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  • 51. Chang, Ellen T.
    et al.
    Ekström Smedby, Karin
    Zhang, Shumin M.
    Hjalgrim, Henrik
    Melbye, Mads
    Öst, Åke
    Wolk, Alicja
    Adami, Hans-Olov
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Alcohol intake and risk of non-Hodgkin lymphoma in men and women2004In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 15, no 10, p. 1067-1076Article in journal (Other academic)
    Abstract [en]

    OBJECTIVE: The effect of alcohol intake on risk of NHL is unclear. We therefore conducted a population-based case-control study to examine the association between alcohol and NHL risk. METHODS: 613 NHL cases and 480 population controls in Sweden reported their average consumption of beer, wine, and liquor 2 years before the study. Unconditional logistic regression was used to estimate the odds ratios (OR) and corresponding 95% confidence intervals (CI) for associations between alcohol intake and NHL risk. RESULTS: Intake of total alcohol, beer, wine, or liquor was not associated with risk of overall NHL. There was no difference in risk of NHL among those who habitually consumed above 19.1 g of ethanol per day, compared to those who consumed on average 0-2.2 g of ethanol per day (OR = 1.2 (95% CI: 0.8, 1.7); Ptrend = 0.29). However, the association was significantly positive among males (OR = 1.8 (95% CI: 1.1, 2.9); Ptrend = 0.06). Total alcohol, beer, wine, or liquor intake was not associated with any major histopathologic subtype of NHL examined, apart from an association between high wine consumption and increased risk of chronic lymphocytic leukemia. CONCLUSIONS: Alcohol does not appear to be a major etiologic factor for overall NHL, nor its common subtypes.

  • 52. Chang, Ellen T.
    et al.
    Hjalgrim, Henrik
    Ekström Smedby, Karin
    Åkerman, Måns
    Tani, Edneia
    Johnsen, Hans E.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Adami, Hans-Olov
    Melbye, Mads
    Body mass index and risk of malignant lymphoma in Scandinavian men and women2005In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 97, no 3, p. 210-218Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The incidence of non-Hodgkin lymphoma and prevalence of obesity are increasing globally. A suggested positive association between obesity and risk of non-Hodgkin lymphoma has prompted us to investigate the relationship between body mass index (BMI) and risk of malignant lymphoma subtypes in a population-based case-control study. METHODS: Telephone interviews were conducted with 3055 case patients with non-Hodgkin lymphoma and 618 case patients with Hodgkin lymphoma diagnosed between October 1, 1999, and August 30, 2002, and 3187 population-based control subjects. The interviews assessed current height, normal adult weight, and other possible risk factors. Multivariable odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for risk of lymphoma were estimated by unconditional logistic regression. All statistical tests were two-sided. RESULTS: BMI was not associated with risk of overall non-Hodgkin lymphoma or of Hodgkin lymphoma (for example, comparing the highly obese group [BMI > or =35.0 kg/m2] with the normal-weight group [BMI = 18.5-24.9 kg/m2], OR for risk of non-Hodgkin lymphoma = 0.9, 95% CI = 0.6 to 1.3; P(trend) across all categories of BMI = .27). BMI was also not associated with risk of any non-Hodgkin lymphoma subtype evaluated, although there was some evidence of a positive association with risk of diffuse large B-cell lymphoma (for example, comparing the highly obese group with the normal-weight group, OR for diffuse large B-cell lymphoma = 1.5, 95% CI = 0.9 to 2.4; P(trend) =.05). CONCLUSIONS: Excess weight does not appear to be associated with an increased risk of malignant lymphoma in general, or with a risk of most major lymphoma subtypes. Hence, the growing incidence of obesity is unlikely to be an important contributor to the increasing incidence of non-Hodgkin lymphoma worldwide.

  • 53. Chang, Ellen T.
    et al.
    Smedby, Karin Ekström
    Hjalgrim, Henrik
    Schöllkopf, Claudia
    Porwit-MacDonald, Anna
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Tani, Edneia
    d'Amore, Francesco
    Melbye, Mads
    Adami, Hans-Olov
    Glimelius, Bengt
    Medication use and risk of non-Hodgkin's lymphoma2005In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 162, no 10, p. 965-974Article in journal (Refereed)
    Abstract [en]

    Conflicting results from previous epidemiologic studies shed little light on whether medication use is associated with risk of non-Hodgkin's lymphoma (NHL). To investigate this question, the authors conducted a population-based case-control study in Denmark and Sweden from 1999 to 2002, including 3,055 incident NHL cases and 3,187 controls. Participants reported their past use of medications and history of particular medical conditions. Unconditional logistic regression was used to estimate multivariate odds ratios and 95% confidence intervals for the associations between medication use and risk of NHL; all statistical tests were two sided. Use of antibiotics more than 10 times during adulthood was positively associated with risk of NHL and most major NHL subtypes; when users were compared with nonusers, the odds ratio for NHL was 1.8 (95% confidence interval: 1.4, 2.3); p(trend) for total antibiotic use <0.001. In addition, high cumulative use of nonsteroidal anti-inflammatory drugs was marginally associated with elevated NHL risk. Other medications evaluated were not associated with risk of NHL or its most common subtypes. Findings suggest that inflammation, infections, susceptibility to infections, and/or use of antibiotics or nonsteroidal anti-inflammatory drugs to treat these conditions may increase the risk of NHL. However, most of the medications examined were not associated with NHL risk.

  • 54.
    Chen, Lingjing
    et al.
    Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.
    Eloranta, Sandra
    Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.
    Martling, Anna
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Glimelius, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.
    Neovius, Martin
    Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Smedby, Karin E.
    Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.
    Short- and long-term risks of cardiovascular disease following radiotherapy in rectal cancer in four randomized controlled trials and a population-based register2018In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 126, no 3, p. 424-430Article in journal (Refereed)
    Abstract [en]

    Aim: A population-based cohort and four randomized trials enriched with long-term register data were used to clarify if radiotherapy in combination with rectal cancer surgery is associated with increased risks of cardiovascular disease (CVD). Methods: We identified 14,901 rectal cancer patients diagnosed 1995-2009 in Swedish nationwide registers, of whom 9227 were treated with preoperative radiotherapy. Also, we investigated 2675 patients with rectal cancer previously randomized to preoperative radiotherapy or not followed by surgery in trials conducted 1980-1999. Risks of CVD overall and subtypes were estimated based on prospectively recorded hospital visits during relapse-free follow-up using multivariable Cox regression. Maximum follow-up was 18 and 33 years in the register and trials, respectively. Results: We found no association between preoperative radiotherapy and overall CVD risk in the register (Incidence Rate Ratio, IRR = 0.99, 95% confidence interval (CI) 0.92-1.06) or in the pooled trials (IRR = 1.07, 95% CI 0.93-1.24). We noted an increased risk of venous thromboembolism among irradiated patients in both cohorts (lRR(register) = 1.41, 95% CI 1.15-2.72; IRRtrials = 1.41, 95% CI 0.97-2.04), that remained during the first 6 months following surgery among patients treated 2006-2009, after the introduction of antithrombotic treatment (IRR6 (months) = 2.30, 95% CI 1.01-5.21). However, the absolute rate difference of venous thromboembolism attributed to RT was low (10 cases per 1000 patients and year). Discussion: Preoperative radiotherapy did not affect rectal cancer patients' risk of CVD overall. Although an excess risk of short-term venous thromboembolism was noted, the small increase in absolute numbers does not call for general changes in routine prophylactic treatment, but might do so for patients already at high risk of venous thromboembolism. (C) 2017 Elsevier B.V. All rights reserved.

  • 55. Dewdney, Alice
    et al.
    Cunningham, David
    Tabernero, Josep
    Capdevila, Jaume
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Cervantes, Andres
    Tait, Diana
    Brown, Gina
    Wotherspoon, Andrew
    de Castro, David Gonzalez
    Chua, Yu Jo
    Wong, Rachel
    Barbachano, Yolanda
    Oates, Jacqueline
    Chau, Ian
    Multicenter Randomized Phase II Clinical Trial Comparing Neoadjuvant Oxaliplatin, Capecitabine, and Preoperative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision in Patients With High-Risk Rectal Cancer (EXPERT-C)2012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 14, p. 1620-1627Article in journal (Refereed)
    Abstract [en]

    Purpose To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer.

