A randomised controlled trial of forward-planned radiotherapy (IMRT) for early breast cancer: baseline characteristics and dosimetry results.

BACKGROUND AND PURPOSE: This large trial was designed to investigate whether correction of dose inhomogeneities using intensity-modulated radiotherapy (IMRT) reduces late toxicity and improves quality of life in patients with early breast cancer. This paper reports baseline characteristics of trial participants and dosimetry results. MATERIALS AND METHODS: Standard tangential plans of 1145 trials were analysed. Patients with inhomogeneous plans, defined by ICRU recommendations, were randomised to forward-planned IMRT or standard radiotherapy. RESULTS: Twenty-nine percentage of patients had adequate dosimetry with standard 2D radiotherapy. In the randomised patients, the decreases in mean volumes receiving greater than 107% (Vol>107) and less than 95% (Vol<95) of the prescribed dose in the IMRT compared with the control group were 34.0 cm(3) (95% CI 26.4-41.6; P<0.0001) and 48.1 cm(3) (95% CI 34.4-61.9; P<0.0001), respectively. In this study, 90% of patients who had a breast separation greater > or = 21 cm had Vol>107>2 cm(3) on standard radiotherapy plans. CONCLUSION: This large trial, in which patients with all breast sizes were eligible, confirmed that breast dosimetry can be significantly improved with a simple method of forward-planned IMRT and has little impact on radiotherapy resources. It is shown that patients with larger breasts are more likely to have dose inhomogeneities and breast separation gives some indication of this likelihood. Photographic assessment of patients at 2 years after radiotherapy, as the next part of this randomised controlled trial, will show whether these results for IMRT translate into improved cosmetic outcome in patients with early breast cancer. This would provide impetus for the widespread adoption of 3D planning and IMRT.

High definition three-dimensional ultrasound to localise the tumour bed: a breast radiotherapy planning study.

BACKGROUND AND PURPOSE: Complex radiation techniques, such as conformal radiotherapy for partial breast irradiation, require accurate localisation of the tumour bed. This study investigated high definition 3D ultrasound for breast tumour bed localisation. Study aims were: firstly, to determine how easily a tumour cavity could be visualised with 3D ultrasound; secondly, to determine the accuracy of computed tomography (CT) and 3D ultrasound co-registration; thirdly, to compare 3D ultrasound with other methods of localisation. MATERIALS AND METHODS: 3D ultrasound examinations were carried out in 40 women attending for breast radiotherapy. 3D position data were co-registered with the radiotherapy planning CT. 2D ultrasound and CT, surgical clips and CT, and CT alone were also used to localise the tumour bed in 32/40, 14/40 and 5/40 patients, respectively. Tumour bed volume and centre of gravity measurements for all methods of localisation were compared. RESULTS: Mean surgery to imaging interval was 44 days (range 23-86 days). The post-operative cavity was seen in all cases using the 3D ultrasound, and was graded as highly visible, visible and subtle in 21/40 (53%), 12/40 (30%) and 7/40 (17%) cases, respectively. There was a statistically significant improvement in the ability of 3D ultrasound to localise the tumour bed compared with 2D ultrasound. CT-ultrasound registration was achieved in all cases. Two-dimensional and 3D ultrasound showed smaller tumour bed volumes than clips. CONCLUSIONS: Three-dimensional ultrasound localisation of the tumour bed appears superior to 2D ultrasound. It can also be co-registered with a planning CT, thus allowing additional information on the size and location of the tumour bed to be integrated into complex radiotherapy planning.

Post-Operative Radiotherapy for Soft Tissue Sarcoma of the Anterior Compartment of the Thigh: Should the Sartorius Muscle be Included?

PURPOSE: The clinical target volume (CTV) of post-operative radiotherapy for soft tissue sarcoma of the limbs conventionally includes the whole of the transverse cross-section of the affected anatomical compartment. In the anterior thigh sartorius appears to lie within its own fascial compartment and can be safely excluded. We investigated the potential impact of omitting sartorius from the anterior muscle compartment on patients with soft tissue sarcoma of the thigh. PATIENTS AND METHODS: We used the planning CT data from six patients who had previously received post-operative radiotherapy for soft tissue sarcoma of the thigh. The anterior compartments were outlined twice, initially including and then excluding the sartorius muscle. The volumes of the anterior compartment (i.e., the CTVs), both with and without sartorius, and the corresponding planning target volumes (PTVs) were calculated. Treatment plans were prepared for each PTV. For both volumes the unirradiated normal tissue corridor was outlined on each CT slice. The volume and circumference of the unirradiated corridor were then calculated. RESULTS: For all six patients there was an important improvement in normal tissue sparing by excluding sartorius. The mean reduction in volume of the anterior compartment when sartorius was excluded was 10% (95% Confidence Interval 8-12%), whilst the mean decrease in PTV was 11% (95% CI 7-14%). There was a substantial increase in the volume of the unirradiated normal tissue corridor, with a mean value of 77% (95% CI 41-114%) when sartorius was excluded. In addition, the percentage increase in the size of the unirradiated normal tissue corridor, expressed as a percentage of the whole leg circumference, was 10% (95% CI 8-13%). When sartorius was included in the anterior compartment, the circumference of the unirradiated corridor was less than one-third of the whole leg circumference in four of the six patients. When sartorius was excluded, the circumference of the unirradiated corridor was greater than one-third of the leg circumference over the entire length of the target volume in all patients. DISCUSSION: It is essential to know the anatomy of the sartorius muscle to be able to exclude it from the anterior compartment. The increase in the size of the normal tissue corridor when sartorius is excluded should deliver clinical advantage by decreasing the normal tissue adverse effects.

