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  • 1.
    Ardenfors, Oscar
    et al.
    Stockholm University, Sweden.
    Gudowska, Irena
    Stockholm University, Sweden.
    Flejmer, Anna M.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Dasu, Alexandru
    The Skandion Clinic, Sweden.
    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.

  • 2.
    Dasu, Alexandru
    et al.
    The Skandion Clinic, Uppsala, Sweden.
    Flejmer, Anna M.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. The Skandion Clinic, Uppsala, Sweden.
    Edvardsson, Anneli
    Medical Radiation Physics, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
    Witt Nyström, Petra
    The Skandion Clinic, Uppsala, Sweden.
    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.

  • 3.
    Droog Tesselaar, Erik
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Flejmer, Anna M.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Dasu, Alexandru
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. The Skandion Clinic, Uppsala, Sweden.
    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]

    Abstract:

    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.

  • 4.
    Flejmer, Anna M.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Radiation burden from modern radiation therapy techniques including proton therapy for breast cancer treatment - clinical implications2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The purpose of this thesis was to study the clinical implications of modern radiotherapy techniques for breast cancer treatment. This was investigated in several individual studies.

    Study I investigated the implications of using the analytical anisotropic algorithm (AAA) from the perspective of clinical recommendations for breast cancer radiotherapy. Pencil beam convolution plans of 40 breast cancer patients were recalculated with AAA. The latter plans had a significantly worse coverage of the planning target volume (PTV) with the 93% isodose, higher maximum dose in hotspots, higher volumes of the ipsilateral lung receiving doses below 25 Gy and smaller volumes with doses above 25 Gy. AAA also predicted lower doses to the heart.

    Study II investigated the implications of using the irregular surface compensator (ISC), an electronic compensation algorithm, in comparison to three‐dimensional conformal radiotherapy (3D‐CRT) for breast cancer treatment. Ten breast cancer patients were planned with both techniques. The ISC technique led to better coverage of the clinical target volume of the tumour bed (CTV‐T) and PTV in almost all patients with significant improvement in homogeneity.

    Study III investigated the feasibility of using scanning pencil beam proton therapy for regional and loco‐regional breast cancer with comparison of ISC photon planning. Ten patients were included in the study, all with dose heterogeneity in the target and/or hotspots in the normal tissues outside the PTV. The proton plans showed comparable or better CTV‐T and PTV coverage, with large reductions in the mean doses to the heart and the ipsilateral lung.

    Study IV investigated the added value of enhanced inspiration gating (EIG) for proton therapy. Twenty patients were planned on CT datasets acquired during EIG and freebreathing (FB) using photon 3D‐CRT and scanning proton therapy. Proton spot scanning has a high potential to reduce the irradiation of organs‐at‐risk for most patients, beyond what could be achieved with EIG and photon therapy, especially in terms of mean doses to the heart and the left anterior descending artery.

    Study V investigated the impact of physiological breathing motion during proton radiotherapy for breast cancer. Twelve thoracic patients were planned on CT datasets during breath‐hold at inhalation phase and breath‐hold at exhalation phase. Between inhalation and exhalation phase there were very small differences in dose delivered to the target and cardiovascular structures, with very small clinical implication.

    The results of these studies showed the potential of various radiotherapy techniques to improve the quality of life for breast cancer patients by limiting the dose burden for normal tissues.

    List of papers
    1. Analytical Anisotropic Algorithm versus Pencil Beam Convolution for treatment planning of breast cancer: implications for target coverage and radiation burden of normal tissue
    Open this publication in new window or tab >>Analytical Anisotropic Algorithm versus Pencil Beam Convolution for treatment planning of breast cancer: implications for target coverage and radiation burden of normal tissue
    Show others...
    2015 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 5, p. 2841-2848Article in journal (Refereed) Published
    Abstract [en]

