation of treatment networks in Europe as well as in several countries. This process have important implications for both patient outcomes and innovation of existing treatment strategies through clinical research, making improvement of clinical pathways a priority for health care authorities. This article will discuss issues with management of patients with STS, such as pathological diagnosis and adherence to guidelines, and the definition of referral centres and networks will be illustrated along with existing experiences and population-based data.

Background Quality of cancer care (QoCC) has become an important item for providers, regulators and purchasers of care worldwide. Aim of this study is to present the results of some evidence-based quality indicators (QI) for prostate cancer (PC) at the population-based level and to compare the outcomes with data available in the literature. Methods The study included all PC diagnosed on a three years period analysis (01.01.2011–31.12.2013) in the population of Canton Ticino (Southern Switzerland) extracted from the Ticino Cancer Registry database. 13 QI, approved through the validated Delphi methodology, were calculated using the “available case” approach: 2 for diagnosis, 4 for pathology, 6 for treatment and 1 for outcome. The selection of the computed QI was based on the availability of medical documentation. QI are presented as proportion (%) with the corresponding 95% confidence interval. Results 700 PC were detected during the three-year period 2011–2013: 78.3% of them were diagnosed through a prostatic biopsy and for 72.5% 8 or more biopsy cores were taken. 46.5% of the low risk PC patients underwent active surveillance, while 69.2% of high risk PC underwent a radical treatment (radical prostatectomy, radiotherapy or brachytherapy) and 73.5% of patients with metastatic PC were treated with hormonal therapy. The overall 30-day postoperative mortality was 0.5%. Conclusions Results emerging from this study on the QoCC for PC in Canton Ticino are encouraging: the choice of treatment modalities seems to respect the international guidelines and our results are comparable to the scarce number of available international studies. Additional national and international standardisation of the QI and further QI population-based studies are needed in order to get a real picture of the PC diagnostic-therapeutic process progress through the definition of thresholds of minimal standard of care. Electronic supplementary material The online version of this article (10.1186/s12885-018-4604-2) contains supplementary material, which is available to authorized users.

Socioeconomic inequalities in cancer stage at diagnosis and survival are important public health issues. This study investigates the association between socioeconomic position (SEP) and colorectal cancer (CRC) stage at diagnosis and survival in Switzerland, a European country with highest level of medical facilities and life expectancy. We used population‐based CRC data from seven Swiss cantonal cancer registries 2001–2008 (N = 10,088) linked to the Swiss National Cohort (SNC). Follow‐up information was available until the end of 2013. SEP was estimated based on education. The association between cancer stage and SEP was assessed using logistic regression models including cancer localization (colon/rectum), sex, age, civil status, urbanity of residence, language region, and nationality (Swiss/non‐Swiss). Survival was analyzed using competing risk regressions reporting subhazard ratios (SHRs) for the risk of dying due to CRC. We observed a social gradient for later stage CRC with adjusted odds ratios (ORs) of 1.11 (95% CI: 0.97–1.19) and 1.28 (95% CI: 1.08–1.50) for middle and low SEP compared to high SEP. Further, single compared to married people had elevated odds of being diagnosed at later stages. Survival was lower in patients with CRC with low SEP in the unadjusted model (SHR: 1.18, 95% CI: 1.07–1.30). After adjustment for stage at diagnosis and further sociodemographic characteristics, significant survival inequalities by SEP disappeared but remained for non‐Swiss compared to Swiss citizens and for patients living in nonurban areas compared to their urban counterparts. Swiss public health strategies should facilitate equal access to CRC screening and optimal CRC care for all social groups and in all regions of Switzerland.

Germ-cell tumours (GCT) of the testis and penile squamous cell carcinoma (PeSCC) are a rare and a very rare uro-genital cancers, respectively. Both tumours are well defined entities in terms of management, where specific recommendations - in the form of continuously up-to-dated guide lines- are provided. Impact of these tumour is relevant. Testicular GCT affects young, healthy men at the beginning of their adult life. PeSCC affects older men, but a proportion of these patients are young and the personal consequences of the disease may be devastating. Deviation from recommended management may be a reason of a significant prognostic worsening, as proper treatment favourably impacts on these tumours, dramatically on GCT and significantly on PeSCC. RARECAREnet data may permit to analyse how survivals may vary according to geographical areas, histology and age, leading to assume that non-homogeneous health-care resources may impact the cure and definitive outcomes. In support of this hypothesis, some epidemiologic datasets and clinical findings would indicate that survival may improve when appropriate treatments are delivered, linked to a different accessibility to the best health institutions, as a consequence of geographical, cultural and economic barriers. Finally, strong clues based on epidemiological and clinical data support the hypothesis that treatment delivered at reference centres or under the aegis of a qualified multi-institutional network is associated with a better prognosis of patients with these malignancies. The ERN EURACAN represents the best current European effort to answer this clinical need.

