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  • 1. Bondy, M L
    et al.
    Scheurer, M E
    Malmer, Beatrice
    Onkologi.
    Barnholtz-Sloan, J S
    Davis, F G
    Il'yasova, D
    Kruchko, C
    McCarthy, B J
    Rajaraman, P
    Schwartzbaum, J A
    Sadetzki, S
    Schlehofer, B
    Tihan, T
    Wiemels, J L
    Wrensch, M
    Buffler, P A
    Brain tumor epidemiology: Consensus from the Brain Tumor Epidemiology Consortium2008In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 113, p. 1953-1968Article in journal (Refereed)
    Abstract [en]

    Epidemiologists in the Brain Tumor Epidemiology Consortium (BTEC) have prioritized areas for further research. Although many risk factors have been examined over the past several decades, there are few consistent findings, possibly because of small sample sizes in individual studies and differences between studies in patients, tumor types, and methods of classification. Individual studies generally have lacked samples of sufficient size to examine interactions. A major priority based on available evidence and technologies includes expanding research in genetics and molecular epidemiology of brain tumors. BTEC has taken an active role in Promoting understudied groups, such as pediatric brain tumors; the etiology of rare glioma subtypes, such as oligodendroglioma; and meningioma, which, although it is not uncommon, has only recently, been registered systematically in the United States. There also is a pressing need for more researchers, especially junior investigators, to study brain tumor epidemiology. However, relatively poor funding for brain tumor research has made it difficult to encourage careers in this area. In this report, BTEC epidemiologists reviewed the groups Consensus oil the Current state of scientific findings, and they present a consensus oil research priorities to identify which important areas the science should move to address.

  • 2. Bondy, Melissa L
    et al.
    Scheurer, Michael E
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Barnholtz-Sloan, Jill S
    Davis, Faith G
    Il'yasova, Dora
    Kruchko, Carol
    McCarthy, Bridget J
    Rajaraman, Preetha
    Schwartzbaum, Judith A
    Sadetzki, Siegal
    Schlehofer, Brigitte
    Tihan, Tarik
    Wiemels, Joseph L
    Wrensch, Margaret
    Buffler, Patricia A
    Brain tumor epidemiology: consensus from the Brain Tumor Epidemiology Consortium.2008In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 113, no 7 Suppl, p. 1953-1968Article in journal (Refereed)
    Abstract [en]

    Epidemiologists in the Brain Tumor Epidemiology Consortium (BTEC) have prioritized areas for further research. Although many risk factors have been examined over the past several decades, there are few consistent findings, possibly because of small sample sizes in individual studies and differences between studies in patients, tumor types, and methods of classification. Individual studies generally have lacked samples of sufficient size to examine interactions. A major priority based on available evidence and technologies includes expanding research in genetics and molecular epidemiology of brain tumors. BTEC has taken an active role in promoting understudied groups, such as pediatric brain tumors; the etiology of rare glioma subtypes, such as oligodendroglioma; and meningioma, which, although it is not uncommon, has only recently been registered systematically in the United States. There also is a pressing need for more researchers, especially junior investigators, to study brain tumor epidemiology. However, relatively poor funding for brain tumor research has made it difficult to encourage careers in this area. In this report, BTEC epidemiologists reviewed the group's consensus on the current state of scientific findings, and they present a consensus on research priorities to identify which important areas the science should move to address.

  • 3. Forlenza, Michael J
    et al.
    Hall, Per
    Lichtenstein, Paul
    Evengård, Birgitta
    Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Sullivan, Patrick F
    Dept Genetics, Univ of North Carolina, Dept Medical Epid and Biostat, Karol Institutet.
    Epidemiology of cancer-related fatigue in the Swedish twin registry2005In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 104, no 9, p. 2022-2031Article in journal (Refereed)
    Abstract [en]

    A greater proportion of individuals who were listed in a national cancer registry reported experiencing fatigue compared with individuals in the general population.

  • 4.
    Fransson, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Damber, Jan-Erik
    Department of Urology, Göteborg University, Göteborg, Sweden.
    Tomic, Radisa
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Modig, Hans
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nyberg, Gunnar
    Department of Urology, Boden Hospital, Boden, Sweden.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Quality of life and symptoms in a randomized trial of radiotherapy versus deferred treatment of localized prostate carcinoma2001In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 92, no 12, p. 3111-3119Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Treatment of localized prostate carcinoma (LPC) using radiotherapy (RT) can induce disturbances in a patient's quality of life (QOL) and urinary and intestinal function. Late symptoms and QOL were evaluated in a randomized trial between RT and deferred treatment (DT).

    METHODS: Quality of life was evaluated with European Organization for Research and Treatment of Cancer's QLQ-C30 (+3) formula. Urinary and intestinal problems were evaluated with a validated symptom specific self-assessment questionnaire, QUFW94. The questionnaires were sent to 108 randomized patients with LPC and to an age-matched control group (n = 68). Mean age was 72 years. Mean total dose was 65 grays (Gy; 62.3-70 Gy). The median follow-up time from randomization was 40.6 months for the RT group and 30.4 months for the DT group.