    Patients and Methods Patients with operable magnetic resonance imaging-defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX + C). The primary end point was complete response (CR; pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response (RR), progression-free survival (PFS), overall survival (OS), and safety in the wild-type and overall populations and a molecular biomarker analysis.

    Results One hundred sixty-five eligible patients were randomly assigned. Ninety (60%) of 149 assessable tumors were KRAS or BRAF wild type (CAPOX, n = 44; CAPOX + C, n = 46), and in these patients, the addition of cetuximab did not improve the primary end point of CR (9% v 11%, respectively; P = 1.0; odds ratio, 1.22) or PFS (hazard ratio [ HR], 0.65; P = .363). Cetuximab significantly improved RR (CAPOX v CAPOX + C: after chemotherapy, 51% v 71%, respectively; P = .038; after chemoradiation, 75% v 93%, respectively; P = .028) and OS (HR, 0.27; P = .034). Skin toxicity and diarrhea were more frequent in the CAPOX + C arm.

    Conclusion Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.

  • 56. Dias, M M
    et al.
    Pignon, J-P
    Karapetis, C S
    Boige, V
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Kweekel, D M
    Lara, P N
    Laurent-Puig, P
    Martinez-Balibrea, E
    Páez, D
    Punt, C J A
    Redman, M W
    Toffoli, G
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    McKinnon, R A
    Sorich, M J
    The effect of the UGT1A1*28 allele on survival after irinotecan-based chemotherapy: a collaborative meta-analysis2014In: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 14, no 5, p. 424-431Article in journal (Refereed)
    Abstract [en]

    To date, studies of irinotecan pharmacogenetics have mostly focused on the effect of the UGT1A1*28 allele on irinotecan-related toxicity. However, the clinical utility of routine UGT1A1*28 genotyping to pre-emptively adjust irinotecan dosage is dependent upon whether UGT1A1*28 also affects patient survival following irinotecan therapy. Previous observational studies evaluating the influence of UGT1A1*28 on survival have shown contradictory results. A systematic review and meta-analysis of both published and unpublished data were performed to summarize the available evidence of the relationship between the UGT1A1*28 allele and patient survival related to irinotecan therapy. Overall and progression-free survival meta-analysis data were available for 1524 patients and 1494 patients, respectively. The difference in the survival between patients of different UGT1A1*28 genotypes (homozygous, heterozygous or wild-type) who had received irinotecan was not found to be statistically significant. There was also no evidence of irinotecan dose, regimen or line of therapy having an impact on this association.

  • 57.
    D'Souza, Nigel
    et al.
    Croydon Univ Hosp, London, England;Royal Marsden NHS Fdn Trust, London, England;Imperial Coll, London, England.
    Babberich, Michael P. M. de Neree Tot
    Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
    d'Hoore, Andre
    Univ Clin Leuven, Leuven, Belgium.
    Tiret, Emmanuel
    Hosp St Antoine, Paris, France.
    Xynos, Evaghelos
    Interclin Hosp Heraklion, Iraklion, Greece.
    Beets-Tan, Regina G. H.
    Netherlands Canc Inst, Amsterdam, Netherlands.
    Nagtegaal, Iris D.
    Radboud Med Ctr, Nijmegen, Netherlands.
    Blomqvist, Lennart
    Karolinska Univ Hosp, Stockholm, Sweden.
    Holm, Torbjorn
    Karolinska Univ Hosp, Stockholm, Sweden.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Lacy, Antonio
    Hosp Clin Barcelona, Barcelona, Spain.
    Cervantes, Andres
    Univ Valencia, CIBERONC, Biomed Res Inst INCLIVA, Valencia, Spain.
    Glynne-Jones, Robert
    Mt Vernon Hosp, London, England.
    West, Nicholas P.
    Univ Leeds, Leeds, W Yorkshire, England.
    Perez, Rodrigo O.
    Univ Sao Paulo, Sch Med, Sao Paulo, SP, Brazil.
    Quadros, Claudio
    Aristides Maltez Hosp, Salvador, BA, Brazil.
    Lee, Kil Yeon
    Kyung Hee Univ, Med Ctr, Seoul, South Korea.
    Madiba, Thandinkosi E.
    Univ KwaZulu Natal, Durban, South Africa.
    Wexner, Steven D.
    Cleveland Clin Florida, Weston, FL USA.
    Garcia-Aguilar, Julio
    Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
    Sahani, Dushyant
    Massachusetts Gen Hosp, Boston, MA 02114 USA.
    Moran, Brendan
    Basingstoke Hosp, Basingstoke, Hants, England.
    Tekkis, Paris
    Royal Marsden NHS Fdn Trust, London, England;Imperial Coll, London, England.
    Rutten, Harm J.
    Catherina Ziekenhuis, Eindhoven, Netherlands;Maastricht Univ, GROW Sch Dev Biol & Oncol, Maastricht, Netherlands.
    Tanis, Pieter J.
    Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
    Wiggers, Theo
    Univ Med Ctr Groningen, Groningen, Netherlands.
    Brown, Gina
    Royal Marsden NHS Fdn Trust, London, England;Imperial Coll, London, England.
    Definition of the Rectum An International, Expert-based Delphi Consensus2019In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 270, no 6, p. 955-959Article in journal (Refereed)
    Abstract [en]

    Background: The wide global variation in the definition of the rectum has led to significant inconsistencies in trial recruitment, clinical management, and outcomes. Surgical technique and use of preoperative treatment for a cancer of the rectum and sigmoid colon are radically different and dependent on the local definitions employed by the clinical team. A consensus definition of the rectum is needed to standardise treatment. Methods: The consensus was conducted using the Delphi technique with multidisciplinary colorectal experts from October, 2017 to April, 2018. Results: Eleven different definitions for the rectum were used by participants in the consensus. Magnetic resonance imaging (MRI) was the most frequent modality used to define the rectum (67%), and the preferred modality for 72% of participants. The most agreed consensus landmark (56%) was "the sigmoid take-off,'' an anatomic, image-based definition of the junction of the mesorectum and mesocolon. In the second round, 81% of participants agreed that the sigmoid take-off as seen on computed tomography or MRI achieved consensus, and that it could be implemented in their institution. Also, 87% were satisfied with the sigmoid take-off as the consensus landmark. Conclusion: An international consensus definition for the rectumis the point of the sigmoid take-off as visualized on imaging. The sigmoid take-off can be identified as the mesocolon elongates as the ventral and horizontal course of the sigmoid on axial and sagittal views respectively on cross-sectional imaging. Routine application of this landmark during multidisciplinary team discussion for all patients will enable greater consistency in tumour localisation.

  • 58. Dueland, Svein
    et al.
    Guren, Tormod K.
    Hagness, Morten
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Line, Pal-Dag
    Pfeiffer, Per
    Foss, Aksel
    Tveit, Kjell M.
    Chemotherapy or Liver Transplantation for Nonresectable Liver Metastases From Colorectal Cancer?2015In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 261, no 5, p. 956-960Article in journal (Refereed)
    Abstract [en]

    Objective: The primary objective was to compare overall survival (OS) in patients with colorectal cancer (CRC) with nonresectable liver-only metastases treated by liver transplantation or chemotherapy. Background: CRC is the third most common cancer worldwide. About 50% of patients will develop metastatic disease primarily to the liver and the lung. The majority of patients with liver metastases receive palliative chemotherapy, with a median OS of trial patients of about 2 years, and less than 10% are alive at 5 years. Methods: Patients with nonresectable liver-only CRC metastases underwent liver transplantation in the SECA study (n = 21). Disease-free survival (DFS) and OS of patients included in the SECA study were compared with progression-free survival (PFS) and OS in a similar cohort of CRC patients with liver-only disease included in a first-line chemotherapy study, the NORDIC VII study (n = 47). PFS/DFS and OS were estimated by the Kaplan-Meier method. Results: DFS/PFS in both groups were 8 to 10 months. However, a dramatic difference in OS was observed. The 5-year OS rate was 56% in patients undergoing liver transplantation compared with 9% in patients starting first-line chemotherapy. The reason for the large difference in OS despite similar DFS/PFS is likely different metastatic patterns at relapse/progression. Relapse in the liver transplantation group was often detected as small, slowly growing lung metastases, whereas progression of nonresectable liver metastases was observed in the chemotherapy group. Conclusions: Compared with chemotherapy, liver transplantation resulted in a marked increased OS in CRC patients with nonresectable liver-only metastases.

