| 1. |
- Toma-Dasu, Iuliana, et al.
(author)
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RBE for proton radiation therapy – a Nordic view in the international perspective
- 2020
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 59:10, s. 1151-1156
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Journal article (peer-reviewed)abstract
- Background: This paper presents an insight into the critical discussions and the current strategies of the Nordic countries for handling the variable proton relative biological effectiveness (RBE) as presented at The Nordic Collaborative Workshop for Particle Therapy that took place at the Skandion Clinic on 14th and 15th of November 2019.Material and methods: In the current clinical practice at the two proton centres in operation at the date, Skandion Clinic, and the Danish Centre for Particle Therapy, a constant proton RBE of 1.1 is applied. The potentially increased effectiveness at the end of the particle range is however considered at the stage of treatment planning at both places based on empirical observations and knowledge. More elaborated strategies to evaluate the plans and mitigate the problem are intensely investigated internationally as well at the two centres. They involve the calculation of the dose-averaged linear energy transfer (LETd) values and the assessment of their distributions corroborated with the distribution of the dose and the location of the critical clinical structures.Results: Methods and tools for LETd calculations are under different stages of development as well as models to account for the variation of the RBE with LETd, dose per fraction, and type of tissue. The way they are currently used for evaluation and optimisation of the plans and their robustness are summarised. A critical but not exhaustive discussion of their potential future implementation in the clinical practice is also presented.Conclusions: The need for collaboration between the clinical proton centres in establishing common platforms and perspectives for treatment planning evaluation and optimisation is highlighted as well as the need of close interaction with the research academic groups that could offer a complementary perspective and actively help developing methods and tools for clinical implementation of the more complex metrics for considering the variable effectiveness of the proton beams.
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| 2. |
- Bolsi, Alessandra, et al.
(author)
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Practice patterns of image guided particle therapy in Europe : A 2016 survey of the European Particle Therapy Network (EPTN)
- 2018
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In: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 128:1, s. 4-8
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Journal article (peer-reviewed)abstract
- Background and purpose: Image guidance is critical in achieving accurate and precise radiation delivery in particle therapy, even more than in photon therapy. However, equipment, quality assurance procedures and clinical workflows for image-guided particle therapy (IGPT) may vary substantially between centres due to a lack of standardization. A survey was conducted to evaluate the current practice of IGPT in European particle therapy centres.Material and methods: In 2016, a questionnaire was distributed among 19 particle therapy centres in 12 European countries. The questionnaire consisted of 30 open and 37 closed questions related to image guidance in the general clinical workflow, for moving targets, current research activities and future perspectives of IGPT.Results: All centres completed the questionnaire. The IGPT methods used by the 10 treating centres varied substantially. The 9 non-treating centres were in the process to introduce IGPT. Most centres have developed their own IGPT strategies, being tightly connected to their specific technical implementation and dose delivery methods.Conclusions: Insight into the current clinical practice of IGPT in European particle therapy centres was obtained. A variety in IGPT practices and procedures was confirmed, which underlines the need for harmonisation of practice parameters and consensus guidelines.
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| 3. |
- Byskov, Camilla S., et al.
(author)
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Treatment plan comparison of proton vs photon radiotherapy for lower-grade gliomas
- 2021
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In: Physics and Imaging in Radiation Oncology. - : Elsevier. - 2405-6316. ; 20, s. 98-104
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Journal article (peer-reviewed)abstract
- Background and purpose: Patients with lower-grade gliomas are long-term survivors after radiotherapy and may benefit from the reduced dose to normal tissue achievable with proton therapy. Here, we aimed to quantify differences in dose to the uninvolved brain and contralateral hippocampus and compare the risk of radiation-induced secondary cancer for photon and proton plans for lower-grade glioma patients. Materials and methods: Twenty-three patients were included in this in-silico planning comparative study and had photon and proton plans calculated (50.4 Gy(RBE = 1.1), 28 Fx) applying similar dose constraints to the target and organs at risk. Automatically calculated photon plans were generated with a 3 mm margin from clinical target volume (CTV) to planning target volume. Manual proton plans were generated using robust optimisation on the CTV. Dose metrics of organs at risk were compared using population mean dose-volume histograms and Wilcoxon signed-rank test. Secondary cancer risk per 10,000 persons per year (PPY) was estimated using dose-volume data and a risk model for secondary cancer induction. Results: CTV coverage (V95%>98%) was similar for the two treatment modalities. Mean dose (D-mean) to the uninvolved brain was significantly reduced from 21.5 Gy (median, IQR 17.1-24.4 Gy) with photons compared to 10.3 Gy(RBE) (8.1-13.9 Gy(RBE)) with protons. D-mean to the contralateral hippocampus was significantly reduced from 6.5 Gy (5.4-11.7 Gy) with photons to 1.5 Gy(RBE) (0.4-6.8 Gy(RBE)) with protons. The estimated secondary cancer risk was reduced from 6.7 PPY (median, range 3.3-10.4 PPY) with photons to 3.0 PPY (1.3-7.5 PPY) with protons. Conclusion: A significant reduction in mean dose to uninvolved brain and contralateral hippocampus was found with proton planning. The estimated secondary cancer risk was reduced with proton therapy.
