' AgeCare - Academy of Geriatric Cancer Research
Return to Publications overview  Go to Other  
   
     
Peer-Reviewed Publications      
     
2021    
     
Lijie Wang; Afsaneh Mohammadnejad; Weilong Li; Jesper Lund; Shuxia Li; Signe Clemmensen; Maria Timofeeva; Mette Soerensen; Jonas Mengel-From; Kaare Christensen; Jacob Hjelmborg; Qihua Tan
Genetic and Environmental Determinants of O6-methylguanine DNA-methyltransferase (MGMT) Gene Methylation: A 10-year Longitudinal Study of Danish Twins
Clinical Epigenetics
Click to view summary
Background:
   
     
Andreas Glenhøj, Lasse H Jakobssen, Henrik Sengeløv, Syed A Ahmd, Kristian Qvist, Annika Rewes, Christian B Poulsen, Ulrik M Overgaard, Ingolf Mølle, Marianne T Severinsen, Casper N Strandoldt, Jack Maibom, Annette R Kodahl, Jesper Ryg, Pernille Ravn, Isik S Johansen, Søren N Helsø, Søren Jensen-Fangel, Jacek Kisielewicz, Lothar Wiese, Marie Helleberg, Ole Kirk, Michael R Clausen, Henrik Frederiksen
SARS-CoV-2 infection among patients with haematological disorders: Severity and one-month outcome in 66 Danish patients in a nationwide cohort study.
European Journal of Haematology, 2021, 106: 72-81 PMID: 32939853
Click to view summary
Background: Patients with haematological disorders may be particularly vulnerable to respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, this is unknown..
   
     
2020    
     
Eva Jespersen, Stine Brændegaard Winther, Lisbeth Ronsebek Minet, Sören Möller, Per Pfeiffer
Frailty screening for predicting rapid functional impairment, rapid progressive disease, and shorter overall survival in older patients with gastrointestinal cancer receiving palliative chemotherapy - A prospective, clinical study
J Geriatric Oncol https://doi.org/10.1016/j.jgo.2020.10.007
Click to view summary
Background: A growing number of older patients with cancer require well-founded clinical decision-making. Frailty screening is suggested as a service to improve outcomes in vulnerable older patients with cancer. This prospective study examined the value of frailty screening to predict rapid functional decline, rapid progressive disease (PD) and shorter overall survival (OS) in older patients with gastrointestinal cancer receiving palliative chemotherapy.
   
     
Hansen CR, Bertelsen A, Zukauskaite R, Johnsen L, Bernchou U, Thwaites DL, Eriksen JG, Johansen J, Brink C
Prediction of radiation-induced mucositis of H&N cancer patients based on a large patient cohort.
Radiother Oncol. 2020 Jun;147:15-21. doi: 10.1016/j.radonc.2020.03.013. Epub 2020 Mar 28.Radiother Oncol. 2020. PMID: 32224314
Click to view summary
Background: Radiation-induced mucositis is a severe acute side effect, which can jeopardize treatment compliance and cause weight loss during treatment. The study aimed to develop robust models to predict the risk of severe mucositis.
   
     
Christiansen RL, Lars Dysager L, Smedegaard AB, Hansen O, Brink C. Bernchou U.
Accuracy of automatic deformable structure propagation for high-field MRI guided prostate radiotherapy.
Radiat Oncol. 2020 Feb 7;15(1):32. doi: 10.1186/s13014-020-1482-y.Radiat Oncol. 2020. PMID: 32033574
Click to view summary
Background: In this study we have evaluated the accuracy of automatic, deformable structure propagation from planning CT and MR scans for daily online plan adaptation for MR linac (MRL) treatment, which is an important element to minimize re-planning time and reduce the risk of misrepresenting the target due to this time pressure.
   
     
Louise S Rasmussen, Claus W Fristrup, Benny V Jensen, Per Pfeiffer, Britta Weber, Mette K Yilmaz, Laurids Ø Poulsen, Morten Ladekarl, Kell Østerlind, Jim S Larsen, Hella Skuladottir, Carsten P Hansen, Michael B Mortensen, Frank V Mortensen, Mogens Sall, Sönke Detlefsen, Martin Bøgsted, Ursula G Falkmer
Initial treatment and survival in 4163 Danish patients with pancreatic cancer: A nationwide unselected real-world register study.
Eur. J. Cancer. 2020 Apr;129:50-59. doi: 10.1016/j.ejca.2020.01.015 PMID: 32120275
Click to view summary
Background: Nationwide register data on the effect of primary treatment on survival in an unselected population of patients with pancreatic cancer (PC) have not been reported before. The study aim was to investigate the overall survival (OS) related to initial treatment with resection, chemotherapy, or best supportive care (BSC) in all patients diagnosed with PC in Denmark from 2011 to 2016.
   
     
Per Pfeiffer, Mette Yilmaz, Sören Möller, Daniela Zitnjak, Merete Krogh, Lone Nørgård Petersen, Laurids Østergaard Poulsen, Stine Braendegaard Winther, Karina Gravgaard Thomsen, Camilla Qvortrup
TAS-102 with or without bevacizumab in patients with chemorefractory metastatic colorectal cancer: an investigator-initiated, open-label, randomised, phase 2 trial.
Lancet oncol. 2020 Mar;21(3):412-420. doi: 10.1016/S1470-2045(19)30827-7 PMID: 31999946
Click to view summary
Background: TAS-102 (trifluridine-tipiracil) has shown a significant overall survival benefit compared with placebo in patients with chemorefractory metastatic colorectal cancer. Inspired by the encouraging results of a small phase 1-2 study, C-TASK FORCE, which evaluated the combination of TAS-102 plus bevacizumab in patients with chemorefractory metastatic colorectal cancer, we aimed to compare the efficacy of TAS-102 plus bevacizumab versus TAS-102 monotherapy in patients receiving refractory therapy for metastatic colorectal cancer.
   
     
Bagni,K, Chen,IM, Johansen, AZ, Dehlendorff, C, Jensen, BV, Hansen, CP, Hasselby, JP, Holländer, NH, Nissen, M, Bjerregaard, JK, Pfeiffer, P, Yilmaz, MK, Rasmussen, LS, Nielsen, SE, Joansen JS.
Prognostic impact of Charlson's Age-Comorbidity Index and other risk factors in patients with pancreatic cancer.
Eur J Cancer Care (Engl). 2020 Jan 6:e13219. doi: 10.1111/ecc.13219 PMID: 31908093
Click to view summary
Background: Few studies have evaluated the impact of risk factors and comorbidity on overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). The aim was to investigate the prognostic importance of Charlson's age-comorbidity index (CACI) and other risk factors on prognosis in a clinical real-world cohort of PDAC patients.
   
     
Poulsen MH, Feddersen S, Albitar M, Aaberg Poulsen C, Lund M, Brøchner Pedersen
A prospective study of a urine and plasma biomarker test for the prediction of gleason ≥3 + 4 prostate cancer in a mixed cohort
Scandinavian Journal of Urology 2020 Aug;54(4):323-327. doi: 10.1080/21681805.2020.1782979. PMID: 32608296
Click to view summary
Background: Purpose: Definitive diagnosis of prostate cancer is based on biopsies, a procedure associated with side-effects. The use of biomarkers in blood and urine could potentially help clinicians select patients for whom biopsies are needed. The aim of the study was to test a new urine and plasma biomarker test in detecting medium and high grade prostate cancer.Materials and methods: Blood and urine samples were prospectively collected from 41 patients prior to prostate biopsy or TUR-P and again after 3 months. The cohort included patients with suspicion of prostate cancer and patients with prior prostate cancer diagnosis. The mRNA expression of ten selected genes measured by PCR were used together with clinical data in multiple algorithms for prediction of medium-high grade prostate cancer in prostate biopsies. The testing was originally developed and validated in the USA. The method was transferred to a local Danish laboratory. Medium and high grade cancer was defined as Gleason score ≥ 3 + 4.Results: Using the biomarker test, prior to any prostate procedures, the sensitivity for detecting medium-high grade prostate cancer was 100% and the specificity was 56% and 63%, depending on the cut-off point used. When using the biomarker test, following biopsy or TUR-P, the sensitivity and specificity were reduced to 89% and 28-34% respectively. When comparing results, there was a significant difference (p < 0.05), favoring the test performed prior to the procedures.Conclusions: We were able to predict the presence of medium-high grade prostate cancer, thereby confirming earlier findings of the biomarker test.
   
     
Hubackova S, E Davidova, S Boukalova, J Kovarova, M Bajzikova, A Coelho, M Terp, HJ Ditzel, J Rohlena, J Neuzil.
Replication and ribosomal stress induced by targeting pyrimidine synthesis and cellular checkpoints suppress p53-deficient tumors.
Cell Death & Dis, 11(2):110, 2020. PMID: 32034120.
Click to view summary
Background: p53-mutated tumors often exhibit increased resistance to standard chemotherapy and enhanced metastatic potential. Here we demonstrate that inhibition of dihydroorotate dehydrogenase (DHODH), a key enzyme of the de novo pyrimidine synthesis pathway, effectively decreases proliferation of cancer cells via induction of replication and ribosomal stress in a p53- and checkpoint kinase 1 (Chk1)-dependent manner. Mechanistically, a block in replication and ribosomal biogenesis result in p53 activation paralleled by accumulation of replication forks that activate the ataxia telangiectasia and Rad3-related kinase/Chk1 pathway, both of which lead to cell cycle arrest. Since in the absence of functional p53 the cell cycle arrest fully depends on Chk1, combined DHODH/Chk1 inhibition in p53-dysfunctional cancer cells induces aberrant cell cycle re-entry and erroneous mitosis, resulting in massive cell death. Combined DHODH/Chk1 inhibition effectively suppresses p53-mutated tumors and their metastasis, and therefore presents a promising therapeutic strategy for p53-mutated cancers.
   
     
Ehmsen S, HJ Ditzel.
Signaling pathways essential for triple-negative breast cancer stem-like cells.
Stem Cells, 2020 Nov 19. doi: 10.1002/stem.3301. PMID:33211379.
Click to view summary
Background: Since the discovery of breast cancer stem cells (CSCs), a significant effort has been made to identify and characterize these cells. It is a generally believe that CSCs play an important role in cancer initiation, therapy resistance, and progression of triple-negative breast cancer (TNBC), an aggressive breast cancer subtype with poor prognosis. Thus, therapies targeting these cells would be a valuable addition to standard treatments that primarily target more differentiated, rapidly dividing TNBC cells. Although several cell surface and intracellular proteins have been described as biomarkers for CSCs, none of these are specific to this population of cells. Recent research is moving toward cellular signaling pathways as targets and biomarkers for CSCs. The WNT pathway, the nuclear factor-kappa B (NF-κB) pathway, and the cholesterol biosynthesis pathway have recently been identified to play a key role in proliferation, survival, and differentiation of CSCs, including those of breast cancer. In this review, we assess recent findings related to these three pathways in breast CSC, with particular focus on TNBC CSCs, and discuss how targeting these pathways, in combination with current standard of care, might prove effective and improve the prognosis of TNBC patients.
   
     
Løkkegaard S, D Elias, C Alves, M Bennetzen, A-V Lænkholm, M Bak, M Gjerstorff, L Johansen, H Vever, C Bjerre, T Kirkegaard, B Nordenskjöld, T Fornander, O Stål, L Lindström, L Esserman, A Lykkesfeldt, J Andersen, R Leth-Larsen, HJ Ditzel.
MCM3 upregulation confers endocrine resistance in breast cancer and is a predictive marker of diminished tamoxifen benefit.
npj Breast Cancer, 2020 ;7(1):2. doi: 10.1038/s41523-020-00210-8. PMID:33398005.
Click to view summary
Background: Resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer is a major clinical problem with poorly understood mechanisms. There is an unmet need for prognostic and predictive biomarkers to allow appropriate therapeutic targeting. We evaluated the mechanism by which minichromosome maintenance protein 3 (MCM3) influences endocrine resistance and its predictive/prognostic potential in ER+ breast cancer. We discovered that ER+ breast cancer cells survive tamoxifen and letrozole treatments through upregulation of minichromosome maintenance proteins (MCMs), including MCM3, which are key molecules in the cell cycle and DNA replication. Lowering MCM3 expression in endocrine-resistant cells restored drug sensitivity and altered phosphorylation of cell cycle regulators, including p53(Ser315,33), CHK1(Ser317), and cdc25b(Ser323), suggesting that the interaction of MCM3 with cell cycle proteins is an important mechanism of overcoming replicative stress and anti-proliferative effects of endocrine treatments. Interestingly, the MCM3 levels did not affect the efficacy of growth inhibitory by CDK4/6 inhibitors. Evaluation of MCM3 levels in primary tumors from four independent cohorts of breast cancer patients receiving adjuvant tamoxifen mono-therapy or no adjuvant treatment, including the Stockholm tamoxifen (STO-3) trial, showed MCM3 to be an independent prognostic marker adding information beyond Ki67. In addition, MCM3 was shown to be a predictive marker of response to endocrine treatment. Our study reveals a coordinated signaling network centered around MCM3 that limits response to endocrine therapy in ER+ breast cancer and identifies MCM3 as a clinically useful prognostic and predictive biomarker that allows personalized treatment of ER+ breast cancer patients.
   
     
Egholm GJ, Andersen MA, Andersen CL, Frederiksen H, bjerrum, O.W., Niemann CU
Abnormal eosinophil count at CLL diagnosis correlates with shorter treatment free survival.
British Journal of Haematology, Br J Haematol 2020 Dec 14. doi: 10.1111/bjh.17264. .PMID: 33316076
Click to view summary
Background:
   
     
Wästerlid T, Gradel, K.O., Eloranta, S., Glimelius, I., El-Galaly, T.C., Frederiksen H, Smedby K.
Clinical characteristics and outcomes among 2347 patients aged ≥85 years with major lymphoma subtypes: A Nordic Lymphoma Group Study.
British Journal of Haematology 2020 Nov 24. doi: 10.1111/bjh.17250. PMID: 33236363
Click to view summary
Background: There is a lack of data regarding treatment and prognosis for the growing group of oldest old patients with lymphoma. Therefore, we studied 2347 patients aged ≥85 years from the Danish and Swedish lymphoma registers 2000-2016 (Denmark) and 2007-2013 (Sweden). Outcome was assessed using relative survival (RS). The 2-year RS overall for patients with aggressive lymphomas was 38% [95% confidence interval (CI) 35-42%], of whom 845 (66%) patients received active treatment (chemotherapy, radiotherapy, immunotherapy, other). For aggressive lymphomas, not receiving active treatment was associated with an inferior 2-year RS of 12% (95% CI 9-17%) compared to 49% (95% CI 45-53%) for patients who received active treatment (excess mortality rate ratio 2·84, 95% CI 2·3-3·5; P < 0·0001). For patients with indolent lymphoma, the 2-year RS was 77% (95% CI 72-82%). Here, 383 (46%) patients received active treatment at diagnosis, but did not have better 2-year RS (75%, 95% CI 67-81%) compared to those who did not receive active treatment (83%, 95% CI 74-89%). We conclude that outcomes for the oldest old patients with lymphoma are encouraging for several subtypes and that active treatment is associated with improved outcome amongst the oldest old patients with aggressive lymphomas, indicating that age itself should not be a contraindication to treatment.
   
     
Brabrand M, Frederiksen H
Risks of solid and lymphoid malignancies in patients with myeloproliferative neoplasms: clinical implications.
Cancers (Basel). 2020, 12(10):E3061. PMID: 33092233
Click to view summary
Background: In the past decade, several studies have reported that patients with chronic myeloproliferative neoplasms (MPNs) have an increased risk of second solid cancer or lymphoid hematological cancer. In this qualitative review study, we present results from studies that report on these cancer risks in comparison to cancer incidences in the general population or a control group. Our literature search identified 12 such studies published in the period 2009-2018 including analysis of more than 65,000 patients. The results showed that risk of solid cancer is 1.5- to 3.0-fold elevated and the risk of lymphoid hematological cancer is 2.5- to 3.5-fold elevated in patients with MPNs compared to the general population. These elevated risks apply to all MPN subtypes. For solid cancers, particularly risks of skin cancer, lung cancer, thyroid cancer, and kidney cancer are elevated. The largest difference in cancer risk between patients with MPN and the general population is seen in patients below 80 years. Cancer prognosis is negatively affected due to cardiovascular events, thrombosis, and infections by a concurrent MPN diagnosis mainly among patients with localized cancer. Our review emphasizes that clinicians caring for patients with MPNs should be aware of the very well-documented increased risk of second non-myeloid cancers.
   
     
Joachim Baech , Steen Moeller Hansen, Lasse Hjort Jakobsen, Andreas K Øvlisen, Marianne Tang Severinsen, Peter de Nully Brown, Peter Vestergaard, Henrik Frederiksen, Judit Jørgensen, Jørn Starklint, Pär Josefsson, Troels Hammer, Michael Roost Clausen, Christian Torp-Pedersen, Paw Jensen, Tarec Christoffer El-Galaly
Increased risk of osteoporosis following commonly used first-line treatments for lymphoma: A Danish Nationwide Cohort Study.
Leukemia & Lymphoma, 2020, 61(6): 1345-1354. PMID: 32043382
Click to view summary
Background: High-dose prednisolone is used in first-line treatment for lymphoma, but the potential adverse impact on bone health is unclear. Danish patients with diffuse large B-cell lymphoma or follicular lymphoma diagnosed between 2000 and 2012 were matched to the background population. Osteoporotic events (osteoporosis treatment or low-energy fracture) were identified using the Danish National Patient Registry and Prescription Registry. In total, 2589 patients and 12,945 controls were included. Lymphoma patients had increased risk of osteoporotic events compared to the matched population (hazard ratio 1.61 [95% confidence interval 1.40;1.84]). The 5- and 10-year cumulative risks of osteoporotic events for lymphoma patients were 10.0% [8.6;11.4] and 16.3% [13.8;18.7], whereas corresponding risks in the background population were 6.8% [6.3;7.3] and 13.5% [12.4;14.6]. Patients without osteoporotic event in the first two years after treatment were not at higher risk of osteoporotic events in subsequent years. Risk factors for osteoporotic events were female sex and age >70 years.
   
