Tomotherapy planning of small brain tumours

Radiotherapy and Oncology 74 (2005) 49–52 www.elsevier.com/locate/radonline

Short communication

Tomotherapy planning of small brain tumours Slav Yartseva, Tomas Krona,*, Luca Cozzib, Antonella Fogliatab, Glenn Baumana a

London Regional Cancer Centre, 790 Commissioners Rd East, London, Ont., Canada N6A 4L6 b Oncology Institute of Southern Switzerland, Medical Physics, Bellinzona, Switzerland

Received 22 December 2003; received in revised form 13 September 2004; accepted 28 October 2004 Available online 25 November 2004

Abstract Helical tomotherapy (HT) combines a rotating intensity modulated fan beam with integrated CT imaging for high precision radiotherapy. HT plans for 12 patients with small brain tumours were compared with five other radiotherapy techniques. Proton techniques gave overall the best results, while HT was shown to produce better target dose uniformity (average SDZ1.3%) and kept irradiation of organs at risk as good as other photon methods. q 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Helical tomotherapy; Inverse treatment planning; Small brain tumour radiotherapy

1. Introduction The safety and efficacy of radiation therapy is predicated on the ability to deliver a therapeutic dose of radiation to a target volume while minimising exposure of surrounding critical structures. Tumours of the base of skull such as meningiomas, pituitary adenomas and acoustic neuromas are particularly challenging given the proximity of multiple critical structures (brain stem, eyes, optic chiasm and optic nerves) [10]. On the other hand, such tumours typically grow in a ‘benign’ fashion: enlarging without invading surrounding structures, thus presenting a situation requiring precision radiotherapy of the target without the need for larger volume regional treatment of normal tissues. In such cases, an appropriate choice of radiation technique may significantly improve the patient’s quality of life after treatment by minimising the potential for late radiation effects in the surrounding structures. In a previous paper [1], planning results were compared for five different radiation techniques for benign tumours of the base of skull: 3D conformal radiotherapy (3DCRT), stereotactic arc therapy (SRS/T), intensity-modulated radiotherapy with photons (IMRT), and radiotherapy with protons (spot scanning (SSP) or passive scattering (PSp)). In that work, among * Corresponding author. 0167-8140/$ - see front matter q 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.radonc.2004.10.017

the techniques studied, the passive scattering proton technique provided the best target conformality and uniformity and organ at risk sparing. Among the photon techniques, 3DCRT, IMRT and SRT provided similar target coverage and organ sparing with SRT providing slightly better organ at risk sparing but at a cost of slightly worse target dose uniformity and minimum dose. Recently, helical tomotherapy (HT) has become available as a new and promising delivery method for intensity modulated radiation therapy [7,8]. During HT delivery a radiation fan beam of 6 MV photons rotates around the patient while he/she slowly moves through the gantry. This results in a helical beam trajectory from a patient’s perspective. The photon fluence in different sections of the fan beam is modulated by a binary multi leaf collimator (MLC). The MLC configuration is optimised and varied as a function of gantry angle using an inverse treatment planning process [9], which allows delivery of highly conformal radiation doses to a target. In this communication, the results of treatment plans for helical tomotherapy are compared to the previous planning for the five other techniques for the same set of 12 patients with meningioma (five cases), neurinoma (five), and adenoma (two). We hypothesised that tomotherapy, given its excellent conformal avoidance properties [6], might be particularly useful in the cases where tumour is found in close proximity to several organs at risk.

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2. Materials and methods The 12 patients with small brain lesions (five meningiomas, five acoustic neuromas, and two pituitary adenomas) previously reported [1] were re-planned with the helical tomotherapy planning system for this study. Target sizes ranged from 0.49 to 14.3 cm3 (average 4.6 cm3) and target dose from 50 to 60 Gy in 25–30 fractions (average 56 Gy in 28 fractions). Planning target volumes (PTV) and organs at risk (OAR) were delineated on 3 mm CT data sets as in the previous paper [1] and used for HT planning without modification. The doselimiting organ at risk was identified as brain stem in seven patients and optic chiasm in five. Using the DICOM RT protocol the CT data sets and structures were transferred to the tomotherapy planning workstation (TomoTherapy Inc.). In the planning system the helical delivery is approximated by 51 projections per rotation and the dose calculation uses a total of 24 different angles for the dose spread array of the incident 6 MV beam with the beam quality assumed to be identical in all parts [2]. The dose was calculated using a superposition/convolution approach based on minimisation of an objective function through least squares optimisation [9]. Included in the objective function are target and organ at risk dose limits and penalties, desired DVH points and weighting factors. In this study, the prescription was specified for 95% coverage of the PTV with the meningiomas receiving 60 Gy, acoustic neuromas 55 Gy, and pituitary adenomas 50 Gy with a conventional schedule of 2 Gy per fraction. In re-planning the patients with the HT system, two main strategies were employed: (a) optimal PTV coverage (delivery of at least 95% of the prescribed dose to every

