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  • 251. Edlund, Per
    et al.
    Ahlgren, Johan
    Bjerre, Karsten
    Andersson, Michael
    Bergh, Jonas
    Mouridsen, Henning
    Holmberg, Stig B
    Bengtsson, Nils-Olof
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jakobsen, Erik
    Møller, Susanne
    Lindman, Henrik
    Blomqvist, Carl
    Dose-tailoring of FEC adjuvant chemotherapy based on leukopenia is feasible and well tolerated. Toxicity and dose intensity in the Scandinavian Breast Group phase 3 adjuvant Trial SBG 2000-12011In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 50, no 3, p. 329-337Article in journal (Refereed)
    Abstract [en]

    The SBG 2000-1 trial is a randomised study that investigates if dose-tailored adjuvant FEC therapy based on the individual's leukocyte nadir value can improve outcome. The study has included 1535 women with medium and high-risk breast cancer. Patients and methods. After a first standard dosed FEC course (5-fluorouracil 600 mg/m2, epirubicin 60 mg/mg2 and cyclophosphamide 600 mg/m2), patients who did not reach leukopenia grade III or IV were randomised to standard doses (group standard) or doses tailored to achieve grade III leukopenia (group tailored) at courses 2–7. Patients who achieved leukopenia grade III or more after the first course were not randomised but continued on standard doses (group registered). Results. Both planned and actually delivered number of courses (seven) were the same in all three arms. The relative dose intensity was increased by a factor of 1.31 (E 1.22, C 1.43) for patients in the tailored arm compared to the expected on standard dose. Ninety percent of the patients in the tailored arm achieved leukopenia grade III–IV compared with 29% among patients randomised to standard dosed therapy. Dose tailoring was associated with acceptable acute non-haematological toxicity with more total alopecia, nausea, vomiting and fatigue. Conclusion. Dose tailoring according to leukopenia was feasible. It led to an increased dose intensity and was associated with acceptable excess of acute non-haematological toxicity.Read More: http://informahealthcare.com/doi/abs/10.3109/0284186X.2011.554435

  • 252.
    Edwinsdotter Ardnor, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Rosén, Anna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    The BRCA1 exon 13 duplication: clinical characteristics of 22 families in Northern Sweden2019In: Familial Cancer, ISSN 1389-9600, E-ISSN 1573-7292, Vol. 18, no 1, p. 37-42Article in journal (Refereed)
    Abstract [en]

    The clinical management of BRCA1/2 mutation carriers requires accurate cancer risk estimates. Cancer risks vary according to type and location of the mutation and since there is limited information about mutation-specific cancer risks, genotype-phenotype correlation studies are needed. This is a report of 22 families with the same mutation, BRCA1 duplication exon 13, a mutation that is found world-wide, with the objective to describe the cancer history found in these families. We studied 69 confirmed carriers, 53 women and 16 men, and additionally 29 women who were clinically expected carriers. Among the confirmed carriers, 27 women (51%) were diagnosed with breast cancer, 10 (19%) with ovarian cancer, 5 (9%) with breast and ovarian cancer and 17 (32%) without cancer. Nine women (17%) with breast cancer were 35 years or younger at diagnose. Also, two cases of early onset colon cancer were found, and 37,5% of the male carriers were diagnosed with prostate cancer. These data may have implications for risk assessment and cancer prevention decision making for carriers of the BRCA1 duplication exon 13 mutation.

  • 253.
    Egberg Thyme, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    What do you see?: studies on time-limited psychodynamic art psychotherapy2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The main purpose of this thesis is to explore experiences of two different psychological interventions based on art psychotherapy in women with a psychological or physical illness. The two interventions are art psychotherapy and art therapy. The difference between these two interventions is that the art therapist works with the transference in art psychotherapy but not in art therapy. The thesis consists of two studies of art psychotherapy: An art psychotherapy intervention is evaluated in Study 1 (papers III and V) which examines a group of patients diagnosed with depression and Study 2 (paper II) which examines experiences in a group of six patients diagnosed with vulva vestibulitis. An art therapy intervention is evaluated in the third study (papers I and IV); where experiences in patients diagnosed with breast cancer are examined.

    In Study 1, forty-three (n=43) depressed women were randomly assigned to either an intervention group or a control group (verbal psychotherapy). The aim was to examine the outcome of time limited psychodynamic art therapy compared to time-limited psychodynamic verbal therapy for patients with depressive symptoms. Interviews were performed before, immediately after, and three months after the termination of psychotherapy, and self-rating scales which focus on stress reactions, depression and symptoms as well as an observer rating scale on depression were used. The interviews and the art sessions were video-recorded, and the verbal psychotherapy was tape-recorded. The results showed that the art and verbal psychotherapies were comparable. The conclusion was that short-term psychodynamic art psychotherapy could be a valuable treatment for depressed women. In an in-depth content analysis, the method of scribbling was further investigated and exemplified with the therapies of two participants. In this study, the patients’ pictures and verbal expressions of progress, along with considerations of how to interpret the pictures were in focus. When leaving therapy the two patients took advantage of the paper, made complete forms, symbolised in words what they have expressed in pictures; in pace with psychotherapy the themes alter towards separation, individuation, and attempt to relate in a new way. The conclusion was that limelimited psychodynamic art therapy suggests giving a safer place for the self as the cohesion is firmer with better boundaries.

    Study 2 is a pilot study, which involved six young patients newly diagnosed with vulva vestibulitis. The aim of the study was to investigate pain at vestibulum, mental health, and self-image after fifteen sessions of art psychotherapy. Five of the patients were judged to have less pain three months after termination of therapy. The conclusion was that art psychotherapy with its openness seemed to affect young women in their experiences of vulva vestibulitis in a positive direction.

    Study 3 examined the potential benefit of art therapy for women with primary breast cancer. The sample comprised forty-one (n=41) patients who were randomly assigned either to an art therapy group or to a control group. The art therapy was going on during five weeks radiation treatment, one session per week. The aim was to investigate the outcome of art therapy, to quantify and compare the participant coping s, self-image, and the symptoms with the participant in the control group. Interviews were performed before, immediately after, and six month after inclusion. A set of self-rating scales was used: Coping Resources Inventory, the Structural Analysis of Social Behavior, and Symptom Check List – 90. The result showed that the patients in the art therapy group rated their coping s and especially their social s, higher than the control group, and that the average patients in the art therapy group improved in depressive symptoms and symptoms of anxiety, and that the general psychiatric symptoms improved as well. A linear regression analysis showed a tendency that the coping s increased in the art therapy group and decreased in the control group or even stagnated in the social domain. A second report on self-image, symptoms, treatment, and social variables showed that art therapy was related to lower ratings of depression, anxiety, and general symptoms after treatment; chemotherapeutic treatment predicted lower depressive symptoms and general symptoms in contrast to axilliary surgery and hormonal treatment. The results showed that art therapy could be valuable complementary therapy in routine oncology practise. The conclusion is that art therapy can have a positive long-term effect on the crisis following the primary breast cancer and its consequences.

    Conclusion: The results show that time-limited psychodynamic art psychotherapy is valuable for depressed women; that it is a valuable complement for women with vulva vestibulitis; and that art therapy is a valuable complement in the care and cure of women with primary breast cancer.

  • 254.
    Egberg Thyme, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Sundin, Eva C.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Wiberg, Britt
    Division of Psychology, Nottingham Trent University, Nottinham, United Kingdom.
    Öster, Inger
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Åström, Sture
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lindh, Jack
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Individual brief art therapy can be helpful for women with breast cancer: A randomized controlled clinical study2009In: Palliative & Supportive Care, ISSN 1478-9515, E-ISSN 1478-9523, Vol. 7, no 1, p. 87-95Article in journal (Refereed)
    Abstract [en]

    Objective: Recent research shows that almost every second woman with breast cancer is depressed or has anxiety; the risk for younger women is even higher. Moreover, research shows that women are at risk for developing depression, also a threat for women with breast cancer. The aim of this randomized controlled clinical trial was to study the outcome of five sessions of art therapy given at a 5-week period of postoperative radiotherapy.

    Methods: The participants were between 37 and 69 years old; six participants in each group were below 50 years of age. Half of the participants (n = 20) received art therapy and the other half (n = 21) were assigned to a control group. At the first measurement, at least 17% (n = 7) of the participants medicated with antidepressants. Data were collected before and after art therapy and at a 4-month follow-up using self-rating scales that measure self-image (the Structural Analysis of Social Behaviour) and psychiatric symptoms (the Symptom Check List–90).

    Results: At follow-up, significant lower ratings of depression, anxiety, and somatic symptoms and less general symptoms were reported for the art therapy group compared to the control group. The regression analysis showed that art therapy relates to lower ratings of depression, anxiety, and general symptoms; chemotherapeutic treatment predicts lower depressive symptoms; in contrast to axilliary surgery and hormonal treatment as well as being a parent predicts higher ratings of anxiety and general symptoms.

    Significance of results: The conclusion suggests that art therapy has a long-term effect on the crisis following the breast cancer and its consequences.

  • 255.
    Egberg Thyme, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wiberg, Britt
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Sundin, Eva
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    The entangled butterfly and the blue cactus: two case studies on time-limited psychodynamic art psychotherapyManuscript (Other academic)
    Abstract [en]

    The aim of these two case studies is an in-depth analysis of the practice of scribbling in time- limited psychodynamic art psychotherapy. Our hypothesis is that the answers to "What do you see?" change as therapy proceeds, due to changes in emotions and cognitions expressed in scribbles and amplifications. The treatment is one hour per week for ten weeks, exempli- fied by two women with depression selected for differences in age, demographics and art expression. Analysis of the pictures and words is in two steps. The pictures were first tran- scribed into words using a phenomenological approach and then analysed according to con- tent analysis. Correspondingly, the words of the sessions were first transcribed verbatim and then analysed according to content analysis. The results show that the even if the two women have the same diagnosis at inclusion according to DSM IV, the symptoms of depression are expressed differently both in how they are manifested and in latent messages in the content analysis. The two women’s therapies can be divided into three phases each marked by turning points in the pictures – hence the pictures rather than the words set the theme for the phase. On leaving therapy the patients are able to use their drawings, their amplifications are in a complete form, they symbolise in words what they have expressed in pictures.