     
Sonja Zweegman, Claudia A M Stege, Einar Haukas, Fredrik H Schjesvold, Mark-David Levin, Anders Waage, Rineke B L Leys, Saskia K Klein, Damian Szatkowski, Per Axelsson, Trung Hieu Do, Dorota Knut-Bojanowska, Ellen van der Spek, Asta Svirskaite, Anja Klostergaard, Morten Salomo, Celine Blimark, Paula F Ypma, Ulf-Henrik Mellqvist, Pino J Poddighe, Marian Stevens-Kroef, Niels W C J van de Donk, Pieter Sonneveld, Markus Hansson, Bronno van der Holt, Niels Abildgaard.
Ixazomib-Thalidomide-low dose dexamethasone induction followed by maintenance therapy with ixazomib or placebo in newly diagnosed multiple myeloma patients not eligible for autologous stem cell transplantation; results from the randomized phase II HOVON-126/NMSG 21.13 trial.
Haematologica. 2020 Feb 13;105(12):2879-2882. doi: 10.3324/haematol.2019.240374. PMID: 33256392; PMCID: PMC7716358.
Click to view summary
Background: .
   
     
Larsen RF, Jarden M, Minet LR, Frølund UC, Möller S, Abildgaard N.
Physical function in patients newly diagnosed with multiple myeloma; a Danish cohort study.
BMC Cancer. 2020 Mar 3;20(1):169. doi: 10.1186/s12885-020-6637-6. PMID: 32126972; PMCID: PMC7055017.
Click to view summary
Background: Multiple myeloma is a cancer in the bone marrow causing bone destruction. Patients experience various symptoms related to the disease and/or treatment, such as pain and fatigue, leading to poorer quality of life. The symptom burden might affect physical function and physical activity levels, posing a risk of physical deterioration. The aim was to investigate whether physical function in newly diagnosed patients with multiple myeloma differs from the reference values of the normal population and other cancer patients.
   
     
Jespersen E, Nielsen LK, Larsen RF, Möller S, Jarlbæk L.
Everyday living with pain - reported by patients with multiple myeloma. Scand J Pain.
2020 Oct 27:/j/sjpain.ahead-of-print/sjpain-2020-0087/sjpain-2020-0087.xml. doi: 10.1515/sjpain-2020-0087. Epub ahead of print. PMID: 33108340.
Click to view summary
Background: Objectives The prevalence and impact of pain among patients with multiple myeloma (MM) in their everyday life require renewed attention. MM patients' survival has increased considerably over the last decades and active disease episodes are interrupted by longer periods with disease inactivity. The aim with this study is to explore pain intensity and pain interference with daily activities during periods of stable or inactive MM disease. Methods In a cross-sectional study from September 2017 to May 2019, self-reliant MM patients in stable disease filled a comprehensive selection of validated questionnaires regarding pain, other symptoms and quality of life, which they experienced in their daily living. Patient reported pain intensity and interference with daily activities were analyzed for associations with several clinical and demographic factors and discussed from a total pain perspective. The two outcomes, pain intensity and pain interfering with daily activities, were analyzed in two age groups (<65 years or ≥65 years). Results Among 92 participants, 80% experienced pain to interfere with their daily activities (equal in both age groups), and 63% reported moderate to severe pain intensity; (75% ≥65 years, and 49% <65 years). Pain intensity was significantly associated with signs of depression (OR 4.0 [95% CI: 1.2-13.9]) and age ≥65 years (OR 3.3 [95% CI: 1.2-9.2]). Pain interfering with daily activities was nearly significantly associated with bone involvement (OR 3.4 [95% CI: 1.0-11.6]) and signs of depression (OR 5.9 [95% CI: 1.0-36.3]). The patients were bothered with many problems in addition to pain; fatigue (91%), bone involvement (74%), signs of depression (41%), signs of anxiety (32%), comorbidity (29%) and uncertainty in relation to employment or pension (25%). Neuropathic pain was more prevalent in the feet (33% [95% CI: 23%, 43%]) compared with pain in the hands (13% [95% CI: 7%, 22%]). Conclusions In periods of stable disease, many MM patients continue to live with intense pain interfering with their daily activities. Additional or associated problems are the presence of bone involvement, neuropathic pain, older age, uncertainty in relation to employment or pension, comorbidity, signs of depression, anxiety and fatigue. This highlights the importance of health professionals being receptive to the patients' experience of pain throughout their trajectories, to assess pain systematically and to interpret this experience from a total pain perspective. While pain problems in relation to diagnosing and treating MM is well known, this study brings the message that even during periods of stable or inactive MM disease, the patients experience pain with a moderate to severe intensity, that interferes with their everyday living. The improved survival and the consequential long trajectories make coherence in the pain treatment even more important for the patients, who may see different professionals in different health care settings for different reasons. The patient group requires a coordinated, holistic patient-centered pain treatment throughout the disease trajectory.
   
     
Redder L, Klausen TW, Vangsted AJ, Gregersen H, Andersen NF, Pedersen RS, Szabo AG, Frederiksen M, Frølund UC, Helleberg C, Nielsen LK, Pedersen PT, Salomo M, Gimsing P, Frederiksen H, Abildgaard N.
Validation of the UK myeloma research alliance risk profile, a new clinical prediction model for outcome in patients with newly diagnosed multiple myeloma not eligible for autologous stem cell transplantation; a population-based study from the Danish national multiple myeloma registry.
Br J Haematol. 2020 Jun 9. doi: 10.1111/bjh.16806. Online ahead of print. PMID: 32515050
Click to view summary
Background: In 2019 the UK Myeloma Research Alliance introduced the Myeloma Risk Profile (MRP) for prediction of outcome in patients with newly diagnosed multiple myeloma (MM), ineligible for autologous stem cell transplantation. To validate the MRP in a population-based setting we performed a study of the entire cohort of transplant ineligible MM patients above 65 years in the Danish National MM Registry. Our data confirmed the value of the MRP. In a cohort of 1,377 patients, the MRP score separated patients into three distinct risk-groups with an observed hazard ratio of 2.91 for early death in high-risk versus low-risk patients.
   
     
M.K. Jakobsen, Morten F. Gjerstorff
Car T-Cell cancer therapy targeting surface cancer/testis antigens
Frontiersn immunology, 11: 1568; 2020 https://doi.org/10.3389/fimmu.2020.01568
Click to view summary
Background:
   
     
Tove Weasterlid, Kim Oren Gradel, Sandra Eloranta, Ingrid Glimelius, Tarec C. El-Galaly, Henrik Frederiksen, Karin E. Smedby.
Clinical characteristics and outcomes among 2347 patients aged ≥85 years with major lymphoma subtypes: a Nordic Lymphoma Group study
British Journal of Haematology 2020 Nov 24. doi: 10.1111/bjh.17250. PMID: 33236363
Click to view summary
Background: There is a lack of data regarding treatment and prognosis for the growing group of oldest old patients with lymphoma. Therefore, we studied 2347 patients aged ≥85 years from the Danish and Swedish lymphoma registers 2000-2016 (Denmark) and 2007-2013 (Sweden). Outcome was assessed using relative survival (RS). The 2-year RS overall for patients with aggressive lymphomas was 38% [95% confidence interval (CI) 35-42%], of whom 845 (66%) patients received active treatment (chemotherapy, radiotherapy, immunotherapy, other). For aggressive lymphomas, not receiving active treatment was associated with an inferior 2-year RS of 12% (95% CI 9-17%) compared to 49% (95% CI 45-53%) for patients who received active treatment (excess mortality rate ratio 2·84, 95% CI 2·3-3·5; P < 0·0001). For patients with indolent lymphoma, the 2-year RS was 77% (95% CI 72-82%). Here, 383 (46%) patients received active treatment at diagnosis, but did not have better 2-year RS (75%, 95% CI 67-81%) compared to those who did not receive active treatment (83%, 95% CI 74-89%). We conclude that outcomes for the oldest old patients with lymphoma are encouraging for several subtypes and that active treatment is associated with improved outcome amongst the oldest old patients with aggressive lymphomas, indicating that age itself should not be a contraindication to treatment.
   
     
Stefan S. Jeppesen, Kristian K. Bentsen, Trine L. Jørgensen, Hanne S. Holm, Linda Holst-Christensen, Line S. Tarpgaard, Rikke H. Dahlrot, Lise Eckhoff
Quality of life in patients with cancer during the COVID-19 pandemic – a Danish cross-sectional study (COPICADS)
Acta Oncol. 2020 Oct 8;1-9. doi: 10.1080/0284186X.2020.1830169.
Click to view summary
Background: The COVID-19 pandemic is an international public health crisis. The risk of getting an infection with COVID-19 might impact the emotional well-being in patients with cancer. The aim of this study was to investigate quality of life (QoL) for patients with cancer during the COVID-19 pandemic.
   
     
Rosenbaek, F., Holm, H. S., Hjelmborg, J. V. B., Ewertz, M. & Jensen, J. D.
Effect of cryotherapy on dose of adjuvant paclitaxel in early-stage breast cancer
aug. 2020, I : Supportive Care in Cancer. 28, 8, s. 3763-3769
Click to view summary
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of paclitaxel. Though no pharmacological agents have been identified to prevent CIPN, cryotherapy with frozen gloves and socks may reduce the risk of developing CIPN and thereby increase the likelihood of patients completing the planned dose of paclitaxel.
   
     
Rizzi, S., Wensink, M., Ahrenfeldt, L. J., Christensen, K. & Lindahl-Jacobsen, R.
Age-specific cancer rates: a bird's-eye view on progress
ug. 2020, I : Annals of Epidemiology. 48, s. 51-54.e1
Click to view summary
Background: We aim to shed light on progress in cancer medicine through studying time trends in age-specific rates of cancer incidence and mortality over the last quarter century.
   
     
Marianne Vogsen, Camilla Bille, Anne Marie Bak Jylling, Maj-Britt Jensen, Marianne Ewertz & on behalf of the Academy for Geriatric Cancer Research (AgeCare)
Adherence to treatment guidelines and survival in older women with early-stage breast cancer in Denmark 2008–2012
Acta Oncologica, DOI: 10.1080/0284186X.2020.1757148
Click to view summary
Background: The aims of this study were to compare patients 70 years or older with younger patients, to examine whether Danish patients with early-stage breast cancer aged 70 years or more received treatment according to guidelines, the reasons for deviating from the guidelines, and to analyze whether such deviations affected survival.
   
     
Birte Østergaard, Anne M Clausen, Hanne Agerskov, Anne Brødsgaard, Karin B. Dieperink, Karen F. Funderskov, Dorthe Nielsen, Anne D. Sorknæs, Barbara Voltelen, Hanne Konradsen
Nurses' attitudes regarding the importance of families in nursing care: A cross‐sectional study
Journal of clinical nursing, 29:7-8. 2020. https://doi.org/10.1111/jocn.15196
Click to view summary
Background: Evidence suggests that nurses hold both supportive and less supportive attitudes about involvement of family members in the care of patients, and the existing findings are limited to specific healthcare contexts.
   
     
Karin Brochstedt Dieperink, Caroline Matilde Elnegaard, Bodil Winther, Anna Lohman, Ida Zerlang, Sören Möller and Graziella Zangger
Preliminary validation of the insomnia severity index in Danish outpatients with a medical condition
Journal of Patient-Reported Outcomes (2020) 4:18. https://doi.org/10.1186/s41687-020-0182-6
Click to view summary
Background: Insomnia is a frequent sleeping disorder in the general and clinical population. With an increasing proportion of health care services being provided as outpatient care, a short, valid and reliable tool is needed to identify insomnia in medical patients under outpatient care in Denmark. The Insomnia Severity Index (ISI) could be the needed tool if found valid and reliable. Hence, the aim of this study is to evaluate elements of the psychometric properties of the Danish version of ISI (ISI-DK).
   
     
Nadja Buch Petersson, Ane Løvendahl Jørgensen, Dorthe Boe Danbjørg, Karin Brochstedt Dieperink
Video-consulted rounds with caregivers: The experience of patients with cancer
European Journal of Oncology Nursing, 2020-06-01, Volume 46, Article 101763 https://doi.org/10.1016/j.ejon.2020.101763
Click to view summary
Background: This study aim to explore how adult patients admitted to an oncology ward experience video-consulted rounds with caregivers as a mean for family involvement.
   
     
Coyne, E., Heynsbergh, N. & Dieperink, K. B
Acknowledging cancer as a family disease: A systematic review of family care in the cancer setting
European Journal of Oncology Nursing https://doi.org/10.1016/j.ejon.2020.101841
Click to view summary
Background: Family members are a part of the team to improve the outcomes of the person with cancer. Families require support and information to optimise their care, however, their needs are often unacknowledged and within clinical areas there is a lack of family focused interventions. Studies highlight families' needs but lack a family representation. The aim was to explore research with family as the unit-of-care during cancer treatment.
   
     
Dieperink, K. B., Hansen, S., Wagner, L., Minet, L. R. & Hansen, O
Long-term follow-up 3 years after a randomized rehabilitation study among radiated prostate cancer survivors
Journal of Cancer Survivorship. http://doi.org/10.1007/s11764-020-00958-9
Click to view summary
Background: In the Rehabilitation of Prostate Cancer (RePCa) study, the intervention reduced early adverse effects in prostate cancer 6 months after radiotherapy. This 3-year follow-up study assesses late adverse effects, evaluates rehabilitative long-term effects and identifies patients who benefit the most.
   
     
Hanne Konradsen, Anne Brødsgaard, Birte Østergaard, Erla Svavarsdottir, Karin B. Dieperink, Lorenz Imhof, Marie Louise Luttik, Romy Mahrer, Cristina Garcıa-Vivar
Health practices in Europe towards families of older patients with cancer: a scoping review
Scand J Caring Sci; 2020. doi: 10.1111/scs.12855
Click to view summary
Background: In Europe, cancer is one of the predominant causes of mortality and morbidity among older people aged over 65. A diagnosis of cancer can imply a negative impact on the quality of life of the older patients and their families. Despite research examining the impact of cancer on the family, it is unclear what kind of information is available about the types of clinical practice towards older patients with cancer and their families. The aim is to determine the extent, range and variety of research in Europe describing health practices towards families of older patients with cancer and to identify any existing gaps in knowledge.
   
     
Damberg Nissen, R., Falkø, E., Toudal Viftrup, D., Assing Hvidt, E., Søndergaard, J., Büssing, A., . . . Hvidt, N. C.
The Catalogue of Spiritual Care Instruments: A Scoping Review.
Religions, 11(5). 2020. doi:10.3390/rel11050252
Click to view summary
Background:
   
     
Hvidt, Niels Christian, Nielsen, Kristina Tomra, Kørup, Alex K, Prinds, Christina et al
What is spiritual care? Professional perspectives on the concept of spiritual care identified through group concept mapping
BMJ Open 2020 Dec 28;10(12):e042142. 10.1136/bmjopen-2020-042142 PMID: 33372078
Click to view summary
Background: The overall study aim was to synthesise understandings and experiences regarding the concept of spiritual care (SC). More specifically, to identify, organise and prioritise experiences with the way SC is conceived and practised by professionals in research and the clinic.
   
     
Kørup, Alex Kappel, Søndergaard, Jens, Christensen, René dePont Nielsen, Connie Thurøe, Hvidt, Niels Christian et al
Religious Values in Clinical Practice are Here to Stay
Journal of Religion and Health 10.1007/s10943-018-0715-y PMID: 30328542
Click to view summary
Background: Research to date has shown that health professionals often practice according to personal values, including values based on faith, and that these values impact medicine in multiple ways. While some influence of personal values are inevitable, awareness of values is important so as to sustain beneficial practice without conflicting with the values of the patient. Detecting when own personal values, whether based on a theistic or atheistic worldview, are at work, is a daily challenge in clinical practice. Simultaneously ethical guidelines of tone-setting medical associations like American Medical Association, the British General Medical Council and Australian Medical Association have been updated to encompass physicians' right to practice medicine in accord with deeply held beliefs. Framed by this context, we discuss the concept of value-neutrality and value-based medical practice of physicians from both a cultural and ethical perspective, and reach the conclusion that the concept of a completely value-neutral physician, free from influence of personal values and filtering out value-laden information when talking to patients, is simply an unrealistic ideal in light of existing evidence. Still we have no reason to suspect that personal values, whether religious, spiritual, atheistic or agnostic, should hinder physicians from delivering professional and patient-centered care.
   
     
Kørup, Alex Kappel, Wehberg, Sonja, Hvidt, Elisabeth Assing, Hvidt, Niels Christian, Fitchett, George, Hansen, Dorte Gilså
Age‐stratified validation of the Functional Assessment of Chronic Illness Therapy‐Spiritual Well‐Being based on a large cohort of Danish cancer survivors
Psycho‐Oncology. 2020 Jul;29(7):1217-1223 10.1002/pon.5412 PMID: 32419270
Click to view summary
Background: Previous research indicates that the FACIT-Sp instrument is susceptible to bias when measuring spiritual well-being in older patients. Our first focus was to evaluate the two-factor vs the three-factor model of the FACIT-Sp and our second focus was to explore how these models behave for different age groups.
   
     
Herold, Steffen Christensen, Hvidt, Niels Christian, Möller, Sören, Christensen, Kaare, Ahrenfeldt, Linda Juel
Is Religiousness Associated with Better Lifestyle and Health Among Danes? Findings from SHARE
Journal of Religion and Health. 2020 Jun 2 10.1007/s10943-020-01050-3 PMID: 32488829
Click to view summary
Background: Evidence of a possible association between religion and health in secular societies is sparse. We therefore conducted a nationwide study using data from 1596 Danes aged 50 + who participated in the Survey of Health, Ageing and Retirement in Europe (SHARE) wave 1 (2004-2005) and were followed up between 2006 and 2015, to investigate the association between religiousness and health including a lifestyle index. Results from the longitudinal models adjusted for age and gender showed that being religiously educated by parents, taking part in a religious organization, and praying were factors associated with fewer risk factors of unhealthy lifestyle. Furthermore, being religiously educated was associated with lower odds of self-rated poor health and depressive symptoms. Results were overall consistent across the cross-sectional and longitudinal models and persisted after further adjustment for education and marital status. These findings provide support for a positive relationship between religiousness and health among Danes, particularly for those being religiously educated by their parents.
   
