Anne Kiil Berthelsen

IT University of Copenhagen, København, Capital Region, Denmark

Are you Anne Kiil Berthelsen?

Claim your profile

Publications (86)310.61 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Angiosarcomas are rare and only represent about 2% of all soft tissue sarcomas. They arise from vascular or lymphatic endothelial cells and are most commonly located in the heart, liver, breast, and skin. Cutaneous angiosarcoma of the scalp is highly malignant and with dismal prognosis. Reported five-year survival is <30%. The mainstay of treatment is surgical resection and adjuvant radiation therapy, but failure rates following local therapy are high. Cutaneous angiosarcoma of the scalp has a predilection for pulmonary metastases with a variety of morphologic patterns on imaging. Metastatic disease in terms of pulmonary thin-walled, cystic lesions, may not be hypermetabolic on (18)F-FDG PET and, as such, could be misinterpreted as benign findings. We present a case demonstrating the diagnostic uncertainty and delay in an elderly male with angiosarcoma of the scalp presenting with metastatic lung lesions following failure of local therapy.
    Preview · Article · Dec 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A first-inhuman clinical trial with Positron Emission Tomography (PET) imaging of the uroki-nase-type plasminogen activator receptor (uPAR) in patients with breast, prostate and bladder cancer, is described. uPAR is expressed in many types of human cancers and the expression is predictive of invasion, metastasis and indicates poor prognosis. uPAR PET imaging therefore holds promise to be a new and innovative method for improved cancer diagnosis, staging and individual risk stratification. The uPAR specific peptide AE105 was conjugated to the macrocyclic chelator DOTA and labeled with 64 Cu for targeted molecular imaging with PET. The safety, pharmacoki-netic, biodistribution profile and radiation dosimetry after a single intravenous dose of 64 Cu-DOTA-AE105 were assessed by serial PET and computed tomography (CT) in 4 prostate, 3 breast and 3 bladder cancer patients. Safety assessment with laboratory blood screening tests was performed before and after PET ligand injection. In a subgroup of the patients, the in vivo stability of our targeted PET ligand was determined in collected blood and urine. No adverse or clinically detectable side effects in any of the 10 patients were found. The ligand exhibited good in vivo stability and fast clearance from plasma and tissue compartments by renal excretion. In addition, high uptake in both primary tumor lesions and lymph node metastases was seen and paralleled high uPAR expression in excised tumor tissue. Overall, this first-inhuman study therefore provides promising evidence for safe use of 64 Cu-DOTA-AE105 for uPAR PET imaging in cancer patients.
    Full-text · Article · Sep 2015 · Theranostics
  • Source

