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  • 1
    Keywords: CELLS ; COMBINATION ; Germany ; THERAPY ; DIAGNOSIS ; DISEASE ; PATIENT ; TRANSPLANTATION ; tumour ; PROGRESSION ; MALIGNANCIES ; ASSAY ; chemotherapy ; PCR ; REGION ; BONE-MARROW-TRANSPLANTATION ; POLYMERASE-CHAIN-REACTION ; KINETICS ; HEMATOPOIETIC-CELLS ; real-time PCR ; relapse ; MULTIPLE-MYELOMA ; MINIMAL RESIDUAL DISEASE ; molecular ; AUTOLOGOUS TRANSPLANTATION ; MOLECULAR REMISSION ; multiple myeloma ; monitoring ; IgH rearrangement ; HIGH-DOSE THERAPY ; REMISSION ; DISEASE PROGRESSION ; non-myeloablative allogeneic transplantation
    Abstract: Background: Non-myeloablative allogeneic stem cell transplantation followed by immunomodulatory therapies is considered a potentially curative approach in the treatment of multiple myeloma and most effective in a minimal residual disease setting. Patients and methods: The aim of this study was to find the most sensitive real-time PCR assay (TaqMan), based on the IGH rearrangement, to quantify the tumour load of 11 patients with multiple myeloma after non-myeloablative allogeneic transplantation. Patient-allele specific primers (ASO) and the TaqMan probe were derived from CDR2 and CDR3 hypervariable regions of IGH, while consensus primers were located within the FR3 and FR4/JH regions. Four different approaches of primer combinations were tested. Results: ASO-forward and -reverse primers together with the clone-specific TaqMan probe were the most sensitive approach compared with the III (P=0.071) or the FR3 consensus primer (P〈0.001). The detection limit amounted to 1/10(4) 1/10(5) cells. Consecutively, 120 samples from 11 patients prior and post allogeneic transplantation were analysed. Three patients reached complete clinical remission accompanied by molecular remission. Disease progression or relapse was seen in six patients. In five, molecular progressive disease was detected prior to the clinical diagnosis of progression or relapse. Conclusion: Patient-specific real-time IGH-PCR provides the opportunity for earlier treatment intervention
    Type of Publication: Journal article published
    PubMed ID: 15737985
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  • 2
  • 3
    Keywords: brain ; radiotherapy ; SURVIVAL ; Germany ; THERAPY ; TOXICITY ; DISEASE ; SITE ; SITES ; TIME ; PATIENT ; RESPONSES ; SKIN ; CYCLE ; TRIAL ; CLINICAL-TRIALS ; metastases ; chemotherapy ; MELANOMA ; METASTATIC MELANOMA ; PROGNOSTIC-FACTORS ; INVOLVEMENT ; SAFETY ; MALIGNANT-MELANOMA ; MELANOMA PATIENTS ; brain metastases ; MULTICENTER ; INITIATION ; FOTEMUSTINE ; PHASE-II ; RE ; GRADE ; PHASE ; temozolomide ; prospective ; ONSET ; CEREBRAL METASTASES ; ONCOLOGY GROUP ; AGGRESSIVE TREATMENT ; PARTITIONING ANALYSIS RPA
    Abstract: Background: Temozolomide has shown some efficacy in metastatic melanoma and recently received extended approval to treat brain tumours. The purpose of this study was to test a dose-intensified regimen of temozolomide in melanoma patients with brain metastases in a prospective, open-label, multicentre phase II trial. Patients and methods: Forty-five patients with asymptomatic brain metastases from melanoma were stratified into arm A (no prior chemotherapy; n = 21) and arm B (previous chemotherapy; n = 24). Patients received oral temozolomide either 150 mg/m(2)/day (arm A) or 125 mg/m(2)/day (arm B), days 1-7 and 15-21, every 28 days. The primary study end point was objective response, and secondary end points were overall survival and safety. Results: Two patients (4.4%) achieved a partial response (PR) in brain metastases (one in each arm), one of them (2.2%) also showing a PR in extracerebral disease. An additional five patients (11.1%; two in arm A, three in arm B) showed disease stabilisation (SD) in brain and other sites. However, 82% revealed progressive disease (PD) already evident 8 weeks after therapy initiation. Median survival time from therapy onset was 3.5 months (range 0.7-8.3; arm B) and 4.3 months (range 1.6-11.8; arm A), P = 0.43. Dose modifications and prolongations of therapy cycles due to toxicity were required in 20% of patients. Grade 3/4 toxicity was observed in one patient only (2.2%). Conclusions: Oral administration of temozolomide given bi-weekly is well-tolerated in melanoma patients with cerebral involvement. However, the efficacy is limited, with lower than 5% objective responses observed in brain and extracerebral metastases
    Type of Publication: Journal article published
    PubMed ID: 17005632
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  • 4
