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  • 1. Buunen, Mark
    et al.
    Veldkamp, Ruben
    Hop, Wim C J
    Kuhry, Esther
    Jeekel, Johannes
    Haglind, Eva
    Påhlman, Lars
    Cuesta, Miguel A
    Msika, Simon
    Morino, Mario
    Lacy, Antonio
    Bonjer, Hendrik J
    Lundberg, Owe
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Survival after laparoscopic surgery versus open surgery for colon cancer: long-term outcome of a randomised clinical trial.2009In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 10, no 1, p. 44-52Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Laparoscopic surgery for colon cancer has been proven safe, but debate continues over whether the available long-term survival data justify implementation of laparoscopic techniques in surgery for colon cancer. The aim of the COlon cancer Laparoscopic or Open Resection (COLOR) trial was to compare 3-year disease-free survival and overall survival after laparoscopic and open resection of solitary colon cancer. METHODS: Between March 7, 1997, and March 6, 2003, patients recruited from 29 European hospitals with a solitary cancer of the right or left colon and a body-mass index up to 30 kg/m(2) were randomly assigned to either laparoscopic or open surgery as curative treatment in this non-inferiority randomised trial. Disease-free survival at 3 years after surgery was the primary outcome, with a prespecified non-inferiority boundary at 7% difference between groups. Secondary outcomes were short-term morbidity and mortality, number of positive resection margins, local recurrence, port-site or wound-site recurrence, and blood loss during surgery. Neither patients nor health-care providers were blinded to patient groupings. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00387842. FINDINGS: During the recruitment period, 1248 patients were randomly assigned to either open surgery (n=621) or laparoscopic surgery (n=627). 172 were excluded after randomisation, mainly because of the presence of distant metastases or benign disease, leaving 1076 patients eligible for analysis (542 assigned open surgery and 534 assigned laparoscopic surgery). Median follow-up was 53 months (range 0.03-60). Positive resection margins, number of lymph nodes removed, and morbidity and mortality were similar in both groups. The combined 3-year disease-free survival for all stages was 74.2% (95% CI 70.4-78.0) in the laparoscopic group and 76.2% (72.6-79.8) in the open-surgery group (p=0.70 by log-rank test); the difference in disease-free survival after 3 years was 2.0% (95% CI -3.2 to 7.2). The hazard ratio (HR) for disease-free survival (open vs laparoscopic surgery) was 0.92 (95% CI 0.74-1.15). The combined 3-year overall survival for all stages was 81.8% (78.4-85.1) in the laparoscopic group and 84.2% (81.1-87.3) in the open-surgery group (p=0.45 by log-rank test); the difference in overall survival after 3 years was 2.4% (95% CI -2.1 to 7.0; HR 0.95 [0.74-1.22]). INTERPRETATION: Our trial could not rule out a difference in disease-free survival at 3 years in favour of open colectomy because the upper limit of the 95% CI for the difference just exceeded the predetermined non-inferiority boundary of 7%. However, the difference in disease-free survival between groups was small and, we believe, clinically acceptable, justifying the implementation of laparoscopic surgery into daily practice. Further studies should address whether laparoscopic surgery is superior to open surgery in this setting.

  • 2. Dabestani, Saeed
    et al.
    Marconi, Lorenzo
    Hofmann, Fabian
    Stewart, Fiona
    Lam, Thomas B. L.
    Canfield, Steven E.
    Staehler, Michael
    Powles, Thomas
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bex, Axel
    Local treatments for metastases of renal cell carcinoma: a systematic review2014In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 15, no 12, p. E549-E561Article, review/survey (Refereed)
    Abstract [en]

    Local treatment of metastases such as metastasectomy or radiotherapy remains controversial in the treatment of metastatic renal cell carcinoma. To investigate the benefits and harms of various local treatments, we did a systematic review of all types of comparative studies on local treatment of metastases from renal cell carcinoma in any organ. Interventions included metastasectomy, radiotherapy modalities, and no local treatment. The results suggest that patients treated with complete metastasectomy have better survival and symptom control (including pain relief in bone metastases) than those treated with either incomplete or no metastasectomy. Nevertheless, the available evidence was marred by high risks of bias and confounding across all studies. Although the findings presented here should be interpreted with caution, they and the identified gaps in knowledge should provide guidance for clinicians and researchers, and directions for further research.

