Publications by authors named "Jann Mortensen"

134 Publications

Intraglandular Off-the-Shelf Allogeneic Mesenchymal Stem Cell Treatment in Patients with Radiation-Induced Xerostomia: A Safety Study (MESRIX-II).

Stem Cells Transl Med 2022 Apr 18. Epub 2022 Apr 18.

Department of Otolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

No effective therapy exists for the most common long-term side effect of radiation therapy for head and neck cancer (HNC)âxerostomia. The objective was to evaluate safety and provide proof of concept for efficacy of allogeneic adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) injected into the major salivary glands of irradiated patients. This open-label, first-in-human, phase 1b, and single-center trial was conducted with repeated measurements days 0, 1, 5, and 30 and 4 months. Eligible patients with objective and subjective signs of radiation-induced salivary gland damage after treatment of oropharyngeal squamous cell carcinoma stages I-II (UICC 8) were enrolled. Twenty-five million cryopreserved AT-MSCs were injected into each submandibular and 50 million AT-MSCs into each parotid gland. Data were collected on adverse events, unstimulated and stimulated whole saliva (UWS and SWS) flow rates and saliva composition, patient-reported outcomes (EORTC QLQ-H&N35 and Xerostomia Questionnaire [XQ]), blood samples and salivary gland scintigraphy. Data were analyzed using repeated measures linear mixed models. Ten patients (7 men, 3 women, 59.5 years [range: 45-70]) were treated in 4 glands. No treatment-related serious adverse events occurred. During 4 months, UWS flow rate increased from 0.13 mL/minute at baseline to 0.18 mL/minute with a change of 0.06 â¨(P = .0009) mL/minute. SWS flow rate increased from 0.66 mL/minute at baseline to 0.75 mL/minute with a change of 0.09 (P = .017) mL/minute. XQ summary score decreased by 22.6 units (P = .0004), EORTC QLQ-H&N35 dry mouth domains decreased by 26.7 (P = .0013), sticky saliva 23.3 â¨(P = .0015), and swallowing 10.0 (P = .0016). Our trial suggests treatment of the major salivary glands with allogenic AT-MSCs is safe, warranting confirmation in larger trials.
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http://dx.doi.org/10.1093/stcltm/szac011DOI Listing
April 2022

Fulminant H1N1 and severe acute respiratory syndrome coronavirus-2 infections with a 4-year interval without an identifiable underlying cause: a case report.

J Med Case Rep 2021 Oct 8;15(1):505. Epub 2021 Oct 8.

Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.

Background: The clinical presentation of severe acute respiratory syndrome coronavirus-2 infection is highly variable from asymptomatic infection to fulminant disease. The reasons for the variation are only starting to unravel, with risk factors including age and certain comorbidities as well as genetic defects causing immunological perturbations in the interferon pathways.

Case Presentation: We report the case of an otherwise healthy Caucasian man, who at ages 60 and 64 years suffered from severe H1N1 influenza virus infection and severe acute respiratory syndrome coronavirus-2 infections, respectively. In both cases, there were acute kidney impairment and the need for intensive care unit admission as well as mechanical ventilation. Fortunately, after both infections there was full clinical recovery. The severity of the infections indicates an underlying impairment in the ability to control these kinds of infections. Challenge of patient peripheral blood mononuclear cells showed impaired type I and III antiviral interferon responses and reduced interferon-stimulated gene expression. However, despite investigation of patient samples by whole exome sequencing and enzyme-linked immunosorbent assay, no known disease-causing genetic variants related to interferon pathways were found, nor were interferon autoantibodies demonstrated. Thus, any underlying immunological cause of this unusual susceptibility to severe viral infections remains unresolved.

Conclusion: The patient experienced very similar severe clinical pictures triggered by H1N1 and severe acute respiratory syndrome coronavirus-2 infections, indicating an underlying inability to contain these infections. We were unable to show that the patient had any of the currently known types of immune incompetence but identified genetic changes possibly contributing to the severe course of both infections. Further analyses to delineate contribution factors are needed.
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http://dx.doi.org/10.1186/s13256-021-03113-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499611PMC
October 2021

Therapeutic benefits of proning to improve pulmonary gas exchange in severe respiratory failure: focus on fundamentals of physiology.

Exp Physiol 2021 Jul 9. Epub 2021 Jul 9.

Department of Anaesthesia and Intensive Care, Copenhagen University Hospital - Hvidovre Hospital, Hvidovre, Denmark.

New Findings: What is the topic of this review? The use of proning for improving pulmonary gas exchange in critically ill patients. What advances does it highlight? Proning places the lung in its 'natural' posture, and thus optimises the ventilation-perfusion distribution, which enables lung protective ventilation and the alleviation of potentially life-threatening hypoxaemia in COVID-19 and other types of critical illness with respiratory failure.

Abstract: The survival benefit of proning patients with acute respiratory distress syndrome (ARDS) is well established and has recently been found to improve pulmonary gas exchange in patients with COVID-19-associated ARDS (CARDS). This review outlines the physiological implications of transitioning from supine to prone on alveolar ventilation-perfusion ( ) relationships during spontaneous breathing and during general anaesthesia in the healthy state, as well as during invasive mechanical ventilation in patients with ARDS and CARDS. Spontaneously breathing, awake healthy individuals maintain a small vertical (ventral-to-dorsal) ratio gradient in the supine position, which is largely neutralised in the prone position, mainly through redistribution of perfusion. In anaesthetised and mechanically ventilated healthy individuals, a vertical ratio gradient is present in both postures, but with better matching in the prone position. In ARDS and CARDS, the vertical ratio gradient in the supine position becomes larger, with intrapulmonary shunting in gravitationally dependent lung regions due to compression atelectasis of the dorsal lung. This is counteracted by proning, mainly through a more homogeneous distribution of ventilation combined with a largely unaffected high perfusion dorsally, and a consequent substantial improvement in arterial oxygenation. The data regarding proning as a therapy in patients with CARDS is still limited and whether the associated improvement in arterial oxygenation translates to a survival benefit remains unknown. Proning is nonetheless an attractive and lung protective manoeuvre with the potential benefit of improving life-threatening hypoxaemia in patients with ARDS and CARDS.
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http://dx.doi.org/10.1113/EP089405DOI Listing
July 2021

uPAR PET/CT for Prognostication and Response Assessment in Patients with Metastatic Castration-Resistant Prostate Cancer Undergoing Radium-223 Therapy: A Prospective Phase II Study.