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| 4. |
- Dasu, Alexandru, et al.
(author)
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Normal tissue sparing potential of scanned proton beams with and without respiratory gating for the treatment of internal mammary nodes in breast cancer radiotherapy
- 2018
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In: Physica medica (Testo stampato). - : Elsevier BV. - 1120-1797 .- 1724-191X. ; 52, s. 81-85
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Journal article (peer-reviewed)abstract
- Proton therapy has shown potential for reducing doses to normal tissues in breast cancer radiotherapy. However data on the impact of protons when including internal mammary nodes (IMN) in the target for breast radiotherapy is comparatively scarce. This study aimed to evaluate normal tissue doses when including the IMN in regional RT with scanned proton beams, with and without respiratory gating. The study cohort was composed of ten left-sided breast patients CT-scanned during enhanced inspiration gating (EIG) and free-breathing (FB). Proton plans were designed for the target including or excluding the IMN. Targets and organs-at-risk were delineated according to RTOG guidelines. Comparison was performed between dosimetric parameters characterizing target coverage and OAR radiation burden. Statistical significance of differences was tested using a paired, two-tailed Student's t-test. Inclusion of the IMN in the target volume led to a small increase of the cardiopulmonary burden. The largest differences were seen for the ipsilateral lung where the mean dose increased from 6.1 to 6.6 Gy (RBE) (P < 0.0001) in FB plans and from 6.9 to 7.4 Gy (RBE) (P = 0.003) in EIG plans. Target coverage parameters were very little affected by the inclusion of IMN into the treatment target. Radiotherapy with scanned proton beams has the potential of maintaining low cardiovascular burden when including the IMN into the target, irrespective of whether respiratory gating is used or not.
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| 5. |
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| 6. |
- Eekers, Danielle B. P., et al.
(author)
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The EPTN consensus-based atlas for CT- and MR-based contouring in neuro-oncology
- 2018
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In: Radiotherapy and Oncology. - : ELSEVIER IRELAND LTD. - 0167-8140 .- 1879-0887. ; 128:1, s. 37-43
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Journal article (peer-reviewed)abstract
- Purpose: To create a digital, online atlas for organs at risk (OAR) delineation in neuro-oncology based on high-quality computed tomography (Cr) and magnetic resonance (MR) imaging. Methods: CT and 3 Tesla (3T) MR images (slice thickness 1 mm with intravenous contrast agent) were obtained from the same patient and subsequently fused. In addition, a 7T MR without intravenous contrast agent was obtained from a healthy volunteer. Based on discussion between experienced radiation oncologists, the clinically relevant organs at risk (OARs) to be included in the atlas for neuro-oncology were determined, excluding typical head and neck OARs previously published. The draft atlas was delineated by a senior radiation oncologist, 2 residents in radiation oncology, and a senior neuro-radiologist incorporating relevant available literature. The proposed atlas was then critically reviewed and discussed by European radiation oncologists until consensus was reached. Results: The online atlas includes one CT-scan at two different window settings and one MR scan (3T) showing the OARs in axial, coronal and sagittal view. This manuscript presents the three-dimensional descriptions of the fifteen consensus OARs for neuro-oncology. Among these is a new OAR relevant for neuro-cognition, the posterior cerebellum (illustrated on 7T MR images). Conclusion: In order to decrease inter- and intra-observer variability in delineating OARs relevant for neuro-oncology and thus derive consistent dosimetric data, we propose this atlas to be used in photon and particle therapy. The atlas is available online at w.cancerdata.c and will be updated whenever required.
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| 7. |
- Flejmer, Anna M., et al.
(author)
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Potential benefit of scanned proton beam versus photons as adjuvant radiation therapy in breast cancer
- 2015
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In: International Journal of Particle Therapy. - 2331-5180. ; 1:4, s. 845-855
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Journal article (peer-reviewed)abstract
- Purpose: To investigate the feasibility of using scanned proton beams as adjuvant radiation therapy for breast cancer. Long-term cardiopulmonary complications may worsen the quality of life and reduce the positive contribution of radiation therapy, which has been known to improve long-term control of locoregional disease as well as the long-term survival for these patients.Materials and Methods: Ten patients with stage I-III cancer (either after mastectomy or lumpectomy, left- or right-sided) were included in the study. The patients were identified from a larger group where dose heterogeneity in the target and/or hotspots in the normal tissues qualified them for irregular surface compensator planning with photons. The patients underwent planning with 2 scanned proton beam planning techniques, single-field uniform dose and intensity-modulated proton therapy, and the results were compared with those from irregular surface compensator. All volumes of interest were delineated and reviewed by experienced radio-oncologists. The patients were prescribed 50 GyRBE in 25 fractions. Dosimetric parameters of interest were compared with a paired, 2-tailed Student t test.Results: The proton plans showed comparable or better target coverage than the original photon plans. There were also large reductions with protons in mean doses to the heart (0.2 versus 1.3 GyRBE), left anterior descending artery (1.4 versus 6.4 GyRBE), and the ipsilateral lung (6.3 versus 7.7 GyRBE). This reduction is important from the point of view of the quality of life of the patients after radiation therapy. No significant differences were found between single-field uniform dose and intensity-modulated proton therapy plans.Conclusion: Spot scanning technique with protons may improve target dose homogeneity and further reduce doses to the organs at risk compared with advanced photon techniques. The results from this study indicate a potential for protons as adjuvant radiation therapy in breast cancer and a further step toward the individualization of treatment based on anatomic and comorbidity characteristics.
