Secondary malignancy risk for patients with localized prostate cancer after intensity-modulated radiotherapy with and without flattening filter.

Men treated for localized prostate cancer by radiotherapy have often a remaining life span of 10 yr or more. Therefore, the risk for secondary malignancies should be taken into account. Plans for ten patients were evaluated which had been performed on an Oncentra® treatment planning system for a treatment with an Elekta Synergy™ linac with Agility™ head. The investigated techniques involved IMRT and VMTA with and without flattening filter. Different dose response models were applied for secondary carcinoma and sarcoma risk in the treated region and also in the periphery. As organs at risk we regarded for carcinoma risk urinary bladder, rectum, colon, esophagus, thyroid, and for sarcoma risk bone and soft tissue. The excess absolute risk (EAR) was found very similar in the treated region for both techniques (IMRT and VMAT) and also for both with and without flattening filter. The secondary sarcoma risk resulted about one magnitude smaller than the secondary carcinoma risk. The EAR to the peripheral organs was statistically significant reduced by application of the flattening filter free mode concerning the flattening filter as main source of scattered dose. Application of flattening filter free mode can thus support to reduce second malignancy risk for patients with localized prostate cancer.

The influence of radiotherapy techniques on the plan quality and on the risk of secondary tumors in patients with pituitary adenoma.

BACKGROUND: This planning study compares different radiotherapy techniques for patients with pituitary adenoma, including flatness filter free mode (FFF), concerning plan quality and secondary malignancies for potentially young patients. The flatness filter has been described as main source of photon scatter. MATERIAL AND METHODS: Eleven patients with pituitary adenoma were included. An Elekta Synergy™ linac was used in the treatment planning system Oncentra® and for the measurements. 3D plans, IMRT, and VMAT plans and non-coplanar varieties were considered. The plan quality was evaluated regarding homogeneity, conformity, delivery time and dose to the organs at risk. The secondary malignancy risk was calculated from dose volume data and from measured dose to the periphery using different models for carcinoma and sarcoma risk. RESULTS: The homogeneity and conformity were nearly unchanged with and without flattening filter, neither was the delivery time found substantively different. VMAT plans were more homogenous, conformal and faster in delivery than IMRT plans. The secondary cancer risk was reduced with FFF both in the treated region and in the periphery. VMAT plans resulted in a higher secondary brain cancer risk than IMRT plans, but the risk for secondary peripheral cancer was reduced. Secondary sarcoma risk plays a minor role. No advantage was found for non-coplanar techniques. The FFF delivery times were not shortened due to additional monitor units needed and technical limitations. The risk for secondary brain cancer seems to depend on the irradiated volume. Secondary sarcoma risk is much smaller than carcinoma risk in accordance to the results of the atomic bomb survivors. The reduction of the peripheral dose and resulting secondary malignancy risk for FFF is statistically significant. However, it is negligible in comparison to the risk in the treated region. CONCLUSION: Treatments with FFF can reduce secondary malignancy risk while retaining similar quality as with flattening filter and should be preferred. VMAT plans show the best plan quality combined with lowest peripheral secondary malignancy risk, but highest level of second brain cancer risk. Taking this into account VMAT FFF seems the most advantageous technique for the treatment of pituitary adenomas with the given equipment.

Second cancer risk after radiation therapy of ependymoma using the flattening filter free irradiation mode of a linear accelerator.

Pediatric patients suffering from ependymoma are usually treated with cranial or craniospinal three-dimensional (3D) conformal radiotherapy (3DCRT). Intensity-modulated techniques spare dose to the surrounding tissue, but the risk for second malignancies may be increased due to the increase in low-dose volume. The aim of this study is to investigate if the flattening filter free (FFF) mode allows reducing the risk for second malignancies compared to the mode with flattening filter (FF) for intensity-modulated techniques and to 3DCRT. A reduction of the risk would be advantageous for treating pediatric ependymoma. 3DCRT was compared to intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) with and without flattening filter. Dose-volume histograms (DVHs) were compared to evaluate the plan quality and used to calculate the excess absolute risk (EAR) to develop second cancer in the brain. Dose verification was performed with a two-dimensional (2D) ionization chamber array and the out-of-field dose was measured with an ionization chamber to determine the EAR in peripheral organs. Delivery times were measured. Both VMAT and IMRT achieved similar plan quality in terms of dose sparing in the OAR and higher PTV coverage as compared to 3DCRT. Peripheral dose in low-dose region, which is proportional to the EAR in organs located in this region, for example, gonads, bladder, or bowel, could be significantly reduced using FFF. The lowest peripheral EAR and lowest delivery times were hereby achieved with VMATFFF . The EAR calculated based on DVH in the brain could not be reduced using FFF mode. VMATFFF improved the target coverage and homogeneity and kept the dose in the OAR similar compared to 3DCRT. In addition, delivery times were significantly reduced using VMATFFF . Therefore, for radiotherapy of ependymoma patients, VMATFFF may be considered advantageous for the combination of Elekta Synergy linac and Oncentra External Beam planning system used in this study.

