Anne Kiil Berthelsen

IT University of Copenhagen, København, Capital Region, Denmark

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Publications (77)290.76 Total impact

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    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.
    Journal of Nuclear Medicine 05/2015; 56(6):847-854. DOI:10.2967/jnumed.115.156539 · 5.56 Impact Factor
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    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.
    International journal of radiation oncology, biology, physics 03/2015; 92(1). DOI:10.1016/j.ijrobp.2015.01.013 · 4.18 Impact Factor
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    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.
    Acta oncologica (Stockholm, Sweden) 07/2014; DOI:10.3109/0284186X.2014.932435 · 3.71 Impact Factor
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    ABSTRACT: 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.
    Radiotherapy and Oncology 06/2014; 111(3). DOI:10.1016/j.radonc.2014.06.001 · 4.86 Impact Factor
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    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.
    International journal of radiation oncology, biology, physics 05/2014; 89(1):49–58. DOI:10.1016/j.ijrobp.2014.01.006 · 4.18 Impact Factor
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    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.
    Pediatric Blood & Cancer 04/2014; 61(4):717-22. DOI:10.1002/pbc.24861 · 2.56 Impact Factor
  • Liselotte Højgaard, Anne Kiil Berthelsen, Annika Loft
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    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.
    PET Clinics 01/2014; 9(2):141–145. DOI:10.1016/j.cpet.2013.11.002
  • Annika Loft, Anne Kiil Berthelsen
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    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.
    Diseases of the Abdomen and Pelvis 2014–2017, 01/2014: pages 254-256; , ISBN: 978-88-470-5658-9
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    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.
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    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.
    Scandinavian Journal of Gastroenterology 11/2013; 49(2). DOI:10.3109/00365521.2013.863967 · 2.33 Impact Factor
  • International Journal of Radiation OncologyBiologyPhysics 10/2013; 87(2):S599-S600. DOI:10.1016/j.ijrobp.2013.06.1587 · 4.18 Impact Factor
  • International Journal of Radiation OncologyBiologyPhysics 10/2013; 87(2):S62. DOI:10.1016/j.ijrobp.2013.06.162 · 4.18 Impact Factor
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    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.
    Medical Physics 08/2013; 40(8):081717. DOI:10.1118/1.4816308 · 3.01 Impact Factor
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    ABSTRACT: Radiation therapy (RT) is the most effective single modality for local control of Hodgkin lymphoma (HL) and an important component of therapy for many patients. These guidelines have been developed to address the use of RT in HL in the modern era of combined modality treatment. The role of reduced volumes and doses is addressed, integrating modern imaging with 3-dimensional (3D) planning and advanced techniques of treatment delivery. The previously applied extended field (EF) and original involved field (IF) techniques, which treated larger volumes based on nodal stations, have now been replaced by the use of limited volumes, based solely on detectable nodal (and extranodal extension) involvement at presentation, using contrast-enhanced computed tomography, positron emission tomography/computed tomography, magnetic resonance imaging, or a combination of these techniques. The International Commission on Radiation Units and Measurements concepts of gross tumor volume, clinical target volume, internal target volume, and planning target volume are used for defining the targeted volumes. Newer treatment techniques, including intensity modulated radiation therapy, breath-hold, image guided radiation therapy, and 4-dimensional imaging, should be implemented when their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control. The highly conformal involved node radiation therapy (INRT), recently introduced for patients for whom optimal imaging is available, is explained. A new concept, involved site radiation therapy (ISRT), is introduced as the standard conformal therapy for the scenario, commonly encountered, wherein optimal imaging is not available. There is increasing evidence that RT doses used in the past are higher than necessary for disease control in this era of combined modality therapy. The use of INRT and of lower doses in early-stage HL is supported by available data. Although the use of ISRT has not yet been validated in a formal study, it is more conservative than INRT, accounting for suboptimal information and appropriately designed for safe local disease control. The goal of modern smaller field radiation therapy is to reduce both treatment volume and treatment dose while maintaining efficacy and minimizing acute and late sequelae. This review is a consensus of the International Lymphoma Radiation Oncology Group (ILROG) Steering Committee regarding the modern approach to RT in the treatment of HL, outlining a new concept of ISRT in which reduced treatment volumes are planned for the effective control of involved sites of HL. Nodal and extranodal non-Hodgkin lymphomas (NHL) are covered separately by ILROG guidelines.
