Redefining radiotherapy for early-stage breast cancer with single dose ablative treatment: a study protocol.

BACKGROUND: A shift towards less burdening and more patient friendly treatments for breast cancer is currently ongoing. In low-risk patients with early-stage disease, accelerated partial breast irradiation (APBI) is an alternative for whole breast irradiation following breast-conserving surgery. MRI-guided single dose ablative APBI has the potential to offer a minimally burdening, non-invasive treatment that could replace current breast-conserving therapy. METHODS: The ABLATIVE study is a prospective, single arm, multicenter study evaluating preoperative, single dose, ablative radiation treatment in patients with early-stage breast cancer. Patients with core biopsy proven non-lobular invasive breast cancer, (estrogen receptor positive, Her2 negative, maximum tumor size 3.0 cm on diagnostic MRI) and a negative sentinel node biopsy are eligible. Radiotherapy (RT) planning will be performed using a contrast enhanced (CE) planning CT-scan, co-registered with a CE-MRI, both in supine RT position. A total of twenty-five consecutive patients will be treated with a single ablative RT dose of 20 Gy to the tumor and 15 Gy to the tumorbed. Follow-up MRIs are scheduled within 1 week, 2, 4 and 6 months after single-dose RT. Breast-conserving surgery is scheduled at six months following RT. Primary study endpoint is pathological complete response. Secondary study endpoints are the radiological response and toxicity. Furthermore, patients will fill out questionnaires on quality of life and functional status. Cosmetic outcome will be evaluated by the treating radiation oncologist, patient and 'Breast Cancer Conservation Treatment cosmetic results' software. Recurrence and survival rates will be assessed. The patients will be followed up to 10 years after diagnosis. If patients give additional informed consent, a biopsy and a part of the irradiated specimen will be stored at the local Biobank and used for future research on radiotherapy response associated genotyping. DISCUSSION: The ABLATIVE study evaluates MRI-guided single dose ablative RT in patients with early-stage breast cancer, aiming at a less burdening and non-invasive alternative for current breast-conserving treatment. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT02316561 . The trial was registrated prospectively on October 10th 2014.

Dosimetric evaluation of off-axis fields and angular transmission for the 1.5 T MR-linac.

Objective.GPU-oriented Monte Carlo dose (GPUMCD) is a fast dose calculation algorithm used for treatment planning on the Unity MR-linac. Treatments for the MR-linac must be calculated quickly and accurately, and must account for two important MR-linac aspects: off-axis positions and angular transmission through the cryostat, couch and MR-coils. Therefore, the aim of this research is to quantify the system-related errors for GPUMCD calculations over the range of clinically-relevant field configurations and gantry angles.Approach.Dose profiles (crossline, inline and PDD) were measured and calculated for varying field sizes, off-axis positions and depths. Eleven different (off-axis) positions were included. The angular transmission was investigated by measuring and calculating the transmission for multiple angles, taking the cryostat, couch and coils into account.Main results.Differences between absolute point doses were found to be within 1.7% for field sizes 2 × 2 cm2and larger. The relative dose profiles in the crossline, inline and PDD direction illustrated maximum mean dose differences of 0.9pp, 0.8pp and 0.7pp ofDmaxin the central region for field sizes 2 × 2 cm2and larger. The 1 × 1 cm2field size showed larger dosimetric errors for absolute point doses and relative dose profiles. The maximum mean DTA in the penumbra was 0.7 mm. The mean difference in angular transmission ranged from -0.33% ± 0.60% to 0.27% ± 0.91% using three treatment machines. Additionally, 77.1%-93.7% of the datapoints remained within 1% transmission difference. The largest transmission differences were present at the edges of the table.Significance.This research showed that the GPUMCD algorithm provides reliable dose calculations with a low uncertainty for field sizes 2 × 2 cm2and larger, focusing on off-axis fields and angular transmission.

First experimental exploration of real-time cardiorespiratory motion management for future stereotactic arrhythmia radioablation treatments on the MR-linac.