  • 3. Goldbrunner, Roland
    et al.
    Minniti, Giuseppe
    Preusser, Matthias
    Jenkinson, Michael D.
    Sallabanda, Kita
    Houdart, Emmanuel
    von Deimling, Andreas
    Stavrinou, Pantelis
    Lefranc, Florence
    Lund-Johansen, Morten
    Moyal, Elizabeth Cohen-Jonathan
    Brandsma, Dieta
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Centre Stockholm, Stockholm, Sweden.
    Soffietti, Riccardo
    Weller, Michael
    EANO guidelines for the diagnosis and treatment of meningiomas2016In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 17, no 9, p. E383-E391Article, review/survey (Refereed)
    Abstract [en]

    Although meningiomas are the most common intracranial tumours, the level of evidence to provide recommendations for the diagnosis and treatment of meningiomas is low compared with other tumours such as high-grade gliomas. The meningioma task force of the European Association of Neuro-Oncology (EANO) assessed the scientific literature and composed a framework of the best possible evidence-based recommendations for health professionals. The provisional diagnosis of meningioma is mainly made by MRI. Definitive diagnosis, including histological classification, grading, and molecular profiling, requires a surgical procedure to obtain tumour tissue. Therefore, in many elderly patients, observation is the best therapeutic option. If therapy is deemed necessary, the standard treatment is gross total surgical resection including the involved dura. As an alternative, radiosurgery can be done for small tumours, or fractionated radiotherapy in large or previously treated tumours. Treatment concepts combining surgery and radiosurgery or fractionated radiotherapy, which enable treatment of the complete tumour volume with low morbidity, are being developed. Pharmacotherapy for meningiomas has remained largely experimental. However, antiangiogenic drugs, peptide receptor radionuclide therapy, and targeted agents are promising candidates for future pharmacological approaches to treat refractory meningiomas across all WHO grades.

  • 4. Hoang-Xuan, Khe
    et al.
    Bessell, Eric
    Bromberg, Jacoline
    Hottinger, Andreas F.
    Preusser, Matthias
    Ruda, Roberta
    Schlegel, Talli
    Soussain, Carole
    Abacioglu, Ufuk
    Cassoux, Nathalie
    Deckert, Martina
    Dirven, Siemens M. F.
    Ferreri, Andres J. M.
    Graus, Francesc
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Center Stockholm County, Stockholm, Sweden.
    Herdinger, Ulric
    Taphoorn, Martin
    Soffietti, Riccardo
    Weller, Michael
    Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology2015In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 16, no 7, p. E322-E332Article, review/survey (Refereed)
    Abstract [en]

    The management of primary CNS lymphoma is one of the most controversial topics in neuro-oncology because of the complexity of the disease and the very few controlled studies available. In 2013, the European Association of Neuro-Oncology created a multidisciplinary task force to establish evidence-based guidelines for immunocompetent adults with primary CNS lymphoma. In this Review, we present these guidelines, which provide consensus considerations and recommendations for diagnosis, assessment, staging, and treatment of primary CNS lymphoma. Specifically, we address aspects of care related to surgery, systemic and intrathecal chemotherapy, intensive chemotherapy with autologous stem-cell transplantation, radiotherapy, intraocular manifestations, and management of elderly patients. The guidelines should aid clinicians in their daily practice and decision making, and serve as a basis for future investigations in neuro-oncology.

  • 5. Lacas, Benjamin
    et al.
    Bourhis, Jean
    Overgaard, Jens
    Zhang, Qiang
    Gregoire, Vincent
    Nankivell, Matthew
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Szutkowski, Zbigniew
    Suwinski, Rafal
    Poulsen, Michael
    O'Sullivan, Brian
    Corvo, Renzo
    Laskar, Sarbani Ghosh
    Fallai, Carlo
    Yamazaki, Hideya
    Dobrowsky, Werner
    Cho, Kwan Ho
    Garden, Adam S.
    Langendijk, Johannes A.
    Viegas, Celia Maria Pais
    Hay, John
    Lotayef, Mohamed
    Parmar, Mahesh K. B.
    Auperin, Anne
    van Herpen, Carla
    Maingon, Philippe
    Trotti, Andy M.
    Grau, Cai
    Pignon, Jean-Pierre
    Blanchard, Pierre
    Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis2017In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 18, no 9, p. 1221-1237Article in journal (Refereed)
    Abstract [en]

    Background: The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck(MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials.