Objective To study the impact of subtypes and comorbidities on breast cancer (BC) relapse and survival in the heterogeneous patients of the real world. Methods We identified patients diagnosed with BC between January 2003 and December 2005 from six population-based Swiss cancer registries. Clinicopathologic data was completed with information on locoregional and distant relapse and date and cause of death for over 10-years. We approximated BC subtypes using grade and the immunohistochemical panel for oestrogen, progesterone and human epidermal growth factor 2 (HER2) receptor status. We studied factors affecting relapse and survival. Results Luminal A-like subtype represented 46% of all newly diagnosed BC (N = 1831), followed by luminal B-like (N = 1504, 38%), triple negative (N = 436, 11%) and HER2 enriched (N = 204, 5%). We observed regional disparities in subtype prevalence that contribute to explain regional differences in survival formerly described. Disease relapse and BC specific mortality differed by subtype and were lower for luminal A like tumours than for other subtypes for any stage at diagnosis. After a median follow-up of 10.9 years, 1311 (33%) had died, half of them 647 (16%) due to another disease, showing the importance of comorbidities. Omission of systemic therapies in selected patients was not associated with poorer BC specific survival, BC subtype and life expectancy playing a role. Conclusions Information on tumour subtype is necessary for an adequate interpretation of population-based BC studies. Measures of comorbidity or frailty help in the evaluation of quality of care in the highly heterogeneous patients of the real world.

Purpose Mutated KIT and platelet-derived growth factor alpha gene (PDGFRA) drive GI stromal tumor (GIST) oncogenesis, but the clinical significance of their single mutations is known incompletely. Patients and Methods We identified 11 population-based series of patients with GIST through a literature search and pooled individual data from 3,067 patients treated with macroscopically complete tumor excision. Mutation analysis was done from 1,505 tumors. We analyzed associations between KIT and PDGFRA mutations and recurrence-free survival (RFS) in the subsets in which patients were treated with surgery alone. Results We identified 301 different single mutations in KIT and 33 in PDGFRA. Patients with PDGFRA mutations had more favorable RFS than those with KIT mutations (hazard ratio, 0.34; P = .004). Only one of the 35 GISTs with KIT exon 11 duplication mutations recurred. Patients with deletions of only one codon of KIT exon 11 had better RFS than those with another deletion type, and some KIT exon 11 substitution mutations (Trp557Arg, Val559Ala, and Leu576Pro) were also associated with favorable RFS. Patients with an identical mutation had greatly variable outcomes depending on the standard prognostic factors, notably, mitotic count. Commonly used risk stratification schemes tended to overestimate the risk for recurrence in subgroups with prognostically favorable mutations. Conclusion GISTs with an identical KIT or PDGFRA mutation may have widely varying risks for recurrence. Most of the patients with PDGFRA mutations and those with KIT exon 11 duplication mutation or deletion of one codon have favorable RFS with surgery alone and are usually not candidates for adjuvant therapy.

During the last 20 years, relevant diagnostic procedures and advanced treatments have been progressively introduced in the management of hepatocellular carcinoma (HCC). The aim of the present study was to assess up-to-date survival trends for HCC in southern Switzerland, a region with one of the highest incidence rates in the country.HCCs diagnosed in 1996-2009 were selected by the Ticino Cancer Registry. Cancer-specific survival (CSS) analysis was performed using the Kaplan-Meier method by calendar period: 1996-2000, 2001-2005 and 2006-2009. The log-rank test was used to detect differences in survival curves. Simultaneous assessment of prognostic factors was performed by a multivariate analysis using the Cox proportional-hazards regression model.619 HCCs were analysed. There was a significant increase of patients undergoing transarterial chemoembolisation (TACE), whereas patients undergoing curative or palliative supportive treatments remained unchanged (p0.0001). No shift to earlier stages was detected. Significant differences in CCS were observed by age-group (p0.0001), diagnosis period (p0.0001), diagnosis technique (p = 0.0035), Barcelona-Clinic liver cancer stage (p0.0001), treatment (p0.0001). Multivariate analysis confirmed the independent impact on CSS of factors above mentioned, not including the diagnosis technique. Death risk was higher for patients diagnosed in 1996-2000 (HR: 1.32; 95% CI: 1.03; 1.68) and 2001-2005 (HR: 1.33; 95% CI: 1.05; 1.67) in comparison with 2006-2009 (reference group).The current population-based report describes a major increase in HCC survival. Simultaneously an increased use of TACE has been detected, probable cofactor of the observed survival increase. Possibly additional efforts could be made to decrease the HCC stage at diagnosis through active surveillance of cirrhotic patients to allow an increase in curative treatments. For sure efforts should be made to comply with a standardised staging system for HCC, particularly for comparative population-based issues.