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| 8. |
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| 9. |
- Flejmer, Anna M., et al.
(author)
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Respiratory gating for proton beam scanning versus photon 3D-CRT for breast cancer radiotherapy
- 2016
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 55:5, s. 577-583
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Journal article (peer-reviewed)abstract
- Background Respiratory gating and proton therapy have both been proposed to reduce the cardiopulmonary burden in breast cancer radiotherapy. This study aims to investigate the additional benefit of proton radiotherapy for breast cancer with and without respiratory gating.Material and methods Twenty left-sided patients were planned on computed tomography (CT)-datasets acquired during enhanced inspiration gating (EIG) and free-breathing (FB), using photon three-dimensional conformal radiation therapy (3D-CRT) and scanned proton beams. Ten patients received treatment to the whole breast only (WBO) and 10 were treated to the breast and the regional lymph nodes (BRN). Dosimetric parameters characterizing the coverage of target volumes and the cardiopulmonary burden were compared using a paired, two-tailed Student’s t-test.Results Protons ensured comparable or better target coverage than photons in all patients during both EIG and FB. The heterogeneity index decreased from 12% with photons to about 5% with protons. The mean dose to the ipsilateral lung was reduced in BRN patients from 12 Gy to 7 Gy (RBE) in EIG and from 14 Gy to 6-7 Gy (RBE) in FB, while for WBO patients all values were about 5-6 Gy (RBE). The mean dose to heart decreased by a factor of four in WBO patients [from 1.1 Gy to 0.3 Gy (RBE) in EIG and from 2.1 Gy to 0.5 Gy (RBE) in FB] and 10 in BRN patients [from 2.1 Gy to 0.2 Gy (RBE) in EIG and from 3.4 Gy to 0.3 Gy (RBE) in FB]. Similarly, the mean and the near maximum dose to left anterior descending artery (LAD) were significantly lower (p<0.05) with protons in comparison with photons.Conclusion Proton spot scanning has a high potential to reduce the irradiation of organs at risk and other normal tissues for most patients, beyond what could be achieved with EIG and photon therapy. The largest dose sparing has been seen for BRN patients, both in terms of cardiopulmonary burden and integral dose.
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| 10. |
- Fuglsang Jensen, Maria, et al.
(author)
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Proton therapy for early breast cancer patients in the DBCG proton trial : planning, adaptation, and clinical experience from the first 43 patients
- 2022
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In: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 61:2, s. 223-230
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Journal article (peer-reviewed)abstract
- BackgroundThe Danish Breast Cancer Group (DBCG) Proton Trial randomizes breast cancer patients selected on high mean heart dose (MHD) or high lung dose (V20Gy/V17Gy) in the photon plan between photon and proton therapy. This study presents the proton plans and adaptation strategy for the first 43 breast cancer patients treated with protons in Denmark.Material and methodsForty-four proton plans (one patient with bilateral cancer) were included; 2 local and 42 loco-regional including internal mammary nodes (IMN). Nineteen patients had a mastectomy and 25 a lumpectomy. The prescribed dose was either 50 Gy in 25 fractions (n = 30) or 40 Gy in 15 fractions (n = 14) wherefrom five received simultaneous integrated boost to the tumor bed. Using 2-3 en face proton fields, single-field optimization, robust optimization and a 5 cm range shifter ensured robustness towards breathing motion, setup- and range uncertainties. An anatomical evaluation was performed by evaluating the dose after adding/removing 3 mm and 5 mm tissue to/from the body-outline and used to define treatment tolerances for anatomical changes.ResultsThe nominal and robust criteria were met for all patients except two. The median MHD was 1.5 Gy (0.5–3.4 Gy, 50 Gy) and 1.1 Gy (0.0–1.5 Gy, 40 Gy). The anatomical evaluations showed how 5 mm shrinkage approximately doubled the MHD while 5 mm swelling reduced target coverage of the IMN below constraints. Ensuring 3–5 mm robustness toward swelling was prioritized but not always achieved by robust optimization alone emphasizing the need for a distal margin. Twenty-eight patients received plan adaptation, eight patients received two, and one received five.ConclusionThis proton planning strategy ensured robust treatment plans within a pre-defined level of acceptable anatomical changes that fulfilled the planning criteria for most of the patients and ensured low MHD.
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| 11. |
- Langegård, Ulrica, 1969, et al.