    Methods: For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival.

    Findings: Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90–0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3–4·9) and at 10 years of 1·2% (−0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74–0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (−0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05–1·42; p=0·0098), with absolute differences at 5 years of −5·8% (−11·9 to 0·3) and at 10 years of −5·1% (−13·0 to 2·8).

    Interpretation: This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested.

  • 6.
    Lindholm, Lars H
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blood-pressure drugs and cancer: much ado about nothing?2011In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 12, no 1, p. 6-8Article in journal (Refereed)
  • 7. Malmström, Annika
    et al.
    Grønberg, Bjørn Henning
    Marosi, Christine
    Stupp, Roger
    Frappaz, Didier
    Schultz, Henrik
    Abacioglu, Ufuk
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lhermitte, Benoit
    Hegi, Monika E
    Rosell, Johan
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial.2012In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 13, no 9, p. 916-926Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Most patients with glioblastoma are older than 60 years, but treatment guidelines are based on trials in patients aged only up to 70 years. We did a randomised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma.

    METHODS: Patients with newly diagnosed glioblastoma were recruited from Austria, Denmark, France, Norway, Sweden, Switzerland, and Turkey. They were assigned by a computer-generated randomisation schedule, stratified by centre, to receive temozolomide (200 mg/m(2) on days 1-5 of every 28 days for up to six cycles), hypofractionated radiotherapy (34·0 Gy administered in 3·4 Gy fractions over 2 weeks), or standard radiotherapy (60·0 Gy administered in 2·0 Gy fractions over 6 weeks). Patients and study staff were aware of treatment assignment. The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered, number ISRCTN81470623.

    FINDINGS: 342 patients were enrolled, of whom 291 were randomised across three treatment groups (temozolomide n=93, hypofractionated radiotherapy n=98, standard radiotherapy n=100) and 51 of whom were randomised across only two groups (temozolomide n=26, hypofractionated radiotherapy n=25). In the three-group randomisation, in comparison with standard radiotherapy, median overall survival was significantly longer with temozolomide (8·3 months [95% CI 7·1-9·5; n=93] vs 6·0 months [95% CI 5·1-6·8; n=100], hazard ratio [HR] 0·70; 95% CI 0·52-0·93, p=0·01), but not with hypofractionated radiotherapy (7·5 months [6·5-8·6; n=98], HR 0·85 [0·64-1·12], p=0·24). For all patients who received temozolomide or hypofractionated radiotherapy (n=242) overall survival was similar (8·4 months [7·3-9·4; n=119] vs 7·4 months [6·4-8·4; n=123]; HR 0·82, 95% CI 0·63-1·06; p=0·12). For age older than 70 years, survival was better with temozolomide and with hypofractionated radiotherapy than with standard radiotherapy (HR for temozolomide vs standard radiotherapy 0·35 [0·21-0·56], p<0·0001; HR for hypofractionated vs standard radiotherapy 0·59 [95% CI 0·37-0·93], p=0·02). Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation (9·7 months [95% CI 8·0-11·4] vs 6·8 months [5·9-7·7]; HR 0·56 [95% CI 0·34-0·93], p=0·02), but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy (HR 0·97 [95% CI 0·69-1·38]; p=0·81). As expected, the most common grade 3-4 adverse events in the temozolomide group were neutropenia (n=12) and thrombocytopenia (n=18). Grade 3-5 infections in all randomisation groups were reported in 18 patients. Two patients had fatal infections (one in the temozolomide group and one in the standard radiotherapy group) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed.

    INTERPRETATION: Standard radiotherapy was associated with poor outcomes, especially in patients older than 70 years. Both temozolomide and hypofractionated radiotherapy should be considered as standard treatment options in elderly patients with glioblastoma. MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide. FUNDING: Merck, Lion's Cancer Research Foundation, University of Umeå, and the Swedish Cancer Society.