  • 59. Dueland, Svein
    et al.
    Kyrre, Tormod
    Hagness, Guren Morten
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Line, Pal-Dag
    Pfeiffer, Per
    Foss, Aksel
    Tveit, Kjell Magne
    Outcome after liver transplantation compared with chemotherapy in colorectal cancer patients with nonresectable liver-only disease.2014In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, no 3Article in journal (Other academic)
  • 60. Ekström, Karin
    et al.
    Wuu, Joanne
    Hsieh, Chung-Cheng
    Glimelius, Bengt
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Lambe, Mats
    Childbearing and the risk of leukemia in Sweden2002In: Cancer Causes & Control, Vol. 13, p. 47-53Article in journal (Refereed)
  • 61. Ekström Smedby, Karin
    et al.
    Hjalgrim, Henrik
    Chang, Ellen T.
    Rostgaard, Klaus
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Adami, Hans-Olov
    Melbye, Mads
    Childhood social environment and risk of non-Hodgkin lymphoma in adults2007In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 67, no 22, p. 11074-11082Article in journal (Refereed)
    Abstract [en]

    Better hygiene and sanitation and decreasing family size parallel the increasing incidence of non-Hodgkin lymphoma (NHL) in many populations around the world. However, whether sibship size, birth order, and crowding are related to adult NHL risk is not clear. We investigated how family structure and childhood social environment were related to the risk of NHL and NHL subtypes in a large Scandinavian population-based case control study with 6,242 participants aged 18 to 74 years. Detailed exposure information was obtained through telephone interviews. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using logistic regression, and all statistical tests were two-sided. Having four or more siblings was associated with a moderately increased risk of NHL, compared with having no siblings (OR 1.34, 95% CI 1.11-1.62, P(trend) < 0.001). Having four or more older siblings was associated with a similar risk increase (OR 1.33, 95% CI 1.12-1.59, P(trend) = 0.003) compared with being the oldest, whereas number of younger siblings was unrelated overall. The associations were independent of other environmental exposures and did not vary by country, age, or sex. High household crowding was also positively associated with risk of NHL. Results were slightly stronger for diffuse large B-cell and T-cell lymphomas than for other major NHL subtypes. Our findings add to the evidence that large sibship size, late birth order, and childhood crowding are associated with an elevated risk of NHL. Effect mechanisms may be related to early age at onset and high frequency of specific infections or total microbial exposure in childhood.

  • 62.
    Elander, N. O.
    et al.
    Univ Liverpool, Canc Res UK Liverpool Canc Trials Unit, Liverpool, Merseyside, England.
    Aughton, K.
    Univ Liverpool, Canc Res UK Liverpool Canc Trials Unit, Liverpool, Merseyside, England.
    Ghaneh, P.
    Univ Liverpool, Canc Res UK Liverpool Canc Trials Unit, Liverpool, Merseyside, England.
    Neoptolemos, J. P.
    Univ Liverpool, Canc Res UK Liverpool Canc Trials Unit, Liverpool, Merseyside, England.
    Palmer, D. H.
    Univ Liverpool, Canc Res UK Liverpool Canc Trials Unit, Liverpool, Merseyside, England.
    Cox, T. F.
    Univ Liverpool, Canc Res UK Liverpool Canc Trials Unit, Liverpool, Merseyside, England.
    Campbell, F.
    Univ Liverpool, Canc Res UK Liverpool Canc Trials Unit, Liverpool, Merseyside, England.
    Costello, E.
    Univ Liverpool, Canc Res UK Liverpool Canc Trials Unit, Liverpool, Merseyside, England.
    Halloran, C. M.
    Univ Liverpool, Canc Res UK Liverpool Canc Trials Unit, Liverpool, Merseyside, England.
    Mackey, J. R.
    Cross Canc Ctr, Edmonton, AB, Canada;Univ Alberta, Edmonton, AB, Canada.
    Scarfe, A. G.
    Cross Canc Ctr, Edmonton, AB, Canada;Univ Alberta, Edmonton, AB, Canada.
    Valle, J. W.
    Univ Manchester, Christie NHS Fdn Trust, Manchester, Lancs, England.
    McDonald, A. C.
    Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland.
    Carter, R.
    Glasgow Royal Infirm, Glasgow, Lanark, Scotland.
    Tebbutt, N. C.
    Austin Hlth, Melbourne, Vic, Australia.
    Goldstein, D.
    Univ New South Wales, Prince Wales Hosp, Sydney, NSW, Australia;Univ New South Wales, Clin Sch, Sydney, NSW, Australia.
    Shannon, J.
    Nepean Canc Ctr, Camperdown, NSW, Australia;Univ Sydney, Camperdown, NSW, Australia.
    Dervenis, C.
    Agia Olga Hosp, Athens, Greece.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Deakin, M.
    Univ Hosp, North Staffordshire, Staffs, England.
    Charnley, R. M.
    Freeman Rd Hosp, Newcastle Upon Tyne, Tyne & Wear, England.
    Anthoney, A.
    St James Univ Hosp, Leeds, W Yorkshire, England.
    Lerch, M. M.
    Univ Med Greifswald, Dept Med A, Greifswald, Germany.
    Mayerle, J.
    Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Med 2, Munich, Germany.
    Olah, A.
    Petz Aladar Hosp, Gyor, Hungary.
    Buchler, M. W.
    Heidelberg Univ, Dept Surg, Heidelberg, Germany.
    Greenhalf, W.
    Univ Liverpool, Canc Res UK Liverpool Canc Trials Unit, Liverpool, Merseyside, England.
    Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy2018In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 118, no 8, p. 1084-1088Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma.

    METHODS: Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups.

    RESULTS: Neither log-rank testing on dichotomised strata or Cox proportional hazard regression showed any relationship of DCTD or RRM1 expression levels to survival overall or by treatment group.

    CONCLUSIONS: Expression of either DCTD or RRM1 was not prognostic or predictive in patients with pancreatic adenocarcinoma who had had post-operative chemotherapy with either gemcitabine or 5-fluorouracil with folinic acid.

  • 63. Elliot, A. H.
    et al.
    Martling, A.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nordenvall, C.
    Johansson, H.
    Nilsson, P. J.
    Preoperative treatment selection in rectal cancer: A population-based cohort study2014In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 40, no 12, p. 1782-1788Article in journal (Refereed)
    Abstract [en]

    Background: Preoperative radiotherapy and chemoradiotherapy for rectal cancer reduce local recurrence rates but is also associated with side effects. Thus, it is important to identify patients in whom the benefits exceed the risks. This study assessed the pretherapeutic parameters influencing the selection to preoperative treatment. Methods: Data on all patients in the Stockholm-Gotland area, Sweden, who underwent elective trans-abdominal surgery for rectal cancer in 2000-2010, was retrieved from the Regional Cancer Registry and the Swedish National Patient Register. Clinical variables were analysed in relation to selected preoperative therapy. Odds Ratios were derived from univariable and multivariable logistic regression models. Results: In total 2619 patients were included. Of these 1789 (68.3%) received preoperative radiotherapy or chemoradiotherapy. Over time, use of preoperative therapy increased (p < 0.001). In a multivariable model, age (>= 80 years) and comorbidity (Charlson Comorbidity Index score >= 2) were strongly correlated to omittance of preoperative treatment (OR: 0.05; 95% CI: 0.04-0.07 and 0.29; 95% CI: 0.21-0.39) but there was no difference between genders. Pre-treatment tumour stage was a strong predictor for selection to preoperative (chemo-) radiotherapy. However, 8.2% of patients with intermediate or advanced tumours were selected to no preoperative treatment while 55.0% of patients with early tumours were selected to preoperative therapy. Conclusions: The use of preoperative (chemo-) radiotherapy increased over time. Suboptimal adherence to guidelines appears to exist leading to a risk of overtreatment and to a small extent also undertreatment. More robust selection criteria, also including age and comorbidity should be developed.

