Online adaptive radiotherapy compared to plan selection for rectal cancer: quantifying the benefit.

BACKGROUND: To compare online adaptive radiation therapy (ART) to a clinically implemented plan selection strategy (PS) with respect to dose to the organs at risk (OAR) for rectal cancer. METHODS: The first 20 patients treated with PS between May-September 2016 were included. This resulted in 10 short (SCRT) and 10 long (LCRT) course radiotherapy treatment schedules with a total of 300 Conebeam CT scans (CBCT). New dual arc VMAT plans were generated using auto-planning for both the online ART and PS strategy. For each fraction bowel bag, bladder and mesorectum were delineated on daily Conebeam CTs. The dose distribution planned was used to calculate daily DVHs. Coverage of the CTV was calculated, as defined by the dose received by 99% of the CTV volume (D99%). The volume of normal tissue irradiated with 95% of the prescribed fraction dose was calculated by calculating the volume receiving 95% of the prescribed fraction or more dose minus the volume of the CTV. For each fraction the difference between the plan selection and online adaptive strategy of each DVH parameter was calculated, as well as the average difference per patient. RESULTS: Target coverage remained the same for online ART. The median volume of the normal tissue irradiated with 95% of the prescribed dose dropped from 642 cm3 (PS) to 237 cm3 (online-ART)(p < 0.001). Online ART reduced dose to the OARs for all tested dose levels for SCRT and LCRT (p < 0.001). For V15Gy of the bowel bag the median difference over all fractions of all patients was - 126 cm3 in LCRT, while the average difference per patient ranged from - 206 cm3 to - 40 cm3. For SCRT the median difference was - 62 cm3, while the range of the average difference per patient was - 105 cm3 to - 51 cm3. For V15Gy of the bladder the median difference over all fractions of all patients was 26% in LCRT, while the average difference per patient ranged from - 34 to 12%. For SCRT the median difference of V95% was - 8%, while the range of the average difference per patient was - 29 to 0%. CONCLUSIONS: Online ART for rectal cancer reduces dose the OARs significantly compared to a clinically implemented plan selection strategy, without compromising target coverage. TRIAL REGISTRATION: Medical Research Involving Human Subjects Act (WMO) does not apply to this study and was retrospectively approved by the Medical Ethics review Committee of the Academic Medical Center (W19_357 # 19.420; Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands).

Automatic bi-objective parameter tuning for inverse planning of high-dose-rate prostate brachytherapy.

We present an automatic bi-objective parameter-tuning approach for inverse planning methods for high-dose-rate prostate brachytherapy, which aims to overcome the difficult and time-consuming manual parameter tuning that is currently required to obtain patient-specific high-quality treatment plans. We modelled treatment planning as a bi-objective optimization problem, in which dose-volume-based planning criteria related to target coverage are explicitly separated from organ-sparing criteria. When this model is optimized, a large set of high-quality plans with different trade-offs can be obtained. This set can be visualized as an insightful patient-specific trade-off curve. In our parameter-tuning approach, the parameters of inverse planning methods are automatically tuned, aimed to maximize the two objectives of the bi-objective planning model. By generating trade-off curves for different inverse planning methods, their maximally achievable plan quality can be insightfully compared. Automatic parameter tuning furthermore allows to construct standard parameter sets (class solutions) representing different trade-offs in a principled way, which can be directly used in current clinical practice. In this work, we considered the inverse planning methods IPSA and HIPO. Thirty-nine previously treated prostate cancer patients were included. We compared automatic parameter tuning, random parameter sampling, and the maximally achievable plan quality obtained by directly optimizing the bi-objective planning model with the state-of-the-art optimization software GOMEA. We showed that for each patient, a set of plans with a wide range of trade-offs could be obtained using automatic parameter tuning for both IPSA and HIPO. By tuning HIPO, better trade-offs were obtained than by tuning IPSA. For most patients, automatic tuning of HIPO resulted in plans close to the maximally achievable plan quality obtained by optimizing the bi-objective planning model directly. Automatic parameter tuning was shown to improve plan quality significantly compared to random parameter sampling. Finally, from the automatically-tuned plans, three class solutions were successfully constructed representing different trade-offs.