Diagnostics (Basel) 2021 Jun 14;11(6). Epub 2021 Jun 14.

Department of Clinical Physiology, Nuclear Medicine & PET, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark.

The aim of this Phase II study was to investigate the potential for response assessment and prognostication of positron emission tomography (PET) using the ligand Ga-NOTA-AE105 targeting the urokinase-type plasminogen activator receptor (uPAR) in patients receiving Radium-223-dichloride therapy (RaCl). A combined whole-body uPAR PET and computed tomography (CT) was performed before initiation of RaCl and after two cycles of therapy. Standardized uptake value (SUV) in selected bone metastases was measured and the lesion with the highest SUV was considered the index lesion. Clinical outcomes were overall survival (OS), radiographic progression free survival (rPFS) and occurrence of symptomatic skeletal event (SSE). A total of 17 patients were included and 14 patients completed both baseline and follow-up uPAR-PET/CT. Baseline SUV of the index lesion was associated with OS; hazard ratio 2.51 (95% CI: 1.01-6.28, = 0.05) per unit increase in SUV. No association between changes in SUV from baseline to follow-up and OS, progression during therapy, or rPFS was found. Baseline SUV was a significant predictor of SSE with receiver operating characteristics (ROC) area under the curve (AUC) = 0.81 (95% CI: 0.58-1.00, = 0.034). A cut-off for tumor SUV could be established with an odds ratio of 14.0 (95% CI: 1.14-172.6, = 0.023) for occurrence of SSE within 12 months. Although based on a small number of patients, uPAR-PET SUV in bone metastases was predictive for OS and risk of SSE in mCRPC patients receiving RaCl. However, a relatively low uptake of the uPAR ligand in bone metastases impedes visual evaluation and requires another modality for lesion delineation.
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http://dx.doi.org/10.3390/diagnostics11061087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232164PMC
June 2021

Influence of reduced diffusing capacity and FEV on outcome after cardiac surgery.

Acta Anaesthesiol Scand 2021 Oct 23;65(9):1221-1228. Epub 2021 Jun 23.

Department of Cardiothoracic Anaesthesiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Background: Impaired lung function is a well-known risk factor in cardiac surgery patients and reduced forced expiratory volume in 1 second (FEV ) is associated with increased mortality. However, there is limited knowledge regarding the influence of impaired diffusing capacity of the lungs for carbon monoxide (DLCO) in unselected cardiac surgery patients. The aim of this study was to investigate the association of impaired DLCO and/or reduced FEV on post-operative mortality and morbidity in cardiac surgery patients.

Methods: In a prospective cohort study, 390 patients scheduled for elective cardiac surgery underwent preoperative lung function test including spirometry and DLCO measurements. We defined reduced FEV as FEV below lower limit of normal (LLN) and impaired DLCO as DLCO <60% of predicted.

Results: Mortality within 1 year (90-570 days) was significantly higher in patients with impaired DLCO (12% vs 3%, P = .010) and with reduced FEV (9% vs 3%, P = .028). Mortality was higher in patients with impaired DLCO both in the presence and absence of FEV  < LLN. In multivariate analysis, only impaired DLCO [OR: 3.3, 95% confidence interval (CI) 1.4-7.5; P = .005] and age (OR: 1.1 per year, 95% CI 1.0-1.2; P = .001) were independent predictors of the combined outcome of mortality and prolonged intensive care unit (ICU) stay. Impaired DLCO was also associated with post-operative respiratory complications.

Conclusion: In patients undergoing elective cardiac surgery, preoperative impaired FEV and DLCO were associated with increased mortality and morbidity. In multivariate analysis, only DLCO and age were independent predictors of a combined outcome of mortality and prolonged ICU stay.
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http://dx.doi.org/10.1111/aas.13935DOI Listing
October 2021

Somatostatin Receptor Imaging PET in Neuroendocrine Neoplasm.

PET Clin 2021 Apr;16(2):191-203

Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen, Denmark; European Neuroendocrine Tumor Society Center of Excellence, Rigshospitalet, Copenhagen, Denmark; Medical Faculty, University of Copenhagen, Denmark. Electronic address:

PET/computed tomography (CT) imaging increasingly is used in neuroendocrine neoplasms (NENs) for diagnosis, staging, monitoring, prognostication, and choosing treatment. Somatostatin PET analog tracers have added to the specificity by obtaining higher affinity to somatostatin receptors with Ga-labeled or Cu-labeled DOTA peptides compared with single-photon emission CT imaging isotopes. PET uptake correlates to tumor grade and is an essential part of theranostics with peptide receptor radionuclide treatment. This article focuses on the literature on head-to-head studies and meta-analyses of different combinations of peptide agonists and a few antagonists. Overall, the published data support the diagnostic capability of PET/CT imaging in NENs.
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http://dx.doi.org/10.1016/j.cpet.2020.12.011DOI Listing
April 2021

Prognostic impact of ventilation-perfusion defects and pulmonary diffusing capacity after single lung transplantation.

Clin Physiol Funct Imaging 2021 Mar 22;41(2):221-225. Epub 2020 Nov 22.

Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Background: Ventilation-perfusion (VQ) scintigraphy and lung function testing are often used to assess allograft function after single lung transplantation (SLTX). However, it is unknown whether allograft defects on VQ scintigraphy presage all-cause mortality after SLTX.

Objective: To investigate whether allograft defects on VQ scintigraphy portend poorer lung function and increased mortality after SLTX.

Methods: We retrospectively identified 45 consecutive patients in which a VQ scintigraphy was performed as part of the routine workup 12 weeks after SLTX. VQ scintigraphies were scored for matched and mismatched perfusion defects in the allograft. Lung function testing was performed according to established guidelines six months after SLTX. Time to all-cause mortality was the endpoint.

Results: 19 (42%) patients had matched VQ defects. After a median follow-up of 4.1 (IQR 1.5-7.9) years since SLTX, 35 (78%) had died. Those with matched defects in the allograft had lower diffusing capacity (mean 42 [SD 14] versus mean 54 [SD 18] % of predicted, p < .05) and increased mortality (univariable HR 2.06, 95% CI: 1.05-4.06, p = .04). However, in multivariate analysis, only lower post-transplantation diffusing capacity remained associated with mortality (HR 1.08, 95% CI: 1.02-1.30 per % lower diffusing capacity of predicted, p = .003).

