Scanning irradiation device for mice in vivo with pulsed and continuous proton beams.

A technical set-up for irradiation of subcutaneous tumours in mice with nanosecond-pulsed proton beams or continuous proton beams is described and was successfully used in a first experiment to explore future potential of laser-driven particle beams, which are pulsed due to the acceleration process, for radiation therapy. The chosen concept uses a microbeam approach. By focusing the beam to approximately 100 × 100 µm(2), the necessary fluence of 10(9) protons per cm(2) to deliver a dose of 20 Gy with one-nanosecond shot in the Bragg peak of 23 MeV protons is achieved. Electrical and mechanical beam scanning combines rapid dose delivery with large scan ranges. Aluminium sheets one millimetre in front of the target are used as beam energy degrader, necessary for adjusting the depth-dose profile. The required procedures for treatment planning and dose verification are presented. In a first experiment, 24 tumours in mice were successfully irradiated with 23 MeV protons and a single dose of 20 Gy in pulsed or continuous mode with dose differences between both modes of 10%. So far, no significant difference in tumour growth delay was observed.

Measurements to predict the time of target replacement of a helical tomotherapy.

Intensity-modulated radiation therapy (IMRT) requires more beam-on time than normal open field treatment. Consequently, the machines wear out and need more spare parts. A helical tomotherapy treatment unit needs a periodical tungsten target replacement, which is a time consuming event. To be able to predict the next replacement would be quite valuable. We observed unexpected variations towards the end of the target lifetime in the performed pretreatment measurements for patient plan verification. Thus, we retrospectively analyze the measurements of our quality assurance program. The time dependence of the quotient of two simultaneous dose measurements at different depths within a phantom for a fixed open field irradiation is evaluated. We also assess the time-dependent changes of an IMRT plan measurement and of a relative depth dose curve measurement. Additionally, we performed a Monte Carlo simulation with Geant4 to understand the physical reasons for the measured values. Our measurements show that the dose at a specified depth compared to the dose in shallower regions of the phantom declines towards the end of the target lifetime. This reproducible effect can be due to the lowering of the mean energy of the X-ray spectrum. These results are supported by the measurements of the IMRT plan, as well as the study of the relative depth dose curve. Furthermore, the simulation is consistent with these findings since it provides a possible explanation for the reduction of the mean energy for thinner targets. It could be due to the lowering of low energy photon self-absorption in a worn out and therefore thinner target. We state a threshold value for our measurement at which a target replacement should be initiated. Measurements to observe a change in the energy are good predictors of the need for a target replacement. However, since all results support the softening of the spectrum hypothesis, all depth-dependent setups are viable for analyzing the deterioration of the tungsten target. The suggested measurements and criteria to replace the target can be very helpful for every user of a TomoTherapy machine.

A planning comparison of dynamic IMRT for different collimator leaf thicknesses with helical tomotherapy and RapidArc for prostate and head and neck tumors.

PURPOSE: A comparative analysis of the three most advanced intensity-modulated radiotherapy (IMRT) techniques currently commercially available was performed. Treatment plans made in rotational techniques (helical tomotherapy [HT] and RapidArc) were compared with sliding-window IMRT (dIMRT) on a conventional linear accelerator using different leaf thicknesses (2.5 mm, 5 mm, and 10 mm). The influence of the different planning techniques on the coverage of planning volume and sparing of organs at risk (OARs) was investigated. PATIENTS AND METHODS: Nine patients with localized prostate and nine patients with head and neck cancer were chosen for this study. Treatment planning was performed in Eclipse (Varian) and in Tomotherapy planning software. Treatment plans were compared according to target volume coverage and sparing OARs, as well as by conformity and homogeneity index. RESULTS: For both investigated tumor sites, the dosimetric effects of leaf widths between 2.5 mm, 5 mm and 10 mm were shown to be small in regard to target coverage. Tomotherapy plans had better target coverage (higher minimum dose). For prostate cancer, better sparing of bladder and rectum was achieved with RapidArc and dIMRT plans. For head and neck cancer, best sparing of parotid glands was achieved in HT plans. There was no significant difference (p > 0.05) in sparing of OARs between the dIMRT plans with different leaf widths neither for prostate cancer nor for head and neck cancer. CONCLUSION: For prostate and head and neck cases, all investigated IMRT techniques provide highly conformal treatment plans in terms of both target coverage and critical structure sparing.

