CancerIndex Home - Guide to Internet Resources for Cancer Home > Locations > Europe
Found this page useful?

Albania, Austria, Belarus, Belgium, Bosnia Herzegovina, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Macedonia, Malta, Moldova, Montenegro, Netherlands, Nordic Countries, Norway, Poland, Portugal, Romania, Russian Federation, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, UK, Ukraine

Europe: cancer statistics from IARC GlobalCan (2012)

Population in 2012: 741.3m
People newly diagnosed with cancer (excluding NMSC) / yr: 3,442,300
Age-standardised rate, incidence per 100,000 people/yr: 255.4
Risk of getting cancer before age 75:25.8%
People dying from cancer /yr: 1,755,800

Menu: European Cancer Organisisations

Europe: Cancer Organisations
Latest Research Publications about cancer in Europe

Europe: Cancer Organisations (31 links)

Latest Research Publications about cancer in Europe

Young RJ, Natukunda A, Litière S, et al.
First-line anthracycline-based chemotherapy for angiosarcoma and other soft tissue sarcoma subtypes: pooled analysis of eleven European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group trials.
Eur J Cancer. 2014; 50(18):3178-86 [PubMed] Related Publications
BACKGROUND: Angiosarcoma is a rare subtype of soft tissue sarcoma (STS). Doxorubicinis the standard first-line chemotherapy for advanced STS. It is not known whether angiosarcoma response to anthracycline-based chemotherapy is different to other STS subtypes.
METHODS: Pooled data were analysed from 11 prospective randomised and non-randomized European Organisation for Research and Treatment of Cancer (EORTC) clinical trials of first-line anthracycline-based chemotherapy for advanced STS. Baseline patient characteristics, chemotherapy response, progression free survival (PFS) and overall survival (OS) of angiosarcoma patients were compared with other STS patients. Analysis was performed to identify factors prognostic for angiosarcoma response to chemotherapy, PFS and OS.
RESULTS: With a median follow-up of 4.2 years, data from 108 locally advanced and metastatic angiosarcoma patients and 2557 patients with other STS histologies were analysed. 25% of angiosarcoma patients had a complete or partial response to chemotherapy compared to 21% for other STS histotypes. The median PFS was 4.9 months and OS 9.9 months, which were not significantly different from other STS histotypes. In univariate analysis, bone metastases were an adverse prognostic factor for OS (hazard ratio (HR) 1.66, 95% confidence interval (CI) 1.03–2.67; p = 0.036). Tumour grade was as an adverse prognostic factor for PFS (HR 1.72, 95% CI 1.01–2.92; p = 0.044) and OS (HR 2.03; 95% CI 1.16–3.56; p = 0.011). Compared to single agent anthracyclines, doxorubicin + ifosfamide was associated with improved PFS (HR 0.53, 95% CI 0.33–0.86; p = 0.010) and OS (HR 0.53, 95% CI 0.32–0.90; p = 0.018).
CONCLUSIONS: Angiosarcoma response and survival following first-line anthracycline-based chemotherapy was similar to other STS histotypes. Our analysis provides a useful measure of angiosarcoma response to chemotherapy for comparison with future clinical trials.

Related: Doxorubicin Soft Tissue Sarcomas

Ades F, Senterre C, Zardavas D, et al.
An exploratory analysis of the factors leading to delays in cancer drug reimbursement in the European Union: the trastuzumab case.
Eur J Cancer. 2014; 50(18):3089-97 [PubMed] Related Publications
BACKGROUND: The European Union (EU) has adopted a common procedure for granting marketing authorisation for cancer drugs. Nevertheless, pricing and reimbursement decisions are a competency of EU national governments, and their policies are diverse. We aimed to evaluate the time for trastuzumab reimbursement approval and its association to health expenditure, to health policy performance, to the availability of cost-effectiveness studies and to breast cancer outcome.
METHODS: Breast cancer outcome was estimated by the mortality/incidence (M/I) ratio. Trastuzumab reimbursement approval dates were provided by Roche. Spearman's rank correlation and Wilcoxon rank-sum test were used to evaluate associations and/or differences between the variables studied. Additional analyses were made by grouping countries according to compliance to the 180 day timeframe stipulated in the EU 89/105/EEC Directive for drug pricing and reimbursement.
RESULTS: A statistically significant inverse and strong correlation between breast cancer M/I ratio and health expenditure (r(s)=-0.730, p<0.001) and health policy performance (r(s)=-0.711, p<0.001) was found, meaning the better the score and the higher the expenditure, the fewer patients died after a breast cancer diagnosis. Factors associated with trastuzumab faster reimbursement and compliance to the 89/105/EEC Directive were better health policy score, higher health expenditure and availability of cost-effectiveness studies.
CONCLUSION: Higher health policy scores and health expenditure are associated with faster reimbursement of trastuzumab and better breast cancer outcome. Although the study design does not allow inference of causal associations, a marked difference is observed between Eastern and Western Europe, with long delays and increased breast cancer mortality identified in Eastern European countries.

Related: Breast Cancer Trastuzumab (Herceptin)

Weinberg OK, Seetharam M, Ren L, et al.
Mixed phenotype acute leukemia: A study of 61 cases using World Health Organization and European Group for the Immunological Classification of Leukaemias criteria.
Am J Clin Pathol. 2014; 142(6):803-8 [PubMed] Related Publications
OBJECTIVES: The 2008 World Health Organization (WHO) classification system grouped bilineal and biphenotypic acute leukemias together under a new heading of mixed phenotype acute leukemia (MPAL). The lineage-specific marker criteria have also changed for a diagnosis of MPAL. The goal of this study was to characterize clinical significance of this new group.
METHODS: Sixty-one patients diagnosed with MPAL using either European Group for the Immunological Classification of Leukaemias (EGIL) criteria or 2008 WHO criteria were included in this study.
RESULTS: Sixteen patients (26%) diagnosed with acute biphenotypic leukemia using EGIL criteria did not fulfill 2008 WHO criteria for MPAL. Cytogenetic data were available for 32 patients, and the most common abnormality was t(9;22) (five of 32 cases). Clinical outcome data suggested that younger patients with MPAL (≤21 years) had better overall survival (OS) in both the EGIL and WHO groups (EGIL, P = .0403; WHO, P = .0601). Compared with 177 patients with acute myeloid leukemia (AML), MPAL patients had better OS (P = .0003) and progression-free survival (P = .0001). However, no difference in OS between MPAL and 387 patients with acute lymphoblastic leukemia was present (P = .599).
CONCLUSIONS: As defined by the 2008 WHO classification, fewer patients are now classified as having MPAL than with the EGIL criteria. In this study, patients with MPAL have a better clinical outcome compared with patients with AML.

