Comparison of intensity modulated radiotherapy (IMRT) with intensity modulated particle therapy (IMPT) using fixed beams or an ion gantry for the treatment of patients with skull base meningiomas
© Kosaki et al; licensee BioMed Central Ltd. 2012
Received: 25 December 2011
Accepted: 22 March 2012
Published: 22 March 2012
To examine the potential improvement in treatment planning for patients with skull base meningioma using IMRT compared to carbon ion or proton beams with and without a gantry.
Five patients originally treated with photon IMRT were selected for the study. Ion beams were chosen using a horizontal beam or an ion gantry. Intensity controlled raster scanning and the intensity modulated particle therapy mode were used for plan optimization. The evaluation included analysis of dose-volume histograms of the target volumes and organs at risk.
In comparison with carbon and proton beams only with horizontal beams, carbon ion treatment plans could spare the OARs more and concentrated on the target volumes more than proton and photon IMRT treatment plans. Using only a horizontal fixed beam, satisfactory plans could be achieved for skull base tumors.
The results of the case studies showed that using IMPT has the potential to overcome the lack of a gantry for skull base tumors. Carbon ion plans offered slightly better dose distributions than proton plans, but the differences were not clinically significant with established dose prescription concepts.
KeywordsPlan comparison Photon IMRT Carbon ions Protons Gantry
Treatment of skull base tumors is a challenge for the radiation oncologist. Optimization of dose distributions to complex target volumes has been a main goal over the last decades, and modern photon techniques such as Intensity Modulated Radiotherapy (IMRT) have significantly improved treatment of base of skull tumors. Histological subtypes in the skull base region include highly malignant tumors such as high-grade hemangiopericytomas, squamous cell carcinomas or sarcomas, but also benign lesions, such as meningiomas. In these patients, high local doses for tumor control are also required, however, also sparing of normal tissue to prevent treatment-related side effects impairing quality of life is of high importance.
Several publications reported comparison studies in the head and neck region and the central nervous system using proton or carbon ion therapy as well as conventional and/or IMRT [1–8]. In photon treatments, a gantry is standard today and is necessary to obtain good dose distributions and conformity and to avoid high doses to organs at risk (OAR). IMRT can create distributions with higher concentration to be desired target volumes and to spare OARs. Several comparative studies using protons or ions showed a potential superiority over photons, especially for larger target volumes . This is mostly due to the distinct characteristics of particle beams: Particle therapy has physical advantages with a sharp increase of dose in a well-defined depth (Bragg peak) and a rapid dose falloff beyond that maximum.
Experience with carbon ion radiotherapy has been acquired in the past mainly using horizontal beam lines. Excellent dose distributions can be achieved for numerous clinical cases using only horizontal beams. However the freedom to apply the beam on a gantry that rotates around the patient is expected to offer significant advantages, especially for certain anatomical regions, such as gastrointestinal tumors, paraspinal tumors, but also skull base lesions, as pointed out in Jäkel and Debus . There is an extreme variation of density in these areas. These heterogeneities affect the energy distribution in the beam, e.g. a bone, decreases the particle's physical range as an air cavity extends the physical range as compared to water . One of the advantages of a gantry is that it is possible to choose beam angles which pass through more homogeneous tissue, thus avoiding or reducing range uncertainties.
The Heidelberg Ion Therapy Center (HIT) started clinical operation in November 2009. At HIT, 3 treatment rooms, two with a horizontal fixed beam and one with a carbon ion and proton gantry, are available for treatment.
In the present study, we performed a comparative planning study for complex skull base tumors focusing on meningioma patients evaluating IMRT, protons and carbon ions with and without a gantry in an institutional "real-time szenario". The IMPT mode is available at HIT and we adopted this mode for the calculation. The focus was put on evaluation of dose distributions, and DVH analysis with special respect to OAR.