    The study’s conclusion is that the practice of scribbling seems to give a better capacity to regulate affects and, hence, a better regulation of the self. The women used not only their intellects but also their bodies in making latent communications manifest; their self-esteem improved as therapy proceeded, and they regained a sensitivity of "me – not me", i.e. better boundaries. The clinical implications are that the time-limited model of art psychotherapy is well suited to process emotions connected with depression, and that the patient’s problem should determine the length of the time limit.

     

  • 256. Ejlertsen, Bent
    et al.
    Mouridsen, Henning T
    Jensen, Maj-Britt
    Bengtsson, Nils-Olof
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergh, Jonas
    Cold, Soren
    Edlund, Per
    Ewertz, Marianne
    de Graaf, Peter W
    Kamby, Claus
    Nielsen, Dorte L
    Similar efficacy for ovarian ablation compared with cyclophosphamide, methotrexate, and fluorouracil: from a randomized comparison of premenopausal patients with node-positive, hormone receptor-positive breast cancer2006In: J Clin Oncol, ISSN 1527-7755, Vol. 24, no 31, p. 4956-4962Article in journal (Refereed)
  • 257.
    Ekblad, Lars
    et al.
    Lund Univ, Dept Oncol, Lund, Sweden.
    Lindgren, Gustaf
    Lund Univ, Dept Otorhinolaryngol Head & Neck Surg, Lund, Sweden.
    Persson, Emma
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kjellen, Elisabeth
    Lund Univ, Dept Oncol, Lund, Sweden.
    Wennerberg, Johan
    Lund Univ, Dept Otorhinolaryngol Head & Neck Surg, Lund, Sweden.
    Cell-line-specific stimulation of tumor cell aggressiveness by wound healing factors - a central role for STAT32013In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, p. 33-Article in journal (Refereed)
    Abstract [en]

    Background: Local recurrence is a major factor affecting survival after treatment for head and neck squamous cell carcinoma (HNSCC). It is possible that the normal processes involved in wound healing after surgical removal of a primary tumor can boost the regrowth of residual cancer cells, thereby contributing to the recurrent growth. In this work, we collected human wound fluids and used them to investigate the effect of wound healing factors on HNSCC cell lines in vitro. Methods: Wound fluids were collected from thyroidectomized patients diagnosed with benign disease and were included in assays of cell proliferation, migration, cell scattering, and invasion. The involvement of intracellular signaling pathways and membrane receptors were investigated by western blotting and the inclusion of specific inhibitors. Results: One out of four cell lines was greatly stimulated in proliferation, migration, cell scattering, and invasion by the addition of wound fluid as compared with addition of fetal bovine or human serum. These effects were accompanied by a sharp increase in activation of signal transducer and activator of transcription 3 (STAT3). Inhibition of STAT3 activation abolished the wound fluid response, showing that STAT3 plays an important role in the wound healing response. Several of the observed phenotypic changes were epithelial-to-mesenchymal transition (EMT)-like, but the appropriate changes were not seen in any of the EMT markers investigated. The involvement of c-Met or epidermal growth factor receptor family members was excluded, while the interleukin-6 receptor was found to be partly responsible for the activation of STAT3. Conclusions: In conclusion, we found cell-line-specific effects of wound healing factors on HNSCC, setting the stage for therapy development and predictive opportunities.

  • 258.
    Ekdahl, Ludvig
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    What shapes the tumor genome landscape? Systematical identifcation of essential genes2016Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 259. Ekman, Simon
    et al.
    Eriksson, Peter
    Bergström, Stefan
    Johansson, Peter
    Goike, Helena
    Gullbo, Joachim
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Larsson, Anders
    Bergqvist, Michael
    Clinical value of using serological cytokeratins as therapeutic markers in thoracic malignancies.2007In: Anticancer Res, ISSN 0250-7005, Vol. 27, no 5B, p. 3545-3553Article in journal (Refereed)
  • 260. Ellingson, Benjamin
    et al.
    Abrey, Lauren
    Garcia, Josep
    Chinot, Olivier
    Aftab, Dana
    Schwab, Gisela
    Revil, Cedric
    Saran, Frank
    Nishikawa, Ryo
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Center Stockholm, Stockholm, Sweden.
    Hessel, Colin
    Harris, Robert
    Woodworth, Davis
    Leu, Kevin
    Lai, Albert
    Sahebjam, Solmaz
    Pope, Whitney
    Mason, Warren
    Wick, Wolfgang
    Wen, Patrick
    Cloughesy, Timothy
    RESIDUAL ENHANCING TUMOR VOLUME IS A STRONG PROGNOSTIC BIOMARKER FOR SURVIVAL IN BOTH NEWLY DIAGNOSED AND RECURRENT GBM REGARDLESS OF THERAPY: EVIDENCE FROM 1,535 PATIENTS IN SINGLE AND MULTICENTER TRIALS2016In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 18, p. 131-131Article in journal (Refereed)
  • 261. Ellingson, Benjamin M.
    et al.
    Abrey, Lauren E.
    Garcia, Josep
    Chinot, Olivier
    Wick, Wolfgang
    Saran, Frank
    Nishikawa, Ryo
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Center Stockholm, Stockholm, Sweden.
    Mason, Warren P.
    Harris, Robert J.
    Leu, Kevin
    Woodworth, Davis C.
    Mehta, Arnav
    Raymond, Catalina
    Chakhoyan, Ararat
    Pope, Whitney B.
    Cloughesy, Timothy F.
    Post-chemoradiation volumetric response predicts survival in newly diagnosed glioblastoma treated with radiation, temozolomide, and bevacizumab or placebo2018In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 20, no 11, p. 1525-1535Article in journal (Refereed)
    Abstract [en]

    Background. In the current study we used contrast-enhanced T1 subtraction maps to test whether early changes in enhancing tumor volume are prognostic for overall survival (OS) in newly diagnosed glioblastoma (GBM) patients treated with chemoradiation with or without bevacizumab (BV). Methods. Seven hundred ninety-eight patients (404 BV and 394 placebo) with newly diagnosed GBM in the AVAglio trial (NCT00943826) had baseline MRI scans available, while 337 BV-treated and 269 placebo-treated patients had > 4 MRI scans for response evaluation. The volume of contrast-enhancing tumor was quantified and used for subsequent analyses. Results. A decrease in tumor volume during chemoradiation was associated with a longer OS in the placebo group (hazard ratio [HR] = 1.578, P < 0.0001) but not BV-treated group (HR = 1.135, P = 0.4889). Results showed a higher OS in patients on the placebo arm with a sustained decrease in tumor volume using a post-chemoradiation baseline (HR = 1.692, P = 0.0005), and a trend toward longer OS was seen in BV-treated patients (HR = 1.264, P = 0.0724). Multivariable Cox regression confirmed that sustained response or stable disease was prognostic for OS (HR = 0.7509, P = 0.0127) when accounting for age (P = 0.0002), KPS (P = 0.1516), postsurgical tumor volume (P < 0.0001), O6-methylguanine-DNA methyltransferase status (P < 0.0001), and treatment type (P = 0.7637) using the post-chemoradiation baseline. Conclusions. The post-chemoradiation timepoint is a better baseline for evaluating efficacy in newly diagnosed GBM. Early progression during the maintenance phase is consequential in predicting OS, supporting the use of progression-free survival rates as a meaningful surrogate for GBM.

  • 262. Ellingson, Benjamin M.
    et al.
    Abrey, Lauren E.
    Nelson, Sarah J.
    Kaufmann, Timothy J.
    Garcia, Josep
    Chinot, Olivier
    Saran, Frank
    Nishikawa, Ryo
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Center Stockholm.
    Mason, Warren P.
    Wick, Wolfgang
    Butowski, Nicholas
    Ligon, Keith L.
    Gerstner, Elizabeth R.
    Colman, Howard
    de Groot, John
    Chang, Susan
    Mellinghoff, Ingo
    Young, Robert J.
    Alexander, Brian M.
    Colen, Rivka
    Taylor, Jennie W.
    Arrillaga-Romany, Isabel
    Mehta, Arnav
    Huang, Raymond Y.
    Pope, Whitney B.
    Reardon, David
    Batchelor, Tracy
    Prados, Michael
    Galanis, Evanthia
    Wen, Patrick Y.
    Cloughesy, Timothy F.
    Validation of postoperative residual contrast-enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma2018In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 20, no 9, p. 1240-1250Article in journal (Refereed)
    Abstract [en]

    Background. In the current study, we pooled imaging data in newly diagnosed glioblastoma (GBM) patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial consortiums to identify the relationship between postoperative residual enhancing tumor volume and overall survival (OS). Methods. Data from 1511 newly diagnosed GBM patients from 5 data sources were included in the current study: (i) a single institution database from UCLA (N = 398; Discovery); (ii) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N = 262 from 8 centers; Confirmation); (iii) the chemoradiation placebo arm from an international phase III trial (AVAglio; N = 394 from 120 locations in 23 countries; Validation); (iv) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N = 404 from 120 locations in 23 countries; Exploratory Set 1); and (v) an Alliance (N0874) phase I/II trial of vorinostat plus chemoradiation (N = 53; Exploratory Set 2). Postsurgical, residual enhancing disease was quantified using T1 subtraction maps. Multivariate Cox regression models were used to determine influence of clinical variables, O-6-methylguanine-DNA methyltransferase (MGMT) status, and residual tumor volume on OS. Results. A log-linear relationship was observed between postoperative, residual enhancing tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation. Postoperative tumor volume is a prognostic factor for OS (P < 0.01), regardless of therapy, age, and MGMT promoter methylation status. Conclusion. Postsurgical, residual contrast-enhancing disease significantly negatively influences survival in patients with newly diagnosed GBM treated with chemoradiation with or without concomitant experimental therapy.