Objective.Stereotactic arrhythmia radioablation (STAR) is a novel, non-invasive treatment for refractory ventricular tachycardia (VT). The VT isthmus is subject to both respiratory and cardiac motion. Rapid cardiac motion presents a unique challenge. In this study, we provide first experimental evidence for real-time cardiorespiratory motion-mitigated MRI-guided STAR on the 1.5 T Unity MR-linac (Elekta AB, Stockholm, Sweden) aimed at simultaneously compensating cardiac and respiratory motions.Approach.A real-time cardiorespiratory motion-mitigated radiotherapy workflow was developed on the Unity MR-linac in research mode. A 15-beam intensity-modulated radiation therapy treatment plan (1 × 25 Gy) was created in Monaco v.5.40.01 (Elekta AB) for the Quasar MRI4Dphantom (ModusQA, London, ON). A film dosimetry insert was moved by combining either artificial (cos4, 70 bpm, 10 mm peak-to-peak) or subject-derived (59 average bpm, 15.3 mm peak-to-peak) cardiac motion with respiratory (sin, 12 bpm, 20 mm peak-to-peak) motion. A balanced 2D cine MRI sequence (13 Hz, field-of-view = 400 × 207 mm2, resolution = 3 × 3 × 15 mm3) was developed to estimate cardiorespiratory motion. Cardiorespiratory motion was estimated by rigid registration and then deconvoluted into cardiac and respiratory components. For beam gating, the cardiac component was used, whereas the respiratory component was used for MLC-tracking. In-silico dose accumulation experiments were performed on three patient data sets to simulate the dosimetric effect of cardiac motion on VT targets.Main results.Experimentally, a duty cycle of 57% was achieved when simultaneously applying respiratory MLC-tracking and cardiac gating. Using film, excellent agreement was observed compared to a static reference delivery, resulting in a 1%/1 mm gamma pass rate of 99%. The end-to-end gating latency was 126 ms on the Unity MR-linac. Simulations showed that cardiac motion decreased the target's D98% dose between 0.1 and 1.3 Gy, with gating providing effective mitigation.Significance.Real-time MRI-guided cardiorespiratory motion management greatly reduces motion-induced dosimetric uncertainty and warrants further research and development for potential future use in STAR.

Excised and irradiated volumes in relation to the tumor size in breast-conserving therapy.

In early-stage breast cancer and DCIS patients, breast-conserving therapy is today's standard of care. The purpose of this study was to evaluate the relation between the microscopic tumor diameter (mTD), the excised specimen (ES) volume, and the irradiated postoperative complex (POC) volume, in patients treated with breast-conserving therapy. In 186 patients with pTis-2N0 breast cancer, the mTDs, ES, and POC volumes (as delineated on the radiotherapy-planning CT scan), were retrospectively determined. Linear regression analysis was performed to study the association between the mTD, and the ES and POC volumes. The explained variance (r (2)) was calculated to establish the proportion of variation in the outcome variable that could be explained by the determinant (P ≤ 0.05). Moreover, the influence of tumor characteristics, age, surgical procedures, and breast size was studied. Median mTD was 1.2 cm (range 0.1-3.6 cm), median ES volume was 60 cm(3) (range 6-230 cm(3)) and median POC volume was 15 cm(3) (range 0.5-374 cm(3)). The POC was not clearly visible on the majority of the CT scans, based on a median assigned cavity visualization score of 3 (range 1-5). The explained variance for the mTD on the ES volume was low (r(2) = 0.08, P < 0.001). A slightly stronger association was observed in palpable tumors (r(2) = 0.23, P < 0.001) and invasive lobular carcinomas (r(2) = 0.39, P = 0.01). Furthermore, weak associations were observed between POC volume and mTD (r(2) = 0.04, P = 0.01), and POC and ES volume (r(2) = 0.23, P < 0.001). A weak association was observed between breast volume and ES volume (r(2) = 0.27, P < 0.001). In conclusion, both the excised and the irradiated POC volumes did not show a clinically relevant association with the mTD in women with early-stage breast cancer treated with breast-conserving therapy. Future studies should focus on improvement of surgical localization, development of image-guided, minimally invasive operation techniques, and more accurate image-guided target volume delineation in radiotherapy.

Synthetic CT for single-fraction neoadjuvant partial breast irradiation on an MRI-linac.