Materials and methods
Clinical features of five meningioma patients
Target volume (cm3)
left skull base
right skull base
skull base - left temporal lobe
left skull base
Target volume definition for different techniques and dose concepts
For benign meningiomas the gross tumor volume (GTV) is defined as the macroscopically visible tumor on contrast-enhanced imaging; a clinical target volume (CTV) of about 1-2 mm is added to allow for potential microscopic spread. A planning target volume (PTV) is added depending on the technique used and the known setup inaccuracies, between 1-3 mm.
At HIT, we have established target volume and dosing concepts for different radiation techniques depending on the histology, the necessary clinical target volume, the required dose and the beam quality. With photons, skull base menigniomas are treated with total doses of 52.2-57.6 Gy depending on the size of the lesion and the vicinity to OAR, in single doses of 1.8 Gy. Since protons are associated with an overall comparable RBE, the same dose and fractionation schemes are applied with photons. For carbon ions, due to the reduced beam broadening as well as the known higher RBE, slightly hypofractionated regimens (with 3 Gy E single doses) have been established within our clinical routine at HIT, based on the favourable clinical data obtained at GSI. To compare plans in our "real time scenario", these dose and fractionation schedules were used in the present analysis.
For target volume definition, PTV margins at HIT include not only setup inaccuracy as for photons, but also range uncertainties. For example, for skull base tumors, commonly, a median PTV margin of 3 mm is used in our institution for protons and carbon ions.
Treatment plans and delivery
Couch and gantry angles for patients
original photon IMRT
carbon/proton ion horizontal
proton gantry plan
(8, 90) (172, 90) (272, 90)
8 beam IMRT
(8, 90) (330, 90)
(8, 70) (8, 120)
8 beam IMRT
(172, 90) (210, 90)
(355, 240) (355, 270)
8 beam IMRT
(8,90) (335, 90)
8 beam IMRT
(8,90) (172, 90) (320, 90)
(0,150) (0, 305) (270, 60)
Dose prescripition for patients (original dose, proton dose, carbon ion dose)
original photon IMRT
carbon ion plan
The evaluation included analysis of dose-volume histograms of the target volumes and organs at risk. For each patient and each organ, a set of physical parameters was computed from the DVHs to assess the general characteristics of different techniques. The same dose constraints were adopted for optimization of the same patient's plan. Plans were also assessed by visual inspection of dose distributions.
Each patient was analyzed individually. PTV size data for each patient are reported in Table 1. The mean volume was 79.2 cm3, median 76.6 cm3, minimum 17.0 cm3, and maximum 170.3 cm3.
Dose distributions and dose volume histograms for each case
Results of the dose distribution for the PTV and OARs of case 1
photon IMRT (%)
carbon ion (%)
Right optic nerve
Results of the dose distribution for the PTV and OAR of case 5
photon IMRT (%)
horizontal plan (%)
In the present work we compared treatment planning using IMRT, protons and carbon ions for complex-shaped menigiomas in the skull base region. In most cases, IMRT provided excellent dose distributions, and only for certain OAR particle therapy showed a substantial benefit. Even for complex shapes a gantry was not essential in most cases. However, to avoid air-filled cavities in some clinical situations to reduce uncertainties, beam angles provided by a gantry are most likely to be highly superior. A quantitative analysis of the robustness of the treatment plans against these effects was beyond the scope of this work.
Compared to other intracranial tumors, skull base meningiomas often have complex shapes [21–27]. Particle therapy may be offered to patients with meniningiomas, especially as they are characterized by long-term survival, and minimization of treatment related side effects is of high importance, including neurocognitive sequelae [18–20, 28]. Therefore, increasing dose conformality and reducing dose to normal tissue is of high importance. Particle therapy could offer highly conformal irradiation for complex-shaped intracranial meningiomas, since it is characterized by excellent dose conformity. In this study, two comparisons were examined. First, original photon plans and demonstration plans using proton and carbon ion were compared. Second, these comparison plans were made as well to examine the benefits of a gantry when skull base tumors were treated with particle therapy. Comparisons were carried out in terms of physical parameters derived from 3D dose distributions and DVH calculations. Since the aim of the study was to provide some rationaly as to which patients clearly benefit from a gantry as opposed to a horizontal beam (since at HIT, both possibilities are available) a "real-time-szenario" was chosen respecting the institutional dose and fractionation schemes for photons, protons and carbon ions. For example, due to the biological and physical characteristics of the carbon beam, carbon ions are applied with 3 Gy E single doses in our institution . This includes not only dose and fractionation schemes, but also dose constraints and dose-volume-parameters used for treatment plan optimization.