The management of patients with mesothelioma and thymic malignancy requires continuous multidisciplinary expertise at any step of the disease. A dramatic improvement in our knowledge has occurred in the last few years, through the development of databases, translational research programs, and clinical trials. Access to innovative strategies represents a major challenge, as there is a lack of funding for clinical research in rare cancers and their rarity precludes the design of robust clinical trials that could lead to specific approval of drugs. In this context, patient-centered initiatives, such as the establishment of dedicated networks, are warranted. International societies, such as IMIG (International Mesothelioma Interest Group) and ITMIG (International Thymic Malignancy Interest Group) provide infrastructure for global collaboration, and there are many advantages to having strong regional groups working on the same issues. There may be regional differences in risk factors, susceptibility, management and outcomes. The ability to address questions both regionally as well as globally is ideal to develop a full understanding of mesothelioma and thymic malignancies. In Europe, through the integration of national networks with EURACAN, the collaboration with academic societies and international groups, the development of networks in thoracic oncology provides multiplex integration of clinical care and research, ultimately ensuring equal access to high quality care to all patients, with the opportunity of conducting high level clinical and translational research projects.

Head and neck cancer (HNC) is a rare disease that can affect different sites and is characterized by variable incidence and 5-year survival rates across Europe. Multiple factors need to be considered when choosing the most appropriate treatment for HNC patients, such as age, comorbidities, social issues, and especially whether to prefer surgery or radiation-based protocols. Given the complexity of this scenario, the creation of a highly specialized multidisciplinary team is recommended to guarantee the best oncological outcome and prevent or adequately treat any adverse effect. Data from literature suggest that the multidisciplinary team-based approach is beneficial for HNC patients and lead to improved survival rates. This result is likely due to improved diagnostic and staging accuracy, a more efficacious therapeutic approach and enhanced communication across disciplines. Despite the benefit of MTD, it must be noted that this approach requires considerable time, effort and financial resources and is usually more frequent in highly organized and high-volume centers. Literature data on clinical research suggest that patients treated in high-accrual centers report better treatment outcomes compared to patients treated in low-volume centers, where a lower radiotherapy-compliance and worst overall survival have been reported. There is general agreement that treatment of rare cancers such as HNC should be concentrated in high volume, specialized and multidisciplinary centers. In order to achieve this goal, the creation of international collaboration network is fundamental. The European Reference Networks for example aim to create an international virtual advisory board, whose objectives are the exchange of expertise, training, clinical collaboration and the reduction of disparities and enhancement of rationalize migration across Europe. The purpose of our work is to review all aspects and challenges in and outside this network setting planned for the management of HNC patients.

To investigate differences in prostate cancer incidence between two distinct Swiss regions from 1996 to 2013 stratified by age group, grade, and T-stage. The dataset included 17,495 men living in Zurich and 3,505 men living in Ticino, diagnosed with prostate cancer between 1996 and 2013. We computed age-standardized incidence rates per 100,000 person-years using the European Standard Population. Trends were assessed using JoinPoint regression analysis Software. Age-standardized incidence rates were generally higher in Zurich compared to Ticino but the difference decreased over time. Incidence rates increased significantly up to 2002 in Zurich and 2007 in Ticino and then decreased. A statistically significant increase was observed for men aged

