Finsen Center

Copenhagen, Denmark

Finsen Center

Copenhagen, Denmark

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Vilmar A.C.,Finsen Center | Santoni-Rugiu E.,Copenhagen University | Sorensen J.B.,Finsen Center
Annals of Oncology | Year: 2013

Background: Platinum-based doublets (PBDs) remain the cornerstone of treatment in non-small-cell lung cancer (NSCLC) and may include gemcitabine. A biomarker predicting sensitivity to this antimetabolite would represent a major step forward. Accordingly, we explored the predictive role of ribonucleotide reductase subunit M (RRM1) in advanced NSCLC. Patients and methods: A total of 443 patients were randomly assigned to regimen A [paclitaxel (Taxol) and cisplatin with gemcitabine] or regimen B (cisplatin and vinorelbine). Immunohistochemical evaluation of RRM1 was correlated to clinical end-points. Results: A total of 261 (58.9%) patients had representative tissue samples for RRM1 evaluation. Disease control rate, progression-free survival (PFS) and overall survival (OS) were substantially improved in patients with RRM-negative (neg) tumors receiving regimen B when compared with patients with RRM-positive (pos) tumors (68.8% versus 31.2%, P = 0.046, 6.90 months versus 3.93 months, P = 0.000 and 11.57 months versus 7.4 months, P = 0.002, respectively). Interaction analysis between RRM1-neg status and adenocarcinomas yielded a hazard ratio (HR) of 0.36 for death (P = 0.000). Conclusions: RRM1 protein expression was without any predictive impact in patients treated with cisplatin, paclitaxel and gemcitabine. Surprisingly, the predictive power was demonstrated in the cisplatin and vinorelbine arm and may suggest that RRM1 is involved in vinorelbine sensitivity warranting further research. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Karlsen R.V.,Danish Cancer Society | Frederiksen K.,Danish Cancer Society | Larsen M.B.,Danish Cancer Society | von Heymann-Horan A.B.,Danish Cancer Society | And 7 more authors.
Acta Oncologica | Year: 2016

Background The improved survival after breast cancer has prompted knowledge on the effect of a breast cancer diagnosis on health-related quality of life (HQoL). This study compared changes in HQoL among women from before to after breast cancer diagnosis with longitudinal changes among women who remained breast cancer-free. Material and methods The Danish Diet, Cancer and Health study included 57 053 cancer-free persons aged 50–64 years at baseline (1993–1997). We used data from first follow-up (1999–2002) and second follow-up (2010–2012) on HQoL [Medical Outcomes Survey, short form (SF-36)] obtained from 542 women aged 64–82 years with primary breast cancer (stages I–III) and a randomly matched sample of 729 women who remained breast cancer-free. Linear regression models were used to estimate the differences in changes in HQoL between women with and without breast cancer; the analyses were repeated with stratification according to age, comorbidity, partner support and time since diagnosis. Results Women with breast cancer reported significantly larger decreases in HQoL from before to after diagnosis than those who remained breast cancer-free (physical component summary, −2.0; 95% CI −2.8; −1.2, mental component summary, −1.5, 95% CI −2.3; −0.6). This association was significantly modified by comorbidity and time since diagnosis. Conclusions Women with breast cancer reported significantly larger HQoL declines than breast cancer-free women. Breast cancer diagnosis seems to have the greatest impact on HQoL closest to diagnosis and in women with comorbidity indicating that this group should be offered timely and appropriate follow-up care to prevent HQoL declines. © 2016 Informa UK Limited, trading as Taylor & Francis Group.


Vilmar A.C.,Finsen Center | Santoni-Rugiu E.,Copenhagen University | Sorensen J.B.,Finsen Center
Annals of Oncology | Year: 2010