  • 64.
    Elliot, Anders H.
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Ctr Digest Dis, Stockholm, Sweden.
    Blomqvist, Lennart
    Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Dept Imaging & Physiol, Stockholm, Sweden.
    Sigurdsson, Arni
    Rontgen Orkuhusid, Reykavik, Iceland.
    Martling, Anna
    Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Ctr Digest Dis, Stockholm, Sweden.
    Johansson, Hemming
    Karolinska Univ Hosp, Karolinska Inst, Dept Oncol Pathol OnkPat, Stockholm, Sweden.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Nilsson, Per J.
    Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Ctr Digest Dis, Stockholm, Sweden.
    An audit of performance, interpretation, and influence of pretherapeutic MRI in rectal cancer: a Swedish population-based cohort study2019In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 60, no 8, p. 955-961Article in journal (Refereed)
    Abstract [en]

    Background: The performance of magnetic resonance imaging (MRI) interpretation and communication of findings and its implication on treatment decisions has not fully been explored in rectal cancer.

    Purpose: To investigate in a region the adherence to MRI protocol standards and the relation between MRI interpretation and selection to preoperative therapy in rectal cancer.

    Material and Methods: Data on consecutive patients who underwent elective rectal cancer surgery in the region from January to June 2010 were obtained from the National Colorectal Cancer Registry. Pretherapeutic MRI images were re-evaluated. Agreement between the original reports and the re-evaluation was compared using Cohen's kappa coefficient.

    Results: Among the 94 patients included, 81 (86%) had pretherapeutic MRI in accordance with defined imaging guidelines. In 34% of the original MR reports, data on extramural venous invasion (mrEMVI) and mrT category were not reported. Complete tumor staging was not possible because of missing data in 33 (35%) of the patients. The agreement between the original MR reports and the re-evaluation regarding tumor stage was moderate (kappa = 0.48). For decided treatment compared to recommended preoperative treatment according to the re-evaluation, the agreement was fair (kappa = 0.33).

    Conclusion: Established MRI protocol standards were not universally applied. Missing data and inadequacies in original MRI reports resulted in moderate agreement between the original report and the re-evaluation indicating a risk of inappropriate treatment selection. The results call for further educational efforts in rectal cancer MRI acquisition and repeated audits of image protocol adherence and interpretation quality.

  • 65.
    Eloranta, S.
    et al.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Smedby, K. E.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Med, Div Hematol, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Ekberg, S.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Chang, E.
    Exponent Inc, Hlth Sci Practice, Ctr Epidemiol & Computat Biol, Menlo Pk, CA USA.;Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, Stanford, CA 94305 USA..
    Neovius, M.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Uppsala Akad Hosp, Uppsala, Sweden..
    Healthcare Use Among Young Hodgkin Lymphoma Survivors In The Era Of Intensified Chemotherapy And Limited Radiotherapy2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 64-65Article in journal (Refereed)
  • 66. Enciso-Mora, Victor
    et al.
    Broderick, Peter
    Ma, Yussanne
    Jarrett, Ruth F.
    Hjalgrim, Henrik
    Hemminki, Kari
    van den Berg, Anke
    Olver, Bianca
    Lloyd, Amy
    Dobbins, Sara E.
    Lightfoot, Tracy
    van Leeuwen, Flora E.
    Foersti, Asta
    Diepstra, Arjan
    Broeks, Annegien
    Vijayakrishnan, Jayaram
    Shield, Lesley
    Lake, Annette
    Montgomery, Dorothy
    Roman, Eve
    Engert, Andreas
    von Strandmann, Elke Pogge
    Reiners, Katrin S.
    Nolte, Ilja M.
    Smedby, Karin E.
    Adami, Hans-Olov
    Russell, Nicola S.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Hamilton-Dutoit, Stephen
    de Bruin, Marieke
    Ryder, Lars P.
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sorensen, Karina Meden
    Chang, Ellen T.
    Taylor, Malcolm
    Cooke, Rosie
    Hofstra, Robert
    Westers, Helga
    van Wezel, Tom
    van Eijk, Ronald
    Ashworth, Alan
    Rostgaard, Klaus
    Melbye, Mads
    Swerdlow, Anthony J.
    Houlston, Richard S.
    A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3)2010In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 42, no 12, p. 1126-1130Article in journal (Refereed)
    Abstract [en]

    To identify susceptibility loci for classical Hodgkin's lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 × 10−8), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 × 10−13) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 × 10−8). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 × 10−50). These data provide new insight into the pathogenesis of cHL.

  • 67.
    Englund, Annika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Rostgaard, K.
    Statens Serum Inst, Dept Epidemiol Res, Copenhagen S, Denmark..
    Eloranta, S.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Kuusk, T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Brown, P. de Nully
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Kamper, P.
    Aarhus Univ Hosp, Dept Haematol, Aarhus, Denmark..
    Smedby, K. E.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Hjalgrim, H.
    Statens Serum Inst, Dept Epidemiol Res, Copenhagen S, Denmark..
    Ljungman, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hjalgrim, L. Lyngsie
    Statens Serum Inst, Dept Epidemiol Res, Copenhagen S, Denmark.;Rigshosp, Dept Paediat Haematol & Oncol, Child & Youth Clin, Copenhagen, Denmark..
    Hodgkin Lymphoma In Children, Adolescents And Young Adults-A Comparative Study Of Clinical Presentation And Treatment Outcome2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 36-36Article in journal (Other academic)
  • 68.
    Erlandsson, J.
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Dept Colorectal Surg, Stockholm, Sweden.
    Pettersson, D.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Norrtalje Sjukhus, Dept Surg, Norrtalje, Sweden.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Holm, T.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Dept Colorectal Surg, Stockholm, Sweden.
    Martling, A.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Dept Colorectal Surg, Stockholm, Sweden.
    Postoperative complications in relation to overall treatment time in patients with rectal cancer receiving neoadjuvant radiotherapy2019In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 106, no 9, p. 1248-1256Article in journal (Refereed)
    Abstract [en]

    Background: The optimal timing of surgery for rectal cancer after radiotherapy (RT) is disputed. The Stockholm III trial concluded that it was oncologically safe to delay surgery for 4-8weeks after short-course RT (SRT), with fewer postoperative complications compared with SRT with surgery within a week. Other studies have indicated that an even shorter interval between RT and surgery (0-3 days) might be beneficial. The aim of this study was to identify the optimal interval to surgery after RT.

    Methods: Patients were analysed as treated, in terms of overall treatment time (OTT), the interval from the start of RT until the day of surgery. Patients receiving SRT (5x5Gy) were categorized according to OTT: 7 days (group A), 8-13 days (group B), 5-7weeks (group C) and 8-13weeks (group D). Patients receiving long-course RT (25x2Gy) were grouped into those with an OTT of 9-11weeks (group E) or 12-14weeks (group F). Outcomes assessed were postoperative complications and early mortality.

    Results: A total of 810 patients were analysed (group A, 100; group B, 247; group C, 192; group D, 160; group E, 52; group F, 59). Baseline patient characteristics were similar. There were significantly more overall complications in group B than in groups C and D. Adjusted odds ratios, with B as the reference group, were: 0.72 (95 per cent c. i. 0.40 to 1.32; P = 0.289), 0.50 (0.30 to 0.84; P = 0.009) and 0.39 (0.23 to 0.65; P < 0.001) for groups A, C and D respectively. Early mortality was similar in all groups. There were no significant differences between long-course RT groups.

    Conclusion: These results suggest that surgery should optimally be delayed for 4-12weeks (OTT 5-13weeks) after SRT.