A synthetic computed tomography (sCT) is required for daily plan optimization on an MRI-linac. Yet, only limited information is available on the accuracy of dose calculations on sCT for breast radiotherapy. This work aimed to (1) evaluate dosimetric accuracy of treatment plans for single-fraction neoadjuvant partial breast irradiation (PBI) on a 1.5 T MRI-linac calculated on a) bulk-density sCT mimicking the current MRI-linac workflow and b) deep learning-generated sCT, and (2) investigate the number of bulk-density levels required. For ten breast cancer patients we created three bulk-density sCTs of increasing complexity from the planning-CT, using bulk-density for: (1) body, lungs, and GTV (sCTBD1); (2) volumes for sCTBD1plus chest wall and ipsilateral breast (sCTBD2); (3) volumes for sCTBD2plus ribs (sCTBD3); and a deep learning-generated sCT (sCTDL) from a 1.5 T MRI in supine position. Single-fraction neoadjuvant PBI treatment plans for a 1.5 T MRI-linac were optimized on each sCT and recalculated on the planning-CT. Image evaluation was performed by assessing mean absolute error (MAE) and mean error (ME) in Hounsfield Units (HU) between the sCTs and the planning-CT. Dosimetric evaluation was performed by assessing dose differences, gamma pass rates, and dose-volume histogram (DVH) differences. The following results were obtained (median across patients for sCTBD1/sCTBD2/sCTBD3/sCTDLrespectively): MAE inside the body contour was 106/104/104/75 HU and ME was 8/9/6/28 HU, mean dose difference in the PTVGTVwas 0.15/0.00/0.00/-0.07 Gy, median gamma pass rate (2%/2 mm, 10% dose threshold) was 98.9/98.9/98.7/99.4%, and differences in DVH parameters were well below 2% for all structures except for the skin in the sCTDL. Accurate dose calculations for single-fraction neoadjuvant PBI on an MRI-linac could be performed on both bulk-density and deep learning sCT, facilitating further implementation of MRI-guided radiotherapy for breast cancer. Balancing simplicity and accuracy, sCTBD2showed the optimal number of bulk-density levels for a bulk-density approach.

Technical Note: Consistency of PTW30013 and FC65-G ion chamber magnetic field correction factors.

PURPOSE: Reference dosimetry in a strong magnetic field is made more complex due to (a) the change in dose deposition and (b) the change in sensitivity of the detector. Potentially it is also influenced by thin air layers, interfaces between media, relative orientations of field, chamber and radiation, and minor variations in ion chamber stem or electrode construction. The PTW30013 and IBA FC65-G detectors are waterproof Farmer-type ion chambers that are suitable for reference dosimetry. The magnetic field correction factors have previously been determined for these chamber types. The aim of this study was to assess the chamber-to-chamber variation and determine whether generic chamber type-specific magnetic field correction factors can be applied for each of the PTW30013 and FC65-G type ion chambers when they are oriented anti-parallel (ǁ) to, or perpendicular (⊥) to, the magnetic field. METHODS: The experiment was conducted with 12 PTW30013 and 13 FC65-G chambers. The magnetic field correction factors were measured using a practical method. In this study each chamber was cross-calibrated against the local standard chamber twice; with and without magnetic field. Measurements with 1.5 T magnetic field were performed with the 7 MV FFF beam of the MRI-linac. Measurements without magnetic field (0 T) were performed with the 6 MV conventional beam of an Elekta Agility linac. A prototype MR-compatible PTW MP1 phantom was used along with a prototype holder that facilitated measurements with the chamber aligned 90° counter-clockwise (⊥) and 180° (ǁ) to the direction of the magnetic field. A monitor chamber was also mounted on the holder and all measurements were normalized so that the effect of variations in the output of each linac was minimized. Measurements with the local standard chamber were repeated during the experiment to quantify the experimental uncertainty. Recombination was measured in the 6 MV beam. Beam quality correction factors were applied. Differences in recombination and beam quality between beams are constant within each chamber type. By comparing the results for the two cross calibrations the magnetic field correction factors can be determined for each chamber, and the variation within the chamber-type determined. RESULTS: The magnetic field correction factors within both PTW30013 and FC65-G chamber-types were found to be very consistent, with observed standard deviations for the PTW30013 of 0.19% (ǁ) and 0.13% (⊥), and for the FC65-G of 0.15% (ǁ) and 0.17% (⊥). These variations are comparable with the standard uncertainty (k = 1) of 0.24%. CONCLUSION: The consistency of the results for the PTW30013 and FC65-G chambers implies that it is not necessary to derive a new factor for every new PTW30013 or FC65-G chamber. Values for each chamber-type (with careful attention to beam energy, magnetic field strength and beam-field-chamber orientations) can be applied from the literature.

Single dose partial breast irradiation using an MRI linear accelerator in the supine and prone treatment position.

