The impact of ion chamber components onkB,Qfor reference dosimetry in MRgRT.

For reference dosimetry in MRgRT,kB,Qis used to correct for the impact of the magnetic field on the chamber calibration coefficient. It has been demonstrated that for accurate simulation ofkB,Qthe dead volume (DV) must be considered. This work goes one step further by analysing the contribution of secondary electrons generated in the various chamber components tokB,Q. The Farmer-type chamber PTW 30013 geometry was modelled for two different DVs. Monte Carlo simulations were performed for a60Co source and a 7 MV MRI-linac and the model was validated against measurements. Both parallel (α = 0° or 180°) and perpendicular (α = 90° or 270°) orientations of the chamber and the magnetic (B) field were considered, and severalB-field strengths between 0 T and 1.5 T. To study the dose contribution to the reduced volume (RV = cavity - DV) from the secondary electrons produced in certain components of the chamber the labelling of the particles was implemented in the PENELOPE user code PENMAIN. A separate model with each solid component of the chamber modelled as liquid water was used to investigate the impact of material choice onkB,Q. Results show that simulatedkB,Qvalues agree better with the measuredkB,Qwhen the DV is considered. It is demonstrated that small components of the chamber impactkB,Qconsiderably, since the contribution to the RV-dose from the bodies closer to the RV is higher than withoutB. Moreover, it is seen that the impact to the dose in the RV is reduced when the material of each component is modelled as liquid water. Therefore, chamber design and, to a lesser extent, choice of material affectkB,Q, and an accurate geometrical model of the chamber components and its further validation are important for correct calculations ofkB,Q.

Reference dosimetry in MRI-linacs: evaluation of available protocols and data to establish a Code of Practice.

With the rapid increase in clinical treatments with MRI-linacs, a consistent, harmonized and sustainable ground for reference dosimetry in MRI-linacs is needed. Specific for reference dosimetry in MRI-linacs is the presence of a strong magnetic field. Therefore, existing Code of Practices (CoPs) are inadequate. In recent years, a vast amount of papers have been published in relation to this topic. The purpose of this review paper is twofold: to give an overview and evaluate the existing literature for reference dosimetry in MRI-linacs and to discuss whether the literature and datasets are adequate and complete to serve as a basis for the development of a new or to extend existing CoPs. This review is prefaced with an overview of existing MRI-linac facilities. Then an introduction on the physics of radiation transport in magnetic fields is given. The main part of the review is devoted to the evaluation of the literature with respect to the following subjects: • beam characteristics of MRI-linac facilities; • formalisms for reference dosimetry in MRI-linacs; • characteristics of ionization chambers in the presence of magnetic fields; • ionization chamber beam quality correction factors; and • ionization chamber magnetic field correction factors. The review is completed with a discussion as to whether the existing literature is adequate to serve as basis for a CoP. In addition, it highlights subjects for future research on this topic.

Direct measurement of ion chamber correction factors, k Q and k B, in a 7 MV MRI-linac.

The output of MRI-integrated photon therapy (MRgXT) devices is measured in terms of absorbed dose to water, D w. Traditionally this is done with reference type ion chambers calibrated in a beam quality Q 0 without magnetic field. To correct the ion chamber response for the application in the magnetic field, a factor needs to be applied that corrects for both beam quality Q and the presence of the magnetic field B, k Q,B. This can be expressed as the product of k Q, without magnetic field, and ion chamber magnetic field correction, k B. k B depends on the magnetic field strength and its direction, the direction of the beam and the orientation and type of the ion chamber. In this study, for the first time, both k Q and k B were measured directly for six waterproof ion chambers (3 × PTW 30013 and 3 × IBA FC65-G) in a pre-clinical 7 MV MRI-linac at 0 T and at 1.5 T. Measurements were done with the only available primary standard built for this purpose, a water calorimeter. Resulting k Q factors for PTW and IBA chambers were 0.985(5) and 0.990(4), respectively. k B factors were measured with the chambers in antiparallel direction to the magnetic field (|| 180°), and perpendicular direction (⊥ -90°). k B|| and k B⊥ for the PTW chambers were 0.985(6) and 0.963(4), respectively and for IBA chambers 0.995(4) and 0.956(4). Agreement with the available literature values was shown, partly caused by the relatively large standard deviation (SD) in those values. The values in this study are currently the only available measured values for k Q and k B in an MRI-linac that are directly linked to the international traceability framework for the quantity absorbed dose to water, D w.

