EPID in vivo dosimetry in RapidArc technique

Aim

The aim of the study was to estimate the dose at the reference point applying an aSi-EPID device in the course of patient treatment.

Materials and methods

The method assumes direct proportionality between EPID signal and dose delivered to the patient reference point during the treatment session. The procedure consists of treatment plan calculation for the actual patient in the arc technique. The plan was realized with an elliptic water-equivalent phantom. An ionization chamber inside the phantom measured the dose delivered to the reference point. Simultaneously, the EPID matrix measured the CU distribution. EPID signal was also registered during patient irradiation with the same treatment plan. The formula for in vivo dose calculation was based on the CU(g) function, EPID signal registered during therapy and the relation between the dose and EPID signal level measured for the phantom. In vivo dose was compared with dose planned with the treatment planning system.Irradiation was performed with a Clinac accelerator by Varian Medical Systems in the RapidArc technique. The Clinac was equipped with an EPID matrix (electronic portal image device) of aSi-1000. Treatment plans were calculated with the Eclipse/Helios system. The phantom was a Scanditronix/Wellhöfer Slab phantom, and the ionization chamber was a 0.6 ccm PTW chamber.

Results

In vivo dose calculations were performed for five patients. Planned dose at the reference point was 2 Gy for each treatment plan. Mean in vivo dose was in the range of 1.96–2.09.

Conclusions

Our method was shown to be appropriate for in vivo dose evaluation in the RapidArc technique.     

Measuring dose from radiotherapy treatments in the vicinity of a cardiac pacemaker

This study investigated the dose absorbed by tissues surrounding artificial cardiac pacemakers during external beam radiotherapy procedures. The usefulness of out-of-field reference data, treatment planning systems, and skin dose measurements to estimate the dose in the vicinity of a pacemaker was also examined. Measurements were performed by installing a pacemaker onto an anthropomorphic phantom, and using radiochromic film and optically stimulated luminescence dosimeters to measure the dose in the vicinity of the device during the delivery of square fields and clinical treatment plans. It was found that the dose delivered in the vicinity of the cardiac device was unevenly distributed both laterally and anteroposteriorly. As the device was moved distally from the square field, the dose dropped exponentially, in line with out-of-field reference data in the literature. Treatment planning systems were found to substantially underestimate the dose for volumetric modulated arc therapy, helical tomotherapy, and 3D conformal treatments. The skin dose was observed to be either greater or lesser than the dose received at the depth of the device, depending on the treatment site, and so care should be if skin dose measurements are to be used to estimate the dose to a pacemaker. Square field reference data may be used as an upper estimate of absorbed dose per monitor unit in the vicinity of a cardiac device for complex treatments involving multiple gantry angles.     

Assessment of clinically relevant dose distributions in pelvic IOERT using Gafchromic EBT3 films

PurposeIn IOERT a single dose of radiation is delivered to the tumour site during surgery. Manual dose calculations are used and the irradiation target volume, electron energy and applicator are decided on site by the radiation oncologist. This work assesses the effect that irregular and curved surfaces, typical of pelvic IOERT, may have on the expected dose distribution.MethodsThe feasibility of using Gafchromic EBT3 films and a slab phantom to obtain 2D dose distributions was investigated. Different set-ups were tested by comparison with water tank measurements, applying the gamma function analysis with 2% and 2 mm criteria. The validated set-up was then used to obtain reference dose distributions, which were converted to colour-coded graphical representations. Phantoms with step-like and curved surfaces were created to simulate typical pelvic IOERT irradiation surfaces, and the dose distributions were obtained and compared with the reference distributions.ResultsGood agreement with water tank measurements was obtained for all applicators below 2 mm, using the chosen setup in reference conditions. In non-reference conditions, the presence of a step-like surface creates an adjacent hotspot, followed by a quick reduction of the dose in depth. With curved surfaces, the dose distribution is shifted forward, becoming curved and deeper, but when the applicator is larger than the hole, hotspots are also observed.ConclusionsThe shape of the irradiation surfaces alters the dose distribution. Visualization of these effects is important to assess target coverage and interpret in vivo measurements in pelvic IOERT.     