A new modification of combining vacuum therapy and brachytherapy in large subfascial soft -tissue sarcomas of the extremities.

PURPOSE: To present a modification of a technique combining the advantages of brachytherapy for local radiation treatment and vacuum therapy for wound conditioning after resection of subfascial soft-tissue sarcomas (STS) of the extremities. PATIENTS AND METHODS: Between January and May 2008, four patients with large (> 10 cm) subfascial STS of the thigh underwent marginal tumor excision followed by early postoperative HDR (high-dose-rate) brachytherapy (iridium-192) and vacuum therapy as part of their interdisciplinary treatment. The sponge of the vacuum system was used to stabilize brachytherapy applicators in parallel positions and to allow for a maximal wound contraction in the early postoperative phase, thus preventing seroma and deterioration of local dose distribution as optimized in computed tomography-(CT-)based three-dimensional conformal treatment planning. In three patients this was followed by external-beam radiotherapy. Acute wound complications and late effects according to LENT-SOMA after 4-8 months of follow-up were recorded. RESULTS: The combination of vacuum and brachytherapy was applicable in all patients. CT scans from the 1st postoperative day showed the shrinkage of the sponge located in the tumor bed with the brachytherapy applicators in the intended position and easily visible. 15-18 Gy in fractions of 3 Gy bid prescribed to 5 mm tissue depth were applied over the next days with removal of the sponge and applicators on days 5-8. No early or late toxicity exceeding grade 2 was observed. The mean Enneking Score for functional outcome was 63% (perfect function = 100%). CONCLUSION: The combination of vacuum and brachytherapy is applicable and safe in the treatment of large subfascial STS.

A method for improved verification of entire IMRT plans by film dosimetry.

BACKGROUND AND PURPOSE: : In one entire intensity-modulated radiation therapy (IMRT) plan, beams coming from different directions have different penetration depths in the phantom. Therefore, verifying an entire IMRT plan with a calibration curve for a single depth is error-prone. The aim of this study is to improve the quality of the dose verification of entire IMRT plans with film dosimetry. MATERIAL AND METHODS: : The dose response of the Kodak EDR2 film to 6-MV photon beams was investigated in a solid-water phantom for different field sizes and depths. A method is proposed for evaluating measurements of the optical density with a calibration curve that takes the response at different depths into account. The described method was tested for three entire IMRT plans. For this purpose, calculated and measured dose distributions were compared, where the measured dose distribution was evaluated using a calibration curve for one depth (5 cm) and a calibration curve derived according to the proposed method. RESULTS: : All measurements suggest that the dose response significantly depends on the depth in the phantom, while dependencies on field size and off-axes distance are smaller. For tested plans, gamma index < 1 (using 3 mm distance and 3% dose as constrains) was reached for 81% and 91% of the points for one plan (prostate), 81% and 86% for the second plan (prostate), and 74% and 85% for the third plan (liver) when using two calibration curves, respectively. CONCLUSION: : The method described here corrects for the change of the film response due to the variation of the scattered radiation with the penetration depth. This is achieved by a modified calibration curve, which can enhance the accuracy of the verification of entire IMRT plans.

Comparison of three different mediastinal radiotherapy techniques in female patients: Impact on heart sparing and dose to the breasts.

