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  • 1. Ardenfors, Oscar
    et al.
    Dasu, Alexandru
    Kopeć, Mariusz
    Gudowska, Irena
    Modelling of a proton spot scanning system using MCNP62017In: Journal of Physics: Conference Series, ISSN 1742-6588, Vol. 860, p. 012025-Article in journal (Refereed)
  • 2. Ardenfors, Oscar
    et al.
    Dasu, Alexandru
    Lillhök, Jan
    Persson, Linda
    Gudowska, Irena
    Out-of-field doses from secondary radiation produced in proton therapy and the associated risk of radiation-induced cancer from a brain tumor treatment.2018In: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 53, p. 129-136Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To determine out-of-field doses produced in proton pencil beam scanning (PBS) therapy using Monte Carlo simulations and to estimate the associated risk of radiation-induced second cancer from a brain tumor treatment.

    METHODS: Simulations of out-of-field absorbed doses were performed with MCNP6 and benchmarked against measurements with tissue-equivalent proportional counters (TEPC) for three irradiation setups: two irradiations of a water phantom using proton energies of 78-147 MeV and 177-223 MeV, and one brain tumor irradiation of a whole-body phantom. Out-of-field absorbed and equivalent doses to organs in a whole-body phantom following a brain tumor treatment were subsequently simulated and used to estimate the risk of radiation-induced cancer. Additionally, the contribution of absorbed dose originating from radiation produced in the nozzle was calculated from simulations.

    RESULTS: Out-of-field absorbed doses to the TEPC ranged from 0.4 to 135 µGy/Gy. The average deviation between simulations and measurements of the water phantom irradiations was about 17%. The absorbed dose contribution from radiation produced in the nozzle ranged between 0 and 70% of the total dose; the contribution was however small in absolute terms. The absorbed and equivalent doses to the organs ranged between 0.2 and 60 µGy/Gy and 0.5-151 µSv/Gy. The estimated lifetime risk of radiation-induced second cancer was approximately 0.01%.

    CONCLUSIONS: The agreement of out-of-field absorbed doses between measurements and simulations was good given the sources of uncertainties. Calculations of out-of-field organ doses following a brain tumor treatment indicated that proton PBS therapy of brain tumors is associated with a low risk of radiation-induced cancer.

  • 3. Ardenfors, Oscar
    et al.
    Gudowska, Irena
    Flejmer, Anna Maria
    Dasu, Alexandru
    Impact of irradiation setup in proton spot scanning brain therapy on organ doses from secondary radiation2018In: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 180, no 1-4, p. 261-266Article in journal (Refereed)
    Abstract [en]

    A Monte Carlo model of a proton spot scanning pencil beam was used to simulate organ doses from secondary radiation produced from brain tumour treatments delivered with either a lateral field or a vertex field to one adult and one paediatric patient. Absorbed doses from secondary neutrons, photons and protons and neutron equivalent doses were higher for the vertex field in both patients, but the differences were low in absolute terms. Absorbed doses ranged between 0.1 and 43 μGy.Gy-1 in both patients with the paediatric patient receiving higher doses. The neutron equivalent doses to the organs ranged between 0.5 and 141 μSv.Gy-1 for the paediatric patient and between 0.2 and 134 μSv.Gy-1 for the adult. The highest neutron equivalent dose from the entire treatment was 7 mSv regardless of field setup and patient size. The results indicate that different field setups do not introduce large absolute variations in out-of-field doses produced in patients undergoing proton pencil beam scanning of centrally located brain tumours.

  • 4. Ardenfors, Oscar
    et al.
    Henry, Thomas
    Gudowska, Irena
    Poludniowski, Gavin
    Dasu, Alexandru
    Organ doses from a proton gantry-mounted cone-beam computed tomography system characterized with MCNP6 and GATE2018In: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 53, p. 56-61Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To determine organ doses from a proton gantry-mounted cone-beam computed tomography (CBCT) system using two Monte Carlo codes and to study the influence on organ doses from different acquisition modes and repeated imaging.

    METHODS: The CBCT system was characterized with MCNP6 and GATE using measurements of depth doses in water and spatial profiles in air. The beam models were validated against absolute dose measurements and used to simulate organ doses from CBCT imaging with head, thorax and pelvis protocols. Anterior and posterior 190° scans were simulated and the resulting organ doses per mAs were compared to those from 360° scans. The influence on organ doses from repeated imaging with different imaging schedules was also investigated.