    Keywords: CANCER ; SURVIVAL ; Germany ; INFORMATION ; SYSTEM ; COHORT ; LONG-TERM ; prognosis ; tumour ; NERVOUS-SYSTEM ; MALIGNANCIES ; EXPERIENCE ; COUNTRIES ; DATABASE ; REGION ; LONG-TERM SURVIVAL ; REGIONS ; CENTRAL-NERVOUS-SYSTEM ; CHILDREN ; time trends ; EUROPE ; MALIGNANCY ; ONCOLOGY ; CHILDHOOD ; REGISTRY ; RE ; monitoring ; cancer registries ; PATIENT SURVIVAL ; analysis ; methods ; UNIT ; EXTENT ; REGISTRIES ; IMPROVEMENT ; improvement of ; central nervous system ; ADOLESCENCE ; ACCIS ; childhood cancer ; period survival ; PIEDMONT ; POPULATION-BASED SURVIVAL ; UP-TO-DATE ; CNS TUMORS ; CNS tumours ; EUROCARE ; long-term prognosis ; population -based
    Abstract: Background: Tumours of the central nervous system (CNS) account for 15-20% of all malignant childhood tumours in developed countries. Steady improvement of survival of children with CNS tumours has been reported for the past decades. However, these results, obtained by cohort analysis of survival, do not reflect the full extent of recent improvement. Methods: Using selected registries from the database of the Automated Childhood Cancer Information System (ACCIS), we calculated period survival estimates for the years 1995-99 for children diagnosed with a malignant CNS tumour. Results: The overall 10-year period survival estimate for the years 1995-99 was 59% for children with all CNS tumours combined, 73% for children with astrocytoma, 53% for children with ependymoma and 45% for children with primitive neuroectodermal tumours. On average, estimates derived by cohort analysis (pertaining to children diagnosed in 1985-89) were around 4% units lower. Region-specific analysis revealed that recent progress was largest in Eastern Europe, where prognosis nevertheless remained lower than in other European regions. In Northern and Southern Europe, 10-year survival remained essentially unchanged. Conclusion: Although period survival of children with CNS tumours is higher than previously reported cohort survival, their long-term prognosis remains modest compared to other childhood malignancies
    Type of Publication: Journal article published
    PubMed ID: 17709803
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  • 5
    Keywords: CANCER ; SURVIVAL ; evaluation ; COMMON ; FOLLOW-UP ; INFORMATION ; SYSTEM ; COHORT ; LONG-TERM ; TIME ; PATIENT ; prognosis ; COUNTRIES ; RATES ; DATABASE ; LONG-TERM SURVIVAL ; CANCER-PATIENTS ; CHILDREN ; CANCER PATIENTS ; PROJECT ; TRENDS ; EUROPE ; ONCOLOGY ; CHILDHOOD ; RE ; monitoring ; cancer registries ; PATIENT SURVIVAL ; PERIOD ANALYSIS ; analysis ; methods ; survival analysis ; population-based ; E ; EMPIRICAL-EVALUATION ; cancer survival ; childhood cancer ; period survival ; UP-TO-DATE ; EUROCARE ; POINT ; LATE MORTALITY
    Abstract: Background: A few years ago, a new method of survival analysis, denoted 'period' analysis, was introduced to provide more up-to-date survival estimates of cancer patients. Patients and methods: We evaluated the period survival method using the large database of the Automated Childhood Cancer Information System (ACCIS). Our evaluation is based on data from 35 191 children diagnosed with cancer in 13 European countries between 1975 and 1989 and followed for vital status until around 1999. Results: Using the follow-up data available in 1989, 10-year survival for all children with cancer calculated by the period method for the 1985-89 period was 58%, while it was 43% when calculated by traditional 'cohort' life-table analysis (based on children diagnosed in 1975-79). The period method provided a better estimate of the true 10-year survival of 62%, observed 10 years later in the cohort of patients diagnosed in 1985-89. Similar results were observed for each of the common groups of childhood cancer. Conclusion: Period analysis is especially useful for monitoring childhood cancer survival, because at a given point in time it provides more timely estimates of long-term survival expectations than the cohort life-table method. Using the ACCIS database, up-to-date estimates of period survival for childhood cancer are derived in subsequent papers in this journal
    Type of Publication: Journal article published
    PubMed ID: 17698836
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  • 6