    Full-text · Article · Aug 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: In cancer of the uterine cervix, lymph node metastases are associated with a poor prognosis. Even so, the International Federation of Gynecology and Obstetrics (FIGO) does not take into account diagnostic results of methods such as PET/CT, since these are not readily available everywhere. As undetected lymph node metastases can lead to undertreatment, any difference in the underlying prevalence of false-negative scans between CT and PET/CT may be reflected in treatment outcomes. This study investigated survival outcomes in node-negative patients before and after the introduction of PET/CT. This was a single-institution retrospective analysis of 301 patients with a histopathological diagnosis of cervical cancer. The patients were receiving chemoradiotherapy with curative intent according to the standard protocol of the department for patients without lymph node metastases as assessed by pretreatment CT or PET/CT. Patients were stratified into two groups: PET/CT and non-PET/CT. Patient characteristics and treatment outcomes were acquired from the treatment database. Significant differences of 23 % (95 % CI 17 - 29 %), 19 % (95 % CI 13 - 25 %) and 12 % (95 % CI 6 - 18 %) in 5-year overall, disease-free and disease-specific survival, respectively, were observed between the two patient groups. The difference remained significant in univariate and multivariate analyses of overall survival (hazard ratio 0.61, 95 % CI 0.42 - 0.89; p = 0.010), including age, FIGO stage, performance status, BMI, and histopathology. Inclusion of PET/CT in the preradiotherapy diagnostic protocol may lead to nodal stage migration not reflected in the FIGO stage. It was found to be a significant covariate, and could lead to selection bias that needs to be taken into account when designing and reporting on clinical trials.
    No preview · Article · Jul 2015 · European Journal of Nuclear Medicine
  • Umberto Ricardi · Lena Specht · Annibale Versari · Anne Kiil Berthelsen
    [Show abstract] [Hide abstract]
    ABSTRACT: Most lymphoma types are fluorodeoxyglucose positron emission tomography (FDG-PET) positive, and FDG-PET/computed tomography (CT) is used routinely in staging and treatment evaluation of lymphomas. PET/CT imaging is important for contouring of the target for radiotherapy and changes the radiation volumes significantly compared with radiotherapy planning based on CT alone. Modern advanced imaging techniques with image fusion and inspiration breath hold have enabled further refinements of radiotherapy for lymphoma, reducing the risks of long-term side effects while maintaining the high cure rate for these diseases.
    No preview · Article · Jul 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neuroendocrine tumors (NETs) can be visualized using radiolabeled somatostatin analogs. We have previously shown the clinical potential of (64)Cu-DOTATATE in a small first-in-human feasibility study. The aim of the present study was, in a larger prospective design, to compare on a head-to-head basis the performance of (64)Cu-DOTATATE and (111)In-DTPA-octreotide ((111)In-DTPA-OC) as basis for implementing (64)Cu-DOTATATE as a routine. We prospectively enrolled 112 patients with pathologically confirmed NETs of gastro-entero-pancreatic or pulmonary origin. All patients underwent both PET/CT with (64)Cu-DOTATATE and SPECT/CT with (111)In-DTPA-OC within 60 days. PET scans were acquired 1 hour post-injection of 202 MBq (range 183 - 232 MBq) (64)Cu-DOTATATE following a diagnostic contrast-enhanced CT scan. Patients were followed for 42-60 months for evaluation of discrepant imaging findings. McNemar's test was used to compare the diagnostic performance. 87 patients were congruently PET and SPECT positive. No SPECT positive cases were PET negative, while 10 false-negative SPECT cases were identified using PET. Diagnostic sensitivity and accuracy of (64)Cu-DOTATATE (97% for both) were significantly better than that of (111)In-DTPA-OC (87% and 88% respectively, P = 0.017). In 84 patients (75%) (64)Cu-DOTATATE identified more lesions than (111)In-DTPA-OC and always at least as many. In total, twice as many lesions were detected using (64)Cu-DOTATATE compared to (111)In-DTPA-OC. Moreover, in 40 of 112 cases (36%) lesions were detected by (64)Cu-DOTATATE in organs not identified as disease-involved by (111)In-DTPA-OC. With these results, we demonstrate that (64)Cu-DOTATATE is far superior to (111)In-DTPA-OC in diagnostic performance in NET patients. Therefore, we do not hesitate to recommend implementation of (64)Cu-DOTATATE as replacement for (111)In-DTPA-OC. Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Full-text · Article · May 2015 · Journal of Nuclear Medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hodgkin lymphoma (HL) survivors have an increased risk of cardiovascular disease (CD), lung cancer, and breast cancer. We investigated the risk for the development of CD and secondary lung, breast, and thyroid cancer after radiation therapy (RT) delivered with deep inspiration breath-hold (DIBH) compared with free-breathing (FB) using 3-dimensional conformal RT (3DCRT) and intensity modulated RT (IMRT). The aim of this study was to determine which treatment modality best reduced the combined risk of life-threatening late effects in patients with mediastinal HL. Twenty-two patients with early-stage mediastinal HL were eligible for the study. Treatment plans were calculated with both 3DCRT and IMRT on both DIBH and FB planning computed tomographic scans. We reported the estimated dose to the heart, lung, female breasts, and thyroid and calculated the estimated life years lost attributable to CD and to lung, breast, and thyroid cancer. DIBH lowered the estimated dose to heart and lung regardless of delivery technique (P<.001). There was no significant difference between IMRT-FB and 3DCRT-DIBH in mean heart dose, heart V20Gy, and lung V20Gy. The mean breast dose was increased with IMRT regardless of breathing technique. Life years lost was lowest with DIBH and highest with FB. In this cohort, 3DCRT-DIBH resulted in lower estimated doses and lower lifetime excess risks than did IMRT-FB. Combining IMRT and DIBH could be beneficial for a subgroup of patients. Copyright © 2015 Elsevier Inc. All rights reserved.
    Preview · Article · Mar 2015 · International journal of radiation oncology, biology, physics

