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  • 251.
    Micke, Patrick
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Edlund, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Lohr, Miriam
    Jirstrom, Karin
    Berglund, Anders
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Rahnenfuehrer, Joerg
    Marincevic, Millaray
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Hengstler, Jan
    Woell, Stefan
    Sahin, Ugur
    Tuereci, Oezlem
    Aberrantly activated claudin 6 and 18.2 as potential therapy targets in non-small-cell lung cancer2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 9, p. 2206-2214Article in journal (Refereed)
    Abstract [en]

    Claudins (CLDNs) are central components of tight junctions that regulate epithelial-cell barrier function and polarity. Altered CLDN expression patterns have been demonstrated in numerous cancer types and lineage-specific CLDNs have been proposed as therapy targets. The objective of this study was to assess which fraction of patients with non-small-cell lung cancer (NSCLC) express CLDN6 and CLDN18 isoform 2 (CLDN18.2). Protein expression of CLDN6 and CLDN18.2 was examined by immunohistochemistry on a tissue microarray (n=355) and transcript levels were supportively determined based on gene expression microarray data from fresh-frozen NSCLC tissues (n=196). Both were analyzed with regard to frequency, distribution and association with clinical parameters. Immunohistochemical analysis of tissue sections revealed distinct membranous positivity of CLDN6 (6.5%) and CLDN18.2 (3.7%) proteins in virtually non-overlapping subgroups of adenocarcinomas and large-cell carcinomas. Pneumocytes and bronchial epithelial cells were consistently negative. Corresponding to the protein expression, in subsets of non-squamous lung carcinoma high mRNA levels of CLDN6 (7-16%) and total CLDN18 (5-12%) were observed. Protein expression correlated well with total mRNA expression of the corresponding gene (rho=0.4-0.8). CLDN18.2 positive tumors were enriched among slowly proliferating, thyroid transcription factor 1 (TTF-1)-negative adenocarcinomas, suggesting that isoform-specific CLDN expression may delineate a specific subtype. Noteworthy, high CLDN6 protein expression was associated with worse prognosis in lung adenocarcinoma in the univariate [hazard ratio (HR): 1.8; p=0.03] and multivariate COX regression model (HR: 1.9; p=0.02). These findings encourage further clinical exploration of targeting ectopically activated CLDN expression as a valuable treatment concept in NSCLC.

  • 252.
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Framgångens baksida: Sena biverkningar av strålbehandling vid Hodgkins lymfom2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 44, p. 2731-2732Article in journal (Other (popular science, discussion, etc.))
  • 253.
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Framgångens baksida: Sena biverkningar av strålbehandling vid Hodgkins lymfom2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 44, p. 2731-2732Article in journal (Refereed)
  • 254.
    Molin, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Edström, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Glimelius, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Nilsson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Mast cell infiltration correlates with poor prognosis in Hodgkin's lymphoma2002In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 119, no 1, p. 122-124Article in journal (Refereed)
    Abstract [en]

    Hodgkin's lymphoma (HL) is characterized by a few Hodgkin, Reed-Sternberg cells (HRS) surrounded by benign cells. We recently reported that mast cells were the predominant CD30L-positive cells in HL tumours, and that they activate HRS in vitro through CD30L-CD30 interaction. Here, we investigated the clinical importance of mast cell infiltration in the tumours of 123 patients. Tumour specimens were stained with a mast-cell-specific antibody that detects tryptase. Mast cells were detected in virtually every case and increasing numbers of mast cells correlated to nodular sclerosis histology (P = 0.008). Patients with higher mast cell infiltration had a worse relapse-free survival (P = 0.01).

  • 255.
    Mosavi, Firas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Silvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sandberg, Dan T
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Turesson, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Whole-Body Diffusion-Weighted MRI Compared With 18F-NaF PET/CT for Detection of Bone Metastases in Patients With High-Risk Prostate Carcinoma2012In: American Journal of Roentgenology, ISSN 0361-803X, E-ISSN 1546-3141, Vol. 199, no 5, p. 1114-1120Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    The purpose of this study was to evaluate the accuracy of whole-body diffusion-weighted MRI (DWI) and 18F-NaF PET/CT for detection of bone metastases in patients with high-risk prostate cancer.

    SUBJECTS AND METHODS:

    Both patient- and lesion-based analyses were performed on 49 consecutive patients (median age, 67 years; age range, 57-80 years) with recently diagnosed high-risk prostate cancer. All patients underwent bone scintigraphy, whole-body MRI including DWI and 18F-NaF PET/CT before treatment. Bone scintigraphy, conventional MR images, and follow-up images were used as the standard of reference to evaluate 18F-NaF PET/CT and DWI.

    RESULTS:

    On patient-based analysis, five patients had skeletal metastases on reference imaging that both DWI and 18F-NaF PET/CT could verify, and 18F-NaF PET/CT and DWI showed false-positive findings in four and one patient, respectively. With lesion-based analysis, 18F-NaF PET/CT and DWI showed nine and five true-positive lesions, zero and four false-negative lesions, and seven and two false-positive lesions, respectively. Two patients with uncountable bone metastases were analyzed separately. In these patients, 18F-NaF PET/CT showed more bone metastases than did DWI.

    CONCLUSION:

    We believe 18F-NaF PET/CT is a sensitive modality for detection of bone metastases caused by prostate cancer. Whole-body DWI shows a higher specificity but lower sensitivity than 18F-NaF PET/CT. Future studies with a larger patient cohort along with analyses of costs and clinical availability are needed before implementation of these methods can be considered.

  • 256.
    Mosavi, Firas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ullenhag, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Whole-body MRI including diffusion-weighted imaging compared to CT for staging of malignant melanoma2013In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 2, p. 91-97Article in journal (Refereed)
    Abstract [en]

    Background. Whole-body (WB) magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), has been increasingly used for the detection of metastatic disease. Purpose. To assess the value of WB MRI including DWI compared to computed tomography (CT) for staging of malignant melanoma. A second aim was to assess the value of DWI in addition to conventional MR sequences for the detection of lesions. Material and methods. WB MRI with DWI and CT chest, abdomen, and pelvis were performed in 23 patients with histologically confirmed malignant melanoma. CT before and after the MRI examinations and the clinical follow-up was utilized as the standard of reference. Results. WB MRI and WB DWI detected 345 and 302 lesions, respectively, compared to 397 lesions with CT. The sensitivity of WB MRI and WB DWI varied considerably in different regions of the body. In the lungs, WB MRI and WB DWI showed 63% and 47% true-positive lesions, respectively. WB MRI and WB DWI detected 56 bone lesions in 12 patients compared to 42 lesions in 8 patients with CT. In addition, WB MRI and WB DWI could detect 68 lesions outside the field of view of CT in six patients. Conclusion. WB MRI is still not ready to replace CT for staging of malignant melanoma, especially in the thorax region. However, WB MRI is advantageous for detection of bone lesions and lesions outside the investigated volume of the conventional CT. When WB MRI is evaluated, both DWI and conventional MRI sequences must be scrutinized.