  • 263. Emaus, Marleen J.
    et al.
    van Gils, Carla H.
    Bakker, Marije F.
    Bisschop, Charlotte N. Steins
    Monninkhof, Evelyn M.
    Bueno-de-Mesquita, H. B(as)
    Travier, Noemie
    Berentzen, Tina Landsvig
    Overvad, Kim
    Tjonneland, Anne
    Romieu, Isabelle
    Rinaldi, Sabina
    Chajes, Veronique
    Gunter, Marc J.
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Mesrine, Sylvie
    Chang-Claude, Jenny
    Kaaks, Rudolf
    Boeing, Heiner
    Aleksandrova, Krasimira
    Trichopoulou, Antonia
    Naska, Androniki
    Orfanos, Philippos
    Palli, Domenico
    Agnoli, Claudia
    Tumino, Rosario
    Vineis, Paolo
    Mattiello, Amalia
    Braaten, Tonje
    Borch, Kristin Benjaminsen
    Lund, Eiliv
    Menendez, Virginia
    Sanchez, Maria-Jose
    Navarro, Carmen
    Barricarte, Aurelio
    Amiano, Pilar
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Andersson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Borgquist, Signe
    Olsson, Asa
    Khaw, Kay-Tee
    Wareham, Nick
    Travis, Ruth C.
    Riboli, Elio
    Peeters, Petra H. M.
    May, Anne M.
    Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 12, p. 2887-2899Article in journal (Refereed)
    Abstract [en]

    Long-term weight gain (i.e., weight gain since age 20) has been related to higher risk of postmenopausal breast cancer, but a lower risk of premenopausal breast cancer. The effect of weight change in middle adulthood is unclear. We investigated the association between weight change in middle adulthood (i.e., women aged 40-50 years) and the risk of breast cancer before and after the age of 50. We included female participants of the European Prospective Investigation into Cancer and Nutrition cohort, with information on anthropometric measures at recruitment and after a median follow-up of 4.3 years. Annual weight change was categorized using quintiles taking quintile 2 and 3 as the reference category (-0.44 to 0.36 kg/year). Multivariable Cox proportional hazards regression analysis was used to examine the association. 205,723 women were included and 4,663 incident breast cancer cases were diagnosed during a median follow-up of 7.5 years (from second weight assessment onward). High weight gain (Q5: 0.83-4.98 kg/year) was related to a slightly, but significantly higher breast cancer risk (HRQ5_versus_Q2/3: 1.09, 95% CI: 1.01-1.18). The association was more pronounced for breast cancer diagnosed before or at age 50 (HRQ5_versus_Q2/3: 1.37, 95% CI: 1.02-1.85). Weight loss was not associated with breast cancer risk. There was no evidence for heterogeneity by hormone receptor status. In conclusion, high weight gain in middle adulthood increases the risk of breast cancer. The association seems to be more pronounced for breast cancer diagnosed before or at age 50. Our results illustrate the importance of avoiding weight gain in middle adulthood.

  • 264.
    Emilsson, Sofia
    et al.
    Mellannorrlands Hosp AB, Sundsvall, Sweden.
    Svensk, Ann-Christine
    Olsson, Karolina
    Lindh, Jack
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Öster, Inger
    Umeå University, Faculty of Medicine, Department of Nursing.
    Experiences from having breast cancer and being part of a support group: Notes written in diaries by women during radiotherapy2012In: Palliative & Supportive Care, ISSN 1478-9515, E-ISSN 1478-9523, Vol. 10, no 2, p. 99-105Article in journal (Refereed)
    Abstract [en]

    Objective:The purpose of this study was to examine the experiences of breast cancer patients participating in a support group.

    Method:This study explores 28 stories of women with breast cancer as expressed through written diaries. Diaries were written during a 5-week period in parallel with radiotherapy and participation in a support group in a hospital. Answers to six open-ended evaluative questions concerning the support group were included in the majority of the written diaries. A qualitative content analysis was used to identify themes.

    Results:Three themes were constructed during the analysis: "positive group development." "Inhibited group development." and "the individual living with the disease." Hopes and fears for the future in regards to illness and getting better, the value of family and friends, and feelings related to daily life with breast cancer such as fatigue and changes in body image were also expressed in the diaries.

    Significance of results:The findings suggest that the women with breast cancer found it valuable to be able to share experiences with other women in a similar situation in the context of a support group. Being part of such a group provided a space and an opportunity for reflection.

  • 265.
    Emilsson, Sofia
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Svensk, Ann-Christine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lindh, Jack
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Support group participation during the post-operative radiotherapy period increases levels of coping resources among women with breast cancer.2012In: European Journal of Cancer Care, ISSN 0961-5423, E-ISSN 1365-2354, Vol. 21, no 5, p. 591-598Article in journal (Refereed)
    Abstract [en]

    Support group participation during the post-operative radiotherapy period increases levels of coping resources among women with breast cancer Being diagnosed with breast cancer is a traumatic experience that can elevate levels of distress and cause depletion of coping resources in many of the disease's victims. This non-randomised case-control study among breast cancer patients undergoing radiotherapy indicates that participation in a support group that focuses on communication and mutual sharing between its member's has positive effects and increases levels of coping resources assessed with the Coping Resources Inventory (CRI). Results of the CRI showed a significant difference between the study group and control group in the social domain at the second occasion of measurement (P= 0.007) and in the emotional domain at the third occasion (P= 0.028). Within the study group, over time, increased levels of coping resources reached significant levels concerning the emotional domain at the second occasion (P= 0.025). Conversely, coping resources were decreased in the same domain within the control group over time, at the third occasion (P= 0.053). Additionally, anxiety and depression were assessed using the Hospital Anxiety and Depression Scale, showing no difference between the groups. This study shows that participation in a support group during post-operative radiotherapy can be socially and emotionally strengthening because of the opportunity for the patients to mutually share experiences.

  • 266.
    Eriksson, Björn
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Johansson, Ann-Sofie
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Levan, Göran
    Holmberg, Dan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Establishment and characterization of a mouse strain (TLL) that spontaneously develops T-cell lymphomas/leukemia1999In: Experimental Hematology, ISSN 0301-472X, E-ISSN 1873-2399, Vol. 27, no 4, p. 682-688Article in journal (Refereed)
    Abstract [en]

    In this study, a mouse strain (TLL) that spontaneously develops T-cell lymphomas/leukemia with an early onset and high incidence was established and characterized. All tumors analyzed were found to express the alpha,beta T-cell receptor, and the majority of them had a mature, CD3+CD4+CD8- immunophenotype. In a few cases, tumors with a more immature CD3+CD4+CD8+ phenotype were isolated. Expanded phenotyping using a broad panel of lymphocyte differentiation markers confirmed the mature T-cell phenotype of the tumors. Histologic and cell cycle analysis of the tumors revealed an aggressive lymphoblastic malignancy with a very high proliferation rate and widespread engagement of bone marrow and lymphoid as well as nonlymphoid organs. Thus, the TLL mouse strain represents a unique model for the analysis of the oncogenesis and progression of mature T-cell tumors and for the development of therapeutic measures to combat such tumors.

  • 267.
    Eriksson, Carola
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Salander, Pär
    Umeå University, Faculty of Social Sciences, Department of Social Work. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hamberg, Katarina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine. Umeå University, Faculty of Social Sciences, Umeå Centre for Gender Studies (UCGS).
    Men's experiences of intense fear related to childbirth investigated in a Swedish qualitative study2007In: Journal of Men's health and gender, Vol. 4, p. 409-418Article in journal (Refereed)
  • 268.
    Eriksson, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kahari, Jenna
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vestman, Amanda
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hallmans, Mattias
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergenheim, A. Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Improved treatment of glioblastoma: changes in survival over two decades at a single regional Centre2019In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, no 3, p. 334-341Article in journal (Refereed)
    Abstract [en]

    Background: Glioblastoma (GBM) is an aggressive brain tumor with a short overall survival (OS) in general. The treatment of GBM has evolved over the last decades and is today multimodal including surgical resection followed by radiochemotherapy and adjuvant chemotherapy for patients in good performance status. The aim of this study was to evaluate the development of treatment and the outcome for GBM patients at a single regional center.

    Patients and methods: Survival was studied for 571 patients in our region diagnosed with GBM between 1995 and 2015. Samples from 244 patients out of those treated 2005-2015 have been included in a tissue/blood bank and a clinical database has been set up with basic patient characteristics and details on surgery and non-surgical treatment.

    Results: The median OS for all patients from 1995 to 2015 was 9.3 months. There was a stepwise improvement from 6.9 to 10.3 months for patients diagnosed 1995-1996 and 2010-2015, respectively (p<.05). The 2-year survival for the same time periods improved from 7% to 18% (p<.01). After introduction of postoperative radiochemotherapy for patients in good performance status in 2005 an increased OS was noted and following implementation of intraoperative 5-aminolevulinic acid the number of tumor resection 95% did increase from 33% to 54% (p<.001). Positive prognostic factors for survival were young age, good performance status, absence of inflammatory disease, absence of diabetes or metabolic disease, tumor resection 95%, and completion of postoperative radiochemotherapy.

    Discussion: The results of this study are consistent with earlier results regarding survival and prognostic factors and confirm results from randomized controlled trials in a clinical setting. Despite the improvements made, the prognosis is still dismal and the need for further research on GBM treatment is great.

  • 269.
    Eriksson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Epidemiological studies on multiple myeloma1992Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Multiple myeloma is a painful and uncurable malignant disease with an increasing incidence and mortality in several countries, e.g., Sweden. Some factors are suspected to be of aetiological significance, such as ionising radiation and chronic antigenic stimulation in certain inflammatory diseases. A familial factor has also been indicated. Furthermore, some studies have demonstrated farming as an occupation entailing an increased risk for the disease.

    The aim of this investigation was to further elucidate the impact of different aetiological factors in relation to multiple myeloma. The knowledge of aetiology is always a prerequisite for prevention.

    A case-control study on multiple myeloma was performed in a high-inddence area, the northern part of Sweden. One part of this study dealt with occupations and different exposures. The results supported farming as being an occupation with an increased risk. Within farming two kinds of pesticides, phenoxyacetic adds and DDT, and contact with certain domestic animals, i.e., cattle, horses and goats, were assodated with multiple myeloma.

    Farming as a risk factor was also confirmed by a register-based linkage study using the Swedish Cancer Environment Register. In this study a time trend was indicated, with increasing standardized inddence ratios over the different time periods studied.

    Another part of the case-control study showed that rheumatoid arthritis entailed an increased risk for multiple myeloma, a finding earlier suggested from register-based linkage studies, but not from any çase-control study.

    A third part of the case-control study indicated an increased risk for multiple myeloma if any first-degree relative had a history of haematological malignancy, or other malignant tumour, espedally prostatic cancer, brain tumour, and renal cancer.