Background: Rare cancers pose challenges for diagnosis, treatments, and clinical decision making. Information about rare cancers is scant. The RARECARE project defined rare cancers as those with an annual incidence of less than six per 100 000 people in European Union (EU). We updated the estimates of the burden of rare cancers in Europe, their time trends in incidence and survival, and provide information about centralisation of treatments in seven European countries. Methods: We analysed data from 94 cancer registries for more than 2 million rare cancer diagnoses, to estimate European incidence and survival in 2000–07 and the corresponding time trends during 1995–2007. Incidence was calculated as the number of new cases divided by the corresponding total person-years in the population. 5-year relative survival was calculated by the Ederer-2 method. Seven registries (Belgium, Bulgaria, Finland, Ireland, the Netherlands, Slovenia, and the Navarra region in Spain) provided additional data for hospitals treating about 220 000 cases diagnosed in 2000–07. We also calculated hospital volume admission as the number of treatments provided by each hospital rare cancer group sharing the same referral pattern. Findings: Rare cancers accounted for 24% of all cancers diagnosed in the EU during 2000–07. The overall incidence rose annually by 0.5% (99·8% CI 0·3–0·8). 5-year relative survival for all rare cancers was 48·5% (95% CI 48·4 to 48·6), compared with 63·4% (95% CI 63·3 to 63·4) for all common cancers. 5-year relative survival increased (overall 2·9%, 95% CI 2·7 to 3·2), from 1999–2001 to 2007–09, and for most rare cancers, with the largest increases for haematological tumours and sarcomas. The amount of centralisation of rare cancer treatment varied widely between cancers and between countries. The Netherlands and Slovenia had the highest treatment volumes. Interpretation: Our study benefits from the largest pool of population-based registries to estimate incidence and survival of about 200 rare cancers. Incidence trends can be explained by changes in known risk factors, improved diagnosis, and registration problems. Survival could be improved by early diagnosis, new treatments, and improved case management. The centralisation of treatment could be improved in the seven European countries we studied., peer-reviewed

A quick rebound for Antarctic crust Earth's crust deforms under the load of glaciers and ice sheets. When these masses are removed, the crust rebounds at a time scale determined by the viscosity of the upper mantle. Using GPS, Barletta et al. found that the viscosity of the mantle under the West Antarctic Ice Sheet is much lower than expected. This means that as ice is lost, the crust rebounds much faster than previously expected. Although estimates of total ice loss have to be revised upward, the surprising finding indicates that the ice sheet may stabilize against catastrophic collapse. Science , this issue p. 1335

As the global climate changes, understanding short-term variations in water storage is increasingly important. Continuously operating Global Positioning System (cGPS) stations in Iceland record annual periodic motion—the elastic response to winter accumulation and spring melt seasons—with peak-to-peak vertical amplitudes over 20 mm for those sites in the Central Highlands. Here for the first time for Iceland, we demonstrate the utility of these cGPS-measured displacements for estimating seasonal and shorter-term ice cap mass changes. We calculate unit responses to each of the five largest ice caps in central Iceland at each of the 62 cGPS locations using an elastic half-space model and estimate ice mass variations from the cGPS time series using a simple least squares inversion scheme. We utilize all three components of motion, taking advantage of the seasonal motion recorded in the horizontal. We remove secular velocities and accelerations and explore the impact that seasonal motions due to atmospheric, hydrologic, and nontidal ocean loading have on our inversion results. Our results match available summer and winter mass balance measurements well, and we reproduce the seasonal stake-based observations of loading and melting within the 1 math formula confidence bounds of the inversion. We identify nonperiodic ice mass changes associated with interannual variability in precipitation and other processes such as increased melting due to reduced ice surface albedo or decreased melting due to ice cap insulation in response to tephra deposition following volcanic eruptions, processes that are not resolved with once or twice-yearly stake measurements.