    International journal of radiation oncology, biology, physics 06/2013; 89(4). DOI:10.1016/j.ijrobp.2013.05.005 · 4.18 Impact Factor
  • 04/2013; 3(2 Suppl 1):S10. DOI:10.1016/j.prro.2013.01.034
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    ABSTRACT: OBJECTIVE: To evaluate SUVmax in the assessment of endometrial cancer preoperatively with particular focus on myometrial invasion (MI), cervical invasion (CI), FIGO stage, risk-stratification and lymph node metastases (LNM). METHODS: A total of 268 women with endometrial cancer or atypical endometrial hyperplasia underwent FDG PET/CT imaging before surgical treatment. SUVmax of the primary tumour was compared with histological prognostic factors. RESULTS: SUVmax was significantly higher in patients with high FIGO stages (p<0.0001), deep MI (p=0.002), CI (p=0.04), LNM (p=0.04) and high risk tumours (p=0.003). Linear regression found that SUVmax was dependent of MI (p=0.001, 95%CI 2.863-11.098), CI (p=0.001, 95%CI 2.896-11.499), risk (p=0.004, 95%CI 0.077-0.397), LNM (p=0.04, 95%CI 0.011-0.482) and FIGO stage (p<0.0001, 95%CI 0.158-0.473). CONCLUSIONS: Preoperative PET/CT scanning and SUVmax measurements of the primary tumour may provide additional clinical and prognostic information about MI, CI, LNM and high risk disease in patients with endometrial cancer and allow for individualization of patient care. However, the sensitivity and specificity of the SUVmax in staging endometrial cancer is not high enough to reliably replace surgical staging.
    Gynecologic Oncology 01/2013; 129(2). DOI:10.1016/j.ygyno.2013.01.019 · 3.69 Impact Factor
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    ABSTRACT: Combined PET/MRI systems are now commercially available and are expected to change the medical imaging field by providing combined anato-metabolic image information. We believe this will be of particular relevance in imaging of cancer patients. At the Department of Clinical Physiology, Nuclear Medicine & PET at Rigshospitalet in Copenhagen we installed an integrated PET/MRI in December 2011. Here, we describe our first clinical PET/MR cases and discuss some of the areas within oncology where we envision promising future application of integrated PET/MR imaging in clinical routine. Cases described include brain tumors, pediatric oncology as well as lung, abdominal and pelvic cancer. In general the cases show that PET/MRI performs well in all these types of cancer when compared to PET/CT. However, future large-scale clinical studies are needed to establish when to use PET/MRI. We envision that PET/MRI in oncology will prove to become a valuable addition to PET/CT in diagnosing, tailoring and monitoring cancer therapy in selected patient populations.
    MAGMA Magnetic Resonance Materials in Physics Biology and Medicine 12/2012; DOI:10.1007/s10334-012-0357-0 · 2.87 Impact Factor
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    ABSTRACT: OBJECTIVES: The aim of this prospective multicenter study was to evaluate and compare the diagnostic performance of PET/CT, MRI and transvaginal two-dimensional ultrasound (2DUS) in the preoperative assessment of endometrial cancer (EC). METHODS: 318 consecutive women with EC were included when referred to three Danish tertiary gynecological centers for surgical treatment. Preoperatively they were PET/CT-, MRI-, and 2DUS scanned. The imaging results were compared to the final pathological findings. This study was approved by the National Committee on Health Research Ethics. RESULTS: For predicting myometrial invasion, we found sensitivity, specificity, PPV, NPV, and accuracy for PET/CT to be 93%, 49%, 41%, 95% and 61%, for MRI to be 87%, 57%, 44%, 92%, and 66% and for 2DUS they were 71%, 72%, 51%, 86% and 72%. For predicting cervical invasion the values were 43%, 94%, 69%, 85% and 83%, respectively, for PET/CT, 33%, 95%, 60%, 85%, and 82%, respectively, for MRI, and 29%, 92%, 48%, 82% and 78% for 2DUS. Finally, for lymph node metastases 74%, 93%, 59%, 96%, and 91% for PET/CT and 59%, 93%, 40%, 97% and 90% for MRI. When comparing the diagnostic performance we found PET/CT, MRI and 2DUS to be comparable in predicting myometrial invasion. For cervical invasion and lymph node metastases, however, PET/CT was best. CONCLUSIONS: None of the modalities can yet replace surgical staging. However, they all contributed to important knowledge and were, furthermore, able to upstage low-risk patients who would not have been recommended lymph node resection based on histology and grade alone.
    Gynecologic Oncology 11/2012; DOI:10.1016/j.ygyno.2012.11.025 · 3.69 Impact Factor
  • International Journal of Radiation OncologyBiologyPhysics 11/2012; 84(3):S71-S72. DOI:10.1016/j.ijrobp.2012.07.291 · 4.18 Impact Factor
  • International Journal of Radiation OncologyBiologyPhysics 11/2012; 84(3):S642-S643. DOI:10.1016/j.ijrobp.2012.07.1715 · 4.18 Impact Factor

Publication Stats

2k Citations
290.76 Total Impact Points


  • 2010–2015
    • IT University of Copenhagen
      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
  • 2011
    • Rigshospitalet
      • Department of Radiation Biology
      København, Capital Region, Denmark
  • 2008
    • National University (California)
      San Diego, California, United States
  • 1997
    • Aarhus University Hospital
      • Department of Experimental Clinical Oncology (ECO)
      Aarhus, Central Jutland, Denmark
  • 1991
    • Herlev Hospital
      Herlev, Capital Region, Denmark