voxel within the PTV with maximum homogeneity) (b) improved OAR sparing. The flexibility of the tomotherapy delivery allowed ‘tuning’ of the plans according to specific goals set by a clinical oncologist without additional readjustments of beam angles and field sizes. Standard output of the tomotherapy planning workstation includes dose volume histograms (differential and cumulative DVH: dose in Gy vs. %volume) for all organs. As we wished to compare the results for patients planned with different prescribed doses, all DVHs were re-scaled and the doses were normalised to the mean dose to the PTV for each patient such that all doses are reported as a percentage of the mean target dose. Dose metrics used for comparison correspond to those previously reported [1]: target mean, minimum, and maximum doses and SD, and OAR maximum and mean doses. In addition, the total treatment time for both conventionally fractionated and single fraction treatments for each of the patients planned were estimated using parameters of the HiArtI system at the London Regional Cancer Centre (Output 9.5 Gy/min at central axis at 85 cm, TPR20 10 Z 0:61). Statistical analysis was performed using the ANOVA tool in Microsoft Excel comparing data for individual patients. A Bonferroni correction was applied to account for the fact that multiple tests are performed simultaneously [3]. Following this, the alpha level for 95% confidence (P-value !0.05) in detecting a difference between treatment plans was set at 0.00333 (for comparison of all six treatment approaches) and at 0.00833 (for comparison of photon treatment techniques only). Differences between treatment planning parameters achieved with different planning techniques were confirmed using a paired, two-sided t-test with a P-value for significance set at !0.05.

Table 1 Results of dose distribution for the target and OARs Organ

Parameter (%)

HT

SRS/T

3DCRT

IMRT

PSp

SSP

PTV

SD Min pt V90 V95 Mean V20 V40 Mean Max pt Mean Max pt Mean Max pt Mean Max pt Mean V20

1.31G0.32 96.1G0.32 100G0.0 99.5G1.0 26.8G11.3 60.9G25.6 20.1G19.0 34.3G28.6 57.9G40.5 20.7G16.0 34.6G30.6 14.0G8.7 19.3G12.0 9.6G4.5 16.8G7.7 6.7G3.4 3.7G3.3

3.13G1.1 81.0G11.4 98.8G1.0 94.9G2.8 14.1G10.7 21.7G25.3 8.4G11.2 26.1G28.4 51.3G46.8 8.2G11.3 22.7G30.7 5.3G6.3 8.1G12.1 2.9G1.4 4.9G3.3 7.3G2.8 7.8G5.9

3.00G0.54 91.0G2.5 99.8G0.2 94.8G2.6 26.4G14.9 55.6G29.3 23.3G26.0 34.8G30.9 54.9G43.4 16.2G17.5 32.4G29.5 10.4G8.8 18.4G13.6 6.7G5.5 14.5G6.4 6.7G2.7 9.8G6.0

2.34G0.59 93.2G1.3 100.0G0.0 98.2G1.9 29.8G14.4 59.9G29.5 28.9G21.2 41.5G35.1 59.0G43.8 18.6G18.3 36.5G33.8 14.2G13.4 24.3G18.4 8.4G5.8 18.7G8.3 8.0G2.8 11.2G5.9

1.82G0.44 92.8G4.5 99.9G0.4 99.0G0.4 7.6G7.9 11.7G12.3 7.6G8.8 20.9G27.6 47.5G50.8 4.7G9.9 21.6G33.3 0.4G0.7 4.8G11.1 0.0G0.1 0.8G2.0 2.2G1.3 3.6G2.3

2.83G0.56 91.0G2.7 99.8G0.6 96.0G2.4 8.0G0.7 12.8G12.7 7.4G8.3 21.4G26.8 50.0G52.4 6.6G11.1 24.7G33.3 0.7G1.3 5.6G10.8 0.1G0.1 1.0G1.9 1.8G0.9 3.2G1.5

Brain stem

Chiasm Optic nerve omolateral Optic nerve controlateral Eyes Brain—(brain stemCtarget)

HT, helical tomotherapy; SRS/T, stereotactic arc therapy; 3DCRT, 3D conformal radiotherapy; IMRT, intensity modulated radiotherapy with photons; PSp, passive scattering radiotherapy with protons; SSP, spot scanning radiotherapy with protons; SD, standard deviation. Vx denotes the fractional volume irradiated to a percentage dose higher than x% of the mean target dose.

