Simo Hyödynmaa

Optimization of the Dose Level for a Given Treatment Plan to Maximize the Complication-free Tumor Cure

During the past decade, tumor and normal tissue reactions after radiotherapy have been increasingly quantified in radiobiological terms. For this purpose, response models describing the dependence of tumor and normal tissue reactions on the irradiated volume, heterogeneity of the delivered dose distribution and cell sensitivity variations can be taken into account. The probability of achieving a good treatment outcome can be increased by using an objective function such as P+, the probability of complication-free tumor control. A new procedure is presented, which quantifies P+ from the dose delivery on 2D surfaces and 3D volumes and helps the user of any treatment planning system (TPS) to select the best beam orientations, the best beam modalities and the most suitable beam energies. The final step of selecting the prescribed dose level is made by a renormalization of the entire dose plan until the value of P+ is maximized. The index P+ makes use of clinically established dose-response parameters, for tumors and normal tissues of interest, in order to improve its clinical relevance. The results, using P+, are compared against the assessments of experienced medical physicists and radiation oncologists for two clinical cases. It is observed that when the absorbed dose level for a given treatment plan is increased, the treatment outcome first improves rapidly. As the dose approaches the tolerance of normal tissues the complication-free cure begins to drop. The optimal dose level is often just below this point and it depends on the geometry of each patient and target volume. Furthermore, a more conformal dose delivery to the target results in a higher control rate for the same complication level. This effect can be quantified by the increased value of the P+ parameter.

Optimization of conformal electron beam therapy using energy- and fluence-modulated beams.

Fluence modulation of multiple electron beams of various energies has been used to optimize the delivereddose distribution during electron beamradiation therapy. By maximizing the probability of achieving tumor control without causing severe complications electron beam fluence profiles have been optimized for superficial target volumes. It is possible to use several equiportal fluence‐modulated electron beams to modify the energy deposition with depth in a controlled manner making it possible to use the technique as an alternative to bolus. The technique was tested in two representative phantom geometries and in three clinical patient geometries using a set of five and two different energies. The local maxima in dose for the plans with five energies were typically lower than with the conventional or advanced bolus techniques. The principles for how the technique could be carried out in the future with a fourth generation radiotherapy accelerator are also indicated.

Performance of dose calculation algorithms from three generations in lung SBRT: comparison with full Monte Carlo-based dose distributions

The accuracy of dose calculation is a key challenge in stereotactic body radiotherapy (SBRT) of the lung. We have benchmarked three photon beam dose calculation algorithms — pencil beam convolution (PBC), anisotropic analytical algorithm (AAA), and Acuros XB (AXB) — implemented in a commercial treatment planning system (TPS), Varian Eclipse. Dose distributions from full Monte Carlo (MC) simulations were regarded as a reference. In the first stage, for four patients with central lung tumors, treatment plans using 3D conformal radiotherapy (CRT) technique applying 6 MV photon beams were made using the AXB algorithm, with planning criteria according to the Nordic SBRT study group. The plans were recalculated (with same number of monitor units (MUs) and identical field settings) using BEAMnrc and DOSXYZnrc MC codes. The MC‐calculated dose distributions were compared to corresponding AXB‐calculated dose distributions to assess the accuracy of the AXB algorithm, to which then other TPS algorithms were compared. In the second stage, treatment plans were made for ten patients with 3D CRT technique using both the PBC algorithm and the AAA. The plans were recalculated (with same number of MUs and identical field settings) with the AXB algorithm, then compared to original plans. Throughout the study, the comparisons were made as a function of the size of the planning target volume (PTV), using various dose‐volume histogram (DVH) and other parameters to quantitatively assess the plan quality. In the first stage also, 3D gamma analyses with threshold criteria 3%/3 mm and 2%/2 mm were applied. The AXB‐calculated dose distributions showed relatively high level of agreement in the light of 3D gamma analysis and DVH comparison against the full MC simulation, especially with large PTVs, but, with smaller PTVs, larger discrepancies were found. Gamma agreement index (GAI) values between 95.5% and 99.6% for all the plans with the threshold criteria 3%/3 mm were achieved, but 2%/2 mm threshold criteria showed larger discrepancies. The TPS algorithm comparison results showed large dose discrepancies in the PTV mean dose (D50%), nearly 60%, for the PBC algorithm, and differences of nearly 20% for the AAA, occurring also in the small PTV size range. This work suggests the application of independent plan verification, when the AAA or the AXB algorithm are utilized in lung SBRT having PTVs smaller than 20‐25 cc. The calculated data from this study can be used in converting the SBRT protocols based on type ‘a’ and/or type ‘b’ algorithms for the most recent generation type ‘c’ algorithms, such as the AXB algorithm. PACS numbers: 87.55.‐x, 87.55.D‐, 87.55.K‐, 87.55.kd, 87.55.Qr

Optimization of 3D conformal electron beam therapy in inhomogeneous media by concomitant fluence and energy modulation

