The impact of cancer patient pathway on timing of radiotherapy and survival: a cohort study in glioblastoma patients.

PURPOSE: Glioblastoma (GBM) is an aggressive brain tumor in which primary therapy is standardized and consists of surgery, radiotherapy (RT), and chemotherapy. However, the optimal time from surgery to start of RT is unknown. A high-grade glioma cancer patient pathway (CPP) was implemented in Norway in 2015 to avoid non-medical delays and regional disparity, and to optimize information flow to patients. This study investigated how CPP affected time to RT after surgery and overall survival. METHODS: This study included consecutive GBM patients diagnosed in South-Eastern Norway Regional Health Authority from 2006 to 2019 and treated with RT. The pre CPP implementation group constituted patients diagnosed 2006-2014, and the post CPP implementation group constituted patients diagnosed 2016-2019. We evaluated timing of RT and survival in relation to CPP implementation. RESULTS: A total of 1212 patients with GBM were included. CPP implementation was associated with significantly better outcomes (p < 0.001). Median overall survival was 12.9 months. The odds of receiving RT within four weeks after surgery were significantly higher post CPP implementation (p < 0.001). We found no difference in survival dependent on timing of RT below 4, 4-6 or more than 6 weeks (p = 0.349). Prognostic factors for better outcomes in adjusted analyses were female sex (p = 0.005), younger age (p < 0.001), solitary tumors (p = 0.008), gross total resection (p < 0.001), and higher RT dose (p < 0.001). CONCLUSION: CPP implementation significantly reduced time to start of postoperative RT. Survival was significantly longer in the period after the CPP implementation, however, timing of postoperative RT relative to time of surgery did not impact survival.

Stable glioma incidence and increased patient survival over the past two decades in Norway: a nationwide registry-based cohort study.

BACKGROUND: Surveillance of incidence and survival of central nervous system tumors is essential to monitor disease burden and epidemiological changes, and to allocate health care resources. Here, we describe glioma incidence and survival trends by histopathology group, age, and sex in the Norwegian population. MATERIAL AND METHODS: We included patients with a histologically verified glioma reported to the Cancer Registry of Norway from 2002 to 2021 (N = 7,048). Population size and expected mortality were obtained from Statistics Norway. Cases were followed from diagnosis until death, emigration, or 31 December 2022, whichever came first. We calculated age-standardized incidence rates (ASIR) per 100,000 person-years and age-standardized relative survival (RS).  Results: The ASIR for histologically verified gliomas was 7.4 (95% CI: 7.3-7.6) and was higher for males (8.8; 95% CI: 8.5-9.1) than females (6.1; 95% CI: 5.9-6.4). Overall incidence was stable over time. Glioblastoma was the most frequent tumor entity (ASIR = 4.2; 95% CI: 4.1-4.4). Overall, glioma patients had a 1-year RS of 63.6% (95% CI: 62.5-64.8%), and a 5-year RS of 32.8% (95% CI: 31.6-33.9%). Females had slightly better survival than males. For most entities, 1- and 5-year RS improved over time (5-year RS for all gliomas 29.0% (2006) and 33.1% (2021), p < 0.001). Across all tumor types, the RS declined with increasing age at diagnosis. INTERPRETATION: The incidence of gliomas has been stable while patient survival has increased over the past 20 years in Norway. As gliomas represent a heterogeneous group of primary CNS tumors, regular reporting from cancer registries at the histopathology group level is important to monitor disease burden and allocate health care resources in a population.

The impact of the COVID-19 pandemic on cancer diagnosis based on pathology notifications: A comparison across the Nordic countries during 2020.

The severity of the COVID-19 pandemic and subsequent mitigation strategies have varied across the Nordic countries. In a joint Nordic population-based effort, we compared patterns of new cancer cases and notifications between the Nordic countries during 2020. We used pathology notifications to cancer registries in Denmark, the Faroe Islands, Finland, Iceland, Norway and Sweden to determine monthly numbers of pathology notifications of malignant and in situ tumours from January to December 2020 compared to 2019 (2017-2019 for Iceland and the Faroe Islands). We compared new cancer cases per month based on unique individuals with pathology notifications. In April and May 2020, the numbers of new malignant cases declined in all Nordic countries, except the Faroe Islands, compared to previous year(s). The largest reduction was observed in Sweden (May: -31.2%, 95% CI -33.9, -28.3), followed by significant declines in Finland, Denmark and Norway, and a nonsignificant decline in Iceland. In Denmark, Norway, Sweden and Finland the reporting rates during the second half of 2020 rose to almost the same level as in 2019. However, in Sweden and Finland, the increase did not compensate for the spring decline (annual reduction -6.2% and -3.6%, respectively). Overall, similar patterns were observed for in situ tumours. The COVID-19 pandemic led to a decline in rates of new cancer cases in Sweden, Finland, Denmark and Norway, with the most pronounced reduction in Sweden. Possible explanations include the severity of the pandemic, temporary halting of screening activities and changes in healthcare seeking behaviour.