    RESULTS: The agreement between MCNP6, GATE and measurements with regard to depth doses and beam profiles was within 4% for all protocols and the corresponding average agreement in absolute dose validation was 4%. Absorbed doses for in-field organs from 360° scans ranged between 6 and 8 mGy, 15-17 mGy and 24-54 mGy for the head, thorax and pelvis protocols, respectively. Cumulative organ doses from repeated CBCT imaging ranged between 0.04 and 0.32 Gy for weekly imaging and 0.2-1.6 Gy for daily imaging. The anterior scans resulted in an average increase in dose per mAs of 24% to the organs of interest relative to the 360° scan, while the posterior scan showed a 37% decrease.

    CONCLUSIONS: A proton gantry-mounted CBCT system was accurately characterized with MCNP6 and GATE. Organ doses varied greatly depending on acquisition mode, favoring posterior scans.

  • 5. Bennati, Paolo
    et al.
    Dasu, Alexandru
    Colarieti-Tosti, Massimiliano
    Lönn, Gustaf
    Larsson, David
    Fabbri, Andrea
    Galasso, Matteo
    Cinti, Maria Nerina
    Pellegrini, Rosanna
    Pani, Roberto
    Preliminary study of a new gamma imager for on-line proton range monitoring during proton radiotherapy2017In: Journal of Instrumentation, ISSN 1748-0221, E-ISSN 1748-0221, Vol. 12, no 5, p. C05009-Article in journal (Refereed)
  • 6. Bolsi, Alessandra
    et al.
    Peroni, Marta
    Amelio, Dante
    Dasu, Alexandru
    Stock, Markus
    Toma-Dasu, Iuliana
    Witt Nyström, Petra
    Hoffmann, Aswin
    Practice patterns of image guided particle therapy in Europe: A 2016 survey of the European Particle Therapy Network (EPTN)2018In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 128, no 1, p. 4-8Article in journal (Refereed)
    Abstract [en]

    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.

  • 7. Dasu, Alexandru
    et al.
    Flejmer, Anna M.
    Dohlmar, Frida
    Josefsson, Dan
    Witt Nyström, Petra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    The Potential Benefit of Scanned Proton Beam Versus Intensity Modulated Photon Therapy as Adjuvant Radiation Therapy in Breast Cancer2014In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 10, p. 5873-5874Article in journal (Other academic)
  • 8. Dasu, Alexandru
    et al.
    Flejmer, Anna M.
    Edvardsson, Anneli
    Witt Nyström, Petra
    Normal tissue sparing potential of scanned proton beams with and without respiratory gating for the treatment of internal mammary nodes in breast cancer radiotherapy2018In: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 52, p. 81-85Article in journal (Refereed)
    Abstract [en]

    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.

  • 9. Dasu, Alexandru
    et al.
    Toma-Dasu, Iuliana
    Models for the risk of secondary cancers from radiation therapy2017In: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 42, p. 232-238Article in journal (Refereed)
    Abstract [en]

    The interest in the induction of secondary tumours following radiotherapy has greatly increased as developments in detecting and treating the primary tumours have improved the life expectancy of cancer patients. However, most of the knowledge on the current levels of risk comes from patients treated many decades ago. As developments of irradiation techniques take place at a much faster pace than the progression of the carcinogenesis process, the earlier results could not be easily extrapolated to modern treatments. Indeed, the patterns of irradiation from historically-used orthovoltage radiotherapy and from contemporary techniques like conformal radiotherapy with megavoltage radiation, intensity modulated radiation therapy with photons or with particles are quite different. Furthermore, the increased interest in individualised treatment options raises the question of evaluating and ranking the different treatment plan options from the point of view of the risk for cancer induction, in parallel with the quantification of other long-term effects. It is therefore inevitable that models for risk assessment will have to be used to complement the knowledge from epidemiological studies and to make predictions for newer forms of treatment for which clinical evidence is not yet available. This work reviews the mathematical models that could be used to predict the risk of secondary cancers from radiotherapy-relevant dose levels, as well as the approaches and factors that have to be taken into account when including these models in the clinical evaluation process. These include the effects of heterogeneous irradiation, secondary particles production, imaging techniques, interpatient variability and other confounding factors.

