Initial experience of hypofractionated radiation retreatment with true beam and flattening filter free beam in selected case reports of recurrent nasopharyngeal carcinoma

AimTo show our preliminary experience in using TrueBeam with RapidArc technology and FFF beam for stereotactic re-irradiation of nasopharyngeal carcinoma.BackgroundThanks to new advanced techniques, as well as intensity modulated radiation therapy, it is possible to approach head and neck recurrences in selected patients. Volumetric Modulated Arc Therapy (VMAT) in its RapidArc^® format, permits to reduce significantly the time to deliver complex intensity modulated plans, allowing to treat hypofractionated regimes within a few minutes. With TrueBeam it is possible to perform photon beams without usage of the flattening filter. It seems possible to expect a reduction of out-of-field dose when flattening filter free (FFF) beams are used. While research into the physics domain for FFF beams is increasing, there are very few clinical data where FFF beams are applied in clinical practice.Materials and methodsWe present here the cases of 4 patients with local or regional recurrence of nasopharyngeal carcinoma. All patients were treated using TrueBeam with RapidArc technology and FFF beam for stereotactic hypofractionated re-irradiation.ResultsAll patients concluded SBRT and showed good tolerability. During follow-up, complete response at imaging evaluation (PET and/or MRI) for all treated patients was documented.ConclusionsOur preliminary experience using TrueBeam with RapidArc technology and FFF beam for stereotactic hypofractionated re-irradiation of nasopharyngeal carcinoma was safe and effective in all 4 treated patients. Longer follow-up and a larger population of study is needed to confirm these promising results.     

Monte Carlo comparison of superficial dose between flattening filter free and flattened beams

This study investigates the superficial dose from FFF beams in comparison with the conventional flattened ones using a Monte Carlo (MC) method. Published phase-space files which incorporated real geometry of a TrueBeam accelerator were used for the dose calculation in phantom and clinical cases. The photon fluence on the central axis is 3 times that of a flattened beam for a 6 MV FFF beam and 5 times for a 10 MV beam. The mean energy across the field in air at the phantom surface is 0.92–0.95 MeV for the 6 MV FFF beam and 1.18–1.30 MeV for the corresponding flattened beam. At 10 MV, the values are 1.52–1.72 and 2.15–2.87 MeV for the FFF and flattened beams, respectively. The phantom dose at the depth of 1 mm in the 6 MV FFF beam is 6% ± 2.5% (of the maximum dose) higher compared to the flattened beam for a 25 × 25 cm² field and 14.6% ± 1.9% for the 2 × 2 cm² field. For the 10 MV beam, the corresponding differences are 3.4% ± 1.5% and 10.7% ± 0.6%. The skin dose difference at selected points on the patient's surface between the plans using FFF and flattened beams in the head-and-neck case was 6.5% ± 2.3% (1SD), and for the breast case it was 6.4% ± 2.3%. The Monte Carlo simulations showed that due to the lower mean energy in the FFF beam, the clinical superficial dose is higher without the flattening filter compared to the flattened beam.     

Use of IAEA’s phase-space files for virtual source model implementation: Extension to large fields

In a previous work, phase-space data files (phsp) provided by the International Atomic Energy Agency (IAEA) were used to develop a hybrid virtual source model (VSM) for clinical photon beams. Very good agreement with dosimetric measurements performed on linear accelerators was obtained for field sizes up to 15 × 15 cm². In the present work we extend the VSM to larger field sizes, for which phsp are not available. We incorporate a virtual flattening filter to our model, which can be determined from dose measurements for larger fields. In this way a fully functional VSM can be built, from publicly available IAEA’s phsps and standard dose measurements, for fields of any size and tailored to a particular linac.     