    Aim: The present study aimed to investigate the implications of using the analytical anisotropic algorithm (AAA) for calculation of target coverage and radiation burden of normal tissues. Most model parameters, recommendations and planning guidelines associated with a certain outcome are from the era of pencil beam convolution (PBC) calculations on relatively simple assumptions of energy transport in media. Their relevance for AAA calculations that predict more realistic dose distributions needs to be evaluated. Patients and Methods: Forty patients with left-sided breast cancer receiving 3D conformal radiation therapy were planned using PBC with a standard protocol with 50 Gy in 25 fractions according to existing re-commendations. The plans were subsequently recalculated with the AAA and relevant dose parameters were determined and compared to their PBC equivalents. Results: The majority of the AAA-based plans had a significantly worse coverage of the planning target volume and also a higher maximum dose in hotspots near sensitive structures, suggesting that these criteria could be relaxed for AAA-calculated plans. Furthermore, the AAA predicts higher volumes of the ipsilateral lung will receive doses below 25 Gy and smaller volume doses above 25 Gy. These results indicate that lung tolerance criteria might also have to be relaxed for AAA planning in order to maintain the level of normal tissue toxicity. The AAA also predicts lower doses to the heart, thus indicating that this organ might be more sensitive to radiation than thought from PBC-based calculations. Conclusion: The AAA should be preferred over the PBC algorithm for breast cancer radiotherapy as it gives more realistic dose distributions. Guidelines for plan acceptance might have to be re-evaluated to account for differences in dose predictions in order to maintain the current levels of control and complication rates. The results also suggest an increased radiosensitivity of the heart, thus indicating that a revision of the current models for cardiovascular complications may be needed.

    Place, publisher, year, edition, pages
    International Institute of Anticancer Research, 2015
    Keywords
    breast radiotherapy, dose calculation algorithm, analytical anisotropic algorithm, pencil beam convolution, planning guidelines
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-117854 (URN)000354267200045 ()25964565 (PubMedID)
    Available from: 2015-05-11 Created: 2015-05-11 Last updated: 2017-12-04
    2. Clinical implications of the ISC technique for breast cancer radiotherapy and comparison with clinical recommendations
    Open this publication in new window or tab >>Clinical implications of the ISC technique for breast cancer radiotherapy and comparison with clinical recommendations
    Show others...
    2014 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 7, p. 3563-3568Article in journal (Refereed) Published
    Abstract [en]

    Purpose: The project studied the implications of using the irregular surface compensator (ISC) technique in comparison to three-dimensional conformal radiation therapy (3D-CRT) for breast cancer treatment. ISC is an electronic compensation algorithm that modulates the fluence across the radiation fields to compensate for irregularly shaped surfaces and deliver a homogeneous dose to a compensation plane. Methods: Ten breast cancer patients (five left- and five right-sided) were planned with both techniques. The planning was done for 50 Gy in 25 fractions with 2 Gy per fraction in all patients. Physical parameters such as doses to the clinical target volume (CTV-T) and the planned target volume (PTV), heterogeneity index and doses to lung and heart were determined and compared for the treatment plans. Results: The ISC technique led to significantly better coverage of the CTV-T and PTV in almost all patients with statistically significant better homogeneity of the dose distribution. The contralateral lung and the heart receive the same doses with both ISC and 3D-CRT plans. However, ISC showed a trend towards decreasing the volumes of the ipsilateral lung irradiated with high doses. Consequently this led to better compliance with the national recommendations for breast radiotherapy. Conclusion: The ISC technique leads to an improvement of the target coverage and the radiation burden of the ipsilateral lung thus allowing better compliance with the national recommendations and increasing the potential for improved quality of life for breast cancer patients. It should therefore be preferred over 3D-CRT for breast cases with difficult dose homogeneity to the PTV or CTV-T.

    Place, publisher, year, edition, pages
    International Institute of Anticancer Research, 2014
    Keywords
    breast radiotherapy, irregular surface compensator, fractionated radiotherapy, irradiation technique
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-106944 (URN)000338780300044 ()24982370 (PubMedID)
    Available from: 2014-05-28 Created: 2014-05-28 Last updated: 2017-12-05Bibliographically approved
    3. Potential benefit of scanned proton beam versus photons as adjuvant radiation therapy in breast cancer
    Open this publication in new window or tab >>Potential benefit of scanned proton beam versus photons as adjuvant radiation therapy in breast cancer
    Show others...
    2015 (English)In: International Journal of Particle Therapy, ISSN 2331-5180, Vol. 1, no 4, p. 845-855Article in journal (Refereed) Published
    Abstract [en]

    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.