Eggermont AM, Caldas C, Ringborg U, et al.
Cancer Core Europe: a consortium to address the cancer care-cancer research continuum challenge.
Eur J Cancer. 2014; 50(16):2745-6 [PubMed] Related Publications
European cancer research for a transformative initiative by creating a consortium of six leading excellent comprehensive cancer centres that will work together to address the cancer care-cancer research continuum. Prerequisites for joint translational and clinical research programs are very demanding. These require the creation of a virtual single 'e-hospital' and a powerful translational platform, inter-compatible clinical molecular profiling laboratories with a robust underlying computational biology pipeline, standardised functional and molecular imaging, commonly agreed Standard Operating Procedures (SOPs) for liquid and tissue biopsy procurement, storage and processing, for molecular diagnostics, 'omics', functional genetics, immune-monitoring and other assessments. Importantly also it requires a culture of data collection and data storage that provides complete longitudinal data sets to allow for: effective data sharing and common database building, and to achieve a level of completeness of data that is required for conducting outcome research, taking into account our current understanding of cancers as communities of evolving clones. Cutting edge basic research and technology development serve as an important driving force for innovative translational and clinical studies. Given the excellent track records of the six participants in these areas, Cancer Core Europe will be able to support the full spectrum of research required to address the cancer research- cancer care continuum. Cancer Core Europe also constitutes a unique environment to train the next generation of talents in innovative translational and clinical oncology.

Related: Cancer Prevention and Risk Reduction

Surdu S, Fitzgerald EF, Bloom MS, et al.
Polymorphisms in DNA repair genes XRCC1 and XRCC3, occupational exposure to arsenic and sunlight, and the risk of non-melanoma skin cancer in a European case-control study.
Environ Res. 2014; 134:382-9 [PubMed] Related Publications
X-ray repair cross-complementing group 1 (XRCC1) and group 3 (XRCC3) polymorphisms are relatively frequent in Caucasian populations and may have implications in skin cancer modulation. A few studies have evaluated their association with non-melanoma skin cancer (NMSC), but the results are inconsistent. In the current study, we aim to assess the impact of XRCC1 R399Q and XRCC3 T241M polymorphisms on the risk of NMSC associated with sunlight and arsenic exposure. Study participants consist of 618 new cases of NMSC and 527 hospital-based controls frequency matched on age, sex, and county of residence from Hungary, Romania, and Slovakia. Adjusted effects are estimated using multivariable logistic regression. The results indicate an increased risk of squamous cell carcinoma (SCC) for the homozygous variant genotype of XRCC1 R399Q (OR 2.53, 95% CI 1.14-5.65) and a protective effect against basal cell carcinoma (BCC) for the homozygous variant genotype of XRCC3 T241M (OR 0.61, 95% CI 0.41-0.92), compared with the respective homozygous common genotypes. Significant interactions are detected between XRCC3 T241M and sunlight exposure at work, and between XRCC3 T241M and exposure to arsenic in drinking water (p-value for interaction <0.10). In conclusion, the current study demonstrates that polymorphisms in XRCC genes may modify the associations between skin cancer risk and exposure to sunlight or arsenic. Given the high prevalence of genetic polymorphisms modifying the association between exposure to environmental carcinogens and NMSC, these results are of substantial relevance to public health.

Related: Polymorphisms Skin Cancer

Hasan B, Greillier L, Pallis A, et al.
Progression free survival rate at 9 and 18 weeks predict overall survival in patients with malignant pleural mesothelioma: an individual patient pooled analysis of 10 European Organisation for Research and Treatment of Cancer Lung Cancer Group studies and an independent study validation.
Eur J Cancer. 2014; 50(16):2771-82 [PubMed] Related Publications
BACKGROUND: Response criteria have always been difficult to apply to malignant pleural mesothelioma (MPM), due to its unique pattern of growth. We developed some models to show that progression free survival rate (PFSR) could be a better predictor of overall survival (OS) than the response rate (RR) in MPM patients. The results were validated independently in the European Organisation for Research and Treatment of Cancer (EORTC) 08052, a phase II study in MPM.
METHODS: Individual patient data from 10 EORTC-Lung Cancer Group (LCG) studies of first-line chemotherapy in MPM were pooled. Response to therapy was assessed according to World Health Organisation (WHO) criteria in all except the two most recent trials, which used Response Evaluation Criteria in Solid Tumours (RECIST). Landmark analyses (LA) at 9 weeks and 18 weeks after registration/randomisation were performed to assess the association between PFSR and OS. Independent validation of the results was conducted in EORTC 08052 study (82 patients) employing the same LA.
RESULTS: All 10 studies (N=523 patients) were included in the LA of PFSR at 9 and 18 weeks (PFSR-9 and PFSR-18). PFSR-9 and PFSR-18 were confirmed as predictors of OS, with hazard ratio (HR) of 0.37 (95% confidence interval (CI), 0.30-0.47) and 0.50 (0.38-0.65) and C-index of 0.62 and 0.58, respectively. In the validation study, 28.4% achieved CR/PR and 77.8% had disease control (CR/PR/SD) as their best overall response. PFSR-9 and PFSR-18 weeks were both strongly correlated with OS (HR of 0.35 [80% CI, 0.25-0.49] and 0.46 (0.32-0.67) and C-index of 0.66 and 0.60, respectively).
CONCLUSION: PFSR-18 was strongly correlated and discriminated patients with better OS from the poorer prognosis patients. An earlier end-point, PFSR-9 was also strongly correlated to OS with better discriminating capacity. The results were independently validated.