  • 10. de Las Heras Gala, Hugo
    et al.
    Torresin, Alberto
    Dasu, Alexandru
    Rampado, Osvaldo
    Delis, Harry
    Hernández Girón, Irene
    Theodorakou, Chrysoula
    Andersson, Jonas
    Holroyd, John
    Nilsson, Mats
    Edyvean, Sue
    Gershan, Vesna
    Hadid-Beurrier, Lama
    Hoog, Christopher
    Delpon, Gregory
    Sancho Kolster, Ismael
    Peterlin, Primož
    Garayoa Roca, Julia
    Caprile, Paola
    Zervides, Costas
    Quality control in cone-beam computed tomography (CBCT): EFOMP-ESTRO-IAEA protocol2017Report (Refereed)
    Abstract [en]

    Quality control of cone-beam computed tomography (CBCT) systems is an essential part of quality assurance to periodically check that quality requirements are met, reduce uncertainties and errors and reduce the likelihood of accidents and incidents. Radiation exposure levels must be measured to ensure that patient doses associated with CBCT examinations are kept as low as reasonably achievable consistent with the required diagnostic information. The main purpose of this document is to present procedures for quality control of CBCT systems used for dental, radiotherapy, interventional radiology and guided surgery applications.

  • 11. de Las Heras Gala, Hugo
    et al.
    Torresin, Alberto
    Dasu, Alexandru
    Rampado, Osvaldo
    Delis, Harry
    Hernández Girón, Irene
    Theodorakou, Chrysoula
    Andersson, Jonas
    Holroyd, John
    Nilsson, Mats
    Edyvean, Sue
    Gershan, Vesna
    Hadid-Beurrier, Lama
    Hoog, Christopher
    Delpon, Gregory
    Sancho Kolster, Ismael
    Peterlin, Primož
    Garayoa Roca, Julia
    Caprile, Paola
    Zervides, Costas
    Quality control in cone-beam computed tomography (CBCT) EFOMP-ESTRO-IAEA protocol (summary report)2017In: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 39, p. 67-72Article in journal (Refereed)
    Abstract [en]

    The aim of the guideline presented in this article is to unify the test parameters for image quality evaluation and radiation output in all types of cone-beam computed tomography (CBCT) systems. The applications of CBCT spread over dental and interventional radiology, guided surgery and radiotherapy. The chosen tests provide the means to objectively evaluate the performance and monitor the constancy of the imaging chain. Experience from all involved associations has been collected to achieve a consensus that is rigorous and helpful for the practice. The guideline recommends to assess image quality in terms of uniformity, geometrical precision, voxel density values (or Hounsfield units where available), noise, low contrast resolution and spatial resolution measurements. These tests usually require the use of a phantom and evaluation software. Radiation output can be determined with a kerma-area product meter attached to the tube case. Alternatively, a solid state dosimeter attached to the flat panel and a simple geometric relationship can be used to calculate the dose to the isocentre. Summary tables including action levels and recommended frequencies for each test, as well as relevant references, are provided. If the radiation output or image quality deviates from expected values, or exceeds documented action levels for a given system, a more in depth system analysis (using conventional tests) and corrective maintenance work may be required.

  • 12. Flejmer, Anna M.
    et al.
    Chehrazi, Behnaz
    Josefsson, Dan
    Toma-Dasu, Iuliana
    Dasu, Alexandru
    Impact of physiological breathing motion for breast cancer radiotherapy with proton beam scanning - An in silico study2017In: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 39, p. 88-94Article in journal (Refereed)
    Abstract [en]

    This study investigates the impact of breathing motion on proton breast treatment plans. Twelve patients with CT datasets acquired during breath-hold-at-inhalation (BHI), breath-hold-at-exhalation (BHE) and in free-breathing (FB) were included in the study. Proton plans were designed for the left breast for BHI and subsequently recalculated for BHE or designed for FB and recalculated for the extreme breath-hold phases. The plans were compared from the point of view of their target coverage and doses to organs-at-risk. The median amplitude of breathing motion determined from the positions of the sternum was 4.7mm (range 0.5-14.6mm). Breathing motion led to a degradation of the dose coverage of the target (heterogeneity index increased from 4-7% to 8-11%), but the degraded values of the dosimetric parameters of interest fulfilled the clinical criteria for plan acceptance. Exhalation decreased the lung burden [average dose 3.1-4.5Gy (RBE)], while inhalation increased it [average dose 5.8-6.8Gy (RBE)]. The individual values depended on the field arrangement. Smaller differences were seen for the heart [average dose 0.1-0.2Gy (RBE)] and the LAD [1.9-4.6Gy (RBE)]. Weak correlations were generally found between changes in dosimetric parameters and respiratory motion. The differences between dosimetric parameters for various breathing phases were small and their expected clinical impact is consequently quite small. The results indicated that the dosimetric parameters of the plans corresponding to the extreme breathing phases are little affected by breathing motion, thus suggesting that this motion might have little impact for the chosen beam orientations with scanned proton beams.