High-dose continuous venous infusion of interleukin-2: Influence of dose and infusion rate on tumoricidal function and lymphocyte subsets

Previous clinical studies have demonstrated a dose-response relationship between enhancement of certain immune parameters and interleukin-2 (IL-2) dose in trials with low dosages of the cytokine. This has not been demonstrated for high-dose (greater than 18×10⁶ IU/m² per day) IL-2. We completed phase II trials of sustained administration of indomethacin and ranitidine with IL-2 given as a continuous infusion over 5 days for three courses. Peripheral blood mononuclear cells, both fresh and cultured in vitro with IL-2 or IL-2 and indomethacin, were tested for tumoricidal function against K562 and Daudi targets; these results were then correlated with actual delivered dose and mean infusion rate per course. Similar correlations were calculated between delivered dose or infusion rate and absolute and proportional counts of lymphocyte subsets as determined by flow cytometry. No enhancement of in vitro tumoricidal function with either increasing delivered dose or increasing infusion rate was seen. No consistent pattern of correlation was found between the absolute counts of lymphocyte subsets after each course of IL-2 with delivered dose or infusion rate. The percent rise in absolute counts of selected T- and NK-cell subsets at the end of course 1 compared with baseline values correlated positively with infusion rate; however, a similar correlation between the infusion rate and an increase in lymphocyte tumoricidal function was lacking. Little evidence was found for improved tumoricidal function of mononuclear cells or consistent enhancement of lymphocyte subset counts in patients able to tolerate doses of IL-2 beyond 18×10⁶ IU/m² per day in a 5-day continuous infusion schedule.Presented in part at the Twenty-eighth Annual Meeting of the American Society of Clinical Oncology, May 17–19, 1992, San Diego, Calif.     

Dose to pelvic lymph nodes in image based high dose rate brachytherapy of carcinoma cervix

AimThe aim of this study is to analyse the dosimetry to the pelvic lymph nodes and its correlation to point B using CT based high dose rate brachytherapy of carcinoma cervix.BackgroundConventionally, dose to pelvic lymph nodes from intracavitary brachytherapy was reported by point B and by the reference points of the lymphatic trapezoid.Materials and methods30 consecutive CT based high dose rate applications were reviewed between February and March 2016. The high risk clinical target volume and the organs at risk and the pelvic nodal groups were contoured. DVH parameters for the right and left obturator nodal group, right and left external iliac nodal group and right and left internal iliac nodal group were recorded. Right and left point B doses were also recorded.ResultsOn analysis of the combined dose, it was found that all the DVH parameters were significantly different from point B, except the D100 obturator and D2cc internal iliac lymph node. There was a significant correlation between all DVH parameters and point B, except D2cc, D1cc and D0.1cc of external iliac. The obturator group received the highest dose contribution from brachytherapy. The mean D90 dose received per fraction for the obturator, external iliac and internal iliac nodes was 2.7 Gy, 1.17 Gy and 1.41 Gy, respectively.ConclusionsThere is a significant dose contribution to the pelvic lymph nodal groups during intracavitary brachytherapy. There is a low degree of correlation between point B dose and dosimetric parameters of the individual nodal groups. Hence, it is important to analyse the dose delivered to individual nodal groups during intracavitary brachytherapy, at least in patients with enlarged lymph nodes to calculate the cumulative dose delivered.     

Sterilization of plastic containers using electron beam irradiation directed through the opening

AIMS: Studies were performed to demonstrate the efficacy of a novel electron beam irradiation system for the on-line sterilization of polymeric containers using energetic electrons directed through the container opening. METHODS AND RESULTS: The distribution of dosage delivered during conveyance beneath the electron beam treatment system was determined for two sizes (8 or 16 ounces) of high-density polyethylene (HDPE) blow-moulded bottles. The biological effects of treatment were then determined using Bacillus pumilus ATCC 27142 spores inoculated as 10 microl droplets dried (i) onto the surface of flat coupons of the high-density polyethylene bottle material, and (ii) onto the region of lowest delivered dose (the bottom side wall) within each bottle. The inactivation obtained was determined by examining the level of survival after swab recovery of the inoculated spores, with reference to the level recovered from untreated control samples. CONCLUSIONS: The inactivation of B. pumilus spores during treatment was reproducible and proportional to the applied dose. In each instance, the logarithm of the surviving fraction of spores was well fitted by linear regression models and in good general agreement with values reported for inactivation of the same organism using gamma irradiation. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this work demonstrate the potential of a new physical method capable of high throughput for in-line sterilization of polymeric containers. The ability of the process to eliminate the washing step involved with traditional chemical sterilants, such as hydrogen peroxide, greatly reduces the size and environmental impact of these systems.     