     
Andersen, Aida Hougaard, Assing Hvidt, Elisabeth, Hvidt, Niels Christian Roessler, Kirsten K.
Maybe we are losing sight of the human dimension – physicians’ approaches to existential, spiritual, and religious needs among patients with chronic pain or multiple sclerosis. A qualitative interview-study
Health Psychology and Behavioral Medicine 10.1080/21642850.2020.1792308
Click to view summary
Background:
   
     
2019    
     
Jørgensen TL, Herrstedt J; Academy of Geriatric Cancer Research (AgeCare), Odense University Hospital, Odense, Denmark.
The influence of polypharmacy, potentially inappropriate medications, and drug interactions on treatment completion and prognosis in older patients with ovarian cancer.
J Geriatr Oncol. 2019 Dec 26. pii: S1879-4068(19)30293-0. doi: 10.1016/j.jgo.2019.12.005. [Epub ahead of print] PubMed PMID: 31883969.
Click to view summary
Background: Older patients with cancer are at increased risk of exposure to polypharmacy (PP), potential drug interactions (PDIs), and Potentially inappropriate Medications (PIMs). Objectives of this study were to describe PP, PIMs, and PDIs, and to analyse the associations with completion of 1st line chemotherapy and prognosis in ovarian cancer (OC) patients.
   
     
Andersen NL. Nielsen CI. Danbjørg DB. Møller PK. Dieperink KB.
Caregivers' Need for Support in an Outpatient Cancer Setting.
2019 Oncology Nursing Forum 2019 DOI 10.1188/19.ONF.757-767
Click to view summary
Background: xxxxxxx.
 
     
Vestergaard LV. Østervang C. Danbjørg DB. Dieperink KB.
Video-Based Patient Rounds for Caregivers of Patients With Cancer.
Oncology Nursing Forum 2019 Jul 1;46(4):485-492. doi: 10.1188/19.ONF.485-492
Click to view summary
Background: To investigate caregivers' experiences and level of involvement with video-based patient rounds.
   
     
Østervang C. Vestergaard LV. Dieperink KB. Danbjørg DB
Patient Rounds With Video-Consulted Relatives: Qualitative Study on Possibilities and Barriers From the Perspective of Healthcare Providers.
Journal of Medical Internet Research JMIR Vol 21, No. 3 (2019) DOI: doi:10.2196/12584
Click to view summary
Background: In cancer settings, relatives are often seen as a resource as they are able to support the patient and remember information during hospitalization. However, geographic distance to hospitals, work, and family obligations are reasons that may cause difficulties for relatives' physical participation during hospitalization. This provided inspiration to uncover the possibility of telehealth care in connection with enabling participation by relatives during patient rounds. Telehealth is used advantageously in health care systems but is also at risk of failing during the implementation process because of, for instance, health care professionals' resistance to change. Research on the implications for health care professionals in involving relatives' participation through virtual presence during patient rounds is limited.
   
     
Bjørnhart B, Hansen KH, Jørgensen TL, Herrstedt J, Schytte T.
Efficacy and safety of immune checkpoint inhibitors in a Danish real life non-small cell lung cancer population: a retrospective cohort study.
Acta Oncol. 2019 Jul;58(7):953-961. doi: 10.1080/0284186X.2019.1615636. Epub 2019 May 12. PubMed PMID: 31081424.
Click to view summary
Background: To investigate effect and toxicity of immune checkpoint inhibition (ICI) in a Danish real-life non-small cell lung cancer (NSCLC) population. By including patients underrepresented in clinical trials, such as those with brain metastasis (BM), higher age, more comorbidity and poorer performance status (ECOG), comparison of unselected patients to clinical trial populations is possible.
   
     
Hvidt NC, Mikkelsen TB, Zwisler AD, Tofte JB, Assing Hvidt E.
Spiritual, religious, and existential concerns of cancer survivors in a secular country with focus on age, gender, and emotional challenges.
Support Care Cancer. 2019.
Click to view summary
Background: The purpose of this study was to examine the associations between self-reported spiritual/religious concerns and age, gender, and emotional challenges among cancer survivors who have completed a 5-day rehabilitation course at a rehabilitation center in Denmark (the former RehabiliteringsCenter Dallund (RC Dallund)).
   
     
Kørup AK, Søndergaard J, Lucchetti G, Ramakrishnan P, Baumann K, Lee E, Frick E, Büssing A, Alyousefi NA, Karimah A, Schouten E, Wermuth I, Hvidt NC.
Religious values of physicians affect their clinical practice: A meta-analysis of individual participant data from 7 countries.
Medicine. 2019;98 (38):e17265.
Click to view summary
Background: Observational studies indicate that religious values of physicians influence clinical practice. The aim of this study was to test prior hypotheses of prevalence of this influence using a meta-analysis design.
   
     
Opsahl T, Ahrenfeldt L, Möller S, Christensen K, Hvidt NC.
Religiousness and depressive symptoms in Europeans: findings from the Survey of Health, Ageing, and Retirement in Europe.
Public Health. 2019.
Click to view summary
Background: Religiousness has been found to protect against depression based on studies conducted in the United States, though there are limited data in the European population. We sought to evaluate the associations between religiousness and six depressive symptoms in Europeans aged 50+ years.
   
     
Schrøder K, Lamont R, Jørgensen J, Hvidt N.
Second victims need emotional support after adverse events: even in a just safety culture.
BJOG: An International Journal of Obstetrics & Gynaecology. 2019;126(4):440-2.
Click to view summary
Background:
   
     
Hvidt, N. C., Mikkelsen, T. B., Zwisler, A. D., Tofte, J. B., & Assing Hvidt, E.
Spiritual, religious, and existential concerns of cancer survivors in a secular country with focus on age, gender, and emotional challenges.
Supportive Care in Cancer. doi:10.1007/s00520-019-04775-4
Click to view summary
Background: The purpose of this study was to examine the associations between self-reported spiritual/religious concerns and age, gender, and emotional challenges among cancer survivors who have completed a 5-day rehabilitation course at a rehabilitation center in Denmark (the former RehabiliteringsCenter Dallund (RC Dallund)).
   
     
van Randwijk, C. B., Opsahl, T., Hvidt, E. A., Korup, A. K., Bjerrum, L., Thomsen, K. F., & Hvidt, N. C.
Characteristics of Religious and Spiritual Beliefs of Danish Physicians: And Likelihood of Addressing Religious and Spiritual Issues with Patients
Journal of religion and health. doi:10.1007/s10943-018-0662-7
Click to view summary
Background: This study investigated the association between physicians' R/S characteristics and frequency of addressing patients' R/S issues. Information was obtained through a questionnaire mailed to 1485 Danish physicians (response rate 63%) (42% female). We found significant associations between physicians' personal R/S and the frequency of addressing R/S issues. Moreover, we identified significant gender differences in most R/S characteristics. However, no differences in frequency of addressing R/S issues were identified across gender. This raises some questions regarding the effects of gender on associations between R/S characteristics and frequency of addressing R/S issues.
   
     
Nadaraja S, Matzen LE, Jørgensen TL, Dysager L, Knudsen AØ, Jeppesen SS, Möller S, Herrstedt J; Academy of Geriatric Cancer Research (AgeCare).
The impact of comprehensive geriatric assessment for optimal treatment of older patients with cancer: A randomized parallel-group clinical trial.
J Geriatr Oncol 2019 Jul 3. pii: S1879-4068(19)30124-9.
Click to view summary
Background: The aim was to investigate if oncologic treatment decision based on G8 screening followed by comprehensive geriatric assessment (CGA) and a multidisciplinary team conference in patients with G8 ≤ 14 was better than treatment decision based on standard assessment. ClinicalTrials.gov Identifier: NCT02671994.
   
     
Winther SB, Liposits G, Skuladottir H, Hofsli E, Shah CH, Poulsen LØ, Ryg J, Osterlund P, Berglund Å, Qvortrup C, Glimelius B, Sorbye H, Pfeiffer P.
Reduced-dose combination chemotherapy (S-1 plus oxaliplatin) versus full-dose monotherapy (S-1) in older vulnerable patients with metastatic colorectal cancer (NORDIC9): a randomised, open-label phase 2 trial.
Lancet Gastroenterol Hepatol 2019; 4: 376-88.
Click to view summary
Background: Older or vulnerable patients with metastatic colorectal cancer are seldom included in randomised trials. The multicentre NORDIC9 trial evaluated reduced-dose combination chemotherapy compared with full-dose monotherapy in older, vulnerable patients.
   
     
Bahij R, Jeppesen SS, Olsen KE, Halekoh U, Holmskov K, Hansen O.
Outcome of treatment in patients with small cell lung cancer in poor performance status.
Acta Oncol 2019; 58: 1612-7.
Click to view summary
Background: Patients with small cell lung cancer (SCLC) with poor performance status (PS) especially in the elderly may not benefit from chemotherapy. The aim of this study was to compare survival of treated patients with PS 3-4 with untreated patients.Material and methods: We reviewed the medical records and pathology data for 448 patients diagnosed with small cell carcinoma from 2010 to 2015 and selected all patients in PS 3-4 for review.Results: A total of 87 patients fulfilled the inclusion criteria. Of these, 53 (61%) received chemotherapy (CT), while 34 (39%) did not. The median overall survival (OS) was 5.1 months for the treated patients and 0.7 month for the untreated (p < .001). Multivariate analysis identified lack of treatment with chemotherapy, extensive disease, and PS 4 as independent factors associated with poor prognosis, while age and gender were not. Also, patients with aged ≥70 years who had extended disease had significant improved OS when treated with CT. However, the chance of being treated with CT was significantly influenced by age.Conclusion: CT was associated with improved survival in patients with SCLC with PS 3-4 independent of age and stage of disease. Neither ED, high age, nor poor PS should be used as criteria for omitting CT.
   
     
Larsen RF, Jarden M, Minet LR, Frølund UC, Abildgaard N.
Supervised and home-based physical exercise in patients newly diagnosed with multiple myeloma-a randomized controlled feasibility study.
Pilot Feasibility Stud. 2019 Nov 12;5:130. eCollection 2019. PubMed PMID: 31741745
Click to view summary
Background: The study evaluated the feasibility and safety of the exercise intervention and physical test procedures of our ongoing randomized controlled trial, examining the effect of physical exercise in newly diagnosed patients with multiple myeloma.
   
     
Nielsen LK, King M, Möller S, Abildgaard N.
Strategies to improve patient-reported outcome completion rates in longitudinal studies.
Qual Life Res. 2019 Sep 23. doi: 10.1007/s11136-019-02304-8. [Epub ahead of print] PubMed PMID: 31549365.
Click to view summary
Background: The quality of patient-reported outcome (PRO) data can be compromised by non-response (NR) to scheduled questionnaires, particularly if reasons for NR are related to health problems, which may lead to unintended bias. The aim was to investigate whether electronic reminders and real-time monitoring improve PRO completion rate.
   
     
Nielsen LK, Abildgaard N, Jarden M, Klausen TW.
Methodological aspects of health-related quality of life measurement and analysis in patients with multiple myeloma.
Br J Haematol. 2019 Apr;185(1):11-24. Review. PubMed PMID: 30656677.
Click to view summary
Background: Multiple myeloma (MM) is an incurable but treatment-sensitive cancer. For most patients, this means treatment with multiple lines of anti-myeloma therapy and a life with disease- and treatment-related symptoms and complications. Health-related quality of life (HRQoL) issues play an important role in treatment decision-making. Methodological challenges in longitudinal HRQoL measurements and analyses have been identified, including non-responses (NR) to scheduled questionnaires. Publications were identified for inclusion in a systematic review of longitudinal HRQoL studies in MM, focussing on methodological aspects of HRQoL measurement and analysis. Diversity in timing of HRQoL data collection and applied statistical methods were noted. We observed a high rate of NR, but the impact of NR was investigated in only 8/23 studies. Thus, evidence-based knowledge of HRQoL in patients with MM is compromised. To improve quality of HRQoL results and their implementation in daily practice, future studies should follow established guidelines.
   
     
Nielsen LK, Stege C, Abildgaard N, Zweegman S.
Health-related quality of life in transplant ineligible newly diagnosed multiple myeloma patients treated with either thalidomide or lenalidomide-based regimen until progression: a prospective, open-label, multicenter, randomized, phase 3 study.
Haematologica. 2019 Sep 12. PubMed PMID: 31515355
Click to view summary
Background: Data on the impact of long term treatment with IMiDs on health-related quality of life is limited. The HOVON-87/NMSG18 study was a randomized, phase 3 study in newly diagnosed transplant ineligible patients with multiple myeloma, comparing melphalan-prednisolone in combination with thalidomide or lenalidomide, followed by maintenance therapy until progression (MPT-T or MPR-R). The EORTC QLQ-C30 and MY20 questionnaires were completed at baseline, after 3 and 9 induction cycles and 6 and 12 months of maintenance therapy. Linear mixed models and minimal important differences were used for evaluation. 596 patients participated in health-related quality of life reporting. Patients reported clinically relevant improvement in global quality of life, future perspective and role and emotional functioning, and less fatigue and pain in both arms. The latter being of large effect size. In general, improvement occurred after 6 to 12 months of maintenance only and was independent of WHO performance at baseline. Patients treated with MPR-R reported clinically relevant worsening of diarrhea, and patients treated with MPT-T reported a higher incidence of neuropathy. Patients who remained on lenalidomide maintenance therapy for at least 3 months reported clinically meaningful improvement in global QoL and role functioning at 6 months, remaining stable thereafter. There were no clinically meaningful deteriorations, but patients on thalidomide reported clinically relevant worsening in neuropathy. In general, health-related quality of life improves both during induction and maintenance therapy with IMiDs. Side effect profile of treatment did not negatively affect global quality of life, but it was, however, clinically relevant for the patients. (Clinicaltrials.gov identifier: NTR1630).
   
     
Bertelsen AS, Schytte T, Møller PK, Mahmood F, Riis HL, Gottlieb KL, Agergaard SN, Dysager L, Hansen O, Gornitzka J, Veldhuizen E, ODwyer DB, Christiansen RL, Nielsen M, Jensen HR, Brink C, Bernchou U.
First clinical experiences with a high field 1.5 T MR linac.
Acta Oncologica, 58:1352–1357, 2019
Click to view summary
Background: A 1.5 T MR Linac (MRL) has recently become available. MRL treatment workflows (WF) include online plan adaptation based on daily MR images (MRI). This study reports initial clinical experiences after five months of use in terms of patient compliance, cases, WF timings, and dosimetric accuracy.
   
     
Finnegan R, Lorenzen E, Dowling J, Holloway L, Thwaites D, Brink C.
Localised delineation uncertainty for iterative atlas selection in automatic cardiac segmentation.
Physics in Medicine & Biology, 2019
Click to view summary
Background: The heart is an important organ at risk during thoracic radiotherapy. Many studies have demonstrated a correlation between the mean heart dose and an increase in cardiovascular disease. Different treatments result in significant dose variation within the heart and individualised dose estimation increasingly requires more attention to delineation of various cardiac structures. Automatic segmentation tools are critical for consistent and accurate delineation of organs at risk in large, retrospective studies, however the challenge of ensuring a robust method must be addressed. In a multi-atlas based segmentation framework the uncertainty in delineation can be modelled over the surface of the heart. We extend this concept with an iterative atlas selection procedure designed to remove inconsistent atlas contours, in turn improving the reliability of the segmentation. Two independent datasets comprising 15 and 20 planning computed tomography (CT) images of Danish and Australian breast cancer patients, respectively, had the whole heart and left anterior descending coronary artery (LADCA) delineated. Using a cross-validation strategy, where each dataset is used as an atlas set to segment each image in the other, we assess segmentation performance qualitatively and quantitatively, using the dice similarity coefficient (DSC), mean surface-to-surface distance (MASD) and Hausdorff distance (HD). After using the iterative atlas selection procedure, every segmentation error was removed. For the whole heart, the resulting segmentation achieved a DSC, MASD and HD of [Formula: see text], [Formula: see text] mm, and [Formula: see text] mm.
   
     
Hansen O, Kristiansen C, Nielsen M, Schytte T, Starup Jeppesen S.
Survival after stereotactic radiotherapy in patients with early-stage non-small cell lung cancer.
Acta Oncologica, 58(10):1399–1403, 2019
Click to view summary
Background: Stereotactic radiotherapy (SBRT) is the treatment of choice for inoperable early stage non-small cell lung cancer (NSCLC). We report analyses of the influence of age on survival after SBRT.
   
     
Poulsen MH, Jakobsen JS, Mortensen MA, Høilund-Carlsen PF, Lund L.
Does therapy of the primary tumor matter in oligometastatic prostate cancer? A prospective 10-year follow-up study.
Res Rep Urol. 2019 Jul 30;11:215-221. doi: 10.2147/RRU.S190140. eCollection 2019.
Click to view summary
Background: The effect of curative treatment for oligometastatic prostate cancer patients is unsolved, both with regard to morbidity and mortality. With this study, we provide some of the first long-term follow-up data on progression and mortality in oligometastatic prostate cancer patients after curative treatment of their primary tumor.
   
     
Poulsen MH, Frost M, Abrahamsen B, Gerke O, Walter S, Lund L.
Osteoporosis and prostate cancer; a 24-month prospective observational study during androgen deprivation therapy.
Scand J Urol. 2019 Feb;53(1):34-39. doi: 10.1080/21681805.2019.1570328. Epub 2019 Feb 19.
Click to view summary
Background: Treatment and prognosis of prostate cancer necessitate management of long-term consequences of A.D.T., including accelerated bone loss resulting in osteoporosis; osteoporotic fractures are associated with excess morbidity and mortality.
   
     
Bjerre ED, Petersen TH, Jørgensen AB, Johansen C, Krustrup P, Langdahl B, Poulsen MH, Madsen SS, Østergren PB, Borre M, Rørth M, Brasso K, Midtgaard J.
Community-based football in men with prostate cancer: 1-year follow-up on a pragmatic, multicentre randomised controlled trial.
PLoS Med. 2019 Oct 1;16(10):e1002936. doi: 10.1371/journal.pmed.1002936. eCollection 2019 Oct.
Click to view summary
Background: Physical exercise has been shown to be effective in relation to fatigue, aerobic fitness, and lower body strength in men with prostate cancer. However, research into the clinically relevant effects of interventions conducted in heterogeneous patient populations and in real-life clinical practice settings is warranted.
   
