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Does Intensity-modulated Stereotactic Radiotherapy Achieve Superior Target Conformity than Conventional Stereotactic Radiotherapy in Different Intracranial Tumours?
Clinical Oncology (2009) 21: 408e416 doi:10.1016/j.clon.2009.02.002
Original Article
Does Intensity-modulated Stereotactic Radiotherapy Achieve Superior Target Conformity than Conventional Stereotactic Radiotherapy in Different Intracranial Tumours? S. D. Sharma*, R. Jalaliy, R. D. Phurailatpamz, T. Guptaz *Department of Medical Physics, Tata Memorial Hospital, Dr. Ernest Borges Marg, Parel, Mumbai, India; yDepartment of Radiation Oncology, Tata Memorial Hospital, Dr. Ernest Borges Marg, Parel, Mumbai, India; zDepartment of Radiation Oncology, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, India
ABSTRACT: Aims: To compare the dosimetric outcome of various conventional stereotactic radiotherapy (SRT) techniques with intensity-modulated stereotactic radiotherapy (IMSRT) in brain tumours of varying shape, size, location and proximity to organs at risk (OARs). Materials and methods: Fused computed tomography and magnetic resonance imaging datasets of four patients with different brain tumours previously treated with non-coplanar static conformal fields (SCF) were re-planned on the BrainScan treatment planning system using non-coplanar conformal arcs (CA), dynamic conformal arcs (DCA) and IMSRT with coplanar (IMSRT_CP) or non-coplanar (IMSRT_NCP) beam arrangement. Beam shaping and intensity modulation were carried out using a BrainLab micromultileaf collimator. The primary objective for each plan was to encompass R99% of the planning target volume (PTV) by O95% of the prescribed dose while minimising the dose to OARs. Results: The mean PTV coverage in SCF, CA, DCA, IMSRT_NCP and IMSRT_CP was 99.2, 99.5, 99.4, 99.2 and 99.2%, respectively. The highest dose within the target was !107% of the prescribed dose in all plans. Conformity was found to vary depending on the shape and location of the target. The best mean conformity index, ranging from 0.74 (CA) to 0.84 (IMSRT_NCP) was observed in spherical tumours. Among the three conventional SRT techniques, DCA and SCF appeared comparable (mean conformity index 0.72 and 0.71, respectively) and more conformal than CA (mean conformity index 0.67). In all cases, IMSRT showed better target conformity than conventional SRT techniques with a mean conformity index of 0.83 for non-coplanar and 0.81 for coplanar beam arrangement. The maximum improvement in conformity index was observed for IMSRT_NCP in complex, concave and irregularly shaped targets. The volume of normal brain and other OARs irradiated to high ( R80%) and low ( R30%) dose varied depending on the tumour shape, size, and location, but was essentially comparable in all three conventional SRT techniques. IMSRT (both coplanar as well as non-coplanar) reduced the volume of normal brain being irradiated to moderate to high doses compared with conventional SRT techniques, more so for large and irregular targets. Conclusions: DCA and SCF are preferred conventional SRT techniques in terms of target conformity and reduction of doses to OARs. The use of IMSRT_NCP further improves conformity and reduces doses to OARs in a range of brain tumours commonly considered for stereotactic irradiation. Sharma, S. D. et al. (2009). Clinical Oncology 21, 408—416 ª 2009 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. Key words: Brain tumour, conformity index, IMSRT, SRT
Introduction Stereotactic radiosurgery (SRS) techniques using a linear accelerator have evolved from the initial arc-based approach with standard circular cones to miniature multileaf collimator (MLC)-shaped dynamic conformal arcs (DCA) [1e4]. The radiobiological advantages of fractionation combined with localisation precision and repositioning accuracy of stereotactic systems has made fractionated stereotactic radiotherapy (SRT) a widely accepted standard treatment for several benign to low-grade intracranial 0936-6555/09/210408þ09 $36.00/0
tumours. In the recent past, the potential of beam intensity modulation using miniature MLC combined with the precision of stereotactic positioning has been explored for superior dose conformation in intensity-modulated stereotactic radiotherapy (IMSRT) [5,6]. Although the data for a formal qualitative dosimetric comparison of conventional SRT techniques with IMSRT are available for geometrical targets and meningiomas [5,6], most commonly in the skull base, similar data are lacking for other histologies, as well as brain tumours having complex, concave, or irregular shapes and at differing locations. Moreover, it is not
ª 2009 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
DOSIMETRIC COMPARISON OF IMSRT AND CONVENTIONAL SRT IN INTRACRANIAL TUMOURS Table 1 e Patient characteristics and target volumes
Case 1 2 3 4
Diagnosis
Site
GTV (cm3)
PTV (cm3)
Craniopharyngioma Optic chiasmatic glioma Cerebellar astrocytoma Schwannoma
Sellar/suprasellar Sellar/suprasellar Posterior fossa Right parasellar
20.62 6.43 14.13 34.09
51.92 29.53 49.65 88.28
GTV, gross tumour volume; PTV, planning target volume.
entirely clear how IMSRT would compare with other existing and well-established SRT techniques for spherical targets. This study was undertaken to compare the dosimetric outcome of various SRT techniques and to evaluate the potential role of IMSRT in the treatment of brain tumours of different shape, size, location and proximity to organs at risk (OARs) using the same device for beam shaping and intensity modulation. The dosimetric outcome of IMSRT using coplanar fields (IMSRT_CP) was compared with different conventional stereotactic irradiation techniques, including multiple non-coplanar static conformal fields (SCF), conformal arcs (CA) and DCA. Moreover, the role of non-coplanar beam arrangement in IMSRT planning (IMSRT_NCP) was also evaluated for improvement in conformity and reduction of OAR doses.
Materials and Methods Patient Selection Four paediatric patients with different benign and lowgrade brain tumours were selected for this dosimetric study (Table 1). These cases were selected to represent tumours varying in shape, size, location and proximity to critical organs. The mean planning target volume (PTV) of the selected cases was 55 cm3 (range 29.5e88.3 cm3).