The possibilities of using simultaneous fluence and energy modulation techniques in electron beam therapy to shape the dose distribution and almost eliminate the influences of tissue inhomogeneities have been investigated. By using a radiobiologically based optimization algorithm the radiobiological properties of the tissues can be taken into account when trying to find the best possible dose delivery. First water phantoms with differently shaped surfaces were used to study the effect of surface irregularities. We also studied water phantoms with internal inhomogeneities consisting of air or cortical bone. It was possible to improve substantially the dose distribution by fluence modulation in these cases. In addition to the fluence modulation the most suitable single electron energy in each case was also determined. Finally, the simultaneous use of several preselected electron beam energies was also tested, each with an individually optimized fluence profile. One to six electron energies were used, resulting in a slow improvement in complication-free cure with increasing number of beam energies. To apply these techniques to a more clinically relevant situation a post-operative breast cancer patient was studied. For simplicity this patient was treated with only one anterior beam portal to clearly illustrate the effect of inhomogeneities like bone and lung on the dose distribution. It is shown that by using fluence modulation the influence of dose inhomogeneities can be significantly reduced. When two or more electron beam energies with individually optimized fluence profiles are used the dose conformality to the internal target volume is further increased, particularly for targets with complex shapes.

Radiological pulmonary findings after breast cancer irradiation: A prospective study

The aim of this study was to evaluate radiation-induced pulmonary abnormalities of breast cancer patients. Altogether 202 consecutive patients receiving postoperative radiotherapy entered the study. Plain chest radiographs taken at entry and 3, 6 and 12 months after radiotherapy were evaluated according to modified Arriagada classification. In addition, pulmonary symptoms were recorded. Supplementary high-resolution computed tomography (HRCT) was employed in a subgroup of patients (n = 15). Plain radiographs were interpreted by a radiologist, and uncertain findings were re-evaluated by a radiologist together with a radiation oncologist. Grade 2 pneumonitis was the most common abnormality. The proportion of patients yielding a grade 2 finding was 22.5%, 28.1%, and 16.0% at three, six, and twelve months, respectively. There were 2 normal findings in HRCTscans, and 8 in plain radiographs of the same patients. Radiological lung abnormalities are common after radiotherapy, but they are usually reversible, and their significance for the patients well-being is minor. No correlation between symptoms and lung or pleural reactions was seen.

Optimal electron and combined electron and photon therapy in the phase space of complication-free cure

The possibility of using intensity-modulated high-energy electrons beams alone or in combination with photon beams to treat tumours located at depths from 5 cm to 25 cm has been investigated. A radiobiologically based optimization algorithm using the probability of complication-free tumour control has been used to calculate the optimal dose distributions. Two different target volumes have been used; one advanced cervical cancer with locally involved lymph nodes and one astrocytoma in the upper brain hemisphere. Treatments with only electron beams and also combinations between electron and photon beams have been investigated. The dependence of the expected treatment outcome on the beam energy and directions was investigated, and to some extent on the number of beam portals. It is shown that the beam direction intervals resulting in a high expected treatment outcome increase with increasing electron energy and also with some electron-photon combinations. For an eccentrically placed, not too deeply situated tumour surrounded by sensitive normal tissue it is shown that the expected treatment outcome can be improved by using electron beams in combination with photon beams compared with using two photon beams, and using two electron beams results in almost as high an expected treatment outcome. The possibility of improving the dose conformity from electron beams by adding photon fields parallel or orthogonal to the electron beams is demonstrated.

Evaluation of dose-response models and parameters predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy.

The purpose of this work is to evaluate the predictive strength of the relative seriality, parallel and LKB normal tissue complication probability (NTCP) models regarding the incidence of radiation pneumonitis, in a large group of patients following breast cancer radiotherapy, and furthermore, to illustrate statistical methods for examining whether certain published radiobiological parameters are compatible with a clinical treatment methodology and patient group characteristics. The study is based on 150 consecutive patients who received radiation therapy for breast cancer. For each patient, the 3D dose distribution delivered to lung and the clinical treatment outcome were available. Clinical symptoms and radiological findings, along with a patient questionnaire, were used to assess the manifestation of radiation-induced complications. Using this material, different methods of estimating the likelihood of radiation effects were evaluated. This was attempted by analysing patient data based on their full dose distributions and associating the calculated complication rates with the clinical follow-up records. Additionally, the need for an update of the criteria that are being used in the current clinical practice was also examined. The patient material was selected without any conscious bias regarding the radiotherapy treatment technique used. The treatment data of each patient were applied to the relative seriality, LKB and parallel NTCP models, using published parameter sets. Of the 150 patients, 15 experienced radiation-induced pneumonitis (grade 2) according to the radiation pneumonitis scoring criteria used. Of the NTCP models examined, the relative seriality model was able to predict the incidence of radiation pneumonitis with acceptable accuracy, although radiation pneumonitis was developed by only a few patients. In the case of modern breast radiotherapy, radiobiological modelling appears to be very sensitive to model and parameter selection giving clinically acceptable results in certain cases selectively (relative seriality model with Seppenwoolde et al and Gagliardi et al parameter sets). The use of published parameters should be considered as safe only after their examination using local clinical data. The variation of inter-patient radiosensitivity seems to play a significant role in the prediction of such low incidence rate complications. Scoring grades were combined to give stronger evidence of radiation pneumonitis since their differences could not be strictly associated with dose. This obviously reveals a weakness of the scoring related to this endpoint, and implies that the probability of radiation pneumonitis induction may be too low to be statistically analysed with high accuracy, at least with the latest advances of dose delivery in breast radiotherapy.