Commissioning of a water calorimeter as a primary standard for absorbed dose to water in magnetic fields.

MRI guided radiotherapy devices are currently in clinical use. Detector responses are affected by the magnetic field and need to be characterized in terms of absorbed dose to water, D w, against primary standards under these conditions. The aim of this study was to commission a water calorimeter, accepted as the Dutch national standard for D w in MV photons and to validate its claimed standard uncertainty of 0.37% in the 7 MV photon beam of a pre-clinical MRI-linac in a 1.5 T magnetic field. To evaluate the primary standard on a fundamental basis, realisation of D w at 1.5 T was evaluated parameter by parameter. A thermodynamic description was given to demonstrate potential temperature effects due to the magneto-caloric effect (MCE). Methods were developed for measurement of depth, variation in detector distance and beam output in the bore of the MRI-linac. This resulted in D w measurements with a magnetic field of 1.5 T and, after ramp-down, without magnetic field. It was shown that the measurement of ΔT w and calorimeter corrections are either independent of or can be determined in a magnetic field. The chemical heat defect, h, was considered zero within its stated uncertainty, as for 0 T. Evaluation of the MCE and measurements done during magnet ramp-down, indicated no changes in the specific heat capacity of water. However, variations of the applied monitor system increased the uncertainty on beam output normalization. This study confirmed that the uncertainty for measurement of D w with a water calorimeter in a 1.5 T magnetic field is estimated to be the same as under conventional reference conditions. The VSL water calorimeter can be applied as a primary standard for D w in magnetic fields and is currently the only primary standard operable in a magnetic field that provides direct access to the international traceability framework.

Comparison of k Q factors measured with a water calorimeter in flattening filter free (FFF) and conventional flattening filter (cFF) photon beams.

Recently flattening filter free (FFF) beams became available for application in modern radiotherapy. There are several advantages of FFF beams over conventional flattening filtered (cFF) beams, however differences in beam spectra at the point of interest in a phantom potentially affect the ion chamber response. Beams are also non-uniform over the length of a typical reference ion chamber and recombination is usually larger. Despite several studies describing FFF beam characteristics, only a limited number of studies investigated their effect on k Q factors. Some of those studies predicted significant discrepancies in k Q factors (0.4% up to 1.0%) if TPR20,10 based codes of practice (CoPs) were to be used. This study addresses the question to which extent k Q factors, based on a TPR20,10 CoP, can be applied in clinical reference dosimetry. It is the first study that compares k Q factors measured directly with an absorbed dose to water primary standard in FFF-cFF pairs of clinical photon beams. This was done with a transportable water calorimeter described elsewhere. The measurements corrected for recombination and beam radial non-uniformity were performed in FFF-cFF beam pairs at 6 MV and 10 MV of an Elekta Versa HD for a selection of three different Farmer-type ion chambers (eight serial numbers). The ratio of measured k Q factors of the FFF-cFF beam pairs were compared with the TPR20,10 CoPs of the NCS and IAEA and the %dd(10) x CoP of the AAPM. For the TPR20,10 based CoPs differences less than 0.23% were found in k Q factors between the corresponding FFF-cFF beams with standard uncertainties smaller than 0.35%, while for the %dd(10) x these differences were smaller than 0.46% and within the expanded uncertainty of the measurements. Based on the measurements made with the equipment described in this study the authors conclude that the k Q factors provided by the NCS-18 and IAEA TRS-398 codes of practice can be applied for flattening filter free beams without additional correction. However, existing codes of practice cannot be applied ignoring the significant volume averaging effect of the FFF beams over the ion chamber cavity. For this a corresponding volume averaging correction must be applied.

