Elizabeth J Adams

A comparison of clinical target volumes determined by CT and MRI for the radiotherapy planning of base of skull meningiomas

PURPOSE To assess the utility of image registration and to compare the localization of clinical target volumes (CTV) using CT and MRI for patients with base of skull meningiomas undergoing radiotherapy. METHODS AND MATERIALS Seven patients were imaged using CT and a T1-weighted MR volumetric sequence. Following image registration using a chamfer-matching algorithm, transaxial MR slices were reconstructed to match the planning CT slices. The accuracy of the image fusion was assessed in a preliminary study with matching accuracy better than 1.5 mm. The CTV in each patient was separately segmented by two independent observers for both CT and reconstructed MR image sets. Scalar and vector assessments were made of the difference in radial extent between the two outlines on each transaxial plane for all patients. A positive vector value corresponded to a greater extension of the tumor on MR compared to CT and vice versa. Scalar measurements compared the modulus of the differences between MR and CT, regardless of which volume was more extensive. Qualitative comparisons were also performed. RESULTS Interobserver difference was small with a mean (+/- 1SD) volume difference of 1.5 +/- 1.5 cm(3) for CT and 0.5 +/- 1.0 cm(3) for MRI. The mean CT- and MR- CTVs were 17.6 +/-10.8 and 19.6 +/-14.2 cm(3) respectively. The mean overlap and composite volumes were 13.8 +/-10. 1 and 23.3 +/-14.8 cm(3) respectively. Average scalar differences in the left, right, anterior, and posterior directions were 6.0 +/- 7.0, 3.3 +/- 2.5, 4.9 +/- 3.9, and 4.5 +/- 5.0 mm respectively. The average vector differences were 3.3 +/- 8.5, -0.3 +/- 3.8, 1.1 +/- 5. 8, 1.5 +/- 6.4 mm (for left, right, anterior, and posterior directions respectively). Qualitatively, MR appeared to discern more tumor involvement in soft tissue regions adjacent to the skull base whereas CT appeared to provide larger target volumes within bony regions. CONCLUSIONS MRI appeared to define CTVs that were larger but not inclusive of CT-defined CTVs. Although the average vector differences were small, the differences on individual borders could be large. In some instances, the CT or MR volumes were vastly different, each providing separate information. Therefore, the use of MRI and CT is complementary. Until accurate histological confirmation of disease extent is available, it is prudent to consider composite CT/MR volumes for the radiotherapy planning of base of skull meningiomas.

Comparison of intensity-modulated tomotherapy with stereotactically guided conformal radiotherapy for brain tumors

PURPOSE Intensity-modulated radiotherapy (IMRT) offers the potential to more closely conform dose distributions to the target, and spare organs at risk (OAR). Its clinical value is still being defined. The present study aims to compare IMRT with stereotactically guided conformal radiotherapy (SCRT) for patients with medium size convex-shaped brain tumors. METHODS AND MATERIALS Five patients planned with SCRT were replanned with the IMRT-tomotherapy method using the Peacock system (Nomos Corporation). The planning target volume (PTV) and relevant OAR were assessed, and compared relative to SCRT plans using dose statistics, dose-volume histograms (DVH), and the Radiation Therapy Oncology Group (RTOG) stereotactic radiosurgery criteria. RESULTS The median and mean PTV were 78 cm3 and 85 cm3 respectively (range 62-119 cm3). The differences in PTV doses for the whole group (Peacock-SCRT +/-1 SD) were 2%+/-1.8 (minimum PTV), and 0.1%+/-1.9 (maximum PTV). The PTV homogeneity achieved by Peacock was 12.1%+/-1.7 compared to 13.9%+/-1.3 with SCRT. Using RTOG guidelines, Peacock plans provided acceptable PTV coverage for all 5/5 plans compared to minor coverage deviations in 4/5 SCRT plans; acceptable homogeneity index for both plans (Peacock = 1.1 vs. SCRT = 1.2); and comparable conformity index (1.4 each). As a consequence of the transaxial method of arc delivery, the optic nerves received mean and maximum doses that were 11.1 to 11.6%, and 10.3 to 15.2% higher respectively with Peacock plan. The maximum optic lens, and brainstem dose were 3.1 to 4.8% higher, and 0.6% lower respectively with Peacock plan. However, all doses remained below the tolerance threshold (5 Gy for lens, and 50 Gy for optic nerves) and were clinically acceptable. CONCLUSIONS The Peacock method provided improved PTV coverage, albeit small, in this group of convex tumors. Although the OAR doses were higher using the Peacock plans, all doses remained within the clinically defined threshold and were clinically acceptable. Further improvements may be expected using other methods of IMRT planning that do not limit the treatment delivery to transaxial arcs. Each IMRT system needs to be individually assessed as the paradigm utilized may provide different outcomes.