Effect of neutron and gamma radiation on physical endurance of rats in the swimming test

Three groups of adult male Wistar rats were exposed to neutrons (a single dose of 2 Gy) and gamma radiation (a continuous dose of 6 Gy delivered within 10.5 days) and a combination of both types of radiation. The physical fitness of irradiated and control rats was measured using a forced swimming test in the course and after the termination of the irradiation. A marked decrease in the physical fitness of all irradiated animals was followed by its normalization 3 weeks after irradiation.     

Impact of interfractional changes in head and neck cancer patients on the delivered dose in intensity modulated radiotherapy with protons and photons

PurposeTo investigate the influence of interfractional changes on the delivered dose of intensity modulated proton (IMPT) and photon plans (IMXT).Methods and materialsFive postoperative head and neck cancer patients, previously treated with tomotherapy at our institute, were analyzed. The planning study is based on megavoltage (MV) control images. For each patient one IMPT plan and one IMXT plan were generated on the first MV-CT and recalculated on weekly control MV-CTs in the actual treatment position. Dose criteria for evaluation were coverage and conformity of the planning target volume (PTV), as well as mean dose to parotids and maximum dose to spinal cord.ResultsConsiderable dosimetric changes were observed for IMPT and IMXT plans. Proton plans showed a more pronounced increase of maximum dose and decrease of minimum dose with local underdosage occurring even in the center of the PTV (worst IMPT vs. IMXT coverage: 66.7% vs. 85.0%). The doses to organs at risk (OARs) increased during the treatment period. However, the OAR doses of IMPT stayed below corresponding IMXT values at any time. For both modalities treatment plans did not necessarily worsen monotonically throughout the treatment.ConclusionsAlthough absolute differences between planned and reconstructed doses were larger in IMPT plans, doses to OARs were higher in IMXT plans. Tumor coverage was more stable in IMXT plans; IMPT dose distributions indicated a high risk for local underdosage during the treatment course.     

Exit fluence analysis using portal dosimetry in volumetric modulated arc therapy

AimIn measuring exit fluences, there are several sources of deviations which include the changes in the entrance fluence, changes in the detector response and patient orientation or geometry. The purpose of this work is to quantify these sources of errors.BackgroundThe use of the volumetric modulated arc therapy treatment with the help of image guidance in radiotherapy results in high accuracy of delivering complex dose distributions while sparing critical organs. The transit dosimetry has the potential of Verifying dose delivery by the linac, Multileaf collimator positional accuracy and the calculation of dose to a patient or phantom.Materials and methodsThe quantification of errors caused by a machine delivery is done by comparing static and arc picket fence test for 30 days. A RapidArc plan, created for the pelvis site was delivered without and with Rando phantom and exit portal images were acquired. The day to day dose variation were analysed by comparing the daily exit dose images during the course of treatment. The gamma criterion used for analysis is 3% dose difference and 3 mm distance to agreement with a threshold of 10% of maximum dose.ResultsThe maximum standard deviation for the static and arc picket fence test fields were 0.19 CU and 1.3 CU, respectively. The delivery of the RapidArc plans without a phantom shows the maximum standard deviation of 1.85 CU and the maximum gamma value of 0.59. The maximum gamma value for the RapidArc plan delivered with the phantom was found to be 1.2. The largest observed fluence deviation during the delivery to patient was 5.7% and the maximum standard deviation was 4.1 CU.ConclusionIt is found from this study that the variation due to patient anatomy and interfraction organ motion is significant.     