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3. Results Table 1 compares target volume irradiation by HT to the other treatment modalities. We note that the homogeneity of the target irradiation predicted by the tomotherapy system (SD of 1.3%) is significantly better (P!0.05) than for any other technique including proton beam therapy. Tomotherapy also provided a significantly better minimum target dose (96.1%, P!0.05) coverage than the other modalities and excellent V90 and V95. Normalisation was made to the mean target dose, so in absolute values the target volumes lie well within the 95% of the prescription dose as required by the International Commission on Radiation Units and Measurements [4,5]. There was no significant difference between helical tomotherapy and IMRT and the proton techniques in regards to V90. Table 1 also summarises the results for the organs at risk obtained from the same optimisation plans as the data for tumours using the strategy of optimal PTV coverage for HT. Except for V20 for brain, the proton techniques proved to be significantly better in regards to normal tissue sparing than all photon techniques. When using ANOVA to compare the four photon based treatment techniques only, stereotactic radiosurgery was better in achieving lower doses to brain stem, optic nerves and the eyes. However, this advantage was compensated in HT by a lower V20 for the brain than all other photon techniques. Tolerance doses were not reached for any of the OARs considered and the results for tomotherapy are close to those offered by other photon plans. For example, the maximum dose to clinically significant volume of 1 cm3 of the brain stem was found to be 40G11 Gy (minimum 22 Gy, maximum 54 Gy), below tolerance level of 54 Gy for this structure. In five of the patients planned, both optimum PTV and optimum OAR sparing plans provided similar results. In these cases, there was sufficient separation between the PTV and OAR to enable both objectives to be met. In five cases, generally with an OAR abutting the PTV, use of a better OAR sparing strategy was able to improve OAR sparing with some compromise on the PTV. This is shown in Fig. 1(a): the plan with emphasis on good target coverage for the neurinoma case which belongs to the group of three patients with highest irradiation of the brain stem is shown. With a few changes in optimisation constraints for brain stem only it was possible to reduce the mean dose to the brain stem twofold, while accepting a reduction of quality in PTV coverage (V90: from 100 to 96.6%, V95: from 100 to 93.1%) as shown in Fig. 1(b). In two cases, with extensive overlap of an OAR with the PTV, the resulting plan was a compromise with neither PTV coverage nor OAR sparing optimisation strategies achieving significantly different results. The mean time of delivery of 2 Gy per fraction in HT was calculated to be 4.66G1.17 min (range 2.41– 5.84 min). Helical tomotherapy also allows delivery of dose in a single fraction as per common radiosurgery protocols.

Fig. 1. Cumulative DVHs of tumour, brain stem, brain and eyes for an acoustic neuroma case: (a) plan with good tumour coverage priority and (b) plan with a priority for sparing the brain stem. DVHs for brain exclude PTV and brain stem voxels. For PTV and brain stem, dose-volume planning constraints are shown by circles and stars, respectively.

However, it was impossible to give a prescribed dose of 15 Gy in a single fraction with the chosen fan beam thickness and pitch factor values due to limitation of a 56 s maximum rotation period for the tomotherapy machine in its current version. It would be possible to deliver this clinically by breaking a single treatment into two consecutive delivery runs with the mean time per run 12.9G3.5 min resulting in a total beam-on time for the treatment between 7 and 21 min. Leakage of HT unit was measured on the HiArt system in London at approximately 0.1% of the primary irradiation. Assuming an output irradiation of 9.5 Gy/min, a 10 min treatment would add a dose of ca. 10 cGy to the patient outside the irradiated volume. This is comparable to doses received outside the treated volume with other radiosurgery techniques like gamma knife [12].

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4. Discussion

Acknowledgements

As in the previous report by Bolsi [1], our treatment comparisons confirmed that the passive scatter proton plans achieved the best critical organ sparing also compared to tomotherapy. However, cost and accessibility considerations may limit the ability to treat all patients with base of skull tumours with protons and many of these patients will be treated with photon techniques instead. While the stereotactic radiotherapy photon plans demonstrated the best organ at risk sparing of the photon plans, this was at a cost of somewhat lower target minimum dose and increased target dose heterogeneity. In addition, these comparisons relate to quite small targets (average 4 cm3) and with larger base of skull tumours the potential advantages of stereotactic photon or proton techniques may not be as evident [11]. In our comparison, helical tomotherapy appeared in many respects to be at least as good as the other photon techniques studied and carried some advantages in terms of dose homogeneity of minimum dose delivered while maintaining acceptable OAR sparing. The estimated overall delivery time for helical tomotherapy was comparatively short (approximately 5 min) rendering tomotherapy competitive with other photon delivery techniques. A potential advantage of the helical tomotherapy technique not modelled in this study is the integration of megavoltage CT imaging in the unit. Acquisition of a megavoltage CT image prior to treatment each day may increase the overall treatment time somewhat (typically less than 5 min) but does permit the co-registration of pre-treatment and treatment CT images for daily positioning correction. Such frameless stereotactic localization should allow the reduction of PTV margins (for increased conformality and OAR sparing) and overcomes some of the logistical challenges associated with traditional stereotactic radiosurgery/radiotherapy using invasive frames identified in the previous study [1].

The Ontario Cancer Research Network and ORCDF are acknowledged for financial support of the study.

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