  • 257. Muren, Ludvig P
    et al.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    And they lived happily ever after… The marriage of Nordic Association for Clinical Physics and Acta Oncologica2011In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 50, no 6, p. 835-837Article in journal (Refereed)
  • 258. Muren, Ludvig P.
    et al.
    Rossi, Carl
    Hug, Eugen
    Lee, Andrew
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Establishing and expanding the indications for proton and particle therapy2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 3, p. 459-462Article in journal (Other academic)
  • 259.
    Månsson, Christopher
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Bergenfeldt, Magnus
    Brahmstaedt, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Karlson, Britt-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Safety and Preliminary Efficacy of Ultrasound-guided Percutaneous Irreversible Electroporation for Treatment of Localized Pancreatic Cancer2014In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 1A, p. 289-293Article in journal (Refereed)
    Abstract [en]

    Background:

    Irreversible electroporation (IRE) is a local tumor treatment. Thin needles are placed percutaneously around the tumor under ultrasound guidance. Short pulses of direct current sent through the tissue irreversibly increase cell membrane permeability leading to cell death. We report a phase I study assessing the safety of ultrasound guided percutaneous IRE in patients with localized pancreatic cancer (LPC).

    Patients and Methods:

    Five patients (three males) with LPC, judged unsuitable for surgery, chemotherapy, or non-resectable after standard oncological treatment, were treated with IRE. The treatment was given under general anesthesia with muscle relaxation.

    Results:

    No serious treatment-related adverse events were observed. There was no 30-day mortality. One patient went on to laparotomy and had a R0 pancreaticoduodenectomy with portal vein resection. Six months after the treatment, two patients had no signs of recurrence on computed tomography or contrast-enhanced ultrasound.

    Conclusion:

    IRE for LPC can be safely performed percutaneously under ultrasound guidance, with promising initial results regarding efficacy.

  • 260.
    Mörth, Charlott
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Valachis, Antonis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Single-agent versus combination chemotherapy as first-line treatment for patients with advanced non-small cell lung cancer and performance status 2: A literature-based meta-analysis of randomized studies2014In: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 84, no 3, p. 209-214Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The purpose of this study was to compare the efficacy and tolerability of first-line treatment with combination versus single agent chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and performance status (PS) 2.

    METHODS: A systematic literature search was performed to identify randomized trials comparing combination versus single agent chemotherapy in patients with advanced NCSLC. Both trials dedicated to PS 2 patients and trials that performed a subset analysis according to PS were included in the meta-analysis. Standard meta-analytic procedures were used to analyze the study outcomes.

    RESULTS: Twelve trials were considered eligible and were further analyzed. The use of combination chemotherapy resulted in a statistically significant better overall survival compared to single agent chemotherapy (11 trials, 1114 patients; hazard ratio (HR), 0.79, 95% confidence interval (CI): 0.71-0.88). The survival benefit was pronounced when platinum-based combination was used (HR: 0.71, 95% CI: 0.61-0.81) while no survival benefit was observed in non-platinum based combinations (HR: 0.96, 95% CI: 0.80-1.15). Grade 3/4 anemia (OR: 3.12, 95% CI: 1.55-6.27), thrombocytopenia (OR: 12.81, 95% CI: 4.65-33.10), and neutropenia (OR: 7.91, 95% CI: 3.97-15.78) but not febrile neutropenia were significantly more frequent with combination chemotherapy.

    CONCLUSION: This meta-analysis provides evidence supporting the use of combination chemotherapy in patients with NSCLC and PS 2. However, the patients should be informed about the higher risk for toxicity with the combination chemotherapy and the final treatment strategy should be individualized.

  • 261. Nearchou, Andreas Demetrios
    et al.
    Valachis, Antonis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lind, Pehr
    Akre, Olof
    Sandstrom, Per
    Acquired hypothyroidism as a predictive marker of outcome in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine-kinase inhibitors (TKIs): A literature-based meta-analysis.2014In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, no 4SArticle in journal (Other academic)
  • 262. Neoptolemos, John P.
    et al.
    Moore, Malcolm J.
    Cox, Trevor F.
    Valle, Juan W.
    Palmer, Daniel H.
    McDonald, Alexander C.
    Carter, Ross
    Tebbutt, Niall C.
    Dervenis, Christos
    Smith, David
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Charnley, Richard M.
    Lacaine, Francois
    Scarfe, Andrew G.
    Middleton, Mark R.
    Anthoney, Alan
    Ghaneh, Paula
    Halloran, Christopher M.
    Lerch, Markus M.
    Olah, Attila
    Rawcliffe, Charlotte L.
    Verbeke, Caroline S.
    Campbell, Fiona
    Buechler, Markus W.
    Effect of Adjuvant Chemotherapy With Fluorouracil Plus Folinic Acid or Gemcitabine vs Observation on Survival in Patients With Resected Periampullary Adenocarcinoma: The ESPAC-3 Periampullary Cancer Randomized Trial2012In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 308, no 2, p. 147-156Article in journal (Refereed)
    Abstract [en]

    Context  Patients with periampullary adenocarcinomas undergo the same resectional surgery as that of patients with pancreatic ductal adenocarcinoma. Although adjuvant chemotherapy has been shown to have a survival benefit for pancreatic cancer, there have been no randomized trials for periampullary adenocarcinomas.

    Objective  To determine whether adjuvant chemotherapy (fluorouracil or gemcitabine) provides improved overall survival following resection.

    Design, Setting, and Patients  The European Study Group for Pancreatic Cancer (ESPAC)-3 periampullary trial, an open-label, phase 3, randomized controlled trial (July 2000-May 2008) in 100 centers in Europe, Australia, Japan, and Canada. Of the 428 patients included in the primary analysis, 297 had ampullary, 96 had bile duct, and 35 had other cancers.

    Interventions  One hundred forty-four patients were assigned to the observation group, 143 patients to receive 20 mg/m2 of folinic acid via intravenous bolus injection followed by 425 mg/m2 of fluorouracil via intravenous bolus injection administered 1 to 5 days every 28 days, and 141 patients to receive 1000 mg/m2 of intravenous infusion of gemcitabine once a week for 3 of every 4 weeks for 6 months.

    Main Outcome Measures  The primary outcome measure was overall survival with chemotherapy vs no chemotherapy; secondary measures were chemotherapy type, toxic effects, progression-free survival, and quality of life.

    Results  Eighty-eight patients (61%) in the observation group, 83 (58%) in the fluorouracil plus folinic acid group, and 73 (52%) in the gemcitabine group died. In the observation group, the median survival was 35.2 months (95%% CI, 27.2-43.0 months) and was 43.1 (95%, CI, 34.0-56.0) in the 2 chemotherapy groups (hazard ratio, 0.86; (95% CI, 0.66-1.11; χ2 = 1.33; P = .25). After adjusting for independent prognostic variables of age, bile duct cancer, poor tumor differentiation, and positive lymph nodes and after conducting multiple regression analysis, the hazard ratio for chemotherapy compared with observation was 0.75 (95% CI, 0.57-0.98; Wald χ2 = 4.53, P = .03).

    Conclusions  Among patients with resected periampullary adenocarcinoma, adjuvant chemotherapy, compared with observation, was not associated with a significant survival benefit in the primary analysis; however, multivariable analysis adjusting for prognostic variables demonstrated a statistically significant survival benefit associated with adjuvant chemotherapy.