In particle therapy planning, spot-scanning delivery methods were used and the IMPT mode was used for optimization. From a physical point of view, carbon ions show a sharper Bragg peak and less lateral scattering than protons, but also a significant dose in the fragmentation tail behind the peak . In our comparison study, carbon ion plans could achieve better conformation of the dose to the target volumes than proton plans especially in the high dose areas and better sparing of dose to most of the organs at risk. But the differences were small and proton plans resulted in better sparing of some of the organs at risk as compared to photon IMRT. Concerning the additional improvement of dose concentration using carbon ions, however, there is no clear picture. Carbon beams show a higher dose behind the target because of the fragmentation tail. Therefore the low dose area around 30% isodose for carbon ions plans is larger in the distal region than for proton plans. Photon IMRT could also spare some organs at risk well in some cases, but the low-dose area in the photon IMRT plans were obviously much larger than in particle therapy plans. It should be kept in mind, however, that an additional benefit from carbon ions which is expected due to their radiobiological properties is not displayed in the treatment plan. E.g. a higher RBE is expected in the tumor as compared to the normal tissue, but a fixed RBE table is currently used for all tissues in the TPS. Additionally, is should be kept in mind that differences in pencil beam size can potentially contribute to differences in the treatment plan differences between ions themselves, but also compared to photons.
Baumert et al. reported that protons were generally better than photons at sparing dose to the OAR which was close to the target. But when they used only two fields to one patient, protons showed higher doses to surrounding OARs. A higher number of fields may result in a better conformity . It was also experienced in our study. Compared to photon IMRT, small numbers of beams are employed for particle therapy. That means one beam has a big influence on the dose distribution and beam arrangements are very important. In making demonstration plans, we avoided to use an anterior beam to spare dose from sensitive OARs such as the eyes. Additionally an anterior field would have to pass through the oral cavity which poses large problems for proton and carbon ion calculations due to the large variability of position and interfaces between materials with large density differences.
The calculation results showed that the OARs which were far from targets were irradiated with lower mean doses in particle therapy than in photon IMRT. For the maximum dose, some cases showed higher doses in particle plans than in photon plans, possibly due to the use of only two or three radiation fields. Depending on the tumor location, even a third beam was not necessary. Lomax et al. performed a comparison study between IMRT and proton radiotherapy and nine beams were employed to compare the plans . They used the identical beam geometry, dose constraints, importance factor, but changed dose-volume constraints depending on the plans. In this study, they reported the use of nine proton fields could well be sub-optimal in paranasal sinus area tumor, and the use of a smaller number of well chosen fields could achieve a similar level of target coverage and sparing of critical structures.