Auditing local methods for quality assurance in radiotherapy using the same set of predefined treatment plans.

BACKGROUND AND PURPOSE: Local implementation of plan-specific quality assurance (QA) methods for intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) treatment plans may vary because of dissimilarities in procedures, equipment and software. The purpose of this work is detecting possible differences between local QA findings and those of an audit, using the same set of treatment plans. METHODS: A pre-defined set of clinical plans was devised and imported in the participating institute's treatment planning system for dose computation. The dose distribution was measured using an ionisation chamber, radiochromic film and an ionisation chamber array. The centres performed their own QA, which was compared to the audit findings. The agreement/disagreement between the audit and the institute QA results were assessed along with the differences between the dose distributions measured by the audit team and computed by the institute. RESULTS: For the majority of the cases the results of the audit were in agreement with the institute QA findings: ionisation chamber: 92%, array: 88%, film: 76% of the total measurements. In only a few of these cases the evaluated measurements failed for both: ionisation chamber: 2%, array: 4%, film: 0% of the total measurements. CONCLUSION: Using predefined treatment plans, we found that in approximately 80% of the evaluated measurements the results of local QA of IMRT and VMAT plans were in line with the findings of the audit. However, the percentage of agreement/disagreement depended on the characteristics of the measurement equipment used and on the analysis metric.

An on-site dosimetry audit for high-energy electron beams.

BACKGROUND AND PURPOSE: External dosimetry audits are powerful quality assurance instruments for radiotherapy. The aim of this study was to implement an electron dosimetry audit based on a contemporary code of practice within the requirements for calibration laboratories performing proficiency tests. This involved the determination of suitable acceptance criteria based on thorough uncertainty analyses. MATERIALS AND METHODS: Subject of the audit was the determination of absorbed dose to water, D w, and the beam quality specifier, R 50,dos. Fifteen electron beams were measured in four institutes according to the Belgian-Dutch code of practice for high-energy electron beams. The expanded uncertainty (k = 2) for the D w values was 3.6% for a Roos chamber calibrated in 60Co and 3.2% for a Roos chamber cross-calibrated against a Farmer chamber. The expanded uncertainty for the beam quality specifier, R 50,dos, was 0.14 cm. The audit acceptance levels were based on the expanded uncertainties for the comparison results and estimated to be 2.4%. RESULTS: The audit was implemented and validated successfully. All D w audit results were satisfactory with differences in D w values mostly smaller than 0.5% and always smaller than 1%. Except for one, differences in R 50,dos were smaller than 0.2 cm and always smaller than 0.3 cm. CONCLUSIONS: An electron dosimetry audit based on absorbed dose to water and present-day requirements for calibration laboratories performing proficiency tests was successfully implemented. It proved international traceability of the participants value with an uncertainty better than 3.6% (k = 2).

A water calorimeter for on-site absorbed dose to water calibrations in (60)Co and MV-photon beams including MRI incorporated treatment equipment.

In reference dosimetry the aim is to establish the absorbed dose to water, D w, under reference conditions. However, existing dosimetry protocols are not always applicable for rapidly emerging new treatment modalities. For primary standard dosimetry laboratories it is generally not feasible to acquire such modalities. Therefore it is strongly desired that D w measurements with primary standards can be performed on-site in clinical beams for the new treatment modalities in order to characterize and calibrate detectors. To serve this need, VSL has developed a new transportable water calorimeter serving as a primary D w standard for (60)Co and MV-photons including MRI incorporated treatment equipment. Special attention was paid to its operation in different beam geometries and beam modalities including the application in magnetic fields. The new calorimeter was validated in the VSL (60)Co beam and on-site in clinical MV-photon beams. Excellent agreement of 0.1% was achieved with previous (60)Co field calibrations, i.e. well within the uncertainty of the previous calorimeter, and with measurements performed in horizontal and vertical MV-photon beams. k Q factors, determined for two PTW 30013 ionization chambers, agreed very well with available literature data. The relative combined standard uncertainty (k = 1) for D w measurements in (60)Co and MV-photons is 0.37%. Calibrations are carried out with a standard uncertainty of 0.42% and k Q -factors are determined with a relative standard uncertainty of 0.40%.

