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  • 1.
    Abdulla, Maysaa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Laszlo, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Triumf, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Hedström, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Berglund, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Biosci & Nutr, Novum, Huddinge, Sweden..
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Amini, Rose-Marie
    Uppsala Univ, Dept Immunol Genet & Pathol, Unit Pathol, Uppsala, Sweden.;Univ Uppsala Hosp, S-75185 Uppsala, Sweden..
    A population-based study of cellular markers in R-CHOP treated diffuse large B-cell lymphoma patients2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 9-10, p. 1126-1131Article in journal (Refereed)
    Abstract [en]

    Aim: To determine the prognostic significance of co-expression of MYC, BCL-2 and BCL-6 proteins in combination with other biomarkers and clinical characteristics within a population-based cohort of diffuse large B-cell lymphoma (DLBCL) patients uniformly treated with R-CHOP.

    Patients and methods: The immunohistochemical (IHC) expression of CD10, BCL-2, BCL-6, MUM1, MYC, CD5, CD30, Ki-67 and p53 was evaluated in a retrospective, population-based study comprising 188 DLBCL patients treated with R-CHOP and diagnosed in Sweden between 2002 and 2012.

    Results: Patients had a median age at diagnosis of 64 years (26-85 years) with a male:female ratio of 1.4:1. Approximately half (52%) of the patients presented with an International Prognostic Index (IPI) age adjusted (IPIaa)2. Median follow-up time was 51 months (range 0.4-158) and the five-year lymphoma-specific survival (LSS) was 76%, five-year overall survival (OS) was 65% and five-year progression-free survival (PFS) was 61%. A high Ki-67 value was found in 59% of patients, while p53 overexpression was detected in 12% of patients and MYC, BCL-2 and BCL-6 expression were detected in 42%, 55% and 74% of patients, respectively. IPIaa2 (p=0.002), Ki-6770% (p=0.04) and p53 overexpression50% (p=0.02) were associated with inferior LSS and OS. Co-expression of both MYC (>40%) and BCL-2 (>70%) proteins was detected in 27% of patients and correlated with a significantly inferior LSS (p=0.0002), OS (p=0.009) and PFS (p=0.03). In addition, triple expression of MYC, BCL-2 and BCL-6, also correlated with a significantly inferior LSS (p=0.02).

    Conclusion: Concurrent expression of MYC and BCL-2 proteins, as detected by IHC, was strongly associated with an inferior survival in DLBCL patients treated with R-CHOP. Other markers affecting survival were triple expression of MYC, BCL-2 and BCL-6, IPIaa, high Ki-67 and p53 overexpression.

  • 2.
    Abdulla, Maysaa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Univ Uppsala Hosp, S-75185 Uppsala, Sweden..
    Laszlo, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Univ Uppsala Hosp, S-75185 Uppsala, Sweden..
    Triumf, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Univ Uppsala Hosp, S-75185 Uppsala, Sweden..
    Hedström, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Univ Uppsala Hosp, S-75185 Uppsala, Sweden..
    Berglund, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Univ Uppsala Hosp, S-75185 Uppsala, Sweden.;Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden..
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Univ Uppsala Hosp, S-75185 Uppsala, Sweden..
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Univ Uppsala Hosp, S-75185 Uppsala, Sweden..
    Core needle biopsies for the diagnosis of diffuse large B-cell lymphoma - a great concern for research2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 1, p. 106-109Article in journal (Refereed)
  • 3.
    Ahlin, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Gruhne, Bettina
    Holmqvist, Marit
    Zetterberg, Anders
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Aberrant expression of cyclin E in low-risk node negative breast cancer2008In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 47, no 8, p. 1539-1545Article in journal (Refereed)
    Abstract [en]

    Background. Cyclin E is a cell cycle regulatory protein which occurs in G1, peaks in late G1 and is degraded in early S-phase. Cyclin E overexpression appears to be an independent prognostic factor for overall survival in breast cancer. Material and Methods. Nuclear cyclin A is a reliable marker for S-and G2-phases. Consequently, aberrant expression of cyclin E can be detected by simultaneous immunostainings for cyclin A and cyclin E. Studies have shown that aberrant cyclin E might provide additional prognostic information compared to that of cyclin E alone. This study aimed to investigate cyclin E and aberrant cyclin E expression in low-risk node negative breast cancer. We compared women that died from their breast cancer (n=17) with women free from relapse>8 years after initial diagnosis (n=24). All women had stage I, low risk breast cancer. The groups were matched regarding tumour size, receptor status, adjuvant chemotherapy and tumour differentiation. Tumour samples were analysed regarding expression of cyclin A, cyclin E and double-stained tumour cells using immunoflourescence staining and digital microscopy. Results. No differences were seen regarding expression of cyclin E or aberrant cyclin E in cases compared to controls. Discussion. We conclude that neither cyclin E nor aberrant cyclin E is a prognostic factor in low-risk node negative breast cancer patients.

  • 4.
    Ahlström, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Carlsson, L
    Hedin, A
    Lörelius, L-E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    An experimental model for pharmacokinetic studies of monoclonal antibodies in human colonic cancer1987In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 26, no 6, p. 447-451Article in journal (Refereed)
    Abstract [en]

    An experimental model consisting of athymic rats carrying human colonic tumours from cell line LS 174T in both hind legs was used. 125I-labelled anti-carcinoembryonic antigen (anti-CEA) monoclonal antibodies were injected intra-arterially (i.a.), either alone (21 rats) or together with degradable starch microspheres (6 rats). As a control, an irrelevant antibody was injected i.a., alone (6 rats) or together with microspheres (3 rats). An intra-arterial injection was given on the side bearing one tumour in each rat, while the contralateral tumour served as an 'intravenous' control. The rats were submitted to external gamma measurements daily for four days. On the fourth day they were killed and pieces from the tumours and from various organs were examined by in vitro measurements. The results indicate strong expression of CEA in LS 174T cells grafted to athymic rats. No lasting enhancement of the tumour uptake was achieved by intra-arterial injection of antibodies as compared with the control tumours.

  • 5.
    Ahlström, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Carlsson, L
    Hedin, A
    Lörelius, L-E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Enhanced uptake of intra-arterially injected anti-CEA monoclonal antibodies in human colonic cancer after mannitol infusion in an experimental model1987In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 26, no 6, p. 453-458Article in journal (Refereed)
    Abstract [en]

    In a previous report athymic rats carrying transplanted human colonic tumours from cell line LS 174T in both hind legs were injected intra-arterially (i.a.) with 125I-labelled anti-carcinoembryonic (anti-CEA) monoclonal antibodies. The i.a. injection was given on one side bearing a tumour in each rat, while the contralateral tumour served as an 'intravenous' control. In the same experimental model and treated in the same way, 10 rats were injected i.a. with anti-CEA monoclonal antibodies after an i.a. mannitol infusion. In both groups of rats external gamma measurements were performed daily for four days. On the fourth day the rats were killed and pieces of the tumours and of various organs were weighed and the activity was determined with a gamma-counter. The tumour uptake of antibodies was significantly enhanced after mannitol infusion.

  • 6.
    Ahlström, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Andersson, A
    Lörelius, L-E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    The spatial distribution of parenterally administered monoclonal antibodies against CEA in a human colorectal tumour xenograft1989In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 28, no 1, p. 81-86Article in journal (Refereed)
    Abstract [en]

    A recently developed experimental model consisting of athymic rats carrying human colonic tumours from the cell line LS 174 T in both hind legs was used. 125I-labelled anti-carcinoembryonic (anti-CEA) monoclonal antibodies were injected either intra-arterially after a bolus injection of mannitol, or intra-peritoneally with or without mannitol. On the fourth day the rats were killed and pieces from the tumours and various organs were measured in a well scintillation counter. Tumour pieces were then submitted to autoradiography and immunohistochemistry for examination of the antibody distribution at the cellular level. In all examined tumours injected with anti-CEA antibodies, most of the antibodies were located in the periphery close to fibrovascular septa. It appears, in addition to the specificity of the antibody for the CEA, that the tumour vascular permeability and anatomy are of utmost importance for tumour targeting in this experimental model with the particular antibody used.