    RESULTS: Social functioning was the only QOL scale in which a significant difference was found between the two patient groups and compared with the control group. Multivariate regression analysis showed that hematuria, incontinence, mucus, and planning of daily activities in response to intestinal problems caused this decrease in QOL in the RT group. A significant increase of intestinal problems was observed in the RT versus DT groups regarding mucus, stool leakage, intestinal blood, and planning of daily activity in response to intestinal problems.

    CONCLUSIONS: The RT patients showed increased levels of minor intestinal side effects compared with the DT patients and the controls, but the RT patients reported no decreased QOL except for decreased social functioning. This could be because this group developed coping skills or because of a low magnitude of side effects to influence the QOL.

  • 5.
    Fransson, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Nursing.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Late side effects unchanged 4-8 years after radiotherapy for prostate carcinoma: A comparison with age-matched controls1999In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 85, no 3, p. 678-688Article in journal (Refereed)
    Abstract [en]

    BACKGROUND. The authors of this study previously evaluated pelvic irradiation-induced late side effects in patients with localized prostatic carcinoma 4 years after external irradiation by administering a validated self-assessment questionnaire (QUFW94), and compared the results with those of age-matched controls. The current study was designed to evaluate prospectively the patients' problems 8 years after radiotherapy and to compare them with those reported by the same controls. METHODS. The questionnaire was sent out at a mean of 8 years (range, 72-104 months) after irradiation to 120 patients and 125 controls. For analysis of sexual function, the patient group was divided into two subgroups, one treated with radiotherapy only (RT) and one group treated with radiotherapy plus castration (RT+A). A value of >1 on a 0-10 scale indicated that the patient was having a problem. RESULTS, The mean age was 73 years for both patients and controls. No changes in urinary problems were seen between the 4-year and the 8-year follow-up in the 2 groups. Sixty percent and 54% of the patients (P = 0.096) and 24% and 31% of the controls (P = 0.988) reported urinary problems at the 4-year and 8-year follow-ups, respectively. No changes in gastrointestinal late side effects in the patient group were seen between the 4-year (65%) and the 8-year (62%) follow-ups (P = 0.490). However, there was a decrease in intestinal problems in the control group between the 4-year (12%) and the 8-year (9%) follow-ups (P = 0.001). The sexual problems did not change during the two periods, in the patient groups or in the control groups. Fifty-six percent and 65% of the RT group (P = 0.052), 67% and 54% of the RT + A group (P = 0.555), and 27% and 33% of the control group (P = 0.243) indicated some kind of sexual problem at the 4-year and 8-year follow-ups, respectively. CONCLUSIONS. The amount of pelvic irradiation-induced urinary late side effects, intestinal late side effects, and sexual function, evaluated with a self-assessment questionnaire, did not change between 4 and 8 years after RT. The age-matched controls reported no change in urinary or sexual problems despite advanced age, but there was a reported decrease in intestinal problems, Cancer 1999;85:678-88. (C) 1999 American Cancer Society.

  • 6.
    Fransson, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Self-assessed sexual function after pelvic irradiation for prostate carcinoma: Comparison with an age-matched control group1996In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 78, no 5, p. 1066-1078Article in journal (Refereed)
    Abstract [en]

    BACKGROUND. Treatment of localized prostate carcinoma is often accompanied by disturbances in sexual function. The patient's own opinion and experience with these problems can be of great importance for his quality of life. In men older than 50 years, disturbances in sexual function are common. Treatment such as radiotherapy (RT), which can induce sexual dysfunction, should be evaluated in relation to the problems in an age-matched population without prostate carcinoma. METHODS. Sexual function was evaluated with a self-assessment questionnaire using linear-analogue scales. The questionnaire was sent to 199 patients with prostate carcinoma, median age 71 years (range, 51-86 years), who had received pelvic RT with curative intent and to 200 age-matched men in northern Sweden. Mean follow-up time after RT was 48 months (range, 24-56 months). RESULTS. The response rate was high: 141 (71%) and 181 (91%) in the control and patient groups, respectively. Field reduction and treatment pause during RT was not associated with decreased problems in the patient groups. A failure to achieve erection was indicated in 12% of the control subjects, 56% of the patients who had received (RT only) and 87% of the RT + castration (RT + A) patients. In general, patients < 70 years treated with RT + A indicated more sexual problems than the RT only patients < 70 years. There was a strong negative correlation between age and sexual problems in the RT 9 A < 70 years group. However, in patients < 70 years, sexual activity after RT only, was not significantly different from the age-matched control population. CONCLUSIONS. Patients with prostate carcinoma treated with RT only indicated higher levels of sexual dysfunction than age-matched controls. This was most obvious in patients younger than 70 years, although their sexual activity was comparable to age-matched controls. The addition of castration to RT tended to increase sexual problems, especially in patients < 70 years. In men between 70 and 74 years, the maintenance of sexual function seems to be very susceptible to disturbances. For patients older than 74 years, decreased sexual function was not perceived as such a significant problem, despite abolished desire and erection. (C) 1996 American Cancer Society.