The evaluation of the neutron dose equivalent in the two-bend maze

The purpose of this study was to explore the effect of the second bend of the maze, on the neutron dose equivalent, in the 15 MV linear accelerator vault, with two bend maze. These two bends of the maze were covered by 32 points where the neutron dose equivalent was measured. There is one available method for estimation of the neutron dose equivalent at the entrance door of the two bend maze which was tested using the results of the measurements. The results of this study show that the neutron equivalent dose at the door of the two bend maze was reduced almost three orders of magnitude. The measured TVD in the first bend (closer to the inner maze entrance) is about 5 m. The measured TVD result is close to the TVD values usually used in the proposed models for estimation of neutron dose equivalent at the entrance door of the single bend maze. The results also determined that the TVD in the second bend (next to the maze entrance door) is significantly lower than the TVD values found in the first maze bend.     

Characterization of a new unshielded diode for small field dosimetry under flattening filter free beams

PurposeTo characterize the performance of a new unshielded silicon diode (Razor-IBA) for dose measurements in small flattening filter free beams.MethodsThe Razor has an active volume of 0.6 mm in diameter and 20 µm in length. The detector response stability in measured dose, dose rate, dose per pulse, and dark current were evaluated. The detector response in square fields (0.6–5.0 cm) was determined using PDD curves, axial beam profiles and output ratios. The performances were compared to that of the previously available SFD-IBA and PFD-IBA diodes.Results and discussionThe Razor short term stability relative to the SFD was much improved (<±0.1% after 1.2 kGy). The linearity was <±1% (0.05–30 Gy range) and the dose rate dependence was <±0.5% (4–24 Gy/min range). The dose per pulse dependence was <±0.7% (0.08–0.21 cGy/pulse range). The PDDs measured with Razor and PFD differed <1%. A larger dark current was observed with increase in dose (0.0025 pA/Gy) compared to the SFD (0.0002 pA/Gy). This characteristic is attributed to an increased concentration of recombination centers. The beam profile showed good agreement with the SFD. Penumbra differences were <±0.3 mm relative to PFD, with a slight overestimation of the tails (<1%), due to the absence of diode shielding. Output ratios were in good agreement for fields up to 5 × 5 cm² (<1%).ConclusionsThe Razor diode has the same spatial resolution and performance reliability as its predecessor (SFD), but exhibits the additional advantage of improved stability. These features make the Razor diode detector a good candidate for small field dosimetry.     

Determination of an inflection point for a dosimetric analysis of unflattened beam using the first principle of derivatives by python code programming

BackgroundPractice of Unflattened or Flattening filter free (FFF) beam has become the high dose standard in radiotherapy (RT), such as stereotactic radio-surgery (SRS) and stereotactic radiotherapy (SRT). The removal of a flattening filter (FF) from the path of a photon beam alters the characteristics of FFF beam. Since the conventional route for dosimetric analysis of FF beam cannot be applied to FFF beam, the procedure of analyzing beam characteristics for FFF beam based on inflection points (IPs) is used. IP is a point where the concavity change observed corresponds to its change in sign (±) of the second derivative.AimThe objective of the study is to determine IPs for dosimetric analysis of the FFF beam profile.Methods and materialsIn this study, IPs are determined through the python code programming based on the mathematical first principle of the derivative. They are compared with IPs estimated by the conventional graphical manual method using Microsoft Excel (MS). IPs and their dependent dosimetric parameters determined by both mathematical and graphical manual methods are compared.ResultPercentage differences between the IPs determined by both methods, for 6MVFFF inline and crossline beam profile are found to be 2.7% and 0.8% respectively. Similarly, the average penumbra differences for 6MVFFF inline and crossline beam profile are found to be 0.15 mm and 0.9 mm, respectively. However, differences in the field width between both methods are found insignificant.ConclusionGraphical manual method is very time-consuming, tedious and user dependent. However, the mathematical method through python code programming is more precise, faster and independent of individual users.     