  • 263. Nielsen, Martin S.
    et al.
    Nyström, M. W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Carl, Jesper
    Potential position errors using fiducial markers for gated image guided radiotherapy2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 7, p. 1472-1476Article in journal (Refereed)
    Abstract [en]

    Background. Fiducials can be used as surrogate for target position during radiotherapy. However, fiducial motion could lead to potential position errors when using fiducials in four-dimensional computed tomography (4DCT) treatment planning and for gated image guided radiotherapy (IGRT). Material and methods. One gold marker (GM) and 5, 10 and 15 mm nickel-titanium (NiTi) stents were inserted in a moving phantom for the purpose of fiducial detection in 4DCT and gated IGRT. Fiducial position errors in 4DCT and BrainLAB's gated IGRT were defined as residuals between fiducial detection and the actual physical position at the instance of image acquisition. Results. Fiducials position errors correlate to speed, fiducial type and orientation during 4DCT acquisition. Lower detection accuracy was measured for the 5 mm NiTi-stent relative to the 10 and 15 mm NiTi stents and GM. Fiducials with orientation 45 degrees relative to the scan direction showed a lower detection accuracy relative to parallel and perpendicular orientations. The standard deviation of position errors in 4DCT were up to 2.2 mm with a maximum deviation of 4.0 mm. Using BrainLAB's gated IGRT the fiducials were detected with a standard deviation of 0.6 mm and a maximum deviation of 1.9 mm. For gated IGRT no correlation to fiducial speed was found. Conclusions. Clinical use of fiducials in combination with treatment planning on mid-ventilation CT phase for moving target should include margins up to 5.5 mm due to potential systematic position errors.

  • 264.
    Nilsson, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Holmqvist, Marit
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Hedenfalk, Ingrid
    Lambe, Mats
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Similarities and differences in the characteristics and primary treatment of breast cancer in men and women: a population based study (Sweden)2011In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 50, no 7, p. 1083-1088Article in journal (Refereed)
    Abstract [en]

    Purpose. Male breast cancer (MBC) is an uncommon disease. In the absence of randomized studies, current guidelines are mainly based on data on the management of female breast cancer (FBC). In light of concerns regarding the quality and extent of management in men, the aim of the present study was to investigate whether there are differences in tumor characteristics, treatment and outcome in male compared with FBC patients.

    Methods. Cohorts of male and female breast cancer were retrospectively analyzed. All male patients diagnosed with invasive breast cancer between 1993 and 2007 were identified from the Regional Breast Cancer Register of the Uppsala-rebro Region in Sweden. To increase the power of the study and obtain comparable cohorts we sampled four FBC patients (n = 396) for each MBC patient (n = 99) with similar age at diagnosis and time of diagnosis.

    Results. No differences were seen in stage at diagnosis between MBC and FBC. Men underwent mastectomy more often than women (92% vs. 44%, p < 0.001). Radiotherapy was delivered less often to MBC than FBC (44% vs. 56%, p = 0.034), but radiotherapy given after mastectomy (44% vs. 39%, p = 0.47) did not differ between the groups. No differences were found regarding adjuvant chemotherapy (16% vs. 21%; p = 0.31) or adjuvant endocrine therapy (59% vs. 52%, p = 0.24). Both overall survival (41% vs. 55%, p = 0.001) and relative survival (74% vs. 88%, p = 0.015) were inferior in MBC compared to FBC.

    Conclusion. Concerns regarding less extensive treatment in MBC patients were not supported by this study. Although no differences in the stage of the disease or treatment intensity could be demonstrated, outcome was inferior in the male group.

  • 265.
    Nilsson, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Johansson, Ida
    Department of Oncology, Clinical Sciences and CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund.
    Ahlin, Cecilia
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Thorstenson, Sten
    Department of Pathology, Linköping University Hospital, Linköping, Sweden.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Holmqvist, Marit
    Uppsala-Örebro Regional Oncologic Center, Uppsala, Sweden .
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedenfalk, Ingrid
    Department of Oncology, Clinical Sciences and CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund, Sweden.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Molecular subtyping of male breast cancer using alternative definitions and its prognostic impact2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 1, p. 102-109Article in journal (Refereed)
    Abstract [en]

    Background.

    Male breast cancer (MBC) is an uncommon disease and there is limited information on the prognostic impact of routinely used clinicopathological parameters.

    Material and methods.

    In a retrospective setting, we reviewed 197 MBC patients with accessible paraffin-embedded tumor tissue and clinicopathological data. Immunohistochemical (IHC) stainings were performed on tissue microarrays and histological grading on conventional slides. Cox proportional regression models were applied for uni- and multivariate analyses using breast cancer death as the event.

    Results.

    Estrogen receptor (ER) and progesterone receptor positivity were demonstrated in 93% and 77% of patients, respectively. Nottingham histologic grade (NHG) III was seen in 41% and HER2 positivity in 11%. Classification into molecular subtypes using IHC markers according to three alternative definitions revealed luminal A and luminal B in 81% vs. 11%; 48% vs. 44% and 41% vs. 42% of cases. Two cases of basal-like were identified, but no cases of HER2-like. Factors associated with an increased risk of breast cancer death were node positivity (HR 4.5; 95% CI 1.8-11.1), tumor size > 20 mm (HR 3.3; 95% CI 1.4-7.9) and ER negativity (HR 10.9; 95% CI 3.2-37.9). No difference in breast cancer death between the luminal subgroups was demonstrated, regardless of definition.

    Conclusion.

    MBC tumors were more often of high grade, whereas HER2 overexpression was as frequent as in FBC. Lymph nodes, tumor size and ER status were independent predictors of breast cancer death. The prognostic impact of molecular subtyping in MBC seems to differ from that previously established in FBC.

  • 266.
    Nilsson, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Koliadi, Anthoula
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Johansson, Ida
    Department of Oncology, Clinical Sciences and CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund.
    Ahlin, Cecilia
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Thorstenson, Sten
    Department of Pathology, Linköping University Hospital, Linköping, Sweden.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedenfalk, Ingrid
    Department of Oncology, Clinical Sciences and CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund, Sweden.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    High proliferation is associated with inferior outcome in male breast cancer patients2013In: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 26, no 1, p. 87-94Article in journal (Refereed)
    Abstract [en]

    Assessment of proliferation is important in female breast cancer and individual treatment decisions are based upon its results, especially in the lumina! subgroups. Gene expression analyses fail to group male breast cancer into the intrinsic subgroups previously established in female breast cancer. Even though proliferation has been shown to divide malebreast cancer into molecular subgroups with different prognoses, the clinical importance ofproliferation markers has not yet been elucidated. Previous studies in male breast cancer have demonstrated contradictory results regarding the prognostic impact of histological grade and Ki-67, parameters strongly associated with proliferation. The aim of the present project was to studyproliferation in male breast cancer by assessing other proliferation-related markers viz. cyclins A, B, D1 and mitotic count. A total of 197 male breast cancer cases with accessible paraffin-embedded material and outcome data were investigated. Immunohistochemical stainings were performed on tissue microarrays. Kaplan-Meier estimates and the Cox proportional regression models were used for survival analyses with breast cancer death as the event. The subset ofpatients with high expression of cyclin A (hazard ratio (HR) 3.7; P=0.001) and B (HR 2.7; P=0.02) demonstrated a poorer survival. Furthermore, high mitotic count was associated with an increased risk of breast cancer death (HR 2.5; P=0.01). In contrast, cyclin D1 overexpression was predictive of better breast cancer survival (HR 0.3; P=0.001). In conclusion, high levels of cyclin A and B expression and an elevated mitotic count result in a two to threefold higher risk forbreast cancer death, whereas cyclin D1 overexpression halves the risk. The clinical utility of these proliferation markers needs further elucidation. 