(author)
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The Art of Living With Symptoms : A Qualitative Study Among Patients With Primary Brain Tumors Receiving Proton Beam Therapy
- 2020
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In: Cancer Nursing. - Philadelphia : LIPPINCOTT WILLIAMS & WILKINS. - 0162-220X .- 1538-9804. ; 43:2, s. E79-E86
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Journal article (peer-reviewed)abstract
- Background: Symptom management in conjunction with proton beam therapy (PBT) from patient's perspective has not been explored. Such knowledge is essential to optimize the care in this relatively new treatment modality.Objective: The aim of this study was to explore the process of symptom management in patients with brain tumor receiving PBT.Methods: Participants were 22 patients with primary brain tumor who received PBT, recruited in collaboration with a national center for proton therapy and 2 oncology clinics at 2 university hospitals in Sweden. Interviews using open-ended questions were conducted before, during, and/or after treatment. Verbatim interview transcripts were analyzed using classic Grounded Theory.Results: "The art of living with symptoms" emerged as the core concept. This encompassed 3 interconnected symptom management concepts: "Adapting to limited ability," "Learning about oneself," and "Creating new routines." These concepts were summarized in a substantive theoretical model of symptom management. Despite the struggle to manage symptoms, participants lived a satisfactory life.Conclusions: Symptom management in conjunction with PBT comprises a process of action, thoughts, and emotions. The concepts that emerged indicated patients' symptom management strategies were based on their own resources.Implications for Practice: It is important that PBT facilities develop an approach that facilitates the symptom management process based on patients' experiences of symptoms, as well as their actions and available resources.
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| 12. |
- Lo Mauro, Antonella, et al.
(author)
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Comparison of different methods for lung immobilization in an animal model
- 2020
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In: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 150, s. 151-158
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: Respiratory-induced motion introduces uncertainties in the delivery of dose in radiotherapy treatments. Various methods are used clinically, e.g. breath-holding, while there is limited experience with other methods such as apneic oxygenation and high frequency jet ventilation (HFJV). This study aims to compare the latter approaches for lung immobilization and their clinical impact on gas exchange in an animal model.MATERIALS AND METHODS: Two radiopaque tumor surrogate markers (TSM) were placed in the central (cTSM) and peripheral (dTSM) regions of the lungs in 9 anesthetized and muscle relaxed pigs undergoing 3 ventilatory interventions (1) HFJV at rates of 200 (JV200), 300 (JV300) and 400 (JV400) min-1; (2) apnea at continuous positive airway pressure (CPAP) levels of 0, 8 and 16 cmH2O; (3) conventional mechanical ventilation (CMV) as reference mode. cTSM and dTSM were visualized using fluoroscopy and their coordinates were computed. The ventilatory pattern was registered, and oxygen and carbon dioxide (pCO2) partial pressures were measured.RESULTS: The highest range of TSM motion, and ventilation was found during CMV, the lowest during apnea. During HFJV the amount of motion varied inversely with increasing frequency. The reduction of TSM motion at JV300, JV400 and all CPAP levels came at the cost of increased pCO2, however the relatively low frequency of 200 min-1 for HFJV was the only ventilatory setting that enabled adequate CO2 removal.CONCLUSION: In this model, HFJV at 200 min-1 was the best compromise between immobilization and gas exchange for sessions of 10-min duration.
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| 13. |
- Martinsson, Ulla, et al.
(author)
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Complications after proton radiotherapy in children, focusing on severe late complications. A complete Swedish cohort 2008-2019
- 2023
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In: ACTA ONCOLOGICA. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 62:10, s. 1348-1356
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Journal article (peer-reviewed)abstract
- Background: Proton radiotherapy (RT) is an attractive tool to deliver local therapy with minimal dose to uninvolved tissue, however, not suitable for all patients. The aim was to explore complications, especially severe late complications (grades 3-4), following proton RT delivered to a complete Swedish cohort of paediatric patients aged <18 years treated 2008-2019.Material and Methods: Data was downloaded from a national registry. Complications with a possible causation with RT are reported. Proton treatments until July 2015 was performed with a fixed horizontal 172 MeV beam (The Svedberg Laboratory (TSL), Uppsala) in a sitting position and thereafter with gantry-based pencil-beam scanning technique (Skandion Clinic, Uppsala) in a supine position.Results: 219 courses of proton RT (77 at TSL and 142 at Skandion) were delivered to 212 patients (mean age 9.2 years) with various tumour types (CNS tumours 58%, sarcomas 26%, germ cell tumours 7%). Twenty-five patients had severe acute complications (skin, mucous membrane, pharynx/oesophagus, larynx, upper gastrointestinal canal, lower gastrointestinal canal, eyes, ears). Fifteen patients had severe late complications; with increased proportion over time: 4% at 1-year follow-up (FU), 5% at 3-year, 11% at 5-year. Organs affected were skin (1 patient), subcutaneous tissue (4), salivary glands (1), upper GI (1), bone (7), joints (2), CNS (2), PNS (1), eyes (1) and ears (5). Twenty-one of the 28 patients with 10-year FU had at least one late complication grades 1-4 and fourteen of them had more than one (2-5 each).Conclusion: The most important result of our study is the relatively low proportion of severe late complications, comparable with other proton studies on various tumours. Furthermore, the numbers of late complications are lower than our own data set on a mixed population of photon and proton treated paediatric patients, assuring the safety of using proton therapy also in the clinical practice.