    A case study encompassing 942 patients with haematological malignandes in the county of Jämtland, Sweden, during a 22-year period showed that about 5% of the patients had at least one relative who also suffered from such a disease. An espedally strong familial occurrence was found in the group of chronic lymphoprohferative diseases, including multiple myeloma.

  • 270.
    Fallbjörk, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Karlsson, Stig
    Umeå University, Faculty of Medicine, Department of Nursing.
    Salander, Pär
    Umeå University, Faculty of Social Sciences, Department of Social Work. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Rasmussen, Birgit H
    Umeå University, Faculty of Medicine, Department of Nursing.
    Differences between women who have and have not undergone breast reconstruction after mastectomy due to breast cancer2010In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 49, no 2, p. 174-179Article in journal (Refereed)
    Abstract [en]

    Aim: This study compares potential differences between women with breast cancer who after mastectomy had undergone breast reconstruction with those who had not. Material and methods: All women (N=149) in the northern medical region of Sweden who had undergone mastectomy in 2003 received a self-reported questionnaire entitled “Life After Mastectomy (LAM)” that included standardized measures of sociodemographic, decision-making process, breast reconstruction (BR) yes or no, sexuality, and body image. SPSS was used for data processing. Results: In total 85% of the women returned the questionnaire and of these 25% had undergone BR. In accordance with previous studies, we found that the mean age of the women in the BR group was significantly lower (52 vs. 64 years), they had a higher education, and a higher proportion were employed, influenced by the physician's opinion regarding BR, sexually active, and rated a negative impact concerning the factors attractiveness and body disclosure. A multiple regression analysis, however, showed that the choice to undergo breast reconstruction or not was only independently associated with age, feeling of attractiveness and sexual interest. Discussion: Age explained most differences found between the two groups. When researchers try to identify what differentiates the groups of women who undergo reconstruction between those who do not undergo reconstruction after mastectomy, it is thus necessary to take into consideration that the meanings of mastectomy, body image, attractiveness and similar variables may vary due to the phase of a woman's life. In conclusion, considering the impact of age is of paramount importance in future studies for our understanding of women's experiences.

  • 271. Fanidi, Anouar
    et al.
    Carreras-Torres, Robert
    Larose, Tricia L.
    Yuan, Jian-Min
    Stevens, Victoria L.
    Weinstein, Stephanie J.
    Albanes, Demetrius
    Prentice, Ross
    Pettinger, Mary
    Cai, Qiuyin
    Blot, William J.
    Arslan, Alan A.
    Zeleniuch-Jacquotte, Anne
    McCullough, Marjorie L.
    Le Marchand, Loic
    Wilkens, Lynne R.
    Haiman, Christopher A.
    Zhang, Xuehong
    Stampfer, Meir J.
    Smith-Warner, Stephanie A.
    Giovannucci, Edward
    Giles, Graham G.
    Hodge, Allison M.
    Severi, Gianluca
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Langhammer, Arnulf
    Brumpton, Ben M.
    Wang, Renwei
    Gao, Yu-Tang
    Ericson, Ulrika
    Bojesen, Stig E.
    Arnold, Susanne M.
    Koh, Woon-Puay
    Shu, Xiao-Ou
    Xiang, Yong-Bing
    Li, Honglan
    Zheng, Wei
    Lan, Qing
    Visvanathan, Kala
    Hoffman-Bolton, Judith
    Ueland, Per M.
    Midttun, Oivind
    Caporaso, Neil E.
    Purdue, Mark
    Freedman, Neal D.
    Buring, Julie E.
    Lee, I-Min
    Sesso, Howard D.
    Gaziano, J. Michael
    Manjer, Jonas
    Relton, Caroline L.
    Hung, Rayjean J.
    Amos, Chris, I
    Johansson, Mattias
    Brennan, Paul
    Is high vitamin B12 status a cause of lung cancer?2019In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 145, no 6, p. 1499-1503Article in journal (Refereed)
    Abstract [en]

    Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer etiology via direct measurements of pre‐diagnostic circulating vitamin B12 concentrations in a nested case–control study, complemented with a Mendelian randomization (MR) approach in an independent case–control sample. We used pre‐diagnostic biomarker data from 5183 case–control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre‐diagnostic blood samples from the nested case–control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12] = 1.15, 95% confidence interval (95%CI) = 1.06–1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD] = 1.08, 95%CI = 1.00–1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.

  • 272. Fanidi, Anouar
    et al.
    Muller, David C
    Yuan, Jian-Min
    Stevens, Victoria L
    Weinstein, Stephanie J
    Albanes, Demetrius
    Prentice, Ross
    Thomsen, Cynthia A
    Pettinger, Mary
    Cai, Qiuyin
    Blot, William J
    Wu, Jie
    Arslan, Alan A
    Zeleniuch-Jacquotte, Anne
    McCullough, Marjorie L
    Le Marchand, Loic
    Wilkens, Lynne R
    Haiman, Christopher A
    Zhang, Xuehong
    Han, Jiali
    Stampfer, Meir J
    Smith-Warner, Stephanie A
    Giovannucci, Edward
    Giles, Graham G
    Hodge, Allison M
    Severi, Gianluca
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Langhammer, Arnulf
    Krokstad, Steinar
    Næss, Marit
    Wang, Renwei
    Gao, Yu-Tang
    Butler, Lesley M
    Koh, Woon-Puay
    Shu, Xiao-Ou
    Xiang, Yong-Bing
    Li, Honglan
    Zheng, Wei
    Lan, Qing
    Visvanathan, Kala
    Bolton, Judith Hoffman
    Ueland, Per Magne
    Midttun, Øivind
    Ulvik, Arve
    Caporaso, Neil E
    Purdue, Mark
    Ziegler, Regina G
    Freedman, Neal D
    Buring, Julie E
    Lee, I-Min
    Sesso, Howard D
    Gaziano, J Michael
    Manjer, Jonas
    Ericson, Ulrika
    Relton, Caroline
    Brennan, Paul
    Johansson, Mattias
    Circulating Folate, Vitamin B6, and Methionine in Relation to Lung Cancer Risk in the Lung Cancer Cohort Consortium (LC3)2018In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 110, no 1, article id djx119Article in journal (Refereed)
    Abstract [en]

    Background: Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown.

    Methods: Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models.

    Results: Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1 ) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups.

    Conclusions: Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6.

  • 273. Fanidi, Anouar
    et al.
    Relton, Caroline
    Ueland, Per Magne
    Midttun, Øivind
    Vollset, Stein Emil
    Travis, Ruth C.
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Bueno-de-Mesquita, H. B(as)
    Ros, Martine
    Boeing, Heiner
    Tumino, Rosario
    Panico, Salvatore
    Palli, Domenico
    Sieri, Sabina
    Vineis, Paolo
    Sánchez, María-José
    Huerta, José María
    Barricarte Gurrea, Aurelio
    Luján-Barroso, Leila
    Quirós, J. Ramón
    Tjønneland, Anne
    Halkjær, Jytte
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Cadeau, Claire
    Weiderpass, Elisabete
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Riboli, Elio
    Brennan, Paul
    Johansson, Mattias
    International Agency for Research on Cancer, Lyon, France.
    A prospective study of one-carbon metabolism biomarkers and cancer of the head and neck and esophagus2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, no 4, p. 915-927Article in journal (Refereed)
    Abstract [en]

    Experimental and epidemiological data suggest that factors of one-carbon metabolism are important in the pathogenesis of several cancers, but prospective data on head and neck cancer (HNC) and esophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants from 10 countries who donated a blood sample. The current study included 516 cancer cases of the head and neck and esophagus and 516 individually matched controls. Plasma levels of vitamins B2, B6, B9 (folate), B12, and methionine and homocysteine were measured in pre-diagnostic plasma samples and analyzed in relation to HNC and esophagus cancer risk, as well as post-diagnosis all-cause mortality. After controlling for risk factors, study participants with higher levels of homocysteine had elevated risk of HNC, the odds ratio (OR) in conditional analysis when comparing the top and bottom quartiles of homocysteine [ORQ4vs. Q1] being 2.13 (95% confidence interval [95% CI] 1.13-4.00, p for trend 0.009). A slight decrease in HNC risk was also seen among subjects with higher levels of folate (ORQ4vs. Q1 0.63, 95% CI 0.35-1.16, p for trend 0.02). Subgroup analyses by anatomical sub-site indicated particularly strong associations with circulating homocysteine for oral cavity and gum cancer (p for trend 8 x 10(-4)), as well as for oropharynx cancer (p for trend 0.008). Plasma concentrations of the other investigated biomarkers did not display any clear association with risk or survival. In conclusion, study participants with elevated circulating levels of homocysteine had increased risk of developing squamous cell carcinoma of the head and neck. What's new? One-carbon metabolism (OCM) involves the transfer of a carbon unit from methyl donor nutrients to molecules involved in the synthesis and methylation of DNA. As a result, dietary imbalances or deficiencies in nutrients crucial for OCM may affect DNA replication, repair, and regulation, potentially facilitating cancer development. This analysis of circulating levels of OCM nutrients in head and neck cancer and esophageal cancer patients and matched controls reveals an association between elevated levels of the amino acid homocysteine and increased risk of squamous cell carcinoma of the head and neck. Risk was decreased slightly by elevated folate levels.

  • 274.
    Faraz, Mahmood
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Investigations of Leucine-rich repeats and immunoglobulin-like domain-proteins 1 and 2 (LRIG1 and LRIG2) and their genes in cancer2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The mammalian leucine-rich repeats and immunoglobulin-like domains (LRIG) gene family consists of three different members, LRIG1, LRIG2, and LRIG3. These genes are expressed in all human and mouse tissues analyzed to date. All LRIG proteins share similar and evolutionary conserved structural domains including a leucine-rich repeat domain, three immunoglobulin-like domains, a transmembrane domain, and a cytosolic tail. Since the discovery of this family, around 20 years ago, various research groups have shown the importance of this family in cancer biology and prognosis. The aim of this thesis was to further investigate the role of LRIG1 and LRIG2 in cancer.