  • 69.
    Erlandsson, Johan
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden..
    Holm, Torbjörn
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden..
    Pettersson, David
    Karolinska Inst, Dept Mol Med & Surg, Norrtalje, Sweden.;Norrtalje Hosp, Dept Surg, Norrtalje, Sweden..
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Cedermark, Björn
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden..
    Radu, Calin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Johansson, Hemming
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Machado, Mikael
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.;Karolinska Inst, Ersta Hosp, Stockholm, Sweden..
    Hjern, Fredrik
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.;Karolinska Inst, Ersta Hosp, Stockholm, Sweden..
    Hallböök, Olof
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Syk, Ingvar
    Lund Univ, Dept Surg, Malmo, Sweden..
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Martling, Anna
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden..
    Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial2017In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 18, no 3, p. 336-346Article in journal (Refereed)
    Abstract [en]

    Background: Radiotherapy reduces the risk of local recurrence in rectal cancer. However, the optimal radiotherapy fractionation and interval between radiotherapy and surgery is still under debate. We aimed to study recurrence in patients randomised between three different radiotherapy regimens with respect to fractionation and time to surgery.

    Methods: In this multicentre, randomised, non-blinded, phase 3, non-inferiority trial (Stockholm III), all patients with a biopsy-proven adenocarcinoma of the rectum, without signs of non-resectability or distant metastases, without severe cardiovascular comorbidity, and planned for an abdominal resection from 18 Swedish hospitals were eligible. Participants were randomly assigned with permuted blocks, stratified by participating centre, to receive either 5 x 5 Gy radiation dose with surgery within 1 week (short-course radiotherapy) or after 4-8 weeks (short-course radiotherapy with delay) or 25 x 2 Gy radiation dose with surgery after 4-8 weeks (long-course radiotherapy with delay). After a protocol amendment, randomisation could include all three treatments or just the two short-course radiotherapy treatments, per hospital preference. The primary endpoint was time to local recurrence calculated from the date of randomisation to the date of local recurrence. Comparisons between treatment groups were deemed non-inferior if the upper limit of a double-sided 90% CI for the hazard ratio (HR) did not exceed 1.7. Patients were analysed according to intention to treat for all endpoints. This study is registered with ClinicalTrials.gov, number NCT00904813.

    Findings: Between Oct 5, 1998, and Jan 31, 2013, 840 patients were recruited and randomised; 385 patients in the three-arm randomisation, of whom 129 patients were randomly assigned to short-course radiotherapy, 128 to short-course radiotherapy with delay, and 128 to long-course radiotherapy with delay, and 455 patients in the two-arm randomisation, of whom 228 were randomly assigned to short-course radiotherapy and 227 to short-course radiotherapy with delay. In patients with any local recurrence, median time from date of randomisation to local recurrence in the pooled short-course radiotherapy comparison was 33.4 months (range 18.2-62.2) in the short-course radiotherapy group and 19.3 months (8.5-39.5) in the short-course radiotherapy with delay group. Median time to local recurrence in the long-course radiotherapy with delay group was 33.3 months (range 17.8-114.3). Cumulative incidence of local recurrence in the whole trial was eight of 357 patients who received short-course radiotherapy, ten of 355 who received short-course radiotherapy with delay, and seven of 128 who received long-course radiotherapy (HR vs short-course radiotherapy: short-course radiotherapy with delay 1.44 [95% CI 0.41-5.11]; long-course radiotherapy with delay 2.24 [0.71-7.10]; p=0.48; both deemed non-inferior). Acute radiation-induced toxicity was recorded in one patient (<1%) of 357 after short-course radiotherapy, 23 (7%) of 355 after short-course radiotherapy with delay, and six (5%) of 128 patients after long-course radiotherapy with delay. Frequency of postoperative complications was similar between all arms when the three-arm randomisation was analysed (65 [50%] of 129 patients in the short-course radiotherapy group; 48 [38%] of 128 patients in the short-course radiotherapy with delay group; 50 [39%] of 128 patients in the long-course radiotherapy with delay group; odds ratio [OR] vs short-course radiotherapy: short-course radiotherapy with delay 0.59 [95% CI 0.36-0.97], long-course radiotherapy with delay 0.63 [0.38-1.04], p=0.075). However, in a pooled analysis of the two short-course radiotherapy regimens, the risk of postoperative complications was significantly lower after short-course radiotherapy with delay than after short-course radiotherapy (144 [53%] of 355 vs 188 [41%] of 357; OR 0.61 [95% CI 0.45-0.83] p=0.001).

    Interpretation: Delaying surgery after short-course radiotherapy gives similar oncological results compared with short-course radiotherapy with immediate surgery. Long-course radiotherapy with delay is similar to both short-course radiotherapy regimens, but prolongs the treatment time substantially. Although radiation-induced toxicity was seen after short-course radiotherapy with delay, postoperative complications were significantly reduced compared with short-course radiotherapy. Based on these findings, we suggest that short-course radiotherapy with delay to surgery is a useful alternative to conventional short-course radiotherapy with immediate surgery.

  • 70.
    Erlandsson, Johan
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden;Karolinska Univ Hosp, Dept Colorectal Canc, Stockholm, Sweden;Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, S-17176 Stockholm, Sweden.
    Lorinc, Ester
    Skane Univ Hosp, Dept Pathol & Cytol, Div Pathol Lund, Lund, Sweden;Dept Clin Sci, Div Oncol & Pathol, Barngatan 2B, SE-22185 Lund, Sweden.
    Ahlberga, Madelene
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden;Karolinska Univ Hosp, Dept Colorectal Canc, Stockholm, Sweden;Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, S-17176 Stockholm, Sweden.
    Pettersson, David
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden;Norrtalje Sjukhus, Dept Surg, Norrtalje, Sweden;TioHundra AB, Kirurgmottagningen, Box 905, S-76129 Norrtalje, Sweden.
    Holm, Torbjorn
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden;Karolinska Univ Hosp, Dept Colorectal Canc, Stockholm, Sweden;Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, S-17176 Stockholm, Sweden.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Martling, Anna
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden;Karolinska Univ Hosp, Dept Colorectal Canc, Stockholm, Sweden;Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, S-17176 Stockholm, Sweden.
    Tumour regression after radiotherapy for rectal cancer - Results from the randomised Stockholm III trial2019In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 135, p. 178-186Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Neoadjuvant radiotherapy (RT) in rectal cancer induces tumour regression with a possible complete response (pCR). The optimal fractionation and timing to surgery is not established. The Stockholm III trial randomly assigned 840 patients to 5 x 5 Gy surgery within one week (SRT), 5 x 5 Gy with surgery after 4-8 weeks, and 2 Gy x 25 with surgery after 4-8 weeks (LRT-delay). The aim of this substudy was to assess tumour regression and correlation to survival. Material and methods: All available microscopy slides were assessed by one pathologist, blinded to treatment, regarding tumour regression, graded according to the Dworak system (TRG), TNM-stage and other standard histopathology characteristics. Patients' data were collected from the Swedish ColoRectal Cancer Registry. Outcomes were TRG, pCR-rates, overall survival (OS) and time to recurrence (TTR). Results: 318, 285 and 94 patients were included in the SRT, SRT-delay and LRT-delay groups. Median follow up was 5.7 years. There were significantly lower tumour stages after SRT-delay. pCR was seen in 1 (0.3%), 29 (10.4%) and 2 (2.2%) patients in SRT, SRT-delay and LRT-delay, respectively. The pCR and Dworak grade 4 were associated with superior survival. pCR vs no-pCR Hazard Ratio (95% Confidence Interval) OS: 0.51 (0.26-0.99) p = 0.046, TTR: 0.27 (0.09-0.86) p = 0.027. Conclusion: SRT-delay induces pCR in about 10% of the patients and is in this aspect superior to 25 x 2 Gy. A complete tumour response, TRG 4 using the Dworak system, or a pCR, is associated with superior OS and TTR.