  • 8. Malmström, Annika
    et al.
    Stupp, Roger
    Hegi, Monika
    Rosell, Johan
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Treatment options in elderly patients with glioblastoma: authors' reply2012In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 13, no 11, p. E461-E462Article in journal (Refereed)
  • 9. Nilsson, Sten
    et al.
    Franzén, Lars
    Länssjukhuset Sundsvall-Härnösand, Sundsvall, Sweden.
    Parker, Christopher
    Tyrrell, Christopher
    Blom, René
    Tennvall, Jan
    Lennernäs, Bo
    Petersson, Ulf
    Johannessen, Dag C
    Sokal, Michael
    Pigott, Katharine
    Yachnin, Jeffrey
    Garkavij, Michael
    Strang, Peter
    Harmenberg, Johan
    Bolstad, Bjørg
    Bruland, Oyvind S
    Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study.2007In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 8, no 7, p. 587-594Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The alpha-emitter radium-223 ((223)Ra) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer. We aimed to study mature outcomes from a randomised, multicentre, phase II study of (223)Ra.

    METHODS: Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy were assigned to four intravenous injections of (223)Ra (50 kBq/kg, 33 patients) or placebo (31 patients), given every 4 weeks. Primary endpoints were change in bone-alkaline phosphatase (ALP) concentration and time to skeletal-related events (SREs). Secondary endpoints included toxic effects, time to prostate-specific-antigen (PSA) progression, and overall survival. All tests were done at a 5% significance level, based on intention to treat.

    FINDINGS: Median relative change in bone-ALP during treatment was -65.6% (95% CI -69.5 to -57.7) and 9.3% (3.8-60.9) in the (223)Ra group and placebo groups, respectively (p<0.0001, Wilcoxon ranked-sums test). Hazard ratio for time to first SRE, adjusted for baseline covariates, was 1.75 (0.96-3.19, p=0.065, Cox regression). Haematological toxic effects did not differ significantly between two groups. No patient discontinued (223)Ra because of treatment toxicity. Median time to PSA progression was 26 weeks (16-39) versus 8 weeks (4-12; p=0.048) for (223)Ra versus placebo, respectively. Median overall survival was 65.3 weeks (48.7-infinity) for (223)Ra and 46.4 weeks (32.1-77.4) for placebo (p=0.066, log rank). The hazard ratio for overall survival, adjusted for baseline covariates was 2.12 (1.13-3.98, p=0.020, Cox regression).

    INTERPRETATION: (223)Ra was well tolerated with minimum myelotoxicity, and had a significant effect on bone-ALP concentrations. Larger clinical trials are warranted to study (223)Ra on the prevention of SREs and on overall survival in patients with hormone-refractory prostate cancer. Bone-targeting properties of (223)Ra could also potentially be used for treating skeletal metastasis from other primary cancers.

  • 10. Pace, Andrea
    et al.
    Dirven, Linda
    Koekkoek, Johan A. F.
    Golla, Heidrun
    Fleming, Jane
    Ruda, Roberta
    Marosi, Christine
    Le Rhun, Emilie
    Grant, Robin
    Oliver, Kathy
    Oberg, Ingela
    Bulbeck, Helen J.
    Rooney, Alasdair G.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Reg Canc Ctr Stockholm Gotland, Stockholm, Sweden.
    Pasman, H. Roeline W.
    Oberndorfer, Stefan
    Weller, Michael
    Taphoorn, Martin J. B.
    European Association for Neuro-Oncology (EANO) guidelines for palliative care in adults with glioma2017In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 18, no 6, p. E330-E340Article, review/survey (Refereed)
    Abstract [en]

    Patients with glioma present with complex palliative care needs throughout their disease trajectory. The life-limiting nature of gliomas and the presence of specific symptoms related to neurological deterioration necessitate an appropriate and early palliative care approach. The multidisciplinary palliative care task force of the European Association of Neuro-Oncology did a systematic review of the available scientific literature to formulate the best possible evidence-based recommendations for the palliative care of adult patients with glioma, with the aim to reduce symptom burden and improve the quality of life of patients and their caregivers, particularly in the end-of-life phase. When recommendations could not be made because of the scarcity of evidence, the task force either used evidence from studies of patients with systemic cancer or formulated expert opinion. Areas of palliative care that currently lack evidence and thus deserve attention for further research are fatigue, disorders of behaviour and mood, interventions for the needs of caregivers, and timing of advance care planning.