  • 267.
    Nilsson, Greger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Cardiovascular Side Effects of Radiotherapy in Breast Cancer2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of the thesis was to study cardiovascular side effects of radiotherapy (RT) in breast cancer (BC).

    In a study base of 25,171 women with BC diagnosed 1970-2000, we found a statistically significant 12% increase of stroke, compared to the stroke incidence in the background population.

    A case-control study of 282 cases with BC followed by a stroke and 1:1 matched controls with BC but not stroke was performed. In women irradiated to internal mammary chain (IMC) and supraclavicular lymph nodes (SCL) vs. a pooled group of women not irradiated or irradiated to targets other than IMC and SCL, a statistically significant increase of stroke with an odds ratio of 1.8 was observed. There were no associations between BC laterality, targets of RT, and hemisphere location of stroke. The radiation targets IMC and SCL, showed a statistically significant trend for an increased risk of stroke with daily fraction dose.

    A study of 199 patients with BC, examined by coronary angiography, detected a four- to seven-fold increase of high grade coronary artery stenosis in mid and distal left anterior descending artery (LAD), including distal diagonal branch, when comparing women with irradiated left-sided BC to those with right-sided. An increase of clinically significant coronary artery stenosis was found in pre-specified hotspot areas for radiation among women irradiated to the left breast/chest wall or to the IMC. Thus, the coronary arteries should be regarded as organs at risk in RT of BC.

    In a study of 15 BC patients treated with 3D conformal RT, a marked difference in dose distribution in mid and distal LAD between left- and right-sided BC was demonstrated. Irradiated right-sided BC mainly received low doses of scattered and transmitted radiation to the coronary arteries. On the contrary, tangential RT to the left breast without regional lymph node irradiation yielded coronary artery max doses of approximately 50 Gray to distal LAD, probably not safe concerning late radiation vascular effects.

    To conclude, we found cardiovascular side effects in women irradiated for BC, resulting in stroke and coronary artery disease, and showed an association between the targets for RT and the anatomical location of these vascular events.

    List of papers
    1. Increased incidence of stroke in women with breast cancer
    Open this publication in new window or tab >>Increased incidence of stroke in women with breast cancer
    Show others...
    2005 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 41, no 3, p. 423-429Article in journal (Refereed) Published
    Abstract [en]

    Meta-analyses have shown an excess of vascular deaths in women with breast cancer given radiotherapy (RT). In women with breast cancer, RT to the supraclavicular lymph nodes gives a substantial radiation dose to the proximal carotid artery. RT is known to increase the risk of carotid stenosis and ischaemic stroke in head and neck cancer. A study base of 25,171 women with breast cancer was defined. A linkage between the study base and the Hospital Discharge Register yielded 1766 women who were diagnosed with a stroke after a breast cancer. The observed number of strokes was compared with the expected number in the background population. The Relative Risk (RR) of stroke in the study group with breast cancer was 1.12 (95% Confidence Interval (CI)=1.07-1.17). The increased risk was confined to the subtype cerebral infarction, RR=1.12 (95% CI=1.05-1.19). A statistically significant increase in the risk of stroke was seen among women with a history of breast cancer. Whether this risk is associated with the breast cancer disease per se or related to any treatment requires further study.

    Keywords
    Breast Neoplasms/complications/*epidemiology/mortality, Cause of Death, Cerebrovascular Accident/complications/*epidemiology/mortality, Female, Follow-Up Studies, Humans, Incidence, Middle Aged, Registries, Research Support; Non-U.S. Gov't, Risk Factors, Sweden/epidemiology
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-70414 (URN)10.1016/j.ejca.2004.11.013 (DOI)000227187400019 ()15691643 (PubMedID)
    Available from: 2006-05-08 Created: 2006-05-08 Last updated: 2017-11-21Bibliographically approved
    2. Radiation to supraclavicular and internal mammary lymph nodes in breast cancer increases the risk of stroke
    Open this publication in new window or tab >>Radiation to supraclavicular and internal mammary lymph nodes in breast cancer increases the risk of stroke
    Show others...
    2009 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 100, no 5, p. 811-816Article in journal (Refereed) Published
    Abstract [en]

    The aim of this study was to assess whether adjuvant treatment of breast cancer (BC) affects the risk of stroke, and to explore radiation targets and fraction doses regarding risk and location of stroke. In a Swedish BC cohort diagnosed during 1970-2003, we carried out a nested case-control study of stroke after BC, with relevant details extracted from medical records. The odds ratio (OR) for radiotherapy (RT) vs that of no RT did not differ between cases and controls (OR=0.85; confidence interval, CI=0.6-1.3). Radiotherapy to internal mammary chain (IMC) and supraclavicular (SCL) lymph nodes vs that of no RT was associated with a higher, although not statistically significant, risk of stroke (OR=1.3; CI=0.8-2.2). In a pooled analysis, RT to IMC and SCL vs the pooled group of no RT and RT to breast/chest wall/axilla (but not IMC and SCL), showed a significant increase of stroke (OR=1.8; CI=1.1-2.8). There were no associations between cancer laterality, targets of RT, and location of stroke. The radiation targets, IMC and SCL, showed a statistically significant trend for an increased risk of stroke with daily fraction dose. Our finding of a target-specific increased risk of stroke and a dose-response relationship for daily fraction dose, indicate that there may be a causal link between RT to the IMC and SCL and risk of stroke.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-103408 (URN)10.1038/sj.bjc.6604902 (DOI)000263905900022 ()19259096 (PubMedID)
    Available from: 2009-05-19 Created: 2009-05-19 Last updated: 2017-12-13Bibliographically approved
    3. Distribution of Coronary Artery Stenosis After Radiation for Breast Cancer
    Open this publication in new window or tab >>Distribution of Coronary Artery Stenosis After Radiation for Breast Cancer
    Show others...
    2012 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 4, p. 380-386Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE

    To study distribution of coronary artery stenosis among patients with breast cancer (BC) and to assess correlation between radiotherapy (RT) and location of stenosis.

    PATIENTS AND METHODS

    A Swedish BC cohort diagnosed from 1970 to 2003 was linked to registers of coronary angiography from 1990 to 2004, which yielded 199 patients. Stenoses of the coronary arteries were graded from 0 to 5, where 0 indicated a normal vessel and 5 indicated occlusion. Two hotspot areas for radiation were defined: proximal right coronary artery (prox RCA), mid and distal left anterior descending artery and distal diagonal (mdLAD + dD). RT regimens were categorized as high or low risk of irradiating the hotspot areas. Left breast/chest wall was considered high risk for mdLAD + dD; left internal mammary chain (IMC), high risk for prox RCA and mdLAD + dD from 1970 to 1995 and thereafter solely for mdLAD + dD; and right IMC, high risk for prox RCA. Other RT targets and no RT were considered low risk. Results were expressed in odds ratios (ORs) and 95% CIs.

    RESULTS

    For irradiated left- versus right-sided BC, the OR for grade 3 to 5 stenosis in mdLAD + dD was 4.38 (95% CI, 1.64 to 11.7), and for grade 4 to 5 stenosis, the OR was 7.22 (95% CI, 1.64 to 31.8). For high-risk RT versus low-risk or no RT, the OR for grade 3 to 5 stenosis in hotspot areas was 1.90 (95% CI, 1.11 to 3.24).

    CONCLUSION

    An increase of stenosis in mdLAD + dD in irradiated left-sided BC and an association between high-risk RT and stenosis in hotspot areas for radiation indicate a direct link between radiation and location of coronary stenoses.