POTENTIAL ROLE OF INTENSITY-MODULATED RADIOTHERAPY IN THE TREATMENT OF TUMORS OF THE MAXILLARY SINUS

PURPOSE To assess 3-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) techniques to see whether doses to critical structures could be reduced while maintaining planning target volume (PTV) coverage in patients receiving conventional radiotherapy (RT) for carcinoma of the maxillary sinus because of the risk of radiation-induced complications, particularly visual loss. METHODS AND MATERIALS Six patients who had recently received conventional RT for carcinoma of the maxillary sinus were studied. Conventional RT, 3D-CRT, and step-and-shoot IMRT plans were prepared using the same 2-field arrangement. The effect of reducing the number of segments in the IMRT beams was investigated. RESULTS 3D-CRT and IMRT reduced the brain and ipsilateral parotid gland doses compared with the conventional plans. IMRT reduced doses to both optic nerves; for the contralateral optic nerve, 15-segment IMRT plans delivered an average maximal dose of 56.4 Gy (range 53.9-59.3) compared with 65.7 Gy (range 65.3-65.9) and 64.2 Gy (range 61.4-65.6) for conventional RT and 3D-CRT, respectively. IMRT also gave improved PTV homogeneity and improved coverage, with an average of 8.5% (range 7.0-11.7%) of the volume receiving <95% of the prescription dose (64 Gy) compared with 14.7% (range 14.1-15.9%) and 15.1% (range 14.4-16.1%) with conventional RT and 3D-CRT, respectively. Little difference was found between the 15 and 7-segment plans, but 5 segments resulted in a reduced minimal PTV dose. CONCLUSIONS IMRT offers significant advantages over conventional RT and 3D-CRT techniques for treatment of maxillary sinus tumors. Good results can be obtained from 7 segments per beam without compromising the PTV coverage. This number of segments is practical for implementation in a busy RT department.

Stereotactically guided conformal radiotherapy for progressive low-grade gliomas of childhood.

PURPOSE To describe the rationale, technique, and early results of stereotactically guided conformal radiotherapy (SCRT) in the treatment of progressive or inoperable low-grade gliomas (LGGs) of childhood. METHODS AND MATERIALS Between September 1994 and May 1999, 14 children (median age 6 years, range 5-16) with LGG were treated with SCRT at the Royal Marsden NHS Trust. Tumors were located at the optic chiasm (n = 9), third ventricle (n = 2), hypothalamus, craniocervical junction, and pineal region (each n = 1). Four patients received chemotherapy before SCRT. Immobilization was in a Gill-Thomas-Cosman frame (n = 12) and subsequently in a specially designed pediatric version of the frame (n = 2). Stereotactic coordinates and the tumor were defined by CT scanning with a fiducial system and MRI fusion. The median tumor volume was 19.5 cm(3) (range 7.5-180). The planning target volume was defined as the area of enhancing tumor plus a 5-10-mm margin. The treatment technique consisted of 4 isocentric, noncoplanar, conformal, fixed fields. Treatment was delivered in 30-33 daily fractions to a total dose of 50-55 Gy. RESULTS SCRT was well tolerated, with transient hair loss the only acute toxicity. The median follow-up was 33 months (range 2-53). At 6 months after SCRT, 4 of 12 children with neurologic deficits improved and 5 remained stable. Twelve children were available for MRI evaluation. Two had a complete response, 6 a partial response, and 4 stable disease. One child with optic chiasm glioma had local progression at 25 months, and 1 developed diffuse leptomeningeal disease without local progression at 27 months. The 3-year local progression-free survival and overall survival rate after SCRT was 87% and 100%, respectively, compared with 89% and 98% for an historic control treated with conventional RT. New endocrine deficiencies were noted in 2 children after a follow-up of 20 and 23 months. CONCLUSION SCRT is a feasible, high-precision technique of RT for children with LGGs for whom RT is considered appropriate. The local control and acute toxicity of SCRT are comparable to a historic control of patients with conventionally delivered RT. The frequency of delayed hypothalamic-pituitary axis dysfunction reflects tumor location adjacent to the hypothalamus and pituitary. Additional follow-up is required to demonstrate that SCRT contributes to a reduction in treatment-related late toxicity, while maintaining the local control achieved with conventionally delivered RT in children with progressive LGGs.