BACKGROUND: In selected patients with early-stage and low-risk breast cancer, an MRI-linac based treatment might enable a radiosurgical, non-invasive alternative for current standard breast conserving therapy. AIM: To investigate whether single dose accelerated partial breast (APBI) to the intact tumor in both the prone and supine radiotherapy positions on the MRI-linac is dosimetrically feasible with respect to predefined coverage and organs at risk (OAR) constraints. MATERIAL & METHODS: For 20 patients with cTis or low-risk cT1N0M0 non-lobular breast carcinoma, previously treated with single dose preoperative APBI in the supine (n = 10) or prone (n = 10) position, additional intensity modulated radiotherapy plans with 7 coplanar beams in the presence of a 1.5T magnetic field were generated. A 20 Gy and 15 Gy dose was prescribed to the gross tumor and clinical target volume, respectively. The percentage of plans achieving predefined organ at risk (OAR) constraints, currently used in clinical practice, was assessed. Dosimetry differences between the prone versus supine approach and the MRI-linac versus clinically delivered plans were evaluated. RESULTS: All MRI-linac plans met the coverage and predefined OAR constraints. The prone approach appeared to be more favorable with respect to the chest wall, and ipsilateral lung dose compared to the supine position. No dosimetric differences were observed for the ipsilateral breast. No treatment position was clearly more beneficial for the skin or heart, since dosimetry varied among parameters. Overall, the MRI-linac and clinical plans were comparable, with minor absolute dosimetric differences. CONCLUSION: MRI-linac based single dose APBI to the intact tumor is a promising and a dosimetrically feasible strategy in patients with low-risk breast cancer. Preliminary OAR dosimetry favored the prone radiotherapy position.

Performance of a PTW 60019 microDiamond detector in a 1.5 T MRI-linac.

Accurate small-field dosimetry is critical for a magnetic resonance linac (MRI-linac). The PTW 60019 microDiamond is close to an ideal detector for small field dosimetry due to its small physical size, high signal-to-noise ratio and approximate water equivalence. It is important to fully characterise the performance of the detector in a 1.5 T magnetic field prior to its use for MRI-linac commissioning and quality assurance. Standard techniques of detector testing have been implemented, or adapted where necessary to suit the capabilities of the MRI-linac. Detector warmup, constancy, dose linearity, dose rate linearity, field size dependence and leakage were within tolerance. Measurements with the detector were consistent with ion chamber measurements for medium sized fields. The effective point of measurement of the detector when used within a 1.5 T magnetic field was determined to be 0.80 ± 0.23 mm below the top surface of the device, consistent with the existing vendor recommendation and alignment mark at 1.0 mm. The angular dependence was assessed. Variations of up to 9.7% were observed, which are significantly greater than in a 0 T environment. Within the expected range of use, the maximum effect is approximately 0.6% which is within tolerance. However for large beams within a magnetic field, the divergence and consequent variation in angle of photon incidence means that the microDiamond would not be ideal for characterising the profiles and it would not be suitable for determining large-field beam parameters such as symmetry. It would also require a correction factor prior to use for patient-specific QA measurements where radiation is delivered from different gantry angles. The results of this study demonstrate that the PTW 60019 microDiamond detector is suitable for measuring small radiation fields within a 1.5 T magnetic field and thus is suitable for use in MRI-linac commissioning and quality assurance.

Spiraling contaminant electrons increase doses to surfaces outside the photon beam of an MRI-linac with a perpendicular magnetic field.

The transverse magnetic field of an MRI-linac sweeps contaminant electrons away from the radiation beam. Films oriented perpendicular to the magnetic field and 5 cm from the radiation beam edge show a projection of the divergent beam, indicating that contaminant electrons spiral along magnetic field lines and deposit dose on surfaces outside the primary beam perpendicular to the magnetic field. These spiraling contaminant electrons (SCE) could increase skin doses to protruding regions of the patient along the cranio-caudal axis. This study investigated doses from SCE for an MRI-linac comprising a 7 MV linac and a 1.5 T MRI scanner. Surface doses to films perpendicular to the magnetic field and 5 cm from the radiation beam edge showed increased dose within the projection of the primary beam, whereas films parallel to the magnetic field and 5 cm from the beam edge showed no region of increased dose. However, the dose from contaminant electrons is absorbed within a few millimeters. For large fields, the SCE dose is within the same order of magnitude as doses from scattered and leakage photons. Doses for both SCE and scattered photons decrease rapidly with decreasing beam size and increasing distance from the beam edge.

A formalism for reference dosimetry in photon beams in the presence of a magnetic field.

