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Radiation burden from modern radiation therapy techniques including proton therapy for breast cancer treatment - clinical implications
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.ORCID iD: 0000-0001-8425-8110
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. , 64 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1505
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-127370DOI: 10.3384/diss.diva-127370ISBN: 978-91-7685-850-9 (print)OAI: oai:DiVA.org:liu-127370DiVA: diva2:922584
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
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
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2015 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 5, 2841-2848 p.Article 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
Keyword
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
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2014 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 7, 3563-3568 p.Article 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
Keyword
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
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2015 (English)In: International Journal of Particle Therapy, ISSN 2331-5180, Vol. 1, no 4, 845-855 p.Article 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.

Keyword
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
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2016 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 5, 577-583 p.Article 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
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2017 (English)In: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 39, 88-94 p.Article 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: 2017-08-09Bibliographically approved

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