    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:uu:diva-165741 (URN)10.1200/JCO.2011.34.5900 (DOI)000302620900016 ()22203772 (PubMedID)
    Available from: 2012-01-09 Created: 2012-01-09 Last updated: 2017-12-08Bibliographically approved
    4. Postoperative radiotherapy for breast cancer and coronary artery stenosis: A dosimetry study of 15 patients examined by coronary angiography after breast cancer treatment
    Open this publication in new window or tab >>Postoperative radiotherapy for breast cancer and coronary artery stenosis: A dosimetry study of 15 patients examined by coronary angiography after breast cancer treatment
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Cancer and Oncology
    Research subject
    Oncology
    Identifiers
    urn:nbn:se:uu:diva-179742 (URN)
    Available from: 2012-08-22 Created: 2012-08-22 Last updated: 2013-01-22
  • 268.
    Nilsson, Greger
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sjögren, Iwar
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Distribution of Coronary Artery Stenosis After Radiation for Breast Cancer2012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 4, p. 380-386Article in journal (Refereed)
    Abstract [en]

    PURPOSE

    To study distribution of coronary artery stenosis among patients with breast cancer (BC) and to assess correlation between radiotherapy (RT) and location of stenosis.

    PATIENTS AND METHODS

    A Swedish BC cohort diagnosed from 1970 to 2003 was linked to registers of coronary angiography from 1990 to 2004, which yielded 199 patients. Stenoses of the coronary arteries were graded from 0 to 5, where 0 indicated a normal vessel and 5 indicated occlusion. Two hotspot areas for radiation were defined: proximal right coronary artery (prox RCA), mid and distal left anterior descending artery and distal diagonal (mdLAD + dD). RT regimens were categorized as high or low risk of irradiating the hotspot areas. Left breast/chest wall was considered high risk for mdLAD + dD; left internal mammary chain (IMC), high risk for prox RCA and mdLAD + dD from 1970 to 1995 and thereafter solely for mdLAD + dD; and right IMC, high risk for prox RCA. Other RT targets and no RT were considered low risk. Results were expressed in odds ratios (ORs) and 95% CIs.

    RESULTS

    For irradiated left- versus right-sided BC, the OR for grade 3 to 5 stenosis in mdLAD + dD was 4.38 (95% CI, 1.64 to 11.7), and for grade 4 to 5 stenosis, the OR was 7.22 (95% CI, 1.64 to 31.8). For high-risk RT versus low-risk or no RT, the OR for grade 3 to 5 stenosis in hotspot areas was 1.90 (95% CI, 1.11 to 3.24).

    CONCLUSION

    An increase of stenosis in mdLAD + dD in irradiated left-sided BC and an association between high-risk RT and stenosis in hotspot areas for radiation indicate a direct link between radiation and location of coronary stenoses.

  • 269.
    Nilsson, Greger
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Witt Nyström, Petra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Iwar, Sjögren
    Kardiolog klin, Falu lasarett.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Postoperative radiotherapy for breast cancer and coronary artery stenosis: A dosimetry study of 15 patients examined by coronary angiography after breast cancer treatmentManuscript (preprint) (Other academic)
  • 270. Nilsson, Per
    et al.
    Ceberg, Crister
    Kjellen, Elisabeth
    Gagliardi, Giovanna
    Blomgren, Klas
    Nilsson, Sten
    Johansson, Mikael
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    A template for writing radiotherapy protocols2015In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 2, p. 275-279Article in journal (Refereed)
    Abstract [en]

    Background. Well-specified and unambiguous treatment protocols are essential both for current practice and for the future development of radiation therapy. In order to provide assistance for writing good protocols, irrespective of treatment intention and complexity, up-to-date guidelines are highly desirable. Methods. We have analysed the radiotherapy work-flow, including clinical and physical aspects, such as preparatory imaging, treatment planning, delivery and evaluation, with the aim to outline a consistent framework covering the entire radiotherapy process. Results. Based on the analysis, a recipe-style template for specifying the description of the radiotherapy process has been designed. The template is written in a general format, which allows for modified phrasing, and should be customised for the specific clinical situation and diagnosis, as well as facility resources. Conclusions. The template can be used as a tool to ensure a consistent and comprehensive description of the radiotherapy section of clinical guidelines, care programmes and clinical trial protocols.

  • 271. Nilsson, Per J.
    et al.
    van Etten, Boudewijn
    Hospers, Geke A. P.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    van de Velde, Cornelis J. H.
    Beets-Tan, Regina G. H.
    Blomqvist, Lennart
    Beukema, Jannet C.
    Kapiteijn, Ellen
    Marijnen, Corrie A. M.
    Nagtegaal, Iris D.
    Wiggers, Theo
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer - the RAPIDO trial2013In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, p. 279-Article in journal (Refereed)
    Abstract [en]

    Background: Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer. Methods and design: Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life. Discussion: Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative chemotherapy. In a multi-centre setting this regimen is compared to current standard with the aim of improving survival for patients with locally advanced rectal cancer.

  • 272.
    Nordin, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Rissanen, Ritva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Ahlgren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Burell, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Borjesson, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Arving, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    How can health care help female breast cancer patients reduce their stress symptoms?: A randomized intervention study with stepped-care2012In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 12, p. 167-Article in journal (Refereed)
    Abstract [en]

    Background: A life threatening illness such as breast cancer can lead to a secondary diagnosis of PTSD (post traumatic stress disorder) with intrusive thoughts and avoidance as major symptoms. In a former study by the research group, 80% of the patients with breast cancer reported a high level of stress symptoms close to the diagnosis, such as intrusive thoughts and avoidance behavior. These symptoms remained high throughout the study. The present paper presents the design of a randomized study evaluating the effectiveness and cost-effectiveness of a stress management intervention using a stepped-care design.

    Method: Female patients over the age of 18, with a recent diagnosis of breast cancer and scheduled for adjuvant treatment in the form of chemotherapy, radiation therapy and/or hormonal therapy are eligible and will consecutively be included in the study. The study is a prospective longitudinal intervention study with a stepped-care approach, where patients will be randomised to one of two interventions in the final stage of treatment. The first step is a low intensity stress-management intervention that is given to all patients. Patients who do not respond to this level are thereafter given more intensive treatment at later steps in the program and will be randomized to more intensive stress-management intervention in a group setting or individually. The primary out-come is subjective distress (intrusion and avoidance) assessed by the Impact of Event Scale (IES). According to the power-analyses, 300 patients are planned to be included in the study and will be followed for one year. Other outcomes are anxiety, depression, quality of life, fatigue, stress in daily living and utilization of hospital services. This will be assessed with well-known psychometric tested questionnaires. Also, the cost-effectiveness of the intervention given in group or individually will be evaluated.

    Discussion: This randomized clinical trial will provide additional empirical evidence regarding the effectiveness of a stress-management program given in group or individually during adjuvant therapy in terms of decreased stress, minimizing fatigue, and maintaining or enhancing patients' quality of life and psychological well-being.