    To investigate the roles of LRIG1 and LRIG2 in physiology and gliomagenesis, we generated Lrig1- and Lrig2-deficient mice and induced platelet-derived growth factor B (PDGFB)-driven gliomagenesis. We studied the effects of Lrig2 ablation on mouse development and survival and investigated if the ablation of Lrig1 or Lrig2 affects the incidence or malignancy of induced gliomas. We also investigated if Lrig2 ablation affects Pdgfr signaling in mouse embryonic fibroblasts (MEFs). Additionally, we analyzed the effects of ectopic LRIG1 expression in human primary glioblastoma cell lines TB101 and TB107, in vivo and in vitro. We reported no macroscopic anatomical defect but reduced growth and increased spontaneous mortality rate in Lrig2-deficient mice. However, the Lrig2-deficient mice were protected against the induced gliomagenesis. Lrig2-deficient MEFs showed faster kinetics of induction of immediate-early genes in response to PDGFB stimulation, whereas the phosphorylations of Pdgfra, Pdgfrb, Erk1/2, and Akt1 appeared unaltered. Lrig1-heterozygote mice showed a higher incidence of high-grade tumors (grade IV) compared to wildtype mice, demonstrating a haploinsufficient function of Lrig1. LRIG1 overexpression suppressed TB107 cell invasion in vivo and in vitro, which was partially mediated through the suppression of the MET receptor tyrosine kinase.

    To identify LRIG1-interacting proteins, we used the yeast-two hybrid system and data-mined the Bio-Plex network of high throughput protein-protein interaction database. To study the function of interactors, we used a triple co-transfection system to overexpress LRIG1 and PDGFRA and downregulate endogenous levels of interactors by short hairpin RNAs (shRNAs), simultaneously. This analysis demonstrated that CNPY3, CNPY4, GAL3ST1, GML, HLA-DRA, LRIG2, LRIG3, LRRC40, PON2, RAB4A, and ZBTB16 were important for the PDGFRA-downregulating function of LRIG1.

    To investigate the clinical significance of LRIG1 copy number alterations (CNAs) in breast cancer, we used droplet digital PCR (ddPCR) to analyze 423 breast cancer tumors. We found that LRIG1 CNAs were significantly different in steroid-receptor-positive vs steroid-receptor-negative tumors and in ERBB2-amplified vs ERBB2-non-amplified tumors. In the whole cohort, patients with LRIG1 loss or gain had a worse metastasis-free survival than patients with normal LRIG1 copy numbers, however, among the early-stage breast cancer subgroup, this difference was not significant. 

    In summary, Lrig1 behaved like a haploinsufficient tumor suppressor gene in malignant glioma, whereas Lrig2 appeared to promote malignant glioma. Our functional analysis of LRIG1 interactome uncovered several unanticipated and novel proteins that might be important for the regulation of receptor tyrosine kinases by LRIG1. LRIG1 CNAs predicted metastasis-free survival time in breast cancer. Hopefully, our findings might lead to a better understanding of the regulation of growth factor signaling and its importance in cancer biology and prognosis.

     

  • 275.
    Faraz, Mahmood
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Herdenberg, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Holmlund, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    A protein interaction network centered on leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) regulates growth factor receptors2018In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 293, no 9, p. 3421-3435Article in journal (Refereed)
    Abstract [en]

    Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a tumor suppressor and a negative regulator of several receptor tyrosine kinases. The molecular mechanisms by which LRIG1 mediates its tumor suppressor effects and regulates receptor tyrosine kinases remain incompletely understood. Here, we performed a yeast two-hybrid screen to identify novel LRIG1-interacting proteins and mined data from the BioPlex (biophysical interactions of ORFeome-based complexes) protein interaction data repository. The putative LRIG1 interactors identified in the screen were functionally evaluated using a triple co-transfection system in which HEK293 cells were co-transfected with platelet-derived growth factor receptor α, LRIG1, and shRNAs against the identified LRIG1 interactors. The effects of the shRNAs on the ability of LRIG1 to down-regulate platelet-derived growth factor receptor α expression were evaluated. On the basis of these results, we present an LRIG1 protein interaction network with many newly identified components. The network contains the apparently functionally important LRIG1-interacting proteins RAB4A, PON2, GAL3ST1, ZBTB16, LRIG2, CNPY3, HLA-DRA, GML, CNPY4, LRRC40, and LRIG3, together with GLRX3, PTPRK, and other proteins. In silico analyses of The Cancer Genome Atlas data sets revealed consistent correlations between the expression of the transcripts encoding LRIG1 and its interactors ZBTB16 and PTPRK and inverse correlations between the transcripts encoding LRIG1 and GLRX3. We further studied the LRIG1 function–promoting paraoxonase PON2 and found that it co-localized with LRIG1 in LRIG1-transfected cells. The proposed LRIG1 protein interaction network will provide leads for future studies aiming to understand the molecular functions of LRIG1 and the regulation of growth factor signaling.

  • 276.
    Faraz, Mahmood
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tellström, A.
    Edwinsdotter, C.
    Grankvist, K.
    Huminiecki, L.
    Tavelin, B.
    Henriksson, R.
    Ingrid, L.
    Hedman, H.
    LRIG1 gene copy number analysis by ddPCR and correlation to clinical factors in breast cancecrManuscript (preprint) (Other academic)
  • 277. Fedirko, Veronika
    et al.
    Jenab, Mazda
    Meplan, Catherine
    Jones, Jeb S.
    Zhu, Wanzhe
    Schomburg, Lutz
    Siddiq, Afshan
    Hybsier, Sandra
    Overvad, Kim
    Tjonneland, Anne
    Omichessan, Hanane
    Perduca, Vittorio
    Boutron-Ruault, Marie-Christine
    Kuehn, Tilman
    Katzke, Verena
    Aleksandrova, Krasimira
    Trichopoulou, Antonia
    Karakatsani, Anna
    Kotanidou, Anastasia
    Tumino, Rosario
    Panico, Salvatore
    Masala, Giovanna
    Agnoli, Claudia
    Naccarati, Alessio
    Bueno-de-Mesquita, Bas
    Vermeulen, Roel C. H.
    Weiderpass, Elisabete
    Skeie, Guri
    Nost, Therese Haugdahl
    Lujan-Barroso, Leila
    Ramon Quiros, J.
    Maria Huerta, Jose
    Rodriguez-Barranco, Miguel
    Barricarte, Aurelio
    Gylling, Björn
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bradbury, Kathryn E.
    Wareham, Nick
    Khaw, Kay-Tee
    Gunter, Marc
    Murphy, Neil
    Freisling, Heinz
    Tsilidis, Kostas
    Aune, Dagfinn
    Riboli, Elio
    Hesketh, John E.
    Hughes, David J.
    Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status2019In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 11, no 4, article id 935Article in journal (Refereed)
    Abstract [en]

    Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengateassays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (PACT = 0.10; PACT significance threshold was P < 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.

  • 278. Fedirko, Veronika
    et al.
    Mandle, Hannah B.
    Zhu, Wanzhe
    Hughes, David J.
    Siddiq, Afshan
    Ferrari, Pietro
    Romieu, Isabelle
    Riboli, Elio
    Bueno-de-Mesquita, Bas
    van Duijnhoven, Franzel J. B.
    Siersema, Peter D.
    Tjonneland, Anne
    Olsen, Anja
    Perduca, Vittorio
    Carbonnel, Franck
    Boutron-Ruault, Marie-Christine
    Kuehn, Tilman
    Johnson, Theron
    Krasimira, Aleksandrova
    Trichopoulou, Antonia
    Makrythanasis, Periklis
    Thanos, Dimitris
    Panico, Salvatore
    Krogh, Vittorio
    Sacerdote, Carlotta
    Skeie, Guri
    Weiderpass, Elisabete
    Colorado-Yohar, Sandra
    Sala, Nuria
    Barricarte, Aurelio
    Sanchez, Maria-Jose
    Quiros, Ramon
    Amiano, Pilar
    Gylling, Björn
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Perez-Cornago, Aurora
    Heath, Alicia K.
    Tsilidis, Konstantinos K.
    Aune, Dagfinn
    Freisling, Heinz
    Murphy, Neil
    Gunter, Marc J.
    Jenab, Mazda
    Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations2019In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 11, no 8, article id 1954Article in journal (Refereed)
    Abstract [en]

    Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini-Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor beta (TGF beta) signaling was associated with CRC risk (P <= 0.001), with most statistically significant genes being SMAD7 (P-BH = 0.008) and SMAD3 (P-BH = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites (P = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction P = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings.

  • 279. Fedirko, Veronika
    et al.
    Romieu, Isabelle
    Aleksandrova, Krasimira
    Pischon, Tobias
    Trichopoulos, Dimitrios
    Peeters, Petra H.
    Romaguera-Bosch, Dora
    Bueno-de-Mesquita, H. B(as)
    Dahm, Christina C.
    Overvad, Kim
    Chirlaque, Maria-Dolores
    Johansen, Christoffer
    Bidstrup, Pernille E.
    Dalton, Susanne O.
    Gunter, Marc J.
    Wark, Petra A.
    Norat, Teresa
    Halkjaer, Jytte
    Tjonneland, Anne
    Dik, Vincent K.
    Siersema, Peter D.
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Bastide, Nadia
    Kuehn, Tilman
    Kaaks, Rudolf
    Boeing, Heiner
    Trichopoulou, Antonia
    Klinaki, Eleni
    Katsoulis, Michalis
    Pala, Valeria
    Panico, Salvatore
    Tumino, Rosario
    Palli, Domenico
    Vineis, Paolo
    Weiderpass, Elisabete
    Skeie, Guri
    Gonzalez, Carlos A.
    Sanchez, Maria-Jose
    Barricarte, Aurelio
    Amiano, Pilar
    Ramon Quiros, J.
    Manjer, Jonas
    Jirstroem, Karin
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Khaw, Kay-Tee
    Wareham, Nick
    Bradbury, Kathryn E.
    Stepien, Magdalena
    Duarte-Salles, Talita
    Riboli, Elio
    Jenab, Mazda
    Pre-diagnostic anthropometry and survival after colorectal cancer diagnosis in Western European populations2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 8, p. 1949-1960Article in journal (Refereed)
    Abstract [en]

    General and abdominal adiposity are associated with a high risk of developing colorectal cancer (CRC), but the role of these exposures on cancer survival has been less studied. The association between pre-diagnostic anthropometric characteristics and CRC-specific and all-cause death was examined among 3,924 men and women diagnosed with CRC between 1992 and 2009 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable Cox proportional hazards models were used to calculate hazard ratios (FIRS) and corresponding 95% confidence intervals (as). Over a mean follow-up period of 49 months, 1,309 deaths occurred of which 1,043 (79.7%) were due to CRC. In multivariable analysis, prediagnostic BMI kg/m2 was associated with a high risk for CRC-specific (HR = 1.26, 95% CI = 1.04-1.52) and all-cause (HR = 1.32, 95% CI = 1.12-1.56) death relative to BMI <25 kg/m(2). Every 5 kg/m(2) increase in BMI was associated with a high risk for CRC-specific (HR = 1.10, 95% CI = 1.02-1.19) and all-cause death (HR = 1.12, 95% Cl = 1.05-1.20); and every 10 cm increase in waist circumference was associated with a high risk for CRC-specific (HR = 1.09, 95% Cl = 1.02-1.16) and allcause death (HR= 1.11, 95% CI= 1.05-1.18). Similar associations were observed for waist-to-hip and waist-to-height ratios. Height was not associated with CRC-specific or all-cause death. Associations tended to be stronger among men than in women. Possible interactions by age at diagnosis, cancer stage, tumour location, and hormone replacement therapy use among postmenopausal women were noted. Pre-diagnostic general and abdominal adiposity are associated with lower survival after CRC diagnosis.