A generic formalism is proposed for reference dosimetry in the presence of a magnetic field. Besides the regular correction factors from the conventional reference dosimetry formalisms, two factors are used to take into account magnetic field effects: (1) a dose conversion factor to correct for the change in local dose distribution and (2) a correction of the reading of the dosimeter used for the reference dosimetry measurements. The formalism was applied to the Elekta MRI-Linac, for which the 1.5 T magnetic field is orthogonal to the 7 MV photon beam. For this setup at reference conditions it was shown that the dose decreases with increasing magnetic field strength. The reduction in local dose for a 1.5 T transverse field, compared to no field is 0.51% ± 0.03% at the reference point of 10 cm depth. The effect of the magnetic field on the reading of the dosimeter was measured for two waterproof ionization chambers types (PTW 30013 and IBA FC65-G) before and after multiple ramp-up and ramp-downs of the magnetic field. The chambers were aligned perpendicular and parallel to the magnetic field. The corrections of the readings of the perpendicularly aligned chambers were 0.967 ± 0.002 and 0.957 ± 0.002 for respectively the PTW and IBA ionization chambers. In the parallel alignment the corrections were small; 0.997 ± 0.001 and 1.002 ± 0.003 for the PTW and IBA chamber respectively. The change in reading due to the magnetic field can be measured by individual departments. The proposed formalism can be used to determine the correction factors needed to establish the absorbed dose in a magnetic field. It requires Monte Carlo simulations of the local dose and measurements of the response of the dosimeter. The formalism was successfully implemented for the MRI-Linac and is applicable for other field strengths and geometries.

Beam characterisation of the 1.5 T MRI-linac.

As a prerequisite for clinical treatments it was necessary to characterize the Elekta 1.5 T MRI-linac 7 MV FFF radiation beam. Following acceptance testing, beam characterization data were acquired with Semiflex 3D (PTW 31021), microDiamond (PTW 60019), and Farmer-type (PTW 30013 and IBA FC65-G) detectors in an Elekta 3D scanning water phantom and a PTW 1D water phantom. EBT3 Gafchromic film and ion chamber measurements in a buildup cap were also used. Special consideration was given to scan offsets, detector effective points of measurement and avoiding air gaps. Machine performance has been verified and the system satisfied the relevant beam requirements of IEC60976. Beam data were acquired for field sizes between 1 × 1 and 57 × 22 cm2. New techniques were developed to measure percentage depth dose (PDD) curves including the electron return effect at beam exit, which exhibits an electron-type practical range of 1.2 ± 0.1 cm. The Lorentz force acting on the secondary charged particles creates an asymmetry in the crossline profiles with an average shift of +0.24 cm. For a 10 × 10 cm2 beam, scatter from the cryostat contributes 1% of the dose at isocentre. This affects the relative output factors, scatter factors and beam profiles, both in-field and out-of-field. The average 20%-80% penumbral width measured for small fields with a microDiamond detector at 10 cm depth is 0.50 cm. MRI-linac penumbral widths are very similar to that of the Elekta Agility linac MLC, as is the near-surface dose PDD(0.2 cm) = 57%. The entrance surface dose is ∼36% of Dmax. Cryostat transmission is quantified for inclusion within the treatment planning system. As a result, the 1.5 T MRI-linac 7 MV FFF beam has been characterised for the first time and is suitable for clinical use. This was a key step towards the first clinical treatments with the MRI-linac, which were delivered at University Medical Center Utrecht in May 2017 (Raaymakers et al 2017 Phys. Med. Biol. 62 L41-50).

Influence of the linac design on intensity-modulated radiotherapy of head-and-neck plans.

In this study, we quantify the impact of linac/MLC design parameters on IMRT treatment plans. The investigated parameters were leaf width in the MLC, leaf transmission, related to the thickness of the leaves, and penumbra related primarily to the source size. Seven head-and-neck patients with stage T1-T3N0-N2cM0 oropharyngeal cancer were studied. For each patient nine plans were made with a different set of linac/MLC parameters. The plans were optimized in Pinnacle(3) v7.6c and PLATO RTS v2.6.4, ITP v1.1.8. A hypothetical ideal linac/MLC was introduced to investigate the influence of one parameter at a time without interaction of other parameters. When any of the three parameters was increased from the ideal set-up values (leaf width 2.5 mm, transmission 0%, penumbra 3 mm), the mean dose to the parotid glands increased, given the same tumour coverage. The largest increase was found for increasing leaf transmission. The investigation showed that by changing more than one parameter of the ideal linac/MLC set-up, the increase in the mean dose was smaller than the sum of dose increments for each parameter separately. As a reference to clinical practice, we also optimized the plans of the seven patients with the clinically used Elekta SLi 15, equipped with a standard MLC with a leaf width of 10 mm. As compared to the ideal linac, this resulted in an increase of the average dose to the parotid glands of 5.8 Gy.