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| 14. |
- Möllerberg, Marie-Louise, et al.
(author)
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Evaluation of skin reactions during proton beam radiotherapy : patient-reported versus clinician-reporte
- 2021
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In: Technical innovations & patient support in radiation oncology. - : Elsevier. - 2405-6324. ; 19, s. 11-17
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Journal article (peer-reviewed)abstract
- Background: Skin reaction is a common side-effect of radiotherapy and often only assessed as clinician-reported outcome (CRO). The aim was to examine and compare patient-reported outcome (PRO) of skin reactions with CRO for signs of acute skin reactions for patients with primary brain tumour receiving proton beam radiotherapy (PBT). A further aim was to explore patients' experiences of the skin reactions.Methods: Acute skin reactions were assessed one week after start of treatment, mid-treatment and end of treatment among 253 patients with primary brain tumour who underwent PBT. PRO skin reactions were assessed with the RSAS and CRO according to the RTOG scale. Fleiss' kappa was performed to measure the inter-rater agreement of the assessments of skin reactions.Results: The results showed a discrepancy between PRO and CRO acute skin reactions. Radiation dose was associated with increased skin reactions, but no correlations were seen for age, gender, education, occupation, other treatment or smoking. There was a poor agreement between patients and clinicians (κ = -0.016) one week after the start of PBT, poor (κ = -0.045) to (κ = 0.396) moderate agreement at mid treatment and poor (κ = -0.010) to (κ = 0.296) moderate agreement at end of treatment. Generally, patients' symptom distress toward skin reactions was low at all time points.Conclusion: The poor agreement between PRO and CRO shows that the patient needs to be involved in assessments of skin reactions for a more complete understanding of skin reactions due to PBT. This may also improve patient experience regarding involvement in their own care.
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| 15. |
- Möllerberg, Marie-Louise, et al.
(author)
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Evaluation of skin reactions during proton beam radiotherapy – Patient-reported versus clinician-reported
- 2021
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In: Technical Innovations and Patient Support in Radiation Oncology. - : Elsevier Ireland Ltd. - 2405-6324. ; 19, s. 11-17
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Journal article (peer-reviewed)abstract
- Background: Skin reaction is a common side-effect of radiotherapy and often only assessed as clinician-reported outcome (CRO). The aim was to examine and compare patient-reported outcome (PRO) of skin reactions with CRO for signs of acute skin reactions for patients with primary brain tumour receiving proton beam radiotherapy (PBT). A further aim was to explore patients’ experiences of the skin reactions. Methods: Acute skin reactions were assessed one week after start of treatment, mid-treatment and end of treatment among 253 patients with primary brain tumour who underwent PBT. PRO skin reactions were assessed with the RSAS and CRO according to the RTOG scale. Fleiss’ kappa was performed to measure the inter-rater agreement of the assessments of skin reactions. Results: The results showed a discrepancy between PRO and CRO acute skin reactions. Radiation dose was associated with increased skin reactions, but no correlations were seen for age, gender, education, occupation, other treatment or smoking. There was a poor agreement between patients and clinicians (κ = −0.016) one week after the start of PBT, poor (κ = −0.045) to (κ = 0.396) moderate agreement at mid treatment and poor (κ = −0.010) to (κ = 0.296) moderate agreement at end of treatment. Generally, patients’ symptom distress toward skin reactions was low at all time points. Conclusion: The poor agreement between PRO and CRO shows that the patient needs to be involved in assessments of skin reactions for a more complete understanding of skin reactions due to PBT. This may also improve patient experience regarding involvement in their own care. © 2021 The Author(s)
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| 16. |
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| 17. |
- Nilsson, Greger, et al.
(author)
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Radiation dose distribution in coronary arteries in breast cancer radiotherapy
- 2016
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 55:8, s. 959-963
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Journal article (peer-reviewed)abstract
- Background: Women irradiated for left-sided breast cancer (BC) have an increased risk of coronary artery disease compared to women with right-sided BC. We describe the distribution of radiation dose in segments of coronary arteries in women receiving adjuvant radiotherapy (RT) for left- or right-sided BC.Material and methods: Fifteen women with BC, seven left-sided and eight right-sided, who had received three-dimensional conformal radiotherapy (3DCRT), constituted the study base. The heart and the segments of the coronary arteries were defined as separate organs at risk (OAR), and the mean and maximum radiation doses were calculated for each OAR.Results: In women with left-sided BC, irrespective of if regional lymph node RT was given or not, maximum dose in mid and distal left anterior descending artery (mdLAD) was approximately 50Gy in 6/7 patients, whereas women with right-sided BC mainly received low doses of radiation. In women with left-sided BC, 6/7 patients had substantially higher mean dose to the distal LAD than to the heart, ranging from 30 to 55Gy and 3 to13Gy, respectively.Conclusion: We found a pronounced difference of radiation dose distribution in the coronary arteries between women with left- and right-sided BC. Women with left-sided BC had almost full treatment dose in parts of mdLAD, regardless of if regional lymph node irradiation was given or not, while women with right-sided BC mainly received low doses to the coronary arteries.