    Keywords: CANCER ; LUNG ; PATHWAY ; PATHWAYS ; PHASE-I ; lung cancer ; LUNG-CANCER ; COHORT ; RISK ; ENZYMES ; GENE ; GENES ; PATIENT ; RISK-FACTORS ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; SUSCEPTIBILITY ; VARIANTS ; BREAST-CANCER ; DELETION ; NO ; STRESS ; AGE ; SNP ; smoking ; leukemia ; ACUTE LYMPHOBLASTIC-LEUKEMIA ; bladder cancer ; BLADDER-CANCER ; cancer risk ; gene-environment interaction ; INVOLVEMENT ; case-control studies ; TOBACCO ; OXIDATIVE STRESS ; European Prospective Investigation into Cancer and Nutrition ; nutrition ; glutathione-S-transferase ; DNA-ADDUCTS ; SINGLE ; ONCOLOGY ; case control study ; case-control study ; ASSOCIATIONS ; PATTERN ; VARIANT ; ALLELE ; SINGLE NUCLEOTIDE POLYMORPHISMS ; SNPs ; interaction ; GSTM1 ; METHYLENETETRAHYDROFOLATE REDUCTASE ; MTHFR ; ALLELES ; case control studies ; ENVIRONMENTAL TOBACCO-SMOKE ; INTERVAL ; ENZYME ; methods ; PHASE ; single-nucleotide ; pooled analysis ; prospective ; CANDIDATE ; NEVER SMOKERS ; CANCERS ; CANCER-RISK ; Phase I ; SET ; case control ; METABOLIC PATHWAYS ; GENETIC-SUSCEPTIBILITY ; nonsmokers ; METHYLENE-TETRAHYDROFOLATE REDUCTASE ; metabolic genes ; NULL-GENOTYPE
    Abstract: Background: We chose a set of candidate single nucleotide polymorphisms (SNPs) to investigate gene-environment interactions in three types of cancer that have been related to air pollution (lung, bladder and myeloid leukemia). Patients and methods: The study has been conducted as a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (409 cancer cases and 757 matched controls). We included never and ex-smokers. SNPs were in genes involved in oxidative stress, phase I metabolizing genes, phase 11 metabolizing genes and methylenetetrahydrofolate reductase (MTHFR). Results: The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33-3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73-37.3; homozygotes). Other statistically significant associations were found in subgroups defined by smoking habits (never or ex-smokers), environmental tobacco smoke or gender, with no obvious pattern. When gene variants were organized according to the three main pathways, the emerging picture was of a strong involvement of combined phase I enzymes in leukemia, with an OR of 5 (1.63-15.4) for those having three or more variant alleles. The association was considerably stronger for leukemias arising before the age of 55
    Type of Publication: Journal article published
    PubMed ID: 17496311
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  • 7
    Keywords: CANCER ; SURVIVAL ; LUNG ; PROSTATE ; DIAGNOSIS ; LUNG-CANCER ; MORTALITY ; SITE ; kidney ; FAMILY ; ASSOCIATION ; BREAST ; breast cancer ; BREAST-CANCER ; LYMPHOMA ; HEALTH ; DIFFERENCE ; WOMEN ; cervical cancer ; CERVICAL-CANCER ; COUNTRIES ; prostate cancer ; PROSTATE-CANCER ; MELANOMA ; DATABASE ; COLON-CANCER ; MALIGNANT-MELANOMA ; pancreatic cancer ; education ; ONCOLOGY ; REGRESSION ; FAMILIES ; LEVEL ; methods ; ESOPHAGEAL CANCER ; ENGLAND ; METASTATIC BREAST-CANCER ; SOCIOECONOMIC-STATUS ; SCREENING-PROGRAM ; SOCIAL-CLASS ; SWEDISH MEN
    Abstract: Background: While cancer survival at several sites has historically been shown to vary by education level, a current comprehensive assessment of survival following a cancer diagnosis in Sweden, a country with universal health care and cancer screening, has yet to be carried out. Methods: Using the 2006 update of the Swedish Family-Cancer Database and Cox's proportional hazards regression methods, we calculate the adjusted hazard ratio (HR) and 95% confidence interval to estimate the influence of education level on site-specific cancer survival. Results: Significant positive associations between education level and cancer survival were observed following a diagnosis of upper aerodigestive track cancer, colon cancer, pancreatic cancer, lung cancer, kidney cancer, urinary bladder cancer, melanoma, non-Hodgkin's lymphoma, breast cancer, endometrial cancer, cervical cancer, prostate cancer, and testicular cancer. Although the HRs differed between cancer sites, compared with women and men completing 〈 9 years of education, university graduates were associated with a significant 40% improved survival for all cancer sites combined. Conclusions: Survival differences by education level were observed for both indolent and aggressive malignancies
    Type of Publication: Journal article published
    PubMed ID: 17785761
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  • 8
    Keywords: CANCER ; Germany ; PROSTATE ; DISEASE ; HISTORY ; POPULATION ; RISK ; SITE ; TISSUE ; PATIENT ; FAMILY ; BREAST ; BREAST-CANCER ; NUMBER ; AGE ; family history ; etiology ; COLORECTAL-CANCER ; prostate cancer ; PROSTATE-CANCER ; DATABASE ; familial risk ; TRENDS ; ONCOLOGY ; RE ; FAMILIES ; METAANALYSIS ; methods ; FAMILY-HISTORY ; BONE ; CANCERS ; ENGLAND ; cancer prevalence ; clinical genetic counselling ; familial proportion ; referral of familial cancer