  • 273. Nordlinger, Bernard
    et al.
    Sorbye, Halfdan
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Poston, Graeme J.
    Schlag, Peter M.
    Rougier, Philippe
    Bechstein, Wolf O.
    Primrose, John N.
    Walpole, Euan T.
    Finch-Jones, Meg
    Jaeck, Daniel
    Mirza, Darius
    Parks, Rowan W.
    Mauer, Murielle
    Tanis, Erik
    Van Cutsem, Eric
    Scheithauer, Werner
    Gruenberger, Thomas
    Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial2013In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 14, no 12, p. 1208-1215Article in journal (Refereed)
    Abstract [en]

    Background Previous results of the EORTC intergroup trial 40983 showed that perioperative chemotherapy with FOLFOX4 (folinic acid, fluorouracil, and oxaliplatin) increases progression-free survival (PFS) compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer. Here we present overall survival data after long-term follow-up. Methods This randomised, controlled, parallel-group, phase 3 study recruited patients from 78 hospitals across Europe, Australia, and Hong Kong. Eligible patients aged 18-80 years who had histologically proven colorectal cancer and up to four liver metastases were randomly assigned (1:1) to either perioperative FOLFOX4 or surgery alone. Perioperative FOLFOX4 consisted of six 14-day cycles of oxaliplatin 85mg/m(2), folinic acid 200 mg/m(2) (DL form) or 100 mg/m2 (L form) on days 1-2 plus bolus, and fluorouracil 400 mg/m(2) (bolus) and 600 mg/m(2) (continuous 22 h infusion), before and after surgery. Patients were centrally randomised by minimisation, adjusting for centre and risk score and previous adjuvant chemotherapy to primary surgery for colorectal cancer, and the trial was open label. Analysis of overall survival was by intention to treat in all randomly assigned patients. This trial is registered with ClinicalTrials.gov, number NCT00006479. Findings Between Oct 10, 2000, and July 5, 2004, 364 patients were randomly assigned to a treatment group (182 patients in each group, of which 171 per group were eligible and 152 per group underwent resection). At a median follow-up of 8.5 years (IQR 7.6-9.5), 107 (59%) patients in the perioperative chemotherapy group had died versus 114 (63%) in the surgery-only group (HR 0.88, 95% CI 0.68-1.14; p=0.34). In all randomly assigned patients, median overall survival was 61.3 months (95% CI 51.0-83.4) in the perioperative chemotherapy group and 54.3 months (41.9-79.4) in the surgery alone group. 5-year overall survival was 51.2% (95% CI 43.6-58.3) in the perioperative chemotherapy group versus 47.8% (40.3-55.0) in the surgery-only group. Two patients in the perioperative chemotherapy group and three in the surgery-only group died from complications of protocol surgery, and one patient in the perioperative chemotherapy group died possibly as a result of toxicity of protocol treatment. Interpretation We found no difference in overall survival with the addition of perioperative chemotherapy with FOLFOX4 compared with surgery alone for patients with resectable liver metastases from colorectal cancer. However, the previously observed benefit in PFS means that perioperative chemotherapy with FOLFOX4 should remain the reference treatment for this population of patients.

  • 274. Nordlinger, Bernard
    et al.
    Sorbye, Halfdan
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Poston, Graeme John
    Schlag, Peter M.
    Rougier, Philippe
    Bechstein, Wolf
    Primrose, John Neil
    Walpole, Euan Thomas
    Finch-Jones, Meg
    Jaeck, Daniel
    Mirza, Darius
    Parks, Rowan W.
    Collette, Laurence
    Praet, Michel
    Van Cutsem, Eric
    Scheithauer, Werner
    Mauer, Murielle E.
    Gruenberger, Thomas
    Long term survival data from EORTC study 40983: Perioperative chemotherapy for resectable liver metastases from colorectal cancer2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, p. 18-18Article in journal (Other academic)
  • 275. Nordström, Lena
    et al.
    Sernbo, Sandra
    Eden, Patrik
    Grønbaek, Kirsten
    Kolstad, Arne
    Räty, Riikka
    Karjalainen, Marja-Liisa
    Geisler, Christian
    Ralfkiaer, Elisabeth
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Delabie, Jan
    Ehinger, Mats
    Jerkeman, Mats
    Ek, Sara
    SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma: a Nordic Lymphoma Group study2014In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 166, no 1, p. 98-108Article in journal (Refereed)
    Abstract [en]

    Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, where survival has been remarkably improved by use of protocols including high dose cytarabine, rituximab and autologous stem cell transplantation, such as the Nordic MCL2/3 protocols. In 2008, a MCL international prognostic index (MIPI) was created to enable stratification of the clinical diverse MCL patients into three risk groups. So far, use of the MIPI in clinical routine has been limited, as it has been shown that it inadequately separates low and intermediate risk group patients. To improve outcome and minimize treatment-related morbidity, additional parameters need to be evaluated to enable risk-adapted treatment selection. We have investigated the individual prognostic role of the MIPI and molecular markers including SOX11, TP53 (p53), MKI67 (Ki-67) and CCND1 (cyclin D1). Furthermore, we explored the possibility of creating an improved prognostic tool by combining the MIPI with information on molecular markers. SOX11 was shown to significantly add prognostic information to the MIPI, but in multivariate analysis TP53 was the only significant independent molecular marker. Based on these findings, we propose that TP53 and SOX11 should routinely be assessed and that a combined TP53/MIPI score may be used to guide treatment decisions.

  • 276. Norling, Rikke
    et al.
    Grau, Cai
    Nielsen, Michael B.
    Homøe, Preben
    Sørensen, Jens A.
    Lambertsen, Karin
    Bundgaard, Troels
    Mäkitie, Antti
    Grenman, Reidar
    Larenne, Jussi
    Koivunen, Petri
    Virtaniemi, Jukka
    Gudjonsson, Arnar
    Jetlund, Olav
    Abendstein, Helmut
    Rikardsen, Oddveig
    Lybak, Stein
    Wennerberg, Johan
    Högmo, Anders
    Laurell, Göran
    Westerborn, Anders
    Hammerlid, Eva
    Tytor, Wieslaw
    Cederblad, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    von Buchwald, Christian
    Radiological imaging of the neck for initial decision-making in oral squamous cell carcinomas: a questionnaire survey in the Nordic countries2012In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 3, p. 355-361Article in journal (Refereed)
    Abstract [en]

    Background. Fast and accurate work-up is crucial to ensure the best possible treatment and prognosis for patients with head and neck cancer. The presence or absence of neck lymph node metastases is important for the prognosis and the choice of treatment. Clinical lymph node (N)-staging is done by palpation and diagnostic imaging of the neck. We investigated the current practice of the initial radiological work-up of patients with oral squamous cell carcinomas (OSCC) in the Nordic countries. Methods. A questionnaire regarding the availability and use of guidelines and imaging modalities for radiological N-staging in OSCC was distributed to 21 Head and Neck centres in Denmark (n = 4), Finland (n = 5), Iceland (n = 1), Norway (n = 4) and Sweden (n = 7). We also asked for a description of the radiological criteria for determining the lymph nodes as clinical positive (cN+) or negative (cN0). Results. All 21 Head and Neck centres responded to the questionnaire. Denmark and Finland have national guidelines, while Norway and Sweden have local or regional guidelines. Seventeen of the 19 centres with available guidelines recommended computed tomography (CT) of the cN0 neck. The waiting time may influence the imaging modalities used. Lymph node size was the most commonly used criteria for radiological cN+, but the cut-off measures vary from 0.8 to 2.0 cm. Conclusion. Overall, CT is the most commonly recommended and used imaging modality for OSCC. Despite availability of national guidelines the type and number of radiological examinations vary between centres within a country, but the implementation of a fast-track programme may facilitate fast access to imaging. The absence of uniform criteria for determining the lymph nodes of the neck as cN+ complicates the comparison of the accuracy of the imaging modalities. Well-defined radiological strategies and criteria are needed to optimise the radiological work-up in OSCC.