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| 18. |
- Ording, Anne Gulbech, et al.
(author)
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Comorbid Diseases Interact with Breast Cancer to Affect Mortality in the First Year after Diagnosis-A Danish Nationwide Matched Cohort Study
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10, s. e76013-
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Journal article (peer-reviewed)abstract
- Background: Survival of breast cancer patients with comorbidity, compared to those without comorbidity, has been well characterized. The interaction between comorbid diseases and breast cancer, however, has not been well-studied. Methods: From Danish nationwide medical registries, we identified all breast cancer patients between 45 and 85 years of age diagnosed from 1994 to 2008. Women without breast cancer were matched to the breast cancer patients on specific comorbid diseases included in the Charlson comorbidity Index (CCI). Interaction contrasts were calculated as a measure of synergistic effect on mortality between comorbidity and breast cancer. Results: The study included 47,904 breast cancer patients and 237,938 matched comparison women. In the first year, the strongest interaction between comorbidity and breast cancer was observed in breast cancer patients with a CCI score of >= 4, which accounted for 29 deaths per 1000 person-years. Among individual comorbidities, dementia interacted strongly with breast cancer and accounted for 148 deaths per 1000 person-years within one year of follow-up. There was little interaction between comorbidity and breast cancer during one to five years of follow-up. Conclusions: There was substantial interaction between comorbid diseases and breast cancer, affecting mortality. Successful treatment of the comorbid diseases or the breast cancer can delay mortality caused by this interaction in breast cancer patients.
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| 19. |
- Ording, Anne Gulbech, et al.
(author)
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Hospital Recorded Morbidity and Breast Cancer Incidence : A Nationwide Population-Based Case-Control Study
- 2012
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10
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Journal article (peer-reviewed)abstract
- Introduction: Chronic diseases and their complications may increase breast cancer risk through known or still unknown mechanisms, or by shared causes. The association between morbidities and breast cancer risk has not been studied in depth. Methods: Data on all Danish women aged 45 to 85 years, diagnosed with breast cancer between 1994 and 2008 and data on preceding morbidities were retrieved from nationwide medical registries. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression associating the Charlson comorbidity score (measured using both the original and an updated Charlson Comorbidity Index (CCI)) with incident breast cancer. Furthermore, we estimated associations between 202 morbidity categories and incident breast cancer, adjusting for multiple comparisons using empirical Bayes (EB) methods. Results: The study included 46,324 cases and 463,240 population controls. Increasing CCI score, up to a score of six, was associated with slightly increased breast cancer risk. Among the Charlson diseases, preceding moderate to severe renal disease (OR = 1.25, 95% CI: 1.06, 1.48), any tumor (OR = 1.17, 95% CI: 1.10, 1.25), moderate to severe liver disease (OR = 1.86, 95% CI: 1.32, 2.62), and metastatic solid tumors (OR = 1.49, 95% CI: 1.17, 1.89), were most strongly associated with subsequent breast cancer. Preceding myocardial infarction (OR = 0.89, 95% CI: 0.81, 0.99), connective tissue disease (OR = 0.87, 95% CI: 0.80, 0.94), and ulcer disease (OR = 0.91, 95% CI: 0.83, 0.99) were most strongly inversely associated with subsequent breast cancer. A history of breast disorders was associated with breast cancer after EB adjustment. Anemias were inversely associated with breast cancer, but the association was near null after EB adjustment. Conclusions: There was no substantial association between morbidity measured with the CCI and breast cancer risk.
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| 20. |
- Ording, Anne Gulbech, et al.
(author)
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Impact of comorbidity on risk of venous thromboembolism in patients with breast cancer : a Danish population-based cohort study
- 2014
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In: BMJ Open. - : BMJ. - 2044-6055. ; 4:6
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Journal article (peer-reviewed)abstract
- Objectives: To assess the interaction between comorbidity and breast cancer (BC) on the rate of venous thromboembolism (VTE) beyond what can be explained by the independent effects of BC and comorbidity. Design: Population-based matched cohort study. Setting: Denmark. Participants: Danish patients with BC (n=62 376) diagnosed in 1995-2010 and a comparison cohort of women without BC (n=304 803) from the general population were matched to the patients with BC on year of birth in 5-year intervals and on the specific diseases included in the Charlson Comorbidity Index (CCI) and atrial fibrillation and obesity. Measures: The rate ratios of VTE per 1000 person-years (PY) were computed by comorbidity levels using the CCI, and interaction contrasts (IC) were calculated as a measure of the excess or deficit VTE rate not explained by the independent effects of BC and comorbidity. Results: Among patients with BC with a CCI score of 1, the 0-1 year VTE rate was 12/1000 PY, and interaction accounted for 10% of the rate (IC=3.2, 95% CI 0.5 to 5.9). Among patients with BC with CCI >= 4, the VTE rate was 17, and interaction accounted for 8% of the rate (IC=1.2, 95% CI -1.8 to 4.2). There was no interaction during 2-5 years of follow-up. Conclusions: There was only little interaction between BC and the CCI score on the rate of VTE.