    Keywords
    breast radiation therapy, proton radiation therapy, pencil beam scanning, irregular surface compensator, fractionated radiation therapy
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-112949 (URN)10.14338/IJPT-14-00013.1 (DOI)
    Available from: 2014-12-31 Created: 2014-12-31 Last updated: 2016-04-27
    4. Respiratory gating for proton beam scanning versus photon 3D-CRT for breast cancer radiotherapy
    Open this publication in new window or tab >>Respiratory gating for proton beam scanning versus photon 3D-CRT for breast cancer radiotherapy
    Show others...
    2016 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 5, p. 577-583Article in journal (Refereed) Published
    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 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.

    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-123274 (URN)10.3109/0284186X.2015.1120883 (DOI)000375566700008 ()
    Note

    Funding agencies:  LiU Cancer research network at Linkoping University; Region Ostergotland; ALF Grants from Region Ostergotland (Sweden)

    Available from: 2015-12-09 Created: 2015-12-09 Last updated: 2017-04-24
    5. Impact of physiological breathing motion for breast cancer radiotherapy with proton beam scanning: An in silico study
    Open this publication in new window or tab >>Impact of physiological breathing motion for breast cancer radiotherapy with proton beam scanning: An in silico study
    Show others...
    2017 (English)In: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 39, p. 88-94Article in journal (Refereed) Published
    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 4.7 mm (range 0.5-14.6 mm). 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 3.1-4.5 Gy (RBE)], while inhalation increased it [average dose 5.8-6.8 Gy (RBE)]. The individual values depended on the field arrangement. Smaller differences were seen for the heart [average dose 0.1-0.2 Gy (RBE)] and the LAD [1.9-4.6 Gy (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.

    Place, publisher, year, edition, pages
    Elsevier, 2017
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-127369 (URN)10.1016/j.ejmp.2017.06.001 (DOI)000405493200012 ()28606833 (PubMedID)
    Note

    Funding agencies: LiU Cancer research network at Linkoping University and Region Ostergotland (Sweden)

    Available from: 2016-04-23 Created: 2016-04-23 Last updated: 2018-05-02Bibliographically approved
  • 5.
    Flejmer, Anna M.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Chehrazi, Behnaz
    Department of Physics, Stockholm University, Stockholm, Sweden.
    Josefsson, Dan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Toma-Dasu, Iuliana
    Medical Radiation Physics, Stockholm University and Karolinska Institutet, Stockholm, Sweden.
    Dasu, Alexandru
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. The Skandion Clinic, Uppsala, Sweden .
    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 4.7 mm (range 0.5-14.6 mm). 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 3.1-4.5 Gy (RBE)], while inhalation increased it [average dose 5.8-6.8 Gy (RBE)]. The individual values depended on the field arrangement. Smaller differences were seen for the heart [average dose 0.1-0.2 Gy (RBE)] and the LAD [1.9-4.6 Gy (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.

  • 6.
    Flejmer, Anna M.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Dohlmar, Frida
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Nilsson, Mats
    Futurum - Academy for Health and Care, Jönköping.
    Stenmarker, Margaretha
    Futurum - Academy for Health and Care, Jönköping.
    Dasu, Alexandru
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Analytical Anisotropic Algorithm versus Pencil Beam Convolution for treatment planning of breast cancer: implications for target coverage and radiation burden of normal tissue2015In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 5, p. 2841-2848Article in journal (Refereed)
    Abstract [en]