Dose Planning Fused computed tomography and magnetic resonance imaging datasets of these four patients previously treated
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with 6 MV X-rays using multiple non-coplanar SCF were selected for the present dosimetry study. All patients were planned on BrainScan (V5.31, BrainLAB GmbH, Heimstetten, Germany) treatment planning system (TPS) using 6 MV X-rays. The SCF plan consisted of six or seven non-coplanar static fields, each field individually shaped to the beams eye view projection of the target using a miniature MLC. The 26 pairs of miniature MLC (BrainLAB) with its variable projected leaf width of 0.3, 0.45 and 0.55 cm at the isocentre can define a maximum field size of 10.2 10.2 cm2 and can operate in the dynamic mode for the modulation of beam intensity. The details of the beam geometry used in this SCF planning and shaping of conformal field have been described elsewhere [7]. Each patient was re-planned on the BrainScan TPS with non-coplanar CA, non-coplanar DCA and IMSRT with coplanar (IMSRT_CP) or non-coplanar (IMSRT_NCP) beam arrangement. Typical plan parameters for all the different planning approaches are summarised in Table 2. These parameters were customised to individual cases by optimising the couch and gantry angles by a few degrees from the typical geometry. The beam geometry of every patient was kept unchanged in CA and DCA. However, unlike CA where the shape of the field aperture remains constant during an arc, in DCA the shape of the miniature MLC was automatically adjusted to the projection of the target in beams eye view for every 10 increment from the gantry start angle. The dynamic sliding window technique was used for IMSRT. The IMSRT_NCP plan was carried out using the same beam arrangement as in SCF for the respective patient, whereas the IMSRT_CP plan was generated for each patient using six equally spaced coplanar fields. In all techniques, a 0.1e0.2 cm isometric margin was added uniformly around the target to account for penumbra and, thereby, improve target coverage. The position of a few miniature MLCs in each field was manually edited in the SCF plans to improve target conformity. The BrainScan TPS uses a pencil beam algorithm for regular dose computation and the dynamically penalised likelihood method, a variant of the maximum likelihood estimator, to obtain optimum fluence in IMSRT planning [8,9]. All plans were generated using a single isocentre. A dose of 54 Gy in
Table 2 e Description of various treatment techniques and typical plan parameters Planning technique
No. fields/arcs
Static conformal fields (SCF)
6e7 uniform-intensity non-coplanar fields
Conformal arcs (CA)
6 uniform-intensity non-coplanar arcs
Dynamic conformal arcs (DCA) Intensity-modulated radiotherapye non-coplanar (IMRT_NCP) Intensity-modulated radiotherapye coplanar (IMRT_CP)
6 uniform-intensity non-coplanar arcs 6e7 intensity-modulated non-coplanar fields 6 intensity-modulated coplanar fields
Typical table (T) and gantry (G) angles (() T ¼ 10, G ¼ 260; T ¼ 350, G ¼ 100; T ¼ 60, G ¼ 60 & 120; T ¼ 300, G ¼ 300 & 240 T ¼ 90, G ¼ 340 T ¼ 0, G ¼ (60e120) T ¼ 30, G ¼ (30e130) T ¼ 60, G ¼ (30e130) Same as CA Same as SCF T ¼ 0, G ¼ 0, 52, 104, 156, 208, 260 and 312
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Fig. 1 e Resultant dose distribution from all five different techniques: (a) non-coplanar static conformal fields (SCF), (b) non-coplanar conformal arcs (CA), (c) dynamic conformal arcs (DCA), (d) intensity-modulated stereotactic radiotherapy with non-coplanar beam arrangement (IMSRT_NCP) and (e) intensity-modulated stereotactic radiotherapy with coplanar beam arrangement (IMSRT_CP) for a complex and irregularly shaped target in the case of a right parasellar schwannoma.
30 fractions was prescribed and normalised to the isocentre, with 100% as the prescription isodose. To facilitate direct comparison between different techniques, the primary planning objective was to encompass R99% of PTV by O95% of the prescribed dose at the isocentre, while maintaining the maximum dose limit at 107%, as recommended by International Commission on Radiation Units and Measurements Report 50 (ICRU 50) [10]. Moreover, maximum effort was made to keep the dose to the OARs as minimum as possible.
Plan Evaluation The dosimetric outcome of different techniques was compared qualitatively and quantitatively in terms of target volume coverage, conformity and irradiation of normal brain and OARs, such as temporal lobe and brainstem, to varying dose levels. Target coverage was estimated as the percentage of the target volume (VT) covered by the prescription dose (VT,Pi), i.e. target coverage ¼ (VT,Pi/VT) 100%. The conformity of the target was
DOSIMETRIC COMPARISON OF IMSRT AND CONVENTIONAL SRT IN INTRACRANIAL TUMOURS
411
(mean conformity index ¼ 0.67, standard deviation ¼ 0.05). The worst mean conformity index was seen in cerebellar astrocytoma in the posterior fossa (case 3). In all cases, IMSRT showed better target conformity with a mean conformity index (standard deviation) of 0.83 (0.02) for noncoplanar and 0.81 (0.02) for coplanar beam arrangements. The maximum improvement in conformity with IMSRT plans was observed in complex, concave and irregular targets, such as cerebellar astrocytoma (case 3) and parasellar schwannoma (case 4). IMSRT_CP and IMSRT_NCP plans were essentially similar in conformity for spherical targets, but IMSRT_NCP achieved better conformity for complex targets (parasellar schwannoma).
estimated using a conformity index defined by Paddick [11] as conformity index ¼ {VT,Pi VT,Pi}/{VT VPi}, where VPi is the volume enclosed by the prescription isodose. This conformity index also takes into account the location of the prescription isodose volume (VPi) relative to the target volume (VT). The volumes of normal brain, temporal lobes and brainstem receiving high (R80%) and low (R30%) doses were also compared. Results are reported as mean values with respective standard deviations.
Results Dose Coverage and Conformity to Target The resultant dose distribution from all five techniques in a complex and irregularly shaped target (case 4: parasellar scwhannoma) is shown in Fig. 1aee. Qualitative evaluation of the dose distribution resulting from different conventional SRT techniques showed better dose conformation to the target volume with DCA and SCF plans as compared with CA. The IMSRT_NCP plan was most favourable with regards to target conformity and avoidance of critical organs as compared with other techniques. Dose homogeneity was within the ICRU 50 recommendations in all plans. Table 3 shows quantitative evaluation of dose-volume indices of interest. All treatment planning techniques covered O99% of the PTV in every patient. The mean target coverage (standard deviation) was 99.2% (0.18), 99.5% (0.10) and 99.4% (0.27) in SCF, CA, and DCA plans, respectively. The corresponding values from IMSRT_NCP and IMSRT_CP plans were 99.2% (0.17) and 99.2% (0.18). The highest dose within the PTV was !107% of the prescribed dose in all plans for all cases. The conformity was found to vary depending on the shape and location of the target. The best mean conformity index, ranging from 0.74 (CA) to 0.84 (IMSRT_NCP) was seen in optic chiasmatic glioma (case 2), which represents the most spherically shaped tumour among the selected cases. Target conformity was seen to decrease with increasing target complexity (large, concave and irregularly shaped targets). Among the three conventional SRT techniques, SCF and DCA were comparable with regard to target conformity, with a mean conformity index of 0.71 (standard deviation 0.05) and 0.72 (standard deviation 0.04), respectively. CA plans were the least conformal
Dose to Normal Brain and Other Organs at Risk The volume of normal brain and other OARs irradiated to high ( R80%) and low ( R30%) doses varied largely depending on the tumour shape, size, location and irradiation technique. Figure 2 shows the percentage volume of normal brain receiving at least 80% (Fig. 2a) and 30% (Fig. 2b) of the prescribed dose at the isocentre from the different treatment planning techniques in all four patients. In all cases, both IMSRT plans showed better sparing of normal brain irradiated to moderate to high doses, the maximum reduction being observed for the largest and most irregularly shaped tumour (case 4: parasellar schwannoma). IMSRT_NCP reduced the high-dose volume of normal brain in all cases as compared with SCF, CA and DCA by an average of 110% (range 34e285%), 143% (69e340%) and 108% (43e289%), respectively. The low-dose volume of normal brain was least with DCA. High-dose volume irradiating the temporal lobes was largest in parasellar schannoma (right) and craniopharyngioma (left). As expected, temporal lobes were not exposed to high-dose volumes in cerebellar astrocytoma. IMSRT_NCP achieved best sparing of temporal lobes (a reduction in high-dose volumes) as compared with other techniques (Fig. 3a, b). IMSRT_NCP also showed better sparing of brainstem volume irradiated to high (Fig. 4a) and low doses (Fig. 4b) as compared with other techniques. The highest reduction (mean 378%) of brainstem volume irradiated to high doses was seen in the most spherical tumour (case 2). The overall
Table 3 e Target coverage (TC) and conformity index (CI) with different techniques SCF
CA
DCA
IMSRT_NCP
IMSRT_CP
Mean (case)
Case
TC%
CI
TC%
CI
TC%
CI
TC%
CI
TC%
CI
TC%
CI
1 2 3 4 Mean (plan)
99.5 99.1 99.2 99.1 99.2
0.72 0.78 0.66 0.70 0.71
99.5 99.6 99.3 99.4 99.5
0.67 0.74 0.62 0.63 0.67
99.5 99.2 99.7 99.1 99.4
0.71 0.79 0.68 0.72 0.72
99.1 99.5 99.2 99.2 99.2
0.81 0.84 0.81 0.84 0.83
99.1 99.4 99.1 99.4 99.2
0.80 0.84 0.81 0.79 0.81
99.3 99.4 99.3 99.2 99.3
0.74 0.80 0.72 0.73 0.75
SCF, static conformal fields; CA, conformal arcs; DCA, dynamic conformal arcs; IMSRT_NCP, non-coplanar intensity-modulated stereotactic radiotherapy; IMSRT_CP, coplanar intensity-modulated stereotactic radiotherapy.
