| 1. |
- Heggebo, L. C., et al.
(författare)
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Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH-mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden
- 2023
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2-3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life.Methods and analysisPRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18-65 years with IDH-mutated diffuse gliomas grade 2-3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints.Ethics and disseminationTo implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2-3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums.Trial registration numberClinicalTrials.gov Registry (NCT05190172).
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| 2. |
- Bonde, J. P. E., et al.
(författare)
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Occupational risk of COVID-19 across pandemic waves: a two-year national follow-up study of hospital admissions
- 2022
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Ingår i: Scandinavian Journal of Work Environment & Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 48:8, s. 672-677
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Tidskriftsartikel (refereegranskat)abstract
- Objective Assuming that preventive measures to mitigate viral transmission of SARS-CoV-2 at the workplace may have been improved in the course of the COVID-19 pandemic, we examined the occupational risk of COVID-19 related hospital admission across the four pandemic waves in Denmark between week 8, 2020, and week 50, 2021. Methods The study included 4416 cases of COVID-19 related hospital admissions among 2.4 million Danish employees aged 20-69 with follow-up in 2020 through 2021. At-risk industrial sectors and a reference population were defined a priory by a job-exposure matrix on occupational risk for COVID-19. Incidence rate ratios (IRR) and potential effect modification by pandemic wave were computed with Poisson regression adjusted for demographic, social and health factors including completed COVID-19 vaccination. Results We observed an overall elevated relative risk in four of six at-risk industrial sectors, but the pandemic wave only modified the risk among healthcare employees, where the excess risk from a high initial level declined to background levels during the latest waves in models not adjusting for COVID-19 vaccination. In social care, education and transport, the elevated risk was not modified by pandemic wave. Conclusion Danish healthcare employees were to some extent protected against occupational transmission of SARS-CoV-2 during the two last pandemic waves even though the absolute risk conferred by occupation may not have been eliminated. Early vaccination of this group seems not to be the only explanation. The risk in other sectors remained elevated indicating a need to revisit preventive measures.
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| 3. |
- Bonde, J P E, et al.
(författare)
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Occupational risk of COVID-19 in foreign-born employees in Denmark
- 2023
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Ingår i: Occupational Medicine. - : Oxford University Press. - 0962-7480 .- 1471-8405.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Foreign-born workers in high-income countries experience higher rates of COVID-19 but the causes are only partially known. AIMS: To examine if the occupational risk of COVID-19 in foreign-born workers deviates from the risk in native-born employees in Denmark. METHODS: Within a registry-based cohort of all residents employed in Denmark (n = 2 451 542), we identified four-digit DISCO-08 occupations associated with an increased incidence of COVID-19-related hospital admission during 2020-21 (at-risk occupations). The sex-specific prevalence of at-risk employment in foreign born was compared with the prevalence in native born. Moreover, we examined if the country of birth modified the risk of a positive SARS-CoV-2 polymerase chain reaction (PCR) test and COVID-19-related hospital admission in at-risk occupations. RESULTS: Workers born in low-income countries and male workers from Eastern Europe more often worked in at-risk occupations (relative risks between 1.16 [95% confidence interval {CI} 1.14-1.17] and 1.87 [95% CI 1.82-1.90]). Being foreign-born modified the adjusted risk of PCR test positivity (test for interaction P < 0.0001), primarily because of higher risk in at-risk occupations among men born in Eastern European countries (incidence rate ratio [IRR] 2.39 [95% CI 2.09-2.72] versus IRR 1.19 [95% CI 1.14-1.23] in native-born men). For COVID-19-related hospital admission, no overall interaction was seen, and in women, country of birth did not consistently modify the occupational risk. CONCLUSIONS: Workplace viral transmission may contribute to an excess risk of COVID-19 in male workers born in Eastern Europe, but most foreign-born employees in at-risk occupations seem not to be at higher occupational risk than native born.
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| 4. |
- Lilja, Gisela, et al.
(författare)
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Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest A Predefined Analysis of the TTM2 Randomized Clinical Trial
- 2023
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Ingår i: Jama Neurology. - 2168-6149 .- 2168-6157. ; 80:10, s. 1070-1079
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. OBJECTIVES To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. DESIGN, SETTING, AND PARTICIPANTS This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. INTERVENTIONS Randomization 1:1 to temperature control with targeted hypothermia at 33 degrees C or targeted normothermia and early treatment of fever (37.8 degrees C or higher). MAIN OUTCOMES AND MEASURES Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. RESULTS At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P =.46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P =.37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P =.62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). CONCLUSIONS In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common.