A new analytical formula for neutron capture gamma dose calculations in double-bend mazes in radiation therapy

BackgroundPhotoneutrons are produced in radiation therapy with high energy photons. Also, capture gamma rays are the byproduct of neutrons interactions with wall material of radiotherapy rooms.AimIn the current study an analytical formula was proposed for capture gamma dose calculations in double bend mazes in radiation therapy rooms.Materials and methodsA total of 40 different layouts with double-bend mazes and a 18 MeV photon beam of Varian 2100 Clinac were simulated using MCNPX Monte Carlo (MC) code. Neutron capture gamma ray dose equivalent was calculated by the MC method along the maze and at the maze entrance door of all the simulated rooms. Then, all MC resulted data were fitted to an empirical formula for capture gamma dose calculations. Wu–McGinley analytical formula for capture gamma dose equivalent at the maze entrance door in single-bend mazes was also used for comparison purposes.ResultsFor capture gamma dose equivalents at the maze entrance door, the difference of 2–11% was seen between MC and the derived equation, while the difference of 36–87% was found between MC and the Wu–McGinley methods.ConclusionOur results showed that the derived formula results were consistent with the MC results for all of 40 different geometries. However, as a new formula, further evaluations are required to validate its use in practical situations. Finally, its application is recommend for capture gamma dose calculations in double-bend mazes to improve shielding calculations.     

DNA strand breaks based on Monte Carlo simulation in and around the Lipiodol with flattening filter and flattening filter-free photon beams

BackgroundThe current study aims to investigate the DNA strand breaks based on the Monte Carlo simulation within and around the Lipiodol with flattening filter (FF) and flattening filter-free (FFF) photon beams.Materials and methodsThe dose-mean lineal energy (y_D) and DNA single- and double strand breaks (DSB/SSB) based on spatial patterns of inelastic interactions were calculated using the Monte Carlo code: particle and heavy ion transport system (PHITS). The ratios of dose using standard radiation (200 kVX) to the dose of test radiation (FF and FFF of 6 MV X-ray (6MVX) and 10 MVX beams) to produce the same biological effects was defined as RBE_DSB. The RBE_DSB within the Lipiodol and in the build-up and build-down regions was evaluated.ResultsThe RBE_DSB values with the Lipiodol was larger than that without the Lipiodol at the depth of 4.9 cm by 4.2% and 2.5% for 6 MVX FFF and FF beams, and 3.3% and 2.5% for 10 MVX FFF and FF beams. The RBE_DSB values with the Lipiodol was larger than that without the Lipiodol at the depth of 6.5 cm by 2.9% and 2.4% for 6 MVX FFF and FF beams, and 1.9% and 1.4% for 10 MVX FFF and FF beams. In the build-down region at the depth of 8.1 cm, the RBE_DSB values with the Lipiodol was smaller than that without the Lipiodol by 4.2% and 2.9% for 6 MVX FFF and FF beams, and 1.4% and 0.1% for 10 MVX FFF and FF beams.ConclusionsThe current study simulated the DNA strand break except for the physical dose difference. The lower and FFF beam occurred the higher biological effect.     

Time motion study to evaluate the impact of flattening filter free beam on overall treatment time for frameless intracranial radiosurgery using Varian TrueBeam® linear accelerator

BackgroundThe aim was to study the impact of the flattening filter free (FFF) beam on overall treatment time for frameless intracranial radiosurgery using TrueBeam^® LINAC.The development of frameless stereotactic radiosurgery (SRS) is possible due to the incorporation of image guidance in the delivery of treatment. It is important to analyze the cost and benefits of FFF beams for treating SRS by understanding the impact of FFF beams in reducing the treatment time.Materials and methodsDynamic conformal arc (DCA ) and volumetric arc therapy (VMAT) plans were generated using 6 MV with a flattening filter (FF) and FFF beams. Overall treatment time was divided into beam on time (BOT) and beam off time (BFT). Percentage beam on time reduction (PBOTR) and Percentage total time reduction (PTTR) factors were defined for the comparison.ResultsBOT reduction was observed to be significant for higher dose per fraction but subjected to the treatment technique and modulation differences. PBOTR values are much higher than PTTR values. The 39.9% of PBOTR resulted in only 8% PTTR for DCA and 65.3% resulted in 15.9% PTTR for VMAT.ConclusionMajor BFT was utilized for imaging and verification. FFF beam significantly reduced the beam on time and was found to be most effective if the fractional dose was as high as that for SRS. Newly defined PBOTR and PTTR factors are very useful indicators to evaluate the efficacy of FFF beams in terms of time reduction.     