  • 277.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Always look at the bright side of drugs?2015In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 2, p. 145-147Article in journal (Other academic)
  • 278.
    Nygren, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Blomqvist, Lennart
    Bergh, Jonas
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Radiological assessment of tumour response to anti-cancer drugs: time to reappraise2008In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 47, no 2, p. 316-8Article in journal (Refereed)
  • 279.
    Nygren, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Fryknäs, Mårten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Anagel, Bengt
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Repositioning of the anthelmintic drug mebendazole for the treatment for colon cancer2013In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 139, no 12, p. 2133-2140Article in journal (Refereed)
    Abstract [en]

    In the present study, we screened a compound library containing 1,600 clinically used compounds with the aim to identify compounds, which potentially could be repositioned for colon cancer therapy. Two established colon cancer cell lines were tested using the fluorometric microculture cytotoxicity assay (FMCA). For compound comparison connectivity map (CMAP) analysis, NCI 60 data mining and protein kinase binding measurements were performed. Sixty-eight compounds were defined as hits with activity in both of these cell lines (< 40 % cell survival compared with control) at 10 mu M drug concentration. Analysis of chemical similarity of the hit compounds revealed several distinct clusters, among them the antiparasitic benzimidazole group. Two of these compounds, mebendazole (MBZ) and albendazole (ABZ) are registered for human use. Data from the NCI 60 cell line panel revealed only modest correlation between MBZ and ABZ, indicating differences in mechanism of action. This was further supported when gene expression signatures were compared in the CMAP database; ABZ ranked very low when MBZ was used as the query signature. Furthermore, MBZ, but not ABZ, was found to significantly interact with several protein kinases including BCR-ABL and BRAF. Analysis of the diagnosis-specific activity of MBZ showed activity in 80 % of the colon cancer cell lines in the NCI 60 panel. Three additional colon cancer cell lines and three cell models with non-malignant phenotypes were subsequently tested, confirming selective colon cancer activity of MBZ. MBZ seemingly has repositioning potential for colorectal cancer therapy.

  • 280. Nyström, Håkan
    et al.
    Blomqvist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Høyer, Morten
    Montelius, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Muren, Ludvig Paul
    Nilsson, Per
    Taheri-Kadkhoda, Zahra
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Particle therapy: a next logical step in the improvement of radiotherapy2011In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 50, no 6, p. 741-744Article in journal (Refereed)
  • 281.
    O. Åström, K. Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, K. Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Hagberg, Hans E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    CT-guided transvertebral core biopsy of a retrocrural mass1997In: American Journal of Roentgenology, ISSN 0361-803X, E-ISSN 1546-3141, Vol. 169, no 4, p. 991-993Article in journal (Refereed)
  • 282.
    Olofsson, Roger
    et al.
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Inst Clin Sci,Dept Surg, S-41345 Gothenburg, Sweden.
    Ny, Lars
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Inst Clin Sci,Dept Oncol, S-41345 Gothenburg, Sweden.
    All-Ericsson, Charlotta
    Eilard, Malin Sternby
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Inst Clin Sci,Tranplant Inst, S-41345 Gothenburg, Sweden.
    Rizell, Magnus
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Inst Clin Sci,Tranplant Inst, S-41345 Gothenburg, Sweden.
    Cahlin, Christian
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Inst Clin Sci,Tranplant Inst, S-41345 Gothenburg, Sweden.
    Stierner, Ulrika
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Inst Clin Sci,Dept Oncol, S-41345 Gothenburg, Sweden.
    Lönn, Ulf
    Linkoping Univ Hosp, Dept Oncol, S-58185 Linkoping, Sweden.
    Hansson, Johan
    Karolinska Univ Hosp, Dept Oncol, S-17176 Stockholm, Sweden.
    Ljuslinder, Ingrid
    Norrlands Univ Hosp, Dept Oncol, S-90185 Umea, Sweden.
    Lundgren, Lotta
    Skane Univ Hosp, Dept Oncol, S-22185 Lund, Sweden.
    Ullenhag, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Kiilgaard, Jens Folke
    Univ Copenhagen, Glostrup Hosp, Dept Ophthalmol, DK-2600 Glostrup, Denmark.
    Nilsson, Jonas
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Sahlgrenska Canc Ctr, S-40530 Gothenburg, Sweden.
    Lindnér, Per
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Inst Clin Sci,Tranplant Inst, S-41345 Gothenburg, Sweden.
    Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial): study protocol for a randomized controlled trial2014In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 15, article id 317Article in journal (Refereed)
    Abstract [en]

    Background: Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in approximately 50% of patients, with the liver being the most common site for metastases. The median survival for patients with liver metastases is between 6 and 12 months, and no treatment has in randomized trials ever been shown to prolong survival. A previous phase II trial using isolated hepatic perfusion (IHP) has suggested a 14-month increase in overall survival compared with a historic control group consisting of the longest surviving patients in Sweden during the same time period (26 versus 12 months). Methods/Design: This is the protocol for a multicenter phase III trial randomizing patients with isolated liver metastases of uveal melanoma to IHP or best alternative care (BAC). Inclusion criteria include liver metastases (verified by biopsy) and no evidence of extra-hepatic tumor manifestations by positron emission tomography-computed tomography (PET-CT). The primary endpoint is overall survival at 24 months, with secondary endpoints including response rate, progression-free survival, and quality of life. The planned sample size is 78 patients throughout five years. Discussion: Patients with isolated liver metastases of uveal melanoma origin have a short expected survival and no standard treatment option exists. This is the first randomized clinical trial to evaluate IHP as a treatment option with overall survival being the primary endpoint.