    Aim: The present study aimed to investigate the implications of using the analytical anisotropic algorithm (AAA) for calculation of target coverage and radiation burden of normal tissues. Most model parameters, recommendations and planning guidelines associated with a certain outcome are from the era of pencil beam convolution (PBC) calculations on relatively simple assumptions of energy transport in media. Their relevance for AAA calculations that predict more realistic dose distributions needs to be evaluated. Patients and Methods: Forty patients with left-sided breast cancer receiving 3D conformal radiation therapy were planned using PBC with a standard protocol with 50 Gy in 25 fractions according to existing re-commendations. The plans were subsequently recalculated with the AAA and relevant dose parameters were determined and compared to their PBC equivalents. Results: The majority of the AAA-based plans had a significantly worse coverage of the planning target volume and also a higher maximum dose in hotspots near sensitive structures, suggesting that these criteria could be relaxed for AAA-calculated plans. Furthermore, the AAA predicts higher volumes of the ipsilateral lung will receive doses below 25 Gy and smaller volume doses above 25 Gy. These results indicate that lung tolerance criteria might also have to be relaxed for AAA planning in order to maintain the level of normal tissue toxicity. The AAA also predicts lower doses to the heart, thus indicating that this organ might be more sensitive to radiation than thought from PBC-based calculations. Conclusion: The AAA should be preferred over the PBC algorithm for breast cancer radiotherapy as it gives more realistic dose distributions. Guidelines for plan acceptance might have to be re-evaluated to account for differences in dose predictions in order to maintain the current levels of control and complication rates. The results also suggest an increased radiosensitivity of the heart, thus indicating that a revision of the current models for cardiovascular complications may be needed.

  • 7.
    Flejmer, Anna M.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Edvardsson, Anneli
    Lund University, Sweden.
    Dohlmar, Frida
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Josefsson, Dan
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Nilsson, Mats
    Futurum - Academy for Health and Care, Jönköping, Sweden.
    Witt Nyström, Petra
    Uppsala University Hospital, Sweden.
    Dasu, Alexandru
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    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 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.

  • 8.
    Flejmer, Anna M.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Josefsson, Dan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Nilsson, Mats
    Futurum - Academy for Health and Care, Jönköping.
    Stenmarker, Margaretha
    Futurum - Academy for Health and Care, Jönköping.
    Dasu, Alexandru
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Clinical implications of the ISC technique for breast cancer radiotherapy and comparison with clinical recommendations2014In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 7, p. 3563-3568Article in journal (Refereed)
    Abstract [en]

    Purpose: The project studied the implications of using the irregular surface compensator (ISC) technique in comparison to three-dimensional conformal radiation therapy (3D-CRT) for breast cancer treatment. ISC is an electronic compensation algorithm that modulates the fluence across the radiation fields to compensate for irregularly shaped surfaces and deliver a homogeneous dose to a compensation plane. Methods: Ten breast cancer patients (five left- and five right-sided) were planned with both techniques. The planning was done for 50 Gy in 25 fractions with 2 Gy per fraction in all patients. Physical parameters such as doses to the clinical target volume (CTV-T) and the planned target volume (PTV), heterogeneity index and doses to lung and heart were determined and compared for the treatment plans. Results: The ISC technique led to significantly better coverage of the CTV-T and PTV in almost all patients with statistically significant better homogeneity of the dose distribution. The contralateral lung and the heart receive the same doses with both ISC and 3D-CRT plans. However, ISC showed a trend towards decreasing the volumes of the ipsilateral lung irradiated with high doses. Consequently this led to better compliance with the national recommendations for breast radiotherapy. Conclusion: The ISC technique leads to an improvement of the target coverage and the radiation burden of the ipsilateral lung thus allowing better compliance with the national recommendations and increasing the potential for improved quality of life for breast cancer patients. It should therefore be preferred over 3D-CRT for breast cases with difficult dose homogeneity to the PTV or CTV-T.

  • 9.
    Flejmer, Anna M.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Witt Nyström, Petra
    Uppsala University Hospital.
    Dohlmar, Frida
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Josefsson, Dan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Dasu, Alexandru
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Potential benefit of scanned proton beam versus photons as adjuvant radiation therapy in breast cancer2015In: International Journal of Particle Therapy, ISSN 2331-5180, Vol. 1, no 4, p. 845-855Article in journal (Refereed)
    Abstract [en]

    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.

  • 10.
    Ödén, Jakob
    et al.
    Stockholm University and RaySearch Laboratories AB, Stockholm, Sweden.
    Toma-Dasu, Iuliana
    Stockholm University and Karolinska Institutet, Stockholm, Sweden.
    Eriksson, Kjell
    RaySearch Laboratories AB, Stockholm, Sweden.
    Flejmer, Anna M.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Dasu, Alexandru
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. The Skandion Clinic, Uppsala, Sweden.
    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.

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