Related: Lung Cancer Mesothelioma

Lecouvet FE, Talbot JN, Messiou C, et al.
Monitoring the response of bone metastases to treatment with Magnetic Resonance Imaging and nuclear medicine techniques: a review and position statement by the European Organisation for Research and Treatment of Cancer imaging group.
Eur J Cancer. 2014; 50(15):2519-31 [PubMed] Related Publications
Assessment of the response to treatment of metastases is crucial in daily oncological practice and clinical trials. For soft tissue metastases, this is done using computed tomography (CT), Magnetic Resonance Imaging (MRI) or Positron Emission Tomography (PET) using validated response evaluation criteria. Bone metastases, which frequently represent the only site of metastases, are an exception in response assessment systems, because of the nature of the fixed bony defects, their complexity, which ranges from sclerotic to osteolytic and because of the lack of sensitivity, specificity and spatial resolution of the previously available bone imaging methods, mainly bone scintigraphy. Techniques such as MRI and PET are able to detect the early infiltration of the bone marrow by cancer, and to quantify this infiltration using morphologic images, quantitative parameters and functional approaches. This paper highlights the most recent developments of MRI and PET, showing how they enable early detection of bone lesions and monitoring of their response. It reviews current knowledge, puts the different techniques into perspective, in terms of indications, strengths, weaknesses and complementarity, and finally proposes recommendations for the choice of the most adequate imaging technique.

Related: Cancer Prevention and Risk Reduction

Zamora-Ros R, Sacerdote C, Ricceri F, et al.
Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
Br J Cancer. 2014; 111(9):1870-80 [PubMed] Related Publications
BACKGROUND: There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
METHODS: A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases.
RESULTS: During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62-0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC.
CONCLUSIONS: Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.

Related: Bladder Cancer Bladder Cancer - Molecular Biology

Schröder FH, Hugosson J, Roobol MJ, et al.
Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up.
Lancet. 2014; 384(9959):2027-35 [PubMed] Related Publications
BACKGROUND: The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up, but screening is controversial because of adverse events such as overdiagnosis. We provide updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9, 11, and 13 years.
METHODS: ERSPC is a multicentre, randomised trial with a predefined centralised database, analysis plan, and core age group (55-69 years), which assesses prostate-specific antigen (PSA) testing in eight European countries. Eligible men aged 50-74 years were identified from population registries and randomly assigned by computer generated random numbers to screening or no intervention (control). Investigators were masked to group allocation. The primary outcome was prostate cancer mortality in the core age group. Analysis was by intention to treat. We did a secondary analysis that corrected for selection bias due to non-participation. Only incidence and no mortality data at 9 years' follow-up are reported for the French centres. This study is registered with Current Controlled Trials, number ISRCTN49127736.
FINDINGS: With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group. The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 (95% CI 1·83-1·99) after 9 years (1·64 [1·58-1·69] including France), 1·66 (1·60-1·73) after 11 years, and 1·57 (1·51-1·62) after 13 years. The rate ratio of prostate cancer mortality was 0·85 (0·70-1·03) after 9 years, 0·78 (0·66-0·91) after 11 years, and 0·79 (0·69-0·91) at 13 years. The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490-1929) men invited for screening or one per 27 (17-66) additional prostate cancer detected. After adjustment for non-participation, the rate ratio of prostate cancer mortality in men screened was 0·73 (95% CI 0·61-0·88).
INTERPRETATION: In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening.
FUNDING: Each centre had its own funding responsibility.

Related: Prostate Cancer

Lerebours A, Stentiford GD, Lyons BP, et al.
Genetic alterations and cancer formation in a European flatfish at sites of different contaminant burdens.
Environ Sci Technol. 2014; 48(17):10448-55 [PubMed] Related Publications
Fish diseases are an indicator for marine ecosystem health since they provide a biological end-point of historical exposure to stressors. Liver cancer has been used to monitor the effects of exposure to anthropogenic pollution in flatfish for many years. The prevalence of liver cancer can exceed 20%. Despite the high prevalence and the opportunity of using flatfish to study environmentally induced cancer, the genetic and environmental factors driving tumor prevalence across sites are poorly understood. This study aims to define the link between genetic deterioration, liver disease progression, and anthropogenic contaminant exposures in the flatfish dab (Limanda limanda). We assessed genetic changes in a conserved cancer gene, Retinoblastoma (Rb), in association with histological diagnosis of normal, pretumor, and tumor pathologies in the livers of 165 fish from six sites in the North Sea and English Channel. The highest concentrations of metals (especially cadmium) and organic chemicals correlated with the presence of tumor pathology and with defined genetic profiles of the Rb gene, from these sites. Different Rb genetic profiles were found in liver tissue near each tumor phenotype, giving insight into the mechanistic molecular-level cause of the liver pathologies. Different Rb profiles were also found at sampling sites of differing contaminant burdens. Additionally, profiles indicated that histological "normal" fish from Dogger sampling locations possessed Rb profiles associated with pretumor disease. This study highlights an association between Rb and specific contaminants (especially cadmium) in the molecular etiology of dab liver tumorigenesis.

Related: Liver Cancer RB1

van der Burg ME, Onstenk W, Boere IA, et al.
Long-term results of a randomised phase III trial of weekly versus three-weekly paclitaxel/platinum induction therapy followed by standard or extended three-weekly paclitaxel/platinum in European patients with advanced epithelial ovarian cancer.
Eur J Cancer. 2014; 50(15):2592-601 [PubMed] Related Publications
BACKGROUND: Weekly paclitaxel/carboplatin might improve survival in platinum-resistant epithelial ovarian cancer (EOC). We compared efficacy of first-line weekly to three-weekly paclitaxel/cis- or carboplatin (PCw and PC3w) induction therapy, followed by either three or six PC3w cycles.
PATIENTS AND METHODS: In this multicentre, randomised phase III trial with 2×2 design, patients with FIGO stage IIb-IV EOC were randomised to six cycles PCw (paclitaxel 90mg/m(2), cisplatin 70mg/m(2) or carboplatin AUC 4) or three cycles PC3w (paclitaxel 175mg/m(2), cisplatin 75mg/m(2) or carboplatin AUC 6), followed by either three or six cycles PC3w. Primary endpoints were progression free survival (PFS) and overall survival (OS). Secondary endpoints were response rate (RR) and toxicity.
RESULTS: Of 267 eligible patients, 133 received PCw and 134 PC3w. The first 105 patients received cisplatin, after protocol amendment the subsequent 162 patients received carboplatin. Weekly cisplatin was less well tolerated than weekly carboplatin. All PC3w cycles were well tolerated. At the end of all treatments, RR was 90.8% with no differences between the treatment arms. After a follow-up of median 10.3years (range 7.1-14.8), median PFS was 18.5 (95% confidence interval (CI) 15.9-21.0) months for PCw and 16.4 (95% CI 13.5-19.2) months for PC3w (p=0.78). Median OS was 44.8 (95% CI 33.1-56.5) months for PCw and 41.1 (95% CI 34.4-47.7) months for PC3w (p=0.98).
CONCLUSIONS: There was no benefit in terms of OS, PFS or RR for a weekly regimen nor for extended chemotherapy as first-line treatment for EOC in European patients.