For facilities equipped with gantries, planning for dose delivery of protons and for carbon ions therapy has the same degrees of freedom as for the photon therapy. The aim of our study was to evaluate which cases are relatively easily accessible with horizontal fixed beam, and in which cases a gantry is really beneficial. In this study, the advantage of a gantry is not obvious. The first reason may be that most of the tumor shapes were irregular and complex and even if the gantry was used, it was difficult to find beam arrangements avoiding organs at risk while fully irradiating the target volumes at the same time. The second reason is probably that the IMPT optimization mode was adopted. IMPT plans can be delivered using the spot scanning system at HIT. Before making IMPT plans, we made demonstration plans with the single beam optimization (SBO) mode. Compared with these two different modes, the results were apparently better using IMPT mode than SBO mode. IMPT mode could improve the conformity inside the target volumes and spare the organs at risk which were in the vicinity of the tumors. Mizumoto et al. have reported the results of the three patients' treatment plans using non-coplanar beams in Tsukuba, Japan . They concluded that non-coplanar proton beam therapy has advantages in selected patients. If the tumor extends mainly along the beam direction, the advantage of the gantry beams would be significant. The major difference of our study as compared to  is the treatment delivery system. The proton facility in Tsukuba used passive beam delivery, while HIT adopts active spot scanning beam delivery. In active beam delivery, the energy of the incoming beam is varied during the treatment . Consequently IMPT can be accomplished. Because of the IMPT mode, it was considered that the advantage of the gantry with active methods seemed to be less than with passive methods. The results in this study showed that clinically satisfactory plans could be achieved by means of a horizontal beam line for skull base tumors with IMPT optimization  and a gantry does not lead to a clinically significant improvement in most cases. The role of uncertainties for both options is, however, not clear yet. That is to say, the IMPT mode has the potential to overcome the lack of the gantry for patients with skull base tumors.
This study attempted to explore the differences of dose distribution between carbon ions and protons compared to photons in an institutional "real-time szenario". Compared to photon IMRT, only marginal improvements may be seen at the required doses and dose distributions. For tumors requiring even higher doses, the additional benefit of a particle beam may be much greater, due to the reduction of integral dose. We also attempted to analyse the potential benefit of the gantry for skull base meningiomas. In the analysis of these five cases, carbon ion plans showed better dose conformation to the target volumes and sparing of OAR than proton plans in most of the cases. These differences were small and the advantage of carbon ions compared with protons is not always obvious. However, this work implied that the IMPT mode may offer treatment plans with improved quality for skull base tumors even if the facility doesn't have a gantry. This finding is likely to change for tumors located in the trunk of the body, e.g. gastrointestinal tumors or paraspinal tumors, where the access through highly sensitive OAR in combination with deeply located target volumes with horizontal beams may be much more difficult.
Dose Volume Histogram
Heidelberg Ion Therapy Center
Intensity Modulated Particle Therapy
Intensity Modulated Radiation Therapy
Organ at risk
Planning Target Volume
Relative Biological Effectiveness
Single Beam Optimization
Treatment Planning System
World Health Organization