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Case 2
Case 3
Case 4
% of normal brain receiving at least 80% of the prescribed dose
a 14 12 10 8 6
Case 4 Case 3 Number of Case 2 Patients
4 2
Case 1
0 SCF
CA
DCA
IMRT_NCP
IMRT_CP
Treatment planning techniques Case 1
Case 2
Case 3
Case 4
% of normal brain receiving at least 30% of the prescribed dose
b 40 35 30 25 20 15
case 4 Case 3 Number of Case 2 patients Case 1
10 5 0
SCF
CA
DCA
IMRT_NCP
IMRT_CP
Treatment planning techniques Fig. 2 e Percentage of normal brain volume receiving at least (a) 80% and (b) 30% of the prescribed dose with different treatment planning techniques for each patient.
reduction of high-dose volume of brainstem with IMSRT_NCP as compared with SCF, CA and DCA was 152, 136 and 127%, respectively. Low-dose volume of brainstem was maximum in SCF plans.
Discussion Linear accelerator-based SRS/SRT techniques have evolved from the initial arc-based approach with standard circular cones to miniature MLC-shaped DCA [1e4]. During the progress of stereotactic planning and delivery, each new method was compared with the previously established best method before being implemented clinically. Numerous reports on the dosimetric comparison of various SRS/SRT techniques are available in peer-reviewed indexed medical literature for various intracranial tumours [5,6,12e14]. For irregularly shaped small targets, the SCF technique has shown superior conformity and homogeneity compared with
circular arcs [12e14]. Solberg et al. [15] dosimetrically compared DCA with SCF and non-coplanar circular arcs and proposed DCA as an efficient and effective method for accurately delivering a homogeneous target dose while simultaneously minimising peripheral doses in radiosurgery applications. More recently, the potential of beam intensity modulation has been evaluated for SRS/SRT [5,6,16,17]. Cardinale et al. [5] showed that IMSRT resulted in superior dose conformation in geometrical targets and better normal brain sparing from high and low doses as compared with circular collimator-based arcs and custom blocked non-coplanar static fields. In a similar study on small (1.2e3.5 cm3) irregularly shaped targets, the same group reported significant dosimetric improvements with intensity-modulated plans in terms of target coverage, normal tissue irradiation, and critical OAR sparing to significant dose levels [16]. However, for spherical and slightly larger tumours, no or very modest advantage has previously been reported for IMSRT [5,18,19]. In a more elaborate study,
DOSIMETRIC COMPARISON OF IMSRT AND CONVENTIONAL SRT IN INTRACRANIAL TUMOURS
Case 1
Case 2
case 3
413
Case 4
a
% of Right temporal lobe receiving at least 80% of the prescribed dose
90 80 70 60 50 40 30 20 Case 4
10
Case 3 0
Case 2
SCF
CA
DCA
IMRT_NCP
Treatment planning techniques Case 1
b
Case 2
Case 3
Case 1 IMRT_CP
Case 4
% of Left temporal lobe receiving at least 80% of the prescribed dose
25
20
15
10
5 Case 4 Case 3 0 SCF
Case 2 CA
DCA
IMRT_NCP
Treatment planning techniques
Case 1
Number of patients
IMRT_CP
Fig. 3 e Percentage volume of (a) right and (b) left temporal lobes receiving at least 80% of the prescribed dose with different treatment planning techniques for each patient.
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% of Brainstem volume receiving at leat 80% of the prescribed dose
a
Case 2
Case 3
Case 4
100 90 80 70 60 50 40 30 20 10 0
Case 4 Case 3 Case 2 Number of Case 1 Patients SCF
CA
DCA
IMRT_NCP
IMRT_CP
Treatment planning techniques
b
Case 1
Case 2
Case 3
Case 4
% of Brainstem volume receiving at least 30% of the prescribed dose
100 90 80 70 60 50 40
Case 4
30
Case 3
20
Case 2
10
Case 1
0 SCF
CA
DCA
IMRT_NCP
Number of Patients
IMRT_CP
Treatment planning techniques Fig. 4 e Percentage of brainstem volume receiving at least (a) 80% and (b) 30% of the prescribed dose with different treatment planning techniques for each patient.
involving meningiomas of the skull base, Baumert et al. [6] reported a higher conformity index with IMSRT (largest improvement seen in multifocal and irregular targets) as compared with the SCF technique. They also reported lower moderate to high doses (50e80%) to OARs, but the volume of normal tissues receiving low doses (!30%) could be larger than for uniform-intensity SCF techniques. In an attempt to optimise the SRT delivery technique, Clark and colleagues [20] compared SCF and DCA with IMSRT in 21 patients with meningiomas of the skull base. The mean Radiation Therapy Oncology Group (RTOG) conformity index was 1.75 each in SCF and DCA, which was significantly inferior to IMSRT (conformity index 1.66, P ! 0.05). The conformity index in IMSRT was inversely proportional to the PTV, with larger tumours (O25 cm3) consistently benefiting with IMSRT. The total volume of normal tissues getting irradiated to various dose levels was also significantly less with IMSRT (P ! 0.05).