Related: Carboplatin Cisplatin Ovarian Cancer Paclitaxel

Datta NR, Samiei M, Bodis S
Radiotherapy infrastructure and human resources in Europe - present status and its implications for 2020.
Eur J Cancer. 2014; 50(15):2735-43 [PubMed] Related Publications
Radiotherapy (RT) is required for nearly half of the newly diagnosed cancer patients. To optimise the quality and availability of RT, guidelines have been proposed by European Society for Radiotherapy and Oncology-QUAntification of Radiation Therapy Infrastructure And Staffing Needs (ESTRO-QUARTS) and the International Atomic Energy Agency (IAEA). This study evaluates the present status of RT capacity in Europe and the projected needs by 2020 as per these recommendations. Thirty-nine of the 53 countries, listed in Europe by the UN Statistical Division, whose cancer incidences, teletherapy and human resources were available in the Global Cancer Incidence, Mortality and Prevalence (GLOBOCAN), International Agency for Research on Cancer (IARC) and DIrectory of RAdiotherapy Centres (DIRAC) (IAEA) databases were evaluated. A total of 3550 teletherapy units (TRT), 7017 radiation oncologists (RO), 3685 medical physicists (MP) and 12,788 radiotherapy technologists (RTT) are presently available for the 3.44 million new cancer cases reported annually in these countries. The present infrastructure and human resources in RT are estimated to provide RT access to 74.3% of the patients requiring RT. The current capacity in TRT, RO, MP and RTT when compared with recommended guidelines has a deficit of 25.6%, 18.3%, 22.7% and 10.6%, respectively. Thus, to respond to requirements by 2020, the existing capacity needs to be augmented by an additional 1698 TRTs, 2429 ROs, 1563 MPs and 2956 RTTs. With an imminent rise in cancer incidence, multifaceted strategic planning at national and international levels within a coordinated comprehensive cancer control programme is highly desirable to give adequate access to all patients who require radiotherapy across Europe. Specific steps to address this issue at national and continental levels involving all major stakeholders are proposed.

Related: Cancer Prevention and Risk Reduction

Blackhall FH, Peters S, Bubendorf L, et al.
Prevalence and clinical outcomes for patients with ALK-positive resected stage I to III adenocarcinoma: results from the European Thoracic Oncology Platform Lungscape Project.
J Clin Oncol. 2014; 32(25):2780-7 [PubMed] Related Publications
PURPOSE: The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non-small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population.
METHODS: Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients with adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. Positive patients were matched with negative patients in a 1:2 ratio, both for IHC and for FISH testing. Testing was performed in 16 participating centers, using the same protocol after passing external quality assessment.
RESULTS: Positive ALK IHC staining was present in 80 patients (prevalence of 6.2%; 95% CI, 4.9% to 7.6%). Of these, 28 patients were ALK FISH positive, corresponding to a lower bound for the prevalence of FISH positivity of 2.2%. FISH specificity was 100%, and FISH sensitivity was 35.0% (95% CI, 24.7% to 46.5%), with a sensitivity value of 81.3% (95% CI, 63.6% to 92.8%) for IHC 2+/3+ patients. The hazard of death for FISH-positive patients was lower than for IHC-negative patients (P = .022). Multivariable models, adjusted for patient, tumor, and treatment characteristics, and matched cohort analysis confirmed that ALK FISH positivity is a predictor for better overall survival (OS).
CONCLUSION: In this large cohort of surgically resected lung adenocarcinomas, the prevalence of ALK positivity was 6.2% using IHC and at least 2.2% using FISH. A screening strategy based on IHC or H-score could be envisaged. ALK positivity (by either IHC or FISH) was related to better OS.

Related: FISH Lung Cancer ALK

Terenziani M, Spinelli M, Jankovic M, et al.
Practices of pediatric oncology and hematology providers regarding fertility issues: a European survey.
Pediatr Blood Cancer. 2014; 61(11):2054-8 [PubMed] Related Publications
BACKGROUND: Fertility is impaired in many survivors of childhood cancer following treatment. Preservation of fertility after cancer has become a central survivorship concern. Nevertheless, several doctors, patients, and families do not discuss fertility and recommendations for fertility preservation in pediatrics are still lacking. Recommendations based on scientific evidence are needed and before their development we wanted to assess the practice patterns of fertility preservation in Europe.
PROCEDURES: On behalf of the PanCare network, we sent a questionnaire to pediatric onco-hematology institutions across Europe. The survey consisted of 21 questions assessing their usual practices around fertility preservation.
RESULTS: One hundred ninety-eight institutional representatives across Europe received the survey and 68 (response rate 34.3%) responded. Pre-treatment fertility counseling was offered by 64 institutions. Counseling was done by a pediatric onco-hematologist in 52% (33/64) and in 32% (20/64) by a team. The majority of institutions (53%) lacked recommendations for fertility preservation. All 64 centers offered sperm banking; eight offered testicular tissue cryopreservation for pre-pubertal males. For females, the possibility of preserving ovarian tissue was offered by 40 institutions.
CONCLUSIONS: There is a high level of interest in fertility preservation among European centers responding to our survey. However, while most recommended sperm cryopreservation, many also recommended technologies whose efficacy has not been shown. There is an urgent need for evidence-based European recommendations for fertility preservation to help survivors deal with the stressful topic of fertility.