Rapid regional warming in the Antarctic Peninsula has led to the significant retreat and eventual collapse of several major ice shelves since the 1970s, triggering the subsequent acceleration and thinning of their feeding glaciers. The Wordie Ice Shelf, lying off the west coast of the Antarctic Peninsula, has undergone long-term disintegration since the 1960s with a substantial calving event occurring around 1989, followed by continuous steady retreat and its almost-complete disappearance. The dynamic response of the upstream glaciers to the ice shelf collapse and the response of the solid Earth to the associated mass loss are not fully understood. To quantify the mass loss from the system, we generated a digital elevation model (DEM) using airborne vertical and oblique imagery from 1966 and compared it to a DEM derived from 2008 SPOT data. This analysis reveals lowering over that time of approximately 60 m at the front of Fleming Glacier. Using IceBridge and ICESat-2/GLAS data spanning 2002–2014, we show an increased rate of mean ice-surface lowering, with rates post-2008 more than twice those of 2002–2008. We use these load change data as a basis for the simulation of viscoelastic solid Earth deformation. We subtract modeled elastic deformation rates, and a suite of modeled viscous rates, from GPS-derived three-dimensional bedrock velocities at sites to the south of Fleming Glacier to infer properties of Earth rheology. Assuming the pre-breakup bedrock uplift was positive due to post-Last Glacial Maximum (LGM) ice retreat, our viscoelastic-corrected GPS uplift rates suggest upper mantle viscosities are >2×1019 Pas and likely >1×1020 Pas in this region, 1–2 orders of magnitude greater than previously found for the northern Antarctic Peninsula. Horizontal velocities at the GPS site nearest the Fleming Glacier, after the application of elastic and plate tectonic corrections, point away from Marguerite Bay rather than the present glacier front. This suggests that horizontal motion in the region reflects the earlier retreat of the glacier system following the LGM, compatible with a relatively strong mantle in this region. These findings highlight the need for improved understanding of ice load changes in this region through the late Holocene in order to accurately model glacial isostatic adjustment.

This study shows the effect of changing the way ice histories are implemented in Glacial Isostatic Adjustment (GIA) codes to solve the sea level equation. The ice history models are being constantly improved and are provided in different formats. The overall algorithmic design of the sea-level equation solver often forces to implement the ice model in a representation that differs from the one originally provided. We show that using different representations of the same ice model gives important differences and artificial contributions to the sea level estimates, both at global and at regional scale. This study is not a speculative exercise. The ICE-5G model adopted in this work is widely used in present day sea-level analysis, but discrepancies between the results obtained by different groups for the same ice models still exist, and it was the effort to set a common reference for the sea-level community that inspired this work. Understanding this issue is important to be able to reduce the artefacts introduced by a non-suitable ice model representation. This is especially important when developing new GIA models, since neglecting this problem can easily lead to wrong alignment of the ice and sea-level histories, particularly close to the deglaciation areas, like Antarctica.

Agriculture plays a significant role in achieving the targets set by the EU with the package "Climate - Energy 20-20-20" (Dir. 2009/28/EC). This sector helps to reduce energy dependence and contributes to combat the climate change. The land plurality offers the opportunity to the farms to diversify their activities both to agricultural high quality food production and toward the production of biomass crops for energy purposes. The political system must adopt strategic tools that ensure a local energy system implementation through the support of the agricultural sector in the long period. The Marches region, which has a great variety of landscapes, environments, cultural traditions and food, promoted the production of renewable energy for farm needs (housing, factories, stables, greenhouses, etc.) and for the energy sale, that ensure a supplementary income to farms. The Marches region has invested several million euro through experimental and demonstration projects and specific financial measures came from Rural Development Plan (RDP) and Sugar beet Action Plan (PSA) for so-called Low Energy Farm (23 plants financed for energy sale and several plants financed for self use energy).

Martin V, Banfi S, Bordoni A, Leoni-Parvex S & Mazzucchelli L (2012) Histopathology 60, 336–346 Presence of cytogenetic abnormalities in Spitz naevi: a diagnostic challenge for fluorescence in-situ hybridization analysis Aims: Spitz naevi are difficult to diagnose, because of significant overlap with melanomas. It has been recently demonstrated that the LSI RREB1(6p25)/LSI MYB(6q23)/LSI CCND1(11q13)/CEP6 fluorescence in-situ hybridization (FISH) assay is a reliable tool with which to distinguish benign naevi and melanomas. Little is known about its diagnostic usefulness in Spitz naevi. Methods and results: We investigated 51 patients with Spitz naevi and long-term median follow-up (8.18 years) with the multicolour FISH probe. Control groups included 11 benign naevi and 14 melanomas. Spitz naevi from 32 (63%) patients did not show cytogenetic abnormalities (FISH−). In contrast, Spitz naevi from 19 (37%) patients showed changes in the investigated loci (FISH+). Spitz naevi with the FISH+ profile showed chromosome X polysomy in 14/18 (78%) patients. All Spitz naevi with the FISH− profile were disomic. All melanomas displayed a FISH+ profile, and 4/11 (36%) showed chromosome X polysomy. No differences in clinicopathological features were detected between Spitz naevi with and without genetic abnormalities. Conclusions: The presence of gene copy number changes in Spitz naevi as detected by FISH is higher than expected, and Spitz naevi at the genetic level represent a heterogeneous group. The findings of similar cytogenetic alterations in Spitz naevi and melanomas suggest that there should be cautious interpretation of FISH analysis in this setting.