In vivo monitoring of total skin electron dose using optically stimulated luminescence dosimeters

AimThis study retrospectively analysed the results of using optically stimulated radiation dosimeters (OSLDs) for in vivo dose measurements during total skin electron therapy (TSET, also known as TSEI, TSEB, TSEBT, TSI or TBE) treatments of patients with mycosis fungoides.BackgroundTSET treatments are generally delivered to standing patients, using treatment plans that are devised using manual dose calculations that require verification via in vivo dosimetry. Despite the increasing use of OSLDs for radiation dosimetry, there is minimal published guidance on the use of OSLDs for TSET verification.Materials and methodsThis study retrospectively reviewed in vivo dose measurements made during treatments of nine consecutive TSET patients, treated between 2013 and 2018. Landauer nanoDot OSLDs were used to measure the skin dose at reference locations on each patient, as well as at locations of clinical interest such as the head, hands, feet, axilla and groin.Results1301 OSLD measurements were aggregated and analysed, producing results that were in broad agreement with previous TLD studies, while providing additional information about the variation of dose across concave surfaces and potentially guiding future refinement of treatment setup. In many cases these in vivo measurements were used to identify deviations from the planned dose in reference locations and to identify anatomical regions where additional shielding or boost treatments were required.ConclusionsOSLDs can be used to obtain measurements of TSET dose that can inform monitor unit adjustments and identify regions of under and over dosage, while potentially informing continuous quality improvement in TSET treatment delivery.     

Three cases of hemolytic Streptococcus infection in guinea-pigs (author's transl)

Three cases of naturally occurring hemolytic streptococcus infection were detected in guinea-pigs which had been delivered from different sources to the Division of Animal Research, Faculty of Medicine, University of Tokyo, Tokyo, during the period from November, 1976, till February, 1977. The clinical manifestations of the infection were differentiated into two types; ie, the acute type with sepsis and pneumonia as main pathologic changes, and the chronic type with abscess formation of submaxillary lymph node. Streptococcus zooepidemicus was isolated from the conjunctiva of about 56% of these guinea-pigs. Healthy guinea-pigs housed with spontaneously infected ones in the same cage suffered from the infection, showing manifestation and pathologic changes similar to the spontaneous cases. Some of them, however, remained apparently healthy for about 2 months harboring the organisms in the conjunctiva or nasal cavity. It is presumed that such carriers become a source of the infection in nature.     

Lymphoid organ alterations enhanced by sub-lethal doses of coronaviruses in experimentally induced Trypanosoma cruzi infection in mice

The effect of sub-lethal doses of coronaviruses on the course of disease in CBA mice experimentally infected with a mildly pathogenic strain of Trypanosoma cruzi was investigated. Mice were inoculated with either T. cruzi, 0.1 median lethal dose (LD50) of coronavirus (mouse hepatitis virus [MHV-3] or virus X), or both pathogens. Levels of parasitemia, mortality, and the extent of pathologic alterations in lymphoid organs were determined. Mice inoculated with T. cruzi had mild alterations in their lymphoid organs and survived infection. In contrast, mice inoculated with both pathogens died, and had significantly higher levels of parasitemia and profound alterations in lymphoid organs. These results indicate that the pathologic profile of T. cruzi infection can be profoundly altered by subclinical infection with coronaviruses.     

Dose-rate effects of protons on in vivo activation of nuclear factor-kappa B and cytokines in mouse bone marrow cells

The objective of this study was to determine the kinetics of nuclear factor-kappa B (NF-κB) activation and cytokine expression in bone marrow (BM) cells of exposed mice as a function of the dose rate of protons. The cytokines included in this study are pro-inflammatory [i.e., tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and IL-6] and anti-inflammatory cytokines (i.e., IL-4 and IL-10). We gave male BALB/cJ mice a whole-body exposure to 0 (sham-controls) or 1.0 Gy of 100 MeV protons, delivered at 5 or 10 mGy min⁻¹, the dose and dose rates found during solar particle events in space. As a reference radiation, groups of mice were exposed to 0 (sham-controls) or 1 Gy of ¹³⁷Cs γ rays (10 mGy min⁻¹). After irradiation, BM cells were collected at 1.5, 3, 24 h, and 1 month for analyses (five mice per treatment group per harvest time). The results indicated that the in vivo time course of effects induced by a single dose of 1 Gy of 100 MeV protons or ¹³⁷Cs γ rays, delivered at 10 mGy min⁻¹, was similar. Although statistically significant levels of NF-κB activation and pro-inflammatory cytokines in BM cells of exposed mice when compared to those in the corresponding sham controls (Student’s t-test, p < 0.05 or <0.01) were induced by either dose rate, these levels varied over time for each protein. Further, only a dose rate of 5 mGy min⁻¹ induced significant levels of anti-inflammatory cytokines. The results indicate dose-rate effects of protons.     