Related: Cancer Prevention and Risk Reduction Children's Cancer Web: Home Page

Di Dalmazi G, Kisker C, Calebiro D, et al.
Novel somatic mutations in the catalytic subunit of the protein kinase A as a cause of adrenal Cushing's syndrome: a European multicentric study.
J Clin Endocrinol Metab. 2014; 99(10):E2093-100 [PubMed] Related Publications
CONTEXT: Somatic mutations in PRKACA gene, encoding the catalytic subunit of protein kinase A (PKA), have been recently found in a high proportion of sporadic adenomas associated with Cushing's syndrome. The aim was to analyze the PRKACA mutation in a large cohort of patients with adrenocortical masses.
METHODS: Samples from nine European centers were included (Germany, n = 4; Italy, n = 4; France, n = 1). Samples were drawn from 149 patients with nonsecreting adenomas (n = 32 + 2 peritumoral), subclinical hypercortisolism (n = 36), Cushing's syndrome (n = 64 + 2 peritumoral), androgen-producing tumors (n = 4), adrenocortical carcinomas (n = 5 + 2 peritumoral), and primary bilateral macronodular adrenal hyperplasias (n = 8). Blood samples were available from patients with nonsecreting adenomas (n = 15), subclinical hypercortisolism (n = 10), and Cushing's syndrome (n = 35). Clinical and hormonal data were collected. DNA amplification by PCR of exons 6 and 7 of the PRKACA gene and direct sequencing were performed.
RESULTS: PRKACA heterozygous mutations were found in 22/64 samples of Cushing's syndrome patients (34%). No mutations were found in peritumoral tissue and blood samples or in other tumors examined. The c.617A>C (p.Leu206Arg) occurred in 18/22 patients. Furthermore, two novel mutations were identified: c.600_601insGTG/p.Cys200_Gly201insVal in three patients and c.639C>G+c.638_640insATTATCCTGAGG/p.Ser213Arg+p.Leu212_Lys214insIle-Ile-Leu-Arg) in one. All the mutations involved a region implicated in interaction between PKA regulatory and catalytic subunits. Patients with somatic PRKACA mutations showed higher levels of cortisol after dexamethasone test and a smaller adenoma size, compared with nonmutated subjects.
CONCLUSIONS: These data confirm and extend previous observations that somatic PRKACA mutations are specific for adrenocortical adenomas causing Cushing's syndrome.

Related: Adrenocortical Cancer Adrenocortical Carcinoma - Molecular Biology

Conway G, Dewailly D, Diamanti-Kandarakis E, et al.
European survey of diagnosis and management of the polycystic ovary syndrome: results of the ESE PCOS Special Interest Group's Questionnaire.
Eur J Endocrinol. 2014; 171(4):489-98 [PubMed] Related Publications
BACKGROUND: There is evidence for differences between endocrinologists and other specialists in their approach to diagnosis and management of the polycystic ovary syndrome (PCOS).
OBJECTIVE: A mailed survey consisting of a simple questionnaire aiming to understand current practice for diagnosis and management of the PCOS by specialists across Europe.
METHODS: The questionnaire consisted of 23 questions grouped to achieve information on i) the general characteristics of the respondents, ii) patients with PCOS seen by endocrinologists, iii) the main diagnostic criteria, iv) biochemical parameters used in the differential diagnosis of hyperandrogenism, v) long-term concerns, and, finally vi) treatment choices. A total of 357 questionnaires representing 13.3% of the members of European Society of Endocrinology (ESE) were available for final analysis; 93% of the respondents were endocrinologists
RESULTS: In relation to the diagnostic criteria, respondents were most likely to select menstrual irregularity as the most frequent criteria used for the diagnosis of PCOS although very high rates were achieved for the use of hirsutism and biochemical hyperandrogenism. It therefore appears that the NIH criteria were followed by the majority of respondents. The most frequent biochemical parameters in the differential diagnosis of hyperandrogenism were total testosterone or free androgen index. Obesity and type 2 diabetes were regarded as the principal long-term concerns for PCOS. The most common treatments for patients with PCOS were metformin (33%), lifestyle modification (25%), and oral contraceptives (22%). More direct treatments of infertility include clomiphene citrate alone or in combination with metformin, prescribed by 9 and 23%, respectively, whereas only 6% used other methods for induction of ovulation.
CONCLUSION: The survey produced by ESE is a good start for evaluating the perspective in the diagnosis and treatment of PCOS by endocrinologists in Europe.

Sant M, Minicozzi P, Mounier M, et al.
Survival for haematological malignancies in Europe between 1997 and 2008 by region and age: results of EUROCARE-5, a population-based study.
Lancet Oncol. 2014; 15(9):931-42 [PubMed] Related Publications
BACKGROUND: More effective treatments have become available for haematological malignancies from the early 2000s, but few large-scale population-based studies have investigated their effect on survival. Using EUROCARE data, and HAEMACARE morphological groupings, we aimed to estimate time trends in population-based survival for 11 lymphoid and myeloid malignancies in 20 European countries, by region and age.
METHODS: In this retrospective observational study, we included patients (aged 15 years and older) diagnosed with haematological malignancies, diagnosed up to Dec 31, 2007, and followed up to Dec 31, 2008. We used data from the 30 cancer registries (across 20 countries) that provided continuous incidence and good quality data from 1992 to 2007. We used a hybrid approach to estimate age-standardised and age-specific 5-year relative survival, for each malignancy, overall and for five regions (UK, and northern, central, southern, and eastern Europe), and four 3-year periods (1997-99, 2000-02, 2003-05, 2006-08). For each malignancy, we also estimated the relative excess risk of death during the 5 years after diagnosis, by period, age, and region.
FINDINGS: We analysed 560 444 cases. From 1997-99 to 2006-08 survival increased for most malignancies: the largest increases were for diffuse large B-cell lymphoma (42·0% [95% CI 40·7-43·4] to 55·4% [54·6-56·2], p<0·0001), follicular lymphoma (58·9% [57·3-60·6] to 74·3% [72·9-75·5], p<0·0001), chronic myeloid leukaemia (32·3% [30·6-33·9] to 54·4% [52·5-56·2], p<0·0001), and acute promyelocytic leukaemia (50·1% [43·7-56·2] to 61·9% [57·0-66·4], p=0·0038, estimate not age-standardised). Other survival increases were seen for Hodgkin's lymphoma (75·1% [74·1-76·0] to 79·3% [78·4-80·1], p<0·0001), chronic lymphocytic leukaemia/small lymphocytic lymphoma (66·1% [65·1-67·1] to 69·0% [68·1-69·8], p<0·0001), multiple myeloma/plasmacytoma (29·8% [29·0-30·6] to 39·6% [38·8-40·3], p<0·0001), precursor lymphoblastic leukaemia/lymphoma (29·8% [27·7-32·0] to 41·1% [39·0-43·1], p<0·0001), acute myeloid leukaemia (excluding acute promyelocytic leukaemia, 12·6% [11·9-13·3] to 14·8% [14·2-15·4], p<0·0001), and other myeloproliferative neoplasms (excluding chronic myeloid leukaemia, 70·3% [68·7-71·8] to 74·9% [73·8-75·9], p<0·0001). Survival increased slightly in southern Europe, more in the UK, and conspicuously in northern, central, and eastern Europe. However, eastern European survival was lower than that for other regions. Survival decreased with advancing age, and increased with time only slightly in patients aged 75 years or older, although a 10% increase in survival occurred in elderly patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic myeloid leukaemia.
INTERPRETATION: These trends are encouraging. Widespread use of new and more effective treatment probably explains much of the increased survival. However, the persistent differences in survival across Europe suggest variations in the quality of care and availability of the new treatments. High-resolution studies that collect data about stage at diagnosis and treatments for representative samples of cases could provide further evidence of treatment effectiveness and explain geographic variations in survival.
FUNDING: Compagnia di San Paolo, Fondazione Cariplo, European Commission, and Italian Ministry of Health.