  • 7.
    Hellquist, Barbro Numan
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Czene, Kamila
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Hjälm, Anna
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History. Umeå University, Faculty of Social Sciences, Centre for Population Studies (CPS).
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Effectiveness of population-based service screening with mammography for women ages 40 to 49 years with a high or low risk of breast cancer: socioeconomic status, parity, and age at birth of first child2015In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 121, no 2, p. 251-258Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Invitation to mammography screening of women aged 40 to 49 years is a matter of debate in many countries and a cost-effective alternative in countries without screening among women aged 40 to 49 years could be inviting those at higher risk. The relative effectiveness of mammography screening was estimated for subgroups based on the breast cancer risk factors parity, age at time of birth of first child, and socioeconomic status (SES).

    METHODS: The SCReening of Young Women (SCRY) database consists of all women aged 40 to 49 years in Sweden between 1986 and 2005 and was split into a study and control group. The study group consisted of women residing in areas in which women aged 40 to 49 years were invited to screening and the control group of women in areas in which women aged 40 to 49 years were not invited to screening. Rate ratio (RR) estimates were calculated for 2 exposures: invitation and attendance.

    RESULTS: There were striking similarities noted in the RR pattern for women invited to and attending screening and no statistically significant difference or trend in the RR was noted by risk group. The RR estimates increased by increasing parity for parity of 0 to 2 and ranged from 0.55 (95% confidence interval [95% CI], 0.38-0.79) to 0.79 (95% CI, 0.65-0.95) for attending women. The RR for women with high SES was lower than that for women with low SES (RR, 0.72 [95% CI, 0.60-0.86] and RR, 0.79 [95% CI, 0.63-0.99], respectively). For women aged 20 to 24 years at the time of the birth of their first child, the RR was 0.73 (95% CI, 0.58-0.91) and estimates for other ages were similar.

    CONCLUSIONS: There was no statistically significant difference noted in the relative effectiveness of mammography screening by parity, age at the time of birth of the first child, or SES. Cancer 2014.

  • 8.
    Hellquist, Barbro Numan
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Unclear methods in estimate of screening effect in women ages 40-49 years Author Reply2012In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 118, no 4, p. 1170-1171Article in journal (Refereed)
  • 9.
    Hellquist Numan, Barbro
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Duffy, Stephen W
    Cancer Research UK, Department of Epidemiology, Mathematics, and Statistics, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
    Abdsaleh, Shahin
    Department of Medical Imaging, Uppsala University Hospital, Uppsala, Sweden.
    Björneld, Lena
    Department of Radiology, Sahlgrenska University Hospital, Sahlgrenska, Sweden.
    Bordás, Pál
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tabár, László
    Department of Mammography, Falun Central Hospital, Falun, Sweden.
    Viták, Bedrich
    Mammography Department, Linköping University Hospital, Linköping, Sweden.
    Zackrisson, Sophia
    Department of Clinical Sciences in Malmö, Diagnostic Radiology, Lund University, Lund, Sweden.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Effectiveness of population-based service screening with mammography for women ages 40 to 49 years: evaluation of the Swedish Mammography Screening in Young Women (SCRY) cohort2011In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 117, no 4, p. 714-722Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The effectiveness of mammography screening for women ages 40 to 49 years still is questioned, and few studies of the effectiveness of service screening for this age group have been conducted.

    METHODS: Breast cancer mortality was compared between women who were invited to service screening at ages 40 to 49 years (study group) and women in the same age group who were not invited during 1986 to 2005 (control group). Together, these women comprise the Mammography Screening of Young Women (SCRY) cohort, which includes all Swedish counties. A prescreening period was defined to facilitate a comparison of mortality in the absence of screening. The outcome measure was refined mortality, ie, breast cancer death for women who were diagnosed during follow-up at ages 40 to 49 years. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated.

    RESULTS: There was no significant difference in breast cancer mortality during the prescreening period. During the study period, there were 803 breast cancer deaths in the study group (7.3 million person-years) and 1238 breast cancer deaths in the control group (8.8 million person-years). The average follow-up was 16 years. The estimated RR for women who were invited to screening was 0.74 (95% CI, 0.66-0.83), and the RR for women who attended screening was 0.71 (95% CI, 0.62-0.80).

    CONCLUSIONS: In this comprehensive study, mammography screening for women ages 40 to 49 years was efficient for reducing breast cancer mortality.