  • No preview · Article · Sep 2014 · International journal of radiation oncology, biology, physics
  • M.C. Aznar · M.V. Maraldo · A.K. Berthelsen · D.A. Schut · A. Loft · L. Specht · P.M. Petersen

    No preview · Article · Sep 2014 · International journal of radiation oncology, biology, physics
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Long-term Hodgkin lymphoma (HL) survivors have an increased risk of late cardiac morbidity and secondary lung cancer after chemotherapy and mediastinal radiotherapy. In this prospective study we investigate whether radiotherapy with deep inspiration breath-hold (DIBH) can reduce radiation doses to the lungs, heart, and cardiac structures without compromising the target dose. Patients and methods: Twenty-two patients (14 female, 8 male), median age 30 years (18-65 years), with supra-diaphragmatic HL were enrolled and had a thoracic PET/CT with DIBH in addition to staging FDG-PET/CT in free breathing (FB) and a planning CT in both FB and DIBH. For each patient an involved-node radiotherapy plan was done for both DIBH and FB, and the doses to the lungs, heart, and female breasts were recorded prospectively. Mean doses to the heart valves and coronary arteries were recorded retrospectively. Patients were treated with the technique yielding the lowest doses to normal structures. Results: Nineteen patients were treated with DIBH and three with FB. DIBH reduced the mean estimated lung dose by 2.0 Gy (median: 8.5 Gy vs. 7.2 Gy) (p < 0.01) and the mean heart dose by 1.4 Gy (6.0 Gy vs. 3.9 Gy) (p < 0.01) compared to FB. The lung and heart V20Gy were reduced with a median of 5.3% and 6.3%. Mean doses to the female breasts were equal with FB and DIBH. Conclusion: DIBH can significantly decrease the estimated mean doses to the heart and lungs without lowering the dose to the target in radiotherapy for patients with mediastinal HL.
    Full-text · Article · Jul 2014 · Acta oncologica (Stockholm, Sweden)
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and purpose: To analyze the recurrence pattern in relation to target volumes and (18)F-fluorodeoxyglucose (FDG) uptake on positron emission tomography in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive chemoradiation. Material and methods: 520 patients received radiotherapy for HNSCC from 2005 to 2009. Among 100 patients achieving complete clinical response and a later recurrence, 39 patients with 48 loco-regional failures had a recurrence CT scan before any salvage therapy. The estimated point of origin of each recurrence was transferred to the planning CT by deformable image co-registration. The recurrence position was then related to the delineated target volumes and iso-SUV-contours relative to the maximum standard uptake value (SUV). We defined the recurrence density as the total number of recurrences in a sub-volume divided by the sum of that volume for all patients. Results: 54% (95% CI 37-69%) of recurrences originated inside the FDG-positive volume and 96% (95% CI 86-99%) in the high dose region. Recurrence density was significantly higher in the central target volumes (P<0.0001) and increased with increasing FDG avidity (P=0.036). Conclusions: The detailed pattern-of-failure data analysis suggests that most recurrences occur in the FDG PET positive areas or the solid tumor.
    No preview · Article · Jun 2014 · Radiotherapy and Oncology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Radiation therapy (RT) is the most effective single modality for local control of non-Hodgkin lymphoma (NHL) and is an important component of therapy for many patients. Many of the historic concepts of dose and volume have recently been challenged by the advent of modern imaging and RT planning tools. The International Lymphoma Radiation Oncology Group (ILROG) has developed these guidelines after multinational meetings and analysis of available evidence. The guidelines represent an agreed consensus view of the ILROG steering committee on the use of RT in NHL in the modern era. The roles of reduced volume and reduced doses are addressed, integrating modern imaging with 3-dimensional planning and advanced techniques of RT delivery. In the modern era, in which combined-modality treatment with systemic therapy is appropriate, the previously applied extended-field and involved-field RT techniques that targeted nodal regions have now been replaced by limiting the RT to smaller volumes based solely on detectable nodal involvement at presentation. A new concept, involved-site RT, defines the clinical target volume. For indolent NHL, often treated with RT alone, larger fields should be considered. Newer treatment techniques, including intensity modulated RT, breath holding, image guided RT, and 4-dimensional imaging, should be implemented, and their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control.
    Preview · Article · May 2014 · International journal of radiation oncology, biology, physics
  • [Show abstract] [Hide abstract]