  • 11. Raaschou-Nielsen, Ole
    et al.
    Andersen, Zorana J
    Beelen, Rob
    Samoli, Evangelia
    Stafoggia, Massimo
    Weinmayr, Gudrun
    Hoffmann, Barbara
    Fischer, Paul
    Nieuwenhuijsen, Mark J
    Brunekreef, Bert
    Xun, Wei W
    Katsouyanni, Klea
    Dimakopoulou, Konstantina
    Sommar, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Modig, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Oudin, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Oftedal, Bente
    Schwarze, Per E
    Nafstad, Per
    De Faire, Ulf
    Pedersen, Nancy L
    Ostenson, Claes-Göran
    Fratiglioni, Laura
    Penell, Johanna
    Korek, Michal
    Pershagen, Göran
    Eriksen, Kirsten T
    Sørensen, Mette
    Tjønneland, Anne
    Ellermann, Thomas
    Eeftens, Marloes
    Peeters, Petra H
    Meliefste, Kees
    Wang, Meng
    Bueno-de-Mesquita, Bas
    Key, Timothy J
    de Hoogh, Kees
    Concin, Hans
    Nagel, Gabriele
    Vilier, Alice
    Grioni, Sara
    Krogh, Vittorio
    Tsai, Ming-Yi
    Ricceri, Fulvio
    Sacerdote, Carlotta
    Galassi, Claudia
    Migliore, Enrica
    Ranzi, Andrea
    Cesaroni, Giulia
    Badaloni, Chiara
    Forastiere, Francesco
    Tamayo, Ibon
    Amiano, Pilar
    Dorronsoro, Miren
    Trichopoulou, Antonia
    Bamia, Christina
    Vineis, Paolo
    Hoek, Gerard
    Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE)2013In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 14, no 9, p. 813-822Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations.

    METHODS: This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 μm (PM10), less than 2·5 μm (PM2·5), and between 2·5 and 10 μm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses.

    FINDINGS: The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03-1·45] per 10 μg/m(3)). For PM2·5 the HR was 1·18 (0·96-1·46) per 5 μg/m(3). The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10-2·08) and 1·55 (1·05-2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99-1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95-1·07] per 20 μg/m(3)) or traffic intensity on the nearest street (HR 1·00 [0·97-1·04] per 5000 vehicles per day).

    INTERPRETATION: Particulate matter air pollution contributes to lung cancer incidence in Europe.

    FUNDING: European Community's Seventh Framework Programme.

  • 12. Raaschou-Nielsen, Ole
    et al.
    Vineis, Paolo
    Brunekreef, Bert
    Nieuwenhuijsen, Mark
    Hoffmann, Barbara
    Forastiere, Francesco
    Oudin, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hoek, Gerard
    Katsouyanni, Klea
    Schwarze, Per
    Beelen, Rob
    Air pollution and lung cancer in Europe - Authors' reply.2013In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 14, no 11, p. e440-Article in journal (Refereed)
  • 13. Sartor, Oliver
    et al.
    Coleman, Robert
    Nilsson, Sten
    Heinrich, Daniel
    Helle, Svein I.
    O'Sullivan, Joe M.
    Fossa, Sophie D.
    Chodacki, Ales
    Wiechno, Pawel
    Logue, John
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johannessen, Dag Clement
    Hoskin, Peter
    James, Nicholas D.
    Solberg, Arne
    Syndikus, Isabel
    Vogelzang, Nicholas J.
    O'Bryan-Tear, C. Gillies
    Shan, Minghua
    Bruland, Oyvind S.
    Parker, Christopher
    Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial2014In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 15, no 7, p. 738-746Article in journal (Refereed)
    Abstract [en]