Analysis of physical parameters and determination of inflection point for Flattening Filter Free beams in medical linear accelerator

Background

Medical Linear accelerators manufactured without flattening filters are increasing popular in recent days. The removal of flattening filter results in increased dose rate, reduced mean energy, reduction in head leakage and lateral scattering, which have shown advantageous when used for special treatment procedures.

Aim

This study aims to analyze physical parameters of FFF beams and to determine the inflection point for standardizing the beam flatness and penumbra.

Materials and methods

The beam profiles and depth dose patterns were measured using Radiation Field Analyzer (RFA) with 0.13 cc cylindrical ion chamber. The beam energy characteristics, head scatter factor (Sc) were obtained for 6FFF and 10FFF beams and compared with 6 MV and 10 MV photons, respectively. The symmetry and stability of unflattened regions were also analyzed. In addition, the study proposes a simple physical concept for obtaining inflection point for FFF beams and results were compared using the Akima spline interpolation method. The inflection point was used to determine the field size and penumbra of FFF beams.

Results

The Sc varied from 0.922 to 1.044 for 6FFF and from 0.913 to 1.044 for 10FFF with field sizes from 3 cm × 3 cm to 40 cm × 40 cm which is much less than FF beams. The obtained value of field size and penumbra for both simple physical concept and Akima spline interpolation methods is within the ±1.0 mm for the field size and ±2 mm penumbra. The results indicate that FFF beams reduce Sc compared with FF beams due to the absence of a flattening filter.

Conclusion

The proposed simple method to find field size and penumbra using inflection point can be accepted as it is closely approximated to mathematical results. Stability of these parameters was ascertained by repeated measurements and the study indicates good stability for FFF beam similar to that of FF beams.     

The duration of aldehyde fixation as a “flattening factor” of synaptic vesicles

Summary Synaptic vesicle flattening can be induced in the excitatory mossy fibre endings of the rat cerebellum by prolonged immersion in aldehyde during fixation (with or without perfusion). The flattening is found in a greater percentage of vesicles if perfusion has been omitted before the prolonged immersion. This is discussed in relation to the various other factors that are thought to cause flattening and the important problem of the classification of different types of synapse.The author wishes to express his thanks to Prof. E.G. Gray, for advice and constant help; to Mrs. H. Samson and M. Lourdes Brito for technical assistance, and to the Instituto de Alta Cultura, Lisbon, for a grant.     

Dosimetric comparison of flattened and unflattened beams for stereotactic body radiation therapy: Impact of the size of the PTV on dynamic conformal arc and volumetric modulated arc therapy

PurposeFlattening filter free (FFF) beams are frequently used for stereotactic body radiation therapy with various treatment modalities: conventional static fields, dynamic conformal arc (DCA) or Rapid Arc (RA). The goal of this study was to obtain some criteria to enable a conscious choice of the employment of FFF beams and of the DCA or RA technique, depending on the PTV size.Methods and materials24 PTVs from 1.52 cm³ to 445.24 cm³ were studied in various sites: virtual phantom, lung and liver. For each PTV, DCA and RA plans were prepared using two flattened (FF) and two unflattened photon beams. Parameters such as conformity index, gradient index, healthy-tissue and organs at risk mean doses, number of monitor units (MU), beam on time (BOT) were used to quantify obtained dose distributions. Friedman tests and Spearman’s rank correlation coefficients were also performed.ResultsNo significant differences were found between FF and FFF beams for RA regarding conformity and gradient indices. For DCA, 10FFF is less suitable and forward planning becomes more challenging as PTV volume increases. FFF beams provided a better sparing of healthy-tissues except for 10FFF used with DCA. 6FFF was slightly better than 10FFF in terms of healthy-tissue mean doses. FFF beams generated significantly reduced BOTs and increased MUs. These effects were more pronounced for larger volumes and especially for RA plans.ConclusionsFFF showed better results than FF beams for the considered plans. 10FFF used with DCA should be used with caution for medium and large volumes.     