Conclusion: In SLTX patients, a lower diffusing capacity appeared to explain the increased mortality among those with matched VQ defects in the allograft.
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http://dx.doi.org/10.1111/cpf.12676DOI Listing
March 2021

Inhaled dry powder alginate oligosaccharide in cystic fibrosis: a randomised, double-blind, placebo-controlled, crossover phase 2b study.

ERJ Open Res 2020 Oct 19;6(4). Epub 2020 Oct 19.

AlgiPharma AS, Sandvika, Norway.

Background: OligoG is a low molecular-weight alginate oligosaccharide that improves the viscoelastic properties of cystic fibrosis (CF) mucus and disrupts biofilms, thereby potentiating the activity of antimicrobial agents. The efficacy of inhaled OligoG was evaluated in adult patients with CF.

Methods: A randomised, double-blind, placebo-controlled multicentre crossover study was used to demonstrate safety and efficacy of inhaled dry powder OligoG. Subjects were randomly allocated to receive OligoG 1050 mg per day (10 capsules three times daily) or matching placebo for 28 days, with 28-day washout periods following each treatment period. The primary end-point was absolute change in percentage predicted forced expiratory volume in 1 s (FEV) at the end of 28-day treatment. The intention-to-treat (ITT) population (n=65) was defined as randomised to treatment with at least one administration of study medication and post-dosing evaluation.

Results: In this study, 90 adult subjects were screened and 65 were randomised. Statistically significant improvement in FEV was not observed in the ITT population. Adverse events included nasopharyngitis, cough and pulmonary exacerbation. The number and proportions of patients with adverse events and serious adverse events were similar between OligoG and placebo group.

Conclusions: Inhalation of OligoG-dry powder over 28 days was safe in adult CF subjects. Statistically significant improvement of FEV was not reached. The planned analyses did not indicate a significant treatment benefit with OligoG compared to placebo. exploratory analyses showed subgroup results that indicate that further studies of OligoG in this patient population are justified.
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http://dx.doi.org/10.1183/23120541.00132-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569163PMC
October 2020

Comparison of 81mKrypton and 99mTc-Technegas for ventilation single-photon emission computed tomography in severe chronic obstructive pulmonary disease.

Nucl Med Commun 2021 Feb;42(2):160-168

Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Introduction: Ventilation and perfusion single-photon emission computed tomography combined with computed tomography (SPECT/CT) is a powerful tool to assess the state of the lungs in chronic obstructive pulmonary disease (COPD). 81mKrypton is a gaseous ventilation tracer and distributes similarly to air, but is not widely available and relatively expensive. 99mTc-Technegas is cheaper and has wider availability, but is an aerosol, which may deposit in hot spots as the severity of COPD increases. In this study, 81mKrypton and 99mTc-Technegas were compared quantitatively in patients with severe COPD.

Methods: The penetration ratio, the heterogeneity index (with and without band filtering for relevant clinical sizes) and hot spot appearance were assessed in eleven patients with severe COPD that underwent simultaneous dual-isotope ventilation SPECT/CT with both 99mTc-Technegas and 81mKrypton.

Results: Significant differences were found in the penetration ratio for the medium energy general purpose (MEGP) collimators, but not for the low energy general purpose (LEGP) collimators. The difference in the overall and the band filtered heterogeneity index was significant in most cases. All patients suffered from 99mTc-Technegas hot spots in at least one lung. Comparison of MEGP 81mKrypton and LEGP Technegas scans revealed similar results as the comparison for the MEGP collimators.

Conclusion: Caution should be taken when replacing 81mKrypton with 99mTc-Technegas as a ventilation tracer in patients with severe COPD as there are significant differences in the distribution of the tracers over the lungs. Furthermore, this patient group is prone to 99mTc-Technegas hot spots and might need additional scanning if hot spots severely hamper image interpretation.
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http://dx.doi.org/10.1097/MNM.0000000000001314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808361PMC
February 2021

F-FDG PET is Superior to WHO Grading as a Prognostic Tool in Neuroendocrine Neoplasms and Useful in Guiding PRRT: A Prospective 10-Year Follow-up Study.

J Nucl Med 2021 06 16;62(6):808-815. Epub 2020 Oct 16.

Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet & University of Copenhagen, Copenhagen, Denmark

Accurate grading of patients with neuroendocrine neoplasms (NENs) is essential for risk stratification and optimal choice of therapy. Currently, grading is based on histologically assessed degree of tumor proliferation. The aim of the present study was to assess the long-term prognostic value of F-FDG PET imaging for risk stratification of NENs and compare it with tumor grading (World Health Organization 2010 classification). We conducted a prospective cohort study evaluating the prognostic value of F-FDG PET imaging and compared it with histologic grading. Enrolled were 166 patients of all grades and with histologically confirmed NENs of gastroenteropancreatic origin. The primary endpoint was overall survival (OS). Progression-free survival (PFS) was a secondary endpoint. In addition, OS in relation to peptide receptor radionuclide therapy (PRRT) was analyzed as an exploratory endpoint. The median follow-up time was 9.8 y. Analysis of the whole cohort revealed that a positive F-FDG PET scan was associated with a shorter OS than a negative F-FDG PET scan (hazard ratio: 3.8; 95% CI: 2.4-5.9; < 0.001). In G1 and G2 patients ( = 140), a positive F-FDG PET scan was the only identifier of high risk for death (hazard ratio: 3.6; 95% CI, 2.2-5.9; < 0.001). In multivariate analysis, F-FDG PET, G3 tumor, ≥2 liver metastases, and ≥2 prior therapies were independent prognostic factors for OS, and F-FDG PET, G3 tumor, and ≥3 liver metastases were independent prognostic factors for PFS. For patients receiving PRRT, F-FDG-negative cases had a significantly longer survival than F-FDG-positive cases, whereas no difference was identified for tumor grading. F-FDG-positive patients receiving PRRT had a significantly longer median survival than patients not receiving PRRT (4.4 vs. 1.4 y, = 0.001), whereas no difference was seen for F-FDG-negative patients. F-FDG PET is useful for risk stratification of all NEN grades and is superior to histologic grading. F-FDG PET could differentiate G1 and G2 tumors into low- and high-risk groups. In the selection of therapy and for risk stratification of NEN patients, F-FDG PET status should be considered.
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http://dx.doi.org/10.2967/jnumed.120.244798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8729872PMC
June 2021

Evidence of unilateral diaphragmatic paralysis on lung scintigraphy after double lung transplantation: impact on lung function and survival.