  • 10.
    Hellquist Numan, Barbro
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Reply to effectiveness of population-based service screening with mammography for women ages 40-49 years: Evaluation of the swedish mammography screening in young women (SCRY) cohort2011In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 117, no 17, p. 4100-4101Article in journal (Refereed)
  • 11. Hoskin, Peter J
    et al.
    Rojas, Ana Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Phillips, Heather
    Saunders, Michele I
    Acute and late morbidity in the treatment of advanced bladder carcinoma with accelerated radiotherapy, carbogen, and nicotinamide2005In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 103, no 11, p. 2287-2297Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Accelerated radiotherapy combined with carbogen and nicotinamide (ARCON) to overcome tumor hypoxia and cell proliferation achieved high tumor control and survival in Phase II studies of patients with advanced head and neck and bladder carcinomas. Thus, morbidity and treatment outcomes from the latter study were analyzed to evaluate the therapeutic potential of ARCON. METHODS: Acute and late morbidity was assessed in 105 patients with high-grade superficial or muscle-invasive bladder carcinoma who were given accelerated radiotherapy (50-55 grays in 4 weeks) with carbogen alone or with ARCON. Urinary dysfunction was scored based on daytime frequency, nocturia, incontinence, dysuria, hematuria, and urgency. Bowel morbidity was based on stool frequency and consistency, rectal discharge, blood loss, and medication. Endpoints for treatment outcome were overall survival, disease-free survival, and locoregional control. RESULTS: Nearly all patients experienced reduced ability to retain urine beyond 2 hours, although 20-30% had almost normal function at night. Incidence of acute moderate or worse dysuria was 41% with ARCON and 56% with carbogen; 96% and 76% of patients, respectively, had bowel frequencies > or = 3 times per day. By 10-12 weeks from the start of radiotherapy, acute reactions returned to baseline levels. At 3 years, the daytime frequency < or = 2 times per hour was approximately 75% in both arms. Incidence of severe hematuria (< or = 25%) and urinary urgency (< or = 16%) was much lower. No more than 6% of patients had severe bowel morbidity. With most assays, the differences between schedules were not significant either for acute or late morbidity. Local tumor control and survival rates at 3 years were 53% and 43%, respectively, for ARCON, similar to the rates for carbogen alone. CONCLUSIONS: Historical comparisons suggested no overt increase in normal tissue radiosensitivity when adding carbogen and nicotinamide. Although, for some endpoints, the incidence of late sequelae was higher than expected, overall morbidity was no worse than reported by others. The data indicated that ARCON could achieve a therapeutic gain in patients with advanced bladder carcinoma. A Phase III, randomized, multicenter trial is underway currently in the United Kingdom to evaluate these findings.

  • 12.
    Häggstrom, Christel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ulmert, David
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Malmö, Sweden.
    Bjørge, Tone
    Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
    Ulmer, Hanno
    nnsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Innsbruck, Austria.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Manjer, Jonas
    Lund Univ, Dept Plast Surg, Skåne Univ Hosp, Malmö, Sweden.
    Engeland, Anders
    Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
    Nagel, Gabriele
    Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany.
    Almqvist, Martin
    Lund Univ, Skåne Univ Hosp, Dept Surg, Malmö, Sweden.
    Selmer, Randi
    Norwegian Inst Publ Hlth, Oslo, Norway.
    Concin, Hans
    Agcy Prevent & Social Med, Bregenz, Austria.
    Tretli, Steinar
    Canc Registry Norway, Inst Populat Based Canc Res, Oslo, Norway.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Prospective study on metabolic factors and risk of prostate cancer2012In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 118, no 24, p. 6199-6206Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There are inconsistent data regarding the association between metabolic factors, separately and combined, and the risk of prostate cancer and death from prostate cancer.

    METHODS: In the Metabolic Syndrome and Cancer Project (Me-Can), data on body mass index (BMI); blood pressure; and blood levels of glucose, cholesterol, and triglycerides were collected for 289,866 men. Cox proportional hazard models were used to calculate relative risks (RRs) by exposures in quintiles as well as for z scores (with a mean of 0 and a standard deviation of 1) together with a composite sum of scores to assess the combined effect of metabolic factors. RRs were corrected for random errors in measurement.

    RESULTS: During a mean follow-up of 12 years, 6673 men were diagnosed with prostate cancer and 961 died of the disease. Men with high levels of glucose and triglycerides were found to have a decreased risk of prostate cancer: top versus bottom quintile of glucose: RR, 0.82 (95% confidence interval [95% CI], 0.62-1.08; P value for trend = .03) and top versus bottom quintile of triglycerides: RR, 0.88 (95% CI, 0.74-1.04; P value for trend = .001). High BMI, elevated blood pressure, and a high composite z score were found to be associated with an increased risk of death from prostate cancer: top versus bottom quintile of BMI: RR, 1.36 (95% CI, 1.08-1.71); systolic blood pressure: RR, 1.62 (95% CI, 1.07-2.45); and per 1-unit increase of the composite z score: RR, 1.13 (95% CI, 1.03-1.25).