BACKGROUND AND PURPOSE: To study different radiotherapy techniques for female patients with mediastinal target volumes. Especially in highly curable diseases such as lymphoma, long-term survivors might develop late cardiac damage and radiation-induced second cancer. PATIENTS AND METHODS: Planning CT scans were obtained in eight cases. We contoured the clinical target volume (three different scenarios with or without lower mediastinum and hili) and organs at risk and compared standard 6MV ap-pa opposed fields to a 3D conformal 4-field technique and a 7-field step-and-shoot IMRT technique and evaluated DVHs for each structure. The planning system was BrainSCAN 5.21 (BrainLAB, Heimstetten, Germany). RESULTS: Target volume coverage did not improve significantly with 4-field or IMRT techniques. However, IMRT resulted in better dose reduction to the heart than the other techniques. The median heart dose (intermediately sized target volume) was 98% (95-100) with ap-pa fields, 56% (52-79) with the 4-field technique, and 39% (36-65) with IMRT, for example (p<0.05). Better heart sparing was achieved at all dose levels down to the 15% isodose. The median maximum dose to the breasts was lowest with IMRT. The breast volume receiving low doses (15% or less), however, was highest with IMRT. There was also a disadvantage in mean lung dose. CONCLUSIONS: IMRT might result in a reduced cardiac complication risk. In younger females, however, this advantage might be offset by the risk of breast cancer. The best technique for a given patient depends on age, comorbidity, and the individual risk estimates for breast cancer and cardiac morbidity, respectively.

Preclinical study investigating the potential of low-dose-rate brachytherapy with 32P stents for the prevention of restenosis of paranasal neo-ostia.

PURPOSE: Ostial restenosis is a common cause of failures in paranasal sinus surgery. The aim of the current study was to investigate the use of low-dose-rate brachytherapy to prevent neo-ostial restenosis in an animal model. METHODS AND MATERIALS: In 14 rabbits, maxillary neo-ostia were created and measured. One side each was stented with a regular silicone stent, the other side was either not stented (n = 7) or stented with a phosphorous-32 implanted stent depositing a low-dose radiation of 15 Gy (n = 7) within 1 week, after which all stents were removed. After a period of additional 12 weeks of recovery, the animals were sacrificed, the neo-ostia were again measured, and the areas and histopathologic changes compared in between the groups. RESULTS: After 15-Gy stenting, the mean ostial areas were even slightly enlarged by 5.1% compared to the area at stent removal, whereas a significant reduction in area, indicating a process of restenosis, by 56.1% or 54.0% was seen in the control groups with no stent and normal stent, respectively. Furthermore, no indication for adverse histopathologic radiation effects was seen in the 15-Gy group. CONCLUSIONS: Low-dose-rate brachytherapy with phosphorous-32 doped silicone stents showed promising results in the prevention of neo-ostium restenosis in this proof-of-concept study, indicating that further preclinical and clinical testing may be warranted.

Dose to the intracranial arteries in stereotactic and intensity-modulated radiotherapy for skull base tumors.

PURPOSE: To examine retrospectively the maximum dose to the large skull base/intracranial arteries in fractionated stereotactic radiotherapy (FSRT) and intensity-modulated radiotherapy (IMRT), because of the potential risk of perfusion disturbances. METHODS AND MATERIALS: Overall, 56 patients with tumors adjacent to at least one major artery were analyzed. Our strategy was to perform FSRT with these criteria: 1.8 Gy per fraction, planning target volume (PTV) enclosed by the 95% isodose, maximum dose 107%. Dose limits were applied to established organs at risk, but not the vessels. If FSRT planning failed to meet any of these criteria, IMRT was planned with the same objectives. RESULTS: In 31 patients (median PTV, 23 cm3), the FSRT plan fulfilled all criteria. No artery received a dose > or =105%. Twenty-five patients (median PTV, 39 cm3) needed IMRT planning. In 11 of 25 patients (median PTV, 85 cm3), no plan satisfying all our criteria could be calculated. Only in this group, moderately increased maximum vessel doses were observed (106-110%, n = 7, median PTV, 121 cm3). The median PTV dose gradient was 29% (significantly different from the 14 patients with satisfactory IMRT plans). Three of the four patients in this group had paranasal sinus tumors. CONCLUSION: The doses to the major arteries should be calculated in IMRT planning for critical tumor locations if a dose gradient >13% within the PTV can not be avoided because the PTV is large or includes air cavities.