Clinical Staging and Prognostic Factors in Folliculotropic Mycosis Fungoides.

IMPORTANCE: Large case series suggest that patients with folliculotropic mycosis fungoides (FMF) have a worse prognosis than patients with classic mycosis fungoides (MF). However, recent studies described a subgroup of patients with FMF with a more favorable prognosis. Distinction between indolent and aggressive FMF may have important therapeutic consequences but is hampered by the inability of the current tumor-node-metastasis-blood (TNMB) staging system to classify patients with FMF in a clinically meaningful way. OBJECTIVE: To differentiate between indolent and aggressive FMF using clinicopathological criteria and to define prognostic factors in patients with FMF. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study, we followed 203 patients with FMF, included in the Dutch Cutaneous Lymphoma Registry between October 1985 and May 2014 at a tertiary referral center hosting the Dutch Cutaneous Lymphoma Registry. Overall, 220 patients with FMF had been registered, but 17 patients with incomplete follow-up data or a history of classic MF were excluded. MAIN OUTCOMES AND MEASURES: Main outcomes included clinical and histological characteristics, disease progression, and survival. Prognostic factors were investigated using Cox proportional hazard regression analysis. Distinction between early plaque-stage FMF and advanced plaque-stage FMF was made by a blinded review of skin biopsy specimens from patients presenting with plaques. RESULTS: In a cohort of 147 men and 56 women (median [range] age, 59 [15-93] years), patients with histologically early plaque-stage FMF had a very similar overall survival (OS) rate to patients with only patches and/or follicular papules (10-year OS, 71% vs 80%), while the survival rate of patients with histologically advanced plaque-stage FMF was almost identical to that of patients presenting with tumors (10-year OS, 25% vs 27%). Subsequently, 3 clinical subgroups with significantly different survival data were distinguished: early skin-limited FMF (group A; n = 84; 5-year and 10-year OS, 92% and 72%); advanced skin-limited FMF (group B; n = 102; 5-year and 10-year OS, 55% and 28%); and FMF presenting with extracutaneous disease (group C; n = 17; 5-year and 10-year OS, 23% and 2%). Age at diagnosis, large cell transformation and secondary bacterial infection were independent risk factors for disease progression and/or poor survival. CONCLUSIONS AND RELEVANCE: The results of this study provide useful criteria to differentiate between indolent and aggressive FMF and confirm the existence of a subgroup of FMF with a favorable prognosis.

Reference dosimetry in the presence of magnetic fields: conditions to validate Monte Carlo simulations.

With the advent of MRI-guided radiotherapy, reference dosimetry must be thoroughly addressed to account for the effects of the magnetic field on absorbed dose to water and on detector dose response. While Monte Carlo plays an essential role in reference dosimetry, it is also crucial for determining quality correction factors in these new conditions. The Fano cavity test is recognized as fundamental to validate Monte Carlo transport algorithms. In the presence of magnetic fields, it is necessary to define special conditions under which such a test can be performed. The present theoretical study proposes two conditions in which the validity of Fano's theorem is demonstrated in the presence of a magnetic field and the analytic expression of energy deposition is verified. It is concluded that the proposed conditions form a valid basis for two types of Fano cavity tests in the presence of a magnetic field.

Automated non-coplanar beam direction optimization improves IMRT in SBRT of liver metastasis.