The authors would like to thank Ms. Xenia Popova and Mr. Steffen Lissner for support with data management.
- Islam MA, Yanagi T, Mizoe J, Mizuno H, Tsujii H: Comparative study of dose distribution between carbon ion radiotherapy and photon radiotherapy for head and neck tumor. Radiat Med 2008, 26: 415-421. 10.1007/s11604-008-0252-9View ArticleGoogle Scholar
- Lomax AJ, Goitein M, Adams J: Intensity modulation in radiotherapy: photons versus protons in the paranasal sinus. Radiother Oncol 2003, 66: 11-18.View ArticlePubMedGoogle Scholar
- Mock U, Georg D, Bogner J, Auberger T, Pötter R: Treatment planning comparison of conventional, 3D conformal, and intensity-modulated photon (IMRT) and proton therapy for paranasal sinus carcinoma. Int J Radiat Oncol Biol Phys 2004, 58: 147-154. 10.1016/S0360-3016(03)01452-4View ArticlePubMedGoogle Scholar
- Cozzi L, Fogliata A, Lomax A, Bolsi A: A treatment planning comparison of 3D conformal therapy, intensity modulated photon therapy and proton therapy for treatment of advanced head and neck tumours. Radiother Oncol 2001, 61: 287-297. 10.1016/S0167-8140(01)00403-0View ArticlePubMedGoogle Scholar
- Baumert BG, Lomax AJ, Miltchev V, Davis JB: A compariosn of dose distributions of proton and photon beams in stereotactic conformal radiotherapy of brain lesions. Int J Radiat Oncol Biol Phys 2001, 49: 1439-1449. 10.1016/S0360-3016(00)01422-XView ArticlePubMedGoogle Scholar
- Cozzi L, Clivio A, Vanetti E, Nicolini G, Fogliata A: Comparative planning study for proton radiotherapy of benign brain tumors. Strahlenther Onkol 2006, 182: 376-81. 10.1007/s00066-006-1500-5View ArticlePubMedGoogle Scholar
- Fuss M, Hug EB, Schaefer RA, et al.: Proton radiation therapy (PRT) for pedoatric optic pathway gliomas: comparison with 3D planned conventional photons and a standard photon technique. Int J Radiat Oncol Biol Phys 1999, 45: 1117-1126. 10.1016/S0360-3016(99)00337-5View ArticlePubMedGoogle Scholar
- Bolsi A, Fogliata A, Cozzi L: Radiotherapy of small intracranial tumours with different advanced techniques using photon and proton beams: a treatment planning study. Radiother Oncol 2003, 68: 1-14. 10.1016/S0167-8140(03)00117-8View ArticlePubMedGoogle Scholar
- Hug EB, Devries A, Thornton AF, et al.: Management of atypical and malignant meningiomas: role of high-dose, 3D-conformal radiation therapy. J Neurooncol 2000, 48: 151-160. 10.1023/A:1006434124794View ArticlePubMedGoogle Scholar
- Wenkel E, Thornton AF, Finkelstein D, et al.: Benign meningioma: partially resected, biopsied, and recurrent intracranial tumors treated with combined proton and photon radiotherapy. Int J Radiat Oncol Biol Phys 2000, 48: 1363-70. 10.1016/S0360-3016(00)01411-5View ArticlePubMedGoogle Scholar
- Boskos C, Feuvret L, Noel G, et al.: Combined proton and photon conformal radiotherapy for intracranial atypical and malignant meningioma. Int J Radiat Oncol Biol Phys 2009, 75: 399-406. 10.1016/j.ijrobp.2008.10.053View ArticlePubMedGoogle Scholar
- Noel G, Bollet MA, Calugaru V, et al.: Functional outcome of patients with benign meningioma treated by 3D conformal irradiation with a combination of photons and protons. Int J Radiat Oncol Biol Phys 2005, 62: 1412-1422. 10.1016/j.ijrobp.2004.12.048View ArticlePubMedGoogle Scholar
- Jäkel O, Debus J: Selection of beam angles for radiotherapy of skull base tumours using charged particles. Phys Med Biol 2000, 45: 1229-41. 10.1088/0031-9155/45/5/311View ArticlePubMedGoogle Scholar
- Suit H, DeLaney T, Goldberg S, et al.: Proton vs carbon ion beams in the definitive radiation treatment of cancer patients. Radiother Oncol 2010, 95: 3-22. 10.1016/j.radonc.2010.01.015View ArticlePubMedGoogle Scholar
- Combs SE, Bischof M, Welzel T, et al.: Radiochemotherapy with temozolomide as re-irradiation using high precision fractionated stereotactic radiotherapy (FSRT) in patients with recurrent gliomas. J Neurooncol 2008, 89: 205-10. 10.1007/s11060-008-9607-4View ArticlePubMedGoogle Scholar