  • 283. Olofsson, Sven-Erik
    et al.
    Tandstad, Torgrim
    Jerkeman, Mats
    Dahl, Olav
    Ståhl, Olof
    Klepp, Olbjörn
    Bremnes, Roy M.
    Cohn-Cedermark, Gabriella
    Langberg, Carl W.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Solberg, Arne
    Stierner, Ulrika
    Wahlqvist, Rolf
    Wijkström, Hans
    Anderson, Harald
    Cavallin-Ståhl, Eva
    Population-Based Study of Treatment Guided by Tumor Marker Decline in Patients With Metastatic Nonseminomatous Germ Cell Tumor: A Report From the Swedish-Norwegian Testicular Cancer Group2011In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 29, no 15, p. 2032-2039Article in journal (Refereed)
    Abstract [en]
    Purpose From 1995 to 2003, 603 adult patients from Sweden and Norway with metastatic testicular nonseminomatous germ cell tumor (NSGCT) were included prospectively in a population-based protocol with strict guidelines for staging, treatment, and follow-up. Patients with extragonadal primary tumor or previous treatment for contralateral testicular tumor were excluded. The basic strategy was to individualize treatment according to initial tumor marker response. Methods Initial treatment for all patients was two courses of standard bleomycin, etoposide, and cisplatin (BEP), with tumor markers analyzed weekly. Good response was defined as a half-life (t(1/2)) for alpha-fetoprotein (AFP) of <= 7 days and/or for beta-human chorionic gonadotropin (beta-HCG) of <= 3 days. Patients with prolonged marker t(1/2) (ie, poor response) received intensification with addition of ifosfamide (BEP-if/PEI) in step 1. If poor response continued, the treatment was intensified with high-dose chemotherapy with stem-cell rescue as step 2. Results Overall, 99% of all patients with metastatic testicular NSGCT in the population were included in the protocol. Median follow-up was 8.2 years. Seventy-seven percent of the patients were treated with BEP alone; 18% received intensification step 1%, and 5% received intensification step 2. Grouped according to International Germ Cell Consensus Classification, 10-year overall survival was 94.7% in good-prognosis patients, 90.0% in intermediate-prognosis patients, and 67.4% in poor-prognosis patients. Conclusion With detailed treatment protocols and a dedicated collaborative group of specialists, treatment results comparable to those reported from large single institutions can be achieved at national level. With the treatment principles used in Swedish-Norwegian Testicular Cancer Group study SWENOTECA IV, the survival of intermediate-prognosis patients is remarkable and close to that of good-prognosis patients.
  • 284.
    Olsson, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Alfonsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Ander, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Brantnell, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Burell, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Grönqvist, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Hauffman, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Held, Claes
    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.
    Lindahl Norberg, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Mattsson, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Norlund, Fredrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Sjöström, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media, Information Systems.
    Toft, Teolinda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    U-CARE – internet-based psychosocial care and psychological treatment in connection to somatic disease2013Conference paper (Refereed)
  • 285.
    Olsson, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Alfonsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Ander, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Burell, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Grönqvist, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lindahl-Norberg, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Lochan, Ruth
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Mattsson, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Norlund, Fredrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Sjöström, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Toft, Teolinda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    U-CARE: a research program on psychosocial care via the internet2012Conference paper (Refereed)
    Abstract [en]

    U-CARE is one of the Swedish government’s strategic research programs atUppsala University. The overarching goal is to promote psychosocial healthamong patients suffering from somatic disease and their significant others by means of self-help programs delivered via an internet platform. Another goal is to reduce costs for individuals and the society caused by emotional distress in response to somatic disease. Professionals within clinical psychology, health economics, and information systems collaborate to reach this goal.

    Approximately 20% of patients suffering from somatic disease as well as theirsignificant others experience a clinically relevant level of emotional distress in response to disease and treatment. This is in itself alerting, but becomes even moreproblematic since physicians and nurses show low sensitivity and specificityin detecting patients and significant others experiencing a clinically relevant level of distress. This can result in persistent distress causing human suffering as well as costs for individuals and the society.

    During 2010-2011 an internet platform: www.u-care.se to provide interactive support and cognitive behavioral therapy has been constructed within the U-CARE program. The platform supports, among other things, rule-based unfolding of self-help material for participants, interaction between participants and therapists, interaction within a participant community, and research including a detailed log of participants’ behaviors on the platform. In addition self-help programs of interactive support and cognitive behavioural therapy for adolescents with cancer: U-CARE: TeenCan, adults with cancer: U-CARE: AdultsCan, and adults having had a myocardial infarct: U-CARE: Heart to be provided via www.u-care.se have been constructed.

    Through a multi-disciplinary and design-oriented approach, the U-CARE program aims at developing new evidence-based knowledge in basic and applied psychosocial health care,and actively promoting its implementation in health care practice as well as in undergraduate and advanced education.

  • 286.
    Olsson, L. I.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centrum för klinisk forskning i D län (CKFD).
    Granström, F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centrum för klinisk forskning i D län (CKFD).
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Socioeconomic inequalities in the use of radiotherapy for rectal cancer: A nationwide study2011In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 47, no 3, p. 347-353Article in journal (Refereed)
    Abstract [en]

    Preoperative radiotherapy (PRT) in rectal cancer reduces the risk of local recurrence by at least half but the influence of the socioeconomic status of patients on the use of PRT is little investigated in Europe. METHODS: Individually attained data on civil status, education and income were linked to the Swedish Rectal Cancer Registry 1995-2005 (n=16,713) and analysed by logistic regression. RESULTS: Forty-six percentage of the patients received PRT and the crude rate varied with age, gender, civil status, education and income as well as with sublocalisation, stage, type of hospital and health care region. In a multivariate analysis, all civil status groups had PRT to a lesser extent compared with married patients; odds ratio (OR) for unmarried patients was 0.67 (95% confidence interval (CI) 0.59-0.76). Patients with secondary and university education had PRT to the same extent as those with compulsory school (OR 1.04 (0.94-1.15) and 0.92 (0.81-1.06)). The use of PRT was associated with income; OR for patients with income Q1 versus Q4 was 0.76 (0.67-0.86). The inequalities by civil status and income remained unchanged also in groups with a relatively stronger indication for adjuvant radiotherapy, i.e. younger patients and in low rectal cancer. CONCLUSION: Unmarried and low-income patients are at increased risk for not receiving PRT in rectal cancer. Comorbidity may explain some differences but increased awareness of the role of non-medical variables for the use of PRT is warranted.

  • 287. Ording, Anne Gulbech
    et al.
    Boffetta, Paolo
    Garne, Jens Peter
    Nyström, Petra Mariann Witt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Cronin-Fenton, Deirdre
    Froslev, Trine
    Silliman, Rebecca
    Sorensen, Henrik Toft
    Lash, Timothy L.
    Relative mortality rates from incident chronic diseases among breast cancer survivors - A 14 year follow-up of five-year survivors diagnosed in Denmark between 1994 and 20072015In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 51, no 6, p. 767-775Article in journal (Refereed)
    Abstract [en]

    Background: It remains unknown whether incident chronic diseases are more often fatal among breast cancer survivors than among women free of breast cancer. Methods: We conducted a nationwide matched cohort study of all Danish breast cancer patients diagnosed between 1994 and 2007, who survived for five years. We compared their long-term mortality with five times as many women from the general population without breast cancer, matched on age. We used time-varying methods to compute mortality rate ratios (MRRs) for incident diseases included in the Charlson Comorbidity Index (CCI). Results: One third of five-year breast cancer survivors developed incident diseases during 14 years of follow-up, with about the same incidence as women without breast cancer. Mortality associated with any incident disease was similar among breast cancer survivors (MRR = 7.1, 95% confidence interval (CI): 6.7, 7.4) and comparison women (MRR = 7.5, 95% CI: 7.3, 7.7). Among breast cancer patients, relative mortality associated with incident diseases was higher among patients treated with chemotherapy (MRR = 10, 95% CI: 8.7, 12) and radiotherapy (MRR = 9.8, 95% CI: 8.8, 11) than among patients who received surgery (MRR = 7.0, 95% CI: 6.7, 7.4) or hormonal therapy (MRR = 6.3, 95% CI: 5.8, 6.9). Conclusion: There were no marked differences in mortality of diseases among breast cancer survivors and women from the general population. Among breast cancer patients, new diseases were more often fatal in patients treated with chemotherapy and radiotherapy. Five-year breast cancer survivors have similar risk of dying from new chronic medical conditions as women from the general population without breast cancer.

  • 288.
    Ording, Anne Gulbech
    et al.
    Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark..
    Garne, Jens Peter
    Aarhus Univ Hosp, Aalborg Hosp, Breast Clin, DK-8000 Aarhus, Denmark..
    Nyström, Petra Mariann Witt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology. Aarhus Univ Hosp, Aalborg Hosp, Dept Oncol, DK-8000 Aarhus, Denmark..
    Cronin-Fenton, Deirdre
    Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark..
    Tarp, Maja
    Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark..