J. Wiersma

Improving locoregional hyperthermia delivery using the 3-D controlled AMC-8 phased array hyperthermia system: A preclinical study

Background: The aim of this study is preclinical evaluation of our newly developed regional hyperthermia system providing 3-D SAR control: the AMC-8 phased array consisting of two rings, each with four 70 MHz waveguides. It was designed to achieve higher tumour temperatures and improve the clinical effectiveness of locoregional hyperthermia. Methods: The performance of the AMC-8 system was evaluated with simulations and measurements aiming at heating a centrally located target region in rectangular (30 × 30 × 110 cm) and elliptical (36 × 24 × 80 cm) homogeneous tissue equivalent phantoms. Three properties were evaluated and compared to its predecessor, the 2-D AMC-4 single ring four waveguide array: (1) spatial control and (2) size of the SAR focus, (3) the ratio between maximum SAR outside the target region and SAR in the focus. Distance and phase difference between the two rings were varied. Results: (1) Phase steering provides 3-D SAR control for the AMC-8 system. (2) The SAR focus is more elongated compared to the AMC-4 system, yielding a lower SAR level in the focus when using the same total power. This is counter-balanced by (3) a superficial SAR deposition which is half of that in the AMC-4 system, yielding a more favourable ratio between normal tissue and target SAR and allowing higher total power and up to 30% more SAR in the focus for 3 cm ring distance. Conclusion: The AMC-8 system is capable of 3-D SAR control and its SAR distribution is more favourable than for the 2-D AMC-4 system. This result promises improvement in clinical tumour temperatures.

High-resolution temperature-based optimization for hyperthermia treatment planning

In regional hyperthermia, optimization techniques are valuable in order to obtain amplitude/phase settings for the applicators to achieve maximal tumour heating without toxicity to normal tissue. We implemented a temperature-based optimization technique and maximized tumour temperature with constraints on normal tissue temperature to prevent hot spots. E-field distributions are the primary input for the optimization method. Due to computer limitations we are restricted to a resolution of 1 x 1 x 1 cm3 for E-field calculations, too low for reliable treatment planning. A major problem is the fact that hot spots at low-resolution (LR) do not always correspond to hot spots at high-resolution (HR), and vice versa. Thus, HR temperature-based optimization is necessary for adequate treatment planning and satisfactory results cannot be obtained with LR strategies. To obtain HR power density (PD) distributions from LR E-field calculations, a quasi-static zooming technique has been developed earlier at the UMC Utrecht. However, quasi-static zooming does not preserve phase information and therefore it does not provide the HR E-field information required for direct HR optimization. We combined quasi-static zooming with the optimization method to obtain a millimetre resolution temperature-based optimization strategy. First we performed a LR (1 cm) optimization and used the obtained settings to calculate the HR (2 mm) PD and corresponding HR temperature distribution. Next, we performed a HR optimization using an estimation of the new HR temperature distribution based on previous calculations. This estimation is based on the assumption that the HR and LR temperature distributions, though strongly different, respond in a similar way to amplitude/phase steering. To verify the newly obtained settings, we calculate the corresponding HR temperature distribution. This method was applied to several clinical situations and found to work very well. Deviations of this estimation method for the AMC-4 system were typically smaller than 0.2 degrees C in the volume of interest, which is accurate enough for treatment planning purposes.

Prospective treatment planning to improve locoregional hyperthermia for oesophageal cancer

Background: In the Academic Medical Center (AMC) Amsterdam, locoregional hyperthermia for oesophageal tumours is applied using the 70 MHz AMC-4 phased array system. Due to the occurrence of treatment-limiting hot spots in normal tissue and systemic stress at high power, the thermal dose achieved in the tumour can be sub-optimal. The large number of degrees of freedom of the heating device, i.e. the amplitudes and phases of the antennae, makes it difficult to avoid treatment-limiting hot spots by intuitive amplitude/phase steering. Aim: Prospective hyperthermia treatment planning combined with high resolution temperature-based optimization was applied to improve hyperthermia treatment of patients with oesophageal cancer. Methods: All hyperthermia treatments were performed with ‘standard’ clinical settings. Temperatures were measured systemically, at the location of the tumour and near the spinal cord, which is an organ at risk. For 16 patients numerically optimized settings were obtained from treatment planning with temperature-based optimization. Steady state tumour temperatures were maximized, subject to constraints to normal tissue temperatures. At the start of 48 hyperthermia treatments in these 16 patients temperature rise (ΔT) measurements were performed by applying a short power pulse with the numerically optimized amplitude/phase settings, with the clinical settings and with mixed settings, i.e. numerically optimized amplitudes combined with clinical phases. The heating efficiency of the three settings was determined by the measured ΔT values and the ΔT-ratio between the ΔT in the tumour (ΔToes) and near the spinal cord (ΔTcord). For a single patient the steady state temperature distribution was computed retrospectively for all three settings, since the temperature distributions may be quite different. To illustrate that the choice of the optimization strategy is decisive for the obtained settings, a numerical optimization on ΔT-ratio was performed for this patient and the steady state temperature distribution for the obtained settings was computed. Results: A higher ΔToes was measured with the mixed settings compared to the calculated and clinical settings; ΔTcord was higher with the mixed settings compared to the clinical settings. The ΔT-ratio was ∼1.5 for all three settings. These results indicate that the most effective tumour heating can be achieved with the mixed settings. ΔT is proportional to the Specific Absorption Rate (SAR) and a higher SAR results in a higher steady state temperature, which implies that mixed settings are likely to provide the most effective heating at steady state as well. The steady state temperature distributions for the clinical and mixed settings, computed for the single patient, showed some locations where temperatures exceeded the normal tissue constraints used in the optimization. This demonstrates that the numerical optimization did not prescribe the mixed settings, because it had to comply with the constraints set to the normal tissue temperatures. However, the predicted hot spots are not necessarily clinically relevant. Numerical optimization on ΔT-ratio for this patient yielded a very high ΔT-ratio (∼380), albeit at the cost of excessive heating of normal tissue and lower steady state tumour temperatures compared to the conventional optimization. Conclusion: Treatment planning can be valuable to improve hyperthermia treatments. A thorough discussion on clinically relevant objectives and constraints is essential.

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.

The impact of the waveguide aperture size of the 3D 70 MHz AMC-8 locoregional hyperthermia system on tumour coverage

The 70 MHz AMC-4 system, with one ring of four waveguides, provides 2D power steering. The newly developed AMC-8 system enables 3D steering, using two rings of four 70 MHz waveguides. The current waveguide aperture size is 20.2 x 34.3 cm(2). Waveguides and water boluses cover a large area of the body, which is not ideal for short patients. The aim of this study is investigating the impact of smaller waveguides on tumour coverage, using treatment planning. Finite-difference time-domain simulations were performed at 2.5 x 2.5 x 5 mm(3) resolution. Virtual AMC-8 systems with waveguide aperture sizes of 20.5 x 34.25, 17.5 x 34.25, 14.5 x 34.25, 11.5 x 34.25, 8.5 x 34.25 cm(2) and the AMC-4 system were modelled. Simulations were performed for elliptical (36 x 24 x 100 cm(3)) tissue-equivalent phantoms and for five cervical cancer patients. For the phantoms S(ratio) (SAR(max_border)/SAR(target)) was evaluated for standard and optimized settings. For the patients, temperature distributions were evaluated after optimization of tumour temperature, while limiting normal tissue temperatures to 45 degrees C. Phantom simulations showed a favourable S(ratio) for all two-ring systems, compared to the AMC-4 system, for optimized phase-amplitude settings. Patient simulations demonstrated that the improvement in T(90) for the operational AMC-8 system was approximately 0.5 degrees C. This improvement was independent of the aperture size. The average number of imminent hot spots and their total volume was almost comparable for 8.5 and 20.5 cm wide apertures, but the locations were different. Two-ring waveguide systems with eight antennas and aperture sizes in the range from 20.5 x 34.25 cm(2) to 8.5 x 34.25 cm(2) showed a stable gain in tumour temperature compared to a single-ring four-antenna system with 20.5 x 34.25 cm(2) wide apertures.

Plan selection strategy for rectum cancer patients: An interobserver study to assess clinical feasibility

BACKGROUND AND PURPOSE In radiotherapy for rectum cancer, the target volume is highly deformable. An adaptive plan selection strategy can mitigate the effect of these variations. The purpose of this study was to evaluate the feasibility of an adaptive strategy by assessing the interobserver variation in CBCT-based plan selection. MATERIAL AND METHODS Eleven patients with rectum cancer, treated with a non-adaptive strategy, were selected. Five CBCT scans were available per patient. To simulate the plan selection strategy, per patient three PTVs were created by varying the anterior upper mesorectum margin. For each CBCT scan, twenty observers selected the smallest PTV that encompassed the target volume. After this initial baseline measurement, the gold standard was determined during a consensus meeting, followed by a second measurement one month later. Differences between both measurements were assessed using the Wilcoxon signed-rank test. RESULTS In the baseline measurement, the concordance with the gold standard was 69% (range: 60-82%), which improved to 75% (range: 60-87%) in the second measurement (p=0.01). For the second measurement, 10% of plan selections were smaller than the gold standard. CONCLUSION With a plan selection consistency between observers of 75%, a plan selection strategy for rectum cancer patients is feasible.

Heart volume reduction during radiotherapy involving the thoracic region in children: An unexplained phenomenon

BACKGROUND AND PURPOSE Radiotherapy involving the thoracic region is associated with cardiotoxicity in long-term childhood cancer survivors. We quantified heart volume changes during radiotherapy in children (<18 years) and investigated correlations with patient and treatment related characteristics. MATERIAL AND METHODS Between 2010 and 2016, 34 children received radiotherapy involving the thoracic region. We delineated heart contours and measured heart volumes on 114 CBCTs. Relative volume changes were quantified with respect to the volume on the first CBCT (i.e., 100%). Cardiac radiation dose parameters expressed as 2 Gy/fraction equivalent doses were calculated from DVHs. Chemotherapy was categorized as treatment with anthracyclines, alkylating agents, vinca-alkaloids, and other. RESULTS The overall median heart volume reduction from the first to the last CBCT was 5.5% (interquartile range1.6-9.7%; p < 0.001). Heart volumes decreased significantly between the baseline measurement and the first week (Bonferronis adjusted p = 0.002); volume changes were not significant during the following weeks. Univariate analysis showed a significant correlation between heart volume reduction and alkylating agents; however, no multivariate analyses could be done to further confirm this. CONCLUSIONS We found a significant heart volume reduction in children during radiotherapy. Elucidation of underlying mechanisms, clinical relevance, and possible long-term consequences of early heart volume reduction require a prospective follow-up study.