    CONCLUSIONS: The authors found no evidence of an association between high levels of metabolic factors and the risk of prostate cancer, but high BMI, elevated blood pressure, and a composite score of all metabolic factors were associated with an increased risk of death from prostate cancer. 

  • 13.
    Johansson, A.
    et al.
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Erlandsson, A.
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Erikssson, D.
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Ullén, A.
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Holm, P.
    Sundström, BE
    Roux, KH
    Stigbrand, T.
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Idiotyppic-anti-idiotypic complexes and their in vivo metabolism.2002In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 94, no S4, p. 1306-1313Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Different strategies can be used to improve the tumor:non-tumor ratio of radiolabeled antibodies in immunotargeting. One approach is to use secondary antibodies to clear out redundant, circulating primary antibodies. In the current study, the in vitro complex formation and in vivo clearing capabilities and metabolism of the monoclonal antibody TS1 and its monoclonal anti-idiotype, alphaTS1, were studied. METHODS: Complex formation studies were performed using polyacrylamide gel electrophoresis (PAGE), gel permeation chromatography, and electron microscopy. The clearance and metabolism of the complexes were studied in nude mice. RESULTS: PAGE and gel permeation chromatography showed that more than 70% of the antibodies formed complexes. The electron microscopy studies revealed that the complexes formed between TS1 and alphaTS1 are mainly ring-shaped (66.6-73.4%), comprising 4 to > 8 antibodies. These rings consist of equal numbers of idiotype and anti-idiotype. The most commonly observed complexes were tetrameric rings (26.8-40.5%), hexameric rings (10.7-11.9%), and rings containing more than eight monoclonal antibodies (6.6-14-4%). The in vivo study illustrated that within 24 hours 80% of the total nuclide content had been degraded and excreted via the urine, compared with 25% for similarly treated mice that did not receive any anti-idiotype. CONCLUSIONS: Interestingly, the electron microscopy study demonstrated that dimers were rare (0.4-1.2%), probably reflecting a location of epitopes incompatible with tight, sterically constrained dimeric interactions; insufficient flexibility of the immunoglobulin G1 subtype hinge regions; or both. The anti-idiotypic clearing mechanisms proved efficient in nude mice. In vivo metabolic studies indicate that the accumulation and degradation of TS1/alphaTS1 immune complexes, to a large extent, take place in the liver, where a substantial amount was detected as soon as 1 hour after anti-idiotype injection. Copyright 2002 American Cancer Society.

  • 14.
    Johansson, Amanda
    et al.
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    Eriksson, David
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    Ullen, Anders
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    Löfroth, Per-Olov
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Åhlström-Riklund, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    The combination of external beam radiotherapy and experimental radioimmunotargeting with a monoclonal anticytokeratin antibody2002In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 94, no S4, p. 1314-1319Article in journal (Refereed)
  • 15. Juliusson, Gunnar
    et al.
    Karlsson, Karin
    Lazarevic, Vladimir Lj
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brune, Mats
    Antunovic, Petar
    Derolf, Asa
    Hägglund, Hans
    Karbach, Holger
    Lehmann, Sören
    Möllgård, Lars
    Stockelberg, Dick
    Hallböök, Helene
    Höglund, Martin
    Hematopoietic stem cell transplantation rates and long-term survival in acute myeloid and lymphoblastic leukemia: Real-World Population-Based Data From the Swedish Acute Leukemia Registry 1997-20062011In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 117, no 18, p. 4238-4246Article in journal (Refereed)
    Abstract [en]

    Background: Allogeneic stem cell transplantation (alloSCT) reduces relapse rates in acute leukemia, but outcome is hampered by toxicity. Population-based data avoid patient selection and may therefore substitute for lack of randomized trials.

    Methods: We evaluated alloSCT rates within the Swedish Acute Leukemia Registry, including 3899 adult patients diagnosed from 1997 through 2006 with a coverage of 98% and a median follow-up of 6.2 years.

    Results:: AlloSCT rates and survival decreased rapidly with age >55 years. The 8-year overall survival (OS) was 65% in patients <30 years and 38% in patients <60 years and was similar for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Among 1073 patients <60 years, alloSCT was performed in 42% and 49% of patients with AML and ALL, respectively. Two-thirds of the alloSCTs were performed in first complete remission, and half used unrelated donors, the same in AML and ALL. Regional differences in management and outcome were found: 60% of AML patients <40 years received alloSCT in all parts of Sweden, but two-thirds of AML patients 40-59 years had alloSCT in one region compared with one-third in other regions (P<.001), with improved 8-year OS among all AML patients in this age cohort (51% vs 30%; P = .005).