    ABSTRACT: The use of radiotherapy (RT) is debated for pediatric patients with Hodgkin lymphoma (HL) due to the late effects of treatment. Radiation doses to the thyroid, heart, lungs, and breasts are compared with the extensive mantle field (MF), Involved Field RT(IFRT), Modified IFRT (mIFRT), and Involved Node RT (INRT) and the risk of radiation-induced cardiovascular disease, secondary cancers, and the corresponding Life Years Lost (LYL) is estimated with each technique. INRT, mIFRT, IFRT, and MF plans (20 and 30 Gy) were simulated for 10 supradiaphragmatic, clinical stage I–II classical HL patients <18 years old, total of 4 x 2 plans for each patient. The lifetime excess risks of cardiac morbidity, cardiac mortality, lung, breast, and thyroid cancer with each technique were estimated. The estimated excess risks attributable to RT were based on HL series with long-term follow-up, treating death from other causes as competing risks. The corresponding LYL were derived from the estimated excess risks. Statistical analyses were performed with repeated measures ANOVA. Both a reduction in field size and in prescribed radiation dose significantly lowered the estimated dose to the heart, lungs, breasts, and thyroid compared to past,extended fields, even for patients with mediastinal disease. This translated into a significantly reduced estimated risk of cardiovascular disease, secondary cancers, and LYL. Involved Node Radiotherapy should be considered for pediatric patients with Hodgkin lymphoma since it is estimated to substantially lower the risk of severe long-term complications.
    No preview · Article · Apr 2014 · Pediatric Blood & Cancer
  • Liselotte Højgaard · Anne Kiil Berthelsen · Annika Loft
    [Show abstract] [Hide abstract]
    ABSTRACT: Positron emission tomography (PET)/computed tomography with FDG of the head and neck region is mainly used for the diagnosis of head and neck cancer, for staging, treatment evaluation, relapse, and planning of surgery and radio therapy. This article is a practical guide of imaging techniques, including a detailed protocol for FDG PET in head and neck imaging, physiologic findings, and pitfalls in selected case stories.
    No preview · Article · Apr 2014 · PET Clinics
  • Annika Loft · Anne Kiil Berthelsen
    [Show abstract] [Hide abstract]
    ABSTRACT: Approximately 50% of cancer patients are estimated to receive radiation therapy as part of their total treatment regimen. External-beam treatment methods most commonly used at the Department of Radiation Oncology at Copenhagen University Hospital include 3D conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), intensity-modulated arc therapy (IMAT), and stereotactic radiation therapy (SRT). Radiation therapy can either cure patients of malignant disease or palliate symptoms caused by malignant disease. Radiation therapy is an inexpensive treatment method compared with, for example, surgery, chemotherapy, and immunotherapy [1]. One of the most pronounced disadvantages of radiation therapy is the acute side effects in normal tissue, e.g., mucous membranes occurring during and after the treatment. Correctly identifying and including all tumor cells in the target volume and avoiding as much normal tissue as possible is the challenge of curative radiation therapy, especially when the new treatment methods, such as 3D-CRT, IMRT, IMAT, and SRT, are used.
    No preview · Chapter · Jan 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and purpose To analyze the recurrence pattern in relation to target volumes and 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive chemoradiation. Material and methods 520 patients received radiotherapy for HNSCC from 2005 to 2009. Among 100 patients achieving complete clinical response and a later recurrence, 39 patients with 48 loco-regional failures had a recurrence CT scan before any salvage therapy. The estimated point of origin of each recurrence was transferred to the planning CT by deformable image co-registration. The recurrence position was then related to the delineated target volumes and iso-SUV-contours relative to the maximum standard uptake value (SUV). We defined the recurrence density as the total number of recurrences in a sub-volume divided by the sum of that volume for all patients. Results 54% (95% CI 37–69%) of recurrences originated inside the FDG-positive volume and 96% (95% CI 86–99%) in the high dose region. Recurrence density was significantly higher in the central target volumes (P < 0.0001) and increased with increasing FDG avidity (P = 0.036). Conclusions The detailed pattern-of-failure data analysis suggests that most recurrences occur in the FDG PET positive areas or the solid tumor.
    No preview · Article · Jan 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Optimal management of colon cancer (CC) requires detailed assessment of extent of disease. This study prospectively investigates the diagnostic accuracy of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (PET/CT) for staging and detection of recurrence in primary CC. Material and methods PET/CT for preoperative staging was performed in 66 prospectively included patients with primary CC. Diagnostic accuracy for PET/CT and CT was analyzed. In addition to routine follow up, 42 stages I–III CC patients had postoperative PET/CT examinations every 6 months for 2 years. Serological levels of tissue inhibitor of metalloproteinase-1 (TIMP-1), carcinoembryonic antigen, and liberated domain I of urokinase plasminogen activator receptor were analyzed. Results Accuracy for tumor, nodal, and metastases staging by PET/CT were 82% (95% confidence interval [CI]: 70; 91), 66% (CI: 51; 78), and 89% (CI: 79; 96); for CT the accuracy was 77% (CI: 64; 87), 60% (CI: 46; 73), and 69% (CI: 57; 80). Cumulative relapse incidences for stages I–III CC at 6, 12, 18, and 24 months were 7.1% (CI: 0; 15); 14.3% (CI: 4; 25); 19% (CI: 7; 31), and 21.4% (CI: 9; 34). PET/CT diagnosed all relapses detected during the first 2 years. High preoperative TIMP-1 levels were associated with significant hazards toward risk of recurrence and shorter overall survival. Conclusions This study indicates PET/CT as a valuable tool for staging and follow up in CC. TIMP-1 provided prognostic information potentially useful in selection of patients for intensive follow up.
    Full-text · Article · Nov 2013 · Scandinavian Journal of Gastroenterology

