Feasibility and clinical usefulness of modelling glioblastoma migration in adjuvant radiotherapy.

Glioblastoma (GBM) is one of the most common primary brain tumours in adults, with a dismal prognosis despite aggressive multimodality treatment by a combination of surgery and adjuvant radiochemotherapy. A detailed knowledge of the spreading of glioma cells in the brain might allow for more targeted escalated radiotherapy, aiming to reduce locoregional relapse. Recent years have seen the development of a large variety of mathematical modelling approaches to predict glioma migration. The aim of this study is hence to evaluate the clinical applicability of a detailed micro- and meso-scale mathematical model in radiotherapy. First and foremost, a clinical workflow is established, in which the tumour is automatically segmented as input data and then followed in time mathematically based on the diffusion tensor imaging data. The influence of several free model parameters is individually evaluated, then the full model is retrospectively validated for a collective of 3 GBM patients treated at our institution by varying the most important model parameters to achieve optimum agreement with the tumour development during follow-up. Agreement of the model predictions with the real tumour growth as defined by manual contouring based on the follow-up MRI images is analyzed using the dice coefficient. The tumour evolution over 103-212 days follow-up could be predicted by the model with a dice coefficient better than 60% for all three patients. In all cases, the final tumour volume was overestimated by the model by a factor between 1.05 and 1.47. To evaluate the quality of the agreement between the model predictions and the ground truth, we must keep in mind that our gold standard relies on a single observer's (CB) manually-delineated tumour contours. We therefore decided to add a short validation of the stability and reliability of these contours by an inter-observer analysis including three other experienced radiation oncologists from our department. In total, a dice coefficient between 63% and 89% is achieved between the four different observers. Compared with this value, the model predictions (62-66%) perform reasonably well, given the fact that these tumour volumes were created based on the pre-operative segmentation and DTI.

Planning study and dose measurements of intracranial stereotactic radiation surgery with a flattening filter-free linac.

PURPOSE: Flattening filter-free (FFF) beams have recently become available for radiation therapy, offering much higher dose rates but complicating treatment owing to the nonflat profile. Stereotactic treatment is one of the most evident scenarios to investigate the use of FFF beams. METHODS AND MATERIALS: We present a planning study of a FFF 7-MV beam for the treatment of brain metastases using multiple noncoplanar arcs. Plan differences as compared with flat 6 MV photon fields are estimated using different measures of quality. Absolute dosimetry and fluence distribution are verified and the out-of-field dose is measured. RESULTS: The FFF 7-MV plans are slightly better than the flat 6-MV plans as evaluated by a number of quality indices, dose to organs at risk, and out-of-field dose, although differences may not be clinically relevant. Verification does not pose any problems. CONCLUSIONS: The FFF 7-MV treatment plans are marginally superior to the flat-beam 6-MV plans in almost all cases, with greatly reduced treatment times (almost 50%).

Commissioning and first clinical application of mARC treatment.

BACKGROUND: The modulated arc (mARC) technique has recently been introduced for Siemens ARTISTE linear accelerators. We present the first experiences with the commissioning of the system and first patient treatments. PATIENTS AND METHODS: Treatment planning and delivery are presented for the Prowess Panther treatment planning system or, alternatively, an in-house code. Dosimetric verification is performed both by point dose measurements and in 3D dose distribution. RESULTS: Depending on the target volume, one or two arcs can be used to create highly conformal plans. Dosimetric verification of the converted mARC plans with step-and-shoot plans shows deviations below 1 % in absolute point dose; in the 3D dose distribution, over 95 % of the points pass the 3D gamma criteria (3 % deviation in local dose and 3 mm distance to agreement for doses > 20 % of the maximum). Patient specific verification of the mARC dose distribution with the calculations has a similar pass rate. Treatment times range between 2 and 5 min for a single arc. CONCLUSIONS: To our knowledge, this is the first report of clinical application of the mARC technique. The mARC offers the possibility to save significant amounts of time, with single-arc treatments of only a few minutes achieving comparable dose distribution to IMRT plans taking up to twice as long.

Comparative planning of flattening-filter-free and flat beam IMRT for hypopharynx cancer as a function of beam and segment number.

Although highly conformal dose distributions can be achieved by IMRT planning, this often requires a large number of segments or beams, resulting in increased treatment times. While flattening-filter-free beams offer a higher dose rate, even more segments may be required to create homogeneous target coverage. Therefore, it is worthwhile to systematically investigate the dependence of plan quality on gantry angles and number of segments for flat vs. FFF beams in IMRT planning. For the practical example of hypopharynx cancer, we present a planning study of flat vs. FFF beams using three different configurations of gantry angles and different segment numbers. The two beams are very similar in physical properties, and are hence well-suited for comparative planning. Starting with a set of plans of equal quality for flat and FFF beams, we assess how far the number of segments can be reduced before the plan quality is markedly compromised, and compare monitor units and treatment times for the resulting plans. As long as a sufficiently large number of segments is permitted, all planning scenarios give good results, independently of gantry angles and flat or FFF beams. For smaller numbers of segments, plan quality decreases both for flat and FFF energies; this effect is stronger for fewer gantry angles and for FFF beams. For low segment numbers, FFF plans are generally worse than the corresponding flat beam plans, but they are less sensitive to a decrease in segment number if many gantry angles are used (18 beams); in this case the quality of flat and FFF plans remains comparable even for few segments.

Visualisation of respiratory tumour motion and co-moving isodose lines in the context of respiratory gating, IMRT and flattening-filter-free beams.

Respiratory motion during percutaneous radiotherapy can be considered based on respiration-correlated computed tomography (4DCT). However, most treatment planning systems perform the dose calculation based on a single primary CT data set, even though cine mode displays may allow for a visualisation of the complete breathing cycle. This might create the mistaken impression that the dose distribution were independent of tumour motion. We present a movie visualisation technique with the aim to direct attention to the fact that the dose distribution migrates to some degree with the tumour and discuss consequences for gated treatment, IMRT plans and flattening-filter-free beams. This is a feasibility test for a visualisation of tumour and isodose motion. Ten respiratory phases are distinguished on the CT, and the dose distribution from a stationary IMRT plan is calculated on each phase, to be integrated into a movie of tumour and dose motion during breathing. For one example patient out of the sample of five lesions, the plan is compared with a gated treatment plan with respect to tumour coverage and lung sparing. The interplay-effect for small segments in the IMRT plan is estimated. While the high dose rate, together with the cone-shaped beam profile, makes the use of flattening-filter-free beams more problematic for conformal and IMRT treatment, it can be the option of choice if gated treatment is preferred. The different effects of respiratory motion, dose build-up and beam properties (segments and flatness) for gated vs. un-gated treatment can best be considered if planning is performed on the full 4DCT data set, which may be an incentive for future developments of treatment planning systems.