More recently, the process, precision and clinical implementation of image-guided IMSRT using helical tomotherapy has been described in detail [21], which should provide further impetus to the adoption of such technology in clinical practice. None of the reported studies compared the miniature MLC-based SRT techniques with IMSRT plans utilising both coplanar and non-coplanar beam arrangements. Moreover, the dosimetric effect of using different beam shaping and intensity modulation devices was not addressed in many of the reported studies. The current study draws strength from the fact that it compares all established conventional SRT techniques (SCF, CA, DCA), and IMSRT with coplanar and noncoplanar beam arrangements (IMSRT_CP and IMRT_NCP), with beam shaping and intensity modulation being carried out using the same hardware and software (miniature MLC and TPS). A drawback was the limited number of patients precluding any formal statistical comparisons.
DOSIMETRIC COMPARISON OF IMSRT AND CONVENTIONAL SRT IN INTRACRANIAL TUMOURS
The dosimetric comparison of the three conventional SRT techniques using uniform beam intensity favoured DCA in terms of conformity and OAR sparing (reduction of doses to normal brain and brainstem), which is in agreement with previously published data [15,17]. However, a quantitative comparison is neither possible nor tenable, as the reported studies lacked quantitative dosimetric parameters and were conducted on small tumours treated with radiosurgery. Although DCA seems to be dosimetrically favourable to SCF, logistical issues, such as the ease of implementation, quality assurance requirements and time-resource burden, also need to be considered while selecting the appropriate SRT technique in the clinic. This study has shown that IMSRT plans achieve superior conformity for a range of targets as compared with arcbased techniques (CA and DCA) as well as SCF. The mean conformity index (0.83) estimated from the IMSRT_NCP plans in this study on a range of benign to low-grade intracranial tumours with differing shapes, volume and location was comparable with that of Baumert et al. [6] who also reported a mean conformity index of 0.83 with a similar technique. However, the mean conformity index of the SCF plans (0.71) used in this study was better than that of Baumert et al. (0.65) using an identical technique. This could primarily be due to the selection of more complex and irregularly shaped targets in Baumert et al.’s study. There was substantial improvement in conformity even for the spherically shaped tumours (cases 1 and 2) with IMSRT. Similar to previous reports, IMSRT_NCP plans resulted in maximum improvement in the conformity index and OAR sparing in the largest and most complex-shaped target (case 4: parasellar schannoma) [5,6,16]. The use of non-coplanar beam arrangement in IMSRT leads to only a marginal increase in conformity index as compared with coplanar beams, but can help in reducing OAR doses. A sixfield arrangement was chosen as the benchmark IMRT_CP technique, as no major dosimetric advantage was seen when the number of fields was increased to nine. Doses outside the target volume were also considerably less at all dose levels in the IMRT_NCP plan as compared with other competing techniques. The volume of normal brain outside the PTV irradiated to various dose levels is generally considered important, as there is a relative lack of anatomically specified regions in the brain correlating with long-term toxicity of irradiation. Neurocognitive dysfunction is perhaps the most important late sequelae of radiotherapy, particularly in children and young adults. All the four selected cases in this study belonged to the paediatric population, wherein a reduction in dose to the normal brain as well as other OARs should potentially translate into maximal clinical benefit. However, even if the comparison was attempted on adults with comparable tumours, the dosimetric outcome of all presented techniques would probably have been similar to the children in the current study. Temporal lobes, particularly mesial temporal lobes and the hippocampus, have been shown to harbour neural stem cells, believed to be responsible for cognitive functions and are therefore increasingly being recognised as distinct avoidance structures [22]. IMSRT plans
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consistently showed a reduction in moderate- to high-dose volumes of both temporal lobes as compared with CA or fixed fields. There is emerging evidence that a reduction in doses to temporal lobes translates into preservation of neurocognitive function in children treated with conformal radiotherapy techniques [23e25]. IMSRT by minimising doses to the temporal lobes as compared with uniform-intensity conformal techniques should potentially further improve the therapeutic index for these patients. Nevertheless, it is pertinent to note that modest differences in dosimetry are unlikely to result in clinically different outcomes. The potential of single-fraction intensity-modulated SRS (IMSRS) has not yet been fully realised. In a planning study [26] involving six patients with small benign tumours of the skull base, it was concluded that RTOG radiosurgery guidelines were best met with the DCA technique rather than the IMSRS approach, which increased the time for planning, delivery and integral doses to the brain. The brainstem is one of the most critical organs in singlefraction SRS applications. CA and fixed-field techniques that are commonly used for uniform-intensity radiosurgery plans strictly need to respect the tolerance of the brainstem, sometimes even at the cost of target coverage or conformity. The favourable dosimetric profile shown by IMSRT may provide a therapeutic window in such settings to apply single-fraction IMSRS as well.
Conclusion Among the three conventional SRT techniques, DCA and SCF seem to be comparable in terms of target conformity and reduction in dose to normal brain, brainstem and other OARs. Both techniques are dosimetrically superior to CA, which seems to be the least preferred technique. IMSRT_NCP achieves superior target conformity and better sparing of OARs compared with all conventional SRT techniques in a range of benign and low-grade brain tumours varying in shape, volume and location, commonly considered for stereotactic irradiation in contemporary neuro-oncology practice. Apart from dosimetric advantages, factors such as ease of implementation, quality assurance requirements, and time-resource burden also need to be considered when selecting the appropriate SRT technique. Clinical validation of the dosimetric comparison needs to be carried out in appropriately designed prospective clinical trials. Author for correspondence: S. D. Sharma, Medical Physics Department, 126G, Annex Building, Tata Memorial Hospital, Dr. Ernest Borges Marg, Parel, Mumbai 400 012, India. Tel: þ91-2224177000x4301, 4307; Fax: þ91-22-4146937; E-mail: dayananda. [email protected] Received 11 March 2008; received in revised form 3 January 2009; accepted 2 February 2009
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and noncoplanar circular arcs. Int J Radiat Oncol Biol Phys 2001;49:1481e1491. Benedict SH, Cardinale R, Wu Q, et al. Intensity-modulated stereotactic radiosurgery using dynamic micro-multileaf collimation. Int J Radiat Oncol Biol Phys 2001;50:751e758. Grabenbauer GG, Stecken AE, Schneider F, et al. Radiosurgery of functioning pituitary adenomas: comparison of different treatment techniques including dynamic and conformal arcs, shaped beams, and IMRT. Int J Radiat Oncol Biol Phys 2006;66: S33eS39. Khoo VS, Oldham M, Adams EJ, et al. Comparison of intensitymodulated tomotherapy with stereotactically guided conformal radiotherapy for brain tumors. Int J Radiat Oncol Biol Phys 1999;45:415e425. Woo SY, Grant WH, Bellezza D, et al. A comparison of intensity modulated conformal therapy with a conventional external beam stereotactic radiosurgery system for the treatment of single and multiple intracranial lesions. Int J Radiat Oncol Biol Phys 1996;35:593e597. Clark BG, Candish C, Voltans E, et al. Optimization of stereotactic radiotherapy treatment delivery technique for base-of-skull meningiomas. Med Dosim 2008;33:239e247. Holmes TW, Hudes R, Dziuba S, et al. Stereotactic image-guided intensity modulated radiotherapy using the HI ART II helical tomotherapy system. Med Dosim 2008;33:135e148. Barani IJ, Benedict SH, Lin PS. Neural stem cells: implications for the conventional radiotherapy of central nervous system malignancies. Int J Radiat Oncol Biol Phys 2007;68:324e333. Jalali R, Goswami S, Sarin R, et al. Neuropsychological status in children and young adults with benign and low-grade brain tumours treated prospectively with focal stereotactic conformal radiotherapy. Int J Radiat Oncol Biol Phys 2006;66:S14eS19. Merchant TE, Mulhern RK, Krasin MW, et al. Preliminary results from a phase II trial of conformal radiation therapy and evaluation of radiation related CNS effects for pediatric patients with localised ependymoma. J Clin Oncol 2004;22:3156e3162. Merchant TE, Kiehna EN, Kun LE, et al. Phase II trial of conformal radiation therapy for pediatric patients with craniopharyngioma and correlation of surgical factors and radiation dosimetry with change in cognitive function. J Neurosurg 2006; 104(2 Suppl):94e102. Ernst-Stecken A, Lambrecht U, Ganslandt O, et al. Radiosurgery of small skull-base lesions. No advantage for intensity modulated stereotactic radiosurgery versus conformal arc technique. Strahlenther Onkol 2005;181:336e344.