  • 13.
    Flejmer, Anna M.
    et al.
    Linkoping Univ, Dept Oncol, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Edvardsson, Anneli
    Lund Univ, Dept Med Radiat Phys, Lund, Sweden..
    Dohlmar, Frida
    Linkoping Univ, Dept Radiat Phys, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Josefsson, Dan
    Linkoping Univ, Dept Radiat Phys, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Nilsson, Mats
    Cty Council Jonkoping Futurum, Acad Hlth & Care, Jonkoping, Sweden..
    Nystrom, Petra Witt
    Univ Uppsala Hosp, Dept Oncol, S-75185 Uppsala, Sweden..
    Dasu, Alexandru
    Linkoping Univ, Dept Radiat Phys, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Respiratory gating for proton beam scanning versus photon 3D-CRT for breast cancer radiotherapy2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 5, p. 577-583Article in journal (Refereed)
    Abstract [en]

    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 12Gy to 7Gy(RBE) in EIG and from 14Gy to 6-7Gy (RBE) in FB, while for WBO patients all values were about 5-6Gy (RBE). The mean dose to heart decreased by a factor of four in WBO patients [from 1.1Gy to 0.3Gy (RBE) in EIG and from 2.1Gy to 0.5Gy (RBE) in FB] and 10 in BRN patients [from 2.1Gy to 0.2Gy (RBE) in EIG and from 3.4Gy to 0.3Gy (RBE) in FB]. Similarly, the mean and the near maximum dose to the 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.

  • 14. Kjellsson Lindblom, Emely
    et al.
    Dasu, Alexandru
    Toma-Dasu, Iuliana
    Hypoxia induced by vascular damage at high doses could compromise the outcome of radiotherapy2019In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 39, no 5, p. 2337-2340Article in journal (Refereed)
  • 15. Kjellsson Lindblom, Emely
    et al.
    Ureba, Ana
    Dasu, Alexandru
    Wersäll, Peter
    Even, Aniek J. G.
    van Elmpt, Wouter
    Lambin, Philippe
    Toma-Dasu, Iuliana
    Impact of SBRT fractionation in hypoxia dose painting - accounting for heterogeneous and dynamic tumour oxygenation2019In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 46, no 5, p. 2512-2521Article in journal (Refereed)
  • 16. Lazzeroni, Marta
    et al.
    Bunea, Hatice
    Grosu, Anca L.
    Baltas, Dimos
    Toma-Dasu, Iuliana
    Dasu, Alexandru
    Mathematical Description of Changes in Tumour Oxygenation from Repeated Functional Imaging2018In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 1072, p. 195-200Article in journal (Refereed)
    Abstract [en]

    Functional imaging of tumour hypoxia has been suggested as a tool for refining target definition and treatment optimization in radiotherapy. The approach, however, has been slow to be adopted clinically as most of the studies on the topic do not take into account the in-treatment changes of hypoxia. The present study aimed to introduce a function that quantifies the changes of oxygen distributions in repeated PET images taken during treatment. The proposed approach for determining the reoxygenation function was tested for feasibility on patients with head and neck cancer, repeatedly imaged with FMISO PET during radiotherapy. Reoxygenation functions were derived by solving the convolution between functions describing the oxygen distributions of successive images. The method was found to be mathematically feasible. The results indicate that the reoxygenation functions describing the change in oxygenation have distinct shapes prompting the hypothesis that oxygenation changes reflected by them might have predictive power for treatment outcome. Future studies on a larger patient population to search for predictive correlations based on the reoxygenation function are planned.