Scand J Clin Lab Invest 2020 Oct 17;80(6):454-455. Epub 2020 Jun 17.

Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

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http://dx.doi.org/10.1080/00365513.2020.1781244DOI Listing
October 2020

Urokinase-Type Plasminogen Activator Receptor (uPAR) PET/MRI of Prostate Cancer for Noninvasive Evaluation of Aggressiveness: Comparison with Gleason Score in a Prospective Phase 2 Clinical Trial.

J Nucl Med 2021 03 6;62(3):354-359. Epub 2020 Aug 6.

Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark

The aim of this study was to evaluate the correlation between uptake of the PET ligand Ga-NOTA-AE105, targeting the urokinase-type plasminogen activator receptor (uPAR), and Gleason score in patients undergoing prostate biopsy. Patients with clinical suspicion of prostate cancer (PCa) or previously diagnosed with PCa were prospectively enrolled in this phase 2 trial. A combination of uPAR PET and multiparametric MRI (mpMRI) was performed, and the SUV in the primary tumor, as delineated by mpMRI, was measured by 2 independent readers. The correlation between the SUV and the Gleason score obtained by biopsy was assessed. A total of 27 patients had histologically verified PCa visible on mpMRI and constituted the study population. There was a positive correlation between the SUV and the Gleason score (Spearman ρ = 0.55; = 0.003). Receiver operating characteristic analysis showed an area under the curve of 0.88 (95% CI, 0.67-1.00) for discriminating a Gleason score of greater than or equal to 3 + 4 from a Gleason score of less than or equal to 3 + 3. A cutoff for the tumor SUV could be established with a sensitivity of 96% (79%-99%) and a specificity of 75% (30%-95%) for detecting a Gleason score of greater than or equal to 3 + 4. For discriminating a Gleason score of greater than or equal to 4 + 3 from a Gleason score of less than or equal to 3 + 4, a cutoff could be established for detecting a Gleason score of greater than or equal to 4 + 3 with a sensitivity of 93% (69%-99%) and a specificity of 62% (36%-82%). SUV measurements from uPAR PET in primary tumors, as delineated by mpMRI, showed a significant correlation with the Gleason score, and the tumor SUV was able to discriminate between low-risk Gleason score profiles and intermediate risk Gleason score profiles with a high diagnostic accuracy. Consequently, uPAR PET/MRI could be a promising method for the noninvasive evaluation of PCa and might reduce the need for repeated biopsies (e.g., in active surveillance).
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http://dx.doi.org/10.2967/jnumed.120.248120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049344PMC
March 2021

Ventilation-perfusion SPECT CTPA in young adult females with suspected pulmonary embolism.

Eur Respir J 2020 06 11;55(6). Epub 2020 Jun 11.

Dept of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark

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http://dx.doi.org/10.1183/13993003.00448-2020DOI Listing
June 2020

Cu-DOTATATE PET in Patients with Neuroendocrine Neoplasms: Prospective, Head-to-Head Comparison of Imaging at 1 Hour and 3 Hours After Injection.

J Nucl Med 2021 01 22;62(1):73-80. Epub 2020 May 22.

Department of Clinical Physiology, Nuclear Medicine, and PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark

Cu-DOTATATE PET/CT imaging 1 h after injection is excellent for lesion detection in patients with neuroendocrine neoplasms (NENs). We hypothesized that the imaging time window can be extended up to 3 h after injection without significant differences in the number of lesions detected. From a prospective study, we compared, on a head-to-head basis, sets of Cu-DOTATATE PET/CT images from 35 patients with NENs scanned 1 and 3 h after injection of 200 MBq of Cu-DOTATATE. The number of lesions on both PET scans was counted and grouped according to organs or regions and compared with negative binomial regression. Discordant lesions (visible on only the 1-h images or only the 3-h Cu-DOTATATE PET images) were considered true if found on simultaneous CT or later MR, CT, or somatostatin receptor imaging. We measured lesion SUV, reference normal-organ or -tissue SUV, and tumor-to-normal-tissue ratios calculated from SUV and SUV We found 822 concordant lesions (visible on both 1-h and 3-h Cu-DOTATATE PET) and 5 discordant lesions, of which 4 were considered true. One discordant case in 1 patient involved a discordant organ system (lymph node) detected on 3-h but not 1-h Cu-DOTATATE PET that did not alter the patient's disease stage (stage IV) because the patient had 11 additional concordant liver lesions. We found no significant differences between the number of lesions detected on 1-h and 3-h Cu-DOTATATE PET. Throughout the 1- to 3-h imaging window, the mean tumor-to-normal-tissue ratio remained high in all key organs: liver (1 h: 12.6 [95% confidence interval (CI), 10.2-14.9]; 3 h: 11.0 [95%CI, 8.7-13.4]), intestines (1 h: 24.2 [95%CI, 14.9-33.4]; 3 h: 28.2 [95%CI, 16.5-40.0]), pancreas (1 h: 42.4 [95%CI, 12.3-72.5]; 3 h: 41.1 [95%CI, 8.7-73.4]), and bone (1 h: 103.0 [95%CI, 38.6-167.4]; 3 h: 124.2 [95%CI, 57.1-191.2]). The imaging time window of Cu-DOTATATE PET/CT for patients with NENs can be expanded from 1 h to 1-3 h without significant differences in the number of lesions detected.
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http://dx.doi.org/10.2967/jnumed.120.244509DOI Listing
January 2021

Survival in patients with scintigraphic evidence of pulmonary thromboembolism 12 weeks after double lung transplantation.

J Heart Lung Transplant 2020 07 28;39(7):719-721. Epub 2020 Feb 28.

Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Medicine, The National Hospital, Torshavn, Faroe Islands.