    Conclusions: More Swedish AML patients received alloSCT, and long-term survival was better than in recently published large international studies, despite our lack of selection bias. There was no correlation between alloSCT rate and survival in ALL. In adult AML patients <60 years of age, a high alloSCT rate was associated with better long-term survival, but there was no such correlation in ALL.

  • 16. Lindholm, Christer
    et al.
    Andersson, Ronny
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Dufmats, Monika
    Hansson, Johan
    Ingvar, Christian
    Möller, Torgil
    Sjödin, Helena
    Stierner, Ulrika
    Wagenius, Gunnar
    Invasive cutaneous malignant melanoma in Sweden, 1990-1999. A prospective, population-based study of survival and prognostic factors2004In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 101, no 9, p. 2067-2078Article in journal (Refereed)
  • 17. Löfstedt, Alexandra
    et al.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Tesi, Bianca
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Nordenskjöld, Magnus
    Bryceson, Yenan T.
    Henter, Jan-Inge
    Meeths, Marie
    Haploinsufficiency of UNC13D increases the risk of lymphoma2019In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 125, no 11, p. 1848-1854Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Experimental models have demonstrated that immune surveillance by cytotoxic lymphocytes can protect from spontaneous neoplasms and cancer. In humans, defective lymphocyte cytotoxicity is associated with the development of hemophagocytic lymphohistiocytosis, a hyperinflammatory syndrome. However, to the best of the authors' knowledge, the degree to which human lymphocyte cytotoxicity protects from cancer remains unclear. In the current study, the authors examined the risk of lymphoma attributable to haploinsufficiency in a gene required for lymphocyte cytotoxicity.

    METHODS: The authors exploited a founder effect of an UNC13D inversion, which abolishes Munc13-4 expression and causes hemophagocytic lymphohistiocytosis in an autosomal recessive manner. Within 2 epidemiological screening programs in northern Sweden, an area demonstrating a founder effect of this specific UNC13D mutation, all individuals with a diagnosis of lymphoma (487 patients) and matched controls (1844 controls) were assessed using polymerase chain reaction for carrier status.

    RESULTS: Among 487 individuals with lymphoma, 15 (3.1%) were heterozygous carriers of the UNC13D inversion, compared with 18 controls (1.0%) (odds ratio, 3.0; P = .002). It is interesting to note that a higher risk of lymphoma was attributed to female carriers (odds ratio, 3.7; P = .004).

    CONCLUSIONS: Establishing a high regional prevalence of the UNC13D inversion, the authors have reported an overrepresentation of this mutation in individuals with lymphoma. Therefore, the results of the current study indicate that haploinsufficiency of a gene required for lymphocyte cytotoxicity can predispose patients to lymphoma, suggesting the importance of cytotoxic lymphocyte-mediated surveillance of cancer. Furthermore, the results of the current study suggest that female carriers are more susceptible to lymphoma.

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  • 18.
    Papworth, Karin E.
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Arroyo, Vidal M.
    Styring, Emelie
    Zaikova, Olga
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lupo, Philip J.
    Soft-tissue sarcoma in adolescents and young adults compared with older adults: a report among 5000 patients from the Scandinavian Sarcoma Group Central Register2019In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 125, no 20, p. 3595-3602Article in journal (Refereed)
    Abstract [en]

    Background: In recent years, there has been growing awareness of the distinct characteristics of adolescents and young adults (AYA) diagnosed with cancer. Soft-tissue sarcoma (STS) accounts for approximately 1% of all cancers diagnosed in adults and 8% of cancers diagnosed in AYA. To the best of our knowledge, only a few sarcoma registers include data regarding histological subtype, age at diagnosis, and detailed clinical information. Therefore, little is known regarding clinical presentation and outcomes in AYA diagnosed with STS.

    Methods: Using the Scandinavian Sarcoma Group Central Register, data were obtained regarding 4977 patients who were diagnosed with STS for the period between 1986 and 2011. AYA (those aged 18-39 years) were compared with older adults (OA; those aged 40-80 years) with respect to clinical presentation, treatment, and outcome.

    Results: There were 868 AYA and 4109 OA. Overall and by STS subtype, there were significant differences noted between AYA and OA with regard to presentation, treatment, and survival. The distribution of STS subtypes was different between OA and AYA (eg, OA were more likely to be diagnosed with malignant fibrous histiocytoma compared with AYA [34% vs 16%; P < .001]). OA also were more likely to have tumors measuring >= 5 cm (68% vs 56%; P < .001) and a higher malignancy grade (75% vs 67%; P < .001). In the majority of STS subtypes AYA had significantly better overall survival and less disease recurrence compared with OA, but this finding was not true for those with malignant peripheral nerve sheath tumors.

    Conclusions: There are several differences between AYA and OA with STS with regard to presentation, treatment, and survival, and such differences must be taken into consideration when designing clinical trials. Additional work also is needed to characterize the potential biological mechanisms underlying these differences.