Original Article
Does Intensity-modulated Stereotactic Radiotherapy Achieve Superior Target Conformity than Conventional Stereotactic Radiotherapy in Different Intracranial Tumours? S. D. Sharma*, R. Jalaliy, R. D. Phurailatpamz, T. Guptaz *Department of Medical Physics, Tata Memorial Hospital, Dr. Ernest Borges Marg, Parel, Mumbai, India; yDepartment of Radiation Oncology, Tata Memorial Hospital, Dr. Ernest Borges Marg, Parel, Mumbai, India; zDepartment of Radiation Oncology, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, India
ABSTRACT: Aims: To compare the dosimetric outcome of various conventional stereotactic radiotherapy (SRT) techniques with intensity-modulated stereotactic radiotherapy (IMSRT) in brain tumours of varying shape, size, location and proximity to organs at risk (OARs). Materials and methods: Fused computed tomography and magnetic resonance imaging datasets of four patients with different brain tumours previously treated with non-coplanar static conformal fields (SCF) were re-planned on the BrainScan treatment planning system using non-coplanar conformal arcs (CA), dynamic conformal arcs (DCA) and IMSRT with coplanar (IMSRT_CP) or non-coplanar (IMSRT_NCP) beam arrangement. Beam shaping and intensity modulation were carried out using a BrainLab micromultileaf collimator. The primary objective for each plan was to encompass R99% of the planning target volume (PTV) by O95% of the prescribed dose while minimising the dose to OARs. Results: The mean PTV coverage in SCF, CA, DCA, IMSRT_NCP and IMSRT_CP was 99.2, 99.5, 99.4, 99.2 and 99.2%, respectively. The highest dose within the target was !107% of the prescribed dose in all plans. Conformity was found to vary depending on the shape and location of the target. The best mean conformity index, ranging from 0.74 (CA) to 0.84 (IMSRT_NCP) was observed in spherical tumours. Among the three conventional SRT techniques, DCA and SCF appeared comparable (mean conformity index 0.72 and 0.71, respectively) and more conformal than CA (mean conformity index 0.67). In all cases, IMSRT showed better target conformity than conventional SRT techniques with a mean conformity index of 0.83 for non-coplanar and 0.81 for coplanar beam arrangement. The maximum improvement in conformity index was observed for IMSRT_NCP in complex, concave and irregularly shaped targets. The volume of normal brain and other OARs irradiated to high ( R80%) and low ( R30%) dose varied depending on the tumour shape, size, and location, but was essentially comparable in all three conventional SRT techniques. IMSRT (both coplanar as well as non-coplanar) reduced the volume of normal brain being irradiated to moderate to high doses compared with conventional SRT techniques, more so for large and irregular targets. Conclusions: DCA and SCF are preferred conventional SRT techniques in terms of target conformity and reduction of doses to OARs. The use of IMSRT_NCP further improves conformity and reduces doses to OARs in a range of brain tumours commonly considered for stereotactic irradiation. Sharma, S. D. et al. (2009). Clinical Oncology 21, 408—416 ª 2009 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. Key words: Brain tumour, conformity index, IMSRT, SRT
Introduction Stereotactic radiosurgery (SRS) techniques using a linear accelerator have evolved from the initial arc-based approach with standard circular cones to miniature multileaf collimator (MLC)-shaped dynamic conformal arcs (DCA) [1e4]. The radiobiological advantages of fractionation combined with localisation precision and repositioning accuracy of stereotactic systems has made fractionated stereotactic radiotherapy (SRT) a widely accepted standard treatment for several benign to low-grade intracranial 0936-6555/09/210408þ09 $36.00/0
tumours. In the recent past, the potential of beam intensity modulation using miniature MLC combined with the precision of stereotactic positioning has been explored for superior dose conformation in intensity-modulated stereotactic radiotherapy (IMSRT) [5,6]. Although the data for a formal qualitative dosimetric comparison of conventional SRT techniques with IMSRT are available for geometrical targets and meningiomas [5,6], most commonly in the skull base, similar data are lacking for other histologies, as well as brain tumours having complex, concave, or irregular shapes and at differing locations. Moreover, it is not
ª 2009 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
DOSIMETRIC COMPARISON OF IMSRT AND CONVENTIONAL SRT IN INTRACRANIAL TUMOURS Table 1 e Patient characteristics and target volumes
Case 1 2 3 4
Diagnosis
Site
GTV (cm3)
PTV (cm3)
Craniopharyngioma Optic chiasmatic glioma Cerebellar astrocytoma Schwannoma
Sellar/suprasellar Sellar/suprasellar Posterior fossa Right parasellar
20.62 6.43 14.13 34.09
51.92 29.53 49.65 88.28
GTV, gross tumour volume; PTV, planning target volume.
entirely clear how IMSRT would compare with other existing and well-established SRT techniques for spherical targets. This study was undertaken to compare the dosimetric outcome of various SRT techniques and to evaluate the potential role of IMSRT in the treatment of brain tumours of different shape, size, location and proximity to organs at risk (OARs) using the same device for beam shaping and intensity modulation. The dosimetric outcome of IMSRT using coplanar fields (IMSRT_CP) was compared with different conventional stereotactic irradiation techniques, including multiple non-coplanar static conformal fields (SCF), conformal arcs (CA) and DCA. Moreover, the role of non-coplanar beam arrangement in IMSRT planning (IMSRT_NCP) was also evaluated for improvement in conformity and reduction of OAR doses.
Materials and Methods Patient Selection Four paediatric patients with different benign and lowgrade brain tumours were selected for this dosimetric study (Table 1). These cases were selected to represent tumours varying in shape, size, location and proximity to critical organs. The mean planning target volume (PTV) of the selected cases was 55 cm3 (range 29.5e88.3 cm3).