In-line assessment of pulmonary drug delivery using light obscuration

A candidate optical technology for characterisation of the value and quality of the drug dose delivered to a patient from an inhaler is examined. The theoretical reasoning behind the design of this technology is presented with reference to the optical scattering of the drug cloud. A technical implementation is presented; based upon the light obscuration signature, observed in the delivery path during drug delivery. Dose evaluation studies are reported, performed on different types of drug formulations using regulatory testing procedures and the proposed optical sensing system. Further applications of this technology are discussed in relation to the identification and evaluation of inhaler-drug formulation combinations, which are most suitable for particular patients.     

The question of relative biological effectiveness and quality factor for auger emitters incorporated into proliferating mammalian cells

The problem of determining RBE values for Auger emitters incorporated into proliferating mammalian cells is examined. In general, the reference radiation plays a key role in obtaining experimental RBE values. Using survival of cultured Chinese hamster V79 cells as the experimental model, new data are provided regarding selection of a reference radiation for internal Auger emitters. These data show that gamma rays delivered acutely (137Cs) are more than twice as lethal as gamma rays delivered chronically with an exponentially decreasing dose rate (99mTc). The results confirm that the reference radiation should be delivered chronically in a manner consistent with the extended exposure received by the cells in the case of incorporated radionuclides. Through a direct comparison of the radiotoxicity of Auger emitters and alpha emitters, the high RBE values reported for DNA-bound Auger emitters are confirmed. These studies reveal that the DNA binding compound [125I]iododeoxyuridine (125IdU) is about 1.6 times more effective in killing V79 cells than 5.3 MeV alpha particles from intracellularly localized 210Po-citrate. In addition, toxicity studies with the radiochemicals 125IdU and [125]-iododeoxycytidine (125IdC) establish the equivalence of the radiosensitivity of thymine and cytosine base sites in the DNA. In view of these results, and information already available, the question of establishing quality factors for Auger emitters is considered. Finally, a method for calculation of the dose equivalent for internal Auger emitters is advanced.     

A GATE/Geant4 beam model for the MedAustron non-isocentric proton treatment plans quality assurance

PurposeTo present a reference Monte Carlo (MC) beam model developed in GATE/Geant4 for the MedAustron fixed beam line. The proposed model includes an absolute dose calibration in Dose-Area-Product (DAP) and it has been validated within clinical tolerances for non-isocentric treatments as routinely performed at MedAustron.Material and MethodsThe proton beam model was parametrized at the nozzle entrance considering optic and energy properties of the pencil beam. The calibration in terms of absorbed dose to water was performed exploiting the relationship between number of particles and DAP by mean of a recent formalism. Typical longitudinal dose distribution parameters (range, distal penumbra and modulation) and transverse dose distribution parameters (spot sizes, field sizes and lateral penumbra) were evaluated. The model was validated in water, considering regular-shaped dose distribution as well as clinical plans delivered in non-isocentric conditions.ResultsSimulated parameters agree with measurements within the clinical requirements at different air gaps. The agreement of distal and longitudinal dose distribution parameters is mostly better than 1 mm. The dose difference in reference conditions and for 3D dose delivery in water is within 0.5% and 1.2%, respectively. Clinical plans were reproduced within 3%.ConclusionA full nozzle beam model for active scanning proton pencil beam is described using GATE/Geant4. Absolute dose calibration based on DAP formalism was implemented. The beam model is fully validated in water over a wide range of clinical scenarios and will be inserted as a reference tool for research and for independent dose calculation in the clinical routine.     

Integral dose: Comparison between four techniques for prostate radiotherapy

Aim

Comparisons of integral dose delivered to the treatment planning volume and to the whole patient body during stereotactic, helical and intensity modulated radiotherapy of prostate.

Background

Multifield techniques produce large volumes of low dose inside the patient body. Delivered dose could be the result of the cytotoxic injuries of the cells even away from the treatment field. We calculated the total dose absorbed in the patient body for four radiotherapy techniques to investigate whether some methods have a potential to reduce the exposure to the patient.