    Background Bone metastases frequently cause skeletal events in patients with metastatic castration-resistant prostate cancer. Radium-223 dichloride (radium-223) selectively targets bone metastases with high-energy, short-range a-particles. We assessed the effect of radium-223 compared with placebo in patients with castration-resistant prostate cancer and bone metastases. Methods In this phase 3, double-blind, randomised ALSYMPCA trial, we enrolled patients who had symptomatic castration-resistant prostate cancer with two or more bone metastases and no known visceral metastases, who were receiving best standard of care, and had previously either received or were unsuitable for docetaxel. Patients were stratified by previous docetaxel use, baseline total alkaline phosphatase level, and current bisphosphonate use, then randomly assigned (2: 1) to receive either six intravenous injections of radium-223 (50 kBq/kg) or matching placebo; one injection was given every 4 weeks. Randomisation was done with an interactive voice response system, taking into account trial stratification factors. Participants and investigators were masked to treatment assignment. The primary endpoint was overall survival, which has been reported previously. Here we report on time to first symptomatic skeletal event, defined as the use of external beam radiation to relieve bone pain, or occurrence of a new symptomatic pathological fracture (vertebral or non-verterbal), or occurence of spinal cord compression, or tumour-related orthopeadic surgical intervention. All events were required to be clinically apparent and were not assessed by periodic radiological review. Statistical analyses of symptomatic skeletal events were based on the intention-to-treat population. The study has been completed and is registered with ClinicalTrials.gov, number NCT00699751. Findings Between June 12, 2008, and Feb 1, 2011, 921 patients were enrolled, of whom 614 (67%) were randomly assigned to receive radium-223 and 307 (33%) placebo. Symptomatic skeletal events occurred in 202 (33%) of 614 patients in the radium-223 group and 116 (38%) of 307 patients in the placebo group. Time to first symptomatic skeletal event was longer with radium-223 than with placebo (median 15.6 months [95% CI 13.5-18.0] vs 9.8 months [7.3-23.7]; hazard ratio [HR] = 0.66, 95% CI 0.52-0.83; p = 0.00037). The risks of external beam radiation therapy for bone pain (HR 0.67, 95% CI 0.53-0.85) and spinal cord compression (HR = 0.52, 95% CI 0.29-0.93) were reduced with radium-233 compared with placebo. Radium-223 treatment did not seem to significantly reduce the risk of symptomatic pathological bone fracture (HR 0.62, 95% CI 0.35-1.09), or the need for tumour-related orthopaedic surgical intervention (HR 0.72, 95% CI 0.28-1.82). Interpretation Radium-223 should be considered as a treatment option for patients with castration-resistant prostate cancer and symptomatic bone metastases.

  • 14. Sullivan, Richard
    et al.
    Peppercorn, Jeffrey
    Sikora, Karol
    Zalcberg, John
    Meropol, Neal J.
    Amir, Eitan
    Khayat, David
    Boyle, Peter
    Autier, Philippe
    Tannock, Ian F.
    Fojo, Tito
    Siderov, Jim
    Williamson, Steve
    Camporesi, Silvia
    McVie, J. Gordon
    Purushotham, Arnie D.
    Naredi, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Eggermont, Alexander
    Brennan, Murray F.
    Steinberg, Michael L.
    De Ridder, Mark
    McCloskey, Susan A.
    Verellen, Dirk
    Roberts, Terence
    Storme, Guy
    Hicks, Rodney J.
    Ell, Peter J.
    Hirsch, Bradford R.
    Carbone, David P.
    Schulman, Kevin A.
    Catchpole, Paul
    Taylor, David
    Geissler, Jan
    Brinker, Nancy G.
    Meltzer, David
    Kerr, David
    Aapro, Matti
    Delivering affordable cancer care in high-income countries2011In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 12, no 10, p. 933-980Article in journal (Refereed)
    Abstract [en]

    The burden of cancer is growing, and the disease is becoming a major economic expenditure for all developed countries. In 2008, the worldwide cost of cancer due to premature death and disability (not including direct medical costs) was estimated to be US$895 billion. This is not simply due to an increase in absolute numbers, but also the rate of increase of expenditure on cancer. What are the drivers and solutions to the so-called cancer-cost curve in developed countries? How are we going to afford to deliver high quality and equitable care? Here, expert opinion from health-care professionals, policy makers, and cancer survivors has been gathered to address the barriers and solutions to delivering affordable cancer care. Although many of the drivers and themes are specific to a particular field-eg, the huge development costs for cancer medicines-there is strong concordance running through each contribution. Several drivers of cost, such as over-use, rapid expansion, and shortening life cycles of cancer technologies (such as medicines and imaging modalities), and the lack of suitable clinical research and integrated health economic studies, have converged with more defensive medical practice, a less informed regulatory system, a lack of evidence-based sociopolitical debate, and a declining degree of fairness for all patients with cancer. Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. A radical shift in cancer policy is also required. Political toleration of unfairness in access to affordable cancer treatment is unacceptable. The cancer profession and industry should take responsibility and not accept a substandard evidence base and an ethos of very small benefit at whatever cost; rather, we need delivery of fair prices and real value from new technologies.