    Abstract: Background: Family history of a disease may point to its heritable or environmental etiology. It can be described by the proportion of the familial disease, i.e. same disease in two or more family members. A family history always needs to be specified as to the number of generations covered and their ages. Patients and methods: Proportions of site-specific familial cancers (familial proportions) were calculated using the Swedish Family-Cancer Database, the largest dataset of its kind in the world, with cancers from the Swedish Cancer Registry. Familial proportions refer to the offspring population up to age 72 years when their parents or siblings were diagnosed with a concordant (same) cancer. Results: A total of 34 cancer sites and 205 638 cases were covered. Prostate cancer showed the highest familial proportion of 20.15%, followed by breast (13.58%) and colorectal (12.80%) cancers. Salivary gland cancers showed the lowest familial proportion of 0.15%, but bone, laryngeal, anal, connective tissue and other genital cancers also remained 〈 1%. The familial proportion depended on the prevalence of the particular cancer and on its familial risk. Conclusions: The derived familial proportions can justifiably be used in statements 'X% of the patients had a family history of the cancer'
    Type of Publication: Journal article published
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  • 9
    Keywords: CANCER ; SURVIVAL ; Germany ; neoplasms ; PROSTATE ; POPULATION ; SITES ; PATIENT ; kidney ; BREAST ; early detection ; LYMPHOMA ; HEALTH ; OVARIAN-CANCER ; COLORECTAL-CANCER ; PROSTATE-CANCER ; LONG-TERM SURVIVAL ; POPULATIONS ; OUTCOMES ; TRENDS ; EUROPE ; RECTAL-CANCER ; REGISTRY ; cancer registries ; PATIENT SURVIVAL ; PERIOD ANALYSIS ; EUROPEAN COUNTRIES ; CANCERS ; EMPIRICAL-EVALUATION ; cancer survival ; EARLY BREAST-CANCER ; SURGICAL TRAINING-PROGRAM
    Abstract: Background: The timely provision and interpretation of trends in population-based cancer survival estimates is an important clinical and public health priority. Materials and methods: We examined survival trends between 1990-1994 and 2000-2004 for 15 common cancers in 10 countries from diverse areas of Europe and provide projected survival estimates for 2005-2009, using novel techniques of model-based period analysis. Results: Between 1990-1994 and 2000-2004, the 5-year relative survival increased significantly in all participating registries among patients with prostate, breast, and colorectal cancers and in at least 7 of 11 registries for stomach, corpus uteri, ovarian, kidney, and thyroid cancers, as well as for non-Hodgkin's lymphoma. Projections suggest further substantial increases in survival in the calendar period 2005-2009. For most cancer sites amenable to effective early detection and treatment, major geographical differences persist with lower survival in Eastern European countries. Conclusions: Model-based period analysis may be useful in providing population-based cancer survival estimates for currently diagnosed cancer patients. Concerted efforts in the organisation and quality control of cancer care will be very important to achieving further improvements in cancer control in Europe, and improving outcomes in Eastern European populations remains a priority
    Type of Publication: Journal article published
    PubMed ID: 19066327
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  • 10
    Keywords: age at onset, AUTOIMMUNE-DISEASE, AUTOIMMUNITY, CANCER, cancer registries, cancer risk, CANCER-RISK,
    Abstract: Background: Patients diagnosed with Crohn disease (CD) are known to be at an increased risk of bowel cancers and lymphoma. CD is an autoimmune disease and we hypothesize that the patients are predisposed to a wider spectrum of cancers. Patients and methods: A CD research database was constructed by identifying hospitalized CD patients from the Hospital Discharge Register and cancer patients from the Swedish Cancer Registry. Follow-up of 21 788 CD patients first hospitalized during the years 1964-2004 identified 1424 cancer cases. Standardized incidence ratios (SIRs) were calculated by comparing cancers in CD patients with subjects without CD. Results: In addition to the known sites, many additional sites were in excess in CD patients. These included liver, pancreatic, lung, prostate, testicular, kidney and skin (squamous cell) cancers; nonthyroid endocrine tumors and leukemia. The previously established sites showed the highest SIRs; however, SIRs 〉 2.0 were noted for the novel sites of the liver, testis and kidney. For testicular cancer, the SIR of seminoma was 2.74. Cancer risks were influences by age at first hospitalization for CD but whether the age effects were increasing or decreasing depending on the cancer type. Conclusions: This large study identified many novel subsequent cancers in CD patients
    Type of Publication: Journal article published
    PubMed ID: 18765463
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