  • 17. Lazzeroni, Marta
    et al.
    Uhrdin, Johan
    Carvalho, Sara
    van Elmpt, Wouter
    Lambin, Philippe
    Dasu, Alexandru
    Wersäll, Peter
    Toma-Dasu, Iuliana
    Evaluation of third treatment week as temporal window for assessing responsiveness on repeated FDG-PET-CT scans in Non-Small Cell Lung Cancer patients2018In: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 46, p. 45-51Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Early assessment of tumour response to treatment with repeated FDG-PET-CT imaging has potential for treatment adaptation but it is unclear what the optimal time window for this evaluation is. Previous studies indicate that changes in SUVmean and the effective radiosensitivity (αeff, accounting for uptake variations and accumulated dose until the second FDG-PET-CT scan) are predictive of 2-year overall survival (OS) when imaging is performed before radiotherapy and during the second week. This study aims to investigate if multiple FDG-PET-derived quantities determined during the third treatment week have stronger predictive power.

    METHODS: Twenty-eight lung cancer patients were imaged with FDG-PET-CT before radiotherapy (PET1) and during the third week (PET2). SUVmean, SUVmax, SUVpeak, MTV41%-50% (Metabolic Tumour Volume), TLG41%-50% (Total Lesion Glycolysis) in PET1 and PET2 and their change (), as well as average αeff (α¯eff) and the negative fraction of αeff values [Formula: see text] ) were determined. Correlations were sought between FDG-PET-derived quantities and OS with ROC analysis.

    RESULTS: Neither SUVmean, SUVmax, SUVpeak in PET1 and PET2 (AUC = 0.5-0.6), nor their changes (AUC = 0.5-0.6) were significant for outcome prediction purposes. Lack of correlation with OS was also found for α¯eff (AUC = 0.5) and [Formula: see text] (AUC = 0.5). Threshold-based quantities (MTV41%-50%, TLG41%-50%) and their changes had AUC = 0.5-0.7. P-values were in all cases ≫0.05.

    CONCLUSIONS: The poor OS predictive power of the quantities determined from repeated FDG-PET-CT images indicates that the third week of treatment might not be suitable for treatment response assessment. Comparatively, the second week during the treatment appears to be a better time window.

  • 18. Lillhök, Jan
    et al.
    Persson, Linda
    Andersen, Claus E.
    Dasu, Alexandru
    Ardenfors, Oscar
    RADIATION PROTECTION MEASUREMENTS WITH THE VARIANCE-COVARIANCE METHOD IN THE STRAY RADIATION FIELDS FROM PHOTON AND PROTON THERAPY FACILITIES2018In: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 180, no 1-4, p. 338-341Article in journal (Refereed)
    Abstract [en]

    The microdosimetric variance-covariance method was used to study the stray radiation fields from the photon therapy facility at the Technical University of Denmark and the scanned proton therapy beam at the Skandion Clinic in Uppsala, Sweden. Two TEPCs were used to determine the absorbed dose, the dose-average lineal energy, the dose-average quality factor and the dose equivalent. The neutron component measured by the detectors at the proton beam was studied through Monte Carlo simulations using the code MCNP6. In the photon beam the stray absorbed dose ranged between 0.3 and 2.4 μGy per monitor unit, and the dose equivalent between 0.4 and 9 μSv per monitor unit, depending on beam energy and measurement position. In the proton beam the stray absorbed dose ranged between 3 and 135 μGy per prescribed Gy, depending on detector position and primary proton energy.

  • 19. Lindblom, Emely
    et al.
    Dasu, Alexandru
    Beskow, Catharina
    Toma-Dasu, Iuliana
    High brachytherapy doses can counteract hypoxia in cervical cancer - a modelling study2017In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 62, no 2, p. 560-572Article in journal (Refereed)
    Abstract [en]

    Tumour hypoxia is a well-known adverse factor for the outcome of radiotherapy. For cervical tumours in particular, several studies indicate large variability in tumour oxygenation. However, clinical evidence shows that the management of cervical cancer including brachytherapy leads to high rate of success. It was the purpose of this study to investigate whether the success of brachytherapy for cervical cancer, seemingly regardless of oxygenation status, could be explained by the characteristics of the brachytherapy dose distributions. To this end, a previously used in silico model of tumour oxygenation and radiation response was further developed to simulate the treatment of cervical cancer employing a combination of external beam radiotherapy and intracavitary brachytherapy. Using a clinically-derived brachytherapy dose distribution and assuming a homogeneous dose delivered by external radiotherapy, cell survival was assessed on voxel level by taking into account the variation of sensitivity with oxygenation as well as the effects of repair, repopulation and reoxygenation during treatment. Various scenarios were considered for the conformity of the brachytherapy dose distribution to the hypoxic region in the target. By using the clinically-prescribed brachytherapy dose distribution and varying the total dose delivered with external beam radiotherapy in 25 fractions, the resulting values of the dose for 50% tumour control, D 50, were in agreement with clinically-observed values for high cure rates if fast reoxygenation was assumed. The D 50 was furthermore similar for the different degrees of conformity of the brachytherapy dose distribution to the tumour, regardless of whether the hypoxic fraction was 10%, 25%, or 40%. To achieve 50% control with external RT only, a total dose of more than 70 Gy in 25 fractions would be required for all cases considered. It can thus be concluded that the high doses delivered in brachytherapy can counteract the increased radioresistance caused by hypoxia if fast reoxygenation is assumed.