     
Thiery-Vuillemin A, Poulsen MH, Lagneau E, Ploussard G, Birtle A, Dourthe LM, Beal-Ardisson D, Pintus E, Trepiakas R, Lefresne F, Lukac M, Van Sanden S, Pissart G, Reid A; AQUARiUS Investigators.
Impact of Abiraterone Acetate plus Prednisone or Enzalutamide on Patient-reported Outcomes in Patients with Metastatic Castration-resistant Prostate Cancer: Final 12-mo Analysis from the Observational AQUARiUS Study.
Eur Urol. 2019 Oct 5. pii: S0302-2838(19)30739-0. doi: 10.1016/j.eururo.2019.09.019.
Click to view summary
Background: Few studies have examined patient-reported outcomes (PROs) with abiraterone acetate plus prednisone (abiraterone) versus enzalutamide in metastatic castration-resistant prostate cancer (mCRPC). OBJECTIVE: To determine the impact of abiraterone and enzalutamide on PROs.
   
     
Brückmann NH, Bennedsen SN, Duijf PHG, Terp MG, Thomassen M, Larsen M, Pedersen CB, Kruse T, Alcaraz N, Ditzel HJ, Gjerstorff MF.
A functional genetic screen identifies the Mediator complex as essential for SSX2-induced senescence.
Cell Death Dis. 2019 Nov 6;10(11):841. doi: 10.1038/s41419-019-2068-1.
Click to view summary
Background: The senescence response to oncogenes is believed to be a barrier to oncogenic transformation in premalignant lesions, and describing the mechanisms by which tumor cells evade this response is important for early diagnosis and treatment. The male germ cell-associated protein SSX2 is ectopically expressed in many types of cancer and is functionally involved in regulating chromatin structure and supporting cell proliferation. Similar to many well-characterized oncogenes, SSX2 has the ability to induce senescence in cells. In this study, we performed a functional genetic screen to identify proteins implicated in SSX2-induced senescence and identified several subunits of the Mediator complex, which is central in regulating RNA polymerase-mediated transcription. Further experiments showed that reduced levels of MED1, MED4, and MED14 perturbed the development of senescence in SSX2-expressing cells. In contrast, knockdown of MED1 did not prevent development of B-Raf- and Epirubicin-induced senescence, suggesting that Mediator may be specifically linked to the cellular functions of SSX2 that may lead to development of senescence or be central in a SSX2-specific senescence response. Indeed, immunostaining of melanoma tumors, which often express SSX proteins, exhibited altered levels of MED1 compared to benign nevi. Similarly, RNA-seq analysis suggested that MED1, MED4, and MED14 were downregulated in some tumors, while upregulated in others. In conclusion, our study reveals the Mediator complex as essential for SSX2-induced senescence and suggests that changes in Mediator activity could be instrumental for tumorigenesis.
   
     
Nadaraja S, Schledermann D, Herrstedt J, Østrup O, Ditzel HJ; Academy of Geriatric Cancer Research (AgeCare).
ARAP1 is an independent prognostic biomarker in older women with ovarian high-grade serous adenocarcinoma receiving first-line platinum-based antineoplastic therapy.
Acta Oncol. 2020 Jan;59(1):40-47. doi: 10.1080/0284186X.2019.1657941. Epub 2019 Sep 3.
Click to view summary
Background: Little is known about the biological factors influencing ovarian cancer (OC) patient outcome, especially in older patients who are often underrepresented in clinical trials. We examined alterations in the transcriptomic profile of primary high-grade serous carcinoma (HGSC) samples from older OC patients (>70 years) receiving first-line platinum-based treatment to identify potential biomarkers for prediction of response to this therapy.
   
     
Ehmsen S, Pedersen MH, Wang G, Terp MG, Arslanagic A, Hood BL, Conrads TP, Leth-Larsen R, Ditzel HJ.
Increased Cholesterol Biosynthesis Is a Key Characteristic of Breast Cancer Stem Cells Influencing Patient Outcome.
Cell Rep. 2019 Jun 25;27(13):3927-3938.e6. doi: 10.1016/j.celrep.2019.05.104.
Click to view summary
Background: Tumor eradication may be greatly improved by targeting cancer stem cells (CSCs), as they exhibit resistance to conventional therapy. To gain insight into the unique biology of CSCs, we developed patient-derived xenograft tumors (PDXs) from ER- breast cancers from which we isolated mammospheres that are enriched for CSCs. Comparative global proteomic analysis was performed on patient tumor tissues and corresponding PDXs and mammospheres. Mammospheres exhibited increased expression of proteins associated with de novo cholesterol synthesis. The clinical relevance of increased cholesterol biosynthesis was verified in a large breast cancer cohort showing correlation with shorter relapse-free survival. RNAi and chemical inhibition of the cholesterol biosynthesis pathway reduced mammosphere formation, which could be rescued by a downstream metabolite. Our findings identify the cholesterol biosynthesis pathway as central for CSC propagation and a potential therapeutic target, as well as providing a mechanistic explanation for the therapeutic benefit of statins in breast cancer.
   
     
Traynor S, Møllegaard NE, Jørgensen MG, Brückmann NH, Pedersen CB, Terp MG, Johansen S, Dejardin J, Ditzel HJ, Gjerstorff MF.
Remodeling and destabilization of chromosome 1 pericentromeric heterochromatin by SSX proteins.
Nucleic Acids Res. 2019 Jul 26;47(13):6668-6684. doi: 10.1093/nar/gkz396.
Click to view summary
Background: Rearrangement of the 1q12 pericentromeric heterochromatin and subsequent amplification of the 1q arm is commonly associated with cancer development and progression and may result from epigenetic deregulation. In many premalignant and malignant cells, loss of 1q12 satellite DNA methylation causes the deposition of polycomb factors and formation of large polycomb aggregates referred to as polycomb bodies. Here, we show that SSX proteins can destabilize 1q12 pericentromeric heterochromatin in melanoma cells when it is present in the context of polycomb bodies. We found that SSX proteins deplete polycomb bodies and promote the unfolding and derepression of 1q12 heterochromatin during replication. This further leads to segregation abnormalities during anaphase and generation of micronuclei. The structural rearrangement of 1q12 pericentromeric heterochromatin triggered by SSX2 is associated with loss of polycomb factors, but is not mediated by diminished polycomb repression. Instead, our studies suggest a direct effect of SSX proteins facilitated though a DNA/chromatin binding, zinc finger-like domain and a KRAB-like domain that may recruit chromatin modifiers or activate satellite transcription. Our results demonstrate a novel mechanism for generation of 1q12-associated genomic instability in cancer cells.
   
     
Alves CL, Elias D, Lyng MB, Bak M, Ditzel HJ
SNAI2 upregulation is associated with an aggressive phenotype in fulvestrant-resistant breast cancer cells and is an indicator of poor response to endocrine therapy in estrogen receptor-positive metastatic breast cancer.
Breast Cancer Res. 2018 Jun 19;20(1):60. doi: 10.1186/s13058-018-0988-9.
Click to view summary
Background: Endocrine resistance in estrogen receptor-positive (ER+) breast cancer is a major clinical problem and is associated with accelerated cancer cell growth, increased motility and acquisition of mesenchymal characteristics. However, the specific molecules and pathways involved in these altered features remain to be detailed, and may be promising therapeutic targets to overcome endocrine resistance.
   
     
Harris JR, Hjelmborg J, Adami HO, Czene K, Mucci L, Kaprio J
The Nordic Twin Study on Cancer - NorTwinCan.
Twin Res Hum Genet. PMID: 31512575 DOI: 10.1017/thg.2019.71
Click to view summary
Background: Nordic twin studies have played a critical role in understanding cancer etiology and elucidating the nature of familial effects on site-specific cancers. The NorTwinCan consortium is a collaborative effort that capitalizes on unique research advantages made possible through the Nordic system of registries. It was constructed by linking the population-based twin registries of Denmark, Finland, Norway and Sweden to their country-specific national cancer and cause-of-death registries. These linkages enable the twins to be followed many decades for cancer incidence and mortality. To date, two major linkages have been conducted: NorTwinCan I in 2011-2012 and NorTwinCan II in 2018. Overall, there are 315,413 eligible twins, 57,236 incident cancer cases and 58 years of follow-up, on average. In the initial phases of our work, NorTwinCan established the world's most comprehensive twin database for studying cancer, developed novel analytical approaches tailored to address specific research considerations within the context of the Nordic data and leveraged these models and data in research publications that provide the most accurate estimates of heritability and familial risk of cancers reported in the literature to date. Our findings indicate an excess familial risk for nearly all cancers and demonstrate that the incidence of cancer among twins mirrors the rate in the general population. They also revealed that twin concordance for cancer most often manifests across, rather than within, cancer sites, and we are currently focusing on the analysis of these cross-cancer associations.
   
     
Dahlrot RH, Larsen P, Boldt HB, Kreutzfeldt MS, Hansen S, Hjelmborg JB, Kristensen BW.
Posttreatment Effect of MGMT Methylation Level on Glioblastoma Survival.
J Neuropathol Exp Neurol. PMID: 31058280 PMCID: PMC6581556 DOI: 10.1093/jnen/nlz032
Click to view summary
Background: The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes temozolomide-induced alkylation, thereby preventing DNA damage and cytotoxicity. We investigated the prognostic effect of different MGMT methylation levels on overall and progression-free survival in 327 patients with primary glioblastoma undergoing standard treatment. We obtained MGMT methylation level in 4 CpG sites using pyrosequencing. The association between MGMT methylation level and survival was investigated using Cox proportional hazards model and an extension to detect time-varying effects. We found an association between MGMT methylation level and overall survival (OS) from around 9 months after the diagnosis, with no association between MGMT methylation level and OS before that. For patients surviving at least 9 months even small increases in MGMT methylation level are significantly beneficial (HR = 0.97, 95% CI [0.96, 0.98]). The predictive ability of MGMT methylation level on OS from 9 months after diagnosis has a Harrel's C of 66%. We conclude that the MGMT methylation level is strongly associated with survival only for patients surviving beyond 9 months with considerable effects for levels much lower than previously reported. Prognostic evaluation of cut-points of MGMT methylation levels and of CpG island site selection should take the time-varying effect on overall survival into account.
   
     
Skytthe A, Harris JR, Czene K, Mucci L, Adami HO, Christensen K, Hjelmborg J, Holm NV, Nilsen TS, Kaprio J, Pukkala E.
Cancer Incidence and Mortality in 260,000 Nordic Twins With 30,000 Prospective Cancers.
Twin Res Hum Genet. 2019, PMID: 31020942 DOI: 10.1017/thg.2019.10
Click to view summary
Background: The Nordic countries have comprehensive, population-based health and medical registries linkable on individually unique personal identity codes, enabling complete long-term follow-up. The aims of this study were to describe the NorTwinCan cohort established in 2010 and assess whether the cancer mortality and incidence rates among Nordic twins are similar to those in the general population. We analyzed approximately 260,000 same-sexed twins in the nationwide twin registers in Denmark, Finland, Norway and Sweden. Cancer incidence was determined using follow-up through the national cancer registries. We estimated standardized incidence (SIR) and mortality (SMR) ratios with 95% confidence intervals (CI) across country, age, period, follow-up time, sex and zygosity. More than 30,000 malignant neoplasms have occurred among the twins through 2010. Mortality rates among twins were slightly lower than in the general population (SMR 0.96; CI 95% [0.95, 0.97]), but this depends on information about zygosity. Twins have slightly lower cancer incidence rates than the general population, with SIRs of 0.97 (95% CI [0.96, 0.99]) in men and 0.96 (95% CI [0.94, 0.97]) in women. Testicular cancer occurs more often among male twins than singletons (SIR 1.15; 95% CI [1.02, 1.30]), while cancers of the kidney (SIR 0.82; 95% CI [0.76, 0.89]), lung (SIR 0.89; 95% CI [0.85, 0.92]) and colon (SIR 0.90; 95% CI [0.87, 0.94]) occur less often in twins than in the background population. Our findings indicate that the risk of cancer among twins is so similar to the general population that cancer risk factors and estimates of heritability derived from the Nordic twin registers are generalizable to the background populations.
   
     
Pedersen JK, Rosholm JU, Ewertz M, Engholm G, Lindahl-Jacobsen R, Christensen K.
Declining cancer incidence at the oldest ages: Hallmark of aging or lower diagnostic activity?
J Geriatr Oncol. 2019. PMID: 30797708 DOI: 10.1016/j.jgo.2019.02.001
Click to view summary
Background: The incidence of most cancers increases with age from early adulthood into old age but tends to level off or decrease at the highest ages. This decline may be caused by age-related mechanisms or due to lower diagnostic activity, leaving some cancers undiagnosed at the oldest ages.
   
     
Hansen JW, Pedersen DA, Larsen LA, Husby S, Clemmensen SB, Hjelmborg J, Favero F, Weischenfeldt J, Christensen K, Grønbæk K
Clonal hematopoiesis in elderly twins: concordance, discordance and mortality.
Blood. 2019. PMID: 31697811 DOI: 10.1182/blood.2019001793
Click to view summary
Background: Clonal hematopoiesis (CH) of indeterminate potential (CHIP) is defined by mutations in myeloid cancer-associated genes with a variant allele frequency of at least 2%. Recent studies have suggested a possible genetic predisposition to CH. To further explore this phenomenon, we conducted a population-based study of 594 twins from 299 pairs aged 73 to 94 years, all with >20 years' follow-up. We sequenced DNA from peripheral blood with a customized 21-gene panel at a median coverage of 6179X. The casewise concordance rates for mutations were calculated to assess genetic predisposition. Mutations were identified in 214 (36%) of the twins. Whereas 20 twin pairs had mutations within the same genes, the exact same mutation was only observed in 2 twin pairs. No significant difference in casewise concordance between monozygotic and dizygotic twins was found for any specific gene, subgroup, or CHIP mutations overall, and no significant heritability could be detected. In pairs discordant for CHIP mutations, we tested if the affected twin died before the unaffected twin, as a direct measurement of the association of having CH when controlling for familial factors. A total of 127 twin pairs were discordant for carrying a mutation, and in 61 (48%) cases, the affected twin died first (P = .72). Overall, we did not find a genetic predisposition to CHIP mutations in this twin study. The previously described negative association of CHIP mutations on survival could not be confirmed in a direct comparison among twin pairs that were discordant for CHIP mutations.
   
     
2018    
     
Nadaraja S, Jørgensen TL, Matzen LE, Herrstedt J
Impact of Age, Comorbidity, and FIGO Stage on Treatment Choice and Mortality in Older Danish Patients with Gynecological Cancer: A Retrospective Register-Based Cohort Study.
Drugs Real World Outcomes. 2018 Dec;5(4):225-235. doi: 10.1007/s40801-018-0145-x.
Click to view summary
Background: The number of older patients with cancer is increasing in general, and ovarian and endometrial cancer are to a large extent cancers of the elderly. Older patients with cancer have a high prevalence of comorbidity. Comorbidity and age may be predictive of treatment choice and mortality in older patients with cancer along with stage and performance status.
Objectives: The aim of this study was to describe comorbidity in a population of older Danish patients with gynecological cancer, and to evaluate the predictive value of comorbidity and age on treatment choice and cancer-specific and all-cause mortality.
   
     
Ahrenfeldt, L. J., Sören Möller, N. C. Hvidt, and R. Lindahl-Jacobsen.
Impact of Age, Comorbidity, and FIGO Stage on Treatment Choice and Mortality in Older Danish Patients with Gynecological Cancer: A Retrospective Register-Based Cohort Study.
Public Health 165 (2018): 74-81. https://doi.org/10.1016/j.puhe.2018.09.009
Click to view summary
OBJECTIVES: Religiousness is associated with longevity and better physical health, which may be due to lifestyle choices. Here, we examine associations between religiousness and health, explained by lifestyle. STUDY DESIGN: This is a longitudinal study. METHODS: Data came from 23,864 people aged 50 and above included in the Survey of Health, Ageing and Retirement in Europe in 2004-2005 and followed up during 11 years.
   
     
van Randwijk, C. B., T. Opsahl, E. A. Hvidt, A. K. Korup, L. Bjerrum, K. F. Thomsen, and N. C. Hvidt.
Characteristics of Religious and Spiritual Beliefs of Danish Physicians: And Likelihood of Addressing Religious and Spiritual Issues with Patients.
J Relig Health (Jul 2 2018). https://doi.org/10.1007/s10943-018-0662-7.
Click to view summary
Background: This study investigated the association between physicians' R/S characteristics and frequency of addressing patients' R/S issues. Information was obtained through a questionnaire mailed to 1485 Danish physicians (response rate 63%) (42% female). We found significant associations between physicians' personal R/S and the frequency of addressing R/S issues. Moreover, we identified significant gender differences in most R/S characteristics. However, no differences in frequency of addressing R/S issues were identified across gender. This raises some questions regarding the effects of gender on associations between R/S characteristics and frequency of addressing R/S issues.
   