  • 7. Arbman, Gunnar
    et al.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    The rise and fall of a longed for clinical trial in patients with generalized colorectal cancer2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 8, p. 1779-1782Article in journal (Refereed)
  • 8. Ask, Anders
    et al.
    Björk-Eriksson, Thomas
    Zackrisson, Björn
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The potential of proton beam radiation therapy in head and neck cancer2005In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, no 8, p. 876-80Article in journal (Refereed)
    Abstract [en]

    A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. In head and neck cancer, including thyroid cancer, it is assessed that at least 300 patients annually will gain sufficiently from proton beam therapy, both to improve tumour control and to decrease toxicity to compensate for the increased treatment costs using protons.

  • 9. Ask, Anders
    et al.
    Johansson, Bengt
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The potential of proton beam radiation therapy in gastrointestinal cancer2005In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, no 8, p. 896-903Article in journal (Refereed)
    Abstract [en]

    A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. In gastrointestinal cancers, it is assessed that at least 345 patients, mainly non-resectable rectal cancers, oesophageal and liver cancers, are eligible. Great uncertainties do however exist both in the number of patients with gastrointestinal cancers suitable for radiation therapy, and in the proportion of those where proton beams may give sufficiently better results.

  • 10. Asklund, Thomas
    et al.
    Malmstrom, Annika
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Bjor, Ove
    Henriksson, Roger
    Brain tumors in Sweden: Data from a population-based registry 1999-20122015In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 3, p. 377-384Article in journal (Refereed)
    Abstract [en]

    Background. The Swedish brain tumor registry has, since it was launched in 1999, provided significant amounts of data on histopathological diagnoses and on important aspects of surgical and medical management of these patients. The purpose is mainly quality control, but also as a resource for research. Methods. Three Swedish healthcare regions, constituting 40% of the Swedish population, have had an almost complete registration. The following parameters are registered: diagnosis according to SNOMED/WHO classification, symptoms, performance status, pre- and postoperative radiology, tumor size and localization, extent of surgery and occurrence of postoperative complications, postoperative treatment, such as radiotherapy and/or chemotherapy, other treatments, complications and toxicity, occurrence of reoperation/s, participation in clinical trials, multidisciplinary conferences and availability of a contact nurse. Results. Surgical radicality has been essentially constant, whereas the use of early (within 72 hours) postoperative CT and MRI has increased, especially for high-grade glioma, which is a reflection of quality of surgery. Survival of patients with high-grade glioma has increased, especially in the age group 60-69. Patients aged 18-39 years had a five-year survival of 40%. Waiting times for the pathological report has been slightly prolonged. Geographical differences do exist for some of the variables. Conclusion. Population-based registration is valuable for assessment of clinical management, which could have impact on patient care. As a result of short survival and/or the propensity to affect cognitive functions this patient group has considerable difficulties to make their voices heard in society. We therefore believe that a report like the present one can contribute to the spread of knowledge and increase the awareness for this patient group among caregivers and policy makers.

  • 11. Asklund, Thomas
    et al.
    Malmstrom, Annika
    Bjor, Ove
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Henriksson, Roger
    Considerable improvement in survival for patients aged 60-84 years with high grade malignant gliomas: Data from the Swedish Brain Tumour Population-based Registry2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 5, p. 1043-1046Article in journal (Refereed)
  • 12. Backman, Malin
    et al.
    Wengstrom, Yvonne
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sköldengen, Ida
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Hellersted Börjesson, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Tärnbro, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    A randomized pilot study with daily walking during adjuvant chemotherapy for patients with breast and colorectal cancer2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 4, p. 510-520Article in journal (Refereed)
    Abstract [en]

    Background. Physical activity during chemotherapy has been shown in several studies to reduce fatigue, improve symptoms and impact positively on health-related quality of life (HRQoL). Challenges associated with intervention studies on physical activity during cancer treatment relate to consistent adherence. The primary objective was to study feasibility and adherence of physical activity intervention among patients with cancer during adjuvant chemotherapy treatment. The secondary objective was to investigate the effects of physical activity on health aspects, including HRQoL, symptoms and surrogate markers for cardiovascular disease. Material and methods. This randomized controlled trial included patients with breast cancer (BRCA) and colorectal cancer (CRC) during adjuvant chemotherapy. The intervention continued for 10 weeks and included daily walks of 10 000 steps and a weekly supervised group walk. Adherence was assessed by a pedometer and the number of participants who reported step counts every week and percentage of participants who achieved the target steps every week. Results. Adherence average reached 91% during the intervention period; in total 74% completed the exercise intervention. The majority of the participants achieved an average of 83% of the target of 10 000 steps per day for 10 weeks. There was a significant increase in daily physical activity (p = 0.016) in the intervention group. Significant differences were also found for some breast cancer-specific symptoms [swelling, mobility and pain (p = 0.045)]. The study showed a relatively small weight gain an average of 0.9 kg in the intervention group and 1.3 kg in the control group. Conclusion. Physical activity in the form of walking is feasible during adjuvant chemotherapy treatment despite increasing symptoms. The physical activity increased in the intervention group during the study time and had a positive impact on breast symptoms and the weight gain was lower in comparison to previous studies.

  • 13. Barlow, Lotti
    et al.
    Westergren, Kerstin
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Talbäck, Mats
    The completeness of the Swedish Cancer Register: a sample survey for year 19982009In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 48, no 1, p. 27-33Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The Swedish Cancer Register (SCR) is used extensively for monitoring cancer incidence and survival and for research purposes. Completeness and reliability of cancer registration are thus of great importance for all types of use of the cancer register. The aim of the study was to estimate the overall coverage of malignant cancer cases in 1998 and to reveal possible reasons behind non-reporting. METHODS: We selected all malignant cancer cases in the Hospital Discharge Register (HDR) from 1998 and compared these records to those reported to the SCR. There were 43,761 discharges for 42,010 individuals of whom 3,429 individuals were not recorded in the SCR. From these 3 429 records we randomly selected 202 patients for review of their medical records to determine whether they should have been registered on the SCR as incident cases in 1998. RESULTS: About half of the 202 cases (93 malignant and 8 benign) should have been reported, which translates into an additional 1 579 malignant cases (95% CI 1 349-1 808), or 3.7% of the cases reported in 1998. The crude incidence rate for males and females combined would increase from 493 per 100,000 to 511 (95% CI 508-514) if these cases were taken into account. CONCLUSION: The overall completeness of the SCR is high and comparable to other high quality registers in Northern Europe. For most uses in epidemiological or public health surveillance, the underreporting will be without major impact. However, for specific research questions our findings have implications, as the degree of underreporting is site specific, increases with age, and does not seem to be random, as diagnoses without histology or cytology verification are overrepresented. An annual comparison of the SCR against the HDR could point to hospitals, geographic areas or specific diagnoses where organizational and administrative changes should be introduced to improve reporting.

  • 14.
    Berglund, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Petersson, Lena-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Eriksson, Karin C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Wallenius, Imke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Roshanai, Afsaneh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Nordin, Karin M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Sjödén, Per-Olow
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    "Between Men": A psychosocial rehabilitation programme for men with prostate cancer2007In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 46, no 1, p. 83-89Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate the effect of psychosocial rehabilitation on newly diagnosed prostate cancer patients. The “Between Men” programme consisted of seven weekly sessions of physical training (Phys) alone, information (Info) alone or physical training plus information (PhysInfo). After diagnoses, patients (n =211) were consecutively included, stratified and randomised to one of four groups: Phys, Info, PhysInfo or standard care control (C). A nurse specialised in urology, an urologist and a physiotherapist performed the interventions. Patients were followed up during one year with mailed standardised questionnaires. It could not be assumed that the “Between Men” programme had any effect on patients’ anxiety and depression (HADS). Health-related quality of life (HRQOL) was associated with stage of disease but not with psychosocial intervention. Thus, Physical Function (PF), Role Function (RF) and Fatigue (FA) were inferior among patients with, than without, metastases of prostate cancer both at baseline and at the 12-month follow-up. This randomized study did not demonstrate any significant effect of psychosocial rehabilitation among prostate cancer patients. Considering the low rate (1/2), of included/eligible patients a less complicated design (intervention versus control) would have been preferred in order to increase power.