The effect of optimization on surface dose in intensity modulated radiotherapy (IMRT).

Although IMRT has been shown clinically to increase skin doses for some patients, it has also been shown that intensity modulated delivery does not, of itself, increase skin doses. The reason for this apparent difference is that inverse planning can result in solutions that give high fluence to tangential beam segments near the skin surface, in an attempt to counter the build-up region. In cases where the clinical target volume (CTV) stops short of the skin surface, but the planning target volume (PTV) does not, there is no clinical reason to treat the skin. The CTV-PTV margin exists purely to ensure that fields are large enough to allow for geometrical uncertainties. With an objective function based on the doses to the PTV, it is possible for a plan that gives excess fluence to the skin to have a lower objective function, and hence to be preferred in an optimization. We describe a technique of plan evaluation, based on analysis of a plan by recalculating several plans in which the isocentre has been offset by a distance equal to the CTV-PTV margin. We demonstrate that changes to a plan that reduce a PTV-based objective can give a worse dose distribution to the CTV when systematic and random set-up errors are accounted for, and increase skin dose. Several possible strategies for avoiding this problem are discussed, including the use of the skin as an organ at risk, modification of the PTV to avoid the skin, and the use of 'pretend bolus' applied in planning but not in treatment. The latter gave the best results. The possibility of using the evaluation method itself, as the basis of an objective function for optimization, is discussed.

The anatomy of sartorius muscle and its implications for sarcoma radiotherapy.

PURPOSE: Controversy exists as to whether sartorius muscle is completely invested in fascia. If it is, then direct tumour involvement from soft tissue sarcoma of the anterior thigh would be unlikely and would justify omitting sartorius from the radiotherapy volume. SUBJECTS AND METHODS: Eight thighs in six cadavers were examined in the dissecting room. Using a previous case, conformal radiotherapy plans were prepared to treat the anterior compartment of the thigh including and excluding sartorius. The corridor of unirradiated normal tissue was outlined separately. RESULTS: In all cases, sartorius was enclosed within a fascial sheath of its own. In four of the six cadavers, there was clear evidence of a fascial envelope surrounding sartorius, fused to the fascia lata and medial intermuscular septum. In two, sartorius was fully ensheathed in the upper half of the thigh; in the lower half the intermuscular septum became thin, and blended with the tendinous aponeurosis on the surface of vastus medialis in an example case. By excluding sartorius, the volume of the anterior compartment was reduced by 8%, but the volume of the unirradiated normal tissue corridor increased by 134%. With sartorius included, the unirradiated corridor became very small inferiorly, only 6% of the circumference of the whole leg, compared to 27% with sartorius excluded. DISCUSSION: The anatomy suggests that sartorius could be safely omitted from the clinical target volume of anterior compartment soft tissue sarcomas. This substantially increases the size of the unirradiated normal tissue corridor, expressed as a volume and a circumference, which could give a clinical advantage by reducing normal tissue complications.

Quantitative assessment of inter-clinician variability of target volume delineation for medulloblastoma: quality assurance for the SIOP PNET 4 trial protocol.

BACKGROUND AND PURPOSE: To assess inter-clinician variability amongst specialist paediatric radiation oncologists in delineating clinical target volumes for treating medulloblastoma as a quality assurance exercise prior to the introduction of the SIOP PNET 4 trial protocol of conformal radiotherapy to the posterior fossa and tumour bed. PATIENTS AND METHODS: Participants from 17 UK centres attended an educational meeting and then completed a clinical planning exercise to outline: (1) the whole posterior fossa and (2) the tumour bed. Quantitative analysis of the volumes, lengths, spatial positioning and axial planes for each individual was carried out and variation between individuals analysed. RESULTS: Outlining of the posterior fossa was reasonably consistent, although most variation was seen in defining the superior border of the tentorium. A major difference was the decision whether or not to include the post-surgical meningocoele in the clinical target volume (CTV). The CTV for the tumour bed was under treated by all participants due to lack of inclusion of pre-operative tumour extent. CONCLUSIONS: This exercise demonstrated several ambiguities in the draft protocol and highlighted particular areas of inter-clinician variation. Consequently the protocol was revised and improved to take account of these findings. We recommend that planning exercises, in conjunction with education and training, should be implemented before the start of any new radiotherapy trial. In the future, the use of image transfer will allow prospective peer review of target volumes before treatment commences. These measures are essential to ensure that alterations in clinical practice are achieved in a uniform way.