  • No preview · Article · Oct 2013 · International Journal of Radiation OncologyBiologyPhysics

  • No preview · Article · Oct 2013 · International Journal of Radiation OncologyBiologyPhysics
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: To demonstrate a data-driven dose-painting strategy based on the spatial distribution of recurrences in previously treated patients. The result is a quantitative way to define a dose prescription function, optimizing the predicted local control at constant treatment intensity. A dose planning study using the optimized dose prescription in 20 patients is performed. Methods: Patients treated at our center have five tumor subvolumes from the center of the tumor (PET positive volume) and out delineated. The spatial distribution of 48 failures in patients with complete clinical response after (chemo)radiation is used to derive a model for tumor control probability (TCP). The total TCP is fixed to the clinically observed 70% actuarial TCP at five years. Additionally, the authors match the distribution of failures between the five subvolumes to the observed distribution. The steepness of the dose-response is extracted from the literature and the authors assume 30% and 20% risk of subclinical involvement in the elective volumes. The result is a five-compartment dose response model matching the observed distribution of failures. The model is used to optimize the distribution of dose in individual patients, while keeping the treatment intensity constant and the maximum prescribed dose below 85 Gy. Results: The vast majority of failures occur centrally despite the small volumes of the central regions. Thus, optimizing the dose prescription yields higher doses to the central target volumes and lower doses to the elective volumes. The dose planning study shows that the modified prescription is clinically feasible. The optimized TCP is 89% (range: 82%-91%) as compared to the observed TCP of 70%. Conclusions: The observed distribution of locoregional failures was used to derive an objective, data-driven dose prescription function. The optimized dose is predicted to result in a substantial increase in local control without increasing the predicted risk of toxicity.
    No preview · Article · Aug 2013 · Medical Physics

Publication Stats

2k Citations
310.61 Total Impact Points

Institutions

  • 2008-2015
    • IT University of Copenhagen
      København, Capital Region, Denmark
    • National University (California)
      San Diego, California, United States
  • 2011-2014
    • Rigshospitalet
      • • Department of Oncology
      • • Department of Radiation Biology
      København, Capital Region, Denmark
  • 2013
    • Fox Chase Cancer Center
      Filadelfia, Pennsylvania, United States
    • København Zoo
      København, Capital Region, Denmark
  • 2005-2013
    • Copenhagen University Hospital
      København, Capital Region, Denmark
  • 2012
    • Sahlgrenska University Hospital
      Goeteborg, Västra Götaland, Sweden
  • 1997-2006
    • Aarhus University Hospital
      • Department of Experimental Clinical Oncology (ECO)
      Aarhus, Central Jutland, Denmark
  • 1991
    • Herlev Hospital
      Herlev, Capital Region, Denmark