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| 21. |
- Ording, Anne Gulbech, et al.
(author)
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Relative mortality rates from incident chronic diseases among breast cancer survivors - A 14 year follow-up of five-year survivors diagnosed in Denmark between 1994 and 2007
- 2015
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 51:6, s. 767-775
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Journal article (peer-reviewed)abstract
- Background: It remains unknown whether incident chronic diseases are more often fatal among breast cancer survivors than among women free of breast cancer. Methods: We conducted a nationwide matched cohort study of all Danish breast cancer patients diagnosed between 1994 and 2007, who survived for five years. We compared their long-term mortality with five times as many women from the general population without breast cancer, matched on age. We used time-varying methods to compute mortality rate ratios (MRRs) for incident diseases included in the Charlson Comorbidity Index (CCI). Results: One third of five-year breast cancer survivors developed incident diseases during 14 years of follow-up, with about the same incidence as women without breast cancer. Mortality associated with any incident disease was similar among breast cancer survivors (MRR = 7.1, 95% confidence interval (CI): 6.7, 7.4) and comparison women (MRR = 7.5, 95% CI: 7.3, 7.7). Among breast cancer patients, relative mortality associated with incident diseases was higher among patients treated with chemotherapy (MRR = 10, 95% CI: 8.7, 12) and radiotherapy (MRR = 9.8, 95% CI: 8.8, 11) than among patients who received surgery (MRR = 7.0, 95% CI: 6.7, 7.4) or hormonal therapy (MRR = 6.3, 95% CI: 5.8, 6.9). Conclusion: There were no marked differences in mortality of diseases among breast cancer survivors and women from the general population. Among breast cancer patients, new diseases were more often fatal in patients treated with chemotherapy and radiotherapy. Five-year breast cancer survivors have similar risk of dying from new chronic medical conditions as women from the general population without breast cancer.
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| 22. |
- Rostami, Elham, 1979-, et al.
(author)
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Recurrent papillary craniopharyngioma with BRAFV600E mutation treated with neoadjuvant-targeted therapy.
- 2017
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In: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 159:11, s. 2217-2221
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Journal article (peer-reviewed)abstract
- Craniopharyngiomas are histologically benign but locally aggressive tumors in the sellar region that may cause devastating neurological and endocrine deficits. They tend to recur following surgery with high morbidity; hence, postoperative radiotherapy is recommended following sub-total resection. BRAFV600E mutation is the principal oncogenic driver in the papillary variant of craniopharyngiomas. Recently, a dramatic tumor reduction has been reported in a patient with BRAFV600E mutated, multiply recurrent papillary craniopharyngioma using a combination therapy of BRAF inhibitor dabrafenib and MEK inhibitor trametinib. Here, we report on near-radical reduction of a growing residual BRAFV600E craniopharyngioma using the same neoadjuvant therapy.
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| 23. |
- Schmidt, J. A., et al.
(author)
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Baseline patterns of adipose tissue fatty acids and long-term risk of breast cancer : a case-cohort study in the Danish cohort Diet, Cancer and Health
- 2014
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In: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 68:10, s. 1088-1094
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Journal article (peer-reviewed)abstract
- BACKGROUND/OBJECTIVES: The evidence regarding fatty acids and breast cancer risk is inconclusive. Adipose tissue fatty acids can be used as biomarkers of fatty acid intake and of endogenous fatty acid exposure. Fatty acids in adipose tissue are correlated. owing to common dietary sources and shared metabolic pathways, which group fatty acids into naturally occurring patterns. We aimed to prospectively investigate associations between adipose tissue fatty acid patterns and long-term risk of total breast cancer and breast cancer subtypes characterised by oestrogen and progesterone receptor status (ER and PR). SUBJECTS/METHODS: This case-cohort study was based on data from the Danish cohort Diet, Cancer and Health. At baseline, a fat biopsy and information on lifestyle and reproductive factors were collected. From the 31 original fatty acids measured, patterns of fatty acids were identified using the treelet transform. During a median follow-up of 5.3 years, 474 breast cancer cases were identified. Hazard ratios and 95% confidence intervals of risk of total breast cancer and of subtypes according to quintiles of factor score were determined by weighted Cox proportional hazards regression. RESULTS: After adjustment for potential confounders, factor scores for the seven patterns identified by the treelet transform were not associated with risk of total breast cancer, nor with risk of ER+, ER, PR+ or PR tumours. CONCLUSIONS: No clear associations between the patterns of fatty acids at baseline and long-term risk of total breast cancer or ER+, ER, PR+ or PR tumours were observed.
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| 24. |
- Thurin, Erik, et al.