Dosimetric benefit of an adaptive treatment by means of plan selection for rectal cancer patients in both short and long course radiation therapy.

BACKGROUND: To compare target coverage and dose to the organs at risk in two approaches to rectal cancer: a clinically implemented adaptive radiotherapy (ART) strategy using plan selection, and a non-adaptive (non-ART) strategy. METHODS: The inclusion of the first 20 patients receiving adaptive radiotherapy produced 10 patients with a long treatment schedule (25x2Gy) and 10 patients with a short schedule (5X5Gy). We prepared a library of three plans with different anterior PTV margins to the upper mesorectum, and selected the most appropriate plan on daily Conebeam CT scans (CBCT). We also created a non-adaptive treatment plan with a 20 mm margin. Bowel bag, bladder and target volume were delineated on CBCT. Daily DHVs were calculated based on the dose distribution of the selected and non-adaptive plans. Coverage of the target volume was compared per fraction between the ART and non-ART plans, as was the dose to the bladder and small bowel, assessing the following dose levels: V15Gy, V30Gy, V40Gy, V15Gy and V95% for long treatment schedules, and V15Gy and V95% for short ones. RESULTS: Target volume coverage was maintained from 98.3% (non-ART) to 99.0% (ART)(p = 0.878). In the small bowel, ART appeared to have produced significant reductions in the long treatment schedule at V15Gy, V40Gy, V45Gy and V95% (p <  0.05), but with small absolute differences. The DVH parameters tested for the short treatment schedule did not differ significantly. In the bladder, all DVH parameters in both schedules showed significant reductions (p <  0.05), also with small absolute differences. CONCLUSIONS: The adaptive treatment maintained target coverage and reduced dose to the organs at risk. TRIAL REGISTRATION: Medical Research Involving Human Subjects Act (WMO) does not apply to this study and was retrospectively approved by the Medical Ethics review Committee of the Academic Medical Center, W19_194 # 19.233.

The development of PdNi thermoseeds for interstitial hyperthermia.

Magnetic induction heating of thermoseed implants can be used to produce highly localized hyperthermia in deep-seated tumors. Automatic temperature control throughout the tumor can be achieved by the self-regulating character of ferromagnetic seeds, which corrects for local variations in heat loss due to blood perfusion. An increased sharpness of the ferromagnetic transition at the Curie temperature, Tc, improves the performance of self-regulating control. This was realized for palladium-nickel alloys by a "cold working" procedure preceded and followed by annealing. Palladium-nickel seeds with a predetermined Tc were produced, showing a sharp decrease at Tc of the magnetic susceptibility and the heat production.

Modelling tissue heating with ferromagnetic seeds.

Interstitial hyperthermia using ferromagnetic seeds demands accurate treatment planning: the seed characteristics and implant geometry must be determined prior to the treatment. A new, finite difference based, seed modelling method is presented. The seed, together with all its surrounding (non-tissue) layers is described as one unit, independent of the tissue grid. The calculation of the seed-tissue interaction is based on the local seed temperature and several tissue temperature samples in the direct vicinity. All the layers between the seed and the surrounding tissue are taken into account in this interaction calculation. The presented implementation describes the analytical solution of the modelled steady-state configurations very accurately. The separation between tissue and seed allows easy assessment of the resulting seed temperature profile which is essential to the optimization of the seed characteristics in treatment planning. The thermal effect due to blood flow in the modelled tissue volume surrounding the seed can be accounted for by inclusion of a heat sink term as well as by inclusion of realistic discrete vasculature.

Power absorption and temperature control of multi-filament palladium-nickel thermoseeds for interstitial hyperthermia.

