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The influence of RBE variations in a clinical proton treatment plan for a hypopharynx cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. (Protonterapi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology. (Protonterapi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
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2005 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, Vol. 50, no 12, 2765-2777 p.Article in journal (Refereed) Published
Abstract [en]

Currently, most clinical range-modulated proton beams are assumed to have a fixed overall relative biological effectiveness (RBE) of 1.1. However, it is well known that the RBE increases with depth in the spread-out Bragg peak (SOBP) and becomes about 10% higher than mid-SOBP RBE at 2 mm from the distal edge (Paganetti 2003 Technol. Cancer Res. Treat. 2 413-26) and can reach values of 1.3-1.4 in vitro at the distal edge (Robertson et al 1975 Cancer 35 1664-77, Courdi et al 1994 Br. J. Radiol. 67 800-4). We present a fast method for applying a variable RBE correction with linear energy transfer (LET) dependent tissue-specific parameters based on the alpharef/betaref ratios suitable for implementation in a treatment planning system. The influence of applying this variable RBE correction on a clinical multiple beam proton dose plan is presented here. The treatment plan is evaluated by RBE weighted dose volume histograms (DVHs) and the calculation of tumour control probability (TCP) and normal tissue complication probability (NTCP) values. The variable RBE correction yields DVHs for the clinical target volumes (CTVs), a primary advanced hypopharynx cancer and subclinical disease in the lymph nodes, that are slightly higher than those achieved by multiplying the absorbed dose with RBE=1.1. Although, more importantly, the RBE weighted DVH for an organ at risk, the spinal cord is considerably increased for the variable RBE. As the spinal cord in this particular case is located 8 mm behind the planning target volume (PTV) and hence receives only low total doses, the NTCP values are zero in spite of the significant increase in the RBE weighted DVHs for the variable RBE. However, high NTCP values for the non-target normal tissue were obtained when applying the variable RBE correction. As RBE variations tend to be smaller for in vivo systems, this study-based on in vitro data since human tissue RBE values are scarce and have large uncertainties-can be interpreted as showing the upper limits of the possible effects of utilizing a variable RBE correction. In conclusion, the results obtained here still indicate a significant difference in introducing a variable RBE compared to applying a generic RBE of 1.1, suggesting it is worth considering such a correction in clinical proton therapy planning, especially when risk organs are located immediately behind the target volume.

Place, publisher, year, edition, pages
2005. Vol. 50, no 12, 2765-2777 p.
Keyword [en]
/*radiotherapy/radiation effects, Models; Protons/*therapeutic use, Radiotherapy Planning; Computer-Assisted/methods
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-94096DOI: 10.1088/0031-9155/50/12/003PubMedID: 15930601OAI: oai:DiVA.org:uu-94096DiVA: diva2:167832
Available from: 2006-03-15 Created: 2006-03-15 Last updated: 2010-01-21Bibliographically approved
In thesis
1. Comparative Treatment Planning in Radiotherapy and Clinical Impact of Proton Relative Biological Effectiveness
Open this publication in new window or tab >>Comparative Treatment Planning in Radiotherapy and Clinical Impact of Proton Relative Biological Effectiveness
2006 (Swedish)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Jämförande dosplaneringsstudier inom strålterapi samt betydelsen av relativ biologisk effekt för protoner
Abstract [en]

The development of new irradiation techniques is presently a very active field of research with increased availability of more sophisticated modalities such as intensity modulated photons (IMRT), protons and light ions. The primary aim of this work is to evaluate if the dose-distributions using IMRT and protons contribute to clinical advantages. A secondary aim is to investigate the potential clinical implication of the increased relative biological effect (RBE) for protons at the end of the Bragg peak.

The potential benefits are evaluated using physical dose measures and dose-response models for normal tissue complication probability (NTCP) and tumour control probability (TCP). Comparative treatment planning was performed using three locally advanced tumour types, left-sided node positive breast cancer, hypopharyngeal cancer, and rectal cancer. All studies showed that both IMRT and protons could improve the dose distributions compared to 3D-CRT, and significantly improve treatment results with lower NTCPs and, concerning hypopharyngeal cancer, higher TCP. Protons always resulted in smaller volumes receiving intermediate and low radiation doses.

Using protons or IMRT for left-sided node-positive breast cancer, the advantage is a significantly decreased risk for cardiac mortality (from 6.7% to 1%) and radiation induced pneumonitis (from 28.2% to less than 3%) compared to 3D-CRT. For hypopharyngeal cancer, protons and IMRT provide more selective treatment plans, higher TCP since a simultaneous boost technique is feasible, and better parotid gland sparing for several patients. For locally advanced rectal cancer, the NTCP for small bowel is potentially reduced by approximately 50% using IMRT or protons; protons have an even greater potential if the structure of the small bowel is parallel.

A variable RBE correction is developed and applied to a clinical proton treatment plan. A significant difference is obtained compared to the commonly accepted RBE correction of 1.1. This indicates that a variable RBE may be of importance in future proton treatment planning.

This thesis provides support for increased use both IMRT and proton radiotherapy, although stronger for protons. Therefore, investments in proton facilities with capacity for large clinical trials can be supported.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 62 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 117
Oncology, Radiotherapy, Comparative studies, Breast cancer, hypopharyngeal cancer, rectal cancer, Proton RBE, Onkologi
National Category
Cancer and Oncology
urn:nbn:se:uu:diva-6593 (URN)91-554-6184-X (ISBN)
Public defence
2006-04-06, Skoogsalen, Akademiska Sjukhuset, ingång 78, 75185 Uppsala, 13:15
Available from: 2006-03-15 Created: 2006-03-15Bibliographically approved

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Tilly, NinaJohansson, JonasIsacsson, UlfBlomquist, ErikGrusell, ErikGlimelius, Bengt
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