Age-specific survival trends and life-years lost in women with breast cancer 1990-2016: the NORDCAN survival studies.

BACKGROUND: A recent overview of cancer survival trends 1990-2016 in the Nordic countries reported continued improvements in age-standardized breast cancer survival among women. The aim was to estimate age-specific survival trends over calendar time, including life-years lost, to evaluate if improvements have benefited patients across all ages in the Nordic countries. METHODS: Data on breast cancers diagnosed 1990-2016 in Denmark, Finland, Iceland, Norway, and Sweden were obtained from the NORDCAN database. Age-standardized and age-specific relative survival (RS) was estimated using flexible parametric models, as was reference-adjusted crude probabilities of death and life-years lost. RESULTS: Age-standardized period estimates of 5-year RS in women diagnosed with breast cancer ranged from 87% to 90% and 10-year RS from 74% to 85%. Ten-year RS increased with 15-18 percentage points from 1990 to 2016, except in Sweden (+9 percentage points) which had the highest survival in 1990. The largest improvements were observed in Denmark, where a previous survival disadvantage diminished. Most recent 5-year crude probabilities of cancer death ranged from 9% (Finland, Sweden) to 12% (Denmark, Iceland), and life-years lost from 3.3 years (Finland) to 4.6 years (Denmark). Although survival improvements were consistent across different ages, women aged ≥70 years had the lowest RS in all countries. Period estimates of 5-year RS were 94-95% in age 55 years and 84-89% in age 75 years, while 10-year RS were 88-91% in age 55 years and 69-84% in age 75 years. Women aged 40 years lost on average 11.0-13.8 years, while women lost 3.8-6.0 years if aged 55 and 1.9-3.5 years if aged 75 years. CONCLUSIONS: Survival for Nordic women with breast cancer improved from 1990 to 2016 in all age groups, albeit with larger country variation among older women where survival was also lower. Women over 70 years of age have not had the same survival improvement as women of younger age.

Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study.

BACKGROUND: Colorectal cancer screening programmes and uptake vary substantially across Europe. We aimed to compare changes over time in colorectal cancer incidence, mortality, and stage distribution in relation to colorectal cancer screening implementation in European countries. METHODS: Data from nearly 3·1 million patients with colorectal cancer diagnosed from 2000 onwards (up to 2016 for most countries) were obtained from 21 European countries, and were used to analyse changes over time in age-standardised colorectal cancer incidence and stage distribution. The WHO mortality database was used to analyse changes over time in age-standardised colorectal cancer mortality over the same period for the 16 countries with nationwide data. Incidence rates were calculated for all sites of the colon and rectum combined, as well as the subsites proximal colon, distal colon, and rectum. Average annual percentage changes (AAPCs) in incidence and mortality were estimated and relevant patterns were descriptively analysed. FINDINGS: In countries with long-standing programmes of screening colonoscopy and faecal tests (ie, Austria, the Czech Republic, and Germany), colorectal cancer incidence decreased substantially over time, with AAPCs ranging from -2·5% (95% CI -2·8 to -2·2) to -1·6% (-2·0 to -1·2) in men and from -2·4% (-2·7 to -2·1) to -1·3% (-1·7 to -0·9) in women. In countries where screening programmes were implemented during the study period, age-standardised colorectal cancer incidence either remained stable or increased up to the year screening was implemented. AAPCs for these countries ranged from -0·2% (95% CI -1·4 to 1·0) to 1·5% (1·1 to 1·8) in men and from -0·5% (-1·7 to 0·6) to 1·2% (0·8 to 1·5) in women. Where high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0·3% (95% CI 0·1 to 0·5) to 1·9% (1·2 to 2·6) in men and from 0·6% (0·4 to 0·8) to 1·1% (0·8 to 1·4) in women. The largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes. INTERPRETATION: We observed divergent trends in colorectal cancer incidence, mortality, and stage distribution across European countries, which appear to be largely explained by different levels of colorectal cancer screening implementation. FUNDING: German Cancer Aid (Deutsche Krebshilfe) and the German Federal Ministry of Education and Research.