PURPOSE: To investigate whether automatically optimized coplanar, or non-coplanar beam setups improve intensity modulated radiotherapy (IMRT) treatment plans for stereotactic body radiotherapy (SBRT) of liver tumors, compared to a reference equi-angular IMRT plan. METHODS: For a group of 13 liver patients, an in-house developed beam selection algorithm (Cycle) was used for generation of 3D-CRT plans with either optimized coplanar-, or non-coplanar beam setups. These 10 field, coplanar and non-coplanar setups, and an 11 field, equi-angular coplanar reference setup were then used as input for generation of IMRT plans. For all plans, the PTV dose was maximized in an iterative procedure by increasing the prescribed PTV dose in small steps until further increase was prevented by constraint violation(s). RESULTS: For optimized non-coplanar setups, D(PTV, max) increased by on average 30% (range 8-64%) compared to the corresponding reference IMRT plan. Similar increases were observed for D(PTV, 99%) and gEUD(a). For optimized coplanar setups, mean PTV dose increases were only approximately 4%. After re-scaling all plans to the clinically applied dose, optimized non-coplanar configurations resulted in the best sparing of organs at risk (healthy liver, spinal cord, bowel). CONCLUSION: Compared to an equi-angular beam setup, computer optimized non-coplanar setups do result in substantial improvements in IMRT plans for SBRT of liver tumors.

Simultaneous tumour dose escalation and liver sparing in Stereotactic Body Radiation Therapy (SBRT) for liver tumours due to CTV-to-PTV margin reduction.

PURPOSE: To quantify potential benefits of CTV-to-PTV margin reduction for SBRT of liver tumours, as allowed by enhanced treatment precision. MATERIALS AND METHODS: For 14 patients plans were generated for the clinical margin and for 3 tighter margins. An in-house developed algorithm was used to optimise beam directions, shapes, and weights for generation of the plan with the highest isocenter dose (D(iso)), while keeping the minimum PTV dose at least 65%xD(iso) and strictly adhering to all imposed hard OAR constraints. Each plan contains 10 optimal beam directions, automatically selected from up to 252 coplanar and non-coplanar input directions. RESULTS: Apart from the expected tumour dose escalation (D(iso), EUD(PTV), gEUD(PTV)) with decreasing margin, a simultaneous improved sparing of the normal liver (D33%, D50%, D(mean)) was also observed. The smaller the margin was, the bigger both effects were. For renormalized plans with D(iso) equal to the clinical value (3x19.2Gy), and a margin reduction of 50% (2.5mm laterally, 5mm longitudinally), normal liver D33% and D50% reduced on average by 22% (maximum 38%), and 26% (maximum 47%), respectively. CONCLUSIONS: Using an algorithm for beam direction, shape and weight optimisation, large increases in the therapeutic ratio of liver plans could be obtained for reduced margins.

PTV dose prescription strategies for SBRT of metastatic liver tumours.

PURPOSE: Recently we have demonstrated that our in-house developed algorithm for automated plan generation for fully non-coplanar SBRT of liver patients (designated Cycle) yields plans that are superior to conventionally generated plans of experienced dosimetrists. Here we use Cycle in the comparison of plans with prescription isodoses of 65% or 80% of the isocentre dose. METHODS: Plans were generated using CT-data of 15 previously treated patients. For each patient, both for the 65%- and the 80% strategy, Cycle was used to generate a plan with the maximum isocentre dose, D(isoc), while strictly obeying a set of hard constraints for the organs at risk (OAR). Plans for the two strategies were compared using D(isoc), D(PTV,99%) (the minimum dose delivered to 99% of the PTV), and the generalised equivalent uniform dose, gEUD(PTV)(a), for several values of the parameter a. Moreover, for the OARs, the distance to the constraint values was analysed. RESULTS: The 65% strategy resulted in treatment plans with a higher D(isoc) (average 17.6%, range 7.6-31.1%) than the 80% strategy, at the cost of a somewhat lower D(PTV,99%) (average -2.0%, range -9.6% to 9.3%). On average, voxels with a dose in the 65% strategy, lower than the minimum PTV dose in the 80% strategy, were within 0.2cm from the PTV surface. For a-10, the 65% strategy yielded on average a significantly (P<0.01) higher gEUD(PTV)(a) than the 80% strategy, whereas for highly negative a-values the 80% approach was slightly better, although not significantly. Large variations between patients were observed. Generally, for the OAR the approach to the constraint levels was similar for the two strategies. CONCLUSION: On average, PTV dose delivery is superior with the 65% strategy. However, apart from the isocentre dose, for each applied PTV dose parameter at least one patient would have been better off with the 80% dose prescription strategy.