Dose Planning Fused computed tomography and magnetic resonance imaging datasets of these four patients previously treated
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with 6 MV X-rays using multiple non-coplanar SCF were selected for the present dosimetry study. All patients were planned on BrainScan (V5.31, BrainLAB GmbH, Heimstetten, Germany) treatment planning system (TPS) using 6 MV X-rays. The SCF plan consisted of six or seven non-coplanar static fields, each field individually shaped to the beams eye view projection of the target using a miniature MLC. The 26 pairs of miniature MLC (BrainLAB) with its variable projected leaf width of 0.3, 0.45 and 0.55 cm at the isocentre can define a maximum field size of 10.2 10.2 cm2 and can operate in the dynamic mode for the modulation of beam intensity. The details of the beam geometry used in this SCF planning and shaping of conformal field have been described elsewhere [7]. Each patient was re-planned on the BrainScan TPS with non-coplanar CA, non-coplanar DCA and IMSRT with coplanar (IMSRT_CP) or non-coplanar (IMSRT_NCP) beam arrangement. Typical plan parameters for all the different planning approaches are summarised in Table 2. These parameters were customised to individual cases by optimising the couch and gantry angles by a few degrees from the typical geometry. The beam geometry of every patient was kept unchanged in CA and DCA. However, unlike CA where the shape of the field aperture remains constant during an arc, in DCA the shape of the miniature MLC was automatically adjusted to the projection of the target in beams eye view for every 10 increment from the gantry start angle. The dynamic sliding window technique was used for IMSRT. The IMSRT_NCP plan was carried out using the same beam arrangement as in SCF for the respective patient, whereas the IMSRT_CP plan was generated for each patient using six equally spaced coplanar fields. In all techniques, a 0.1e0.2 cm isometric margin was added uniformly around the target to account for penumbra and, thereby, improve target coverage. The position of a few miniature MLCs in each field was manually edited in the SCF plans to improve target conformity. The BrainScan TPS uses a pencil beam algorithm for regular dose computation and the dynamically penalised likelihood method, a variant of the maximum likelihood estimator, to obtain optimum fluence in IMSRT planning [8,9]. All plans were generated using a single isocentre. A dose of 54 Gy in
Table 2 e Description of various treatment techniques and typical plan parameters Planning technique
No. fields/arcs
Static conformal fields (SCF)
6e7 uniform-intensity non-coplanar fields
Conformal arcs (CA)
6 uniform-intensity non-coplanar arcs
Dynamic conformal arcs (DCA) Intensity-modulated radiotherapye non-coplanar (IMRT_NCP) Intensity-modulated radiotherapye coplanar (IMRT_CP)
6 uniform-intensity non-coplanar arcs 6e7 intensity-modulated non-coplanar fields 6 intensity-modulated coplanar fields
Typical table (T) and gantry (G) angles (() T ¼ 10, G ¼ 260; T ¼ 350, G ¼ 100; T ¼ 60, G ¼ 60 & 120; T ¼ 300, G ¼ 300 & 240 T ¼ 90, G ¼ 340 T ¼ 0, G ¼ (60e120) T ¼ 30, G ¼ (30e130) T ¼ 60, G ¼ (30e130) Same as CA Same as SCF T ¼ 0, G ¼ 0, 52, 104, 156, 208, 260 and 312
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Fig. 1 e Resultant dose distribution from all five different techniques: (a) non-coplanar static conformal fields (SCF), (b) non-coplanar conformal arcs (CA), (c) dynamic conformal arcs (DCA), (d) intensity-modulated stereotactic radiotherapy with non-coplanar beam arrangement (IMSRT_NCP) and (e) intensity-modulated stereotactic radiotherapy with coplanar beam arrangement (IMSRT_CP) for a complex and irregularly shaped target in the case of a right parasellar schwannoma.
30 fractions was prescribed and normalised to the isocentre, with 100% as the prescription isodose. To facilitate direct comparison between different techniques, the primary planning objective was to encompass R99% of PTV by O95% of the prescribed dose at the isocentre, while maintaining the maximum dose limit at 107%, as recommended by International Commission on Radiation Units and Measurements Report 50 (ICRU 50) [10]. Moreover, maximum effort was made to keep the dose to the OARs as minimum as possible.
Plan Evaluation The dosimetric outcome of different techniques was compared qualitatively and quantitatively in terms of target volume coverage, conformity and irradiation of normal brain and OARs, such as temporal lobe and brainstem, to varying dose levels. Target coverage was estimated as the percentage of the target volume (VT) covered by the prescription dose (VT,Pi), i.e. target coverage ¼ (VT,Pi/VT) 100%. The conformity of the target was
DOSIMETRIC COMPARISON OF IMSRT AND CONVENTIONAL SRT IN INTRACRANIAL TUMOURS
411
(mean conformity index ¼ 0.67, standard deviation ¼ 0.05). The worst mean conformity index was seen in cerebellar astrocytoma in the posterior fossa (case 3). In all cases, IMSRT showed better target conformity with a mean conformity index (standard deviation) of 0.83 (0.02) for noncoplanar and 0.81 (0.02) for coplanar beam arrangements. The maximum improvement in conformity with IMSRT plans was observed in complex, concave and irregular targets, such as cerebellar astrocytoma (case 3) and parasellar schwannoma (case 4). IMSRT_CP and IMSRT_NCP plans were essentially similar in conformity for spherical targets, but IMSRT_NCP achieved better conformity for complex targets (parasellar schwannoma).
estimated using a conformity index defined by Paddick [11] as conformity index ¼ {VT,Pi VT,Pi}/{VT VPi}, where VPi is the volume enclosed by the prescription isodose. This conformity index also takes into account the location of the prescription isodose volume (VPi) relative to the target volume (VT). The volumes of normal brain, temporal lobes and brainstem receiving high (R80%) and low (R30%) doses were also compared. Results are reported as mean values with respective standard deviations.