Simultaneous integrated boost (SIB) radiation therapy of right sided breast cancer with and without flattening filter - A treatment planning study.

BACKGROUND: The aim of the study was to compare the two irradiation modes with (FF) and without flattening filter (FFF) for three different treatment techniques for simultaneous integrated boost radiation therapy of patients with right sided breast cancer. METHODS: An Elekta Synergy linac with Agility collimating device is used to simulate the treatment of 10 patients. Six plans were generated in Monaco 5.0 for each patient treating the whole breast and a simultaneous integrated boost (SIB) volume: intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT) and a tangential arc VMAT (tVMAT), each with and without flattening filter. Plan quality was assessed considering target coverage, sparing of the contralateral breast, the lungs, the heart and the normal tissue. All plans were verified by a 2D-ionisation-chamber-array and delivery times were measured and compared. The Wilcoxon test was used for statistical analysis with a significance level of 0.05. RESULTS: Significantly best target coverage and homogeneity was achieved using VMAT FFF with V95% = (98.7 ± 0.8) % and HI = (8.2 ± 0.9) % for the SIB and V95% = (98.3 ± 0.7) % for the PTV, whereas tVMAT showed significantly lowest doses to the contralateral organs at risk with a Dmean of (0.7 ± 0.1) Gy for the contralateral lung, (1.0 ± 0.2) Gy for the contralateral breast and (1.4 ± 0.2) Gy for the heart. All plans passed the gamma evaluation with a mean passing rate of (99.2 ± 0.8) %. Delivery times were significantly reduced for VMAT and tVMAT but increased for IMRT, when FFF was used. Lowest delivery times were observed for tVMAT FFF with (1:20 ± 0:07) min. CONCLUSION: Balancing target coverage, OAR sparing and delivery time, VMAT FFF and tVMAT FFF are considered the preferable of the investigated treatment options in simultaneous integrated boost irradiation of right sided breast cancer for the combination of an Elekta Synergy linac with Agility and the treatment planning system Monaco 5.0.

Second Cancer Risk after simultaneous integrated boost radiation therapy of right sided breast cancer with and without flattening filter.

BACKGROUND: The aim of this study was to investigate if the flattening filter free mode (FFF) of a linear accelerator reduces the excess absolute risk (EAR) for second cancer as compared to the flat beam mode (FF) in simultaneous integrated boost (SIB) radiation therapy of right-sided breast cancer. PATIENTS AND METHODS: Six plans were generated treating the whole breast to 50.4 Gy and a SIB volume to 63 Gy on CT data of 10 patients: intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and a tangential arc VMAT (tVMAT), each with flattening filter and without. The EAR was calculated for the contralateral breast and the lungs from dose-volume histograms (DVH) based on the linear-exponential, the plateau, and the full mechanistic dose-response model. Peripheral low-dose measurements were performed to compare the EAR in more distant regions as the thyroids and the uterus. RESULTS: FFF reduces the EAR significantly in the contralateral and peripheral organs for tVMAT and in the peripheral organs for VMAT. No reduction was found for IMRT. The lowest EAR for the contralateral breast and lung was achieved with tVMAT FFF, reducing the EAR by 25 % and 29 % as compared to tVMAT FF, and by 44 % to 58 % as compared to VMAT and IMRT in both irradiation modes. tVMAT FFF showed also the lowest peripheral dose corresponding to the lowest EAR in the thyroids and the uterus. CONCLUSION: The use of FFF mode allows reducing the EAR significantly when tVMAT is used as the treatment technique. When second cancer risk is a major concern, tVMAT FFF is considered the preferred treatment option in SIB irradiation of right-sided breast cancer.