Higher than expected and significantly increasing incidence of upper tract urothelial carcinoma. A population based study.

PURPOSE: To register all cases of urothelial cancer and renal cell carcinoma (RCC) in Norway during 1999-2018 to obtain the contemporary incidence of UTUC and UTUC incidence relative to other urothelial cancers and RCC. Further to analyse possible changes over time regarding UTUC incidence, UTUC patient characteristics, tumour characteristics and survival. METHODS: 3502 cases registered with ICD code C65 and C66 during 1999-2018 at the Norwegian cancer registry were entered into a database. After a selection process 3096 cases were included in the study. The crude incidences of UTUC were calculated for each year adjusting for the corresponding population data. Age-standardized rates adjusting to the European standard population (2013) were calculated. Comparisons were made with other cases of urothelial cancer and RCC. For changes over time, the material was split into 5-year periods. Regression analysis was used to calculate yearly changes and for assessing statistical significance. Survival outcomes were calculated using the Kaplan-Meier method. RESULTS: The overall age-standardized incidence rate was 3.88, increasing from 3.21 to 4.70 from first to last 5-year periods. The increase affected all ages except those < 60 years of age, and were observed regardless of gender or anatomical location. UTUC constituted 11.8% of all urothelial cancers, increasing from 9.9 to 12.8%. Mean patient age at diagnosis increased from 71.5 to 73.4 years. The 5-years Cancer-specific survival improved from 57.4 to 65.4%. CONCLUSION: The incidence of UTUC was higher than expected and increasing. Patient age at diagnosis was increasing.

Age dependence of modern clinical risk groups for localized prostate cancer-A population-based study.

BACKGROUND: Optimal prostate cancer (PCa) screening strategies will focus on men likely to have potentially lethal disease. Age-specific incidence rates (ASIRs) by modern clinical risk groups could inform risk stratification efforts for screening. METHODS: This cross-sectional population study identified all men diagnosed with PCa in Norway from 2014 to 2017 (n = 20,356). Age, Gleason score (primary plus secondary), and clinical stage were extracted. Patients were assigned to clinical risk groups: low, favorable intermediate, unfavorable intermediate, high, regional, and metastatic. Chi-square tests analyzed the independence of Gleason scores and modern PCa risk groups with age. ASIRs for each risk group were calculated as the product of Norwegian ASIRs for all PCa and the proportions observed for each risk category. RESULTS: Older age was significantly associated with a higher Gleason score and more advanced disease. The percentages of men with Gleason 8 to 10 disease among men aged 55 to 59, 65 to 69, 75 to 79, and 85 to 89 years were 16.5%, 23.4%, 37.2%, and 59.9%, respectively (P < .001); the percentages of men in the same age groups with at least high-risk disease were 29.3%, 39.1%, 60.4%, and 90.6%, respectively (P < .001). The maximum ASIRs (per 100,000 men) for low-risk, favorable intermediate-risk, unfavorable intermediate-risk, high-risk, regional, and metastatic disease were 157.1 for those aged 65 to 69 years, 183.8 for those aged 65 to 69 years, 194.8 for those aged 70 to 74 years, 408.3 for those aged 75 to 79 years, 159.7 for those aged ≥85 years, and 314.0 for those aged ≥85 years, respectively. At the ages of 75 to 79 years, the ASIR of high-risk disease was approximately 6 times greater than the ASIR at 55 to 59 years. CONCLUSIONS: The risk of clinically significant localized PCa increases with age. Healthy older men may benefit from screening.

Chronic lymphocytic leukemia and secondary hematological malignancies: A nation-wide cancer registry study.