  • 280. Ferrari, Pietro
    et al.
    Rinaldi, Sabina
    Jenab, Mazda
    Lukanova, Annekatrin
    Olsen, Anja
    Tjonneland, Anne
    Overvad, Kim
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Touillaud, Marina
    Kaaks, Rudolf
    von Ruesten, Anne
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Benetou, Vassiliki
    Grioni, Sara
    Panico, Salvatore
    Masala, Giovanna
    Tumino, Rosario
    Polidoro, Silvia
    Bakker, Marije F.
    van Gils, Carla H.
    Ros, Martine M.
    Bueno-de-Mesquita, H. Bas
    Krum-Hansen, Sanda
    Engeset, Dagrun
    Skeie, Guri
    Pilar, Amiano
    Sanchez, Maria-Jose
    Buckland, Genevieve
    Ardanaz, Eva
    Chirlaque, Dolores
    Rodriguez, Laudina
    Travis, Ruth
    Key, Tim
    Khaw, Kay-Tee
    Wareham, Nicholas J.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Slimani, Nadia
    Norat, Teresa
    Aune, Dagfinn
    Riboli, Elio
    Romieu, Isabelle
    Dietary fiber intake and risk of hormonal receptor-defined breast cancer in the European Prospective Investigation into Cancer and Nutrition study2013In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 97, no 2, p. 344-353Article in journal (Refereed)
    Abstract [en]

    Background: Limited scientific evidence has characterized the association between dietary fiber intake and risk of breast cancer (BC) by menopausal status and hormone receptor expression in tumors. ' Objective: We investigated the relation between total dietary fiber and its main food sources (vegetables, fruit, cereals, and legumes) and BC risk by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Design: A total of 11,576 invasive BC cases in 334,849 EPIC women mostly aged 35-70 y at baseline were identified over a median follow-up of 11.5 y. Dietary fiber was estimated from country-specific dietary questionnaires. Multivariable Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk with energy adjustment by using the residual method. Subgroup analyses were performed by menopausal status and estrogen receptor (ER) and progesterone receptor (PR) expression in tumors. Results: BC risk was inversely associated with intakes of total dietary fiber [hazard ratio comparing fifth quintile to first quintile (HRQ5-Q1): 0.95; 95% CI: 0.89, 1.01; P-trend = 0.03] and fiber from vegetables (0.90; 0.84, 0.96; P-trend < 0.01) but not with fiber from fruit, cereals, or legumes. Overall, associations were homogeneous by menopausal status and ER and PR expression in tumors. For vegetable fiber, stronger associations were observed for estrogen receptor-negative and progesterone receptor-negative (HRQ5-Q1: 0.74; 95% CI: 0.59, 0.93; P-trend = 0.01) than for estrogen receptor-positive and progesterone receptor-positive tumors (0.92: 0.81, 1.03; P-trend = 0.05), with P-heterogeneity = 0.09. Conclusion: Diets rich in dietary fiber and, particularly, fiber from vegetables may be associated with a small reduction in risk of BC, independently of menopausal status. 

  • 281.
    Forsberg, Karl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Reasons for hospitalisation and decision to give intravenous fluids during end of life for patients with dementia2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 282. Fossa, Sophie D.
    et al.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Klepp, Olbjørn Harald
    Wiklund, Fredrik
    Angelsen, Anders
    Damber, Jan-Erik
    Ten-and 15-year prostate cancer-specific survival in patients with nonmetastatic high-risk prostate cancer randomized to lifelong hormone treatment alone or combined with radiotherapy (SPCG VII)2014In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, no 4Article in journal (Other academic)
    Abstract [en]

    Background: After a median observation time of 7.6 years, Scandinavian Prostate Cancer Group VII randomized trial showed a significant 12% reduction of prostate cancer-specific mortality in patients with locally advanced or histologically aggressive prostate cancer who received three months of total androgen blockade followed by radiotherapy and continuous antiandrogen therapy compared to patients with hormonal treatment only (Widmark et al :Lancet [2009]; 373,1174). Here we provide the 10 (15)-year survival results after a median observation time of 10.7 years. Methods: Between February 1996 and December 2002, 875 patients with locally advanced prostate cancer were randomized (Randomization ratio 1:1). Primary endpoint was prostate cancer-specific survival analyzed by intention to treat. This updated analysis is based on death registry data of the Norwegian patients (2/3 of the population), and on data recorded in CRF database available for the Swedish patients. A Swedish death registry analysis is underway, and will be included in the final analysis at the meeting. Results: Prostate cancer death occurred in 118 out of 439 of the antiandrogen treatment group and in 45 out of 436 men in the combination treatment group (p< 0.0001), with death due to any cause in 210 out of 439 and 161 out of 436 men (p=0.0006), respectively. The 10 (15) year cumulative prostate cancer-specific mortality was more than halved after combined treatment: 18.9% (30.7%) and 8.3% (12.4%) (HR=0.35;[p<4.1E-10 for 15 year results]), and overall mortality was 35.3% (56.7%) and 26.4% (43.4%) (HR=0.70; P=0.0006 for 15 year results), respectively. Conclusions: Addition of local radiotherapy to hormonal treatment in patients with non-metastatic locally advanced or high-risk prostate cancer more than halved the 10 and 15 year prostate cancer-specific mortality and substantially decreased overall mortality.

  • 283. Fossa, Sophie D.
    et al.
    Wiklund, Fredrik
    Klepp, Olbjorn
    Angelsen, Anders
    Solberg, Arne
    Dumber, Jan-Erik
    Hoyer, Morten
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ten- and 15-yr Prostate Cancer-specific Mortality in Patients with Nonmetastatic Locally Advanced or Aggressive Intermediate Prostate Cancer, Randomized to Lifelong Endocrine Treatment Alone or Combined with Radiotherapy: Final Results of The Scandinavian Prostate Cancer Group-72016In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, no 4, p. 684-691Article in journal (Refereed)
    Abstract [en]

    Background: In high-risk prostate cancer (PCa), no study with observation times beyond 10 yr has demonstrated survival improvement after addition of prostatic radiotherapy (RAD) to endocrine treatment (ET) alone. Objective: To compare mortality rates in patients receiving ET alone versus ET + RAD. Design, settings, and participants: From 1996 to 2002, 875 Scandinavian patients with high-risk (90%) or intermediate PCa were randomized to ET or ET + RAD (The Scandinavian Prostate Cancer Group-7). After 3 mo with total androgen blockade in all patients, all individuals continued lifelong antiandrogen monotherapy. Those randomized to ET + RAD started prostate radiotherapy (70 Gy) at 3 mo. Outcome, measurements and statistical analysis: PCa-specific 15-yr mortality represented the primary endpoint. Assessment of the combination treatment effect and prognostic factors was performed in competing risk analyses and Cox proportional-hazard models. Intervention: RAD added to ET. Results and limitations: With a median observation time of 12 yr, the 15-yr PCa-specific mortality rates were 34% (95% confidence interval, 29-39%) and 17% (95% confidence interval, 13-22%) in the ET and ET + RAD arms respectively (p < 0.001). Compared with the ET arm, the median overall survival in the ET + RAD arm was prolonged by 2.4 yr. Treatment with ET alone, age >= 65 yr and increasing histology grade independently increased the risk of PCa-specific and overall mortality. Limitations include nonformal evaluation of comorbidity, the inability to calculate progression-free survival, and lack of information about salvage therapy and toxicity. Conclusions: In patients with nonmetastatic locally advanced or aggressive PCa, ET + RAD reduces the absolute risk of PCa-specific death by 17% at 15 yr compared with ET alone; the comparable 15-yr PCa-specific mortality rates being 17% and 34%. The results warrant a phase 3 study comparing ET + RAD with radical prostatectomy in high-risk PCa. Patient summary: Adding prostatic therapy to lifelong antiandrogen therapy halves the absolute risk of death from prostate cancer from 34% to 17% 15 yr after diagnosis. 

  • 284.
    Fowler, Christopher J
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Gustafsson, Sofia B
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Chung, Sui Chu
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Persson, Emma
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jacobsson, Stig O P
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Targeting the endocannabinoid system for the treatment of cancer: a practical view2010In: Current Topics in Medicinal Chemistry, ISSN 1568-0266, E-ISSN 1873-4294, Vol. 10, no 8, p. 814-827Article, review/survey (Refereed)
    Abstract [en]

    In recent years, considerable interest has been generated by findings that cannabinoids not only have useful palliative effects, but also can affect the viability and invasivity of a variety of different cancer cells. In the present review, the potential of targeting the cannabinoid system for the treatment of cancer is considered from a practical, rather than a mechanistic viewpoint, addressing questions such as whether human tumour cells express CB receptors; whether the potencies of action of cannabinoids in vitro match the potencies expected on the base of receptor theory; what is known about the in vivo effects of cannabinoids and cancer, and how relevant the experiments undertaken are to the clinical situation; and finally, what approaches can be taken to minimise unwanted effects of cannabinoid treatment. It is concluded that cannabinoids (or agents modulating the endogenous cannabinoid system) are an attractive target for drug development in the cancer area, but that more in vivo studies, particularly those investigating the potential of cannabinoids as an addition to current treatment strategies, are needed.