First patients treated with a 1.5 T MRI-Linac: clinical proof of concept of a high-precision, high-field MRI guided radiotherapy treatment.

The integration of 1.5 T MRI functionality with a radiotherapy linear accelerator (linac) has been pursued since 1999 by the UMC Utrecht in close collaboration with Elekta and Philips. The idea behind this integrated device is to offer unrivalled, online and real-time, soft-tissue visualization of the tumour and the surroundings for more precise radiation delivery. The proof of concept of this device was given in 2009 by demonstrating simultaneous irradiation and MR imaging on phantoms, since then the device has been further developed and commercialized by Elekta. The aim of this work is to demonstrate the clinical feasibility of online, high-precision, high-field MRI guidance of radiotherapy using the first clinical prototype MRI-Linac. Four patients with lumbar spine bone metastases were treated with a 3 or 5 beam step-and-shoot IMRT plan. The IMRT plan was created while the patient was on the treatment table and based on the online 1.5 T MR images; pre-treatment CT was deformably registered to the online MRI to obtain Hounsfield values. Bone metastases were chosen as the first site as these tumors can be clearly visualized on MRI and the surrounding spine bone can be detected on the integrated portal imager. This way the portal images served as an independent verification of the MRI based guidance to quantify the geometric precision of radiation delivery. Dosimetric accuracy was assessed post-treatment from phantom measurements with an ionization chamber and film. Absolute doses were found to be highly accurate, with deviations ranging from 0.0% to 1.7% in the isocenter. The geometrical, MRI based targeting as confirmed using portal images was better than 0.5 mm, ranging from 0.2 mm to 0.4 mm. In conclusion, high precision, high-field, 1.5 T MRI guided radiotherapy is clinically feasible.

Clinical experience with EPID dosimetry for prostate IMRT pre-treatment dose verification.

The aim of this study was to demonstrate how dosimetry with an amorphous silicon electronic portal imaging device (a-Si EPID) replaced film and ionization chamber measurements for routine pre-treatment dosimetry in our clinic. Furthermore, we described how EPID dosimetry was used to solve a clinical problem. IMRT prostate plans were delivered to a homogeneous slab phantom. EPID transit images were acquired for each segment. A previously developed in-house back-projection algorithm was used to reconstruct the dose distribution in the phantom mid-plane (intersecting the isocenter). Segment dose images were summed to obtain an EPID mid-plane dose image for each field. Fields were compared using profiles and in two dimensions with the y evaluation (criteria: 3%/3 mm). To quantify results, the average gamma (gamma avg), maximum gamma (gamma max), and the percentage of points with gamma < 1(P gamma < 1) were calculated within the 20% isodose line of each field. For 10 patient plans, all fields were measured with EPID and film at gantry set to 0 degrees. The film was located in the phantom coronal mid-plane (10 cm depth), and compared with the back-projected EPID mid-plane absolute dose. EPID and film measurements agreed well for all 50 fields, with (gamma avg) =0.16, (gamma max)=1.00, and (P gamma < 1)= 100%. Based on these results, film measurements were discontinued for verification of prostate IMRT plans. For 20 patient plans, the dose distribution was re-calculated with the phantom CT scan and delivered to the phantom with the original gantry angles. The planned isocenter dose (plan(iso)) was verified with the EPID (EPID(iso)) and an ionization chamber (IC(iso)). The average ratio, (EPID(iso)/IC(iso)), was 1.00 (0.01 SD). Both measurements were systematically lower than planned, with (EPID(iso)/plan(iso)) and (IC(iso)/plan(iso))=0.99 (0.01 SD). EPID mid-plane dose images for each field were also compared with the corresponding plane derived from the three dimensional (3D) dose grid calculated with the phantom CT scan. Comparisons of 100 fields yielded (gamma avg)=0.39, gamma max=2.52, and (P gamma < 1)=98.7%. Seven plans revealed under-dosage in individual fields ranging from 5% to 16%, occurring at small regions of overlapping segments or along the junction of abutting segments (tongue-and-groove side). Test fields were designed to simulate errors and gave similar results. The agreement was improved after adjusting an incorrectly set tongue-and-groove width parameter in the treatment planning system (TPS), reducing (gamma max) from 2.19 to 0.80 for the test field. Mid-plane dose distributions determined with the EPID were consistent with film measurements in a slab phantom for all IMRT fields. Isocenter doses of the total plan measured with an EPID and an ionization chamber also agreed. The EPID can therefore replace these dosimetry devices for field-by-field and isocenter IMRT pre-treatment verification. Systematic errors were detected using EPID dosimetry, resulting in the adjustment of a TPS parameter and alteration of two clinical patient plans. One set of EPID measurements (i.e., one open and transit image acquired for each segment of the plan) is sufficient to check each IMRT plan field-by-field and at the isocenter, making it a useful, efficient, and accurate dosimetric tool.