Results Dose Coverage and Conformity to Target The resultant dose distribution from all five techniques in a complex and irregularly shaped target (case 4: parasellar scwhannoma) is shown in Fig. 1aee. Qualitative evaluation of the dose distribution resulting from different conventional SRT techniques showed better dose conformation to the target volume with DCA and SCF plans as compared with CA. The IMSRT_NCP plan was most favourable with regards to target conformity and avoidance of critical organs as compared with other techniques. Dose homogeneity was within the ICRU 50 recommendations in all plans. Table 3 shows quantitative evaluation of dose-volume indices of interest. All treatment planning techniques covered O99% of the PTV in every patient. The mean target coverage (standard deviation) was 99.2% (0.18), 99.5% (0.10) and 99.4% (0.27) in SCF, CA, and DCA plans, respectively. The corresponding values from IMSRT_NCP and IMSRT_CP plans were 99.2% (0.17) and 99.2% (0.18). The highest dose within the PTV was !107% of the prescribed dose in all plans for all cases. The conformity was found to vary depending on the shape and location of the target. The best mean conformity index, ranging from 0.74 (CA) to 0.84 (IMSRT_NCP) was seen in optic chiasmatic glioma (case 2), which represents the most spherically shaped tumour among the selected cases. Target conformity was seen to decrease with increasing target complexity (large, concave and irregularly shaped targets). Among the three conventional SRT techniques, SCF and DCA were comparable with regard to target conformity, with a mean conformity index of 0.71 (standard deviation 0.05) and 0.72 (standard deviation 0.04), respectively. CA plans were the least conformal
Dose to Normal Brain and Other Organs at Risk The volume of normal brain and other OARs irradiated to high ( R80%) and low ( R30%) doses varied largely depending on the tumour shape, size, location and irradiation technique. Figure 2 shows the percentage volume of normal brain receiving at least 80% (Fig. 2a) and 30% (Fig. 2b) of the prescribed dose at the isocentre from the different treatment planning techniques in all four patients. In all cases, both IMSRT plans showed better sparing of normal brain irradiated to moderate to high doses, the maximum reduction being observed for the largest and most irregularly shaped tumour (case 4: parasellar schwannoma). IMSRT_NCP reduced the high-dose volume of normal brain in all cases as compared with SCF, CA and DCA by an average of 110% (range 34e285%), 143% (69e340%) and 108% (43e289%), respectively. The low-dose volume of normal brain was least with DCA. High-dose volume irradiating the temporal lobes was largest in parasellar schannoma (right) and craniopharyngioma (left). As expected, temporal lobes were not exposed to high-dose volumes in cerebellar astrocytoma. IMSRT_NCP achieved best sparing of temporal lobes (a reduction in high-dose volumes) as compared with other techniques (Fig. 3a, b). IMSRT_NCP also showed better sparing of brainstem volume irradiated to high (Fig. 4a) and low doses (Fig. 4b) as compared with other techniques. The highest reduction (mean 378%) of brainstem volume irradiated to high doses was seen in the most spherical tumour (case 2). The overall
Table 3 e Target coverage (TC) and conformity index (CI) with different techniques SCF
CA
DCA
IMSRT_NCP
IMSRT_CP
Mean (case)
Case
TC%
CI
TC%
CI
TC%
CI
TC%
CI
TC%
CI
TC%
CI
1 2 3 4 Mean (plan)
99.5 99.1 99.2 99.1 99.2
0.72 0.78 0.66 0.70 0.71
99.5 99.6 99.3 99.4 99.5
0.67 0.74 0.62 0.63 0.67
99.5 99.2 99.7 99.1 99.4
0.71 0.79 0.68 0.72 0.72
99.1 99.5 99.2 99.2 99.2
0.81 0.84 0.81 0.84 0.83
99.1 99.4 99.1 99.4 99.2
0.80 0.84 0.81 0.79 0.81
99.3 99.4 99.3 99.2 99.3
0.74 0.80 0.72 0.73 0.75
SCF, static conformal fields; CA, conformal arcs; DCA, dynamic conformal arcs; IMSRT_NCP, non-coplanar intensity-modulated stereotactic radiotherapy; IMSRT_CP, coplanar intensity-modulated stereotactic radiotherapy.
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Case 2
Case 3
Case 4
% of normal brain receiving at least 80% of the prescribed dose
a 14 12 10 8 6
Case 4 Case 3 Number of Case 2 Patients
4 2
Case 1
0 SCF
CA
DCA
IMRT_NCP
IMRT_CP
Treatment planning techniques Case 1
Case 2
Case 3
Case 4
% of normal brain receiving at least 30% of the prescribed dose
b 40 35 30 25 20 15
case 4 Case 3 Number of Case 2 patients Case 1
10 5 0
SCF
CA
DCA
IMRT_NCP
IMRT_CP
Treatment planning techniques Fig. 2 e Percentage of normal brain volume receiving at least (a) 80% and (b) 30% of the prescribed dose with different treatment planning techniques for each patient.
reduction of high-dose volume of brainstem with IMSRT_NCP as compared with SCF, CA and DCA was 152, 136 and 127%, respectively. Low-dose volume of brainstem was maximum in SCF plans.
Discussion Linear accelerator-based SRS/SRT techniques have evolved from the initial arc-based approach with standard circular cones to miniature MLC-shaped DCA [1e4]. During the progress of stereotactic planning and delivery, each new method was compared with the previously established best method before being implemented clinically. Numerous reports on the dosimetric comparison of various SRS/SRT techniques are available in peer-reviewed indexed medical literature for various intracranial tumours [5,6,12e14]. For irregularly shaped small targets, the SCF technique has shown superior conformity and homogeneity compared with
circular arcs [12e14]. Solberg et al. [15] dosimetrically compared DCA with SCF and non-coplanar circular arcs and proposed DCA as an efficient and effective method for accurately delivering a homogeneous target dose while simultaneously minimising peripheral doses in radiosurgery applications. More recently, the potential of beam intensity modulation has been evaluated for SRS/SRT [5,6,16,17]. Cardinale et al. [5] showed that IMSRT resulted in superior dose conformation in geometrical targets and better normal brain sparing from high and low doses as compared with circular collimator-based arcs and custom blocked non-coplanar static fields. In a similar study on small (1.2e3.5 cm3) irregularly shaped targets, the same group reported significant dosimetric improvements with intensity-modulated plans in terms of target coverage, normal tissue irradiation, and critical OAR sparing to significant dose levels [16]. However, for spherical and slightly larger tumours, no or very modest advantage has previously been reported for IMSRT [5,18,19]. In a more elaborate study,
DOSIMETRIC COMPARISON OF IMSRT AND CONVENTIONAL SRT IN INTRACRANIAL TUMOURS
Case 1
Case 2
case 3
413
Case 4
a
% of Right temporal lobe receiving at least 80% of the prescribed dose
90 80 70 60 50 40 30 20 Case 4
10
Case 3 0
Case 2
SCF
CA
DCA
IMRT_NCP
Treatment planning techniques Case 1
b
Case 2
Case 3
Case 1 IMRT_CP
Case 4
% of Left temporal lobe receiving at least 80% of the prescribed dose
25
20
15
10
5 Case 4 Case 3 0 SCF
Case 2 CA
DCA
IMRT_NCP
Treatment planning techniques
Case 1
Number of patients
IMRT_CP
Fig. 3 e Percentage volume of (a) right and (b) left temporal lobes receiving at least 80% of the prescribed dose with different treatment planning techniques for each patient.