  • 19. Rossi Norrlund, Rauni
    et al.
    Ullén, Anders
    Sandström, Per
    Holback, Daniel
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hietala, Sven-Ola
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Dosimetry of fractionated experimental radioimmunotargeting with idiotypic and anti-idiotypic anticytokeratin antibodies.1997In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 80, no 12 Suppl, p. 2681-2688Article in journal (Refereed)
    Abstract [en]

    The fractionated strategy can contribute to a significant accumulation of radiolabeled TS1 in the tumors. Furthermore, the use of alphaTS1 makes it possible to increase the tumor-to-nontumor dose ratio and maintain a prolonged high activity accumulation in the tumor.

  • 20. Rossi Norrlund, Rauni
    et al.
    Ullén, Anders
    Sandström, Per
    Holback, Daniel
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hietala, Sven-Ola
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Experimental radioimmunotargeting combining nonlabeled, iodine-125-labeled, and anti-idiotypic anticytokeratin monoclonal antibodies: a dosimetric evaluation.1997In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 80, no 12 Suppl, p. 2689-2698Article in journal (Refereed)
    Abstract [en]

    This study confirms an extensive accumulation of TS1 in the tumor, with peak values as late as 30 days after injection of labeled TS1. Furthermore, both preinjection of nonlabeled TS1 and postinjection of alphaTS1 can improve radioimmunotargeting.

  • 21.
    Rydh, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nilsson, Sten
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Damber, Jan Erik
    Stigbrand, T
    Hietala, Sven-Ola
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Radioimmunoscintigraphy with a novel monoclonal antiprostate antibody (E4): an experimental study in nude mice.1997In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 80, no 12 Suppl, p. 2398-2403Article in journal (Refereed)
    Abstract [en]

    The MoAb E4 is a promising radiotracer for prostate cancer and may be used in radioimmunotherapy. As in earlier studies, TS1 shows significant radioimmunolocalization into necrotic tumor tissue, which also exists in prostate cancer.

  • 22.
    Stocks, Tanja
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lukanova, Annekatrin
    German Cancer Research Center, Germany.
    Björge, Tone
    University of Bergen, Norway.
    Ulmer, Hanno
    Innsbruck Medical University, Austria.
    Manjer, Jonas
    Malmö University Hospital.
    Almquist, Martin
    Malmö University Hospital.
    Concin, Hans
    Agency for Preventive and Social Medicine.
    Engeland, Anders
    University of Bergen, Norway.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Nagel, Gabriele
    Ulm University, Germany.
    Tretli, Steinar
    The Cancer Registry of Norway, Norway.
    Veierod, Marit
    University of Oslo, Norway.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Metabolic factors and risk of colorectal cancer in the metabolic syndrome and cancer project (Me-Can)2011In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 117, no 11, p. 2398-2407Article in journal (Refereed)
    Abstract [en]

    Background

    The metabolic syndrome (MetS) has been related to an increased risk of colorectal cancer in some small studies, but it is unknown which factors in the MetS that are most strongly related to risk, and if there is an interaction between factors.

    Methods and Findings

    In the Metabolic syndrome and Cancer project (Me-Can), data on body mass index (BMI), blood pressure, and blood levels of glucose, cholesterol, and triglycerides were available in 289,866 men and 288,834 women. Mean age at baseline was 44.0 years and mean follow-up time was 12.0 years. During follow-up, 2,834 men and 1,861 women were diagnosed with colorectal cancer. We used Cox regression models to calculate relative risk (RR) of colorectal cancer by exposures transformed into Z scores (mean = 0, standard deviation = 1), and for a MetS Z score, and used regression calibration to correct exposure levels for random error in measurement. Significant increases in risk per one unit increment of factors were observed in men for BMI, RR 1.07 (95% confidence interval, 1.02-1.13), blood pressure, RR 1.10 (1.02-1.18), and triglycerides, RR 1.17 (1.06-1.28), and in women for BMI, RR 1.08 (1.01-1.15). The RR of colorectal cancer per one unit increment of the MetS Z score was 1.24 (1.18-1.31) in men, and 1.14 (1.06-1.22) in women. There was no significant positive interaction for any combination of two metabolic factors. Associations between metabolic factors and risk of fatal colorectal cancer were similar to those for incident cancer.

    Conclusions

    Our data add further evidence for an association between factors in the MetS, in single and combined, and risk of colorectal cancer. Our data do not support an interaction between factors in the MetS on risk.