(author)
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Proton therapy for low-grade gliomas in adults : A systematic review
- 2018
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In: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print). - : Elsevier BV. - 0303-8467 .- 1872-6968. ; 174, s. 233-238
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Journal article (peer-reviewed)abstract
- For adult patients with diffuse low-grade glioma (LGG) proton therapy is an emerging radiotherapy modality. The number of proton facilities is rapidly increasing. However, there is a shortage of published data concerning the clinical effectiveness compared to photon radiotherapy and potential proton-specific toxicity. This study aimed to systematically review and summarize the relevant literature on proton therapy for adult LGG patients, including dosimetric comparisons, the type and frequency of acute and long-term toxicity and the clinical effectiveness. A systematic search was performed in several medical databases and 601 articles were screened for relevance. Nine articles were deemed eligible for in-depth analysis using a standardized data collection form by two independent researchers. Proton treatment plans compared favorably to photon-plans regarding dose to uninvolved neural tissue. Fatigue (27-100%), alopecia (37-85%), local erythema (78-85%) and headache (27-75%) were among the most common acute toxicities. One study reported no significant long-term cognitive impairments. Limited data was available on long-term survival. One study reported a 5-year overall survival of 84% and 5-year progression-free survival of 40%. We conclude that published data from clinical studies using proton therapy for adults with LGG are scarce. As the technique becomes more available, controlled clinical studies are urgently warranted to determine if the potential benefits based on comparative treatment planning translate into clinical benefits.
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| 25. |
- Wennstig, Anna-Karin, et al.
(author)
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Inter-observer variation in delineating the coronary arteries as organs at risk
- 2017
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In: Radiotherapy and Oncology. - : ELSEVIER IRELAND LTD. - 0167-8140 .- 1879-0887. ; 122:1, s. 72-78
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Journal article (peer-reviewed)abstract
- Purpose: To determine the inter-observer variation in delineating the coronary arteries as organs at risk (OAR) in breast cancer (BC) radiotherapy (RT) and how this variation affects the estimated coronary artery radiation dose.Method: Delineation of the left main and the left anterior descending coronary artery (LMCA and LAD), and the right coronary artery (RCA), by using the heart atlas by Feng et al., was performed by three radiation oncologists in 32 women who had received adjuvant RT for BC. Centres of the arteries were calculated and distances between artery centres were measured and the artery radiation doses were estimated. The intraclass correlation coefficient (ICC) was used to quantify the variability in doses.Results: Along the extent of RCA, the median distance between centres of arteries varied from 2 to 9 mm with similar patterns over pairs of oncologists. For the LMCA-LAD the median distance varied from 1 to 4 mm. The estimated maximum radiation doses showed an ICC variation from 0.82 to 0.97.Conclusion: The coronary arteries can be reliably identified and delineated as OARs in BC RT. The spatial variance is limited and the total variation in radiation dose is almost completely determined by the between patient variation.
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| 26. |
- Ödén, Jakob, et al.
(author)
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Spatial correlation of linear energy transfer and relative biological effectiveness with treatment related toxicities following proton therapy for intracranial tumors
- 2020
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In: Medical physics (Lancaster). - : Wiley. - 0094-2405 .- 2473-4209. ; 47:2, s. 342-351
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Journal article (peer-reviewed)abstract
- Purpose: The enhanced relative biological effectiveness (RBE) at the end of the proton range might increase the risk of radiation-induced toxicities. This is of special concern for intracranial treatments where several critical organs at risk (OARs) surround the tumor. In the light of this, a retrospective analysis of dose-averaged linear energy transfer (LETd) and RBE-weighted dose (DRBE) distributions was conducted for three clinical cases with suspected treatment related toxicities following intracranial proton therapy. Alternative treatment strategies aiming to reduce toxicity risks are also presented.Methods: The clinical single-field optimized (SFO) plans were recalculated for 81 error scenarios with a Monte Carlo dose engine. The fractionation DRBE was 1.8 Gy (RBE) in 28 or 30 fractions assuming a constant RBE of 1.1. Two LETd- and α/β-dependent variable RBE models were used for evaluation, including a sensitivity analysis of the α/β parameter. Resulting distributions of DRBE and LETd were analyzed together with normal tissue complication probabilities (NTCPs). Subsequently, four multi-field optimized (MFO) plans, with an additional beam and/or objectives penalizing protons stopping in OARs, were created to investigate the potential reduction of LETd, DRBE and NTCP.Results: The two variable RBE models agreed well and predicted average RBE values around 1.3 in the toxicity volumes, resulting in increased near-maximum DRBE of 7-11 Gy (RBE) compared to RBE=1.1 in the nominal scenario. The corresponding NTCP estimates increased from 0.8%, 0.0% and 3.7% (RBE=1.1) to 15.5%, 1.8% and 45.7% (Wedenberg RBE model) for the three patients, respectively. The MFO plans generally allowed for LETd, DRBE and NTCP reductions in OARs, without compromising the target dose. Compared to the clinical SFO plans, the maximum reduction of the near-maximum LETd was 56%, 63% and 72% in the OAR exhibiting the toxicity for the three patients, respectively.Conclusions: Although a direct causality between RBE and toxicity cannot be established here, high LETd and DRBE correlated spatially with the observed toxicities, whereas setup and range uncertainties had a minor impact. Individual factors, which might affect the patient-specific radiosensitivity, were however not included in these calculations. The MFO plans using both an additional beam and proton track-end objectives allowed the largest reductions in LETd, DRBE and NTCP, and might be future tools for similar cases.
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