Owing to the difficulty in implementing primary preventive measures for breast cancer, secondary prevention is correspondingly important, aimed at maximising detection of small cancers. Early detection diminishes the likelihood of clinical symptoms, disease progression, recurrence, distant metastasis, and death from breast cancer (Tabar et al, 1999). Trials have concluded that mammography screening in women aged from 50 to 69 can reduce breast cancer mortality by 25–30% (Gotzsche and Nielsen, 2006). Although Swiss French-speaking regions are covered by organised screening, the German- and Italian-speaking regions have no such programme. In the Italian- and French-speaking parts, physician-prescribed mammography is more frequent than in the German-speaking parts (Keller et al, 2001). In the south of Switzerland, the proportion of women aged 50–64 years who had undergone at least one mammography examination increased from 85% in 2002 to 88% in 2007 (Federal Office of Statistics, 2008). The current coexistence of systematic screening programmes and opportunistic screening strategies in Switzerland with its high-quality health-care system provides an opportunity to investigate the merits and drawbacks of the two approaches (Zwahlen et al, 2004). Although both methods seem effective in reducing breast cancer mortality, data on opportunistic screening are limited (de Gelder et al, 2009). The aim of this ecological population-based study was to assess such indicators as incidence rates, percentage of small cancers, stage distribution at diagnosis, axillary lymph node status and corresponding time trends for newly detected breast cancers, and to compare our data with those from populations with programmed screening.

Aims and background To evaluate the outcome of adult patients with de novo acute myeloid leukemia in the Italian-speaking part of Switzerland and to identify prognostic factors, time to progression and overall survival. Methods and study design Data of all adult patients diagnosed with acute myeloid leukemia from January 1984 to December 2003 were collected retrospectively. Univariate and multivariate analysis for time to progression and overall survival were performed. Results The incidence of acute myeloid leukemia in the adult population in southern Switzerland is 2.6/100,000 per year. Complete clinical and pathological data and follow-up information were available for 128 patients. The median age was 67 years (range, 18 to 94). The median follow-up was 97 months. Median overall survival was 6 months, with a 2-year overall survival of 16%. Median time to progression was 3 months. Thirty-five patients (median age, 80 years) were given best supportive care and/or palliative chemotherapy. The median survival in this subset was 2 months. Of the 93 patients treated with a curative intent, 48 were older than 60 years. The complete remission rate after induction chemotherapy was 80% for patients younger than 60 years and 31% for those older than 60 years (P 1 (P = 0.001) and treatment given before/after 1993 (P = 0.044) were found to be independent prognostic factors for both overall survival and time to progression. Conclusions Most patients with acute myeloid leukemia are older than 60 years, and their outcome is still disappointing. For younger patients, the prognosis is better if they receive high-dose cytarabine as post-remission therapy and if they are treated in the setting of a clinical trial.

Breast cancer may be classified into distinct molecular subtypes based on gene expression profiling and/or immunophenotypic characteristics. Aim of the study was to investigate prevalence, clinicopathologic features and overall survival (OS) of molecular subtypes, in a large European population-based study.All invasive breast cancers from 2003 to 2007 were selected from the files of Ticino Cancer Registry. Molecular subtypes were defined by immunohistochemical markers. Clinicopathological characteristics and short-term OS were analyzed.Of 1214 invasive breast cancers, 73.2% were luminal A subtype, 13.8% luminal B, 7.4% basal like and 5.6% Her2/neu. Basal like presented largely in premenopausal women and displayed aggressive features, such as large tumor size, poorly differentiated cancers, high Ki-67 proliferation index and the worst 24-month OS. Luminal A included the highest percentage of patients70, the highest proportion of stage I tumors and well/moderately differentiated lesions. Her2/neu was more frequent in postmenopausal women and showed the highest percentage of positive lymph nodes and stage IV cases.This is a comprehensive European population-based study on breast cancer molecular subtypes. We provide strong evidence that the molecular classification is useful for clinical management and superior to World Health Organization classification in terms of short-term prognostic value.