  • 15. Van Hemelrijck, Mieke
    et al.
    Adolfsson, Jan
    Garmo, Hans
    Bill-Axelson, Anna
    Bratt, Ola
    Ingelsson, Erik
    Lambe, Mats
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Holmberg, Lars
    Risk of thromboembolic diseases in men with prostate cancer: results from the population-based PCBaSe Sweden2010In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 11, no 5, p. 450-458Article in journal (Refereed)
    Abstract [en]

    Background

    Cancer is associated with an increased risk of thromboembolic diseases, but data on the association between prostate cancer and thromboembolic diseases are scarce. We investigated the risk of thromboembolic disease in men with prostate cancer who were receiving endocrine treatment, curative treatment, or surveillance.

    Methods

    We analysed data from PCBaSe Sweden, a database based on the National Prostate Cancer Register, which covers over 96% of prostate cancer cases in Sweden. Standardised incidence ratios (SIR) of deep-venous thrombosis (DVT), pulmonary embolism, and arterial embolism were calculated by comparing observed and expected (using the total Swedish male population) occurrences of thromboembolic disease, taking into account age, calendar-time, number of thromboembolic diseases, and time since previous thromboembolic disease.

    Findings

    Between Jan 1, 1997, and Dec 31, 2007, 30 642 men received primary endocrine therapy, 26 432 curative treatment, and 19 526 surveillance. 1881 developed a thromboembolic disease. For men on endocrine therapy, risks for DVT (SIR 2·48, 95% CI 2·25–2·73) and pulmonary embolism (1·95, 1·81–2·15) were increased, although this was not the case for arterial embolism (1·00, 0·82–1·20). Similar patterns were seen for men who received curative treatment (DVT: 1·73, 1·47–2·01; pulmonary embolism: 2·03, 1·79–2·30; arterial embolism: 0·95, 0·69–1·27) and men who were on surveillance (DVT: 1·27, 1·08–1·47; pulmonary embolism: 1·57, 1·38–1·78; arterial embolism: 1·08, 0·87–1·33). Increased risks for thromboembolic disease were maintained when patients were stratified by age and tumour stage.

    Interpretation

    All men with prostate cancer were at higher risk of thromboembolic diseases, with the highest risk for those on endocrine therapy. Our results indicate that prostate cancer itself, prostate cancer treatments, and selection mechanisms all contribute to increased risk of thromboembolic disease. Thromboembolic disease should be a concern when managing patients with prostate cancer.

  • 16. Weller, Michael
    et al.
    van den Bent, Martin
    Hopkins, Kirsten
    Tonn, Jörg C.
    Stupp, Roger
    Falini, Andrea
    Cohen-Jonathan-Moyal, Elizabeth
    Frappaz, Didier
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Balana, Carmen
    Chinot, Olivier
    Ram, Zvi
    Reifenberger, Guido
    Soffietti, Riccardo
    Wick, Wolfgang
    EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma2014In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 15, no 9, p. E395-E403Article, review/survey (Refereed)
    Abstract [en]

    This guideline provides recommendations for diagnostic and therapeutic procedures for patients with malignant gliomas. We differentiate evidence-based standards from reasonable options or non-evidence-based measures that should no longer be considered. The recommendations herein should provide a framework and assurance for the choice of diagnostic procedures and therapeutic measures and aim to reduce complications from unnecessary treatment and cost. The guideline contributes to a critical appreciation of concurrent drugs with a focus on the controlled use of anticonvulsants and steroids. It should serve as a guideline for all professionals involved in the diagnostics and care of glioma patients and also as a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in Europe. Implementation of the recommendations summarised here will need interdisciplinary structures of care for patients with brain tumours and structured processes of diagnostic and therapeutic procedures.

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