Related: Haematological Malignancies & Realted Disorders

Groll AH, Castagnola E, Cesaro S, et al.
Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation.
Lancet Oncol. 2014; 15(8):e327-40 [PubMed] Related Publications
Invasive opportunistic fungal diseases (IFDs) are important causes of morbidity and mortality in paediatric patients with cancer and those who have had an allogeneic haemopoietic stem-cell transplantation (HSCT). Apart from differences in underlying disorders and comorbidities relative to those of adults, IFDs in infants, children, and adolescents are unique with respect to their epidemiology, the usefulness of diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of interventional phase 3 clinical trials for guidance of evidence-based decisions. To better define the state of knowledge on IFDs in paediatric patients with cancer and allogeneic HSCT and to improve IFD diagnosis, prevention, and management, the Fourth European Conference on Infections in Leukaemia (ECIL-4) in 2011 convened a group that reviewed the scientific literature on IFDs and graded the available quality of evidence according to the Infectious Diseases Society of America grading system. The final considerations and recommendations of the group are summarised in this manuscript.

Related: Leukemia Childhood Leukaemia Leukemia - Molecular Biology

Tjalma WA
The ideal cervical cancer screening recommendation for Belgium, an industrialized country in Europe.
Eur J Gynaecol Oncol. 2014; 35(3):211-8 [PubMed] Related Publications
Cervical cancer should be a historical disease, why are we not succeeding! The prophylactic vaccination will reduce cervical cancer by almost 80% in Belgium. Cervical cancer screening should therefore remain in order to prevent the remaining 20%. The current used Pap cytology test misses 50% of all clinically significant precancers and cancers at the time of testing. The test should remain but the analysis should be altered. The screening should be modified based on our knowledge of human papillomavirus (HPV) as causal factor. Instead of looking for a cell abnormality, one should look for the presence of HPV. Then depending on the test, only two to ten percent of all relevant lesions are missed. The introduction of the vaccination should lead to the re-introduction of the screening based on HPV. This will not only lead to a considerable reduction in morbidity and mortality, allow longer screening intervals, but it will also be more cost-effective. More for less should be the driving force in cervical cancer screening if we want to be successful.

Related: Cancer Screening and Early Detection Cervical Cancer

Yanagawa N, Shiono S, Abiko M, et al.
The correlation of the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification with prognosis and EGFR mutation in lung adenocarcinoma.
Ann Thorac Surg. 2014; 98(2):453-8 [PubMed] Related Publications
BACKGROUND: The purpose of this study was to validate the prognostic effect and the frequency of mutations in the gene expressing epidermal growth factor receptor (EGFR) in lung adenocarcinoma of Japanese patients, on the basis of the new adenocarcinoma classification proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society.
METHODS: The new classification was used to reclassify 486 adenocarcinomas. The percentage of each histopathologic subtype and the predominant pattern were determined. EGFR mutation was also investigated. The relationship between these results and clinicopathologic backgrounds was investigated statistically.
RESULTS: No patients with adenocarcinoma in situ or minimally invasive adenocarcinoma died within the follow-up periods, followed by patients with lepidic predominant. Patients with papillary or acinar predominant, or invasive mucinous adenocarcinoma, showed almost similar overall survival (OS). The patients with solid predominant and micropapillary predominant showed the worst OS. Multivariate analysis showed that the new classification was an independent predictor of OS. The frequency of EGFR mutation was adenocarcinoma in situ (62%), minimally invasive adenocarcinoma (60%), lepidic (77%), acinar (49%), papillary (50%), solid (28%), micropapillary (43%), and invasive mucinous adenocarcinoma (0%).
CONCLUSIONS: This new adenocarcinoma classification is a very useful predictive marker to plan and determine a therapeutic strategy for lung adenocarcinoma.

Related: Lung Cancer

Tucunduva L, Ruggeri A, Sanz G, et al.
Impact of minimal residual disease on outcomes after umbilical cord blood transplantation for adults with Philadelphia-positive acute lymphoblastic leukaemia: an analysis on behalf of Eurocord, Cord Blood Committee and the Acute Leukaemia working party of the European group for Blood and Marrow Transplantation.
Br J Haematol. 2014; 166(5):749-57 [PubMed] Related Publications
The status of umbilical cord blood transplantation (UCBT) in adults with Philadelphia-positive acute lymphoblastic leukaemia (Ph+ALL) and the impact of minimal residual disease (MRD) before transplant are not well established. We analysed 98 patients receiving UCBT for Ph+ALL in first (CR1) or second (CR2) complete remission (CR1, n = 79; CR2, n = 19) with MRD available before UCBT (92% analysed by reverse transcription polymerase chain reaction). Median age was 38 years and median follow-up was 36 months; 63% of patients received myeloablative conditioning and 42% received double-unit UCBT. Eighty-three patients were treated with at least one tyrosine kinase inhibitor before UCBT. MRD was negative (-) in 39 and positive (+) in 59 patients. Three-year cumulative incidence of relapse was 34%; 45% in MRD+ and 16% in MRD- patients (P =0·013). Three-year cumulative incidence of non-relapse mortality was 31%; it was increased in patients older than 35 years (P = 0·02). Leukaemia-free survival (LFS) at 3 years was 36%; 27% in MRD+ and 49% in MRD- patients (P = 0·05), and 41% for CR1 and 14% for CR2 (P = 0·008). Multivariate analysis identified only CR1 as being associated with improved LFS. In conclusion, MRD+ before UCBT is associated with increased relapse. Strategies to decrease relapse in UCBT recipients with Ph+ALL and MRD+ are needed.