Materials and methods

We analyzed CyberKnife plans for 10 patients with localized prostate cancer. Five alternative plans for each patient were calculated with the VMAT, IMRT and TomoTherapy techniques. Alternative dose distributions were calculated to achieve the same coverage for PTV. Integral Dose formula was used to calculate the total dose delivered to the PTV and whole patient body.

Results

Analysis showed that the same amount of dose was deposited to the treated volume despite different methods of treatment delivery. The mean values of total dose delivered to the whole patient body differed significantly for each treatment technique. The highest integral dose in the patient''s body was at the TomoTherapy and CyberKnife treatment session. VMAT was characterized by the lowest integral dose deposited in the patient body.

Conclusions

The highest total dose absorbed in normal tissue was observed with the use of a robotic radiosurgery system and TomoTherapy. These results demonstrate that the exposure of healthy tissue is a dosimetric factor which differentiates the dose delivery methods.     

The effect of beam interruption during VMAT delivery on the delivered dose distribution

PurposeThe aim of this study is to investigate the effect of beam interruptions during delivery of volumetric modulated arc therapy (VMAT) on delivered dose distributions.MethodsTen prostate and ten head and neck (H&N) VMAT plans were retrospectively selected. Each VMAT plan was delivered using Trilogy™ without beam interruption, and with 4 and 8 intentional beam interruptions per a single arc. Two-dimensional global and local gamma evaluations with a diode array were performed with gamma criteria of 3%/3 mm, 2%/2 mm, 1%/2 mm and 2%/1 mm for each VMAT plan with and without beam interruptions. The VMAT plans were reconstructed with log files recorded during delivery and the dose-volumetric parameters were calculated for each reconstructed plan. The differences among dose-volumetric parameters due to the beam interruptions were calculated.ResultsThe changes in global gamma passing rates with various gamma criteria were less than 1.6% on average, while the changes in local gamma passing rates were less than 5.3% on average. The dose-volumetric parameter changes for the target volumes of prostate and H&N VMAT plans due to beam interruptions were less than 0.72% and 1.5% on average, respectively.ConclusionThe delivered dose distributions with up to 8 beam interruptions per an arc were clinically acceptable, showing minimal changes in both gamma passing rates and dose-volumetric parameters.     

Radioisotope stents for the prevention of restenosis: what did we learn from pre-clinical studies?

This article will discuss the lessons learned by using stents implanted with low activities of radioisotopes to prevent in-stent restenosis. A continuous low-dose rate radiation delivered by radioisotope stents has been shown to reduce the proliferative activity of smooth muscle cells and to inhibit neointimal growth. However, the radiation also delays endothelialization of the stents. Both the dose rate and the cumulative dose delivered by radioisotope stents appear to affect outcome. The neointima covering radioactive stents is characterized by a reduced cellularity, increased amounts of fibrin and extracellular matrix proteins. Aneurysm formation or excessive tissue destruction due to the radiation were not observed. Animals studies including up to 1 year follow-up periods suggest that beta-particle-radiation as well as gamma-radiation are effective in reducing neointimal hyperplasia. It is still unknown, however, which range of activities are needed and if a combination of radioisotopes, i.e. with short and long halflives, further reduce neotima formation over the long-term. An appropriate stent design for homogenous dose distribution around the stent may be important, i.e. articulations or large cell sizes may have disadvantages. Augmented neointima formation at the ends of radioactive stents, in particular when using beta-particle emitting stents, has been observed in animal models. Future studies will focus on the effects of increasing activity levels at the stent ends, optimal stent designs, alternative isotopes and different dosing strategies.     

Un examen au 18F-FDG d’interprétation délicate : une histoire de diaphragme

We present a clinical case illustrating the difficulty of interpretation of hypermetabolic foci localisation in 18F-FDG-PET/CT exam performed without injection of iodinated contrast. In a patient with cystic fibrosis during infection, the focus appears to be pathologic in subdiaphragmatic and retroperitoneal region. After a careful reading, the focus represents in reality the pillars diaphragmatic muscle attachments. The presence of other uptake in intercostal muscles in this patient presenting with respiratory failure and especially the comparison with an enhanced CT scan demonstrated our assumption.