Background: Customized chemotherapy is likely to improve outcome in patients with advanced non-small-cell lung cancer (NSCLC). Excision repair cross-complementation group 1 (ERCC1) is a promising biomarker; however, current evidence is inadequate. Impact of ERCC1 status was evaluated among patients participating in a large randomized chemotherapy trial. Patients and methods: Four hundred and forty-three patients with advanced NSCLC were enrolled in a phase III trial and were randomly allocated to triplet chemotherapy or standard doublet regimen. Immunohistochemical evaluation for ERCC1 status was mainly carried out on bioptic material. Results: Two hundred and sixty-four (59.5%) patients had representative tissue samples for ERCC1 evaluation. Median overall survival (OS) in the ERCC1-negative and ERCC1-positive population was 11.8 and 9.8 months, respectively (P = 0.028). The median OS among patients with adenocarcinomas (n = 122) was 15.2 and 8.3 months, respectively (P = 0.007). Interaction analysis between ERCC1-negative status and adenocarcinomas yielded a hazard ratio of 0.64 for death (P = 0.002). Conclusions: Clinically applicable evaluation of ERCC1 status predicted cisplatin sensitivity in the largest randomized patient population with advanced NSCLC reported to date. The predictive value can be ascribed to the adenocarcinomas emphasizing the relevance of ERCC1 expression in this subgroup. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Gjetting T.,Finsen Center | Arildsen N.S.,Finsen Center | Christensen C.L.,Finsen Center | Poulsen T.T.,Finsen Center | And 3 more authors.
International Journal of Nanomedicine | Year: 2010

Background: DOTAP/cholesterol-based lipoplexes are successfully used for delivery of plasmid DNA in vivo especially to the lungs, although low systemic stability and circulation have been reported. To achieve the aim of discovering the best method for systemic delivery of DNA to disseminated tumors we evaluated the potential of formulating DOTAP/cholesterol lipoplexes with a polyethylene glycol (PEG)-modified lipid, giving the benefit of the shielding and stabilizing properties of PEG in the bloodstream. Method: A direct comparison of properties in vitro and in vivo of 4 different DOTAP/cholesterol-based lipoplexes containing 0%, 2%, 4%, and 10% PEG was performed using reporter gene activity and radioactive tracer lipid markers to monitor biodistribution. Results: We found that 10% PEGylation of lipoplexes caused reduced retention in lung and heart tissues of nude mice compared to nonPEGylated lipoplexes, however no significant delivery to xenograft flank tumors was observed. Although PEGylated and nonPEGylated lipoplexes were delivered to cells the ability to mediate successful transfection is hampered upon PEGylation, presumably due to a changed uptake mechanism and intracellular processing. Conclusion: The eminent in vivo transfection potency of DOTAP/cholesterol-based lipoplexes is well established for expression in lung tumors, but it is unsuitable for expression in non first pass organs such as xenograft flank tumors in mice even after addition of a PEG-lipid in the formulation. © 2010 Gjetting et al, publisher and licensee Dove Medical Press Ltd.


Ducarroz S.,International Agency for Research on Cancer IARC | Leon M.E.,International Agency for Research on Cancer IARC | Schott A.-M.,Hospices Civils de Lyon | Schott A.-M.,University of Lyon | And 5 more authors.
Acta Oncologica | Year: 2015

Background. Tobacco-related cancers (TRC) represent approximately a third of the cancer incidence in Denmark. However, tobacco consumption levels in immigrants may differ to the native population. We compared incidence rates of nine TRCs among male immigrants of first and second generation in Denmark with those among males of the native population.Material and methods. We used an established cohort of all Danish men (1978-2010) and calculated standardized incidence ratios (SIR) with 95% confidence intervals (CI) to compare incidence by immigration status and region of birth for nine TRCs.Results. We identified 131 317 incident cases of TRCs among 3 508 204 men (280 526 first generation and 129 056 second generation immigrants). Overall, immigrants of both generations experienced approximately 15% lower incidence of TRC than natives, however, with large variations by country of birth and type of TRC. Compared to natives, lung cancer incidence in first and second generation immigrants was 10% and 27% lower, respectively. However, lung cancer incidence increased in first generation immigrants reaching the level of native Danes in the late 2000s. First generation immigrants experienced approximately 50% lower incidence of lower urinary tract cancer than natives. However, only liver and stomach cancer had higher SIRs in immigrants.Conclusion. Overall TRC incidence was lower among immigrants than in native Danes. Lower urinary tract cancer among first generation immigrants warrants further investigation. © 2015 Informa Healthcare.