     
Hvidt, Niels Christian, Jette Ammentorp, Jane Clemensen, Vibeke Østergaard Steenfeldt, Lene Moestrup, and Jens Søndergaard
Eksistentiel Og Åndelig Omsorg I Danmark: Historie, Forskning Og Implikationer
Klinisk Sygepleje (Accepted) (2018)
Click to view summary
Background:
   
     
Ahrenfeldt, L. J., N. C. Hvidt, S. T. Kjøller, S. Möller, and R. Lindahl-Jacobsen.
Religiousness and Diseases in Europe: Findings from Share
Journal of Religion and Health 2018). https://doi.org/10.1007/s10943-018-0664-5
Click to view summary
Background: Recent research in religiousness and health suggests that epidemiological forces can have opposed effects. Here we examine two forms of religiousness and their association with disease. We performed a cross-sectional study of 23,864 people aged 50+ included in wave 1 (2004-2005) of the Survey of Health, Ageing and Retirement in Europe and a longitudinal study including people from wave 1, who were followed up during 11 years. Results suggested that taking part in a religious organization was associated with lower odds of heart attack (OR 0.74, 95% CI 0.60, 0.90), stroke (OR 0.68, 95% CI 0.50, 0.95), and diabetes (OR 0.72, 95% CI 0.58, 0.90) and longitudinally associated with lower odds of cancer (OR 0.78, 95% CI 0.60, 1.00). Conversely, praying was longitudinally associated with higher odds of heart attack (OR 1.27, 95% CI 1.10, 1.48) and high cholesterol (OR 1.12, 95% CI 1.00, 1.26). The most religious people had lower odds of stroke, diabetes, and cancer than other respondents, and in the longitudinal model, people who only prayed had higher odds of heart attack than non-religious people. Our findings lend support to the hypothesis that restful religiousness (praying, taking part in a religious organization, and being religiously educated) was associated with lower odds of some diseases, whereas little evidence was present that crisis religiousness (praying only) was associated with higher odds of disease.
   
     
Klausen TW, Gregersen H, Abildgaard N, Andersen NF, Frølund UC, Gimsing P, Helleberg C, Vangsted AJ
The majority of newly diagnosed myeloma patients do not fulfill the inclusion criteria in clinical phase III trials. Leukemia.
2018 Sep 28. doi: 10.1038/s41375-018-0272-0. [Epub ahead of print]
Click to view summary
Background:
   
     
Christiansen RL, Hansen CR, Dahlrot RH, Bertelsen AS, Hansen O, Brink C, Bernchou U
Plan quality for high-risk prostate cancer treated with high field magnetic resonance imaging guided radiotherapy
Physics and Imaging in Radiation Oncology 7 (2018) 1–8
Click to view summary
Background:
   
     
Brink C , Lorenzen EL, Krogh SL, Westberg J, Berg M, Jensen I, Thomsen MS, Yates ES and Offersen BV
DBCG hypo trial validation of radiotherapy parameters from a national data bank versus manual reporting
ACTA ONCOLOGICA, 2018, VOL. 57, NO. 1, 107–112, https://doi.org/10.1080/0284186X.2017.1406140
Click to view summary
INTRODUCTION: The current study evaluates the data quality achievable using a national data bank for reporting radiotherapy parameters relative to the classical manual reporting method of selected parameters. METHODS: The data comparison is based on 1522 Danish patients of the DBCG hypo trial with data stored in the Danish national radiotherapy data bank. In line with standard DBCG trial practice selected parameters were also reported manually to the DBCG database. Categorical variables are compared using contingency tables, and comparison of continuous parameters is presented in scatter plots.
   
     
Skytthe A, Harris JR, Czene K, Mucci L, Adami H, Christensen K, Hjelmborg J, Holm NV, Nilsen T, Kaprio J, Pukkala E.
Cancer incidence and mortality in 260,000 Nordic twins with 30,000 prospective cancers.
Submitted to Twin Research and Human Genetics (2018).
Click to view summary
Background: The Nordic countries have comprehensive, population-based health and medical registries linkable on individually unique personal identity codes, enabling complete long-term follow-up. The aims of this study were to describe the NorTwinCan cohort established in 2010 and assess whether the cancer mortality and incidence rates among Nordic twins are similar to those in the general population. We analyzed approximately 260,000 same-sexed twins in the nationwide twin registers in Denmark, Finland, Norway and Sweden. Cancer incidence was determined using follow-up through the national cancer registries. We estimated standardized incidence (SIR) and mortality (SMR) ratios with 95% confidence intervals (CI) across country, age, period, follow-up time, sex and zygosity. More than 30,000 malignant neoplasms have occurred among the twins through 2010. Mortality rates among twins were slightly lower than in the general population (SMR 0.96; CI 95% [0.95, 0.97]), but this depends on information about zygosity. Twins have slightly lower cancer incidence rates than the general population, with SIRs of 0.97 (95% CI [0.96, 0.99]) in men and 0.96 (95% CI [0.94, 0.97]) in women. Testicular cancer occurs more often among male twins than singletons (SIR 1.15; 95% CI [1.02, 1.30]), while cancers of the kidney (SIR 0.82; 95% CI [0.76, 0.89]), lung (SIR 0.89; 95% CI [0.85, 0.92]) and colon (SIR 0.90; 95% CI [0.87, 0.94]) occur less often in twins than in the background population. Our findings indicate that the risk of cancer among twins is so similar to the general population that cancer risk factors and estimates of heritability derived from the Nordic twin registers are generalizable to the background populations.
   
     
Andersen MA, Bjerrum OW, Ranjan A, Skov V, Kruse TA, Thomassen M, Skytthe A, Hasselbalch HC, Christensen K.
Myeloproliferative Neoplasms in Danish Twins.
Acta Haematologica 2018;139(3):195-198.
Click to view summary
OBJECTIVE: Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases characterized by clonal hyperproliferation of immature and mature cells of the myeloid lineage. Genetic differences have been proposed to play a role in the development of MPNs. Monozygotic twin pairs with MPNs have been reported in a few case reports, but the MPN concordance pattern in twins remains unknown. METHOD: All twin pairs born in the period 1900-2010 were identified in the nationwide Danish Twin Registry. Only pairs with both twins alive on January 1, 1977, and those born thereafter were included to allow identification in the Danish National Patient Registry.
   
     
Brueckmann NH, Pedersen CB, Ditzel HJ, Gjerstorff MF
Epigenetic reprogramming of pericentromeric satellite DNA in premalignant and malignant lesions.
Mol. Cancer Res. 16 (3):417-427, 2018 PMID 29330295 (IF 5.6).
Click to view summary
Background: Repression of repetitive DNA is important for maintaining genomic stability, but is often perturbed in cancer. For instance, the megabase satellite domain at chromosome 1q12 is a common site of genetic rearrangements, such as translocations and deletions. Polycomb-group proteins can be observed as large subnuclear domains called polycomb bodies, the composition and cellular function of which has remained elusive. This study demonstrates that polycomb bodies are canonical subunits of the multiprotein polycomb repressive complex 1 deposited on 1q12 pericentromeric satellite DNA, which are normally maintained as constitutive heterochromatin by other mechanisms. Furthermore, the data reveal that polycomb bodies are exclusive to premalignant and malignant cells, being absent in normal cells. For instance, polycomb bodies are present in melanocytic cells of nevi and conserved in primary and metastatic melanomas. Deposition of polycomb on the 1q12 satellite DNA in melanoma development correlated with reduced DNA methylation levels. In agreement with this, inhibition of DNA methyltransferases, with the hypomethylating agent guadecitabine (SGI-110), was sufficient for polycomb body formation on pericentromeric satellites in primary melanocytes. This suggests that polycomb bodies form in cancer cells with global DNA demethylation to control the stability of pericentromeric satellite DNA. These results reveal a novel epigenetic perturbation specific to premalignant and malignant cells that may be used as an early diagnostic marker for detection of precancerous changes and a new therapeutic entry point.Implications: Pericentromeric satellite DNA is epigenetically reprogrammed into polycomb bodies as a premalignant event with implications for transcriptional activity and genomic stability.
   
     
Hansen SV, Traynor S, Ditzel HJ, Gjerstorff MF.
Human DREF/ZBED1 is a nuclear protein widely expressed in multiple cell types derived from all three primary germ layers.
PLoS One. 2018 Oct 10;13(10):e0205461. doi: 10.1371/journal.pone.0205461.
Click to view summary
Background: Drosophila DNA replication-related element binding factor (DREF) is a transcription regulatory factor that binds the promoters of many genes involved in replication and cell proliferation and is required for normal cell cycle progression. Human DREF/zinc finger BED domain-containing protein 1 (ZBED1), an orthologue of Drosophila DREF, also has DNA binding activity, but its cellular functions remain largely uncharacterized. Herein, we show that ZBED1 is a chromatin-associated nuclear protein with a wide expression profile in human tissues from all three primary germ layers. For instance, ZBED1 was expressed in mesodermal-derived epithelial cells of the reproductive system and urinary tract, in endodermal-derived epithelial cells throughout the gastrointestinal tract, and in epidermal epithelium from the ectoderm. ZBED1 was also expressed in connective tissue and smooth muscle cells of multiple organs. To investigate whether ZBED1 is implicated in cell proliferation, similar to Drosophila DREF, we compared the tissue distribution of ZBED1 to that of the proliferation marker Ki-67. ZBED1 and Ki-67 were co-expressed in many epithelial tissues, but ZBED1 expression extended widely beyond that of Ki-67-positive cells. In other tissues, ZBED1 expression was more restricted than Ki-67 expression. These results suggest that ZBED1 is not a cell proliferation-associated factor such as Drosophila DREF, and our study adds to the cumulative understanding of the functions of ZBED1 in human cells and tissues.
   
     
Juul MB, Jensen PH, Engberg H, Wehberg S, Dessau-Arp A, Haziri D, Kristensen HB, Baech J, Schurmann L, Clausen MR, Valentin R, Knudsen LM, Munksgaard L, El-Galaly TC, Frederiksen H, Larsen TS
Treatment strategies and outcomes in diffuse large B-cell lymphoma among 1011 patients aged 75 years or older: A Danish population-based cohort study.
Eur J Cancer. 2018 Aug;99:86-96. doi: 10.1016/j.ejca.2018.05.006. Epub 2018 Jun 20.
Click to view summary
Background: Optimal treatment strategy for the oldest patients with diffuse large B-cell lymphoma (DLBCL) remains controversial, as this group often is precluded from clinical trials, and population-based studies are limited.
   
     
Kodahl AR, Ehmsen S, Pallisgaard N, Jylling AMB, Jensen JD, Laenkholm AV, Knoop AS, Ditzel HJ
Correlation between circulating cell-free PIK3CA tumor DNA levels and treatment response in patients with PIK3CA-mutated metastatic breast cancer.
Mol. Oncol., 12(6):925-935, 2018. PMID 29689598
Click to view summary
Background: Liquid biopsies focusing on the analysis of cell-free circulating tumor DNA (ctDNA) may have important clinical implications for personalized medicine, including early detection of cancer, therapeutic guidance, and monitoring of recurrence. Mutations in the oncogene, PIK3CA, are frequently observed in breast cancer and have been suggested as a predictive biomarker for PI3K-selective inhibitor treatment. In this study, we analyzed the presence of PIK3CA mutations in formalin-fixed, paraffin-embedded, metastatic tissue and corresponding ctDNA from serum of patients with advanced breast cancer using a highly sensitive, optimized droplet digital PCR (ddPCR) assay. We found 83% of patients with PIK3CA mutation in the metastatic tumor tissue also had detectable PIK3CA mutations in serum ctDNA. Patients lacking the PIK3CA mutation in corresponding serum ctDNA all had nonvisceral metastatic disease. Four patients with detectable PIK3CA-mutated ctDNA were followed with an additional serum sample during oncological treatment. In all cases, changes in PIK3CA ctDNA level correlated with treatment response. Our results showed high concordance between detection of PIK3CA mutations in tumor tissue and in corresponding serum ctDNA and suggest that serum samples from patients with advanced breast cancer and ddPCR may be used for PIK3CA mutation status assessment to complement imaging techniques as an early marker of treatment response.
   
     
Hubackova S, Davidova E, Rohlenova K, Stursa J, Werner L, Andera L, Dong L, Terp MG, Hodny Z, Ditzel HJ, Rohlena J, Neuzil J
Selective elimination of senescent cells by mitochondrial targeting is regulated by ANT2.
Cell Death Differ. 2018 May 21. doi: 10.1038/s41418-018-0118-3.
Click to view summary
Background: Cellular senescence is a form of cell cycle arrest that limits the proliferative potential of cells, including tumour cells. However, inability of immune cells to subsequently eliminate senescent cells from the organism may lead to tissue damage, inflammation, enhanced carcinogenesis and development of age-related diseases. We found that the anticancer agent mitochondria-targeted tamoxifen (MitoTam), unlike conventional anticancer agents, kills cancer cells without inducing senescence in vitro and in vivo. Surprisingly, it also selectively eliminates both malignant and non-cancerous senescent cells. In naturally aged mice treated with MitoTam for 4 weeks, we observed a significant decrease of senescence markers in all tested organs compared to non-treated animals. Mechanistically, we found that the susceptibility of senescent cells to MitoTam is linked to a very low expression level of adenine nucleotide translocase-2 (ANT2), inherent to the senescent phenotype. Restoration of ANT2 in senescent cells resulted in resistance to MitoTam, while its downregulation in non-senescent cells promoted their MitoTam-triggered elimination. Our study documents a novel, translationally intriguing role for an anticancer agent targeting mitochondria, that may result in a new strategy for the treatment of age-related diseases and senescence-associated pathologies.
   
     
Bao L, Qian Z, Lyng MB, Wang L, Yu Y, Wang T, Zhang X, Yang H, Brünner N, Wang J, Ditzel HJ
Coexisting genomic aberrations associated with lymph node metastasis in breast cancer.
J Clin Invest. 2018 Jun 1;128(6):2310-2324. doi: 10.1172/JCI97449. Epub 2018 Apr 23.
Click to view summary
Background: Single cancer cell-sequencing studies currently use randomly selected cells, limiting correlations among genomic aberrations, morphology, and spatial localization. We laser-captured microdissected single cells from morphologically distinct areas of primary breast cancer and corresponding lymph node metastasis and performed whole-exome or deep-target sequencing of more than 100 such cells. Two major subclones coexisted in different areas of the primary tumor, and the lymph node metastasis originated from a minor subclone in the invasive front of the primary tumor, with additional copy number changes, including chr8q gain, but no additional point mutations in driver genes. Lack of metastasis-specific driver events led us to assess whether other clonal and subclonal genomic aberrations preexisting in primary tumors contribute to lymph node metastasis. Gene mutations and copy number variations analyzed in 5 breast cancer tissue sample sets revealed that copy number variations in several genomic regions, including areas within chr1p, chr8q, chr9p, chr12q, and chr20q, harboring several metastasis-associated genes, were consistently associated with lymph node metastasis. Moreover, clonal expansion was observed in an area of morphologically normal breast epithelia, likely driven by a driver mutation and a subsequent amplification in chr1q. Our study illuminates the molecular evolution of breast cancer and genomic aberrations contributing to metastases.
   
     
Carla L. Alves , Daniel Elias, Maria B. Lyng, Martin Bak and Henrik J. Ditzel
SNAI2 upregulation is associated with an aggressive phenotype in fulvestrantresistant breast cancer cells and is an indicator of poor response to endocrine therapy in estrogen receptor-positive metastatic breast cancer.
Breast Cancer Res. 2018 Jun 19;20(1):60. doi: 10.1186/s13058-018-0988-9.
Click to view summary
Background: Endocrine resistance in estrogen receptor-positive (ER+) breast cancer is a major clinical problem and is associated with accelerated cancer cell growth, increased motility and acquisition of mesenchymal characteristics. However, the specific molecules and pathways involved in these altered features remain to be detailed, and may be promising therapeutic targets to overcome endocrine resistance.
   
     
Jeppesen SS, Matzen LE, Brink C, Bliucukiene R, Kasch S, Schytte T, Kristiansen C, Hansen O.
Impact of comprehensive geriatric assessment on quality of life, overall survival, and unplanned admission in patients with non-small cell lung cancer treated with stereotactic body radiotherapy.
J Geriatr Oncol. 2018 Jun 3. pii: S1879-4068(18)30073-0. doi: 10.1016/j.jgo.2018.05.009.
Click to view summary
Background: Overall survival (OS) for patients with localized non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) is poorer than for patients undergoing surgery. Patients who undergo SBRT are often ineligible for surgery due to significant comorbidities that can impact their mortality. A comprehensive geriatric assessment (CGA) that identifies and treats aging related comorbidities could improve OS and quality of life (QoL). This randomized study investigated if a CGA added to SBRT impacts QoL, survival, and unplanned admissions.
   
     
2017    
     
Lars Lund.
“Population trends in aging and cancer”
Book chapter: “Geriatric Oncology”
Click to view summary
Background:
   
     
Winther SB, Österlund P, Berglund Å, Glimelius B, Qvortrup C, Sorbye H, Pfeiffer P; - on behalf of the Academy of Geriatric Cancer Research (AgeCare).
Randomized study comparing full dose monotherapy (S-1 followed by irinotecan) and reduced dose combination therapy (S-1/oxaliplatin followed by S-1/irinotecan) as initial therapy for older patients with metastatic colorectal cancer: NORDIC 9
BMC Cancer 2017 17(1):548.
Click to view summary
Background: Metastatic colorectal cancer (mCRC) is a disease of older age, but there is a relative lack of knowledge about effects of chemotherapy in older patients as they are under-represented in clinical trials. Little data can guide whether the strategy in older mCRC patients should be a sequential full-dose monotherapy chemotherapy approach or a dose-reduced combination chemotherapy approach. The oral 5FU prodrug S-1 seems to have less side effects than capecitabine and should be an optimal drug for older patients, but few data are available. Improved geriatric assessments are needed to select which older patients should receive therapy.
   
     
Dieperink KB, Sigaard L, Larsen HM. Mikkelsen TB.
Rehabilitation targeted late adverse effects after radiotherapy for cervical cancer - different gains in different settings.
Clinical Nursing studies. Vol 6 no. 2 e-published 8/12 2017
Click to view summary
Background:
   
     
Jensen KR, Brink C, Hansen O, et al
Ventilation measured on clinical 4D-CBCT: Increased ventilation accuracy through improved image quality.
Radiother Oncol 2017;125:459-463
Click to view summary
Background: Ventilation measured on 4D cone-beam computed tomography (CBCT) using deformable image registration (DIR) may predict specific radiation sensitivity, but the measurement is affected by the current image quality. With 4D computed tomography (CT) measured ventilation acting as a gold standard the current study investigates if image improvements increase the accuracy of 4D-CBCT measured ventilation.
   