OBJECTIVE: Chronic lymphocytic leukemia (CLL) treatment has changed dramatically, and landscape of second hematologic malignancies (SHM) evolves in the new era of targeted therapy. No data were available about the real-world burden of SHM. METHODS: All 2631 patients with CLL in the Cancer registry of Norway registered 2003-2012 were included. RESULTS: After median follow-up of 6.6 years, 103 patients (4%) developed SHM. Diffuse large B-cell lymphoma (DLBCL) was most common (n = 65; 63%). Median survival was 9.3 years (95% CI; 8.9-9.8) in non-SHM patients and 1.7 years in DLBCL, 0.8 years in Hodgkin lymphoma (n = 12), and 2.8 years in myeloid neoplasia (n = 15; 95% CI: 0.3-2.6, 0.6-2.9, and 0.4-5.3, respectively; P < .001). Outcomes were poorest for SHM patients treated for CLL (HR 2.76, 95% CI 1.4-5.5, P = 0.003). A higher proportion of men and younger age were found in SHM patients (median age 66 vs 72 years in non-SHM; P < .001; men 68% vs 57%, P = .03). Myeloid neoplasia was rare (incidence rate 1/1000 person-years; 95% CI: 0.6-1.5) and tended to occur later than DLBCL in patients treated for CLL (median time from CLL to SHM 62 vs 45 months; P = .09). CONCLUSIONS: SHM and especially myeloid malignancies were rare in chemoimmunotherapy era.

Trends in cancer survival in the Nordic countries 1990-2016: the NORDCAN survival studies.

BACKGROUND: Differences in cancer survival between the Nordic countries have previously been reported. The aim of this study was to examine whether these differences in outcome remain, based on updated information from five national cancer registers. MATERIALS AND METHODS: The data used for the analysis was from the NORDCAN database focusing on nine common cancers diagnosed 1990-2016 in Denmark, Finland, Iceland, Norway and Sweden with maximum follow-up through 2017. Relative survival (RS) was estimated at 1 and 5 years using flexible parametric RS models, and percentage point differences between the earliest and latest years available were calculated. RESULTS: A consistent improvement in both 1- and 5-year RS was found for most studied sites across all countries. Previously observed differences between the countries have been attenuated. The improvements were particularly pronounced in Denmark that now has cancer survival similar to the other Nordic countries. CONCLUSION: The reasons for the observed improvements in cancer survival are likely multifactorial, including earlier diagnosis, improved treatment options, implementation of national cancer plans, uniform national cancer care guidelines and standardized patient pathways. The previous survival disadvantage in Denmark is no longer present for most sites. Continuous monitoring of cancer survival is of importance to assess the impact of changes in policies and the effectiveness of health care systems.

Breast cancer-specific survival by clinical subtype after 7 years follow-up of young and elderly women in a nationwide cohort.

Age and tumor subtype are prognostic factors for breast cancer survival, but it is unclear which matters the most. We used population-based data to address this question. We identified 21,384 women diagnosed with breast cancer at ages 20-89 between 2005 and 2015 in the Cancer Registry of Norway. Subtype was defined using estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2) status as luminal A-like (ER+PR+HER2-), luminal B-like HER2-negative (ER+PR-HER2-), luminal B-like HER2-positive (ER+PR+/-HER2+), HER2-positive (ER-PR-HER2+) and triple-negative (TNBC) (ER-PR-HER2-). Cox regression estimated hazard ratios (HR) for breast cancer-specific 7-year survival by age and subtype, while adjusting for year, grade, TNM stage and treatment. Young women more often had HER2-positive and TNBC tumors, while elderly women (70-89) more often had luminal A-like tumors. Compared to age 50-59, young women had doubled breast cancer-specific mortality rate (HR = 2.26, 95% CI 1.81-2.82), while elderly had two to five times higher mortality rate (70-79: HR = 2.25, 1.87-2.71; 80-89: HR = 5.19, 4.21-6.41). After adjustments, the association was non-significant among young women but remained high among elderly. Young age was associated with increased breast cancer-specific mortality among luminal A-like subtype, while old age was associated with increased mortality in all subtypes. Age and subtype were strong independent prognostic factors. The elderly always did worse, also after adjustment for subtype. Tumor-associated factors (subtype, grade and stage) largely explained the higher breast cancer-specific mortality among young. Future studies should address why luminal A-like subtype is associated with a higher mortality rate in young women.

Children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor in Norway from 1974 through 2013: Unexplainable regional differences in survival.