Computer optimization of noncoplanar beam setups improves stereotactic treatment of liver tumors.

PURPOSE: To investigate whether computer-optimized fully noncoplanar beam setups may improve treatment plans for the stereotactic treatment of liver tumors. METHODS: An algorithm for automated beam orientation and weight selection (Cycle) was extended for noncoplanar stereotactic treatments. For 8 liver patients previously treated in our clinic using a prescription isodose of 65%, Cycle was used to generate noncoplanar and coplanar plans with the highest achievable minimum planning target volume (PTV) dose for the clinically delivered isocenter and mean liver doses, while not violating the clinically applied hard planning constraints. The clinical and the optimized coplanar and noncoplanar plans were compared, with respect to D(PTV,99%), the dose received by 99% of the PTV, the PTV generalized equivalent uniform dose (gEUD), and the compliance with the clinical constraints. RESULTS: For each patient, the ratio between D(PTV,99%) and D(isoc), and the gEUD(-5) and gEUD(-20) values of the optimized noncoplanar plan were higher than for the clinical plan with an average increase of respectively 18.8% (range, 7.8-24.0%), 6.4 Gy (range, 3.4-11.8 Gy), and 10.3 Gy (range, 6.7-12.5). D(PTV,99%)/D(isoc), gEUD(-5), and gEUD(-20) of the optimized noncoplanar plan was always higher than for the optimized coplanar plan with an average increase of, respectively, 4.5% (range, 0.2-9.7%), 2.7 Gy (range, 0.6-9.7 Gy), and 3.4 Gy (range, 0.6-9.9 Gy). All plans were within the imposed hard constraints. On average, the organs at risk were better spared with the optimized noncoplanar plan than with the optimized coplanar plan and the clinical plan. CONCLUSIONS: The use of automatically generated, fully noncoplanar beam setups results in plans that are favorable compared with coplanar techniques. Because of the automation, we found that the planning workload can be decreased from 1 to 2 days to 1 to 2 h.

Stereotactic body radiation therapy for primary and metastatic liver tumors: A single institution phase i-ii study.

The feasibility, toxicity and tumor response of stereotactic body radiation therapy (SBRT) for treatment of primary and metastastic liver tumors was investigated. From October 2002 until June 2006, 25 patients not suitable for other local treatments were entered in the study. In total 45 lesions were treated, 34 metastases and 11 hepatocellular carcinoma (HCC). Median follow-up was 12.9 months (range 0.5-31). Median lesion size was 3.2 cm (range 0.5-7.2) and median volume 22.2 cm3 (range 1.1-322). Patients with metastases, HCC without cirrhosis, and HCC < 4 cm with cirrhosis were mostly treated with 3 x 12.5 Gy. Patients with HCC > or =4 cm and cirrhosis received 5 x 5 Gy or 3 x 10 Gy. The prescription isodose was 65%. Acute toxicity was scored following the Common Toxicity Criteria and late toxicity with the SOMA/LENT classification. Local failures were observed in two HCC and two metastases. Local control rates at 1 and 2 years for the whole group were 94% and 82%. Acute toxicity grade > or =3 was seen in four patients; one HCC patient with Child B developed a liver failure together with an infection and died (grade 5), two metastases patients presented elevation of gamma glutamyl transferase (grade 3) and another asthenia (grade 3). Late toxicity was observed in one metastases patient who developed a portal hypertension syndrome with melena (grade 3). SBRT was feasible, with acceptable toxicity and encouraging local control. Optimal dose-fractionation schemes for HCC with cirrhosis have to be found. Extreme caution should be used for patients with Child B because of a high toxicity risk.

Fresnel diffraction effects in the frontlight for a liquid-crystal display.

In a new type of illumination system for reflective liquid-crystal displays, the frontlight, unwanted shadows appear in certain viewing directions. It will be shown that for an accurate description of these shadows the geometrical optics approach is not satisfactory and that Fresnel diffraction has to be taken into account. A model for the diffraction effects was developed, and the predicted results correspond well to the measurements. In addition, some remarkable effects were explained from the theory of Fresnel zones.