Validation of a method for automatic image fusion (BrainLAB System) of CT data and 11C-methionine-PET data for stereotactic radiotherapy using a LINAC: first clinical experience.

PURPOSE: (a) To implement a fully automatic method to integrate (11)C-methionine positron emission tomography (MET-PET) data into stereotactic radiation treatment planning using the commercially available BrainLAB System, by means of CT/MET-PET image fusion. (b) To validate the fully automatic CT/MET-PET image fusion technique with respect to accuracy and robustness. (c) To give a short glance at the clinical consequences for patients with brain tumors. METHODS AND MATERIALS: In 12 patients with brain tumors (9 meningeomas, 3 gliomas), CT, MRI, and MET-PET were performed for stereotactic fractionated radiation treatment planning. The CT and MET-PET investigations were performed using a relocatable mask for head fixation. Fifteen external reference markers (5 on each lateral and 5 on the frontal localizer plate) that could be identified in CT and MET-PET were applied on the stereotactic localizer frame; the marker positions were exactly defined for both investigations. The MRI/CT fusion was done completely automatically. The CT/MET-PET fusion was performed using two different methods: The gold standard was the CT/PET fusion based on the reference markers, and the test method was the automatic, intensity-based CT/PET fusion, independent of the external markers. The markers visible on CT and transmission PET were matched using a point-to-line matching algorithm. To quantify the amount of misregistration, the two fusion methods were compared by calculating the mean value of deviation between corresponding points inside a cubic volume of interest of > or =512 cm(3) defined within the cranial cavity. The gross tumor volume (CT/MRI) outlined on CT and T1-MRI with contrast medium was compared with the gross tumor volume (PET) defined in the reoriented MET-PET data sets. The clinical impact of MET-PET in tumor volume definition for stereotactic radiotherapy will be discussed. RESULTS: The fully automatic integration of MET-PET into stereotactic radiation treatment planning was successfully realized in all patients investigated. Mean deviation of the intensity-based automatic CT/PET fusion compared with the external marker-based gold standard was 2.4 mm; the standard deviation was 0.5. The algorithm's robustness was evaluated, and the discrepancy of fusion results due to different initial image alignments was determined to be below 1 mm inside the test volume of interest. In patients with meningiomas and gliomas, MET-PET was shown to deliver additional information concerning tumor extension. CONCLUSION: The precision of the automatic CT/PET image fusion was high. A mean deviation of 2.4 mm is acceptable, considering that it is approximately equal to the pixel size of the PET data sets. MET-PET improves target volume definition for stereotactic fractionated radiotherapy of meningiomas and gliomas.

[Design of an inverse planning system for radiotherapy using linear optimization]. / Entwicklung eines inversen Bestrahlungsplanungssystems mit linearer Optimierung.

Our approach shows that inverse planning for intensity-modulated beams in radiotherapy can be solved efficiently by the mathematical method of linear optimization. The completeness property of this method guarantees that calculated treatment plans fulfill the dose constraints given by the oncologist. Techniques developed by our group can also avoid the possible infeasibility caused by a physically impossible dose distribution. In contrast to other optimization methods, the simplex algorithm used for linear optimization allows a very high optimization speed, i.e., very short planning cycles. These preconditions were integrated in the development of the software system MIPART ("Munich Inverse Planning And Radiotherapy Treatment"). The object-oriented software architecture of MIPART achieves a maximum of extensibility and flexibility. Our clinical tests show that MIPART can be easily integrated in the clinical routine in spite of the complexity of data in the field of intensity-modulated radiotherapy. Moreover, qualitatively better treatment plans can be generated than in conventional treatment planning, especially in complicated cases.