Related: Acute Lymphocytic Leukemia (ALL)

Schöttker B, Jorde R, Peasey A, et al.
Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States.
BMJ. 2014; 348:g3656 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To investigate the association between serum 25-hydroxyvitamin D concentrations (25(OH)D) and mortality in a large consortium of cohort studies paying particular attention to potential age, sex, season, and country differences.
DESIGN: Meta-analysis of individual participant data of eight prospective cohort studies from Europe and the US.
SETTING: General population.
PARTICIPANTS: 26,018 men and women aged 50-79 years.
MAIN OUTCOME MEASURES: All-cause, cardiovascular, and cancer mortality.
RESULTS: 25(OH)D concentrations varied strongly by season (higher in summer), country (higher in US and northern Europe) and sex (higher in men), but no consistent trend with age was observed. During follow-up, 6695 study participants died, among whom 2624 died of cardiovascular diseases and 2227 died of cancer. For each cohort and analysis, 25(OH)D quintiles were defined with cohort and subgroup specific cut-off values. Comparing bottom versus top quintiles resulted in a pooled risk ratio of 1.57 (95% CI 1.36 to 1.81) for all-cause mortality. Risk ratios for cardiovascular mortality were similar in magnitude to that for all-cause mortality in subjects both with and without a history of cardiovascular disease at baseline. With respect to cancer mortality, an association was only observed among subjects with a history of cancer (risk ratio, 1.70 (1.00 to 2.88)). Analyses using all quintiles suggest curvilinear, inverse, dose-response curves for the aforementioned relationships. No strong age, sex, season, or country specific differences were detected. Heterogeneity was low in most meta-analyses.
CONCLUSIONS: Despite levels of 25(OH)D strongly varying with country, sex, and season, the association between 25(OH)D level and all-cause and cause-specific mortality was remarkably consistent. Results from a long term randomised controlled trial addressing longevity are being awaited before vitamin D supplementation can be recommended in most individuals with low 25(OH)D levels.

Related: Cancer Prevention and Risk Reduction USA

Obón-Santacana M, Kaaks R, Slimani N, et al.
Dietary intake of acrylamide and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.
Br J Cancer. 2014; 111(5):987-97 [PubMed] Article available free on PMC after 26/08/2015 Related Publications
BACKGROUND: Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk.
METHODS: Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method.
RESULTS: No associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08-3.62; likelihood ratio test (LRT) P-value: 0.01, n=203).
CONCLUSIONS: Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers.

Related: Endometrial (Uterus) Cancer Endometrial Cancer

Lacombe D, Tejpar S, Salgado R, et al.
European perspective for effective cancer drug development.
Nat Rev Clin Oncol. 2014; 11(8):492-8 [PubMed] Related Publications
Health systems and the clinical research landscape evolve continuously owing to increased risk aversion, scrutiny by funding bodies, and costs of clinical trials. In this context, however, current drug development procedures are far from optimal, as exemplified by the late-stage failure of several drugs. The identification of new drugs urgently requires approaches based on a solid understanding of cancer biology, and that will support the design of robust confirmatory trials. The complexity and the costs of drug development are now beyond the knowledge and operational capacity of single organisations, therefore, a drastic deviation from the traditional path of drug discovery and new forms of multidisciplinary partnerships are needed to succeed in this sector. The European Organisation for Research and Treatment of Cancer (EORTC) proposes the use of collaborative molecular screening platforms (CMSPs) as a new approach to tackle this issue. These CMSPs have the advantage of optimizing the expertise of several partners and combining efforts alongside with cost-sharing models for efficient patient selection. This article describes some of the challenges to advancing drug development and improving medical treatments and how these hurdles can be overcome.

Related: Cancer Prevention and Risk Reduction

Rabasseda X
A report from the 29th Annual Congress of the European Association of Urology (April 11-15 - Stockholm, Sweden).
Drugs Today (Barc). 2014; 50(5):385-95 [PubMed] Related Publications
The annual congress of the European Association of Urology in Stockholm was packed with mixed poster/oral sessions wherein innovative clinical and preclinical research aimed at improving the care of patients with urinary tract diseases was reported and open for discussion. Not everything that was reported during the meeting can be captured in a single report, but the following text will guide readers through the most significant new findings directly related with pharmacotherapy for overactive bladder, urinary tract cancer and other common medical conditions that endanger the quality of life and life expectancy of many patients worldwide.

Related: Kidney Cancer Prostate Cancer Bladder Cancer Bladder Cancer - Molecular Biology

Fong ZV, Tanabe KK
The clinical management of hepatocellular carcinoma in the United States, Europe, and Asia: a comprehensive and evidence-based comparison and review.
Cancer. 2014; 120(18):2824-38 [PubMed] Related Publications
Hepatocellular carcinoma (HCC), the most common primary malignancy of the liver, represents 1 of the leading causes of cancer deaths in the world with an estimated 21,670 deaths in the United States in 2013. In contrast to other malignancies, there is an array of treatment options for HCC involving several specialties in the multidisciplinary care of the patient. Consequently, vast heterogeneity in management tendencies has been observed. The objective of this report was to review and compare guidelines on the management of HCC from the United States (National Comprehensive Cancer Network), Europe (European Association for the Study of the Liver-European Organization for Research and Treatment of Cancer), and Asia (consensus statement from the 2009 Asian Oncology Summit). By and large, all 3 guidelines are similar, with some variance in surveillance and treatment allocation recommendations because of regional differences in disease and other variables (diagnosis, staging systems) secondary to the lack of a concrete, high level of evidence. In contrast to other cancers, the geographic differences in tumor biology and resources make it impractical to have a globally universal guideline for all patients with HCC. Recommendations from the 3 groups are influenced by geographic differences in the prevalence and biology of the disease (ie, areas of increased hepatitis B prevalence) and available resources (organ availability for transplantation, finances, and accessibility to treatment). It is important for both physicians and policy makers to include these considerations when treating patients with HCC as well when structuring policies and guidelines.