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http://dx.doi.org/10.1016/j.healun.2020.02.014DOI Listing
July 2020

Cu-DOTATATE PET/CT and Prediction of Overall and Progression-Free Survival in Patients with Neuroendocrine Neoplasms.

J Nucl Med 2020 10 28;61(10):1491-1497. Epub 2020 Feb 28.

Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark

Overexpression of somatostatin receptors (SSTRs) in patients with neuroendocrine neoplasms (NENs) is used for both diagnosis and treatment. Receptor density may reflect tumor differentiation and thus be associated with prognosis. Noninvasive visualization and quantification of SSTR density is possible by SSTR imaging (SRI) using PET. Recently, we introduced Cu-DOTATATE for SRI, and we hypothesized that uptake of this tracer could be associated with overall survival (OS) and progression-free survival (PFS). We evaluated patients with NENs who underwent Cu-DOTATATE PET/CT SRI in 2 prospective studies. Tracer uptake was determined as the maximal SUV (SUV) for each patient. Kaplan-Meier analysis with log-rank was used to determine the predictive value of Cu-DOTATATE SUV for OS and PFS. Specificity, sensitivity, and accuracy were calculated for prediction of outcome at 24 mo after Cu-DOTATATE PET/CT. In total, 128 patients with NENs were included and followed for a median of 73 mo (range, 1-112 mo). During follow-up, 112 experienced disease progression, and 69 died. The optimal cutoff for Cu-DOTATATE SUV was 43.3 for prediction of PFS, with a hazard ratio of 0.56 (95% confidence interval, 0.38-0.84) for patients with an SUV of more than 43.3. However, no significant cutoff was found for prediction of OS. In multiple Cox regression adjusted for age, sex, primary tumor site, and tumor grade, the SUV cutoff hazard ratio was 0.50 (range, 0.32-0.77) for PFS. The accuracy was moderate for predicting PFS (57%) at 24 mo after Cu-DOTATATE PET/CT. In this first study to report the association of Cu-DOTATATE PET/CT and outcome in patients with NENs, tumor SSTR density as visualized with Cu-DOTATATE PET/CT was prognostic for PFS but not OS. However, the accuracy of prediction of PFS at 24 mo after Cu-DOTATATE PET/CT SRI was moderate, limiting the value on an individual-patient basis.
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http://dx.doi.org/10.2967/jnumed.119.240143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539650PMC
October 2020

Variation in Time to Peak Values for Different Lung Function Parameters After Double Lung Transplantation.

Transplant Proc 2020 Jan - Feb;52(1):295-301. Epub 2020 Jan 3.

Department of Cardiology, Section of Lung Transplantation, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Background: Establishment of baseline values for forced expiratory volume in the first second (FEV), forced vital capacity (FVC), or total lung capacity (TLC) is required when diagnosing and phenotyping chronic lung allograft dysfunction after lung transplant. It is generally accepted that the baseline (peak) values of these parameters occur simultaneously, but this assumption has not been substantiated for TLC.

Methods: All lung function measurements in all double lung transplant recipients from a single center in the period from 1992-2014 were included. Time to baseline FEV was assessed according to standards from the International Society for Heart and Lung Transplantation, and time to peak FVC, TLC, and diffusion capacity for carbon monoxide were evaluated.

Results: A total of 288 double lung transplants surviving more than 3 months after transplant were included. Baseline FEV occurred at a median of 0.77 years post transplant and was statistically different from median times to the peak FVC (1.02 years), to peak TLC (1.37 years), and to peak diffusion capacity for carbon monoxide 1.04 years post transplant (all log-rank P < .001). At the time of baseline FEV1, FVC, and TLC were at a mean of 96% and 95% of their peak values, respectively.

Conclusion: The peak lung function is reached at different time points for different parameters post transplant with FEV baseline occurring first. For most patients values of FVC and TLC obtained at time for baseline FEV is a good estimate of peak values, but in a small percentage of patients this procedure may jeopardize phenotyping of chronic lung allograft dysfunction based solely on lung function parameters.
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http://dx.doi.org/10.1016/j.transproceed.2019.10.009DOI Listing
July 2020

Recurrence and survival rates in node negative patients after sentinel node biopsy for early-stage vulva cancer - A nationwide study.

Gynecol Oncol 2020 01 9;156(1):124-130. Epub 2019 Nov 9.

Department of Gynecology, Copenhagen University Hospital Rigshospitalet, Denmark.

Objective: The sentinel node (SN) procedure is adopted in selected patients with early-stage vulva cancer (VC) in Denmark. Due to the low incidence of VC, large population-based studies on the safety of SN outside multicenter clinical trials are lacking. The current study evaluated the risk of recurrence and survival in SN- negative VC patients.

Methods: Nationwide data was collected and registered prospectively in the Danish Gynecologic Cancer Database from January 2011 to July 2017. Patients with clinically stage IB-II unifocal vulva squamous cell carcinoma, tumor <4 cm and no clinically suspicious groin nodes or distant metastases, who underwent SN-procedure, were included.

Results: The SN-procedure was performed in 286 patients, of these 190 (66.4%) patients were SN-negative. Twenty-three of the 190 SN-negative patients (12.1%) had one or more recurrences during a median follow-up of 30 months (range 1-83). Four patients (2.1%) had an isolated groin recurrence identified from 5 to 17 months after primary surgery. Fourteen patients (7.4%) experienced a local recurrence in vulva, 1 patient (0.5%) had a recurrence in the vulva and the groin and 4 patients (2.1%) had distant recurrences. The 3-year overall (OS) and disease-specific survival (DSS) for SN-negative patients was 84% and 93%, respectively. The 3-year OS for patients with recurrent disease was 58%.

Conclusions: This is the largest prospective nationwide study on SN-procedure in vulva cancer. The study confirms the safety of the SN-procedure in selected early-stage VC patients with a low isolated groin recurrence rate and a good DSS.
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http://dx.doi.org/10.1016/j.ygyno.2019.10.024DOI Listing
January 2020

[Inhalers and inhalation techniques in the treatment of asthma and chronic obstructive pulmonary disease].