Evaluation of the SUV values calculation and 4D PET integration in the radiotherapy treatment planning system.

BACKGROUND AND PURPOSE: To evaluate the SUV calculation and integration of the gated (4D) PET in the iPlan 4.0 treatment planning software (BrainLAB). MATERIALS AND METHODS: Phantom and patient data for different tracers were used. Two comparisons were performed for each patient: for the delineated VOI, the maximum value of SUV in iPlan was compared with the results from TrueD software. For 10 patients lesion volumes were defined in both systems for a given SUV threshold and differences were calculated. For four patients examined with respiratory gated PET, SUV(max) and volume analysis was performed in each phase of the breathing cycle in the gated and the ungated PET. RESULTS: Maximum differences of 6% and 10% were found for phantom and patient measurements of SUV(max). For patient data, maximal differences in delineated volume of 10% for ungated and up to 27% for gated PET were found in both systems. CONCLUSION: This study suggests that for the safe implementation of PET data and delineation algorithms in the radiotherapy planning system, one has to be aware of the differences in SUVs and volumes found in the two systems.

The Munich Fission Neutron Therapy Facility MEDAPP at the research reactor FRM II.

PURPOSE: At the new research reactor FRM II of the Technical University of Munich (TUM), the facility for Medical Applications (MEDAPP) was installed where fast neutrons are available as a beam for medical use. MATERIAL AND METHODS: Thermal neutrons induce fission in a pair of uranium converter plates and generate fast neutrons which are guided to the patient by a beam tube. The maximum opening of the multi leaf collimator (MLC) is 30x20 cm2 WxH. The beam is characterized by neutron-photon mixed beam phantom dosimetry. Specific safety measures are outlined. RESULTS: The neutron and gamma dose rates are 0.52 Gy/min and 0.20 Gy/min, respectively, in 2 cm depth of a water phantom. The half maximum depth of the neutron dose rate in water is 5.4 cm (mean neutron energy 1.9+/-0.1 MeV). Conformity with the European Medical Devices Directive (MDD) 93/42/EEG, was proven so that MEDAPP has a CE mark and since February 2007 also the license for clinical operation. CONCLUSION: The clinical neutron irradiations of malignant tumors, which were performed at the former research reactor FRM until 2000, can be continued at FRM II under improved conditions. First patients were irradiated in June 2007.

Influence of different treatment techniques on radiation dose to the LAD coronary artery.

BACKGROUND: The purpose of this proof-of-principle study was to test the ability of an intensity-modulated radiotherapy (IMRT) technique to reduce the radiation dose to the heart plus the left ventricle and a coronary artery. Radiation-induced heart disease might be a serious complication in long-term cancer survivors. METHODS: Planning CT scans from 6 female patients were available. They were part of a previous study of mediastinal IMRT for target volumes used in lymphoma treatment that included 8 patients and represent all cases where the left anterior descending coronary artery (LAD) could be contoured. We compared 6 MV AP/PA opposed fields to a 3D conformal 4-field technique and an optimised 7-field step-and-shoot IMRT technique and evaluated DVH's for several structures. The planning system was BrainSCAN 5.21 (BrainLAB, Heimstetten, Germany). RESULTS: IMRT maintained target volume coverage but resulted in better dose reduction to the heart, left ventricle and LAD than the other techniques. Selective dose reduction could be accomplished, although not to the degree initially attempted. The median LAD dose was approximately 50% lower with IMRT. In 5 out of 6 patients, IMRT was the best technique with regard to heart sparing. CONCLUSION: IMRT techniques are able to reduce the radiation dose to the heart. In addition to dose reduction to whole heart, individualised dose distributions can be created, which spare, e.g., one ventricle plus one of the coronary arteries. Certain patients with well-defined vessel pathology might profit from an approach of general heart sparing with further selective dose reduction, accounting for the individual aspects of pre-existing damage.