The accuracy of Acuros XB algorithm for radiation beams traversing a metallic hip implant — comparison with measurements and Monte Carlo calculations

In this study, the clinical benefit of the improved accuracy of the Acuros XB (AXB) algorithm, implemented in a commercial radiotherapy treatment planning system (TPS), Varian Eclipse, was demonstrated with beams traversing a high‐Z material. This is also the first study assessing the accuracy of the AXB algorithm applying volumetric modulated arc therapy (VMAT) technique compared to full Monte Carlo (MC) simulations. In the first phase the AXB algorithm was benchmarked against point dosimetry, film dosimetry, and full MC calculation in a water‐filled anthropometric phantom with a unilateral hip implant. Also the validity of the full MC calculation used as reference method was demonstrated. The dose calculations were performed both in original computed tomography (CT) dataset, which included artifacts, and in corrected CT dataset, where constant Hounsfield unit (HU) value assignment for all the materials was made. In the second phase, a clinical treatment plan was prepared for a prostate cancer patient with a unilateral hip implant. The plan applied a hybrid VMAT technique that included partial arcs that avoided passing through the implant and static beams traversing the implant. Ultimately, the AXB‐calculated dose distribution was compared to the recalculation by the full MC simulation to assess the accuracy of the AXB algorithm in clinical setting. A recalculation with the anisotropic analytical algorithm (AAA) was also performed to quantify the benefit of the improved dose calculation accuracy of type ‘c’ algorithm (AXB) over type ‘b’ algorithm (AAA). The agreement between the AXB algorithm and the full MC model was very good inside and in the vicinity of the implant and elsewhere, which verifies the accuracy of the AXB algorithm for patient plans with beams traversing through high‐Z material, whereas the AAA produced larger discrepancies. PACS numbers: 87.55.‐x, 87.55.D‐, 87.55.K‐, 87.55.kd, 87.55.Qr

Dose accuracy check of the 3D electron beam algorithm in a treatment planning system

The accuracy of the recently implemented three-dimensional electron beam dose calculating algorithm in CADPLAN version 2.62 manufactured by Varian Dosetek was investigated. The algorithm uses a generalized Gaussian pencil beam model and the dose distributions are calculated as the sum of three weighted Gaussians. To use the calculating program in an optimum way, one needs to know the dose calculation accuracy of the algorithm as well as its limitations. This investigation includes comparisons of measured relative dose distributions with calculated dose distributions and also comparisons of measured and calculated monitor units. The geometries tested were quadratic fields, irregularly shaped fields, oblique fields, irregularly shaped phantom surfaces and internal heterogeneities and were most often irradiated with 8 and 20 MeV electrons. The results indicate that the algorithm is well suited for clinical three-dimensional dose planning. Some deviations occurred but they were most often within the limits of international criteria of acceptability.

The role of phantom and treatment head generated bremsstrahlung in high-energy electron beam dosimetry

An analytical expression has been derived for the phantom generated bremsstrahlung photons in plane-parallel monoenergetic electron beams normally incident on material of any atomic number (Be, H2O, Al, Cu and U). The expression is suitable for the energy range from 1 to 50 MeV and it is solely based on known scattering power and radiative and collision stopping power data for the material at the incident electron energy. The depth dose distribution due to the bremsstrahlung generated by the electrons in the phantom is derived by convolving the bremsstrahlung energy fluence produced in the phantom with a simple analytical energy deposition kernel. The kernel accounts for both electrons and photons set in motion by the bremsstrahlung photons. The energy loss by the primary electrons, the build-up of the electron fluence and the generation, attenuation and absorption of bremsstrahlung photons are all taken into account in the analytical formula. The longitudinal energy deposition kernel is derived analytically and it is consistent with both the classical biexponential relation describing the photon depth dose distribution and the exponential attenuation of the primary photons. For comparison Monte Carlo calculated energy deposition distributions using ITS3 code were used. Good agreement was found between the results with the analytical expression and the Monte Carlo calculation. For tissue equivalent materials, the maximum total energy deposition differs by less than 0.2% from Monte Carlo calculated dose distributions. The result can be used to estimate the depth dependence of phantom generated bremsstrahlung in different materials in therapeutic electron beams and the bremsstrahlung production in different electron absorbers such as scattering foils, transmission monitors and photon and electron collimators. By subtracting the phantom generated bremsstrahlung from the total bremsstrahlung background the photon contamination generated in the treatment head can be determined to allow accurate dosimetry of heavily photon contaminated electron beams.