Ugeskr Laeger 2019 Aug;181(33)

A wide catalogue of inhalers is available today as described in this review, but many patients and healthcare professionals do not know how to use inhalers correctly. However, knowledge of the working principles and pros and cons of the various inhaler types may improve patient education and the correct choice of device. Which inhaler is the best suited cannot be determined without measuring the patient's inspiration flow and controlling the ability to coordinate and handle a device. Extra-fine particles from pressurised metered dose inhalers, dry powder inhalers and soft mist inhalers give new perspectives on disease control as optimal coordination, and flow pattern is less crucial.
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August 2019

Near-infrared fluorescence imaging improves the nodal yield in neck dissection in oral cavity cancer - A randomized study.

Eur J Surg Oncol 2019 Nov 29;45(11):2151-2158. Epub 2019 Jun 29.

Department of Otolaryngology, Head & Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen East, Denmark. Electronic address:

Introduction: Lymph node yield (LNY) in neck dissection has been identified as a prognostic factor in oral cavity cancer. The purpose of this study was to investigate the impact of additional use of optical imaging on LNY in therapeutic ND in oral cancer.

Methods: Consecutive patients with oral squamous cell carcinoma with clinical neck metastasis planned for primary tumor resection were randomized to conventional neck dissection or near-infrared fluorescence (NIRF)-guided neck dissection, respectively. In the intervention group, patients were injected with ICG-Nanocoll prior to surgery. Intraoperatively, an optical hand-held camera system was used for lymph node identification. Also, NIRF imaging of the neck specimen was performed, and optical signals were pinned with needle markings to guide the pathological examination. The endpoint of the study was LNY per neck side in levels Ib-III.

Results: 31 patients were included with 18 neck sides in the control group and 18 neck sides in the intervention group for evaluation. During NIRF-guided ND, individual lymph nodes could be identified by a bright fluorescent signal and individual tumor-related drainage patterns could be observed in the neck. The LNY in the intervention group was significantly higher compared to the control group (p = 0.032) with a mean of 24 LN (range: 12-33 LN in levels Ib-III compared to 18 LN (range: 10-36 LN) in the control group, respectively.

Conclusions: NIRF-guided ND significantly improved the nodal yield compared to the control group. Intraoperative real-time optical imaging enabled direct visualization of tumor-related drainage patterns within the neck lymphatics.
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http://dx.doi.org/10.1016/j.ejso.2019.06.039DOI Listing
November 2019

Lobar Quantification by Ventilation/Perfusion SPECT/CT in Patients with Severe Emphysema Undergoing Lung Volume Reduction with Endobronchial Valves.

Respiration 2019;98(3):230-238. Epub 2019 Jun 5.

Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark,

Background: Endoscopic lung volume reduction (ELVR) therapy using one-way valves is used to treat chronic obstructive pulmonary disease patients with severe heterogeneous emphysema. A successful treatment results in atelectasis of the treated pulmonary lobe with subsequent reduction of ventilation (V) and perfusion (Q).

Objective: We evaluated the effects of ELVR on the targeted lobe using a new 3-dimensional ventilation and perfusion (V/Q) single-photon emission computed tomography (SPECT)/computed tomography (CT) analysis, which allows for simultaneous semi-automatic lobar pulmonary quantification of volume, ventilation and perfusion, on the first consecutive patients treated with ELVR at Rigshospitalet, Denmark. V/Q planar scintigraphy and V/Q SPECT/CT and lung function measurements were performed before and 6 months after intervention.

Results: We included 24 subjects (60 years, range 46-74 years; 37.5% men) with a baseline FEV1 of 25% predicted and RV of 257% predicted. V/Q SPECT/CT-assessed volume of the targeted lobe decreased by a mean of -395 mL and a relative mean of -26.8%, whilst ventilation and perfusion decreased by a relative mean of -37.1 and -25.7%. There was a significant increase in the same parameters of the non-targeted lobe(s) on the ipsilateral side. None of these changes were found in the analysis of planar V/Q imaging. The total lung volume decreased on average by -420 mL. Six months after ELVR, FEV1 had increased by 22%. Significant correlations were found between changes in FEV1 and changes in the volume of the treated lobe (SPECT/CT).

Conclusion: Semi-automatic SPECT/CT analysis can quantify volume, ventilation and perfusion changes in pulmonary lobes and may be used in the assessment of patient eligibility for ELVR, identifying target lobes, and evaluation of the regional effects of treatment.
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http://dx.doi.org/10.1159/000500407DOI Listing
September 2020

Preoperative pulmonary function in all comers for cardiac surgery predicts mortality†.

Interact Cardiovasc Thorac Surg 2019 Mar 15. Epub 2019 Mar 15.

Department of Cardiothoracic Anesthesiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Objectives: Although reduced lung function and chronic obstructive pulmonary disease (COPD) is associated with higher risk of death following cardiac surgery, preoperative spirometry is not performed routinely. The aim of this study was to investigate the relationship between preoperative lung function and postoperative complications in all comers for cardiac surgery irrespective of smoking or COPD history.

Methods: Preoperative spirometry was performed in elective adult cardiac surgery patients. Airflow obstruction was defined as the ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio below the lower limit of normal (LLN) and reduced forced ventilatory capacity defined as FEV1
Results: A history of COPD was reported by 132 (19%) patients; however, only 74 (56%) had spirometry-verified airflow obstruction. Conversely, 64 (12%) of the 551 patients not reporting a history of COPD had spirometry-verified airflow obstruction. The probability of death was significantly higher in patients with airflow obstruction (8.8% vs 4.5%, P = 0.04) and in patients with a FEV1
Conclusions: Preoperative spirometry reclassified 18% of the patients. A reduced FEV1 independently doubled the risk of death. Inclusion of preoperative spirometry in routine screening of cardiac surgical patients may improve risk prediction and identify high-risk patients.

Clinical Trial Registration Number: NCT01614951 (ClinicalTrials.gov).
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http://dx.doi.org/10.1093/icvts/ivz049DOI Listing
March 2019

Lung Scintigraphy in COPD.

Semin Nucl Med 2019 01 17;49(1):16-21. Epub 2018 Nov 17.

Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark; Faculty of Life Sciences and Education, University of South Wales, Pontypridd, United Kingdom.