BACKGROUND: A previous study based on Norwegian Cancer Registry data suggested regional differences in overall survival (OS) after treatment for medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor (CNS-PNET) in Norway. The purpose of the present study was to confirm in an extended cohort whether there were regional differences in outcome or not, and if so try to identify possible explanations. MATERIAL AND METHODS: Data from patients aged 0-20 years diagnosed with and treated for MB/CNS-PNET at all four university hospitals in Norway from 1974 to 2013 were collected and compared. RESULTS: Of 266 identified patients, 251 fulfilled inclusion criteria. MB was diagnosed in 200 and CNS-PNET in 51 patients. Five-year OS and event-free survival (EFS) were 59% and 52%, respectively. There was a significant difference in five-year OS and EFS between MB and CNS-PNET patients; 62% versus 47% (P =  0.007) and 57% versus 35% (P < 0.001). In multivariable analysis, two factors were found to significantly contribute to improved five-year OS and EFS, whereas one factor contributed to improved five-year OS only. Gross total resection (GTR) versus non-GTR (hazard ratio [HR] 0.53, P =  0.003; HR 0.46, P < 0.001) and cerebrospinal irradiation (CSI) versus non-CSI (HR 0.24, P < 0.001; HR 0.28, P < 0.001) for both, and treatment outside Oslo University Hospital for OS only (HR 0.64, P =  0.048). CONCLUSION: Survival was comparable with data from other population-based studies, and the importance of GTR and CSI was confirmed. The cause for regional survival differences could not be identified.

Antiepileptic and psychiatric medication in a nationwide cohort of patients with glioma WHO grade II-IV.

INTRODUCTION: Glioma is the most common intracranial primary brain tumor. Patients with glioma often suffer from epilepsy, anxiety and depression. Aims of this study were to identify risk factors for drug-treated anxiety and depression, and to determine the use of psychiatric medication in a national glioma cohort. METHODS: Data from the Cancer Registry of Norway on all persons diagnosed with glioma WHO grade II-IV 2004-2010 were linked with data from the Norwegian Prescription Database. Cox regression analysis was used to assess risk factors for drug-treated anxiety and depression. Standardized incidence ratios were calculated for psychiatric medication dispensed to glioma patients and compared to the general population. RESULTS: The glioma cohort consisted of 1056 males and 772 females. Of the 1828 patients, 565 had glioma grade II-III, and 1263 had grade IV. The patients with glioma grade II-III who were treated with levetiracetam had an increased risk for drug-treated anxiety compared to patients without levetiracetam; hazard ratio 2.8 (95% confidence interval 1.7-4.9). Female gender increased the risk for drug-treated anxiety compared to males in patients with glioma grade IV; hazard ratio 1.5 (95% confidence interval 1.2-2.0). Antidepressants were less frequently dispensed to patients with glioma grade II-III and epilepsy than to the general population. CONCLUSIONS: Patients with glioma grade II-III on levetiracetam had an increased risk for drug-treated anxiety. The subgroup of patients with glioma grade II-III and epilepsy received less antidepressants than the general population.

Low proportion of unreported cervical treatments in the cancer registry of Norway between 1998 and 2013.

BACKGROUND: Accurate information about treatment is needed to evaluate cervical cancer prevention efforts. We studied completeness and validity of reporting cervical treatments in the Cancer Registry of Norway (CRN). MATERIAL AND METHODS: We identified 47,423 (92%) high-grade cervical dysplasia patients with and 3983 (8%) without recorded treatment in the CRN in 1998-2013. We linked the latter group to the nationwide registry of hospital discharges in 1998-2015. Of patients still without treatment records, we randomly selected 375 for review of their medical history. Factors predicting incomplete treatment records were assessed by multiple imputation and logistic regression. RESULTS: Registry linkage revealed that 10% (401/3983) of patients received treatment, usually conization, within one year of their initial high-grade dysplasia diagnosis. Of those, 11% (n = 44) were missing due to unreporting and 89% (n = 357) due to misclassification at the CRN. Of all cases in medical review, patients under active surveillance contributed almost 60% (223/375). Other reasons of being without recorded treatment were uncertain dysplasia diagnosis, invasive cancer or death. Coding error occurred in 19% (73/375) of randomly selected cases. CRN undercounted receipt of treatment by 38% (n = 1526) among patients without recorded treatment which translates into 97% overall completeness of treatment data. Incomplete treatment records were particularly associated with public laboratories, patients aged 40-54 years, and the latest study years. CONCLUSIONS: CRN holds accurate information on cervical treatments. Completeness and particularly validity can be further improved through the establishment of new internal routines and regular linkage to hospital discharges.