  • 71.
    Fagerlind, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Kettis, Åsa
    Uppsala University, University Administration, Planning Division. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Bergström, Ida
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ring, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Different perspectives on communication quality and emotional functioning during routine oncology consultations2012In: Patient Education and Counseling, ISSN 0738-3991, E-ISSN 1873-5134, Vol. 88, no 1, p. 16-22Article in journal (Refereed)
    Abstract [en]

    Objective: To determine quality of communication in routine oncology consultations from patient, physician, and observer perspectives, and to determine agreement of emotional function content in consultations from these three perspectives.

    Methods: In total, 69 consultations were included. Perceived quality of communication and whether or not emotional functioning had been discussed was evaluated with patient- and physician-reported questionnaires. Observer perspective was evaluated by content analysis of audio records of the consultations. Agreement between perspectives was analyzed and means compared using linear mixed models.

    Results: The patients' ratings of communication quality differed significantly from those of both the physician and observer. Observer and physician scores did not differ significantly. Physicians rated emotional functioning as discussed more often than was reported from patient and observer perspectives.

    Conclusion: The patients' view of the quality of communication differed from that of the physician and observer. Whether emotional functioning was discussed or not was also perceived differently by patients, physicians, and observer.

    Practice implications: The underpinnings and implications of these results need to be further explored regarding how to move toward a higher degree of shared understanding, where different perspectives are more in alignment, and how to develop more valid methods for evaluating communication.

  • 72.
    Fagerlind, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Kettis, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, University Administration, Planning Division.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ring, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Barriers against psychosocial communication: Oncologists' perceptions2013In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 31, no 30Article in journal (Refereed)
  • 73.
    Folkesson, J
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Nilsson, J
    Påhlman, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Glimelius, B
    Department of Oncology, Radiology and Clinical Immunology.
    Gunnarsson, U
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    The circular stapling device as a risk factor for anastomotic leakage.2004In: Colorectal Dis, ISSN 1462-8910, Vol. 6, no 4, p. 275-9Article in journal (Refereed)
  • 74.
    Folkesson, Joakim
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Birgisson, Helgi
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Pahlman, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Cedermark, Bjorn
    Glimelius, Bengt
    Department of Oncology, Radiology and Clinical Immunology. ONK.
    Gunnarsson, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate.2005In: J Clin Oncol, ISSN 0732-183X, Vol. 23, no 24, p. 5644-50Article in journal (Refereed)
  • 75. Foo, Jia Nee
    et al.
    Smedby, Karin E.
    Akers, Nicholas K.
    Berglund, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Irwan, Ishak D.
    Jia, Xiaoming
    Li, Yi
    Conde, Lucia
    Darabi, Hatef
    Bracci, Paige M.
    Melbye, Mads
    Adami, Hans-Olov
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Khor, Chiea Chuen
    Hjalgrim, Henrik
    Padyukov, Leonid
    Humphreys, Keith
    Enblad, Gunilla
    Skibola, Christine F.
    de Bakker, Paul I. W.
    Liu, Jianjun
    Coding Variants at Hexa-allelic Amino Acid 13 of HLA-DRB1 Explain Independent SNP Associations with Follicular Lymphoma Risk2013In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 93, no 1, p. 167-172Article in journal (Refereed)
    Abstract [en]

    Non-Hodgkin lymphoma represents a diverse group of blood malignancies, of which follicular lymphoma (FL) is a common subtype. Previous genome-wide association studies (GWASs) have identified in the human leukocyte antigen (HLA) class II region multiple independent SNPs that are significantly associated with FL risk. To dissect these signals and determine whether coding variants in HLA genes are responsible for the associations, we conducted imputation, HLA typing, and sequencing in three independent populations for a total of 689 cases and 2,446 controls. We identified a hexa-allelic amino acid polymorphism at position 13 of the HLA-DR beta chain that showed the strongest association with FL within the major histocompatibility complex (MHC) region (multiallelic p = 2.3 x 10(-15)). Out of six possible amino acids that occurred at that position within the population, we classified two as high risk (Tyr and Phe), two as low risk (Ser and Arg), and two as moderate risk (His and Gly). There was a 4.2-fold difference in risk (95% confidence interval = 2.9-6.1) between subjects carrying two alleles encoding high-risk amino acids and those carrying two alleles encoding low-risk amino acids (p = 1.01 x 10(-14)). This coding variant might explain the complex SNP associations identified by GWASs and suggests a common HLA-DR antigen-driven mechanism for the pathogenesis of FL and rheumatoid arthritis.

  • 76.
    Gargiulo, Piera
    et al.
    Swiss Grp Clin Canc Res SAKK Coordinating Ctr, Effingerstr 33, CH-3008 Bern, Switzerland.
    Dietrich, Daniel
    Swiss Grp Clin Canc Res SAKK Coordinating Ctr, Effingerstr 33, CH-3008 Bern, Switzerland.
    Herrmann, Richard
    Univ Hosp, Basel, Switzerland.
    Bodoky, Gyorgy
    Szt Laszlo Teaching Hosp, Budapest, Hungary.
    Ruhstaller, Thomas
    Kantonsspital, St Gallen, Switzerland.
    Scheithauer, Werner
    Univ Vienna, Med Sch, Vienna, Austria.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Berardi, Simona
    Swiss Grp Clin Canc Res SAKK Coordinating Ctr, Effingerstr 33, CH-3008 Bern, Switzerland.
    Pignata, Sandro
    Fdn G Pascale, Ist Nazl Tumori, Dept Urol & Gynecol, Naples, Italy.
    Brauchli, Peter
    Swiss Grp Clin Canc Res SAKK Coordinating Ctr, Effingerstr 33, CH-3008 Bern, Switzerland.
    Predicting mortality and adverse events in patients with advanced pancreatic cancer treated with palliative gemcitabine-based chemotherapy in a multicentre phase III randomized clinical trial: the APC-SAKK risk scores2019In: THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, ISSN 1758-8340, Vol. 11, article id UNSP 1758835918818351Article in journal (Refereed)
    Abstract [en]

    Background: The prognosis of advanced pancreatic cancer (APC) is poor and differs considerably among patients. Therefore, it is clinically relevant to identify patients with APC who are more likely to benefit from palliative chemotherapy with reduced risk of toxicity. To date, there is no prognostic score universally recommended to help clinicians in planning the therapeutic management. Methods: Using individual patient data from 319 cases of APC treated with gemcitabine-based chemotherapy and enrolled in the SAKK 44/00-CECOG/PAN.1.3.001 randomized trial, several baseline variables, including inflammatory markers, were analysed post hoc as predictors of mortality and/or grade 3 or 4 chemotherapy-related toxicity and separate risk scores were developed. Results: Median survival of the study patients was 7.9 months (interquartile range 3.7-13.3 months). Independent predictors of mortality included increased Aspartate transaminase (ASAT), low performance status, increased derived neutrophil to lymphocyte ratio, increased Carbohydrate Antigen 19-9 (CA 19-9), low haemoglobin, presence of pain, presence of metastasis and increased alkaline phosphatase (ALP). During the study, 117 patients experienced at least one grade 3 or 4 adverse event. Independent predictors of toxicity included white blood cells, ALP, renal function and bilirubin levels at baseline. Both models displayed moderate levels of discrimination (C-statistic 0.68 and 0.64 for mortality and toxicity, respectively) and adequate calibration. Conclusions: We developed simple-to-use prognostic scores for mortality and severe toxicity for patients with APC. These scores can be useful in daily practice to identify patients with increased risk of death or toxicity and to plan the most appropriate therapeutic strategy to improve survival and quality of life. Further prospective studies to validate such scores are needed.