Optimization of stereotactically-guided conformal treatment planning of sellar and parasellar tumors, based on normal brain dose volume histograms☆

PURPOSE To investigate the optimal treatment plan for stereotactically-guided conformal radiotherapy (SCRT) of sellar and parasellar lesions, with respect to sparing normal brain tissue, in the context of routine treatment delivery, based on dose volume histogram analysis. METHODS AND MATERIALS Computed tomography (CT) data sets for 8 patients with sellar- and parasellar-based tumors (6 pituitary adenomas and 2 meningiomas) have been used in this study. Treatment plans were prepared for 3-coplanar and 3-, 4-, 6-, and 30-noncoplanar-field arrangements to obtain 95% isodose coverage of the planning target volume (PTV) for each plan. Conformal shaping was achieved by customized blocks generated with the beams eye view (BEV) facility. Dose volume histograms (DVH) were calculated for the normal brain (excluding the PTV), and comparisons made for normal tissue sparing for all treatment plans at > or =80%, > or =60%, and > or =40% of the prescribed dose. RESULTS The mean volume of normal brain receiving > or =80% and > or =60% of the prescribed dose decreased by 22.3% (range 14.8-35.1%, standard deviation sigma = 7.5%) and 47.6% (range 25.8-69.1%, sigma = 13.2%), respectively, with a 4-field noncoplanar technique when compared with a conventional 3-field coplanar technique. Adding 2 further fields, from 4-noncoplanar to 6-noncoplanar fields reduced the mean normal brain volume receiving > or =80% of the prescribed dose by a further 4.1% (range -6.5-11.8%, sigma = 6.4%), and the volume receiving > or =60% by 3.3% (range -5.5-12.2%, sigma = 5.4%), neither of which were statistically significant. Each case must be considered individually however, as a wide range is seen in the volume spared when increasing the number of fields from 4 to 6. Comparing the 4- and 6-field noncoplanar techniques to a 30-field conformal field approach (simulating a dynamic arc plan) revealed near-equivalent normal tissue sparing. CONCLUSION Four to six widely spaced, fixed-conformal fields provide the optimum class solution for the treatment of sellar and parasellar lesions, both in terms of normal brain tissue sparing and providing a relatively straightforward patient setup. Increasing the number of fields did not result in further significant sparing, with no clear benefit from techniques approaching dynamic conformal radiotherapy in the cases examined.

The reproducibility of polyacrylamide gel dosimetry applied to stereotactic conformal radiotherapy

The reproducibility of polyacrylamide gel (PAG) dosimetry has been evaluated when used to verify two radiotherapy treatment plans of increasing complexity. The plans investigated were a three-field coplanar arrangement, using the linac jaws for field shaping, and a four-field, conformal, non-coplanar plan using precision-cast lead alloy shielding blocks. Each treatment was performed three times using phantoms and calibration gels manufactured in-house. Two phantoms were specially designed for this work to aid accurate positioning of the gels for irradiation and imaging. All gels were imaged post-irradiation using a Siemens Vision 1.5T MR scanner. T2 relaxation images were calibrated to absorbed dose distributions using a number of smaller calibration vessels to produce distribution maps of relative dose. The relative dose distributions were found to be reproducible, with the standard deviation on the mean areas enclosed by the > or = 50% isodose lines measured in three orthogonal planes being 6.4% and 4.1% for the coplanar and non-coplanar plans respectively. The measured distributions were also consistent with those planned, with isodose lines generally agreeing to within a few millimetres. However, the measured absolute doses were on average 23.5% higher than those planned. Although the polyacrylamide gel dosimetry technique has some limitations, particularly when calibrating distributions to absolute dose, the ability to resolve sharp dose gradients in three dimensions with millimetre precision is invaluable when verifying complex conformal treatment plans, where avoidance of proximal, critical structures is a treatment criterion.

Head-and-neck IMRT treatments assessed with a Monte Carlo dose calculation engine

IMRT is frequently used in the head-and-neck region, which contains materials of widely differing densities (soft tissue, bone, air-cavities). Conventional methods of dose computation for these complex, inhomogeneous IMRT cases involve significant approximations. In the present work, a methodology for the development, commissioning and implementation of a Monte Carlo (MC) dose calculation engine for intensity modulated radiotherapy (MC-IMRT) is proposed which can be used by radiotherapy centres interested in developing MC-IMRT capabilities for research or clinical evaluations. The method proposes three levels for developing, commissioning and maintaining a MC-IMRT dose calculation engine: (a) development of a MC model of the linear accelerator, (b) validation of MC model for IMRT and (c) periodic quality assurance (QA) of the MC-IMRT system. The first step, level (a), in developing an MC-IMRT system is to build a model of the linac that correctly predicts standard open field measurements for percentage depth-dose and off-axis ratios. Validation of MC-IMRT, level (b), can be performed in a rando phantom and in a homogeneous water equivalent phantom. Ultimately, periodic quality assurance of the MC-IMRT system is needed to verify the MC-IMRT dose calculation system, level (c). Once the MC-IMRT dose calculation system is commissioned it can be applied to more complex clinical IMRT treatments. The MC-IMRT system implemented at the Royal Marsden Hospital was used for IMRT calculations for a patient undergoing treatment for primary disease with nodal involvement in the head-and-neck region (primary treated to 65 Gy and nodes to 54 Gy), while sparing the spinal cord, brain stem and parotid glands. Preliminary MC results predict a decrease of approximately 1-2 Gy in the median dose of both the primary tumour and nodal volumes (compared with both pencil beam and collapsed cone). This is possibly due to the large air-cavity (the larynx of the patient) situated in the centre of the primary PTV and the approximations present in the dose calculation.