Nordic Cancer Registries - an overview of their procedures and data comparability.

BACKGROUND: The Nordic Cancer Registries are among the oldest population-based registries in the world, with more than 60 years of complete coverage of what is now a combined population of 26 million. However, despite being the source of a substantial number of studies, there is no published paper comparing the different registries. Therefore, we did a systematic review to identify similarities and dissimilarities of the Nordic Cancer Registries, which could possibly explain some of the differences in cancer incidence rates across these countries. METHODS: We describe and compare here the core characteristics of each of the Nordic Cancer Registries: (i) data sources; (ii) registered disease entities and deviations from IARC multiple cancer coding rules; (iii) variables and related coding systems. Major changes over time are described and discussed. RESULTS: All Nordic Cancer Registries represent a high quality standard in terms of completeness and accuracy of the registered data. CONCLUSIONS: Even though the information in the Nordic Cancer Registries in general can be considered more similar than any other collection of data from five different countries, there are numerous differences in registration routines, classification systems and inclusion of some tumors. These differences are important to be aware of when comparing time trends in the Nordic countries.

Outcome for children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor (CNS-PNET) - a retrospective analysis spanning 40 years of treatment.

BACKGROUND: Medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor of the central nervous system (CNS-PNET) are among the most common pediatric brain tumors. The diagnosis, treatment, and outcome of MB/CNS-PNET patients treated during the last four decades at Oslo University Hospital (OUH) are described. MATERIAL AND METHODS: All patients younger than 20 years of age diagnosed and treated for MB/CNS-PNET at OUH between 1 January 1974 and 31 December 2013 were identified. RESULTS: We found 175 patients. In 13 of them, the diagnosis was changed upon histopathological review and in 4 patients part of the treatment was administered at other hospitals. Thus, 158 patients were included for further analysis. Eight patients did not receive adjuvant therapy because of a dismal clinical condition. The overall 5-year survival rate for MB and CNS-PNET was 54%, for MB 57%, and for CNS-PNET 41%. Gross total resection (GTR) was achieved in 118 patients and 5-year overall survival for patients with GTR versus those with non-GTR differed significantly with 64% versus 22%. Cytological examination of the cerebrospinal fluid was performed in 52 patients. A total of 126 patients received radiotherapy as part of the primary treatment and 24 did not due to young age. Median time from surgery to start of radiotherapy was 33 days. Duration of radiotherapy was more than 48 days in 22% of patients. At the time of analysis, 63 patients were alive and disease-free, one alive with disease, and 94 patients were deceased; 84 of these due to MB/CNS-PNET and 10 due to supposed late effects from the treatment. CONCLUSIONS: Survival was comparable to data from other population-based studies. The importance of GTR for survival was corroborated. Reporting real-world data remains crucial to know the true outcome of patients treated outside clinical trials.

Pre-diagnostic serum levels of EGFR and ErbB2 and genetic glioma risk variants: a nested case-control study.

Genetic variants have been associated with the risk of developing glioma, but functional mechanisms on disease phenotypic traits remain to be investigated. One phenotypic trait of glioblastoma is the mutation and amplification of the epidermal growth factor receptor (EGFR) gene. We investigated associations between pre-diagnostic serum protein concentrations of EGFR and ErbB2, both members of the EGFR family, and future risk of glioma. Further, we studied if EGFR glioma risk variants were associated with EGFR and ErbB2 serum levels. We assessed the associations between genetic glioma risk variants and serum concentrations of EGFR and ErbB2, as measured in pre-diagnostic cohort serum samples of 593 glioma patients and 590 matched cancer-free controls. High serum EGFR and ErbB2 levels were associated with risk of developing glioblastoma (P = 0.008; OR = 1.58, 95 % CI = 1.13-2.22 and P = 0.017, OR = 1.63, 95 % CI = 1.09-2.44, respectively). High serum ErbB2 concentration was also associated with glioma risk overall (P = 0.049; OR = 1.39, 95 % CI = 1.00-1.93). Glioma risk variants were not associated with high serum protein abundance. In contrast, the EGFR risk variant rs4947986 (T) was correlated with decreased EGFR serum levels (study cohort P = 0.024 and controls P = 0.009). To our knowledge, this is the first study showing an association of EGFR and ErbB2 serum levels with glioma more than a decade before diagnosis, indicating that EGFR and ErbB2 serum proteins are important in early gliomagenesis. However, we did not find evidence that glioma risk variants were associated with high pre-diagnostic serum concentrations of EGFR and ErbB2.