  • 77.
    Ghaneh, Paula
    et al.
    Univ Liverpool, Liverpool Canc Res, UK Canc Trials Unit, Liverpool, Merseyside, England;Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Surg, Liverpool, Merseyside, England.
    Kleeff, Jorg
    Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Surg, Liverpool, Merseyside, England;Martin Luther Univ Halle Wittenberg, Univ Hosp Halle, Dept Surg, Halle, Germany.
    Halloran, Christopher M.
    Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Surg, Liverpool, Merseyside, England.
    Raraty, Michael
    Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Surg, Liverpool, Merseyside, England.
    Jackson, Richard
    Univ Liverpool, Liverpool Canc Res, UK Canc Trials Unit, Liverpool, Merseyside, England.
    Melling, James
    Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Surg, Liverpool, Merseyside, England.
    Jones, Owain
    Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Surg, Liverpool, Merseyside, England.
    Palmer, Daniel H.
    Univ Liverpool, Liverpool Canc Res, UK Canc Trials Unit, Liverpool, Merseyside, England.
    Cox, Trevor F.
    Univ Liverpool, Liverpool Canc Res, UK Canc Trials Unit, Liverpool, Merseyside, England.
    Smith, Chloe J.
    Univ Liverpool, Liverpool Canc Res, UK Canc Trials Unit, Liverpool, Merseyside, England.
    O'Reilly, Derek A.
    Manchester Royal Infirm, Dept Surg, Manchester, Lancs, England.
    Izbicki, Jakob R.
    Univ Hamburg, Dept Surg, Med Inst UKE, Hamburg, Germany.
    Scarfe, Andrew G.
    Univ Alberta, Dept Oncol, Div Med Oncol, Cross Canc Inst 2228, Edmonton, AB, Canada.
    Valle, Juan W.
    The Christie, Dept Med Oncol, Manchester, Lancs, England.
    McDonald, Alexander C.
    Beatson West Scotland Canc Ctr, Dept Med Oncol, Glasgow, Lanark, Scotland.
    Carter, Ross
    Glasgow Royal Infirm, Dept Surg, Glasgow, Lanark, Scotland.
    Tebbutt, Niall C.
    Austin Hlth, Dept Med Oncol, Melbourne, Vic, Australia.
    Goldstein, David
    Univ New South Wales, Prince Wales Hosp, Dept Med Oncol, Sydney, NSW, Australia;Univ New South Wales, Sch Clin, Sydney, NSW, Australia.
    Padbury, Robert
    Flinders Med Ctr, Dept Surg, Adelaide, SA, Australia.
    Shannon, Jennifer
    Nepean Canc Ctr, Dept Med Oncol, Nepean, ON, Australia;Univ Sydney, Sydney, NSW, Australia.
    Dervenis, Christos
    Agia Olga Hosp, Dept Surg, Athens, Greece.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Deakin, Mark
    Univ Hosp North Staffordshire, Dept Surg, Stoke On Trent, Staffs, England.
    Anthoney, Alan
    Univ Leeds, St Jamess Univ Hosp, Div Oncol, Leeds, W Yorkshire, England.
    Lerch, Markus M.
    Univ Med Greifswald, Dept Med A, Greifswald, Germany.
    Mayerle, Julia
    Univ Med Greifswald, Dept Med A, Greifswald, Germany.
    Olah, Attila
    Petz Aladar Hosp, Dept Surg, Gyor, Hungary.
    Rawcliffe, Charlotte L.
    Univ Liverpool, Liverpool Canc Res, UK Canc Trials Unit, Liverpool, Merseyside, England.
    Campbell, Fiona
    Heidelberg Univ, Dept Surg, Heidelberg, Germany.
    Strobel, Oliver
    Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Pathol, Liverpool, Merseyside, England.
    Buechler, Markus W.
    Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Pathol, Liverpool, Merseyside, England.
    Neoptolemos, John P.
    Univ Liverpool, Liverpool Canc Res, UK Canc Trials Unit, Liverpool, Merseyside, England;Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Surg, Liverpool, Merseyside, England;Heidelberg Univ, Dept Surg, Heidelberg, Germany.
    The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma2019In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 269, no 3, p. 520-529Article in journal (Refereed)
    Abstract [en]

    Objective and Background: Local and distant disease recurrence are frequently observed following pancreatic cancer resection, but an improved understanding of resection margin assessment is required to aid tailored therapies

    Methods: Analyses were carried out to assess the association between clinical characteristics and margin involvement as well as the effects of individual margin involvement on site of recurrence and overall and recurrence-free survival using individual patient data from the European Study Group for Pancreatic Cancer (ESPAC)-3 randomized controlled trial.

    Results: There were 1151 patients, of whom 505 (43.9%) had an RI resection. The median and 95% confidence interval (CI) overall survival was 24.9 (22.9-27.2) months for 646 (56.1%) patients with resection margin negative R0 >1 mm) tumors, 25.4 (21.6 30.4) months for 146 (12.7%) patients with RI <1 mm positive resection margins, and 18.7 (17.2-21.1) months for 359 (31.2%) patients with R1-direct positive margins (P < 0.001). In multivariable analysis, overall R 1-direct tumor margins, poor tumor differentiation, positive lymph node status, WHO performance status ≥ 1, maximum tumor size, and RI-direct posterior resection margin were all independently significantly associated with reduced overall and recurrence-free survival. Competing risks analysis showed that overall R1-direct positive resection margin status, positive lymph node status. WHO performance status 1, and R1-direct positive superior mesenteric/medial margin resection status were all significantly associated with local recurrence.

    Conclusions: RI-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence.

  • 78.
    Ghanipour, Lana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Darmanis, Spyros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Detection of prognostic biomarkers with solid-phase proximity ligation assay in patients with colorectal cancer2016In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 9, no 3, p. 251-255Article in journal (Refereed)
    Abstract [en]

    Background: In the search for prognostic biomarkers a significant amount of precious biobanked blood samples is needed if conventional analyses are used. Solid-phase proximity ligation assay (SP-PLA) is an analytic method with the ability to analyse many proteins at the same time in small amounts of plasma. The aim of this study was to explore the potential use of  SP-PLA in patients with colorectal cancer (CRC).

    Material and methods: Plasma from patients with stage I-IV CRC, with (n=31) and without (n=29) disease dissemination at diagnosis or later, was analysed with SP-PLA using 35 antibodies targeting an equal number of proteins in 5 ml plasma. Carcinoembryonic antigen (CEA), analysed earlier on this cohort, was used as a reference.

    Results: A total of 21 of the 35 proteins were detectable with SP-PLA. Patients in stage II-III with disseminated disease had lower plasma concentrations of HCC-4 (p=0.025). Low plasma levels of TIMP-1 were seen in patients with disseminated disease stage II (p=0.003). The level of CEA was higher in patients with disease dissemination compared to those without (p=0.007).

    Conclusion: SP-PLA has the ability to analyse many tumour markers simultaneously in a small amount of blood. However, none of the markers selected for the present SP-PLA analyses gave better prognostic information compared with CEA. 

  • 79.
    Ghanipour, Lana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Jirström, Karin
    Lund Univ, Div Oncol Pathol, Dept Clin Sci, Lund, Sweden..
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Associations of defect mismatch repair genes with prognosis and heredity in sporadic colorectal cancer2017In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 43, no 2, p. 311-321Article in journal (Refereed)
    Abstract [en]

    Background: Microsatellite instability arises due to defect mismatch repair (MMR) and occurs in 10-20% of sporadic colorectal cancer. The purpose was to investigate correlations between defect MMR, prognosis and heredity for colorectal cancer in first-degree relatives.

    Material and methods: Tumour tissues from 320 patients consecutively operated for colorectal cancer were analysed for immunohistochemical expression of MLH1, MSH2 and MSH6 on tissue microarrays. Information on KRAS and BRAF mutation status was available for selected cases.

    Results: Forty-seven (15%) tumours displayed MSI. No correlation was seen between patients exhibiting MSI in the tumour and heredity (p= 1.000). Patients with proximal colon cancer and MSI had an improved cancer-specific survival (p= 0.006) and prolonged time to recurrence (p= 0.040). In a multivariate analysis including MSI status, gender, CEA, vascular and neural invasion, patients with MSS and proximal colon cancer had an impaired cancer-specific survival compared with patients with MSI (HR, 3.87; CI, 1.36-11.01). The same prognostic information was potentially also in distal colon cancer; no recurrences seen in the 8 patients with stages II and III distal colon cancer and MSI, but the difference was not statistically significant.  Conclusion:No correlation between MSI and heredity was seen. Patients with MSI tumours had improved survival.