  • 20. Lindblom, Emely
    et al.
    Dasu, Alexandru
    Uhrdin, Johan
    Even, Aniek
    van Elmpt, Wouter
    Lambin, Philippe
    Wersäll, Peter
    Toma-Dasu, Iuliana
    Defining the hypoxic target volume based on positron emission tomography for image guided radiotherapy - the influence of the choice of the reference region and conversion function2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 6, p. 819-825Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hypoxia imaged by positron emission tomography (PET) is a potential target for optimization in radiotherapy. However, the implementation of this approach with respect to the conversion of intensities in the images into oxygenation and radiosensitivity maps is not straightforward. This study investigated the feasibility of applying two conversion approaches previously derived for 18F-labeled fluoromisonidazole (18F-FMISO)-PET images for the hypoxia tracer 18F-flortanidazole (18F-HX4).

    MATERIAL AND METHODS: Ten non-small-cell lung cancer patients imaged with 18F-HX4 before the start of radiotherapy were considered in this study. PET image uptake was normalized to a well-oxygenated reference region and subsequently linear and non-linear conversions were used to determine tissue oxygenations maps. These were subsequently used to delineate hypoxic volumes based partial oxygen pressure (pO2) thresholds. The results were compared to hypoxic volumes segmented using a tissue-to-background ratio of 1.4 for 18F-HX4 uptake.

    RESULTS: While the linear conversion function was not found to result in realistic oxygenation maps, the non-linear function resulted in reasonably sized sub-volumes in good agreement with uptake-based segmented volumes for a limited range of pO2 thresholds. However, the pO2 values corresponding to this range were significantly higher than what is normally considered as hypoxia. The similarity in size, shape, and relative location between uptake-based sub-volumes and volumes based on the conversion to pO2 suggests that the relationship between uptake and pO2 is similar for 18F-FMISO and 18F-HX4, but that the model parameters need to be adjusted for the latter.

    CONCLUSIONS: A non-linear conversion function between uptake and oxygen partial pressure for 18F-FMISO-PET could be applied to 18F-HX4 images to delineate hypoxic sub-volumes of similar size, shape, and relative location as based directly on the uptake. In order to apply the model for e.g., dose-painting, new parameters need to be derived for the accurate calculation of dose-modifying factors for this tracer.

  • 21.
    Lindblom, Emely Kjellsson
    et al.
    Stockholm Univ, Dept Phys, Med Radiat Phys, Stockholm, Sweden.
    Hui, Susanta
    Beckman Res Inst City Hope, Dept Radiat Oncol, Duarte, CA USA.
    Brooks, Jamison
    Beckman Res Inst City Hope, Dept Radiat Oncol, Duarte, CA USA;Univ Minnesota, Dept Radiat Oncol, Minneapolis, MI USA.
    Dasu, Alexandru
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science. Skandion Clin, Uppsala, Sweden.
    Kujawski, Maciej
    Beckman Res Inst City Hope, Dept Mol Imaging & Therapy, Duarte, CA USA.
    Toma-Dasu, Iuliana
    Stockholm Univ, Dept Phys, Med Radiat Phys, Stockholm, Sweden;Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden.
    Radiation-induced Vascular Damage and the Impact on the Treatment Outcome of Stereotactic Body Radiotherapy2019In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 39, no 6, p. 2721-2727Article in journal (Refereed)
    Abstract [en]

    Background/Aim: The aim of this study was to investigate radiation-induced tumour vascular damage and its impact thereof on the outcome of stereotactic body radiotherapy (SBRT). Materials and Methods: Vessel densities in animal tumours before and after a single dose of 20 Gy were quantified and used as input for simulations of three-dimensional tumours with heterogeneous oxygenation. SBRT treatments of the modelled tumours in 1-8 fractions were simulated. The impact of vessel collapse on the outcome of SBRT was investigated by calculating tumour control probability (TCP) and the dose required to obtain a TCP of 50% (D-50). Results: A radiation-induced increase of acute hypoxia in tumours during SBRT treatment could be simulated based on the experimental data. The D-50 values for these tumours were higher than for the simulated tumours without vessel collapse. Conclusion: The vascular changes after high doses of radiation could compromise the outcome of SBRT by increasing tumour hypoxia.

