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Dasu, A., Flejmer, A. M., Edvardsson, A. & Witt Nyström, P. (2018). Normal tissue sparing potential of scanned proton beams with and without respiratory gating for the treatment of internal mammary nodes in breast cancer radiotherapy. Physica medica (Testo stampato), 52, 81-85
Open this publication in new window or tab >>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 (English)In: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 52, p. 81-85Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-149606 (URN)10.1016/j.ejmp.2018.06.639 (DOI)000442110000011 ()30139613 (PubMedID)
Available from: 2018-07-09 Created: 2018-07-09 Last updated: 2018-09-03
Droog Tesselaar, E., Flejmer, A. M., Farnebo, S. & Dasu, A. (2017). Changes in skin microcirculation during radiation therapy for breast cancer. Acta Oncologica, 56(8), 1072-1080
Open this publication in new window or tab >>Changes in skin microcirculation during radiation therapy for breast cancer
2017 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 8, p. 1072-1080Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Oxfordshire: Taylor & Francis, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-134594 (URN)10.1080/0284186X.2017.1299220 (DOI)000402609100006 ()28281359 (PubMedID)
Available from: 2017-02-20 Created: 2017-02-20 Last updated: 2018-05-03Bibliographically approved
Flejmer, A. M., Chehrazi, B., Josefsson, D., Toma-Dasu, I. & Dasu, A. (2017). Impact of physiological breathing motion for breast cancer radiotherapy with proton beam scanning: An in silico study. Physica medica (Testo stampato), 39, 88-94
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
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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
Ödén, J., Toma-Dasu, I., Eriksson, K., Flejmer, A. M. & Dasu, A. (2017). The influence of breathing motion and a variable relative biological effectiveness in proton therapy of left-sided breast cancer. Acta Oncologica, 56(11), 1428-1436
Open this publication in new window or tab >>The influence of breathing motion and a variable relative biological effectiveness in proton therapy of left-sided breast cancer
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2017 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 11, p. 1428-1436Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Taylor & Francis, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-139955 (URN)10.1080/0284186X.2017.1348625 (DOI)000423464400013 ()28826308 (PubMedID)2-s2.0-85028572416 (Scopus ID)
Note

Funding agnecies: Cancer Research Funds of Radiumhemmet

Available from: 2017-08-22 Created: 2017-08-22 Last updated: 2018-06-14Bibliographically approved
Flejmer, A. M. (2016). Radiation burden from modern radiation therapy techniques including proton therapy for breast cancer treatment - clinical implications. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Radiation burden from modern radiation therapy techniques including proton therapy for breast cancer treatment - clinical implications
2016 (English)Doctoral 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.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. p. 64
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1505
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-127370 (URN)10.3384/diss.diva-127370 (DOI)978-91-7685-850-9 (ISBN)
Public defence
2016-06-01, Hugo Theorell, Campus US, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2016-04-27 Created: 2016-04-23 Last updated: 2016-05-13Bibliographically approved
Flejmer, A. M., Edvardsson, A., Dohlmar, F., Josefsson, D., Nilsson, M., Witt Nyström, P. & Dasu, A. (2016). Respiratory gating for proton beam scanning versus photon 3D-CRT for breast cancer radiotherapy. Acta Oncologica, 55(5), 577-583
Open this publication in new window or tab >>Respiratory gating for proton beam scanning versus photon 3D-CRT for breast cancer radiotherapy
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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
Flejmer, A. M., Dohlmar, F., Nilsson, M., Stenmarker, M. & Dasu, A. (2015). Analytical Anisotropic Algorithm versus Pencil Beam Convolution for treatment planning of breast cancer: implications for target coverage and radiation burden of normal tissue. Anticancer Research, 35(5), 2841-2848
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
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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
Flejmer, A. M., Witt Nyström, P., Dohlmar, F., Josefsson, D. & Dasu, A. (2015). Potential benefit of scanned proton beam versus photons as adjuvant radiation therapy in breast cancer. International Journal of Particle Therapy, 1(4), 845-855
Open this publication in new window or tab >>Potential benefit of scanned proton beam versus photons as adjuvant radiation therapy in breast cancer
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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
Flejmer, A. M., Josefsson, D., Nilsson, M., Stenmarker, M. & Dasu, A. (2014). Clinical implications of the ISC technique for breast cancer radiotherapy and comparison with clinical recommendations. Anticancer Research, 34(7), 3563-3568
Open this publication in new window or tab >>Clinical implications of the ISC technique for breast cancer radiotherapy and comparison with clinical recommendations
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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
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-8425-8110

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