     
Holm, E, Henriksen L, Christensen K.
Aldringsteorier
Sygepleje til Ældre. Jastrup S & Holm E (eds.), Munksgaard, Copenhagen, Vol 1, 1st edition, 2017: 43-52.
Click to view summary
Background:
   
     
Pedersen JK, Elo IT,Schupf N, Perls TT, Stallard E, Yashin Al, Christensen K.
The Survival of Spouses Marrying Into Longevity-Enriched Families.
Journals of Gerontology. Series A, Biological Sciences Medical Sciences 2017;72(1):109-114.
Click to view summary
Background: Studies of longevity-enriched families are an important tool to gain insight into the mechanisms of exceptionally long and healthy lives. In the Long Life Family Study, the spouses of the members of the longevity-enriched families are often used as a control group. These spouses could be expected to have better health than the background population due to shared family environment with the longevity-enriched family members and due to assortative mating.
   
     
Christensen A G, Ehmsen S, Terp M G, Terp M G, Batra R, Alcaraz N, Baumbach J, Noer J B, Moreira J, Leth-Larsen R, Larsen MR, Ditzel HJ*
Elucidation of Altered Pathways in Tumor-Initiating Cells of Triple-Negative Breast Cancer: A Useful Cell Model System for Drug Screening
Stem Cells, 35(8):1898-1912, 2017 (IF 5.9).
Click to view summary
A limited number of cancer cells within a tumor are thought to have self-renewing and tumor-initiating capabilities that produce the remaining cancer cells in a heterogeneous tumor mass. Elucidation of central pathways preferentially used by tumor-initiating cells/cancer stem cells (CSCs) may allow their exploitation as potential cancer therapy targets. We used single cell cloning to isolate and characterize four isogenic cell clones from a triple-negative breast cancer cell line; two exhibited mesenchymal-like and two epithelial-like characteristics. Within these pairs, one, but not the other, resulted in tumors in immunodeficient NOD/Shi-scid/IL-2 Rγ null mice and efficiently formed mammospheres. Quantitative proteomics and phosphoproteomics were used to map signaling pathways associated with the tumor-initiating ability. Signaling associated with apoptosis was suppressed in tumor-initiating versus nontumorigenic counterparts with pro-apoptotic proteins, such as Bcl2-associated agonist of cell death (BAD), FAS-associated death domain protein (FADD), and myeloid differentiation primary response protein (MYD88), downregulated in tumor-initiating epithelial-like cells. Functional studies confirmed significantly lower apoptosis in tumor-initiating versus nontumorigenic cells. Moreover, central pathways, including β-catenin and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related signaling, exhibited increased activation in the tumor-initiating cells. To evaluate the CSC model as a tool for drug screening, we assessed the effect of separately blocking NF-κB and Wnt/β-catenin signaling and found markedly reduced mammosphere formation, particularly for tumor-initiating cells. Similar reduction was also observed using patient-derived primary cancer cells. Furthermore, blocking NF-κB signaling in mice transplanted with tumor-initiating cells significantly reduced tumor outgrowth. Our study demonstrates that suppressed apoptosis, activation of pathways associated with cell viability, and CSCs are the major differences between tumor-initiating and nontumorigenic cells independent of their epithelial-like/mesenchymal-like phenotype. These altered pathways may provide targets for future drug development to eliminate CSCs, and the cell model may be a useful tool in such drug screenings.
   
     
Jacobsen K, J Bertran-Alamillo, MA Molina, C Teixidó, N Karachaliou, MH Pedersen, J Castellví, M Garzón, C Codony-Servat, J Codony-Servat, A Giménez-Capitán, A Drozdowskyj, S Viteri, MR Larsen, U Lassen, E Felip, TG Bivona*, HJ Ditzel*, R Rosell.
Convergent Akt activation drives acquired EGFR inhibitor resistance in lung cancer
Nature Communications, 8(1):410, 2017 (IF 11.5).
Click to view summary
Non-small-cell lung cancer patients with activating epidermal growth factor receptor (EGFR) mutations typically benefit from EGFR tyrosine kinase inhibitor treatment. However, virtually all patients succumb to acquired EGFR tyrosine kinase inhibitor resistance that occurs via diverse mechanisms. The diversity and unpredictability of EGFR tyrosine kinase inhibitor resistance mechanisms presents a challenge for developing new treatments to overcome EGFR tyrosine kinase inhibitor resistance. Here, we show that Akt activation is a convergent feature of acquired EGFR tyrosine kinase inhibitor resistance, across a spectrum of diverse, established upstream resistance mechanisms. Combined treatment with an EGFR tyrosine kinase inhibitor and Akt inhibitor causes apoptosis and synergistic growth inhibition in multiple EGFR tyrosine kinase inhibitor-resistant non-small-cell lung cancer models. Moreover, phospho-Akt levels are increased in most clinical specimens obtained from EGFR-mutant non-small-cell lung cancer patients with acquired EGFR tyrosine kinase inhibitor resistance. Our findings provide a rationale for clinical trials testing Akt and EGFR inhibitor co-treatment in patients with elevated phospho-Akt levels to therapeutically combat the heterogeneity of EGFR tyrosine kinase inhibitor resistance mechanisms.EGFR-mutant non-small cell lung cancer are often resistant to EGFR tyrosine kinase inhibitor treatment. In this study, the authors show that resistant tumors display high Akt activation and that a combined treatment with AKT inhibitors causes synergistic tumour growth inhibition in vitro and in vivo.
   
     
Weisel K, Doyen C, Dimopoulos M, Yee A, Lahuerta JJ, Martin A, Travers K, Abildgaard N; et al
A systematic literature review and network meta-analysis of treatments for patients with untreated multiple myeloma not eligible for stem cell transplantation.
Leukemia and Lymphoma, Bind 58, Nr. 1, 01.2017, s. 153-161
Click to view summary
In newly diagnosed multiple myeloma (MM), patients ineligible for front-line autologous stem cell transplantation (ASCT), melphalan and prednisone (MP) with thalidomide (MPT) or bortezomib (VMP) are standard first-line therapeutic options. Despite new treatment regimens incorporating bortezomib or lenalidomide, MM remains incurable. The FIRST study demonstrated significant improvement in progression-free survival (PFS) and overall survival (OS) for the combination of lenalidomide and low-dose dexamethasone (Rd) until progression vs. MPT in transplant-ineligible ndMM patients. However, to date no head-to-head randomized controlled trials (RCTs) have compared Rd or MPT versus VMP. We conducted a network meta-analysis using RCTs identified through a systematic literature review to evaluate the relative efficacy of Rd versus other regimens on survival endpoints in previously untreated MM patients ineligible for ASCT. In this analysis, Rd was associated with a significant PFS and survival advantage versus other first-line treatments (VMP, MPT, MP), challenging the role of alkylators in this setting.
   
     
Gregersen H, Vangsted AJ, Abildgaard N, Andersen NF, Pedersen RS, Frølund UC, Helleberg C, Broch B, Pedersen PT, Gimsing P, Klausen TW.
The impact of comorbidity on mortality in multiple myeloma: a Danish nationwide population-based study.
Cancer Med. 2017 Jul;6(7):1807-1816
Click to view summary
To describe the prevalence of comorbidity and its impact on survival in newly diagnosed multiple myeloma patients compared with population controls. Cases of newly diagnosed symptomatic multiple myeloma during the 2005-2012 period were identified in the Danish National Multiple Myeloma Registry. For each myeloma patient, 10 members of the general population matched by age and sex were chosen from the national Civil Registration System. Data on comorbidity in the myeloma patients and the general population comparison cohort were collected by linkage to the Danish National Patient Registry (DNPR). Cox proportional hazards regression models were used to evaluate the prognostic significance of comorbidity. The study included 2190 cases of multiple myeloma and 21,900 population controls. The comorbidity was increased in multiple myeloma patients compared with population controls, odds ratio (OR) 1.4 (1.1-1.7). The registration of comorbidity was highly increased within the year preceding diagnosis of multiple myeloma (OR 3.0 [2.5-3.5]), which was attributable to an increased registration of various diseases, in particular, renal disease with OR 11.0 (8.1-14.9). The median follow-up time from diagnosis of multiple myeloma for patients alive was 4.3 years (interquartile range 2.4-6.3). Patients with registered comorbidity had increased mortality compared with patients without comorbidity, hazard ratio 1.6 (1.5-1.8). Multiple myeloma patients have increased comorbidity compared with the background population, in particular during the year preceding the diagnosis of myeloma.
   
     
Nielssen LK, Jarden M, Andersen CL, Frederiksen H, Abildgaard N.
A systematic review of health-related quality of life in longitudinal studies of myeloma patients.
Eur J Haematol. 2017 Jul;99(1):3-17.
Click to view summary
OBJECTIVES: Multiple myeloma (MM) patients report high symptom burden and reduced health-related quality of life (HRQoL) compared to patients with other haematological malignancies. The aim of this review was to analyse published longitudinal studies including MM patients according to a change in HRQoL scores, which is perceived as beneficial to the patient according to two published guidelines.
METHODS: A literature search was performed May 2016. Publications with longitudinal follow-up using the EORTC QLQ-C30 instrument for HRQoL measurement of physical functioning, global quality of life, fatigue and/or pain were included. An analysis of mean change from baseline was carried out according to minimal important difference (MID).
RESULTS: Large and medium HRQoL improvements were reported during first-line treatments. No clinically beneficial change or deteriorations in scores of global QoL or fatigue were reported during relapse treatment. HRQoL data during maintenance therapy are sparse and inconclusive.
CONCLUSIONS: Guidelines for interpreting changes in HRQoL including definitions of MID have been developed; however, consensus is missing. Improvements in HRQoL are far more likely to occur during first-line compared to relapsed treatment regimens. The background of these findings should be in focus in future studies, and HRQoL measurements should be integrated in maintenance studies.
   
     
Christian Rønn Hansen , Morten Nielsen, Anders Smedegaard Bertelsen, Irene Hazell, Eva Holtved, Ruta Zukauskaite , Jon Kroll Bjerregaard , Carsten Brink & Uffe Bernchou
Automatic treatment planning facilitates fast generation of high-quality treatment plans for esophageal cancer
Acta Oncologica 2017; doi:10.1080/0284186X
Click to view summary
Background: The quality of radiotherapy planning has improved substantially in the last decade with the introduction of intensity modulated radiotherapy. The purpose of this study was to analyze the plan quality and efficacy of automatically (AU) generated VMAT plans for inoperable esophageal cancer patients.
   
     
Olfred Hansen, Marianne M. Knap, Azza Khalil, Christa H. Nyhus, Tine McCulloch, Bente Holm, Carsten Brink, Lone Hoffmann, Tine Schytte
A randomized phase II trial of concurrent chemoradiation with two doses of radiotherapy, 60 Gy and 66 Gy, concomitant with a fixed dose of oral vinorelbine in locally advanced NSCLC
Radiotherapy and Oncology 123 (2017) 276–281
Click to view summary
Background: In order to test the best performing radiation dose with a convenient chemotherapy schedule of an oral formulation of radio-sensitizing vinorelbine in inoperable locally advanced non-small cell lung cancer (NSCLC), we performed a randomized phase II trial based on a "pick the winner" design.
   
     
Uffe Bernchou, Rasmus Lübeck Christiansenb, Jon Thor Asmussen, Tine Schytte, Olfred Hansen, Carsten Brink
Extent and computed tomography appearance of early radiation induced lung injury for non-small cell lung cancer
Radiotherapy and Oncology 123 (2017) 93–98
Click to view summary
Background: The present study investigates the extent and appearance of radiologic injury in the lung after radiotherapy for non-small cell lung cancer (NSCLC) patients and correlates radiologic response with clinical and dosimetric factors.
   
     
Rune Slot Thing, Uffe Bernchou, Olfred Hansen, Carsten Brink
Accuracy of dose calculation based on artefact corrected Cone Beam CT images of lung cancer patients.
Physics and Imaging in Radiation Oncology 1 (2017) 6–11
Click to view summary
Background:
   
     
S. S. Jeppesen, N. C. G. Hansen, T. Schytte & O. Hansen
Survival of localized NSCLC patients without active treatment or treated with SBRT
Acta Oncologica 2017;1;doi: .10.1080
Click to view summary
Background: Little information on the natural history of patients with localized NSCLC is available since many of the studies covering the subject lack information on pathological confirmation, staging procedures and comorbidity. No randomized studies have compared SBRT with no treatment for patients with localized NSCLC. The purpose of this study was to evaluate whether SBRT has influence on overall survival for patients with localized NSCLC and investigate the effect of baseline ventilatory lung function on overall survival.
   
     
Karin B. Dieperink MCN, PhD, RN, Postdoc, Elisabeth Coyne PhD, MN, RN, Senior Lecturer, Debra K. Creedy PhD, RN, Professor, Birte Østergaard MSc, PhD, RN,Associate Professor.
Family functioning and perceived support from nurses during cancer treatment among Danish and Australian patients and their families
Wiley Journal of Clinical Nursing; doi: 10.1111/jocn.13894
Click to view summary
Background: Family plays an essential role in supporting the patient with cancer, however, relatively little attention has been given to understanding the strengths and resources of the family unit across different settings and countries. This study aims to investigate the strengths and resources of patients and family members in Australia and Denmark.
   
     
E. Coyne, RN MN Hons PhD Senior Lecturera, K.B. Dieperink, RN, MCN, PhD, Postdoc,B. Østergaard, RN, MSc, PhD Associate Professor, D.K. Creedy, RN PhD. Professor of Perinatal Mental Health
Strengths and resources used by Australian and Danish adult patients and their family caregivers during treatment for cancer
European Journal of Oncology Nursing 29 (2017) 53e59
Click to view summary
Background: Family can have a strong influence on the health of individuals, providing support during a health crisis such as cancer. However, family functioning and supportive care from nurses may vary across cultures and settings.
   
     
K. Agergaard, M. Mau-Sørensen, T.B. Stage, T.L. Jørgensen, R.E. Hassel, K.D. Steffensen, J.W.Pedersen, M.L.H. Milo, S.H. Poulsen, A. Pottegård, J. Hallas, K. Brøsen, T.K. Bergmann
Clopidogrel paclitaxel drug-drug interaction: a pharmacoepidemiologic study
Clin Pharmacol Ther 2017: doi: 10.1002/cpt.674.
Click to view summary
Background: Our study indicates that clopidogrel is associated with a clinically relevant increased risk of neuropathy in patients treated with high dose paclitaxel.
   
     
Alex Kappel Kørup, René dePont Christensen, Connie Thurøe Nielsen, Jens Søndergaard , Nada A Alyousefi, Giancarlo Lucchetti, Klaus Baumann, Eunmi Lee, Azimatul Karimah, Parameshwaran Ramakrishnan, Eckhard Frick, Arndt Büssing, Esther Schouten and Niels Christian Hvidt
The International NERSH Data Pool — A Methodological Description of a Data Pool of Religious and Spiritual Values of Health Professionals from Six Continents
Religions 2017;8:24; doi:10.3390/rel8020024.
Click to view summary
Background: Collaboration within the recently established Network for Research on Spirituality and Health (NERSH) has made it possible to pool data from 14 different surveys from six continents. All surveys are largely based on the questionnaire by Curlin “Religion and Spirituality in Medicine, Perspectives of Physicians” (RSMPP). This article is a methodological description of the process of building the International NERSH Data Pool. The larger contours of the data are described using frequency statistics. 5 subscales in the data pool (including the already established DUREL scale) were tested using Cronbach’s alpha and Principal Component Analysis (PCA) in an Exploratory Factor Analysis (EFA). 5724 individuals were included, of which 57% were female and the mean age was 41.5 years with a 95% confidence interval (CI) ranging from 41.2 to 41.8. Most respondents were physicians (n = 3883), nurses (n = 1189), and midwives (n = 286); but also psychologists (n = 50), therapists (n = 44), chaplains (n = 5), and students (n = 10) were included. The DUREL scale was assessed with Cronbach’s alpha (α = 0.92) and PCA confirmed its reliability and unidimensionality. The new scales covering the dimensions of “Religiosity of Health Professionals (HPs)” (α = 0.89), “Willingness of Physicians to Interact with Patients Regarding R/S Issues” (α = 0.79), “Religious Objections to Controversial Issues in Medicine” (α = 0.78), and “R/S as a Calling” (α = 0.82), also proved unidimensional in the PCAs. We argue that the proposed scales are relevant and reliable measures of religious dimensions within the data pool. Finally, we outline future studies already planned based on the data pool, and invite interested researchers to join the NERSH collaboration.
   
     
Jacob K. Pedersen, Irma T. Elo, Nicole Schupf, Thomas T. Perls, Eric Stallard, Anatoliy I. Yashin, and Kaare Christensen.
The Survival of Spouses Marrying Into Longevity-Enriched Families.
Journals of Gerontology: Medical Sciences cite as: J Gerontol A Biol Sci Med Sci, 2017
Click to view summary
Background: Studies of longevity-enriched families are an important tool to gain insight into the mechanisms of exceptionally long and healthy lives. In the Long Life Family Study, the spouses of the members of the longevity-enriched families are often used as a control group. These spouses could be expected to have better health than the background population due to shared family environment with the longevityenriched family members and due to assortative mating.
   
     
Graff RE, Möller S, Passarelli MN, Witte JS, Skytthe A, Christensen K, Tan Q, Adami H-O, Czene K, Harris JR, Pukkala E, Kaprio J, Giovannucci E, Mucci LA, Hjelmborg JB.
Familial Risk and Heritability of Colorectal Cancer in the Nordic Twin Study of Cancer.
Clinical Gastroenterology and Hepatology 2017
Click to view summary
Background: We analyzed data from twins to determine how much the familial risk of colorectal cancer can be attributed to genetic factors vs environment. We also examined whether heritability is distinct for colon vs rectal cancer, given evidence of distinct etiologies.
   
     
Tina Broby Mikkelsen, Bente Sørensen, Karin B. Dieperink.
Prediction of rehabilitation needs after treatment of cervical cancer: what do late adverse effects tell us?
Support Care Cancer (2017) 25:823–831.
Click to view summary
Background:
   
     
Karin B. Dieperink, Christoffer Johansen, Steinbjørn Hansen, Lis Wagner, Klaus K. Andersen, Lisbeth R. Minet & Olfred Hansen.
Male coping through a long-term cancer trajectory. Secondary outcomes from a RTC examining the effect of a multidisciplinary rehabilitation program (RePCa) among radiated men with prostate cancer.
Acta Oncologica 2017. DOI: 10.1080/0284186X.2016.1267395.
Click to view summary
Background: The objective of this study was to examine if rehabilitation influenced self-reported male coping styles during and up to three years after treatment with radiotherapy for prostate cancer.
   