  • 285. Franceschi, Silvia
    et al.
    Lise, Mauro
    Trépo, Christian
    Berthillon, Pascale
    Chuang, Shu-Chun
    Nieters, Alexandra
    Travis, Ruth C
    Vermeulen, Roel
    Overvad, Kim
    Tjønneland, Anne
    Olsen, Anja
    Bergmann, Manuela M
    Boeing, Heiner
    Kaaks, Rudolf
    Becker, Nikolaus
    Trichopoulou, Antonia
    Lagiou, Pagona
    Bamia, Christina
    Palli, Domenico
    Sieri, Sabina
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    Bueno-de-Mesquita, Bas
    Peeters, Petra HM
    Rodríguez, Laudina
    Barroso, Leila Luján
    Dorronsoro, Miren
    Sánchez, María-José
    Navarro, Carmen
    Barricarte, Aurelio
    Regnér, Sara
    Borgquist, Signe
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Wareham, Nick
    Rinaldi, Sabina
    Hainaut, Pierre
    Riboli, Elio
    Vineis, Paolo
    Infection with hepatitis B and C viruses and risk of lymphoid malignancies in the European Prospective Investigation into Cancer and Nutrition (EPIC)2011In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, no 1, p. 208-214Article in journal (Refereed)
    Abstract [en]

    Chronic HBV infection may increase the risk of lymphoid malignancies among healthy European volunteers. Impact: Treatment directed at control of HBV infection should be evaluated in HBsAg-seropositive patients with lymphoid tissue malignancies. Cancer Epidemiol Biomarkers Prev; 20(1); 208-14. ©2011 AACR.

  • 286.
    Fransson, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Patient-reported lower urinary tract symptoms, urinary incontinence, and quality of life after external beam radiotherapy for localized prostate cancer - 15 years' follow-up. A comparison with age-matched controls2008In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 47, p. 852-861Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To prospectively examine the urinary toxicity and quality of life (QOL) in patients 15 years after external beam radiotherapy (EBRT) for localized prostate cancer (LPC) and compare the outcomes with results for age-matched controls.

    MATERIAL AND METHODS: Urinary symptoms were assessed using the symptom-specific Prostate Cancer Symptom Scale (PCSS) questionnaire, and QOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC)'s Quality of Life Questionnaire (QLQ-C30). Both questionnaires were sent to the surviving 41 patients(25%) and the PCSS questionnaire was sent to 69 age-matched controls for comparison.

    RESULTS: The response rate was 71% in the patient group and 59% in the control group. Two patients and four controls were excluded due to other cancer diagnoses, resulting in a total of 27 patients and 37 controls for inclusion in the analyses. The mean age in both groups was 78 years. In the patient group, incontinence had increased between the 8-year (mean 0.6) and the 15-year follow-up (mean 2.1; p0.038). No other differences in urinary problems were seen between these two follow-ups. Increased incontinence, stress incontinence, and pain while urinating were reported by the patients in comparison with the controls at 15 years. Role function was worse in the patient group (mean 67.3) compared with the controls (mean 82.4; p0.046). The patients also reported more appetite loss, diarrhea, nausea/vomiting, and pain than the controls.

    CONCLUSION: EBRT for LPC has divergent effects on urinary symptoms and QOL in comparison with age-matched controls. In our patient population, urinary incontinence increased between 8 and 15 years of follow-up. Otherwise, no differences in urinary symptoms were seen between 4 and 15 years. Incontinence, stress incontinence, and pain while urinating were increased after EBRT in comparison with the controls. Conventional EBRT did not result in a major deterioration in QOL 15 years after treatment.

  • 287.
    Fransson, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Quality of life and side effects in patients with localized prostate cancer: evaluation with self-assessment questionnaires2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Localized prostate cancer (LPC) is predominantly a tumor among older men, and few patients will get symptoms from the disease. All methods to treat LPC with a curative intent have different types and degrees of side effects. It is therefore very important to evaluate the side effects thoroughly to make sure that treatment complications will not decrease the quality of life more than the disease would have done. In search for new and better treatments, complications has to be registered and evaluated in relation to quality of life (QOL) for the patients. Few validated self-assessment questionnaires for evaluation of external radiotherapy (EBRT) induced side effects has yet been developed. The present project focus on the development of the PC-specific questionnaire, QUFW94, and evaluation of symptoms in patients treated with EBRT and un-treated (watchful waiting) patients with a LPC.

    In the newly developed LPC-specific questionnaire a reliability and responsiveness test was performed. Both the inter-rater test and the test-retest show high correlation coefficients (ICC), above 0.60 for all scales. The internal reliability exceeded the lower acceptable limit (Cronbach a >0.70). The questionnaire was proven to be valid for the evaluations of EBRT side effects in LPC patients.

    Late side effects were evaluated 4 years after treatment in 181 LPC patients, treated with conventional large field EBRT, and compared with 141 age-matched PC disease free men. The most prominent urinary side effects were urgency and leakage which were doubled in the patient group. A ten fold increase was seen in comparison to controls at the most prominent intestinal problems, blood, mucus and leakage. The results support the use 3-D conformai therapy to decrease irradiation dose to the rectum and the bladder and thereby decreased side effects. A prospective additional evaluation 8 years after EBRT did not show any changes in urinary problems between 4 and 8-yr follow-up in the patients or the controls.

    EBRT of LPC is also accompanied by disturbances in sexual function. These problems were therefore evaluated, 4 years after EBRT, in relation to the function in PC free men. Patients treated with EBRT indicated higher levels of sexual dysfunction than age-matched controls. No erection was reported from 12% of the control subjects, 56% of the patients who had only received radiotherapy (RT) and 87% of the RT+castration (RT+A) patients. The extended evaluation 8 years after EBRT show similar sexual function in all groups.

    QOL and late side effects/symptoms were evaluated in the first and only randomized trial between RT and deferred treatment (DT) and compared to age-matched controls. QOL was evaluated with the general QOL formula, EORTC's QLQ-C30 (+3), and LPC specific side effects with QUFW94 in 108 randomized patients with LPC 3 years after diagnosis. Social functioning was the only QOL scale where a significant difference was found between the two patient groups and in comparison with the control group. Multivariate regression analysis showed that hematuria, incontinence, mucus, and planning of the daily activities due to intestinal problems caused this decrease in QOL in the RT group. In conclusion, the LPC specific QUFW94 questionnaire was proven to be valid for evaluation of side effects and showed increased intestinal problems in the patients treated with conventional large field EBRT in comparison to untreated LPC patients. No difference in urinary and intestinal late side effects or sexual function was seen between a 4 year vs. 8 year follow-up.

  • 288.
    Fransson, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Nursing.
    Quality of life for members of Swedish Prostate Cancer Patient Associations2008In: Cancer Nursing, ISSN 0162-220X, E-ISSN 1538-9804, Vol. 31, no 1, p. 23-31Article in journal (Refereed)
    Abstract [en]

    Prostate Cancer Patient Associations (PCPAs) have become common. The aim of this study was to evaluate the quality of life of patients belonging to PCPAs. Members of 10 PCPAs in Sweden with prostate cancer completed 2 quality of life questionnaires (Quality-of-Life Questionnaire [QLQ-C30] and Prostate Cancer Symptom Scale). Of 2,028 members, 1,301 (64%) responded to the survey. Sixty percent of the members felt "healthy," and 38% were "free from the cancer." Ninety-five percent scored >80 on the physical function scale compared with 44% on the overall quality of life/health scale. The most severe symptom was sleeping disturbances (mean = 29). Seventeen percent scored "Quite a bit/Much" tiredness. More than 50% did not report any bladder or bowel problems. Fifty percent had "Much" sexual problems, and almost 80% did not have sufficient erection. Those reported as being "disease free" scored higher on the functioning scales than those with "metastatic disease." Those with an experience of a "metastatic disease" had more symptoms than those with less advanced disease. This is the first descriptive study of quality of life in members of Swedish PCPAs with prostate cancer. These findings show that it is possible to gain valid data to further study the situation of patients living with prostate cancer by collecting data from PCPAs.

  • 289.
    Fransson, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Nursing.
    Recall of pretreatment symptoms among men treated with radiotherapy for prostate cancer2005In: Acta Oncology, ISSN 0284-186X, Vol. 44, no 4, p. 355-361Article in journal (Refereed)
  • 290.
    Fransson, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergström, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Löfroth, Per-Olov
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Five-year prospective patient evaluation of bladder and bowel symptoms after dose-escalated radiotherapy for prostate cancer with the Beamcath (R) technique2006In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 66, no 2, p. 430-438Article in journal (Refereed)
    Abstract [en]

    Purpose: Late side effects were prospectively evaluated up to 5 years after dose-escalated external beam radiotherapy (EBRT) and were compared with a previously treated series with conventional conformal technique.

    Methods and Materials: Bladder and bowel symptoms were prospectively evaluated with the Prostate Cancer Symptom Scale (PCSS) questionnaire up to 5 years posttreatment. In all, 257 patients completed the questionnaire 5 years posttreatment. A total of 168 patients were treated with the conformal technique at doses <71 Gy, and 195 were treated with the dose-escalated stereotactic BeamCath® technique comprising three dose levels: 74 Gy (n = 68), 76 Gy (n = 74), and 78 Gy (n = 53).

    Results: For all dose groups analyzed together, 5 years after treatment, urinary starting problems decreased and urinary incontinence increased in comparison to baseline values. No increase in other bladder symptoms or frequency was detected. When comparing dose groups after 5 years, both the 74-Gy and 78-Gy groups reported increased urinary starting problems compared with patients given the conventional dose (<71 Gy). No increased incontinence was seen in the 76-Gy or the 78-Gy groups. Bowel symptoms were slightly increased during the follow-up period in comparison to baseline. Dose escalation with stereotactic EBRT (74–78 Gy) did not increase gastrointestinal late side effects after 5 years in comparison to doses <71 Gy.

    Conclusion: Dose-escalated EBRT with the BeamCath® technique with doses up to 78 Gy is tolerable, and the toxicity profile is similar to that observed with conventional doses <71 Gy.

  • 291.
    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.