Re-irradiation of spinal column metastases by IMRT: impact of setup errors on the dose distribution.

BACKGROUND: This study investigates the impact of an automated image guided patient setup correction on the dose distribution for ten patients with in-field IMRT re-irradiation of vertebral metastases. METHODS: 10 patients with spinal column metastases who had previously been treated with 3D-conformal radiotherapy (3D-CRT) were simulated to have an in-field recurrence. IMRT plans were generated for treatment of the vertebrae sparing the spinal cord. The dose distributions were compared for a patient setup based on skin marks only and a Cone Beam CT (CBCT) based setup with translational and rotational couch corrections using an automatic robotic image guided couch top (Elekta - HexaPOD™ IGuide® - system). The biological equivalent dose (BED) was calculated to evaluate and rank the effects of the automatic setup correction for the dose distribution of CTV and spinal cord. RESULTS: The mean absolute value (± standard deviation) over all patients and fractions of the translational error is 6.1 mm (±4 mm) and 2.7° (±1.1 mm) for the rotational error. The dose coverage of the 95% isodose for the CTV is considerable decreased for the uncorrected table setup. This is associated with an increasing of the spinal cord dose above the tolerance dose. CONCLUSIONS: An automatic image guided table correction ensures the delivery of accurate dose distribution and reduces the risk of radiation induced myelopathy.

Frameless fractionated stereotactic radiation therapy of intracranial lesions: impact of cone beam CT based setup correction on dose distribution.

BACKGROUND: The purpose of this study was to evaluate the impact of Cone Beam CT (CBCT) based setup correction on total dose distributions in fractionated frameless stereotactic radiation therapy of intracranial lesions. METHODS: Ten patients with intracranial lesions treated with 30 Gy in 6 fractions were included in this study. Treatment planning was performed with Oncentra® for a SynergyS® (Elekta Ltd, Crawley, UK) linear accelerator with XVI® Cone Beam CT, and HexaPOD™ couch top. Patients were immobilized by thermoplastic masks (BrainLab, Reuther). After initial patient setup with respect to lasers, a CBCT study was acquired and registered to the planning CT (PL-CT) study. Patient positioning was corrected according to the correction values (translational, rotational) calculated by the XVI® system. Afterwards a second CBCT study was acquired and registered to the PL-CT to confirm the accuracy of the corrections. An in-house developed software was used for rigid transformation of the PL-CT to the CBCT geometry, and dose calculations for each fraction were performed on the transformed CT. The total dose distribution was achieved by back-transformation and summation of the dose distributions of each fraction. Dose distributions based on PL-CT, CBCT (laser set-up), and final CBCT were compared to assess the influence of setup inaccuracies. RESULTS: The mean displacement vector, calculated over all treatments, was reduced from (4.3 ± 1.3) mm for laser based setup to (0.5 ± 0.2) mm if CBCT corrections were applied. The mean rotational errors around the medial-lateral, superior-inferior, anterior-posterior axis were reduced from (-0.1 ± 1.4)°, (0.1 ± 1.2)° and (-0.2 ± 1.0)°, to (0.04 ± 0.4)°, (0.01 ± 0.4)° and (0.02 ± 0.3)°. As a consequence the mean deviation between planned and delivered dose in the planning target volume (PTV) could be reduced from 12.3% to 0.4% for D95 and from 5.9% to 0.1% for D(av). Maximum deviation was reduced from 31.8% to 0.8% for D95, and from 20.4% to 0.1% for D(av). CONCLUSION: Real dose distributions differ substantially from planned dose distributions, if setup is performed according to lasers only. Thermoplasic masks combined with a daily CBCT enabled a sufficient accuracy in dose distribution.

Stochastic triangulation for prostate positioning during radiotherapy using short CBCT arcs.