  • 22. Lindblom, Emely
    et al.
    Toma-Dasu, Iuliana
    Dasu, Alexandru
    Accounting for Two Forms of Hypoxia for Predicting Tumour Control Probability in Radiotherapy: An In Silico Study2018In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 1072, p. 183-187Article in journal (Refereed)
    Abstract [en]

    The progress in functional imaging and dose delivery has opened the possibility of targeting tumour hypoxia with radiotherapy. Advanced approaches apply quantitative information on tumour oxygenation retrieved from imaging in dose prescription. These do not, however, take into account the potential difference in radiosensitivity of chronically and acutely hypoxic cells. It was the aim of this study to evaluate the implications of assuming the same or different sensitivities for the hypoxic cells. An in silico 3D-model of a hypoxic tumour with heterogeneous oxygenation was used to model the probabilities of tumour control with different radiotherapy regimens. The results show that by taking into account the potential lower radioresistance of chronically hypoxic cells deprived of oxygen and nutrients, the total dose required to achieve a certain level of control is substantially reduced for a given fractionation scheme in comparison to the case when chronically and acutely hypoxic cells are assumed to have similar features. The results also suggest that the presence of chronic hypoxia could explain the success of radiotherapy for some hypoxic tumours. Given the implications for clinical dose escalation trials, further exploration of the influence of the different forms of hypoxia on treatment outcome is therefore warranted.

  • 23. Marcu, Loredana G.
    et al.
    Toma-Dasu, Iuliana
    Dasu, Alexandru
    Mercke, Claes
    Radiotherapy and clinical radiobiology of head and neck cancer2018Book (Refereed)
  • 24. Tesselaar, Erik
    et al.
    Flejmer, Anna M
    Farnebo, Simon
    Dasu, Alexandru
    Changes in skin microcirculation during radiation therapy for breast cancer2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 8, p. 1072-1080Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The majority of breast cancer patients who receive radiation treatment are affected by acute radiation-induced skin changes. The assessment of these changes is usually done by subjective methods, which complicates the comparison between different treatments or patient groups. This study investigates the feasibility of new robust methods for monitoring skin microcirculation to objectively assess and quantify acute skin reactions during radiation treatment.

    MATERIAL AND METHODS: Laser Doppler flowmetry, laser speckle contrast imaging, and polarized light spectroscopy imaging were used to measure radiation-induced changes in microvascular perfusion and red blood cell concentration (RBC) in the skin of 15 patients undergoing adjuvant radiation therapy for breast cancer. Measurements were made before treatment, once a week during treatment, and directly after the last fraction.

    RESULTS: In the treated breast, perfusion and RBC concentration were increased after 1-5 fractions (2.66-13.3 Gy) compared to baseline. The largest effects were seen in the areola and the medial area. No changes in perfusion and RBC concentration were seen in the untreated breast. In contrast, Radiation Therapy Oncology Group (RTOG) scores were increased only after 2 weeks of treatment, which demonstrates the potential of the proposed methods for early assessment of skin changes. Also, there was a moderate to good correlation between the perfusion (r = 0.52) and RBC concentration (r = 0.59) and the RTOG score given a week later.

    CONCLUSION: We conclude that radiation-induced microvascular changes in the skin can be objectively measured using novel camera-based techniques before visual changes in the skin are apparent. Objective measurement of microvascular changes in the skin may be valuable in the comparison of skin reactions between different radiation treatments and possibly in predicting acute skin effects at an earlier stage.