Dosimetric impact of failing to apply correction factors to ion recombination in percentage depth dose measurements and the volume-averaging effect in flattening filter-free beams

PurposeTo examine whether it is essential to apply correction factors for ion recombination (k_S) to percentage depth dose (PDD) measurements and to the volume-averaging effect (k_vol) to ensure accurate absolute dose calibration for flattening filter-free (FFF) beams for the most commonly used ionization chambers.MethodsWe surveyed medical physicists worldwide (n = 159) to identify the five most common ionization chamber combinations used for absolute and relative reference dosimetry of FFF beams. We then assessed the overall absolute dose calibration error for FFF beams of the Artiste Siemens and TrueBeam Varian linear accelerators resulting from failing to apply correction factors k_S in the PDD(10) and the volume-averaging effect (k_vol) to such chamber combinations.ResultsAll the chamber combinations examined—the Farmer PTW 30013 ionization chamber used for absolute dosimetry, and the PTW 31010, PTW 30013, IBA CC04, IBA CC13, and PTW 31021 ionization chambers used for PDD curves measurements—showed non-negligible errors (≥0.5%). The largest error (1.6%) was found for the combination of the Farmer PTW 30013 chamber with the IBA CC13 chamber, which was the most widely used chamber combination in our survey.ConclusionsBased on our findings, we strongly recommend assessing the impact of failing to apply correction factors k_S in the PDD(10) and k_vol prior to using any chamber type for FFF beam reference dosimetry purposes.     

Small field correction factors for the IBA Razor

The IBA Razor diode supersedes the IBA SFD and is intended for use in small fields. However, its behaviour in small fields has not yet been quantified. In this work, we examine the response of the Razor diode against the air core scintillation dosimeter (FOD) and Gafchromic film in photon beams from three Varian linac beams. Fields between 4 mm and 30 mm in width were measured, both with and without a flattening filter and at two energies. The Razor exhibited an over-response of up to 4.5% for MLC collimated fields and 7.1% for stereotactic cone collimated fields. The presence of the flattening filter altered the over-response by up to 1.5%. The small field correction factors are tabulated and agree with the mathematical relation of Liu et al. (2014). Four samples of the Razor were used, two having received a significant prior dose. The correction factors for the four samples differed and may depend on their dose history.     

Software simulation of tumour motion dose effects during flattened and unflattened ITV-based VMAT lung SBRT

PurposeRestricted studies comparing different dose rate parameters are available while ITV-based VMAT lung SBRT planning leads to perform the analysis of the most suitable parameters of the external beams used. The special emphasis was placed on the impact of dose rate on dose distribution variations in target volumes due to interplay effects.MethodsFour VMAT plans were calculated for 15 lung tumours using 6 MV photon beam quality (flattening filter FF vs. flattening filter free FFF beams) and maximum dose rate of 600 MU/min, 1000 MU/min and 1400 MU/min. Three kinds of motion simulations were performed finally giving 180 plans with perturbed dose distributions.Results6FFF-1400 MUs/min plans were characterized by the shortest beam on time (1.8 ± 0.2 min). Analysing the performed motion simulation results, the mean dose (Dmean) is not a sensitive parameter to related interplay effects. Looking for local maximum and local minimum doses, some discrepancies were found, but their significance was presented for individual patients, not for the whole cohort. The same was observed for other verified dose metrics.ConclusionsGenerally, the evaluation of VMAT robustness between FF and FFF concepts against interplay effect showed a negligible effect of simulated motion influence on tumour coverage among different photon beam quality parameters. Due to the lack of FFF beams, smaller radiotherapy centres are able to perform ITV-based VMAT lung SBRT treatment in a safe way. Radiotherapy department having FFF beams could perform safe, fast and efficient ITV-based VMAT lung SBRT without a concern about significance of interplay effects.     