In interstitial hyperthermia using ferromagnetic seeds, multi-filament seeds have gained interest because of a more effective power absorption than solid seeds. Palladium-nickel (PdNi) seeds composed of filaments with diameters in the range from 0.1 to 1.0 mm (maximally 90 filaments) have been investigated to find the conditions for optimal power absorption and temperature control. Magnetic and calorimetric experiments have shown that a decreasing filament radius results in a more effective power absorption. The power absorption approaches a common asymptote for high field intensities at all filament diameters. This asymptotic behaviour can be understood as a consequence of the approach of saturation magnetization of PdNi. The sharpness of the transition at the Curie temperature, which is a measure for the quality of temperature control, improves as the magnetic field strength increases, but it is limited by the asymptote of the power absorption. When the asymptote has been reached the quality of temperature regulation of a seed can only be improved by increasing the amount of PdNi, e.g. by increasing the number of filaments. Calculations of the power absorption, using the generally applied theory based on a linear relation between the magnetization of PdNi and the magnetic field strength, do not correspond quantitatively with experimental results for seeds having an induction number smaller than the 'optimal value' of 2.5. For these seeds the measured heat production is larger than the calculated one.

Dose uniformity of ferromagnetic seed implants in tissue with discrete vasculature: a numerical study on the impact of seed characteristics and implantation techniques.

The results from simulations with a new three-dimensional treatment planning system for interstitial hyperthermia with ferromagnetic seeds are presented in this study. The thermal model incorporates discrete vessel structures as well as a heat sink and enhanced thermal conductivity. Both the discrete vessels and the ferroseeds are described parametrically in separate calculation spaces. This parametric description has the advantage of an arbitrary orientation of the structures within the tissue grid, easy manipulation of the structures and independence from the resolution of the tissue voxels (tissue calculation space). The power absorption of the self-regulating seeds is according to empirical data. The thermal effects of an unlimited number of thin layers surrounding the seed (coatings, catheters) can be modelled. The initial calculations have been performed for an array of 12 identical ferromagnetic seeds in a tissue volume with a computer generated artificial vessel network spanning four vessel generations in both the arterial and venous tree. The heterogeneously distributed large isolated vessels impair the temperature distribution significantly, indicating the limited accuracy of continuum models. Simulations with different types of ferromagnetic seeds have confirmed that the efforts of previous studies to optimize the self-regulating temperature control and the implantation techniques of the ferroseeds will improve the homogeneity of the temperature distribution in the target volume. Multifilament seeds implanted in brachytherapy needles and tubular seeds appear to be the most favourable configurations. The division of long seeds into shorter segments with the appropriate Curie temperature will further improve the homogeneity of the temperature distribution without increasing the average temperature in the volume of interest. Given the proper thermal tissue data, the model presented in this study will prove to be a useful tool in making choices for the implant geometry, seed spacing and Curie temperature.

Delineation of potential hot spots for hyperthermia treatment planning optimisation.

The optimal feed parameters of the generators for a complex-phased hyperthermia array system consisting of 4, 8 or even more applicators cannot be found using only the expertise of the treatment staff or using the limited amount of field and temperature data obtained during treatment. A number of strategies have been proposed to help us with the task to optimise the hyperthermia treatment, including several strategies specifically addressing the occurrence of hot spots. Each of the latter strategies strongly relies on the specification of the potential hot spots. This specification is either based on anatomy or the selection of an arbitrary number of potential hot spots. Therefore it is not guaranteed that all potential hot spots are included. This paper introduces a procedure for the delineation and visualisation of potential (SAR) hot spots. The potential hot spots are delineated by selecting those points for which the maximal SAR exceeds a specific SAR selection level. This SAR selection level is defined relative to the highest achievable SAR in the target volume for a certain fixed heating power. A larger number of potential hot spots and hot spots of larger size are delineated if the selection level is decreased. Although the procedure still includes an arbitrary selection criterion, i.e. the selection level, the selection is solely based on calculated EM-field data. As a result all potential hot spots can be delineated a priori. Three different objective functions are applied to maximise the SAR in the target. The first only maximises the SAR in the target volume for a given system power output. The other two intrinsically set a constraint on the set of potential hot spots as a whole. Additionally the SAR in each delineated potential hot spot separately can be constrained. In two patient cases the SAR in potential hot spots can be kept below the selection value applied for delineation of the potential hot spots. If assessed in terms of constraining the SAR value below the selection level while maximising target heating efficiency the combination of an objective function only maximising the SAR in the target with a separate constraint on each potential hot spots appears to be the most efficient.

Three-dimensional temperature control of palladium-nickel thermoseeds: a computer aided and experimental evaluation.