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| 5. |
- Bonde, J. P. E., et al.
(författare)
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COVID-19-related hospital admission in spouses of partners in at-risk occupations
- 2023
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Ingår i: Scandinavian Journal of Work Environment & Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 49:3, s. 193-200
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study aimed to quantify the risk of COVID-19-related hospital admission in spouses living with partners in at-risk occupations in Denmark during 2020-21.Methods Within a registry-based cohort of all Danish employees (N=2 451 542), we identified cohabiting couples, in which at least one member (spouse) held a job that according to a job exposure matrix entailed low risk of occupational exposure to SARS-CoV-2 (N=192 807 employees, 316 COVID-19 hospital admissions). Risk of COVID-19-related hospital admission in such spouses was assessed according to whether their partners were in jobs with low, intermediate or high risk for infection. Overall and sex-specific incidence rate ratios (IRR) of COVID-19-related hospital admission were computed by Poisson regression with adjustment for relevant covariates.Results The risk of COVID-19-related hospital admission was increased among spouses with partners in highrisk occupations [adjusted IRR (IRRadj)1.59, 95% confidence interval (CI) 1.1-2.2], but not intermediate-risk occupations (IRRadj 0.97 95% 0.8-1.3). IRR for having a partner in a high-risk job was elevated during the first three pandemic waves but not in the fourth (IRRadj 0.48 95% CI 0.2-1.5). Sex did not modify the risk of hospital admission.Conclusions SARS-CoV-2 transmission at the workplace may pose an increased risk of severe COVID-19 among spouses in low-risk jobs living with partners in high-risk jobs, which emphasizes the need for preventive measures at the workplace in future outbreaks of epidemic contagious disease. When available, effective vaccines seem essential.
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| 6. |
- Bonde, J. P. E., et al.
(författare)
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Occupational risk of SARS-CoV-2 infection: a nationwide register-based study of the Danish workforce during the COVID-19 pandemic, 2020-2021
- 2023
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 80:4, s. 202-208
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveMost earlier studies on occupational risk of COVID-19 covering the entire workforce are based on relatively rare outcomes such as hospital admission and mortality. This study examines the incidence of SARS-CoV-2 infection by occupational group based on real-time PCR (RT-PCR) tests. MethodsThe cohort includes 2.4 million Danish employees, 20-69 years of age. All data were retrieved from public registries. The incidence rate ratios (IRRs) of first-occurring positive RT-PCR test from week 8 of 2020 to week 50 of 2021 were computed by Poisson regression for each four-digit Danish Version of the International Standard Classification of Occupations job code with more than 100 male and 100 female employees (n=205). Occupational groups with low risk of workplace infection according to a job exposure matrix constituted the reference group. Risk estimates were adjusted by demographic, social and health characteristics including household size, completed COVID-19 vaccination, pandemic wave and occupation-specific frequency of testing. ResultsIRRs of SARS-CoV-2 infection were elevated in seven healthcare occupations and 42 occupations in other sectors, mainly social work activities, residential care, education, defence and security, accommodation and transportation. No IRRs exceeded 2.0. The relative risk in healthcare, residential care and defence/security declined across pandemic waves. Decreased IRRs were observed in 12 occupations. DiscussionWe observed a modestly increased risk of SARS-CoV-2 infection among employees in numerous occupations, indicating a large potential for preventive actions. Cautious interpretation of observed risk in specific occupations is needed because of methodological issues inherent in analyses of RT-PCR test results and because of multiple statistical tests.
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| 7. |
- Dankiewicz, Josef, et al.
(författare)
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Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
- 2021
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
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Tidskriftsartikel (refereegranskat)abstract
- Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)
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| 8. |
- Deschasaux, M., et al.
(författare)
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Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: Results from the EPIC prospective cohort study
- 2018
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Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- Background Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations. This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus (Q1) = 1.07; 95% CI 1.03-1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out. In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.
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| 9. |
- Finizia, Caterina, 1961, et al.