  • 23. Tabar, Laszlo
    et al.
    Dean, Peter B.
    Chen, Tony Hsiu-Hsi
    Yen, Amy Ming-Fang
    Chen, Sam Li-Sheng
    Fann, Jean Ching-Yuan
    Chiu, Sherry Yueh-Hsia
    Ku, May Mei-Sheng
    Wu, Wendy Yi-Ying
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Hsu, Chen-Yang
    Chen, Yu-Ching
    Beckmann, Kerri
    Smith, Robert A.
    Duffy, Stephen W.
    The incidence of fatal breast cancer measures the increased effectiveness of therapy in women participating in mammography screening2019In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 125, no 4, p. 515-523Article in journal (Refereed)
    Abstract [en]

    Background: Women and their health care providers need a reliable answer to this important question: If a woman chooses to participate in regular mammography screening, then how much will this choice improve her chances of avoiding a death from breast cancer compared with women who choose not to participate? Methods: To answer this question, we used comprehensive registries for population, screening history, breast cancer incidence, and disease-specific death data in a defined population in Dalarna County, Sweden. The annual incidence of breast cancer was calculated along with the annual incidence of breast cancers that were fatal within 10 and within 11 to 20 years of diagnosis among women aged 40 to 69 years who either did or did not participate in mammography screening during a 39-year period (1977-2015). For an additional comparison, corresponding data are presented from 19 years of the prescreening period (1958-1976). All patients received stage-specific therapy according to the latest national guidelines, irrespective of the mode of detection. Results: The benefit for women who chose to participate in an organized breast cancer screening program was a 60% lower risk of dying from breast cancer within 10 years after diagnosis (relative risk, 0.40; 95% confidence interval, 0.34-0.48) and a 47% lower risk of dying from breast cancer within 20 years after diagnosis (relative risk, 0.53; 95% confidence interval, 0.44-0.63) compared with the corresponding risks for nonparticipants. Conclusions: Although all patients with breast cancer stand to benefit from advances in breast cancer therapy, the current results demonstrate that women who have participated in mammography screening obtain a significantly greater benefit from the therapy available at the time of diagnosis than do those who have not participated.

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  • 24. Ullén, Anders
    et al.
    Sandström, Per
    Rossi Norrlund, Rauni
    Rathsman, Sandra
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Hietala, Sven-Ola
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Dosimetry of fractionated administration of 125I-labeled antibody at experimental radioimmunotargeting.1997In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 80, no 12 Suppl, p. 2510-2518Article in journal (Refereed)
    Abstract [en]

    In this antigen target system, a single injection of a large amount of antibody was found to be more efficient than the same antibody dose subdivided into three or ten fractions. It was concluded that not only the radioactivity but also the amount of antibody per fraction should be considered when determining optimal fractionated radioimmunotherapy.

  • 25.
    Van Hemelrijck, Mieke
    et al.
    Cancer Epidemiology Group, Division of Cancer Studies, School of Medicine, King's College London, London, United Kingdom.
    Drevin, Linda
    Regional Cancer Center Uppsala Örebro, Uppsala, Sweden.
    Holmberg, Lars
    Regional Cancer Center Uppsala Örebro, Uppsala, Sweden.
    Garmo, Hans
    Regional Cancer Center Uppsala Örebro, Uppsala, Sweden.
    Adolfsson, Jan
    Oncological Center, CLINTEC Department, Karolinska Institute, Stockholm, Sweden.
    Stattin, Par
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Primary Cancers Before and After Prostate Cancer Diagnosis2012In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 118, no 24, p. 6207-6216Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The occurrence of multiple cancers may indicate common etiology; and, although some studies have investigated the risk of second primary cancers after prostate cancer (PCa), there are no studies on cancers before PCa. METHODS: The PCBaSe Sweden database is based on the National Prostate Cancer Register (NPCR), which covers >96% of PCa cases. The authors estimated the prevalence and cumulative incidence of different cancers before and after PCa diagnosis in 72,613 men according to PCa treatment and disease stage in PCBaSe and their matched comparison cohort of men who were free of PCa. RESULTS: In total, 6829 men were diagnosed with another primary cancer before their PCa diagnosis, including 138 men at the time of PCa diagnosis and 5230 men were diagnosed after PCa diagnosis. Cancer of the bladder or colon and nonmelanoma of the skin were the 3 most frequently observed cancers before and after PCa diagnosis. At the time of PCa diagnosis, the prevalence of these 3 cancers was 1.94% for bladder cancer, 1.08% for colon cancer, and 1.08% for nonmelanoma skin cancer, compared with 1.30%, 0.96%, and 1.03%, respectively, for the matched comparison cohort. Five years after PCa diagnosis, the difference in incidence proportion between PCa men and their comparison cohort was 7% (95% CI, 5.6%-8.5%), 1.3% (0%-2.6%), and 1.6% (0.6%-2.6%) for these 3 cancers, respectively. From a uro-oncologic point of view, it is interesting to note that the prevalence of kidney cancer at the time of PCa diagnosis was 0.42% compared with 0.28% for the matched comparison cohort. CONCLUSIONS: Approximately 17% of all PCa occurred in combination with another primary cancer (before or after PCa diagnosis). Detection bias probably explains part of this observation, but further investigations are required to assess possible underlying mechanisms. 

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