The capability of self-regulating thermoseeds to compensate for nonuniform cooling along their longitudinal axis has been investigated in this study. For this purpose a quasi three-dimensional computer model has been developed. Calculations of the temperature profile in tissue with nonuniform heat loss demonstrated a clear improvement in the longitudinal temperature control of PdNi seeds compared to constant power seeds. Further, two strategies for improved control of nonuniform cooling along the longitudinal axis of ferromagnetic seeds have been investigated: (1) application of a 'normal' undivided seed; and (2) division of a long seed in smaller segments of which each segment is able to respond more directly to local variations in the temperature distribution. Calculations with the quasi three-dimensional model showed that the loose segments do respond more directly to their close proximity. However, the equilibrium temperature of a segment in an area with high local blood flow will be relatively low due the limited heat production of PdNi thermoseeds. In the undivided seeds the high thermal conductivity of PdNi causes some levelling of the longitudinal temperature gradient in the seed. In addition, calorimetric experiments have shown that the heat production of a segmented seed is less effective because of a demagnetizing field. Also, the absence of PdNi between the segments reduces the heat production of the seed.

The effect of catheters and coatings on the performance of palladium-nickel thermoseeds: evaluation and design of implantation techniques.

In the development of materials for self-regulating thermoseeds much effort is put in improvement of the self-regulating temperature control mechanism of the seeds. The catheters and coatings which are needed to implant the seeds or to guarantee biocompatibility, generally impair the optimized performance of the ferromagnetic seeds. The influence of various coatings on the performance of PdNi seeds has been investigated by means of one-dimensional modelling and calorimetric experiments. Implantation using thin walled catheters is acceptable provided that the catheters are filled with water to assure good thermal coupling. Air layers inside catheters should be avoided as they reduce the sharp gradient of the heat production at the Curie temperature significantly. An alternative for the application of catheters is to insert the seeds into metallic needles. The effect of shielding by the metal needle can be minimized by driving the seed into its saturated state using a high magnetic field strength. The thermal interaction between the seed and surrounding tissue can also be enhanced by placing PdNi, e.g. tubular, on the outside of the catheter or brachytherapy needle. An additional advantage of this new design is an increase in the heat production and the quality of temperature control due to an increase in the amount of PdNi. For permanent implantation seeds can be coated with an inert metal, ceramics or plastic. The performance of the seeds is not affected by any of the coatings if certain conditions are met. For plastic coatings the thickness of the coating has to be very thin, preferably < or = 20 microns, to avoid thermal isolation.

The significance of accurate dielectric tissue data for hyperthermia treatment planning.

For hyperthermia treatment planning, dielectric properties of several tissue types are required. Since it is difficult to perform patient specific dielectric imaging, default values based on literature data are used. However, these show a large spread (approximately 50%). Consequently, it is important to know what limit this spread imposes on the accuracy of the SAR and subsequently on the temperature distributions. Hyperthermia treatment plans performed with different values for the dielectric properties were compared. This showed that a spread of 50% resulted in the average absolute difference of approximately 20% in both SAR and temperature distributions (heat sink approach) for regional hyperthermia. For interstitial hyperthermia, a spread of 25% resulted in the averaged absolute difference of approximately 10% in the SAR distributions and 5% in the temperature distributions (heat sink approach). Considering other problems that hamper hyperthermia treatment planning, it can be concluded that default values for the dielectric properties suffice.

Double-integrating-sphere system for measuring the optical properties of tissue.

A system is described and evaluated for the simultaneous measurement of the intrinsic optical properties of tissue: the scattering coefficient, the absorption coefficient, and the anisotropy factor. This system synthesizes the theory of two integrating spheres and an intervening scattering sample with the inverse adding-doubling algorithm, which employs the adding-doubling solution of the radiative transfer equation to determine the optical properties from the measurement of the light flux within each sphere and of the unscattered transmission. The optical properties may be determined simultaneously, which allows for measurements to be made while the sample undergoes heating, chemical change, or some otherexternal stimulus. An experimental validation of the system with tissue phantoms resulted in the determination of the optical properties with a < 5% deviation when the optical density was between 1 and 10 and the albedo was between 0.4 and 0.95.