PubMed | Finsen Center
Type: Clinical Trial, Phase III | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2010

Customized chemotherapy is likely to improve outcome in patients with advanced non-small-cell lung cancer (NSCLC). Excision repair cross-complementation group 1 (ERCC1) is a promising biomarker; however, current evidence is inadequate. Impact of ERCC1 status was evaluated among patients participating in a large randomized chemotherapy trial.Four hundred and forty-three patients with advanced NSCLC were enrolled in a phase III trial and were randomly allocated to triplet chemotherapy or standard doublet regimen. Immunohistochemical evaluation for ERCC1 status was mainly carried out on bioptic material.Two hundred and sixty-four (59.5%) patients had representative tissue samples for ERCC1 evaluation. Median overall survival (OS) in the ERCC1-negative and ERCC1-positive population was 11.8 and 9.8 months, respectively (P = 0.028). The median OS among patients with adenocarcinomas (n = 122) was 15.2 and 8.3 months, respectively (P = 0.007). Interaction analysis between ERCC1-negative status and adenocarcinomas yielded a hazard ratio of 0.64 for death (P = 0.002).Clinically applicable evaluation of ERCC1 status predicted cisplatin sensitivity in the largest randomized patient population with advanced NSCLC reported to date. The predictive value can be ascribed to the adenocarcinomas emphasizing the relevance of ERCC1 expression in this subgroup.


PubMed | Karolinska Institutet, Danish Cancer Society, National Institute of Occupational Health, Finsen Center and 6 more.
Type: Journal Article | Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | Year: 2016

Previous studies have evaluated the effect of medical diagnostic radiation on brain tumors. Recent cohort studies have reported an increased risk associated with exposure to head CT scans.Information regarding medical conditions, including prenatal and postnatal exposure to medical diagnostic radiation, was obtained from CEFALO, a multicenter case-control study performed in Denmark, Norway, Sweden, and Switzerland through face-to-face interview. Eligible cases of childhood and adolescent brain tumors (CABT) were ages 7 to 19 years, diagnosed between January 1, 2004 and August 31, 2008, and living in the participating countries (n = 352). The cases were matched by age, sex, and region to 646 population-based controls.Prenatal exposure to medical diagnostic radiation and postnatal exposure to X-rays were not associated with CABTs. A higher risk estimate of CABTs, although not statistically significant, was found for exposure to head CT scan (OR, 1.86; 95% confidence interval, 0.82-4.22). The associations with head injury, febrile seizure, fever in the first 12 weeks, and general anesthesia were close to unity.Prenatal or postnatal medical conditions, including medical diagnostic radiation, were not associated with CABTs. On the basis of small numbers of exposed children, we observed a nonsignificant increased risk for CT scans of the head.We have presented additional evidence, suggesting that exposure to head CT scan may be associated with the occurrence of CABTs. Cancer Epidemiol Biomarkers Prev; 26(1); 110-5. 2016 AACR.


PubMed | Finsen Center
Type: Clinical Trial, Phase III | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2013

Platinum-based doublets (PBDs) remain the cornerstone of treatment in non-small-cell lung cancer (NSCLC) and may include gemcitabine. A biomarker predicting sensitivity to this antimetabolite would represent a major step forward. Accordingly, we explored the predictive role of ribonucleotide reductase subunit M (RRM1) in advanced NSCLC.A total of 443 patients were randomly assigned to regimen A [paclitaxel (Taxol) and cisplatin with gemcitabine] or regimen B (cisplatin and vinorelbine). Immunohistochemical evaluation of RRM1 was correlated to clinical end-points.A total of 261 (58.9%) patients had representative tissue samples for RRM1 evaluation. Disease control rate, progression-free survival (PFS) and overall survival (OS) were substantially improved in patients with RRM-negative (neg) tumors receiving regimen B when compared with patients with RRM-positive (pos) tumors (68.8% versus 31.2%, P = 0.046, 6.90 months versus 3.93 months, P = 0.000 and 11.57 months versus 7.4 months, P = 0.002, respectively). Interaction analysis between RRM1-neg status and adenocarcinomas yielded a hazard ratio (HR) of 0.36 for death (P = 0.000).RRM1 protein expression was without any predictive impact in patients treated with cisplatin, paclitaxel and gemcitabine. Surprisingly, the predictive power was demonstrated in the cisplatin and vinorelbine arm and may suggest that RRM1 is involved in vinorelbine sensitivity warranting further research.

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