Related: Liver Cancer USA

Zanetti R, Sacchetto L, Calvia M, et al.
Economic evaluation of cancer registration in Europe.
J Registry Manag. 2014; 41(1):31-7 [PubMed] Related Publications
BACKGROUND: Little has been reported on costs of cancer registration, and standard indicators have not yet been identified. This study investigated costs and outcomes of a sample of 18 European registries covering a population of 58.8 million inhabitants.
METHODS: Through a questionnaire, we asked registries for real cost data including personnel, information technology (IT), and infrastructure. Staff costs were grouped by professional position and by activity performed. As outcomes, besides the production of current data, we considered publications in peer-reviewed journals (last 5 years' impact factor [IF]) and characteristics of registry websites.
RESULTS: In our sample, the average cost of cancer registration per inhabitant was €0.27 at purchasing power standard (PPS) (range €0.03-€0.97), while the mean cost per case registered was €50.71 PPS (range €6-€213). Personnel costs accounted for an average of 79 percent of total resources. Resources spent in routine activities (an average of 51 percent, range 28 percent-87 percent) were predominant with respect to those allocated to research, with a few exceptions. Website quality seemed to be independent of total registry budget.
CONCLUSIONS: The variance in costs of cancer registration across Europe can be attributed mainly to the type of registry (whether national or regional), the size of the covered population, and the national economic profile, expressed as gross domestic product.

Related: Cancer Prevention and Risk Reduction

Vegter S, Tolley K
A network meta-analysis of the relative efficacy of treatments for actinic keratosis of the face or scalp in Europe.
PLoS One. 2014; 9(6):e96829 [PubMed] Article available free on PMC after 26/08/2015 Related Publications
BACKGROUND: Several treatments are available for actinic keratosis (AK) on the face and scalp. Most treatment modalities were compared to placebo and therefore little is known on their relative efficacy.
OBJECTIVES: To compare the different treatments for mild to moderate AK on the face and scalp available in clinical practice in Europe.
METHODS: A network meta-analysis (NMA) was performed on the outcome "complete patient clearance". Ten treatment modalities were included: two 5-aminolaevulinic acid photodynamic therapies (ALA-PDT), applied as gel (BF-200 ALA) or patch; methyl-aminolevulinate photodynamic therapy (MAL-PDT); three modalities with imiquimod (IMI), applied as a 4-week or 16-week course with 5% imiquimod, or a 2-3 week course with 3.75% imiquimod; cryotherapy; diclofenac 3% in 2.5% hyaluronic acid; 0.5% 5-fluorouracil (5-FU); and ingenol mebutate (IMB). The only data available for 5% 5-FU was from one small study and was determined to be too limited to be reliably included in the analysis. For BF-200 ALA and MAL-PDT, data from illumination with narrow-band lights were selected as these are typically used in clinical practice. The NMA was performed with a random-effects Bayesian model.
RESULTS: 25 trials on 5,562 patients were included in the NMA. All active treatments were significantly better than placebo. BF-200 ALA showed the highest efficacy compared to placebo to achieve total patient clearance. BF-200 ALA had the highest probability to be the best treatment and the highest SUCRA score (64.8% and 92.1%), followed by IMI 5% 4 weeks (10.1% and 74.2%) and 5-FU 0.5% (7.2% and 66.8%).
CONCLUSIONS: This NMA showed that BF-200 ALA, using narrow-band lights, was the most efficacious treatment for mild to moderate AK on the face and scalp. This analysis is relevant for clinical decision making and health technology assessment, assisting the improved management of AK.

Ose J, Fortner RT, Rinaldi S, et al.
Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition.
Int J Cancer. 2015; 136(2):399-410 [PubMed] Related Publications
The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2 = 0.79, 95% confidence interval [CI] = [0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2 = 1.99 [0.98-4.06]; high grade: ORlog2 = 0.75 [0.61-0.93], phet ≤ 0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed.

Related: Fallopian Tube Cancer Ovarian Cancer

Postel-Vinay S, Collette L, Paoletti X, et al.
Towards new methods for the determination of dose limiting toxicities and the assessment of the recommended dose for further studies of molecularly targeted agents--dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies, an European Organisation for Research and Treatment of Cancer-led study.
Eur J Cancer. 2014; 50(12):2040-9 [PubMed] Related Publications
INTRODUCTION: Traditional dose-limiting toxicity (DLT) definition, which uses grade (G) 3-4 toxicity data from cycle 1 (C1) only, may not be appropriate for molecularly targeted agents (MTAs) of prolonged administration, for which late or lower grade toxicities also deserve attention.
PATIENTS AND METHODS: In collaboration with pharmaceutical companies and academia, an European Organisation for Research and Treatment of Cancer (EORTC)-led initiative, Dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies (DLT-TARGETT), collected data from completed phase 1 trials evaluating MTAs as monotherapy. All toxicities at least possibly related to the study drugs that occurred during C1-6, their type, grade (CTCAEv3.0), and duration as well as patients' relative dose-intensity (RDI), were recorded.
RESULTS: The 54 eligible trials enrolled 2084 evaluable adult patients with solid tumours between 1999 and 2013, and evaluated small molecules (40), antibodies (seven), recombinant peptides (five) and antisense oligodeoxynucleotides (two). A maximum tolerated dose was set in 43 trials. Fifteen percent of the patients received <75% of the intended RDI in C1, but only 9.1% of them presented protocol-defined DLTs. After C1, 16-19% of patients received <75% of the intended RDI. A similar proportion of G ⩾ 3 toxicities was recorded in C1 and after C1 (936 and 1087 toxicities, respectively), with the first G⩾3 toxicity occurring after C1 in 18.6% of patients.
CONCLUSION: Although protocol-defined DLT period is traditionally limited to C1, almost 20% of patients present significant reductions in RDI at any time in phase 1 trials of MTAs. Recommended phase 2 dose assessment should incorporate all available information from any cycle (notably lower grade toxicities leading to such RDI decrease), and be based on achieving >75% RDI.

Related: Cancer Prevention and Risk Reduction

This page last updated: 10th February 2015
Displaying links verified within last 2 weeks at time of update.

CancerIndex Logo

Site Map
Cancer Types

Health Professionals


© 1996-2015