  • 15.
    Berglund, Åke
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Willen, Linda
    Grodeberg, Lina
    Skattum, Lillemor
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Pauksens, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    The response to vaccination against influenza A(H1N1) 2009, seasonal influenza and Streptococcus pneumoniae in adult outpatients with ongoing treatment for cancer with and without rituximab2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 9, p. 1212-1220Article in journal (Refereed)
    Abstract [en]

    It is debated whether cancer patients treated with chemotherapy can mount an adequate response to vaccination. Material and methods. Ninety-six adult outpatients with cancer, who were undergoing chemotherapy and/or monoclonal antibody, tyrosine kinase inhibitor, irradiation or corticosteroid treatments, were studied. Two doses of the pandemic influenza A(H1N1)/09 AS03-adjuvanted split virion vaccine, one dose of the seasonal influenza vaccine and one dose of the 23-valent pneumococcal polysaccharide vaccine were given. Serum haemagglutination inhibition (HI) assays were used to determine antibody titres against the influenza strains. For the pneumococcal vaccine 14 different serotype-specific anti-capsular antibodies were measured by bead assay xMAP (R). Results. Patients treated with rituximab did not respond to vaccination. For patients without rituximab treatment 4% had putatively protective antibodies before vaccination (HI >= 40) to the pandemic-like strain A/California7/2009HINI. After the first and second dose of vaccine, seroprotection rates (SPR) were 62% and 87%, and seroconversion rates (SCR) 62% and 84%, respectively. Before seasonal flu vaccination SPR against influenza A/Brisbane/59/2007H1N1 and A/Uruguay/10/2007H3N2 were 19% and 17%, respectively. After vaccination, SPR were 70% and 59% and SCR 42% and 50%, respectively. For the pneumococcal vaccine protective antibodies were found to 40% of the 14 strains before and to 68% after vaccination. The mean response to pneumococcal vaccination was to 44% of the 14 serotypes. A response to at least 50% of the 14 serotypes was found in 49% of the patients. No serious adverse events were reported. Conclusion. A substantial number of adult cancer patients with ongoing chemotherapy treatment could mount an adequate serological response to influenza and pneumococcal vaccination without severe adverse events. Thus, vaccination should be recommended. Adjuvanted vaccines may improve the vaccine response among this patient group. Patients recently treated with rituximab do not respond to vaccination.

  • 16.
    Bergqvist, Michael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Umea Univ, Dept Radiat Sci, Umea, Sweden.
    Holgersson, Georg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Bondarenko, Igor
    Grechanaya, Elena
    Maximovich, Alexey
    Andor, György
    Klockare, Maria
    Thureson, Marcus
    Jerling, Markus
    Harmenberg, Johan
    Phase II randomized study of the IGF-1R pathway modulator AXL1717 compared to docetaxel in patients with previously treated, locally advanced or metastatic non-small cell lung cancer2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 3, p. 441-447Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The primary objective of this study was to compare the progression-free survival (PFS) at 12 weeks between patients treated with IGF-1R pathway modulator AXL1717 (AXL) and patients treated with docetaxel (DCT).

    MATERIAL AND METHODS: The study was conducted at 19 study centers in five countries. A total of 99 patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) of the squamous cell carcinoma (SCC) or adenocarcinoma (AC) subtypes in need of additional treatment were randomized and treated with either 300 or 400 mg of AXL as daily BID treatment (58 patients) or DCT given as 75 mg/m(2) in three-week cycles (41 patients) as monotherapy in a 3:2 ratio for each NSCLC subtype. Patients were treated in the primary study treatment period for a maximum of four treatment cycles.

    RESULTS: The 12-week PFS rate, median PFS and overall survival (OS), as well Kaplan-Meier hazard ratio for PFS and OS, did not show any statistically significant differences between the treatment groups. For the primary endpoint, the AXL group had a lower percentage of patients (25.9%) who were progression-free at Week 12 as compared to the DCT group (39.0%), although the difference was not statistically significant. The most notable difference in the incidence of treatment emergent adverse effects (TEAEs) was the lower incidence of treatment-related grade 3/4 neutropenia in patients treated with AXL.

    CONCLUSION: These results suggest neither of the treatments to be superior of the other when treating locally advanced or metastatic NSCLC. Considering the lower incidence of grade 3/4 neutropenia in the AXL group this treatment warrants further research.

  • 17.
    Berntsson, Shala
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Malmer, Beatrice
    Bondy, Melissa
    Qu, Mingqi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Tumor-associated epilepsy and glioma: are there common genetic pathways?2009In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 48, no 7, p. 955-963Article, review/survey (Refereed)
    Abstract [en]

    Background. Patients with glioma exhibit a great variability in clinical symptoms apart from variations in response to therapy and survival. Many patients present with epileptic seizures at disease onset, especially in case of low-grade gliomas, but not all have seizures. A large proportion of patients develop refractory seizures. It is likely that the variability in epileptic symptoms cannot exclusively be explained by tumor-related factors, but rather reflects complex interaction between tumor-related, environmental and hereditary factors. Material and methods. No data exist on susceptibility genes associated with epileptic symptoms in patients with glioma. However, an increasing number of candidate genes have been proposed for other focal epilepsies such as temporal lobe epilepsy. Some of the susceptibility candidate genes associated with focal epilepsy may contribute to epileptic symptoms also in patients with glioma. Results. This review presents an update on studies on genetic polymorphisms and focal epilepsy and brings forward putative candidate genes for tumor-associated epilepsy, based on the assumption that common etiological pathways may exist for glioma development and glioma-associated seizures. Conclusion. Genes involved in the immune response, in synaptic transmission and in cell cycle control are discussed that may play a role in the pathogenesis of tumor growth as well as epileptic symptoms in patients with gliomas.

  • 18.
    Birgisson, Helgi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Gunnarsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Late adverse effects of radiation therapy for rectal cancer: a systematic overview2007In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 46, no 4, p. 504-516Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The use of radiation therapy (RT) together with improvement in the surgical treatment of rectal cancer improves survival and reduces the risk for local recurrences. Despite these benefits, the adverse effects of radiation therapy limit its use. The aim of this review was to present a comprehensive overview of published studies on late adverse effects related to the RT for rectal cancer. METHODS: Meta-analyses, reviews, randomised clinical trials, cohort studies and case-control studies on late adverse effects, due to pre- or postoperative radiation therapy and chemo-radiotherapy for rectal cancer, were systematically searched. Most information was obtained from the randomised trials, especially those comparing preoperative short-course 5 x 5 Gy radiation therapy with surgery alone. RESULTS: The late adverse effects due to RT were bowel obstructions; bowel dysfunction presented as faecal incontinence to gas, loose or solid stools, evacuation problems or urgency; and sexual dysfunction. However, fewer late adverse effects were reported in recent studies, which generally used smaller irradiated volumes and better irradiation techniques; although, one study revealed an increased risk for secondary cancers in irradiated patients. CONCLUSIONS: These results stress the importance of careful patient selection for RT for rectal cancer. Improvements in the radiation technique should further be developed and the long-term follow-up of the randomised trials is the most important source of information on late adverse effects and should therefore be continued.

  • 19. Bjelkengren, Göran
    et al.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The potential of proton beam radiation therapy in lung cancer (including mesothelioma)2005In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, no 8, p. 881-3Article in journal (Refereed)
    Abstract [en]

    A Swedish group of oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. It is estimated that about 350 patients with lung cancer and about 20 patients with mesothelioma annually may benefit from proton beam therapy.

  • 20. Björk-Eriksson, Thomas
    et al.
    Ask, Anders
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The potential of proton beam radiation for palliation and reirradiation2005In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, no 8, p. 918-20Article in journal (Refereed)
    Abstract [en]

    A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. If an estimated 1% of the palliative treatments can be administered by protons with substantial benefits to the patient, almost 100 patients per year in Sweden would be eligible. It is further estimated that around 150 patients per year in need of reirradiation would benefit from radiation with protons compared to photons.