Ventilation-perfusion scintigraphy is a functional imaging biomarker that has the potential of captivating the heterogeneity of chronic obstructive pulmonary disease (COPD). It specifically images the distribution of ventilation and perfusion within the lungs, which is a critical pathophysiological component of COPD. The extent of ventilation defects and ventilation inhomogeneity, as well as the ventilation-perfusion ratio distribution thus correlate with severity of disease. Furthermore, specific scintigraphic patterns, such as the "stripe sign" may detect centrilobular emphysematous lesions with a higher sensitivity than other imaging techniques. Although ventilation-perfusion scintigraphy may conceivably detect COPD before any specific changes can be detected by spirometry or high-resolution CT, it is currently mostly used in the workup of lung volume reduction treatment, and for diagnosing various complications and comorbidities of COPD when combined with low-dose CT.
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http://dx.doi.org/10.1053/j.semnuclmed.2018.10.010DOI Listing
January 2019

Osteogenic impact of football training in 55- to 70-year-old women and men with prediabetes.

Scand J Med Sci Sports 2018 Aug 26;28 Suppl 1:52-60. Epub 2018 Jul 26.

Faculty of Health Sciences, Centre of Health Science, University of the Faroe Islands, Tórshavn, Faroe Islands.

The effects of football training on bone health were examined in 55- to 70-year-old sedentary women and men with prediabetes. Patients (n = 50) with prediabetes (age; 61 ± 9 years, BMI 29.7 ± 0.6 kg/m , body fat content; 37 ± 1%, VO ; 22.7 ± 0.8 mL/min/kg and mean arterial pressure; 104 ± 3 mm Hg) were randomized into a football training group (FTG; n = 27, 14 women) and a control group (CON; n = 23, 11 women). At baseline, 73% and 24% were diagnosed with femur osteopenia and osteoporosis, respectively. FTG performed football training twice weekly 30-60-minute sessions in 16 weeks, and both FTG and CON received professional dietary advice. Pre- and post-intervention whole-body and regional bone mineral content (BMC) and density (BMD) were determined with DXA-scans, and venous blood samples were drawn and analyzed for plasma bone turnover markers. Change scores were greater (P < 0.05) in FTG compared to CON in leg BMD (0.023 ± 0.005 vs -0.004 ± 0.001 g/cm ) and in leg BMC (32 ± 8 vs -4 ± 6 g). Between-group changes in favor of FTG (P < 0.05) also occurred in the femur neck BMD (3.2%) and femur shaft BMD (2.5%). Whole-body BMC and BMD were unchanged in both groups during the intervention. In FTG, resting plasma osteocalcin, P1NP, and CTX-1 rose (P < 0.05) by 23 ± 8, 52 ± 9 and 38 ± 7%, with greater change scores (P < 0.05) than in CON. Finally, P1NP (formation)/CTX-1 (resorption) ratio increased (P < 0.05) in FTG (127 ± 15 vs 150 ± 11) from pre- to post-intervention, with no change in CON (124 ± 12 and 123 ± 12). In conclusion, football training provides a powerful osteogenic stimulus and improves bone health in 55- to 70-year-old women and men diagnosed with prediabetes.
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http://dx.doi.org/10.1111/sms.13252DOI Listing
August 2018

Reference equations for pulmonary diffusing capacity of carbon monoxide and nitric oxide in adult Caucasians.

Eur Respir J 2018 07 19;52(1). Epub 2018 Jul 19.

Dept of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

The aim of this study was to determine reference equations for the combined measurement of diffusing capacity of the lung for carbon monoxide (CO) and nitric oxide (NO) (). In addition, we wanted to appeal for consensus regarding methodology of the measurement including calculation of diffusing capacity of the alveolo-capillary membrane () and pulmonary capillary volume (). was measured in 282 healthy individuals aged 18-97 years using the single-breath technique and a breath-hold time of 5 s (true apnoea period). The following values were used: 1) specific conductance of nitric oxide (θ)=4.5 mL·mL·min·mmHg; 2) ratio of diffusing capacity of the membrane for NO and CO (/)=1.97; and 3) 1/red cell CO conductance (1/θ)=(1.30+0.0041·mean capillary oxygen pressure)·(14.6/Hb concentration in g·dL).Reference equations were established for the outcomes of , including and and the calculated values and Independent variables were age, sex, height and age squared.By providing new reference equations and by appealing for consensus regarding the methodology, we hope to provide a basis for future studies and clinical use of this novel and interesting method.
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http://dx.doi.org/10.1183/13993003.00677-2015DOI Listing
July 2018

Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells.

Nat Commun 2018 03 6;9(1):785. Epub 2018 Mar 6.

CytoVac A/S, 2970, Hørsholm, Denmark.

In cancer cells, cancer/testis (CT) antigens become epigenetically derepressed through DNA demethylation and constitute attractive targets for cancer immunotherapy. Here we report that activated CD4 T helper cells treated with a DNA-demethylating agent express a broad repertoire of endogenous CT antigens and can be used as antigen-presenting cells to generate autologous cytotoxic T lymphocytes (CTLs) and natural killer cells. In vitro, activated CTLs induce HLA-restricted lysis of tumor cells of different histological types, as well as cells expressing single CT antigens. In a phase 1 trial of 25 patients with recurrent glioblastoma multiforme, cytotoxic lymphocytes homed to the tumor, with tumor regression ongoing in three patients for 14, 22, and 27 months, respectively. No treatment-related adverse effects were observed. This proof-of-principle study shows that tumor-reactive effector cells can be generated ex vivo by exposure to antigens induced by DNA demethylation, providing a novel, minimally invasive therapeutic strategy for treating cancer.
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http://dx.doi.org/10.1038/s41467-018-03217-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840134PMC
March 2018

[The choice of diagnostic modality for acute pulmonary embolism].

Ugeskr Laeger 2018 Feb;180(8)

The diagnosis of pulmonary embolism (PE) relies on clinical assessment, D-dimer test and diagnostic imaging. Modern CT pulmonary angiography (CTPA), ventilation/perfusion  single-photon emission computed tomography (SPECT) and SPECT/CT are rather equal in terms of sensitivity, specificity and inconclusive results for the diagnosis of PE, outper-forming planar lung scintigraphy. Furthermore, SPECT/CT and CTPA can both provide important information regarding differential diagnoses. Thus, the choice of primary diag-nostic modality relies on local expertise, availability and special circumstances like radiation dose, contraindications and the clinical urgency.
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February 2018

Impact of treatment delay in Radium-223 therapy of metastatic castration-resistant prostate cancer patients.