Consequences of air around an ionization chamber: Are existing solid phantoms suitable for reference dosimetry on an MR-linac?

PURPOSE: A protocol for reference dosimetry for the MR-linac is under development. The 1.5 T magnetic field changes the mean path length of electrons in an air-filled ionization chamber but has little effect on the electron trajectories in a surrounding phantom. It is therefore necessary to correct the response of an ionization chamber for the influence of the magnetic field. Solid phantoms are used for dosimetry measurements on the MR-linac, but air is present between the chamber wall and phantom insert. This study aimed to determine if this air influences the ion chamber measurements on the MR-linac. The absolute response of the chamber and reproducibility of dosimetry measurements were assessed on an MR-linac in solid and water phantoms. The sensitivity of the chamber response to the distribution of air around the chamber was also investigated. METHODS: Measurements were performed on an MR-linac and replicated on a conventional linac for five chambers. The response of three waterproof chambers was measured with air and with water between the chamber and the insert to measure the influence of the air volume on absolute chamber response. The distribution of air around the chamber was varied indirectly by rotating each chamber about the longitudinal chamber axis in a solid phantom and a water phantom (waterproof chambers only) and measuring the angular dependence of the chamber response, and varied directly by displacing the chamber in the phantom insert using a paper shim positioned at different orientations between the chamber casing and the insert. RESULTS: The responses of the three waterproof chambers measured on the MR-linac were 0.7%-1.2% higher with water than air in the chamber insert. The responses of the chambers on the conventional linac changed by less than 0.3% when air in the insert was replaced with water. The angular dependence of the chambers ranged from 0.6% to 1.9% in the solid phantom on the MR-linac but was less than 0.5% in water on the MR-linac and less than 0.3% in the solid phantom on the conventional linac. Inserting a shim around the chamber induced changes of the chamber response in a magnetic field of up to 2.2%, but the change in chamber response on the conventional linac was less than 0.3%. CONCLUSIONS: The interaction between the magnetic field and secondary electrons in the air around the chamber reduces the charge collected from 0.7% to 1.2%. The large angular dependence of ion chambers measured in the plastic phantom in a magnetic field appears to arise from a change of air distribution as the chamber is moved within the insert, rather than an intrinsic isotropy of the chamber sensitivity to radiation. It is recommended that reference dosimetry measurements on the MR-linac can be performed only in water, rather than in existing plastic phantoms.

Development and clinical introduction of automated radiotherapy treatment planning for prostate cancer.

To develop an automated radiotherapy treatment planning and optimization workflow to efficiently create patient specifically optimized clinical grade treatment plans for prostate cancer and to implement it in clinical practice. A two-phased planning and optimization workflow was developed to automatically generate 77Gy 5-field simultaneously integrated boost intensity modulated radiation therapy (SIB-IMRT) plans for prostate cancer treatment. A retrospective planning study (n = 100) was performed in which automatically and manually generated treatment plans were compared. A clinical pilot (n = 21) was performed to investigate the usability of our method. Operator time for the planning process was reduced to <5 min. The retrospective planning study showed that 98 plans met all clinical constraints. Significant improvements were made in the volume receiving 72Gy (V72Gy) for the bladder and rectum and the mean dose of the bladder and the body. A reduced plan variance was observed. During the clinical pilot 20 automatically generated plans met all constraints and 17 plans were selected for treatment. The automated radiotherapy treatment planning and optimization workflow is capable of efficiently generating patient specifically optimized and improved clinical grade plans. It has now been adopted as the current standard workflow in our clinic to generate treatment plans for prostate cancer.

Performance of a cylindrical diode array for use in a 1.5 T MR-linac.