     
2016    
     
Winther SB, Jorgensen T, Pfeiffer P, Qvortrup C - on behalf of the Academy of Geriatric Cancer Research (AgeCare)
Can we predict toxicity and efficacy in older cancer patients? - Older colorectal cancer patients as an example.
ESMO Open 2016;1(3).
Click to view summary
Background: Colorectal cancer is a disease of the elderly. As older and frail patients are under-represented in clinical trials, most of the evidence available on treatment of older metastatic colorectal patients with cancer originates from pooled analyses of the older patients included in large prospective clinical trials and from community-based studies. The aging process is highly individual and cannot be based on the chronological age alone. It is characterised by a decline in organ function with an increased risk of comorbidity and polypharmacy. These issues can result in an increased susceptibility to the complications of both the disease and treatment. Therefore, evaluation of performance status and the chronological age alone is not sufficient, and additionally assessment must be included in the treatment decision process. In the present review, we will focus on clinical aspects of treating older and frail metastatic colorectal patients with cancer, but also on the present knowledge on how to select and tailor therapy for this particular group of patients.
   
     
Thing RS, Bernchou U, Mainegra-Hing E, Hansen O, Brink C.
Hounsfield unit recovery in clinical cone beam CT images of the thorax acquired for image guided radiation therapy.
Phys Med Biol 2016;61:5781-5802.
Click to view summary
Background: This study shows the first clinical results on how sophisticated body scatter corrections do not suffice in realising the best image quality. To realise the best HU correspondence, all the proposed corrections must be applied in conjunction. No patient specific optimisation of the artefact corrections was applied, and the artefact correction methods work as retrospective processing of the clinical projection data already available. With the improved CBCT image quality, CBCT images might have the potential to be used for dose calculation and accumulation, plan adaptation, and biomarker extraction in the same way as CT images.
   
     
Hazell I, Bzdusek K, Kumar P, Hansen CR, Bertelsen A, Eriksen JG, Johansen J, Brink C.
Automatic planning of head and neck treatment plans.
J Appl Clin Med Phys 2016;17:272-282.
Click to view summary
Background: Comparison of autoplans and previous delivered clinical plans showed only small dosimetric differences in target coverage, but significant reduction in dose to OAR for the autoplans. The blinded clinical evaluation of the plans showed that, for 94% of the evaluations, the autoplans were similar to or better than the clinical plans. Auto-Planning software will be able to reduce the manual time spend per treatment plan since the most of the plans could potentially be used clinically without further optimization. Perhaps more importantly, Auto-Planning could be used as a high quality starting point for further plan optimization. This could increase the overall quality of the treatments and reduce the interobserver variation present in manually created treatment plans.
   
     
Maria B. Lyng, Annette R. Kodahl, Harald Binder, Henrik J. Ditzel.
Prospective validation of a blood-based 9-miRNA profile for early detection of breast cancer in a cohort of women examined by clinical mammography.
Molecular Oncology 2016;10:1621-1626
Click to view summary
Background: Mammography is the predominant screening method for early detection of breast cancer, but has limitations and could be rendered more accurate by combination with a bloodbased biomarker profile.
   
     
Michail Ignatiadis, Hatem A. Azim Jr, Christine Desmedt, Isabelle Veys, Denis Larsimont, Roberto Salgado, Maria B. Lyng, Giuseppe Viale, Brian Leyland-Jones, Anita Giobbie-Hurder, Rosita Kammler, Patrizia Dell’Orto, Françoise Rothé, Ioanna Laïos, Henrik J. Ditzel, MD, Meredith M. Regan, Martine Piccart, Stefan Michiels, Christos Sotiriou.
The Genomic Grade Assay Compared With Ki67 to Determine Risk of Distant Breast Cancer Recurrence.
JAMA Oncology 2016;2:217-224.
Click to view summary
Background: Either the GG assay or centrally reviewed Ki67 significantly improves clinicopathological models to determine distant recurrence of breast cancer. Compared with the histological grade, the GG assay can identify a higher proportion of endocrine-only treated patients with very low risk of distant recurrence at 10 years.
   
     
Carla L. Alves, Daniel Elias, Maria Lyng, Martin Bak, Tove Kirkegaard, Anne E. Lykkesfeldt, and Henrik J. Ditzel.
High CDK6 Protects Cells from Fulvestrant-Mediated Apoptosis and is a Predictor of Resistance to Fulvestrant in Estrogen Receptor–Positive Metastatic Breast Cancer.
Clin Cancer Res 2016;22:5514-5526.
Click to view summary
Background: Resistance to endocrine therapy in estrogen receptor–positive (ERþ) breast cancer remains a major clinical problem. Recently, the CDK4/6 inhibitor palbociclib combined with letrozole or fulvestrant was approved for treatment of ERþ advanced breast cancer. However, the role of CDK4/6 in endocrine resistance and their potential as predictive biomarkers of endocrine treatment response remains undefined.
   
     
Stefan S. Jeppesen, Niels-Chr. G. Hansen, Tine Schytte, Morten Nielsen, Olfred hansen & on behalf of the Academy of Geriatric Cancer Research (AgeCare)
Comparison of survival of Chronic obstructive pulmonary disease patients with or without a localized non-small lung cancer
Lung Cancer 2016;100:90-95
Click to view summary
Background: Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are often co-existing diseases with poor prognosis. The main reasons for inoperability in patients with localized NSCLC are advanced age, poor performance status, and comorbidity. The aim of this study was to compare survival in COPD patients with localized NSCLC treated with stereotactic body radiotherapy with COPD patients without a malignant diagnosis.
   
     
Stine Braendegaard Winther, Kanita Zubcevic, Camilla Qvortrup, Lene Weber Vestermark, Helle Anita Jensen, Merete Krogh, Halfdan Sorbye, Per Pfeiffer & on behalf of the Academy of Geriatric Cancer Research (AgeCare)
Experience with S-1 in older Caucasian patientswith metastatic colorectal cancer (mCRC): Findings from an observational chart review.
Acta Oncologica 2016;55:881–885
Click to view summary
Background: The oral fluoropyrimidine S-1 is associated with a lower rate ofadverse events than capecitabine and may therefore be a suitable drug for elderly. However, data on the use of S-1 in Caucasian mCRC patients are lacking/scarce. The study evaluated safety and the efficacy of S-1 alone or in combination with oxaliplatin (SOx) or irinotecan (IRIS) in older mCRC patients. S-1monotherapy, SOx and IRIS were well tolerated for older patients with mCRC and could become alternative regimens in older mCRC patients.
   
     
Stine Braendegaard Winther, Trine Lembrecht Jørgensen, Per Pfeiffer, Camilla Qvortrup, on behalf of the Academy of Geriatric Cancer Research (AgeCare)
Can we predict toxicity and efficacy in older patients with cancer? Older patients with colorectal cancer as an example.
ESMO Open 2016;1:e000021. doi:10.1136/esmoopen-2015-000021
Click to view summary
As older and frail patients are under-represented in clinical trials, most of the evidence available on treatment of older metastatic colorectal patients with cancer originates from pooled analyses of the older patients included in large prospective clinical trials and from community-based studies. The aging process is highly individual and cannot be based on the chronological age alone. It is characterised by a decline in organ function with an increased risk of comorbidity and polypharmacy. These issues can result in an increased susceptibility to the complications of both the disease and treatment. Therefore, evaluation of performance status and the chronological age alone is not sufficient, and additionally assessment must be included in the treatment decision process. In the present review, we will focus on clinical aspects of treating older and frail metastatic colorectal patients with cancer, but also on the present knowledge on how to select and tailor therapy for this particular group of patients.
   
     
Lise Hoejberg, Dorte Gad, Niels Gyldenkerne, Lars Bastholt & On behalf of the Academy of Geriatric Cancer Research (AgeCare)
Trends in melanoma in the elderly in Denmark, 1980–2012
Acta Oncologica 2016;55(suppl 1):52-58.
Click to view summary
Background: The incidence of melanoma is rising in Denmark. In the present paper we describe incidence, mortality and survival in Denmark from 1980 to 2012 focusing on age, comparing persons aged 70 years or more with those aged less than 70 years.
   
     
Marianne Ewertz, Kaare Christensen, Gerda Engholm, Anne Mette T. Kejs, Lars Lund, Lars E. Matzen, Per Pfeiffer, Hans H. Storm, Jørn Herrstedt & On behalf of the Academy of Geriatric Cancer Research (AgeCare)
Trends in cancer in the elderly population in Denmark, 1980–2012
Acta Oncologica 2016;55(suppl 1):1-6.
Click to view summary
Background: Age is the strongest risk factor for developing cancer. The aim of the present analysis is to give an overview of the trends in cancer incidence, mortality, prevalence, and relative survival in Denmark from 1980 to 2012 focusing on age, comparing persons aged 70 years or more with those aged less than 70 years.
   
     
Jeanette D. Jensen, Søren Cold, Mette H. Nielsen, Anne Marie B. Jylling, Katrine L. Søe, Lisbet B. Larsen, Marianne Ewertz & On behalf of the Academy of Geriatric Cancer Research (AgeCare)
Trends in breast cancer in the elderly in Denmark, 1980–2012
Acta Oncologica 2016;55(suppl 1):59-64.
Click to view summary
Background: Breast cancer is the most frequent malignancy among women worldwide and the second most common cause of cancer-related death in developed countries. The aim of the present analysis is to describe trends in incidence, mortality, prevalence, and relative survival in Denmark from 1980 to 2012 focusing on age, comparing persons aged 70 years or more with those aged less than 70 years.
   
     
Anja Ør Knudsen, Doris Schledermann, Gitte-Bettina Nyvang, Ole Mogensen, Jørn Herrstedt & On behalf of the Academy of Geriatric Cancer Research (AgeCare)
Trends in gynecologic cancer among elderly women in Denmark, 1980–2012
Acta Oncologica 2016;55(suppl 1):65-73.
Click to view summary
Background: The aim of this analysis was to describe trends in incidence, mortality, prevalence, and survival in Danish women with gynecologic cancer from 1980–2012 comparing women aged 70 years or more with younger women.
   
     
Mads Hvid Poulsen, Lars Dysager, Oke Gerke, Lars Lund & On behalf of the Academy of Geriatric Cancer Research (AgeCare)
Trends in prostate cancer in elderly in Denmark, 1980–2012
Acta Oncologica 2016;55(suppl 1):74-78.
Click to view summary
Backgound The purpose of the study is to elucidate the epidemiology of elderly patients with prostate cancer in Denmark and identify the differences between younger (57 years) and elderly (≥70 years) patients.
   
     
Nessn H. Azawi, Simon Moeller Joergensen, Niels Viggo Jensen, Peter E. Clark, Lars Lund & On behalf of the Academy of Geriatric Cancer Research (AgeCare)
Trends in kidney cancer among the elderly in Denmark, 1980–2012
Acta Oncologica 2016;55(suppl 1):79-84.
Click to view summary
Background: The purpose of this study is to elucidate incidence, mortality, survival, and prevalence of kidney cancer in elderly persons compared with younger persons in Denmark.
   
     
Thor Knak Jensen, Niels Viggo Jensen, Simon Møller Jørgensen, Peter Clark, Lars Lund & On behalf of the Academy of Geriatric Cancer Research (AgeCare)
Trends in cancer of the urinary bladder and urinary tract in elderly in Denmark, 2008–2012
Acta Oncologica 2016;55(suppl 1):85-90.
Click to view summary
Background: The aim of this study was to examine the trends in incidence, mortality, survival, and prevalence of cancers of the urinary bladder and urinary tract in Denmark from 1980 to 2012 with particular focus on elderly patients over age 70 years.
   
     
Rikke H. Dahlrot, Frantz R. Poulsen, Nina N.T.T. Nguyen, Bjarne W. Kristensen, Steinbjørn Hansen, Niels V. Holm & On behalf of the Academy of Geriatric Cancer Research (AgeCare)
Trends in tumors in the central nervous system in elderly in Denmark, 2008–2012
Acta Oncologica 2016;55(suppl 1):91-97.
Click to view summary
Background: Tumors in the central nervous system (CNS) comprise a heterogeneous group of tumors with different treatment strategies and prognoses. Current treatment regimens are based on studies on patients mainly younger than 70 years. The aim of the present study was to analyze and describe trends in incidence, mortality, prevalence, and relative survival in Denmark from 1980 to 2012 focusing on patients older than 70 years.
   
     
Lukas F. Ocias, Thomas S. Larsen, Hanne Vestergaard, Lone S. Friis, Niels Abildgaard, Henrik Frederiksen & On behalf of the Academy of Geriatric Cancer Research (AgeCare)
Trends in hematological cancer in the elderly in Denmark, 1980–2012
Acta Oncologica 2016;55(suppl 1):98-107.
Click to view summary
Background: The number of hematological malignancies is expected to increase as the Danish population ages within the next few decades. Despite this, data on the course of hematological cancers among the oldest patients are sparse with many intervention studies focusing on younger age groups. The aim of this study is to present Danish incidence and mortality rates among older patients with non-Hodgkin lymphomas (NHL), multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and acute myeloid leukemia (AML).
   
     
Jon Kroll Bjerregaard, Michael Bau Mortensen, Per Pfeiffer & On behalf of the Academy of Geriatric Cancer Research (AgeCare)
Trends in cancer of the liver, gall bladder, bile duct, and pancreas in elderly in Denmark, 1980–2012
Acta Oncologica 2016;55(suppl 1):40-45.
Click to view summary
Background: Cancers of the liver, bile duct, gall bladder and pancreas (HPB-c) are a heterogeneous group, united almost exclusively by a poor prognosis. As the number of elderly in the Western world continues to rise and HPB-c are associated with age, we wanted to examine changes in incidence, mortality, prevalence and relative survival for these cancers.
   
     
Charlotte Kristiansen, Tine Schytte, Karin Holmskov Hansen, Eva Holtved, Olfred Hansen & On behalf of the Academy of Geriatric Cancer Research (AgeCare)
Trends in lung cancer in elderly in Denmark, 1980–2012
Acta Oncologica 2016;55(suppl 1):46-51.
Click to view summary
Background: Lung cancer is an increasing problem in the older patient population due to the improvement in life expectation of the Western population. In this study we examine trends in lung cancer incidence and mortality in Denmark from 1980 to 2012 with special focus on the elderly.
   
     
Katrine R. Schønnemann, Michael B. Mortensen, Merete Krogh, Eva Holtved, Mette Maia S. Andersen, Per Pfeiffer & On behalf of the Academy of Geriatric Cancer Research (AgeCare)
Trends in upper gastro-intestinal cancer among the elderly in Denmark, 1980–2012
Acta Oncologica 2016;55(suppl 1):23-28.
Click to view summary
Background: Upper gastro-intestinal cancer (UGIC) includes malignancies in esophagus, stomach and small intestine, and represents some of the most frequent malignancies worldwide. The aim of the present analysis was to describe incidence, mortality and survival in UGIC patients in Denmark from 1980 to 2012 according to differences in age and time periods.
   
     
Stine Brændegaard Winther, Gunnar Baatrup, Per Pfeiffer, Camilla Qvortrup & On behalf of the Academy of Geriatric Cancer Research (AgeCare)
Trends in colorectal cancer in the elderly in Denmark, 1980–2012
Acta Oncologica 2016;55(suppl 1):29-39.
Click to view summary
Background: Colorectal cancer (CRC) is a disease of the older population. The current demographic ageing leads to more elderly patients and is expected to further increase the number of patients with CRC. The objective of the present paper is to outline incidence, mortality and prevalence from 1980 to 2012 and survival data from 1968 to 2012 in Danish CRC patients focusing on the impact of ageing.
   
     
Jørgen Johansen, Jesper Grau Eriksen & On behalf of the Academy of Geriatric Cancer Research (AgeCare)
Trends in cancer of the head and neck in the elderly in Denmark, 1980–2012
Acta Oncologica 2016;55(suppl 1):13-18.
Click to view summary
Background: Squamous cell carcinoma of the head and neck (HNSCC) comprises a variety of malignant tumors. Due to the rarity of each individual malignant entity, knowledge of epidemiological changes and trends over time may be derived from data compiled in regional and national registries. This study analyzed the development in incidence rates and mortality in elderly HNSCC patients in Denmark between 1980 and 2012 with specific attention to compliance to radiotherapy, the main treatment modality of HNSCC in Denmark.
   
     
Jacob K. Pedersen, Gerda Engholm, Axel Skytthe, Kaare Christensen & on behalf of the Academy of Geriatric Cancer Research (AgeCare)
Cancer and aging: Epidemiology and methodological challenges
Acta Oncologica 2016;55(suppl 1):7-12.
Click to view summary
Epidemiological cancer data shed light on key questions within basic science, clinical medicine and public health. For decades, Denmark has had linkable health registers that contain individual level data on the entire population with virtually complete follow-up. This has enabled high quality studies of cancer epidemiology and minimized the challenges often faced in many countries, such as uncertain identification of the study base, age misreporting, and low validity of the cancer diagnoses.
   
     
Kristine Bjørndal, Stine R. Larsen, Marianne H. Therkildsen, Claus A. Kristensen, Birgitte Charabi, Elo Andersen, Jens Overgaard, Sten Schytte, Henrik B. Pedersen, Lisbeth J. Andersen, Jørgen Johansen, Christian Godballe & On behalf of The Danish Head and Neck Cancer Group (DAHANCA) and Academy of Geriatric Cancer Research (AgeCare)
Does age affect prognosis in salivary gland carcinoma patients? A national Danish study
Acta Oncologica 2016;55(suppl 1):19-22.
Click to view summary
Aim To compare incidence, histology, treatment modalities, disease stages, and outcome in elderly patients (_70 years) compared to younger (570 years).
   