(författare)
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Advanced laryngeal cancer T3-T4 in Sweden: a retrospective study 1986-1990. Survival and locoregional control related to treatment.
- 1996
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Ingår i: Acta oto-laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 116:6, s. 906-12
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Tidskriftsartikel (refereegranskat)abstract
- Different treatment modalities for advanced laryngeal cancer are much discussed in the literature. One-hundred-and-sixty patients with T3-4, N0-3, M0-1 laryngeal cancer diagnosed in Sweden between 1986 and 1990 were retrospectively analysed. One hundred (65 T3: 35 T4) received radical radiotherapy with salvage surgery (RRSS) in case of residual or recurrent disease. Thirty-eight (11T3: 27 T4) patients received surgery with or without radiotherapy (S +/- RT). Twenty-two patients received no treatment. After a median follow up of 4.4 years, the estimated 5-year actuarial corrected survival and 3-year locoregional control were 59% and 44% for T3 RRSS and 47% and 54% for T3 S +/- RT. No significant difference between the different treatment modalities was found. The 5-year corrected survival rate and the locoregional control at 3 years between T4-RRSS (32%; 26%) and T4-S + RT (58%; 68%) groups were significantly different (p < 0.05 and p < 0.01). This might suggest that surgery with or without radiotherapy still has its place as a treatment modality for patients with advanced T4 laryngeal carcinoma.
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| 10. |
- Hallqvist, Andreas, 1973, et al.
(författare)
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Concurrent cetuximab and radiotherapy after docetaxel-cisplatin induction chemotherapy in stage III NSCLC : Satellite-A phase II study from the Swedish Lung Cancer Study Group
- 2011
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Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 71:2, s. 166-172
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several attempts to increase the locoregional control in locally advanced lung cancer including concurrent chemotherapy, accelerated fractionation and dose escalation have been made during the last years. As the EGFR directed antibody cetuximab has shown activity concurrent with radiotherapy in squamous cell carcinoma of the head and neck, as well as in stage IV NSCLC combined with chemotherapy, we wanted to investigate radiotherapy with concurrent cetuximab in locally advanced NSCLC, a tumour type often over expressing the EGF-receptor. Methods: Between February 2006 and August 2007 75 patients in stage Ill NSCLC with good performance status (PS 0 or 1) and adequate lung function (FEV1 > 1.0) were enrolled in this phase II study at eight institutions. Treatment consisted of 2 cycles of induction chemotherapy, docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) with 3 weeks interval. An initial dose of cetuximab 400 mg/m(2) was given before start of 3D-CRT to 68 Gy with 2 Gy per fraction in 7 weeks concurrent with weekly cetuximab 250 mg/m(2). Toxicity was scored weekly during radiotherapy (CTC 3.0), and after treatment the patients were followed every third month with CT-scans, toxicity scoring and QLQ. Results: Seventy-one patients were eligible for analysis as four were incorrectly enrolled. Histology: adenocarcinoma 49%, squamous cell carcinoma 39% and other NSCLC 12%. The majority had PS 0 (62.5%), median age 62.2 (42-81), 50% were women and 37% had a pre-treatment weight loss > 5%. Toxicity: esophagitis grade 1-2: 72%; grade 3:1.4%. Hypersensitivity reactions grade 3-4: 5.6%. Febrile neutropenia grade 3-4: 15.4%. Skin reactions grade 1-2: 74%; grade 3: 4.2%. Diarrhoea grade 1-2: 38%; grade 3: 11.3%. Pneumonitis grade 1-2: 26.8%; grade 3: 4.2%; grade 5:1.4%. The median follow-up was 39 months for patients alive and the median survival was 17 months with a 1-, 2- and 3-year OS of 66%, 37% and 29% respectively. Until now local or regional failure has occurred in 20 patients and 22 patients have developed distant metastases. Weight loss, PS and stage were predictive for survival in univariate as well as in multivariate analysis. Conclusion: Induction chemotherapy followed by concurrent cetuximab and RT to 68 Gy is clearly feasible with promising survival. Toxicity, e.g. pneumonitis and esophagitis is low compared to most schedules with concurrent chemotherapy. This treatment strategy should be evaluated in a randomised manner vs. concurrent chemoradiotherapy to find out if it is a valid treatment option.
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