Ann Nucl Med 2018 Jan 3;32(1):16-21. Epub 2017 Oct 3.

Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.

Background: Radium-223-dichloride (Ra-223) is an alpha-emitting, bone seeking radionuclide therapy approved for patients with metastatic castration-resistant prostate cancer (mCRPC). In the fall of 2014, a global temporary shortage of Ra-223 occurred for 2 months due to production irregularities. The aim of this study was to assess whether prolonged interval between Ra-223 cycles to non-disease related causes had a negative impact on clinical outcome of therapy.

Materials And Methods: Retrospective single-center study of mCRPC patients who initiated Ra-223 therapy in the period from March 2014 to February 2015. End points were number of completed Ra-223 cycles, overall survival (OS) and radiographic progression-free survival (rPFS). Bone scintigraphy, CT of thorax and abdomen, hematological status, PSA and alkaline phosphatase were evaluated prior to first dose and after 3rd and 6th treatment, respectively. Follow-up period was 18 months after first Ra-223 cycle.

Results: A total of 50 consecutive patients initiated Ra-223 therapy in the time period. Seventeen of 50 patients (34%) had prolonged interval between cycles due to delivery problems. Median delay was 4 weeks (range 3-9 weeks). Patients with delayed treatment had significantly longer median rPFS [delayed patients: 7.1 months (95% CI 4.9-9.3) vs. 4.5 months (95% CI 2.8-6.3)]. There was no significant difference in number of completed cycles or median OS.

Conclusion: We find no negative impact of prolonged interval between Ra-223 cycles due to non-disease related reasons on OS, rPFS or number of completed treatment cycles.
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http://dx.doi.org/10.1007/s12149-017-1212-1DOI Listing
January 2018

Ra Therapy of Advanced Metastatic Castration-Resistant Prostate Cancer: Quantitative Assessment of Skeletal Tumor Burden for Prognostication of Clinical Outcome and Hematologic Toxicity.

J Nucl Med 2018 04 1;59(4):596-602. Epub 2017 Sep 1.

Department of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; and.

The aim of this study was to investigate the prognostic value of the quantitative assessment of skeletal tumor burden on bone scintigraphy (Bone Scan Index [BSI]) in patients who have advanced metastatic castration-resistant prostate cancer (mCRPC) and are receiving RaCl We hypothesized that the BSI can serve as a prognostic biomarker of overall survival (OS) and hematologic toxicity and as a tool for response assessment in patients with mCRPC treated with RaCl This study was a retrospective investigation of a Danish cohort of mCRPC patients who received RaCl therapy between March 2014 and October 2015 and for whom baseline bone scintigraphy was available. Bone scintigraphy studies were reviewed and graded according to the extent of disease. Furthermore, an automated BSI (EXINI Bone) was obtained for baseline scintigraphy studies and follow-up scans after 3 cycles as well as at the end of therapy. Clinical outcomes were OS and occurrence of hematologic toxicity of grades 2-5. Associations between the BSI and clinical outcomes were investigated in multivariate regression models including the visual assessment of bone scintigraphy and other relevant covariates. A total of 88 patients were included. The median number of completed RaCl cycles was 4, and 27 patients (31%) completed 6 cycles. The BSI was significantly associated with OS in the multivariate analysis; the median OS for patients with a BSI of greater than 5 was 8.2 mo, and the median OS for patients with a BSI of less than or equal to 5 was 15.0 mo (hazard ratio, 2.65 [95% confidence interval, 1.5-4.71]; = 0.001). Likewise, the baseline BSI was prognostic for the occurrence of hematologic toxicity; patients with a BSI of greater than 5 had an odds ratio of 3.02 (95% confidence interval, 1.2-7.8; = 0.02) for toxicity. The BSI declined during therapy in 44% of the patients who completed 3 cycles of RaCl ( = 52) and in 84% of the patients after the end of therapy ( = 32). There was no significant association between a change in the BSI during therapy and OS. The BSI is a promising biomarker for prognostication of OS and hematologic toxicity in late-stage mCRPC patients receiving RaCl Further prospective studies are needed to evaluate the potential of the BSI for response assessment in RaCl therapy.
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http://dx.doi.org/10.2967/jnumed.117.195677DOI Listing
April 2018

Urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and epidermal growth factor receptor (EGFR): tumor expression patterns and prognostic value in oral cancer.

BMC Cancer 2017 Aug 25;17(1):572. Epub 2017 Aug 25.

Department of Otolaryngology, Head & Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Background: Tumor-specific biomarkers are a prerequisite for the development of targeted imaging and therapy in oral squamous cell carcinoma (OSCC). urokinase-type Plasminogen Activator Receptor (uPAR), Tissue Factor (TF) and Epidermal Growth Factor Receptor (EGFR) are three biomarkers that exhibit enhanced expression in many types of cancers, and have been investigated as potential biomarkers for targeted strategies and prognostication. The aim of the study was to investigate the expression patterns of uPAR, TF and EGFR and their potential prognostic value in OSCC.

Methods: Immunohistochemical expression of uPAR, TF and EGFR in tumor resection specimens from 191 patients with primary OSCC was analyzed. Overall (OS) and disease-free survival (DFS) was calculated. Associations between biomarker expression, clinicopathological factors and patient survival was analyzed using the Cox proportional hazards model for univariate and multivariate analysis, log rank and Kaplan-Meier statistics.

Results: uPAR and TF exhibited a highly tumor-specific expression pattern while EGFR also showed expression in normal tissues outside the tumor compartment. The overall positive expression rate of uPAR, TF and EGFR was 95%, 58% and 98%, respectively. High uPAR expression across the entire cohort was negatively associated with OS (p = 0.031, HR = 1.595 (95%CI 1.044-2.439)) in univariate analysis. The 5-year OS for high and low uPAR expression was 39% and 56%, respectively. The expression of TF and EGFR was not associated with survival outcome.

Conclusions: This study may suggest that uPAR and TF could potentially be attractive targets for molecular imaging and therapy in OSCC due to high positive expression rates and tumor-specific expression patterns. High uPAR expression was significantly associated with a reduced survival. uPAR seems to be a prognostic biomarker in oral cancer.
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http://dx.doi.org/10.1186/s12885-017-3563-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574145PMC
August 2017
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