     

  • 80.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    50 years with Acta Oncologica2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 1, p. 1-2Article in journal (Other academic)
  • 81.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Adjuvant chemotherapy for patients with rectal cancer - will the controversy be resolved?2015In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 4, p. 433-436Article in journal (Other academic)
  • 82.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Any progress in pancreatic cancer?2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 3, p. 255-258Article in journal (Other academic)
  • 83.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Forty-five years in oncology, 25 years with Acta Oncologica2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 12, p. 1593-1598Article in journal (Other academic)
  • 84.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Is the benefit of oxaliplatin in rectal cancer clinically relevant?2015In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 16, no 8, p. 883-885Article in journal (Other academic)
  • 85.
    Glimelius, Bengt
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Long-term sequelae after cancer therapy--a necessary consequence of success?2004In: Acta Oncol, ISSN 0284-186X, Vol. 43, no 2, p. 132-3Article in journal (Other scientific)
  • 86.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    More than 1000 new manuscripts in 20172018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 174-175Article in journal (Other academic)
  • 87.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Multidisciplinary treatment of patients with rectal cancer: Development during the past decades and plans for the future2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 2, p. 225-236Article in journal (Refereed)
    Abstract [en]

    In rectal cancer treatment, both the local primary and the regional and systemic tumour cell deposits must be taken care of in order to improve survival. The three main treatments, surgery, radiotherapy, and chemotherapy, each with their own advantages and limitations, must then be combined to improve results. Several large randomized trials have shown that combinations of the modalities have markedly reduced the loco-regional recurrences, but have not yet had any major influence on overall survival. The best integration of the weakest modality, to date the drugs (conventional cytotoxics and biologicals), is not known. A new generation of trials exploring the best sequence of treatments is required. Furthermore, treatment of rectal cancer is administered to populations of individuals, based upon clinical factors and imaging, and can presently not be further individualized. There is an urgent need to develop response predictors.

  • 88.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Neo-adjuvant radiotherapy in rectal cancer2013In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 19, no 46, p. 8489-8501Article in journal (Refereed)
    Abstract [en]

    In rectal cancer treatment, attention has focused on the local primary tumour and the regional tumour cell deposits to diminish the risk of a loco-regional recurrence. Several large randomized trials have also shown that combinations of surgery, radiotherapy and chemotherapy have markedly reduced the risk of a loco-regional recurrence, but this has not yet had any major influence on overall survival. The best results have been achieved when the radiotherapy has been given preoperatively. Preoperative radiotherapy improves loco-regional control even when surgery has been optimized to improve lateral clearance, i.e., when a total mesorectal excision has been performed. The relative reduction is then 50%-70%. The value of radiotherapy has not been tested in combination with more extensive surgery including lateral lymph node clearance, as practised in some Asian countries. Many details about how the radiotherapy is performed are still open for discussion, and practice varies between countries. A highly fractionated radiation schedule (5 Gy x 5), proven efficacious in many trials, has gained much popularity in some countries, whereas a conventionally fractionated regimen (1.8-2.0 Gy x 25-28), often combined with chemotherapy, is used in other countries. The additional therapy adds morbidity to the morbidity that surgery causes, and should therefore be administered only when the risk of loco-regional recurrence is sufficiently high. The best integration of the weakest modality, to date the drugs (conventional cytotoxics and biologicals) is not known. A new generation of trials exploring the best sequence of treatments is required. Furthermore, there is a great need to develop predictors of response, so that treatment can be further individualized and not solely based upon clinical factors and anatomic imaging.

  • 89.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    On a prolonged interval between rectal cancer (chemo) radiotherapy and surgery2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 1, p. 1-10Article, review/survey (Refereed)
    Abstract [en]

    Preoperative radiotherapy (RT) or chemoradiotherapy (CRT) is often required before rectal cancer surgery to obtain low local recurrence rates or, in locally advanced tumours, to radically remove the tumour. RT/CRT in tumours responding completely can allow an organ-preserving strategy. The time from the end of the RT/CRT to surgery or to the decision not to operate has been prolonged during recent years. After a brief review of the literature, the relevance of the time interval to surgery is discussed depending upon the indication for RT/CRT. In intermediate rectal cancers, where the aim is to decrease local recurrence rates without any need for down-sizing/-staging, short-course RT with immediate surgery is appropriate. In elderly patients at risk for surgical complications, surgery could be delayed 5-8 weeks. If CRT is used, surgery should be performed when the acute radiation reaction has subsided or after 5-6 weeks. In locally advanced tumours, where CRT is indicated, the optimal delay is 6-8 weeks. In patients not tolerating CRT, short-course RT with a 6-8-week delay is an alternative. If organ preservation is a goal, a first evaluation should preferably be carried out after about 6 weeks, with planned surgery for week 8 if the response is inadequate. In case the response is good, a new evaluation should be carried out after about 12 weeks, with a decision to start a 'watch-and-wait' programme or operate. Chemotherapy in the waiting period is an interesting option, and has been the subject of recent trials with promising results.

  • 90.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Potential value of immunoscoring in rectal cancer patients2016In: TRANSLATIONAL CANCER RESEARCH, ISSN 2218-676X, Vol. 5, no 2, p. 94-97Article in journal (Other academic)
  • 91.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Radiotherapy in rectal cancer - What have we learnt?2013In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, no Suppl. 2, p. S24-S24Article in journal (Other academic)
  • 92.
    Glimelius, Bengt
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Rectal cancer irradiation. Long course, short course or something else?2006In: Acta Oncol, ISSN 0284-186X, Vol. 45, no 8, p. 1013-7Article, review/survey (Other (popular scientific, debate etc.))
  • 93.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Tell all the good news as soon as possible2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 9-10, p. 1067-1068Article in journal (Other academic)
  • 94.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    The 50-year anniversary of Acta Oncologica2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 1, p. 1-2Article in journal (Other academic)
  • 95.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The dream of a philologist2008In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 47, no 6, p. 991-993Article in journal (Refereed)
  • 96.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    What is most relevant in preoperative rectal cancer chemoradiotherapy - the chemotherapy, the radiation dose or the timing to surgery?2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 12, p. 1381-1385Article in journal (Refereed)
  • 97.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    What treatments should be skipped or intensified in localized rectal cancer?2018In: Future Oncology, ISSN 1479-6694, E-ISSN 1744-8301, Vol. 14, no 4, p. 313-318Article in journal (Other academic)
  • 98.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    What's new about Acta Oncologica for 2016?2015In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 10, p. 1703-1705Article in journal (Other academic)
  • 99.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Which Rectal Cancers Are Locally Advanced?2012In: Oncology, ISSN 0890-9091, Vol. 26, no 8, p. 743-+Article in journal (Other academic)
  • 100.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Cavalli-Bjorkman, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Metastatic colorectal cancer: Current treatment and future options for improved survival : Medical approach - present status2012In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 47, no 3, p. 296-314Article in journal (Refereed)
    Abstract [en]

    Background. Metastatic colorectal cancer has a poor prognosis, and the majority of patients are left with palliative measures. The development seen using medical treatments are reviewed.

    Material and methods. A systematic approach to the literature-based evidence of effects from palliative chemotherapy and targeted drugs was aimed at.

    Results. The continuous improvements during the past 20-25 years have been documented in several large conclusive trials. At the end of the 1980s, the evidence that chemotherapy should be used at all was very limited, whereas presently most patients can be offered three lines of chemotherapy with or without a targeted drug based upon good scientific evidence. Median survival in trials has gradually improved from about 6 months to above 24 months in the most recent trials. Survival in the populations has, however, not improved to the same extent. Several important issues remain to be solved, such as the best sequence of treatments, what regimens to use in various situations, when to start and when to stop if a response is seen, whether cure may be possible in a small subset of patients, and socioeconomic issues. Integration of surgery and other local methods have further improved outcome for some individuals, but must be fine-tuned.

    Conclusions. Progress has been rapid in advanced colorectal cancer. This is likely a result of well-designed trials in collaboration between academy and industry, showing a great interest in the disease. A multi-professional approach and future collaborations may hopefully introduce new treatment concepts, further improving outcome.

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