  • 21. Björk-Eriksson, Thomas
    et al.
    Bjelkengren, Göran
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The potentials of proton beam radiation therapy in malignant lymphoma, thymoma and sarcoma2005In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, no 8, p. 913-7Article in journal (Refereed)
    Abstract [en]

    A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. Besides sarcomas of the base of skull, which are classical sites for proton beam therapy, it is estimated that about 40 patients yearly in Sweden with sarcomas at other sites are candidates for proton beam therapy. About 20 patients each with malignant lymphomas, chiefly in the mediastinum, and thymomas are also candidates to decrease doses to surrounding heart and lungs.

  • 22. Björk-Eriksson, Thomas
    et al.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The potential of proton beam radiation therapy in breast cancer2005In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, no 8, p. 884-9Article in journal (Refereed)
    Abstract [en]

    A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. In primary breast cancer, it is estimated that about 300 of the annually 3 425 irradiated patients can potentially be candidates for proton beam therapy to reduce late toxicity, mainly from the heart and lungs.

  • 23. Björk-Eriksson, Thomas
    et al.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The potential of proton beam therapy in paediatric cancer2005In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, no 8, p. 871-5Article in journal (Refereed)
    Abstract [en]

    A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. It is estimated that in paediatric cancers, proton beams are of potential importance in 80-100 children annually in Sweden. About 20 of the patients have medulloblastoma. The main purpose is to reduce late sequelae, but these are also increased chances to avoid myelosupression during e.g. concomitant chemo-radiation and to further intensify the chemotherapy.

  • 24.
    Blomquist, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Bjelkengren, Göran
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The potential of proton beam radiation therapy in intracranial and ocular tumours2005In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, no 8, p. 862-70Article in journal (Refereed)
    Abstract [en]

    A group of oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. In intracranial benign and malignant tumours, it is estimated that between 130 and 180 patients each year are candidates for proton beam therapy. Of these, between 50 and 75 patients have malignant glioma, 30-40 meningeoma, 20-25 arteriovenous malformations, 20-25 skull base tumours and 10-15 pituitary adenoma. In addition, 15 patients with ocular melanoma are candidates.

  • 25.
    Blomquist, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ronne Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Borota, Ljubisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Gál, Gyula
    Nilsson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Montelius, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Grusell, Erik
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Positive correlation between occlusion rate and nidus size of proton beam treated brain arteriovenous malformations (AVMs)2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 1, p. 105-112Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Proton beam radiotherapy of arteriovenous malformations (AVM) in the brain has been performed in Uppsala since 1991. An earlier study based on the first 26 patients concluded that proton beam can be used for treating large and medium sized AVMs that were considered difficult to treat with photons due to the risk of side effects. In the present study we analyzed the result from treating the subsequent 65 patients.

    MATERIAL AND METHODS: A retrospective review of the patients' medical records, treatment protocols and radiological results was done. Information about gender, age, presenting symptoms, clinical course, the size of AVM nidus and rate of occlusion was collected. Outcome parameters were the occlusion of the AVM, clinical outcome and side effects.

    RESULTS: The rate of total occlusion was overall 68%. For target volume 0-2cm(3) it was 77%, for 3-10 cm(3) 80%, for 11-15 cm(3) 50% and for 16-51 cm(3) 20%. Those with total regress of the AVM had significantly smaller target volumes (p < 0.009) higher fraction dose (p < 0.001) as well as total dose (p < 0.004) compared to the rest. The target volume was an independent predictor of total occlusion (p = 0.03). There was no difference between those with and without total occlusion regarding mean age, gender distribution or symptoms at diagnosis. Forty-one patients developed a mild radiation-induced brain edema and this was more common in those that had total occlusion of the AVM. Two patients had brain hemorrhages after treatment. One of these had no effect and the other only partial occlusion from proton beams. Two thirds of those presenting with seizures reported an improved seizure situation after treatment.

    CONCLUSION: Our observations agree with earlier results and show that proton beam irradiation is a treatment alternative for brain AVMs since it has a high occlusion rate even in larger AVMs.

  • 26.
    Blomstrand, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Thor, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Erdheim-Chester disease presenting as periodontal disease: Experience of treatment with cladribine, interferon-a, local radiotherapy and anakinra2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 2, p. 248-250Article in journal (Refereed)
  • 27. Bockelman, Camilla
    et al.
    Engelmann, Bodil E.
    Kaprio, Tuomas
    Hansen, Torben F.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Risk of recurrence in patients with colon cancer stage II and III: A systematic review and meta-analysis of recent literature2015In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 1, p. 5-16Article, review/survey (Refereed)
    Abstract [en]

    Background. Adjuvant chemotherapy is established routine therapy for colon cancer (CC) patients with radically resected stage III and 'high-risk' stage II disease. The decision on recommending adjuvant chemotherapy, however, is based on data from older patient cohorts not reflecting improvements in pre-operative staging, surgery, and pathological examination. The aim is to review the current risk of recurrence in stage II and III patients and second, to estimate the relative importance of routinely assessed clinico-pathological variables. Methods. The PubMed/MEDLINE and the Cochrane databases were systematically searched for randomized controlled studies and observational studies published after 1 January 2005 with patients included after January 1995 on prognosis in surgically treated stage II and III CC patients. Results. Of 2596 studies identified, 37 met the inclusion criteria and 25 provided data for meta-analysis. The total patient sample size in the 25 studies reporting either disease-free (DFS) or recurrence-free survival was 15 559 in stage II and 18 425 in stage III. Five-year DFS for stage II patients operated without subsequent adjuvant chemotherapy was 81.4% [95% confidence interval (CI) 75.4-87.4; in studies with good/very good quality of reporting 82.7%, (95% CI 80.8-84.6)]. For stage II patients treated with adjuvant chemotherapy, the five-year DFS was 79.3% (95% CI 75.6-83.1). For stage III patients without chemotherapy, five-year DFS was 49.0% (95% CI 23.2-74.8) and for those treated with adjuvant chemotherapy, 63.6% (95% CI 59.3-67.9). The prognostic impact of commonly investigated clinico-pathological parameters, (pT-stage, pN-stage, differentiation, number of lymph nodes studied, MMR-status, and emergency surgery) were confirmed. Conclusions. In this meta-analysis, studies with good quality of reporting show a FIVE-year DFS of 82.7% for stage II CC without adjuvant chemotherapy, whereas the FIVE-year DFS is 63.8% for stage III CC with adjuvant chemotherapy. Due to insufficient reporting on treatment quality the presented DFS is likely an under-estimation of what is achieved at high-quality centers today.

  • 28.
    Boeckelman, Camilla
    et al.
    Helsinki Univ Hosp, Dept Surg;Univ Helsinki, Res Programs Unit.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Need for adjuvant chemotherapy after colon cancer surgery - has it decreased?2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 5, p. 629-633Article in journal (Other academic)
  • 29. Boman, Krister
    et al.
    Lindahl, Annika
    Karolinska institutet, Inst för kvinnors och barns hälsa.
    Björk, Olle
    Disease-related distress in parents of children with cancer at various stages after the time of diagnosis.2003In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 42, no 2, p. 137-46Article in journal (Refereed)
    Abstract [en]

    This study evaluates and describes disease-related distress in parents, with particular focus on the association between the time elapsed since the child's cancer diagnosis and a number of indicators of distress. In a cross-sectional design, 264 mothers and fathers of children with various malignancies completed a multidimensional questionnaire focusing on 11 illness-specific and general indicators of distress. Parents were assessed from 4 weeks to 14 years after the child's diagnosis, and age of children at onset of illness ranged from newly born to 21 years (mean approximately 6 years). The levels of distress related to loss of control, self-esteem, anxiety, depression, sleep disturbances, and psychological and physical distress were lower among parents for whom a longer period of time had elapsed from the time of diagnosis. However, the time elapsed could not explain all of the variation in these stress reactions, or any of the variation in uncertainty, disease-related fear and loneliness. The child's age at diagnosis and treatment situation at assessment were surpassed by time elapsed since diagnosis as predictors of variance in parental distress. The pattern observed indicates the presence of disease-related distress even years after the completion of medical treatment. The findings point to the need for research to identify parents at particular risk of suffering long-term harmful consequences from the prolonged stress of parenting a child with cancer. The necessity of longitudinal studies to evaluate the proportion of acute stress in relation to chronic or cumulative parental stress is emphasized.

  • 30.
    Brattström, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Wester, Kenneth
    Bergqvist, Michael
    Hesselius, Patrik
    Malmström, Per-Uno
    Nordgren, Hans
    Wagenius, Gunnar
    Brodin, Ola
    HER-2, EGFR, COX-2 expression status correlated to microvessel density and survival in resected non-small cell lung cancers2004In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 43, no 1, p. 80-86Article in journal (Refereed)
    Abstract [en]

    The incidence of lung cancer is increasing throughout the world and is the most common cause of cancer-related death. Early detection followed by surgery has a reasonable, curative potential, but 30-50% of patients experience relapses. The immunohistochemical expressions of HER-2, EGFR and COX-2 were investigated in 53 resected non-small cell lung carcinomas and correlated to microvessel density and clinical data. HER-2, EGFR and COX-2 overexpressions were demonstrated in 15%, 30% and 40% of the tumours, respectively. In adenocarcinomas, HER-2 and COX-2 overexpression were more common, whereas in squamous cell carcinomas, EGFR overexpression was more common. COX-2 expression correlated with HER-2 expression (p = 0.002), and demonstrated a trend towards a correlation with microvessel density (p = 0.10). None of the markers alone had any impact on survival. However, HER-2+/EGFR- tumours proved to have a poor prognosis. In conclusion, adjuvant treatment with HER-2 antagonists might be a future treatment option in resected non-small cell lung cancer patients, especially when HER-2 is overexpressed without a concomitant overexpression of EGFR.

  • 31.
    Byström, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Evaluation of predictive markers for patients with advanced colorectal cancer2012In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 7, p. 849-859Article in journal (Refereed)
    Abstract [en]

    Background.

    To evaluate the predictive and prognostic value of serum and plasma tumor markers, in comparison with clinical and biomedical parameters for response rate (RR), progression-free survival (PFS) and overall survival (OS) among patients with metastatic colorectal cancer (mCRC) treated with combination chemotherapy.

    Material and methods.

    One-hundred and six patients with mCRC from three centers, part of a multicenter study, received irinotecan with the Nordic bolus 5-fluorouracil (5-FU) and folinic acid schedule (FLIRI) or the de Gramont schedule (Lv5FU2-IRI). Blood samples for CEA, CA19-9, TPA, TIMP-1, SAA, transthyretin and CRP were taken at baseline and after two, four and eight weeks of treatment. Tumor marker levels at baseline and longitudinally were compared with responses evaluated (CT/MRI) after two and four months of treatment. The correlations to RR, PFS and OS were evaluated with regression analyses.

    Results.

    A significant correlation to OS was seen for baseline levels of all markers. In multivariate analyses with clinical parameters, TPA, CRP, SAA and TIMP-1 provided independent information. The baseline values of CEA, TPA and TIMP-1 were also significantly correlated to PFS and TPA to RR. Changes during treatment, i.e. the slope gave with the exception of CA19-9 for OS less information about outcomes. The best correlation to response was seen for CEA, CA19-9 and TPA with AUC values of 0.78, 0.83 and 0.79, respectively, using a combined model based upon an interaction between the slope and the baseline value.

    Conclusions.

    Baseline tumor markers together with clinical parameters provide prognostic information about survival in patients with mCRC. The ability of the individual tumor markers to predict treatment response and PFS is limited. Changes in marker levels during the first two months of treatment are less informative of outcome.

  • 32.
    Carlsson, Jörgen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Liljegren, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Sjöström, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Westlin, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Zhao, Qinghai
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Conjugate chemistry and cellular processing of EGF-dextran1999In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 38, no 3, p. 313-321Article in journal (Refereed)
    Abstract [en]

    Conjugates with specific binding to the epidermal growth factor receptor, EGFR, of interest for radionuclide based imaging and therapy were prepared using mouse epidermal growth factor, mEGF, and dextran. In one type of conjugate, mEGF was coupled to dextran by reductive amination in which the free amino group on the mEGF N-terminal reacted with the aldehyde group on the reductive end of dextran. The end-end coupled conjugate could be further activated by the cyanopyridinium agent CDAP, thereby introducing tyrosines to the dextran part. In the other type of conjugate, the cyanylating procedure using CDAP was applied, first to activate dextran and then allowing for the amino terminus of mEGF to randomly attach to the dextran. In the latter case, radionuclide-labelled tyrosines or glycines could be added in the same conjugation step. All types of mEGF-dextran conjugates had EGFR-specific binding since the binding could be displaced by an excess of non-radioactive mEGF. The conjugates were to a large extent internalized in the test cells and the associated radioactivity was retained intracellularly for different times depending on both the type of cells and conjugate applied. Different intracellular 'traffic routes' for the radionuclides are discussed as well as applications for both imaging and therapy.

  • 33.
    Carlsson, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy.
    Strang, Peter
    Educational support programme for gynaecological cancer and their families1998In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 37, no 3, p. 269-275Article in journal (Refereed)
  • 34.
    Cavalli-Björkman, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Implications of patients' socioeconomic status - what oncologists should be aware of2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 2, p. 161-163Article in journal (Other academic)
  • 35.
    Cederblad, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Johansson, Silvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Engström, Mats
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Cancer of the parotid gland; long-term follow-up. A single centre experience on recurrence and survival2009In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226XArticle in journal (Refereed)
  • 36.
    Cederblad, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Johansson, Silvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Engström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Cancer of the parotid gland; long-term follow-up: A single centre experience on recurrence and survival2009In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 48, no 4, p. 549-555Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The aim of the study was to investigate the results of treatment of malignant parotid gland tumours at a single centre during a 56 year period, focusing on tumour control and survival.

    PATIENTS AND METHODS:

    At Uppsala University Hospital, Sweden, 144 patients (73 male and 71 female) with parotid cancer were treated between 1948 and 2004. The mean and median ages were 62 and 65 years, respectively (range 16-89 years). Surgery was the primary treatment in 113 (78%) patients followed by radiotherapy in 81. Postoperative radiotherapy in doses of 64-66 Gy, where the intention was curative and delivered with either split course or not, was administered to a majority of patients after 1970. The split-course mode was practised between 1970 and 1989. The median follow-up time was 8.3 years for patients still alive. There were 57 (40%) relapses, of which 40 were local recurrences with 26 inside the treatment volume.

    RESULTS:

    The overall 5-year survival was 53%. The majority of tumour-related deaths appeared in the first 3-5 years after diagnosis. Age, co-morbidity, the presence of lymph node metastases, adenoid cystic carcinoma and extent of disease were important for outcome; gender, however, was not. We found no difference in the survival between patients following split course therapy versus continuous fractionation. No difference could be seen in the survival of patients treated in the 1970s versus the 1990s.

    CONCLUSIONS:

    Age, nodal engagement, a higher T-stage, adenoid cystic carcinoma histopathology, facial palsy and intercurrent disease worsen the outcome of patients, whereas gender does not. Treatment principles at our hospital have been surgery followed by radiotherapy since the early 1970s even though a split course technique was practised during a part of this period. Survival has not improved markedly. Thus, there is scope for improvement for this group of patients.

  • 37.
    Cunningham, Janet Lynn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Agarwal, Smriti
    Christian Medical College, Vellore, India.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Malignant ileocaecal serotonin-producing carcinoid tumours: the presence of a solid growth pattern and/or Ki67 index above 1% identifies patients with a poorer prognosis2007In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 46, no 6, p. 747-756Article in journal (Refereed)
    Abstract [en]

    Patients with malignant serotonin-producing carcinoid tumours in the jejunum, ileum and caecum generally have long survival expectancy. In some patients, however, tumour progression is more rapid and there is a need to identify them at an early stage. The purpose of this study was to determine if histopathological characteristics and/or Ki67 and apoptotic indices are of prognostic value in cases of metastatic disease. Eighty-one patients with this tumour were included in the study; all had metastases and their survival range was 1-223 months. Five growth patterns were identified and described. For 57 patients whose tumour material was available, the Ki67 and apoptotic indices were calculated for ten randomly selected tumour areas and 'hot spots'. A Cox regression analysis was used to test if histopathology and/or Ki67 index ≥1% could identify patients whose survival might be shorter than anticipated. One of the histopathological growth patterns-the solid (non-organoid) cell pattern-was correlated to shorter survival in both primary tumours and metastases, when compared with the organoid growth patterns (hazard ratio 2.9 and 2.3, p≤0.01). In 75% of primary tumours and 67% of metastases, the average Ki67 index was<0.5%. Ki67 index in 'hot spots' ranged from 0.1 to 14%. Ki67 index ≥1%, in both primary tumour and metastases, identified patients at increased risk of shorter survival (hazard ratio 5.4 and 2.5, p≤0.01). The apoptotic index was very low in all cases. We conclude that in patients with metastazising serotonin-producing carcinoids, two independent criteria, a solid growth pattern and Ki67 index ≥1%, can be used to identify patients with a poorer prognosis. This study also showed that Ki67 index <2% cannot, as previously suggested, be used to indicate a benign progression for this tumour category.

  • 38.
    Derogar, Maryam
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Div Clin Canc Epidemiol,Dept Oncol, Box 100, S-40530 Gothenburg, Sweden..
    Dahlstrand, Hanna
    Karolinska Univ Hosptital, Dept Oncol, Stockholm, Sweden.;Karolinska Inst, Dept Oncol Pathol, Div Clin Canc Epidemiol, Stockholm, Sweden..
    Carlsson, Stefan
    Karolinska Inst, Urol Sect, Dept Mol Med & Surg, Stockholm, Sweden..
    Bjartell, Anders
    Lund Univ, Skane Univ Hosp, Dept Urol, Lund, Sweden..
    Hugosson, Jonas
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol, Gothenburg, Sweden..
    Axen, Elin
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol, Gothenburg, Sweden..
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Lagerkvist, Mikael
    UroClin, Stockholm, Sweden..
    Nyberg, Tommy
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Div Clin Canc Epidemiol,Dept Oncol, Box 100, S-40530 Gothenburg, Sweden.;Karolinska Inst, Urol Sect, Dept Mol Med & Surg, Stockholm, Sweden..
    Stranne, Johan
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol, Gothenburg, Sweden..
    Thorsteinsdottir, Thordis
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Div Clin Canc Epidemiol,Dept Oncol, Box 100, S-40530 Gothenburg, Sweden.;Univ Iceland, Sch Hlth Sci, Fac Nursing, Reykjavik, Iceland..
    Wallerstedt, Anna
    Karolinska Inst, Urol Sect, Dept Mol Med & Surg, Stockholm, Sweden..
    Haglind, Eva
    Univ Gothenburg, Sahlgrenska Acad, SSORG, Dept Surg,Inst Clin Sci, Gothenburg, Sweden..
    Wiklund, Peter
    Karolinska Inst, Urol Sect, Dept Mol Med & Surg, Stockholm, Sweden..
    Steineck, Gunnar
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Div Clin Canc Epidemiol,Dept Oncol, Box 100, S-40530 Gothenburg, Sweden.;Karolinska Inst, Dept Oncol Pathol, Div Clin Canc Epidemiol, Stockholm, Sweden..
    Preparedness for side effects and bother in symptomatic men after radical prostatectomy in a prospective, non-randomized trial, LAPPRO2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 12, p. 1467-1476Article in journal (Refereed)
    Abstract [en]

    Background: Many clinicians believe that preparedness before surgery for possible post-surgery side effects reduces the level of bother experienced from urinary incontinence and decreased sexual health after surgery. There are no published studies evaluating this belief. Therefore, we aimed to study the level of preparedness before radical prostatectomy and the level of bother experienced from urinary incontinence and decreased sexual health after surgery. Material and methods: We prospectively collected data from a non-selected group of men undergoing radical prostatectomy in 14 centers between 2008 and 2011. Before surgery, we asked about preparedness for surgery-induced urinary problems and decreased sexual health. One year after surgery, we asked about bother caused by urinary incontinence and erectile dysfunction. As a measure of the association between preparedness and bothersomeness we modeled odds ratios (ORs) by means of logistic regression. Results: Altogether 1372 men had urinary incontinence one year after surgery as well as had no urinary leakage or a small urinary dribble before surgery. Among these men, low preparedness was associated with bother resulting from urinary incontinence [OR 2.84; 95% confidence interval (CI) 1.59-5.10]. In a separate analysis of 1657 men we found a strong association between preparedness for decreased sexual health and experiencing bother from erectile dysfunction (OR 5.92; 95% CI 3.32-10.55). Conclusion: In this large-sized prospective trial, we found that preparedness before surgery for urinary problems or sexual side effects decreases bother from urinary incontinence and erectile dysfunction one year after surgery.

  • 39. Edlund, Per
    et al.
    Ahlgren, Johan
    Bjerre, Karsten
    Andersson, Michael
    Bergh, Jonas
    Mouridsen, Henning
    Holmberg, Stig B.
    Bengtsson, Nils-Olof
    Jakobsen, Erik
    Moller, Susanne
    Lindman, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    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/m(2), epirubicin 60 mg/mg(2) and cyclophosphamide 600 mg/m(2)), 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.

  • 40.
    Ekman, Simon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Frödin, Jan-Erik
    Harmenberg, Johan
    Bergman, Antonina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Hedlund, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Dahg, Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Alvfors, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Ståhl, Birgitta
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Clinical Phase I study with an Insulin-like Growth Factor-1 Receptor Inhibitor: Experiences in patients with squamous non-small cell lung carcinoma2011In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 50, no 3, p. 441-447Article in journal (Refereed)
    Abstract [en]

    Background. Inhibition of the Insulin-like Growth Factor-1 receptor (IGF-1R) has resulted in extensive anti-tumor effects. Picropdophyllin (PPP, AXL1717) is a small-molecule inhibitor of the IGF-1R without inhibition of closely related receptors including the insulin receptor and has shown extensive effects against a wide range of tumors in animals. PPP is currently tested as an orally administrated single agent treatment in an open-label combined Phase I/II clinical study in advanced cancer patients with solid tumors which progress in spite of several lines of treatment. Patients and methods. The first part (Phase IA) consisted of single day BID dosing every three weeks with consecutive dose escalations. The second part (Phase IB) consists of seven days or longer BID dosing every three weeks, dosing range being 520-700 mg BID. Non-progressing patients could continue treatment within a compassionate use setting. Results and discussion. The present report describes our experience with the four patients with progressive squamous non-small cell lung cancer (NSCLC) that have received treatment with PPP. Despite more than seven months of PPP treatment as third or fourth line treatment, the reported patients did not develop any additional metastases. Furthermore, CT scans as well as (18)FDG-Positron Emission Tomography (PET) scans of the patients demonstrated large central necrotic areas, which may suggest tumor response. At the same time, the study drug is so far well tolerated. The phenomenon of necrosis in the tumors suggestive of tumor response has not been reported before in anti-IGF-1R treatment and will be subject to further studies in the present clinical trial.

  • 41.
    Ekman, Simon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Harmenberg, Johan
    Frödin, Jan-Erik
    Bergström, Stefan
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eksborg, Staffan
    Larsson, Olle
    Axelson, Magnus
    Jerling, Markus
    Abrahmsen, Lars
    Hedlund, Åsa
    Alvfors, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ståhl, Birgitta
    Bergqvist, Michael
    A novel oral insulin-like growth factor-1 receptor pathway modulator and its implications for patients with non-small cell lung carcinoma: A phase I clinical trial.2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 2, p. 140-148Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A phase Ia/b dose-escalation study was performed to characterize the safety, efficacy and pharmacokinetic properties of the oral small molecule insulin-like growth factor-1-receptor pathway modulator AXL1717 in patients with advanced solid tumors.

    MATERIAL AND METHODS: This was a prospective, single-armed, open label, dose-finding phase Ia/b study with the aim of single day dosing (phase Ia) to define the starting dose for multi-day dosing (phase Ib), and phase Ib to define and confirm recommended phase II dose (RP2D) and if possible maximum tolerated dose (MTD) for repeated dosing.

    RESULTS AND CONCLUSION: Phase Ia enrolled 16 patients and dose escalations up to 2900 mg BID were successfully performed without any dose limiting toxicity (DLT). A total of 39 patients were treated in phase Ib. AXL1717 was well tolerated with neutropenia as the only dose-related, reversible, DLT. RP2D dose was found to be 390 mg BID for four weeks. Some patients, mainly with NSCLC, demonstrated signs of clinical benefit, including four partial tumor responses (one according to RECIST and three according to PET). The 15 patients with NSCLC with treatment duration longer than two weeks with single agent AXL1717 in third or fourth line of therapy showed a median progression-free survival of 31 weeks and overall survival of 60 weeks. Down-regulation of IGF-1R on granulocytes and increases of free serum levels of IGF-1 were seen in patients treated with AXL1717. AXL1717 had an acceptable safety profile and demonstrated promising efficacy in this heavily pretreated patient cohort, especially in patients with NSCLC. RP2D was concluded to be 390 mg BID for four weeks. Trial number is NCT01062620.

  • 42. Ellin, Fredrik
    et al.
    Jerkeman, Mats
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Relander, Thomas
    Treatment outcome in T-cell lymphoblastic lymphoma in adults: a population-based study from the Swedish Lymphoma Registry2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 7, p. 927-934Article in journal (Refereed)
    Abstract [en]

    Background. T-cell lymphoblastic lymphoma (T-LBL) is a rare neoplasm of precursor lymphoblast origin, for which there is no standard treatment for adults. Results of current treatment strategies in selected populations do exist but are largely unreported for unselected series. Here, we aimed to investigate treatment outcome in a population-based cohort. Material and methods. Patients were identified through the Swedish Lymphoma Registry and data was retrospectively collected for all adult (>= 18 years) Swedish T-LBL patients diagnosed during 2000-2009. Results. A total of 39 patients with median age 40 years (range 18-78) were identified with females being significantly older than males (median age 66 vs. 37, p = 0.027). The five-year overall survival for all patients was 42%. Female gender was associated with shorter survival also when adjusted for treatment strategy and age [hazard ratio (HR) 4.29; p = 0.002]. Thirty patients received intensive chemotherapy, otherwise used for treatment of acute lymphoblastic leukemia (ALL), which resulted in an overall response rate of 97% and a five-year progression-free survival (PFS) of 49%. In this group only CNS involvement at diagnosis predicted shorter PFS (HR 13.3; p = 0.03). Among patients treated with hyper-CVAD the addition of mediastinal irradiation resulted in prolonged time to progression compared to patients receiving only chemotherapy (p = 0.047). The major reason for treatment failure was relapse and in this series 18-fluoro-deoxyglucose positron emission tomography (PET) did not predict this risk. Conclusion. This population-based study indicates that all fit T-LBL patients should be considered for intensive treatment. Our results also suggest a beneficial effect of mediastinal irradiation in combination with hyper-CVAD treatment. Relapsing patients have a dismal outcome irrespective of salvage treatment.

  • 43. Emdin, Stefan O.
    et al.
    Granstrand, Bengt
    Ringberg, Anita
    Sandelin, Kerstin
    Arnesson, Lars-Gunnar
    Nordgren, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology.
    Anderson, Harald
    Garmo, Hans
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Wallgren, Arne
    SweDCIS: Radiotherapy after sector resection for ductal carcinoma in situ of the breast. Results of a randomised trial in a population offered mammography screening2006In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 45, no 5, p. 536-543Article in journal (Refereed)
    Abstract [en]

    We studied the effect of postoperative radiotherapy (RT) after breast sector resection for ductal carcinoma in situ (DCIS). The study protocol stipulated radical surgery but microscopically clear margins were not mandatory. We randomised 1,046 operated women to postoperative RT or control between 1987 and 1999. The primary endpoint was ipsilateral local recurrence. Secondary endpoints were contralateral breast cancer, distant metastasis and death. After a median follow-up of 5.2 years (range 0.1-13.8) there were 44 recurrences in the RT group corresponding to a cumulative incidence of 0.07 (95% confidence interval (CI) 0.05-0.10). In the control group there were 117 recurrences giving a cumulative incidence of 0.22 (95% CI 0.18-0.26) giving an overall hazard ratio of 0.33 (95% CI 0.24-0.47, p < 0.0001). Twenty two percent of the patients had microscopically unknown or involved margins. We found no evidence for different effects of RT on the relative risk of invasive or in situ recurrence. Secondary endpoints did not differ. Women undergoing sector resection for DCIS under conditions of population based screening mammography benefit from postoperative RT to the breast. Seven patients needed RT-treatment to prevent one recurrence.

  • 44.
    Enblad, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Martinsson, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Population-based experience on primary central nervous system lymphoma 2000-2012: the incidence is increasing2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 4, p. 599-607Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Primary central nervous system lymphomas (PCNSL) are rare lymphomas with a poor prognosis. Recently, an increased incidence has been reported. The present study is a population-based study of all patients with PCNSL in the Uppsala/Örebro region of middle Sweden.

    PATIENTS AND METHODS: All patients diagnosed with a PCNSL at Uppsala University Hospital 2000-2012 were identified. Altogether, 96 patients (50 women and 46 men) were included. The median age at diagnosis was 66 years (17-95).

    RESULTS: There was a statistically significant increase in age-standardized incidence during the study period, 30 patients were diagnosed in the first half and 66 in the second half of the period. No patient had an HIV-infection. Two patients had undergone kidney transplantation and were treated with immunosuppressive drugs. A high proportion of the patients, 29%, had a history of an autoimmune or inflammatory disease. The prognosis was poor with a median survival of only four months. In the 70 (73%) patients treated with curative intention the median survival was 12 months. Patients treated with high-dose methotrexate, radiotherapy and/or temozolomide appeared to have a better survival. There was no improvement in survival during the study period or after the introduction of rituximab. There also was no difference in any of the analyzed variables that could explain the increased incidence.

    CONCLUSION: In this population-based study we could confirm the previously described increased incidence of PCNSL. The prognosis remains poor despite the inclusion of treatment with rituximab during the study period. A high proportion of the patients had a history of an autoimmune or inflammatory disease not previously described but there was no increase during the study period.

  • 45.
    Englund, Annika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Glimelius, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm.
    Rostgaard, Klaus
    Statens Serum Inst, Dept Epidemiol Res, Copenhagen.
    Smedby, Karin E
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm; Karolinska Univ Hosp, Hematol Ctr, Stockholm.
    Eloranta, Sandra
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm.
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Kuusk, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Brown, Peter de Nully
    Rigshosp, Dept Haematol, Copenhagen.
    Kamper, Peter
    Aarhus Univ Hosp, Dept Haematol, Aarhus C.
    Hjalgrim, Henrik
    Statens Serum Inst, Dept Epidemiol Res, Copenhagen; Rigshosp, Dept Haematol, Copenhagen.
    Ljungman, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Hjalgrim, Lisa Lyngsie
    Statens Serum Inst, Dept Epidemiol Res, Copenhagen; Rigshosp, Dept Paediat & Adolescent Med, Copenhagen.
    Hodgkin lymphoma in children, adolescents and young adults - a comparative study of clinical presentation and treatment outcome.2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 276-282Article in journal (Refereed)
    Abstract [en]

    Background: Hodgkin lymphoma (HL) treatment protocols for children, adolescents and young adults traditionally differ, but the biological and clinical justification for this remains uncertain.

    Material and methods: We compared age-dependent clinical presentation and treatment and outcome for 1072 classical HL patients 0–24 years diagnosed in Denmark (1990–2010) and Sweden (1992–2009) in pediatric (n = 315, Denmark <15 years, Sweden <18 years) or adult departments (n = 757). Distribution of clinical characteristics was assessed with Pearson’s chi2-test and Mantel–Haenszel trend test. The Kaplan–Meier method was used for survival analyses. Hazard ratios (HR) were used to compare the different treatment groups and calculated using Cox regression.

    Results: Children (0–9 years) less often presented with advanced disease than adolescents (10–17 years) and young adults (18–24 years) (stage IIB-IV: children 32% vs. adolescents 50%, and adults 55%; p < .005). No variation in overall survival (OS) was seen between pediatric and adult departments or by country. Danish pediatric patients received radiotherapy (36%) less frequently than Swedish pediatric patients (71%) (p < .0001). Ten-year event-free survival (EFS) was lower among Danish pediatric patients (0–14 years) (0.79; 95% confidence interval (CI) 0.70–0.86) than among Swedish pediatric patients (0–17 years) (0.88; 95% CI 0.83–0.92), HR (1.93; 95% CI 1.08–3.46). A similar pattern was seen between adult patients in the two countries: Denmark 10-year EFS 0.85 (95% CI 0.81–0.88), Sweden 0.88 (95% CI 0.84–0.91), adjusted HR 1.51 (95% CI 1.03–2.22).

    Conclusion: Adolescents and young adults shared similar clinical presentation suggesting a rationale of harmonized treatment for these groups. Both adult and pediatric protocols provided high OS with no significant difference between the departments. The less frequent use of radiotherapy in Danish pediatric patients corresponded to a lower EFS, but comparable OS in all groups confirmed effective rescue strategies for the relapsing patients.

  • 46.
    Englund, Annika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hopstadius, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Gustafsson, Göran
    Cancer Research Unit, Karolinska Institutet, Stockholm, Sweden.
    Ljungman, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hodgkin lymphoma - a survey of children and adolescents treated in Sweden 1985-2009.2015In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 1, p. 41-8Article in journal (Refereed)
    Abstract [en]

    Abstract Background. Hodgkin lymphoma (HL) in children constitutes approximately 30% of all pediatric lymphomas in Sweden. The chance of cure is high, but the frequency of late effects has been considerable. Over recent years, efforts have been made to reduce treatment with maintained survival. Material and methods. All patients 0-17 years, identified in the Swedish Childhood Cancer Register as diagnosed between 1985 and 2009, were included. The material was analyzed using descriptive statistics and for survival estimates the Kaplan-Meier method was used. Results. Three hundred and thirty-four patients were identified during this time period. The median age was 14 years. Male sex was over-represented, especially in lower age groups and in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). In nodular sclerosis and in age group 15-17 years, female sex dominated. Most of the cases presented in stages I or II. B-symptoms were present in 38% of cHL, but only in 7% of NLPHL. The number of patients receiving radiotherapy has been significantly reduced during the period studied. The relapse rate in cHL was 10 ± 2% and in NLPHL 16 ± 7%. The relapse rate was significantly higher in cHL stage IIB compared to other stages in the same therapy group. In cHL 6% died, and in NLPHL 0%. The 5-, 10- and 20-year overall survival estimates in cHL were 96 ± 1%, 95 ± 1% and 90 ± 3%, respectively, with no significant difference when comparing different treatment regimens and time periods. The 5- and 10-year overall survival after relapse in cHL was 81 ± 8% and 75 ± 10%, respectively. Conclusion. During the period studied there is no indication of a decline in survival despite changes in treatment. Survival rates in Sweden are high, and even after relapse chances of cure are high. We were not able to identify any characteristics specific for the group of patients that did not survive.

  • 47. Engström, Katarina
    et al.
    Bergh, Peter
    Cederlund, Claes-Göran
    Hultborn, Ragnar
    Willen, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Aman, Pierre
    Kindblom, Lars-Gunnar
    Meis-Kindblom, Jeanne M.
    Irradiation of myxoid/round cell liposarcoma induces volume reduction and lipoma-like morphology2007In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 46, no 6, p. 838-845Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to investigate the clinical and morphological effects of radiotherapy in the treatment of myxoid/round cell liposarcoma (MLS/RCLS). Thirty-three primary and metastatic MLS/RCLS tumours in 15 patients were treated with radiation therapy. Twenty-seven of the 33 tumours were surgically removed after preoperative radiation (34-46 Gy) while six tumours were treated with radiotherapy alone (44-60 Gy). The pretreatment diagnosis was established in all 15 patients based on fine needle aspirates or histological findings. Tumour size was measured by CT or MRI before and after radiotherapy in 30 tumours. Thirteen tumours from 11 patients were genetically characterised before and/or after radiation therapy. Twenty-three of 30 irradiated tumours showed a median reduction in tumour volume of 52% and seven lesions a median progression of 36%. All 27 surgically removed tumours revealed histological features of radiation response. The most striking morphological changes were lipoma-like appearance, paucicellularity and hyalinisation. Twelve of 13 tumours analysed before and/or after radiation therapy showed the FUS-DDIT3 translocation. Radiation therapy of MLS/RCLS induces histopathologic accumulation of mature lipoma-like areas and tumour volume reduction that may facilitate resectability.

  • 48.
    Eriksson, Barbro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bergström, Mats
    Lilja, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Positron emission tomography (PET) in neuroendocrine gastrointestinal tumors1993In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 32, no 2, p. 189-196Article in journal (Refereed)
    Abstract [en]

    Positron emission tomography (PET) makes it possible to study effects of medical treatment in vivo. Carcinoid tumors with liver metastases, especially those of midgut origin, produce serotonin via the precursors tryptophan and 5-hydroxytryptophan (5-HTP) and this overproduction contributes to the clinical symptoms of the carcinoid syndrome. Seven patients with histopathologically verified neuroendocrine tumors and liver metastases, five of whom with ileal carcinoids, one a lung carcinoid and one an endocrine pancreatic tumor, were included in the study. All patients had elevation of urinary 5-HIAA with the exception of one patient with a solitary liver metastasis of midgut origin. After an intravenous injection of 11C-5-HTP, PET was performed and the uptake of radioactivity in tumor tissue, normal liver and plasma were compared. All patients with elevated urinary 5-HIAA and also the patient with a solitary liver metastasis and normal urinary 5-HIAA had high accumulation and signs of a high rate of binding of 5-HTP in the liver metastases. The uptake was relatively homogeneous in midgut carcinoid liver metastases but in large necrotic metastases the radioactivity was localized to the periphery. In three patients PET examination was repeated after 3 months of interferon treatment and in agreement with circulating tumor markers and ultrasonography the uptake of 5-HTP was unchanged. Another patient who received the somatostatin analog somatuline progressed on treatment and accordingly the uptake of 5-HTP also increased. The experience with PET in neuroendocrine gastrointestinal tumors is very limited. Our results so far indicate that 5-HTP can be used to visualize serotonin-producing neuroendocrine tumors and furthermore it might prove to be of value to monitor the effects of treatment, possibly also as an early predictive test of the outcome of treatment.

  • 49.
    Eriksson, Barbro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    An update of the medical treatment of malignant endocrine pancreatic tumors1993In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 32, no 2, p. 203-208Article in journal (Refereed)
    Abstract [en]

    In the present study, we have updated our results with chemotherapy, alpha-interferon, octreotide and combinations of treatment modalities in patients with malignant endocrine pancreatic tumor (EPT). In our patient material of 134 EPT, 92 subjects had malignant tumors as evidenced by the presence of metastases or growth into adjacent organs. Seventy-eight patients had liver metastases. Streptozotocin plus 5-fluorouracil produced objective responses in 17/31 (54%) patients with a median duration of response of 23 months. The use of 5-HT3-antagonists as antiemetics has dramatically improved the quality of life during treatment by reducing the frequency of nausea to only 12.5%. The objective response rate to alpha-interferon (alpha-IFN) treatment, given as first-line treatment in 29 patients and after chemotherapy in 28 patients, was 51% (29/57) with a median duration of response of 20 months. Octreotide, which is still used as third-line treatment in most patients, produced significant biochemical responses in 6/19 (31%) patients with a median duration of 16 months. Combinations of alpha-IFN plus chemotherapy and a alpha-IFN plus octreotide in a small number of patients might indicate additive or synergistic effects. The median survival from start of treatment in the 92 malignant cases was 56.5 months, and for those with liver metastases (n = 78) at start of treatment 50 months. In conclusion, there are at least three effective therapies for malignant EPT and by combining them simultaneously or consecutively, a median survival of more than four years can be obtained.

  • 50.
    Eriksson, Barbro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Peptide hormones as tumors markers in neuroendocrine gastrointestinal tumors1991In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 30, no 4, p. 477-483Article in journal (Refereed)
12345 1 - 50 of 232
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