BACKGROUND AND PURPOSE: Fast and reliable tumor localization is an important part of today's radiotherapy utilizing new delivery techniques. This proof-of-principle study demonstrates the use of a method called herein 'stochastic triangulation' for this purpose. Stochastic triangulation uses very short imaging arcs and a few projections. MATERIALS AND METHODS: A stochastic Maximum A Posteriori (MAP) estimator is proposed based on an uncertainty-driven model of the acquisition geometry and inter-/intra-fractional deformable anatomy. The application of this method was designed to use the available linac-mounted cone-beam computed tomography (CBCT) and/or electronic portal imaging devices (EPID) for the patient setup based on short imaging arcs. For the proof-of-principle clinical demonstration, the MAP estimator was applied to 5 CBCT scans of a prostate cancer patient with 2 implanted gold markers. Estimation was performed for several (18) very short imaging arcs of 5° with 10 projections resulting in 90 estimations. RESULTS: Short-arc stochastic triangulation led to residual radial errors compared to manual inspection with a mean value of 1.4mm and a standard deviation of 0.9 mm (median 1.2mm, maximum 3.8mm) averaged over imaging directions all around the patient. Furthermore, abrupt intra-fractional motion of up to 10mm resulted in radial errors with a mean value of 1.8mm and a standard deviation of 1.1mm (median 1.5mm, maximum 5.6mm). Slow periodic intra-fractional motions in the range of 12 mm resulted in radial errors with a mean value of 1.8mm and a standard deviation of 1.1mm (median 1.6mm, maximum 4.7 mm). CONCLUSION: Based on this study, the proposed stochastic method is fast, robust and can be used for inter- as well as intra-fractional target localization using current CBCT units.

Hybrid plan verification for intensity-modulated radiation therapy (IMRT) using the 2D ionization chamber array I'mRT MatriXX--a feasibility study.

The 2D ionization chamber array I'mRT MatriXX (IBA, Schwarzenbruck, Germany) has been developed for absolute 2D dosimetry and verification of intensity-modulated radiation therapy (IMRT) for perpendicular beam incidence. The aim of this study is to evaluate the applicability of I'mRT MatriXX for oblique beam incidence and hybrid plan verification of IMRT with original gantry angles. For the assessment of angular dependence, open fields with gantry angles in steps of 10 degrees were calculated on a CT scan of I'mRT MatriXX. For hybrid plan verification, 17 clinical IMRT plans and one rotational plan were used. Calculations were performed with pencil beam (PB), collapsed cone (CC) and Monte Carlo (MC) methods, which had been previously validated. Measurements were conducted on an Elekta SynergyS linear accelerator. To assess the potential and limitations of the system, gamma evaluation was performed with different dose tolerances and distances to agreement. Hybrid plan verification passed the gamma test with 4% dose tolerance and 3 mm distance to agreement in all cases, in 82-88% of the cases for tolerances of 3%/3 mm, and in 59-76% of the cases if 3%/2 mm were used. Separate evaluation of the low dose and high dose regions showed that I'mRT MatriXX can be used for hybrid plan verification of IMRT plans within 3% dose tolerance and 3 mm distance to agreement with a relaxed dose tolerance of 4% in the low dose region outside the multileaf collimator (MLC).

Optimization of extracranial stereotactic radiation therapy of small lung lesions using accurate dose calculation algorithms.

BACKGROUND: The aim of this study was to compare and to validate different dose calculation algorithms for the use in radiation therapy of small lung lesions and to optimize the treatment planning using accurate dose calculation algorithms. METHODS: A 9-field conformal treatment plan was generated on an inhomogeneous phantom with lung mimics and a soft tissue equivalent insert, mimicking a lung tumor. The dose distribution was calculated with the Pencil Beam and Collapsed Cone algorithms implemented in Masterplan (Nucletron) and the Monte Carlo system XVMC and validated using Gafchromic EBT films. Differences in dose distribution were evaluated. The plans were then optimized by adding segments to the outer shell of the target in order to increase the dose near the interface to the lung. RESULTS: The Pencil Beam algorithm overestimated the dose by up to 15% compared to the measurements. Collapsed Cone and Monte Carlo predicted the dose more accurately with a maximum difference of -8% and -3% respectively compared to the film. Plan optimization by adding small segments to the peripheral parts of the target, creating a 2-step fluence modulation, allowed to increase target coverage and homogeneity as compared to the uncorrected 9 field plan. CONCLUSION: The use of forward 2-step fluence modulation in radiotherapy of small lung lesions allows the improvement of tumor coverage and dose homogeneity as compared to non-modulated treatment plans and may thus help to increase the local tumor control probability. While the Collapsed Cone algorithm is closer to measurements than the Pencil Beam algorithm, both algorithms are limited at tissue/lung interfaces, leaving Monte-Carlo the most accurate algorithm for dose prediction.