MC safe bunker designing for an 18 MV linac with nanoparticles included primary barriers and effect of the nanoparticles on the shielding aspects

AimThe aim of this study was to design a safe bunker for an 18 MV linac in to configuration; primary barriers made from nanoparticle-containing concrete and pure concrete.BackgroundApplication of some nanoparticles in the shielding materials has been studied and it was shown that the presence of some nanoparticles improved radiation shielding properties.Materials and methodsSome percentage of different nanoparticles were modeled by the MCNP5 code of MC in the megavoltage radiotherapy treatment room's primary barriers. Other parts of the designed room, such as secondary barriers and maze door, were modeled as ordinary pure concrete. A safe bunker was designed according to the MC derived spectra at primary and secondary barriers location using a modeled and benchmarked 18 MV linac in free air. Then, the thickness of the required shielding materials for the door and also concrete for the walls and primary barriers were calculated separately.ResultsAccording to the results, required concrete thickness in primary and secondary barriers was reduced by around 0.8% compared to pure concrete application. Additionally, required lead and BPE decreased by 25% and 15%, respectively, due to primary barriers nanoparticles.ConclusionsIt was concluded that application of some nanoparticles in the shielding materials structures in megavoltage radiotherapy can make the shielding effective.     

Continuous propionic acid production from cheese whey usingin situ spin filter

The potential use of spin filter device to retainPropionibacterium acidipropionici in the bioreactor under continuous mode of fermentation and improve propionic acid productivity, was examined. The yield of propionic acid based on lactose concentration was 51% in batch and 54% in continuous (dilution rate=0.05 h⁻¹) operation. The yield in continuous fermentation with cell retention using spin filter of 10 micron size (dilution rate=0.05 h⁻¹) was even higher at 70% (w/w). The volumetric productivity under batch and continuous mode of operation were 0.312 g L⁻¹ h⁻¹ and 0.718 g L⁻¹ h⁻¹ respectively. Continuous fermentation with cell retention demonstrated even higher volumetric productivities at 0.98 g L⁻¹ h⁻¹ with out clogging problems It could be used for utilization of cheese whey to produce propionic acid at higher yield and productivities.     

Two stable, conducting conformations of the selectivity filter in Shaker K+ channels

We have examined the voltage dependence of external TEA block of Shaker K(+) channels over a range of internal K(+) concentrations from 2 to 135 mM. We found that the concentration dependence of external TEA block in low internal K(+) solutions could not be described by a single TEA binding affinity. The deviation from a single TEA binding isotherm was increased at more depolarized membrane voltages. The data were well described by a two-component binding scheme representing two, relatively stable populations of conducting channels that differ in their affinity for external TEA. The relative proportion of these two populations was not much affected by membrane voltage but did depend on the internal K(+) concentration. Low internal K(+) promoted an increase in the fraction of channels with a low TEA affinity. The voltage dependence of the apparent high-affinity TEA binding constant depended on the internal K(+) concentration, becoming almost voltage independent in 5 mM. The K(+) sensitivity of these low- and high-affinity TEA states suggests that they may represent one- and two-ion occupancy states of the selectivity filter, consistent with recent crystallographic results from the bacterial KcsA K(+) channel. We therefore analyzed these data in terms of such a model and found a large (almost 14-fold) difference between the intrinsic TEA affinity of the one-ion and two-ion modes. According to this analysis, the single ion in the one-ion mode (at 0 mV) prefers the inner end of the selectivity filter twofold more than the outer end. This distribution does not change with internal K(+). The two ions in the two-ion mode prefer to occupy the inner end of the selectivity filter at low K(+), but high internal K(+) promotes increased occupancy of the outer sites. Our analysis further suggests that the four K(+) sites in the selectivity filter are spaced between 20 and 25% of the membrane electric field.     

A review on photoneutrons characteristics in radiation therapy with high-energy photon beams

In radiation therapy with high-energy photon beams (E > 10 MeV) neutrons are generated mainly in linacs head thorough (γ,n) interactions of photons with nuclei of high atomic number materials that constitute the linac head and the beam collimation system. These neutrons affect the shielding requirements in radiation therapy rooms and also increase the out-of-field radiation dose of patients undergoing radiation therapy with high-energy photon beams. In the current review, the authors describe the factors influencing the neutron production for different medical linacs based on the performed measurements and Monte Carlo studies in the literature.