Voxel-level biological optimisation of prostate IMRT using patient-specific tumour location and clonogen density derived from mpMRI.

AIMS: This study aimed to develop a framework for optimising prostate intensity-modulated radiotherapy (IMRT) based on patient-specific tumour biology, derived from multiparametric MRI (mpMRI). The framework included a probabilistic treatment planning technique in the effort to yield dose distributions with an improved expected treatment outcome compared with uniform-dose planning approaches. METHODS: IMRT plans were generated for five prostate cancer patients using two inverse planning methods: uniform-dose to the planning target volume and probabilistic biological optimisation for clinical target volume tumour control probability (TCP) maximisation. Patient-specific tumour location and clonogen density information were derived from mpMRI and geometric uncertainties were incorporated in the TCP calculation. Potential reduction in dose to sensitive structures was assessed by comparing dose metrics of uniform-dose plans with biologically-optimised plans of an equivalent level of expected tumour control. RESULTS: The planning study demonstrated biological optimisation has the potential to reduce expected normal tissue toxicity without sacrificing local control by shaping the dose distribution to the spatial distribution of tumour characteristics. On average, biologically-optimised plans achieved 38.6% (p-value: < 0.01) and 51.2% (p-value: < 0.01) reduction in expected rectum and bladder equivalent uniform dose, respectively, when compared with uniform-dose planning. CONCLUSIONS: It was concluded that varying the dose distribution within the prostate to take account for each patient's clonogen distribution was feasible. Lower doses to normal structures compared to uniform-dose plans was possible whilst providing robust plans against geometric uncertainties. Further validation in a larger cohort is warranted along with considerations for adaptive therapy and limiting urethral dose.

Variation in Lung Tumour Breathing Motion between Planning Four-dimensional Computed Tomography and Stereotactic Ablative Radiotherapy Delivery and its Dosimetric Implications: Any Role for Four-dimensional Set-up Verification?

AIMS: To investigate variation in tumour breathing motion (TBM) between the planning four-dimensional computed tomograph (4DCT) and treatment itself for primary or secondary lung tumours undergoing stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS: Sixteen consecutive patients underwent planning 4DCT at least 1 week after implantation of a fiducial marker. The maximal extent of breathing motion of the intra-tumoural fiducial was measured at 4DCT and again at delivery of each SABR fraction on the linac using stereoscopic kilovoltage imaging. Displacements of the fiducial beyond planned limits were measured in three dimensions and represented as vectors. Variation in breathing motion between the planning 4DCT and treatment, and between individual SABR fractions was analysed. RESULTS: Although TBM at treatment exceeded planned tumour motion limits for at least part of the course for all patients, 31% of patients remained consistently within 1 mm, 50% within 2 mm and 69% consistently within 3 mm of planned parameters. However, 19% of patients experienced TBM variation 5 mm or more beyond planned limits for at least one fraction. For all patients, the median displacement vector at treatment beyond the planned motion envelope was 1.0 mm (mean 2.0 mm, range 0-12.7 mm). Variation in TBM at treatment from 4DCT correlated neither with the magnitude of TBM at 4DCT nor with planning target volume size (rs = 0.13, P = 0.62; rs = 0.02, P = 0.94, respectively). Nor was TBM variation related to tumour type or lobar position (P = 0.35, P = 0.06, respectively). Inter-fraction TBM variation was modest, with an average standard deviation of 1.7 mm (0.3-8.7 mm). CONCLUSIONS: TBM variation between 4DCT and treatment and between SABR fractions was modest for most patients. However, 19% of patients experienced significant TBM variation that could be clinically relevant for those most severely affected. It seems prudent to carry out on-couch assessment of TBM at each SABR fraction to identify such patients who might benefit from respiratory gating or adaptive radiotherapy to maintain tumour motion within the planned limits.

Comparison of dose calculation algorithms in slab phantoms with cortical bone equivalent heterogeneities.

To evaluate the dose values predicted by several calculation algorithms in two treatment planning systems, Monte Carlo (MC) simulations and measurements by means of various detectors were performed in heterogeneous layer phantoms with water- and bone-equivalent materials. Percentage depth doses (PDDs) were measured with thermoluminescent dosimeters (TLDs), metal-oxide semiconductor field-effect transistors (MOSFETs), plane parallel and cylindrical ionization chambers, and beam profiles with films. The MC code used for the simulations was the PENELOPE code. Three different field sizes (10 x 10, 5 x 5, and 2 x 2 cm2) were studied in two phantom configurations and a bone equivalent material. These two phantom configurations contained heterogeneities of 5 and 2 cm of bone, respectively. We analyzed the performance of four correction-based algorithms and one based on convolution superposition. The correction-based algorithms were the Batho, the Modified Batho, the Equivalent TAR implemented in the Cadplan (Varian) treatment planning system (TPS), and the Helax-TMS Pencil Beam from the Helax-TMS (Nucletron) TPS. The convolution-superposition algorithm was the Collapsed Cone implemented in the Helax-TMS. All the correction-based calculation algorithms underestimated the dose inside the bone-equivalent material for 18 MV compared to MC simulations. The maximum underestimation, in terms of root-mean-square (RMS), was about 15% for the Helax-TMS Pencil Beam (Helax-TMS PB) for a 2 x 2 cm2 field inside the bone-equivalent material. In contrast, the Collapsed Cone algorithm yielded values around 3%. A more complex behavior was found for 6 MV where the Collapsed Cone performed less well, overestimating the dose inside the heterogeneity in 3%-5%. The rebuildup in the interface bone-water and the penumbra shrinking in high-density media were not predicted by any of the calculation algorithms except the Collapsed Cone, and only the MC simulations matched the experimental values within the estimated uncertainties. The TLD and MOSFET detectors were suitable for dose measurement inside bone-equivalent materials, while parallel ionization chambers, applying the same calibration and correction factors as in water, systematically underestimated dose by 3%-5%.

Photonuclear isotope characterization of a Siemens KDS 18 MV linac head.

Induced activity due to photonuclear reactions produced in the vacuum window of the accelerating wave-guide, the x-ray target and the beam-flattening filter of an 18 MV Siemens KDS linac has been studied. Measurements were performed using a high-purity portable germanium detector. Radioisotopes such as 196Au, 57Co, 60Co and other traces were detected one week after the last clinical use of the linac.