     
Mucci LA, Hjelmborg JB, Harris JR, Czene K, Havelick DJ, Scheike T, Graff RE, Holst K, Möller S, Unger RH, McIntosh C, Nuttall E, Brandt I, Penney KL, Hartman M, Kraft P, Parmigiani G, Christensen K, Koskenvuo M, Holm NV, Heikkilä K, Pukkala E, Skytthe A, Adami HO, Kaprio J; Nordic Twin Study of Cancer (NorTwinCan) Collaboration
Familial Risk and Heritability of Cancer Among Twins in Nordic Countries.
JAMA. 2016;315:68-76.
Click to view summary
A total of 27,156 incident cancers were diagnosed in 23,980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer, with estimated cumulative risks that were an absolute 5% (95% CI, 4%-6%) higher in dizygotic (37%; 95% CI, 36%-38%) and an absolute 14% (95% CI, 12%-16%) higher in monozygotic twins (46%; 95% CI, 44%-48%) whose twin also developed cancer compared with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin melanoma (58%; 95% CI, 43%-73%), prostate (57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%; 95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%), and corpus uteri (27%; 95% CI, 11%-43%).
In this long-term follow-up study among Nordic twins, there was significant excess familial risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus. This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling.
   
     
2015    
     
Möller S, Mucci LA, Harris JR, Scheike T, Holst K, Halekoh U, Adami HO, Czene K, Christensen K, Holm NV, Pukkala E, Skytthe A, Kaprio J, Hjelmborg JB.
The Heritability of Breast Cancer among Women in the Nordic Twin Study of Cancer.
Cancer Epidemiol Biomarkers Prev. 2015;25:1-6.
Click to view summary
Family history is an established risk factor for breast cancer. Although some important genetic factors have been identified, the extent to which familial risk can be attributed to genetic factors versus common environment remains unclear. From 1943 through 2010, 3,933 twins were diagnosed with breast cancer. The cumulative lifetime incidence of breast cancer taking competing risk of death into account was 8.1% for both zygosities, although the cumulative risk for twins whose co-twins had breast cancer was 28% among monozygotic and 20% among dizygotic twins. The heritability of liability to breast cancer was 31% [95% confidence interval (CI), 10%-51%] and the common environmental component was 16% (95% CI, 10%-32%). For premenopausal breast cancer these estimates were 27% and 12%, respectively, and for postmenopausal breast cancer 22% and 16%, respectively. The relative contributions of genetic and environmental factors were constant between ages 50 and 96. Our results are compatible with the Peto-Mack hypothesis. Our findings indicate that familial factors explain almost half of the variation in liability to develop breast cancer, and results were similar for pre- and postmenopausal breast cancer IMPACT: We estimate heritability of breast cancer, taking until now ignored sources of bias into account. Cancer Epidemiol Biomarkers Prev; 25(1); 1-6. ©2015 AACR
   
     
Karin B. Dieperink, Karen Mark and Tina Broby Mikkelsen
Marital rehabilitation after prostate cancer – a matter of intimacy.
International Journal of Urological Nursing doi:10.1111/ijul.12091.
Click to view summary
Prostate cancer is the most frequent male cancer disease in the western world. Sexual dysfunction is common after prostate cancer with radiation therapy and androgen deprivation therapy, but further research is needed to determine the lived experience of couples struggling with sexual dysfunction after treatment. The purpose of this study was to explore the lived experience of men and their partners experiencing sexual side effects after radiation therapy and androgen deprivation therapy for prostate cancer. In addition, to understand the role of a structured rehabilitation program on the couple’s experience.
   
     
Holmström MO, Gimsing P, Abildgaard N, Andersen NF, Helleberg C, Clausen NA, Klausen TW, Frederiksen M, Kristensen DL, Larsen H, Pedersen PT, Andersen KT, Pedersen RS, Jensen BA, Gregersen H, Vangsted AJ.
Causes of early death in multiple myeloma patients who are ineligible for high-dose therapy with hematopoietic stem cell support: A study based on the nationwide Danish Myeloma Database.
Am J Hematol. 2015 Apr;90(4):E73-4.
Click to view summary
To establish intervention strategies to improve survival, we studied the causes of early death in elderly or frail MM patients ineligible for high-dose chemotherapy in an unselected nationwide population. All medical records from myeloma patients who died within 30 and 180 days of diagnosis were thoroughly analyzed. Since 2005 all newly diagnosed MM patients have been registered in the Danish nationwide population-based database (DMMD). The DMMD includes clinical data, laboratory data, and symptoms at diagnosis [7]. We used the DMMD to identify patients ineligible for high-dose therapy (HDT) who died early. SPSS statistical software was used for all calculations (SPSS for Windows, 19.0.0. 2010, Armonk, NY: IBM Inc). All tests were two-sided and P-values <0.05 were regarded as statistically significant. Fisher's exact test or Pearson's χ2-test were used to compare categorical variables. Continuous variables were analyzed using independent samples t-test. Multivariable analysis was performed using a binary logistic regression and right skewed variables (beta 2 microglobulin(B2M), CRP, and lactate dehydrogenase(LDH)) were log-transformed.
   
     
Ahrenfeldt LJ, Skytthe A, Möller S, Czene K, Adami HO, Mucci LA, Kaprio J, Petersen I, Christensen K, Lindahl-Jacobsen R
Risk of Sex-Specific Cancers in Opposite-Sex and Same-Sex Twins in Denmark and Sweden.
Cancer Epidemiol Biomarkers Prev. 2015; 24:1622-8.
Click to view summary
Increasing evidence shows that some cancers originate in utero. It is hypothesized that elevated exposure to some steroid hormones might increase cancer risk and that hormone transfer between twin fetuses could result in different prenatal exposure to testosterone.
This large-scale prospective twin study compared opposite-sex (OS) and same-sex (SS) twins to test the impact of intrauterine exposures on cancer risk. On the basis of the Danish and Swedish twin and cancer registries, we calculated incidence rate ratios for OS and SS twins, whereas standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated for OS/SS twins compared with the general population.
Our data suggest that having a male co-twin-which may entail higher exposure to prenatal testosterone-does not increase the risk of sex-specific cancers in OS females. Furthermore, the study supports that twinning per se is not a risk factor of cancer.
   
     
Karina G. Thomsen, Mikkel G. Terp, Rikke R. Lund, Rolf Søkilde, Daniel Elias, Martin Bak, Thomas Litman, Hans C. Beck, Maria B. Lyng, Henrik J. Ditzel.
miR-155, identified as anti-metastatic by global miRNA profiling of a metastasis model, inhibits cancer cell extravasation and colonization in vivo and causes significant signaling alterations
Oncotarget. 2015;6:29224-39.
Click to view summary
To gain insight into miRNA regulation in metastasis formation, we used a metastasis cell line model that allows investigation of extravasation and colonization of circulating cancer cells to lungs in mice. Using global miRNA profiling, 28 miRNAs were found to exhibit significantly altered expression between isogenic metastasizing and non-metastasizing cancer cells, with miR-155 being the most differentially expressed. Highly metastatic mesenchymal-like CL16 cancer cells showed very low miR-155 expression, and miR-155 overexpression in these cells lead to significantly decreased tumor burden in lungs when injected intravenously in immunodeficient mice. Our experiments addressing the underlying mechanism of the altered tumor burden revealed that miR-155-overexpressing CL16 cells were less invasive than CL16 control cells in vitro, while miR-155 overexpression had no effect on cancer cell proliferation or apoptosis in established lung tumors.
   
     
Jacob K. Pedersen MSc, Axel Skytthe PhD, Matt McGue PhD, Lawrence S. Honig MD, PhD, Claudio Franceschi PhD, Thomas B.L. Kirkwood PhD, Giuseppe Passarino PhD, P. Eline Slagboom PhD, James W. Vaupel PhD, Kaare Christensen MD, DMSc
Low tobacco-related cancer incidence in offspring of long-lived siblings: a comparison with Danish national cancer registry data
Annals of Epidemiology 25 2015;25:569-574.
Click to view summary
Purpose: Familial clustering of longevity is well documented and includes both genetic and other familial factors, but the specific underlying mechanisms are largely unknown. We examined whether low incidence of specific cancers is a mechanism for familial clustering of longevity. Methods: The study population of individuals from longevity-enriched families consisted of 3267 offspring from 610 Danish long-lived families defined by two siblings attaining an age of 90 years or more. The offspring of the long-lived siblings were followed from 1968 to 2009. Using high-quality registry data, observed numbers of cancers were compared with expected numbers based on gender-, calendar period-, and age-specific incidence rates in the general population. Results: During the 41-year-follow-up period, a total of 423 cancers occurred in 397 individuals. The standardized incidence ratios (95% confidence interval) for offspring of long-lived individuals were 0.78 (0.70e0.86) for overall cancer; 0.66 (0.56e0.77) for tobacco-related cancer; 0.34 (0.22e0.51) for lung cancer; 0.88 (0.71e1.10) for breast cancer; 0.91 (0.62e1.34) for colon cancer. Conclusions: The low incidence of tobacco-related cancers in long-lived families compared with non etobacco-related cancers suggests that health behavior plays a central role in lower early cancer incidence in offspring of long-lived siblings in Denmark.
   
     
Hansen O, Schytte T, Nielsen M, Brink C.
Age dependent prognosis in concurrent chemo-radiation of locally advanced NSLCL
Acta Oncologica 2015;54:333-339.
Click to view summary
Background: Clinical trials indicate that the benefit of adding concurrent chemotherapy to radiotherapy of locally advanced non-small cell lung cancer (NSCLC) for fi t elderly is similar to the benefit for younger patients. However, since elderly patients are under-represented in most trials, the results might be due to selection bias, thus reports from a cohort of consecutively treated patients are warranted. The current single institution study reports on the influence of age on survival of locally advanced NSCLC patients treated with radiotherapy combined with or without concurrent chemotherapy.
Material and methods. Altogether, 478 patients completed radical radiotherapy in doses of 60 – 66 Gy/30 – 33 fractions from 1995 to June 2012; 137 of the patients had concurrent chemotherapy. The data was analyzed in age groups - 60,60 – 69, and - 70 years.
Conclusion. Use of concurrent chemotherapy to radiotherapy of locally advanced NSCLC was associated with a survival benefit in patient younger than 70 years which was not the case for patients older than 70 years, indicating the need to be careful when selecting elderly patients for concurrent chemo-radiation.
   
     
2014    
     
Winther SB, Abildgaard N, Pfeiffer P.
Medicinsk behandling af ældre kræftpatienter.
Best Practice 2014; 16: 22-5.
Click to view summary
Summary:
 
     
Birte Østergaard, RN, PhD, and Lis Wagner, RN, DrPH
The Development of Family Nursing in Denmark: Current Status and Future Perspectives
Journal of Family Nursing 2014,20:487–500.
Click to view summary
Over the past 12 years, a strong foundation for family nursing has been built in Denmark, with rapid growth in the past 3 years. A review of nursing research conducted in Denmark and published between 2002 and 2013 found 15 studies that examined family phenomena. The majority of the studies used descriptive methods with data collected from surveys and interviews involving family members either together or individually. Only five of the studies examined interventions that included families’ perspectives about the intervention being evaluated. Several current research projects lead by Danish nurses examine the implementation of family nursing knowledge to clinical settings. Integration of family nursing theory has begun in Denmark in undergraduate and graduate nursing curricula and in May 2013, the Danish Family Nursing Association was officially established.
 
     
Gunnar Baatrup and Niels Qvist
Local resection of early rectal cancer.
APMIS 2014;122:715-722.
Click to view summary
The introduction of a national screening programme for colorectal cancer will lead to the detection of more early rectal cancers where local excision by TEM must be considered due to the significantly lower risk of morbidity and mortality compared to conventional surgery with total mesorectal excision. However, it should be achieved without compromising oncological control. There are certainly groups of old patients and patients with co-morbidities who will also profit from TEM in terms of long-term survival and reduced treatment- related risks in high risk T1 and >T1 cancers.
   
     
Morten F. Gjerstorff, Mette Marie Relster, Katrine B.V. Greve, Jesper B. Moeller, Daniel Elias, Jonas N. Lindgreen, Steffen Schmidt, Jan Mollenhauer, Bjørn Voldborg, Christina B. Pedersen, Nadine Heidi Brückmann, Niels Erik Møllegaard and Henrik Jørn Ditzel
SSX2 is a novel DNA-binding protein that antagonizes polycomb group body formation and gene repression
Nucleic Acids Res. 2014;42:11433-46.
Click to view summary
Polycomb group (PcG) complexes regulate cellular identity through epigenetic programming of chromatin. Here, we show that SSX2, a germline-specific protein ectopically expressed in melanoma and other types of human cancers, is a chromatin-associated protein that antagonizes BMI1 and EZH2 PcG body formation and derepresses PcG target genes. SSX2 further negatively regulates the level of the PcGassociated histone mark H3K27me3 in melanoma cells, and there is a clear inverse correlation between SSX2/3 expression and H3K27me3 in spermatogenesis. However, SSX2 does not affect the overall composition and stability of PcG complexes, and there is no direct concordance between SSX2 and BMI1/H3K27me3 presence at regulated genes. This suggests that SSX2 antagonizes PcG function through an indirect mechanism, such as modulation of chromatin structure. SSX2 binds double-stranded DNA in a sequence non-specific manner in agreement with the observed widespread association with chromatin. Our results implicate SSX2 in regulation of chromatin structure and function.
   
     
Jacob B. Hjelmborg, Thomas Scheike, Klaus Holst, Axel Skytthe, Kathryn L. Penney, Rebecca E. Graff, Eero Pukkala, Kaare Christensen, Hans-Olov Adami, Niels V. Holm, Elizabeth Nuttall, Steinbjorn Hansen, Mikael Hartman, Kamila Czene, Jennifer R. Harris, Jaakko Kaprio, and Lorelei A. Mucci
The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer
Cancer Epidemiol Biomarkers Prev 2014;23:2303-2310.
Click to view summary
Background: Prostate cancer is thought to be the most heritable cancer, although little is known about how this genetic contribution varies across age.
Methods: To address this question, we undertook the world’s largest prospective study in the Nordic Twin Study of Cancer cohort, including 18,680 monozygotic (MZ) and 30,054 dizygotic (DZ) same-sex male twin pairs. We incorporated time-to-event analyses to estimate the risk concordance and heritability while accounting for censoring and competing risks of death, essential sources of biases that have not been accounted for in previous twin studies modeling cancer risk and liability.
Results: The cumulative risk of prostate cancer was similar to that of the background population. The cumulative risk for twins whose co-twin was diagnosed with prostate cancer was greater for MZ than for DZ twins across all ages. Among concordantly affected pairs, the time between diagnoses was significantly shorter forMZthan DZpairs (median, 3.8 versus 6.5 years, respectively). Genetic differences contributed substantially to variation in both the risk and the liability [heritability = 58% (95% confidence interval, 52%–63)%] of developing prostate cancer. The relative contribution of genetic factors was constant across age through late life with substantial genetic heterogeneity even when diagnosis and screening procedures vary. Conclusions: Results from the population-based twin cohort indicate a greater genetic contribution to the risk of developing prostate cancer when addressing sources of bias. The role of genetic factors is consistently high across age.
Impact: Findings affect the search for genetic and epigenetic markers and frame prevention efforts. Cancer Epidemiol Biomarkers Prev; 1–8.
   
     
Brygger L & Herrstedt J on behalf of the Academy of Geriatric Cancer Research (AgeCare)
5-Hydroxytryptamine3 receptor antagonists and cardiac side effects
Expert Opin Drug Safe 2014;13:1407-22
Click to view summary
Introduction: 5-Hydroxytryptamine3-receptor antagonists (5-HT3-RA) are the most widely used antiemetics in oncology, and although tolerability is high, QTC prolongation has been observed in some patients.
Areas covered: The purpose of this article is to outline the risk of cardiac adverse events (AEs) from 5-HT3-RAs, with focus on the three most commonly used, ondansetron, granisetron and palonosetron.
Expert opinion: Most of the studies analyze electrocardiogram (ECG) changes after 5-HT3-RA administrations in healthy, young adults, or in noncancer patients to treat postoperative nausea and vomiting (PONV). Only a few studies have addressed ECG changes in cancer patients treated for chemotherapyinduced nausea and vomiting (CINV). Investigations in cancer patients are essential, because these patients are older and have a higher incidence of comorbidity, than those usually included in clinical trials. Furthermore, polypharmacy is frequent and drug--drug interactions between chemotherapy and other QTc-prolonging drugs may influence the pharmacokinetics and pharmacodynamics of the 5-HT3-RAs. During the next 10 -- 15 years a huge increase in the number of cancer patients is expected, primarily in the group of 65-plus-year old. Therefore it will be crucial to address the incidence of cardiac AEs in cancer patients with known heart disease receiving chemotherapy and a 5-HT3 RA for the prophylaxis of CINV.
   
   
Brink C, Bernchou U, Bertelsen A, Hansen O, Schytte T, Bentzen S.M.
Locoregional Control of Non-Small Cell Lung Cancer in Relation to Automated Early Assessment of Tumor Regression on Cone Beam Computed Tomography
Int J Rad Oncol Biol Phys 2014;89:916-923
Click to view summary
Large interindividual variations in volume regression of non-small cell lung cancer (NSCLC) are observable on standard cone beam computed tomography (CBCT) during fractionated radiation therapy. Here, a method for automated assessment of tumor volume regression is presented and its potential use in response adapted personalized radiation therapy is evaluated empirically.
Methods and Materials: Automated deformable registration with calculation of the Jacobian determinant was applied to serial CBCT scans in a series of 99 patients with NSCLC. Tumor volume at the end of treatment was estimated on the basis of the first one third and two thirds of the scans. The concordance between estimated and actual relative volume at the end of radiation therapy was quantified by Pearson’s correlation coefficient. On the basis of the estimated relative volume, the patients were stratified into 2 groups having volume regressions below or above the population median value. Kaplan-Meier plots of locoregional disease-free rate and overall survival in the 2 groups were used to evaluate the predictive value of tumor regression during treatment. Cox proportional hazards model was used to adjust for other clinical characteristics.
Conclusions: Evaluation of routinely acquired CBCT images during radiation therapy provides biological information on the specific tumor. This could potentially form the basis for personalized response adaptive therapy.
   
     
     
     
     
     
     
     
Updated on January 31, 2021, UHK