  • 292.
    Fransson, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Damber, Jan-Erik
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Health-related quality of life 10 years after external beam radiotherapy or watchful waiting in patients with localized prostate cancer2009In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 43, no 2, p. 119-126Article in journal (Refereed)
    Abstract [en]

    Objective. To evaluate long-term randomized comparisons of patient-reported outcome of symptoms and health-related quality of life (HRQoL) in men with localized prostate cancer 10 years after external beam radiotherapy (RT) or watchful waiting (WW). Material and methods. Three-year HRQoL and specific symptoms in surviving patients recruited between 1986 and 1996 were previously evaluated in a randomized trial; definitive RT versus WW. Two questionnaires were used: the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the Prostate Cancer Symptom Scale (PCSS). The present study is a prolonged follow-up with the same cohorts. Results. Fifty-four of 72 eligible patients (75%) returned the questionnaires at the present follow-up. The median age was 77 years in the RT group and 78 years in the WW group. The median follow-up time from randomization was 10 years. No differences in HRQoL or bowel symptoms were measured between the RT and WW. Cognitive (RT) and physical function (WW) decreased between 4 years and 10years. Weak urinary stream differed between the RT and WW groups. Fatigue and nocturia were increased in the RT group, and erections decreased in the WW patients over time. No difference in erectile function was seen between the RT and WW groups (p=0.292). Conclusion. The pattern of urinary and bowel symptoms and sexual function was rather similar, independent of RT or WW. Treatment with RT had minimal influence on HRQoL, in comparison with that of WW, at 10-year follow-up.

  • 293.
    Fransson, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lund, Jo-Asmund
    Damber, Jan-Erik
    Klepp, Olbjörn
    Wiklund, Fredrik
    Fosså, Sophie
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Quality of life in patients with locally advanced prostate cancer given endocrine treatment with or without radiotherapy: 4-year follow-up of SPCG-7/SFUO-3, an open-label, randomised, phase III trial.2009In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 10, no 4, p. 370-380Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Androgen treatment for prostate cancer can adversely affect functional domains of quality of life. We aimed to assess quality of life in men with locally advanced prostate cancer in an open-label phase III randomised comparison between lifelong endocrine treatment with and without radiotherapy.

    METHODS: We obtained quality-of-life information from 872 (99%) of 875 eligible men with locally advanced prostate cancer (T3; 78%) who were randomly assigned, between 1996 and 2002, to 3 months of total androgen blockade followed by continuous endocrine treatment (439 patients) or the same hormonal treatment with radiotherapy 3 months after randomisation (436 patients). Prospective outcomes included patient-reported symptoms and quality of life assessed with questionnaires from baseline to 4 years after randomisation. Analysis was by intention to treat. This study is registered as an international standard randomised controlled trial, number ISRCTN01534787.

    FINDINGS: 438 of 439 men assigned endocrine treatment and 434 of 436 assigned endocrine plus radiotherapy completed at least one questionnaire. Missing data at baseline and during follow-up was equally distributed between groups. At 4 years, 64 (18%) of 353 patients on combined therapy and 39 (12%) of 337 on endocrine-alone therapy had moderate to severe urinary bother (p=0.005), and 16 (4%) of 355 on combined therapy and five (2%) of 338 on endocrine treatment alone had pain while urinating (p=0.024). 37 (11%) of 350 in the combined group and 23 (7%) of 35 in the endocrine-only group had overall bother from all bowel symptoms (p=0.022). 281 (85%) of 332 in the combined-treatment group and 227 (72%) of 313 in the endocrine-only group had erectile dysfunction (p=0.0002). Quality of life at 4 years was similar, with the exception of decreased social function in patients receiving endocrine treatment plus radiotherapy.

    INTERPRETATION: Although addition of radiotherapy to endocrine treatment significantly increased some treatment-related symptoms, none were serious. Given the substantial survival benefit of combined treatment, the increase of symptoms seems acceptable and has little extra effect on quality of life after 4 years compared with endocrine treatment alone.

  • 294.
    Fransson, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Olofsson, Sebastian
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Patient-reported gastrointestinal and genitourinary toxicity after prostate cancer treatment: A comparison between radiotherapy including pelvic nodes and prostate-only radiotherapy2015In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 7 SArticle in journal (Other academic)
    Abstract [en]

    Background: To evaluate side effects of radiotherapy (RT) including the pelvic nodes in patients with prostate cancer. Methods: 143 patients with high risk prostate cancer (Pca) receiving whole pelvic radiotherapy (WPRT) was matched to a group of 142 patients receiving RT towards the prostate and seminal vesicles only (PORT). Both groups were given 78 Gy towards the prostate and 50 Gy towards the seminal vesicles. The WPRT group also received 50 Gy towards the pelvic nodes. WPRT was given with intensity modulated RT or volumetric modulated arc therapy technique and the group treated towards the prostate and seminal vesicles only was treated with 3-dimensional conformal RT. Gastrointestinal (GI) and genitourinary (GU) side effects were evaluated with patient-reported questionnaires and with the RTOG scale, scored by treating physician, at baseline and one-year after RT. Results: Overall the side effects were mild. At one-year follow up there were significant differences regarding morning urgency, mucus- and blood in stool between the two groups (Table 1). The WPRT group expressed lesser complications in all of these cases. In the RTOG GU and GI scores there were no differences between the groups. About 20% had RTOG grade 2 GU score and 2%/1% had RTOG grade 3 score in the PORT and WPRT groups, respectively. The numbers for RTOG grade 2 GI scores were 11% and 5% in the PORT and WPRT groups, respectively. None of the groups reported RTOG grade 3 GI symptoms. Conclusions: Whole pelvic RT can be done with a very satisfying profile of side effects. Sometimes even lesser gastrointestinal reported side effects are seen with the newer techniques compared to prostate only radiotherapy with older techniques.

  • 295.
    Fransson, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Reliability and responsiveness of a prostate cancer questionnaire for radiotherapy-induced side effects2001In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 9, no 3, p. 187-198Article in journal (Refereed)
    Abstract [en]

    Few self-assessment cancer-specific questionnaires / modules have yet been developed for radiotherapy-induced side effects. The aim of the present study was to test the reliability and responsiveness of a prostate cancer (PC)specific questionnaire. Thirty-one patients with PC graded their urinary and intestinal symptoms and their sexual function on the questionnaire. A doctor and a nurse performed a structured interview and graded the patient's symptoms with the same questions. The procedure was performed at both the start and the end of the treatment. A high concordance regarding symptom detection was seen between the patient, nurse and the doctor. The inter-rater test shows intraclass correlation coefficient (ICC) values above 0.60 in all scales. The internal reliability exceeded the lower limit (Cronbach alpha > 0.70) for all scales. The test-retest gave acceptable reliability for all scales (ICC greater than or equal to 0.60). All scales indicated increased problems during radiotherapy. The questionnaire was proven to be valid for the evaluations of urinary and intestinal problems and for sexual function in PC patients.

  • 296.
    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.
    15-year prospective follow-up of patient-reported outcomes of late bowel toxicity after external beam radiotherapy for localized prostate cancer. A comparison with age-matched controls2007In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 46, no 4, p. 517-524Article in journal (Refereed)
    Abstract [en]

    We have previously described patient-reported outcomes of late side effects induced by conventional external beam radiotherapy (EBRT), 4 and 8 years after treatment, in 181 patients with localized prostate cancer compared with 141 age-matched controls. In the present study, we compare bowel side effects 15 years after EBRT with the same controls, and with the results of our previous 4-year and 8-year follow-ups. Of the 181 patients and 141 controls at the 4-year follow-up, 45 patients (25%) and 79 controls (56%) were still alive at the 15-year follow-up. Bowel symptoms were assessed using the symptom-specific questionnaire Prostate Cancer Symptom Scale (PCSS), which was sent to these 45 patients and 79 age-matched controls with a mean follow-up time of 15 years (162–197 months) after EBRT. The answer frequency was 64% in the patient group and 52% in the control group. The mean age was 78 years in both groups. At the 15-year follow-up, 39% of the patients and 84% of the controls reported no bowel problems (p <0.001), while 16% of the patients and 0% of the controls reported “Quite a few/many” problems with mucus in the stools (p <0.001). “Quite a bit/much” stool leakage was reported by 20% of the patients at the 15-year follow-up, in comparison to 4% of the patients at the 4-year follow-up (ns). The proportion of patients reporting late bowel symptoms was unchanged 15 years after EBRT in comparison to the 4-year follow-up. Increased bowel symptoms were seen in patients in comparison to the age-matched controls.

  • 297.
    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.
    Does one have a sexual life 15 years after external beam radiotherapy for prostate cancer? Prospective patient-reported outcome of sexual function comparison with age-matched controls2011In: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 29, no 2, p. 137-144Article in journal (Refereed)
    Abstract [en]

    Background and purpose: We previously published research on 4- and 8-year follow-ups of patient-reported sexual function after conventional external beam radiotherapy (EBRT) for localized prostate cancer (LPC) compared with age-matched controls. The current study is a prolonged 15-year follow-up with the same cohorts.

    Material and methods: The cohort consisted of 29 men surviving from a group of 181 men treated between 1986 and 1989, and who were reported on previously. Of the originally reported 141 controls, 62 were eligible and 34 completed the questionnaires. Sexual function was assessed using two questionnaires, Prostate Cancer Symptom Scale (PCSS) and International Index of Erectile Function (IIEF-5).

    Results: Twenty-three patients (78%) and 13 controls (38%) were not sexually active. None of the patients and 14 controls had enough of an erection to perform intercourse. Seventeen patients (94%) and 14 controls (64%) had severe erectile dysfunction. Patients with clinical progression and who had received hormone treatment had decreased sexual desire. No significant differences were measured between patients without progression/hormone treatment and the controls.

    Conclusion: The sexual activity 15 years after EBRT for LPC was very low, as was the probability of achieving an erection. Patients with a progressive disease and treated with hormones reported worse sexual and erectile function. The LPC free men showed higher sexual activity, lower sexual bother, and better erectile function than the patients.

  • 298.
    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.

  • 299.
    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.

  • 300.
    Franzen, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sartor, O.
    Parker, C.
    Garcia-Vargas, J.
    Nilsson, S.
    Long-term safety and real world clinical experience of radium-223 dichloride (Ra-223) in patients (pts) with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases (mets) from the phase 3 ALSYMPCA study2014In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 41, no suppl 2, p. S271-S271, article id OP506Article in journal (Other academic)
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