At the UMC Utrecht, a linear accelerator with integrated magnetic resonance imaging (MRI) has been developed, the MR-linac. Patient-specific quality assurance (QA) of treatment plans for MRI-based image guided radiotherapy requires QA equipment compatible with this 1.5 T magnetic field. The purpose of this study was to examine the performance characteristics of the ArcCHECK-MR in a transverse 1.5 T magnetic field. To this end, the short-term reproducibility, dose linearity, dose rate dependence, field size dependence, dose per pulse dependence and inter-diode dose response variation of the ArcCHECK-MR diode array were evaluated on a conventional linac and on the MR-linac. The ArcCHECK-MR diode array performed well for all tests on both linacs, no significant differences in performance characteristics were observed. Differences in the maximum dose deviations between both linacs were less than 1.5%. Therefore, we conclude that the ArcCHECK-MR can be used in a transverse 1.5 T magnetic field.

Minimizing the magnetic field effect in MR-linac specific QA-tests: the use of electron dense materials.

To address the quality assurance (QA) of a MR-linac which is an MRI combined with a linear accelerator (linac), the traditional linac QA-tests need to be redesigned, since the presence of the static magnetic field in the MR-linac alters the electron trajectory. The latter causes the asymmetry in the dose kernel which is introduced by the magnetic field and hinders accurate geometrical QA-tests for the MR-linac. We introduced the use of electron dense materials (e.g. copper) to reduce the size of the dose kernel and thereby the magnetic field effect on the dose deposition. Two examples of QA-tests are presented in which the geometrical accuracy of the MR-linac was addressed; beam profile and star-shot measurements. The introduced setup was compared with a reference setup and both were tested on a conventional and the MR-linac. The results showed that the symmetry of the recorded beam profile was restored in presence of the copper material and that the isocenter size of the MR-linac can be determined accurately with the introduced star-shot setup. The use of electron dense materials is not limited to the presented QA-tests but has a broad application for beam-specific QA-tests in presence of a magnetic field.

An improved breast irradiation technique using three-dimensional geometrical information and intensity modulation.

BACKGROUND AND PURPOSE: In spite of the complex geometry of the breast, treatment planning for tangential breast irradiation is conventionally performed using two-dimensional patient anatomy information. The purpose of this work was to develop a new technique which takes the three-dimensional (3D) patient geometry into account. MATERIALS AND METHODS: An intensity-modulated radiotherapy (IMRT) technique was developed based on the division of the tangential fields in four multi-leaf collimator (MLC) shaped segments. The shape of these segments was obtained from an equivalent path length map of the irradiated volume. Approximately 88% of the dose was delivered by two open fields covering the whole treated volume. Dose calculations for the IMRT technique and the conventional technique were performed for five patients, using computer tomography (CT) data and a 3D calculation algorithm. A planning target volume (PTV) and ipsilateral lung volume were delineated in these CT data. RESULTS: All patients showed similar equivalent path length patterns. Analysis of the dose distribution showed an improved dose distribution using the IMRT technique. The dose inhomogeneity in the PTV was 9.0% (range 6.4-11.4%) for the conventional and 7.6% (range 6.5-10.3%) for the IMRT technique. The mean lung dose was reduced for the IMRT technique by approximately 10% compared with the conventional technique. CONCLUSION: A new breast irradiation technique has been developed which improves the dose homogeneity within the planning target volume and reduces the dose to the lung. Furthermore, the IMRT technique creates the possibility to improve the field matching in case of multiple field irradiations of the breast and lymph nodes.

Towards reference dosimetry for the MR-linac: magnetic field correction of the ionization chamber reading.

In the UMC Utrecht a prototype MR-linac has been installed. The system consists of a 6 MV Elekta (Crawley, UK) linear accelerator and a 1.5 T Philips (Best, The Netherlands) Achieva MRI system. This paper investigates the feasibility to correct the ionization chamber reading for the magnetic field within the dosimetry calibration method described by Almond et al (1999 Med. Phys. 26 1847-70). Firstly, the feasibility of using an ionization chamber in an MR-linac was assessed by investigating possible influences of the magnetic field on NE2571 Farmer-type ionization chamber characteristics: linearity, repeatability, orientation in the magnetic field; and AAPM TG51 correction factor for voltage polarity and ion recombination. We found that these AAPM correction factors for the NE2571 chamber were not influenced by the magnetic field. Secondly, the influence of the permanent 1.5 T magnetic field on the NE2571 chamber reading was quantified. The reading is influenced by the magnetic field; therefore, a correction factor has been added. For the standardized setup used in this paper, the NE2571 chamber reading increases by 4.9% (± 0.2%) due to the transverse 1.5 T magnetic field. Dosimetry measurements in an MR-linac are feasible, if a setup-specific magnetic field correction factor (P1.5 T) for the charge reading is introduced. For the setup investigated in this paper, the P1.5 T has a value of 0.953.