Comparison of a multi-leaf collimator with conformal blocks for the delivery of stereotactically guided conformal radiotherapy.

Stereotactically-guided conformal radiotherapy is a practical technique for irradiating irregular lesions in the brain. The shaping of the conformal fields may be achieved using lead alloy blocks, a conventional multi-leaf collimator (MLC) or a mini/micro-MLC. Although the former gives more precise shaping, it is labour intensive. The latter methods are more practical as both mould room and treatment room times are reduced, but the shaping is limited by the finite leaf-width. This study compares treatment plans, in terms of normal tissue doses and tumour coverage, for fields shaped using conformal blocks and a conventional MLC in two series of geometrical shapes and nine patient tumours. For the range of tumour sizes considered (volumes 14-264 cm3, minimum dimension 30 mm, maximum 102 mm), the MLC treats, on average, 14% (range 3-34%) and 17% (range 0-36%) more normal brain tissue than conformal blocks to >50% and >80% of the prescription dose, respectively. The large variability is due to strong dependence on tumour shape and the presence of partial leaf-widths in the MLC fit. It is therefore important to consider both of these effects when deciding whether the MLC is appropriate for a particular target volume.

Intensity-modulated radiotherapy allows escalation of the radiation dose to the pelvic lymph nodes in patients with locally advanced prostate cancer: preliminary results of a phase I dose escalation study

AIM Pelvic irradiation in addition to prostate irradiation may improve outcome in locally advanced prostate cancer, but is associated with dose-limiting bowel toxicity. We report the preliminary results of a dose escalation study using intensity-modulated radiotherapy. MATERIALS AND METHODS Eligible patients had high-risk (T3, Gleason > or =8 or prostate-specific antigen > or =20 ng/ml) or lymph node-positive disease. Intensity-modulated radiotherapy was inverse planned giving 70 Gy/35 fractions to the prostate and 50 Gy/55 Gy/60 Gy in sequential cohorts to the pelvis with a 5 Gy boost to positive lymph nodes. Acute and late toxicity were recorded with Radiation Therapy Oncology Group (RTOG) and Late Effects Normal Tissue - Subjective Objective Management LENT-SOM scales. Neoadjuvant androgen suppression was given for 3 years. This report concerns the 50 and 55 Gy cohorts. RESULTS Seventy-nine men were recruited (25 to 50 Gy/54 to 55 Gy) with a median follow-up of 2 years. Patients were divided into two groups according to the total bowel volume outlined (median 450 cm(3)). Acute RTOG (> or =2) bowel toxicity was 40 and 50% for the 50 and 55 Gy groups and 38 and 51% for bowel volume <450 cm(3) and > or =450 cm(3), respectively, suggesting both volume and dose relationships for acute effects. Late RTOG diarrhoea > or =grade 2 was only seen with bowel volume > or =450 cm(3), but no dose effect was apparent (12%/50 Gy and 10%/55 Gy). LENT-SOM bowel > or =grade 2 toxicity occurred in 22%/50 Gy and 15%/55 Gy. Only one patient had grade 3 toxicity. A dose volume histogram analysis showed increased late RTOG diarrhoea > or =grade 2 with larger bowel volume irradiated, significant for BV40 >124 cm(3) (P=0.04), BV45 >71 cm(3) (P=0.03) and BV60 >2 cm(3) (P=0.01). CONCLUSIONS Acute and late bowel toxicity was acceptably low using a pelvic dose of up to 55 Gy over 7 weeks. Both relate to total pelvic bowel volume and dose volume constraints have been defined.

Changes to dose in the build-up region when using multi-leaf collimators in place of lead blocks supported on an accessory tray.

Doses in the build-up region have been compared for regular fields with and without a perspex accessory tray and for two irregular fields defined by either a Philips multi-leaf collimator (MLC) or lead blocks. The results show an increase in doses within the build-up region, by up to a factor of two, primarily due to the presence of the accessory tray. Fields shaped with the MLC exhibited build-up characteristics similar to those in unblocked fields and hence there will be systematic changes to the build-up dose when treatments are transferred from lead blocking techniques to those using an MLC mounted within the treatment head.