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CLINICAL ONCOLOGY Case 1
% of Brainstem volume receiving at leat 80% of the prescribed dose
a
Case 2
Case 3
Case 4
100 90 80 70 60 50 40 30 20 10 0
Case 4 Case 3 Case 2 Number of Case 1 Patients SCF
CA
DCA
IMRT_NCP
IMRT_CP
Treatment planning techniques
b
Case 1
Case 2
Case 3
Case 4
% of Brainstem volume receiving at least 30% of the prescribed dose
100 90 80 70 60 50 40
Case 4
30
Case 3
20
Case 2
10
Case 1
0 SCF
CA
DCA
IMRT_NCP
Number of Patients
IMRT_CP
Treatment planning techniques Fig. 4 e Percentage of brainstem volume receiving at least (a) 80% and (b) 30% of the prescribed dose with different treatment planning techniques for each patient.
involving meningiomas of the skull base, Baumert et al. [6] reported a higher conformity index with IMSRT (largest improvement seen in multifocal and irregular targets) as compared with the SCF technique. They also reported lower moderate to high doses (50e80%) to OARs, but the volume of normal tissues receiving low doses (!30%) could be larger than for uniform-intensity SCF techniques. In an attempt to optimise the SRT delivery technique, Clark and colleagues [20] compared SCF and DCA with IMSRT in 21 patients with meningiomas of the skull base. The mean Radiation Therapy Oncology Group (RTOG) conformity index was 1.75 each in SCF and DCA, which was significantly inferior to IMSRT (conformity index 1.66, P ! 0.05). The conformity index in IMSRT was inversely proportional to the PTV, with larger tumours (O25 cm3) consistently benefiting with IMSRT. The total volume of normal tissues getting irradiated to various dose levels was also significantly less with IMSRT (P ! 0.05).
More recently, the process, precision and clinical implementation of image-guided IMSRT using helical tomotherapy has been described in detail [21], which should provide further impetus to the adoption of such technology in clinical practice. None of the reported studies compared the miniature MLC-based SRT techniques with IMSRT plans utilising both coplanar and non-coplanar beam arrangements. Moreover, the dosimetric effect of using different beam shaping and intensity modulation devices was not addressed in many of the reported studies. The current study draws strength from the fact that it compares all established conventional SRT techniques (SCF, CA, DCA), and IMSRT with coplanar and noncoplanar beam arrangements (IMSRT_CP and IMRT_NCP), with beam shaping and intensity modulation being carried out using the same hardware and software (miniature MLC and TPS). A drawback was the limited number of patients precluding any formal statistical comparisons.
DOSIMETRIC COMPARISON OF IMSRT AND CONVENTIONAL SRT IN INTRACRANIAL TUMOURS
The dosimetric comparison of the three conventional SRT techniques using uniform beam intensity favoured DCA in terms of conformity and OAR sparing (reduction of doses to normal brain and brainstem), which is in agreement with previously published data [15,17]. However, a quantitative comparison is neither possible nor tenable, as the reported studies lacked quantitative dosimetric parameters and were conducted on small tumours treated with radiosurgery. Although DCA seems to be dosimetrically favourable to SCF, logistical issues, such as the ease of implementation, quality assurance requirements and time-resource burden, also need to be considered while selecting the appropriate SRT technique in the clinic. This study has shown that IMSRT plans achieve superior conformity for a range of targets as compared with arcbased techniques (CA and DCA) as well as SCF. The mean conformity index (0.83) estimated from the IMSRT_NCP plans in this study on a range of benign to low-grade intracranial tumours with differing shapes, volume and location was comparable with that of Baumert et al. [6] who also reported a mean conformity index of 0.83 with a similar technique. However, the mean conformity index of the SCF plans (0.71) used in this study was better than that of Baumert et al. (0.65) using an identical technique. This could primarily be due to the selection of more complex and irregularly shaped targets in Baumert et al.’s study. There was substantial improvement in conformity even for the spherically shaped tumours (cases 1 and 2) with IMSRT. Similar to previous reports, IMSRT_NCP plans resulted in maximum improvement in the conformity index and OAR sparing in the largest and most complex-shaped target (case 4: parasellar schannoma) [5,6,16]. The use of non-coplanar beam arrangement in IMSRT leads to only a marginal increase in conformity index as compared with coplanar beams, but can help in reducing OAR doses. A sixfield arrangement was chosen as the benchmark IMRT_CP technique, as no major dosimetric advantage was seen when the number of fields was increased to nine. Doses outside the target volume were also considerably less at all dose levels in the IMRT_NCP plan as compared with other competing techniques. The volume of normal brain outside the PTV irradiated to various dose levels is generally considered important, as there is a relative lack of anatomically specified regions in the brain correlating with long-term toxicity of irradiation. Neurocognitive dysfunction is perhaps the most important late sequelae of radiotherapy, particularly in children and young adults. All the four selected cases in this study belonged to the paediatric population, wherein a reduction in dose to the normal brain as well as other OARs should potentially translate into maximal clinical benefit. However, even if the comparison was attempted on adults with comparable tumours, the dosimetric outcome of all presented techniques would probably have been similar to the children in the current study. Temporal lobes, particularly mesial temporal lobes and the hippocampus, have been shown to harbour neural stem cells, believed to be responsible for cognitive functions and are therefore increasingly being recognised as distinct avoidance structures [22]. IMSRT plans
415
consistently showed a reduction in moderate- to high-dose volumes of both temporal lobes as compared with CA or fixed fields. There is emerging evidence that a reduction in doses to temporal lobes translates into preservation of neurocognitive function in children treated with conformal radiotherapy techniques [23e25]. IMSRT by minimising doses to the temporal lobes as compared with uniform-intensity conformal techniques should potentially further improve the therapeutic index for these patients. Nevertheless, it is pertinent to note that modest differences in dosimetry are unlikely to result in clinically different outcomes. The potential of single-fraction intensity-modulated SRS (IMSRS) has not yet been fully realised. In a planning study [26] involving six patients with small benign tumours of the skull base, it was concluded that RTOG radiosurgery guidelines were best met with the DCA technique rather than the IMSRS approach, which increased the time for planning, delivery and integral doses to the brain. The brainstem is one of the most critical organs in singlefraction SRS applications. CA and fixed-field techniques that are commonly used for uniform-intensity radiosurgery plans strictly need to respect the tolerance of the brainstem, sometimes even at the cost of target coverage or conformity. The favourable dosimetric profile shown by IMSRT may provide a therapeutic window in such settings to apply single-fraction IMSRS as well.
Conclusion Among the three conventional SRT techniques, DCA and SCF seem to be comparable in terms of target conformity and reduction in dose to normal brain, brainstem and other OARs. Both techniques are dosimetrically superior to CA, which seems to be the least preferred technique. IMSRT_NCP achieves superior target conformity and better sparing of OARs compared with all conventional SRT techniques in a range of benign and low-grade brain tumours varying in shape, volume and location, commonly considered for stereotactic irradiation in contemporary neuro-oncology practice. Apart from dosimetric advantages, factors such as ease of implementation, quality assurance requirements, and time-resource burden also need to be considered when selecting the appropriate SRT technique. Clinical validation of the dosimetric comparison needs to be carried out in appropriately designed prospective clinical trials. Author for correspondence: S. D. Sharma, Medical Physics Department, 126G, Annex Building, Tata Memorial Hospital, Dr. Ernest Borges Marg, Parel, Mumbai 400 012, India. Tel: þ91-2224177000x4301, 4307; Fax: þ91-22-4146937; E-mail: dayananda. [email protected] Received 11 March 2008; received in revised form 3 January 2009; accepted 2 February 2009
References 1 Lutz W, Winston K, Maleki R. A system of stereotactic radiosurgery with a linear accelerator. Int J Radiat Oncol Biol Phys 1988;14:373e381.
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