Comparison of non-parametric methods for ungrouping coarsely aggregated data.

BACKGROUND: Histograms are a common tool to estimate densities non-parametrically. They are extensively encountered in health sciences to summarize data in a compact format. Examples are age-specific distributions of death or onset of diseases grouped in 5-years age classes with an open-ended age group at the highest ages. When histogram intervals are too coarse, information is lost and comparison between histograms with different boundaries is arduous. In these cases it is useful to estimate detailed distributions from grouped data. METHODS: From an extensive literature search we identify five methods for ungrouping count data. We compare the performance of two spline interpolation methods, two kernel density estimators and a penalized composite link model first via a simulation study and then with empirical data obtained from the NORDCAN Database. All methods analyzed can be used to estimate differently shaped distributions; can handle unequal interval length; and allow stretches of 0 counts. RESULTS: The methods show similar performance when the grouping scheme is relatively narrow, i.e. 5-years age classes. With coarser age intervals, i.e. in the presence of open-ended age groups, the penalized composite link model performs the best. CONCLUSION: We give an overview and test different methods to estimate detailed distributions from grouped count data. Health researchers can benefit from these versatile methods, which are ready for use in the statistical software R. We recommend using the penalized composite link model when data are grouped in wide age classes.

Aetiologic heterogeneity in pediatric Hodgkin lymphoma? Evidence from the Nordic countries, 1978-2010.

BACKGROUND: In epidemiological studies, Hodgkin lymphomas (HL) in children younger than 15 years and HL in adolescents and younger adults age 15-35 years has traditionally been studied separately, under the assumption that HL at age 0-14 constitute a homogeneous entity. However, the continued validity of this research practice in affluent settings may be questioned. Specifically, the boundary at age 15 years may not be epidemiologically justified, and therefore also questionable clinically. We therefore updated and further characterised recent HL incidence patterns among Nordic children. MATERIAL AND METHODS: We obtained HL incidence data in children aged 0-14 years for the period 1978-2010 from the five nationwide Nordic cancer registries. The data were analysed by log-linear and/or a mixture of Poisson regression models. RESULTS: The analyses showed statistically significantly decreasing and increasing HL incidence rates in children younger and older than eight years, respectively during the study period. Statistical modelling suggested that cases in children age 0-6 years constituted a disease entity of its own, whereas cases in older children were more likely to belong to the younger adult HL entity. CONCLUSION: Diverging incidence trends and statistical modelling suggest that HL in children age 0-14 years cannot be assumed to constitute a homogeneous disease entity in affluent settings.

Association Between Prediagnostic Serum 25-Hydroxyvitamin D Concentration and Glioma.

There are no previous studies of the association between prediagnostic serum vitamin D concentration and glioma. Vitamin D has immunosuppressive properties; as does glioma. It was, therefore, our hypothesis that elevated vitamin D concentration would increase glioma risk. We conducted a nested case-control study using specimens from the Janus Serum Bank cohort in Norway. Blood donors who were subsequently diagnosed with glioma (n = 592), between 1974 and 2007, were matched to donors without glioma (n = 1112) on date and age at blood collection and sex. We measured 25-hydroxyvitamin D [25(OH)D], an indicator of vitamin D availability, using liquid chromatography coupled with mass spectrometry. Seasonally adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for each control quintile of 25(OH)D using conditional logistic regression. Among men diagnosed with high grade glioma >56, we found a negative trend (P = .04). Men diagnosed ≤ 56 showed a borderline positive trend (P = .08). High levels (>66 nmol/L) of 25(OH)D in men >56 were inversely related to high grade glioma from ≥2 yr before diagnosis (OR = 0.59; 95% CI = 0.38, 0.91) to ≥15 yr before diagnosis (OR = 0.61; 95% CI = 0.38,0.96). Our findings are consistent long before glioma diagnosis and are therefore unlikely to reflect preclinical disease.