  • 25. Ureba, Ana
    et al.
    Lindblom, Emely
    Dasu, Alexandru
    Uhrdin, Johan
    Even, Aniek J. G.
    van Elmpt, Wouter
    Lambin, Philippe
    Wersäll, Peter
    Toma-Dasu, Iuliana
    Non-linear conversion of HX4 uptake for automatic segmentation of hypoxic volumes and dose prescription2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 4, p. 485-490Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Tumour hypoxia is associated with increased radioresistance and poor response to radiotherapy. Pre-treatment assessment of tumour oxygenation could therefore give the possibility to tailor the treatment by calculating the required boost dose needed to overcome the increased radioresistance in hypoxic tumours. This study concerned the derivation of a non-linear conversion function between the uptake of the hypoxia-PET tracer 18F-HX4 and oxygen partial pressure (pO2).

    MATERIAL AND METHODS: Building on previous experience with FMISO including experimental data on tracer uptake and pO2, tracer-specific model parameters were derived for converting the normalised HX4-uptake at the optimal imaging time point to pO2. The conversion function was implemented in a Python-based computational platform utilising the scripting and the registration modules of the treatment planning system RayStation. Subsequently, the conversion function was applied to determine the pO2 in eight non-small-cell lung cancer (NSCLC) patients imaged with HX4-PET before the start of radiotherapy. Automatic segmentation of hypoxic target volumes (HTVs) was then performed using thresholds around 10 mmHg. The HTVs were compared to sub-volumes segmented based on a tumour-to-blood ratio (TBR) of 1.4 using the aortic arch as the reference oxygenated region. The boost dose required to achieve 95% local control was then calculated based on the calibrated levels of hypoxia, assuming inter-fraction reoxygenation due to changes in acute hypoxia but no overall improvement of the oxygenation status.

    RESULTS: Using the developed conversion tool, HTVs could be obtained using pO2 a threshold of 10 mmHg which were in agreement with the TBR segmentation. The dose levels required to the HTVs to achieve local control were feasible, being around 70-80 Gy in 24 fractions.

    CONCLUSIONS: Non-linear conversion of tracer uptake to pO2 in NSCLC imaged with HX4-PET allows a quantitative determination of the dose-boost needed to achieve a high probability of local control.

  • 26. Ödén, Jakob
    et al.
    Toma-Dasu, Iuliana
    Eriksson, Kjell
    Flejmer, Anna Maria
    Dasu, Alexandru
    The influence of breathing motion and a variable relative biological effectiveness in proton therapy of left-sided breast cancer2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 11, p. 1428-1436Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Proton breast radiotherapy has been suggested to improve target coverage as well as reduce cardiopulmonary and integral dose compared with photon therapy. This study aims to assess this potential when accounting for breathing motion and a variable relative biological effectiveness (RBE).

    METHODS: Photon and robustly optimized proton plans were generated to deliver 50 Gy (RBE) in 25 fractions (RBE = 1.1) to the CTV (whole left breast) for 12 patients. The plan evaluation was performed using the constant RBE and a variable RBE model. Robustness against breathing motion, setup, range and RBE uncertainties was analyzed using CT data obtained at free-breathing, breath-hold-at-inhalation and breath-hold-at-exhalation.

    RESULTS: All photon and proton plans (RBE = 1.1) met the clinical goals. The variable RBE model predicted an average RBE of 1.18 for the CTVs (range 1.14-1.21) and even higher RBEs in organs at risk (OARs). However, the dosimetric impact of this latter aspect was minor due to low OAR doses. The normal tissue complication probability (NTCP) for the lungs was low for all patients (<1%), and similar for photons and protons. The proton plans were generally considered robust for all patients. However, in the most extreme scenarios, the lowest dose received by 98% of the CTV dropped from 96 to 99% of the prescribed dose to around 92-94% for both protons and photons. Including RBE uncertainties in the robustness analysis resulted in substantially higher worst-case OAR doses.

    CONCLUSIONS: Breathing motion seems to have a minor effect on the plan quality for breast cancer. The variable RBE might impact the potential benefit of protons, but could probably be neglected in most cases where the physical OAR doses are low. However, to be able to identify outlier cases at risk for high OAR doses, the biological evaluation of proton plans taking into account the variable RBE is recommended.

  • 27. Ödén, Jakob
    et al.
    Toma-Dasu, Iuliana
    Witt Nyström, Petra
    Traneus, Erik
    Dasu, Alexandru
    Spatial correlation of linear energy transfer and relative biological effectiveness with suspected treatment related toxicities following proton therapy for intracranial tumors2019In: Medical physics (Lancaster), ISSN 0094-2405Article in journal (Refereed)
1 - 27 of 27
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