- Debus J, Wuendrich M, Pirzkall A, et al.: High efficacy of fractionated stereotactic radiotherapy of large base-of-skull meningiomas: long-term-results. J Clin Oncol 2001, 19: 3547-53.PubMedGoogle Scholar
- Emami B, Lyman J, Brown A, et al.: Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991, 21: 109-22.View ArticlePubMedGoogle Scholar
- Vernimmen FJ, Harris JK, Wilson JA, Melvill R, Smit BJ, Slabbert JP: Stereotactic proton beam therapy of skull base meningiomas. Int J Radiat Oncol Biol Phys 2001, 49: 99-105. 10.1016/S0360-3016(00)01457-7View ArticlePubMedGoogle Scholar
- Gudjonsson O, Blomquist E, Nyberg G, et al.: Stereotactic irradiation of skull base meningiomas with high energy protons. Acta Neurochir (Wien) 1999, 141: 933-940. 10.1007/s007010050399View ArticleGoogle Scholar
- Combs SE, Hartmann C, Nikoghosyan A, et al.: Carbon ion radiation therapy for high-risk meningioma. Radiother Oncol 2010, 95: 54-59. 10.1016/j.radonc.2009.12.029View ArticlePubMedGoogle Scholar
- Glaholm J, Bloom HJ, Crow JH: The role of radiotherapy in the managemant of intracranial meningiomas: The Royal Marsden Hospital experience with 186 patients. Int J Radiat Oncol Biol Phys 1990, 18: 755-761. 10.1016/0360-3016(90)90394-YView ArticlePubMedGoogle Scholar
- Cusimano MD, Sekhar LN, Sen CN, et al.: The results of surgery for benign tumors of the cavernous sinus. Neurosurgery 1995, 37: 1-9. 10.1227/00006123-199507000-00001View ArticlePubMedGoogle Scholar
- De Jesus O, Sekhar LN, Parikh HK, Wright DC, Wagner DP: Long-term follow-up of patients with meningiomas involving the cavernous sinus: Recurrence, progression, and quality of life. Neurosurgery 1996, 39: 915-919.View ArticlePubMedGoogle Scholar
- DeMonte F, Smith HK, al Mefty O: Outcome of aggressive removal of cavernous sinus meningiomas. J Neurosurg 1994, 81: 245-251. 10.3171/jns.1994.81.2.0245View ArticlePubMedGoogle Scholar
- Goel A, Muzumdar D, Desai KI: Tuberculum sellae meningioma: A report on management on the basis of a surgical experience with 70 patients. Neurosurgery 2002, 51: 1358-1363.PubMedGoogle Scholar
- Newman SA: Meningiomas: A quest for the optimum therapy. J Neurosurg 1994, 80: 191-194. 10.3171/jns.1994.80.2.0191View ArticlePubMedGoogle Scholar
- Noel G, Habrand JL, Mammar H, et al.: Highly conformal therapy using proton component in the management of meningiomas. Preliminary experience of the Centre de Proton-therapie d'Orsay. Strahlenther Onkol 2002, 178: 480-485. 10.1007/s00066-002-0960-5View ArticlePubMedGoogle Scholar
- Weber DC, Lomax AJ, Rutz HP, et al.: Spot-scanning proton radiation therapy for recurrent, residual or untreated intracranial meningiomas. Radiother Oncol 2004, 71: 251-258. 10.1016/j.radonc.2004.02.011View ArticlePubMedGoogle Scholar
- Wilkins JJ, Oelfke U: Direct comparison of biologically optimized spread-out bragg peaks for protons and carbon ions. Int J Radiat Oncol Biol Phys 2008, 70: 262-266. 10.1016/j.ijrobp.2007.08.029View ArticleGoogle Scholar
- Mizumoto M, Nakayama H, Tokita M, et al.: Technical considerations for noncoplanar proton-beam therapy of patients with tumors proximal to the optic nerve. Strahlenther Onkol 2010, 186: 36-39. 10.1007/s00066-009-2019-3View ArticlePubMedGoogle Scholar
- Schulz-Ertner D, Tsujii H: Particle radiation therapy using proton and heavier ion beams. J Clin Oncol 2007, 25: 953-64. 10.1200/JCO.2006.09.7816View ArticlePubMedGoogle Scholar
- Combs SE, Nikoghosyan A, Jaekel O, et al.: Carbon ion radiotherapy for pediatric patients and young adults treated for tumors of the skull base. Cancer 2009, 115: 1348-1354. 10.1002/cncr.24153View ArticlePubMedGoogle Scholar
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