Dosimetric verification of dose optimisation algorithm during endovascular brachytherapy of the peripheral vessels

AimDosimetric verification of the dose optimisation model used in endovascular brachytherapy, evaluation of the optimised dose distributions using elaborated indices.BackgroundThe equipment used for standard radiotherapy is used in vascular brachytherapy for prevention of restenosis after angioplasty.Material and MethodA paraffin-wax phantom, thermoluminescent detectors and MD-55 Gafchromic® films were used for dose measurements. The edge dose index (EDI), central dose index (CDI) and treatment length index (TLI) were introduced to compare dose distributions calculated and measured.ResultsObtained values (p>0.05) show no statistically significant differences between calculated doses and measured doses. EDI values showed improvement in dose homogeneity on the edges of the application after optimisation. After optimisation CDI values from 0.9% to 1.6% for calculated and from ?1.8% to 3.1% for measured showed improvement in dose homogeneity in the central part of the application. Observed values of TLI from 3% to 21% for calculated doses and from 7% to 24% for doses measured by Gafchromic® films showed increase of RIL for optimised treatment plans.Conclusions1/ The designed phantom allowed repeatable dosimetric verification of dose distributions in endovascular brachytherapy. 2/ Measurements with thermoluminescent detectors and Gafchromic films proved the accuracy of the calculation algorithm in endovascular brachytherapy conditions. 3/ Elaborated indices were found to be a useful tool in describing dose homogeneity. They allowed the process of optimisation to be controlled and thus an increase in dose homogeneity by 30% at the edges and by 7% in the middle of the treated volume to be achieved.     

Dose-response curves and tolerance doses for late functional changes in the normal rat brain after stereotactic radiosurgery evaluated by magnetic resonance imaging: influence of end points and follow-up time

Late reaction of normal tissue is still a limiting factor in radiotherapy and radiosurgery of patients with brain tumors. Few quantitative data in terms of dose-response curves are available. In the present study, 99 animals were irradiated stereotactically at the right frontal lobe using a linear accelerator and single doses between 26 and 50 Gy. The diameter of the spherical dose distribution was 4.7 mm (80% isodose). Dose-response curves for late changes in the normal brain at 20 months were measured using T1- and T2-weighted magnetic resonance imaging (MRI). The dependence of the dose-response curves on the follow-up time and the definition of the biological end point were determined. Tolerance doses were calculated at several effect probability levels and times after irradiation. The MRI changes were found to be dependent on dose and progressive in time. At 20 months, the tolerance doses at a 50% effect probability level were 39.6 +/- 1.0 Gy and 42.4 +/- 1.4 Gy for changes in T1- and T2-weighted images, respectively. These dose-response curves can be used for further quantitative investigations on the influence of various treatment parameters, such as the application of charged particles, radiopharmaceuticals or the variation of tissue oxygenation.     

Dosimetric and radiobiological comparison in head-and-neck radiotherapy using JO-IMRT and 3D-CRT

IntroductionDosimetric and radiobiological evaluations for the Jaws-only Intensity-modulated radiotherapy (JO-IMRT) technique for head and neck jaws-only intensity-modulated radiation therapy (JO-IMRT) and 3D conformal radiation therapy (3D-CRT). To compare the head-and-neck therapeutic approaches utilizing JO-IMRT and 3D-CRT techniques, different radiation dose indices were calculated, including: conformity index (CI), homogeneity index (HI), and radiobiological variables like Niemierko's equivalent uniform dose based tumor control probability (TCP) of planning target volume (PTV), normal tissue complication probability (NTCP) of organs at risk (OAR) (brainstem, spinal cord, and parotid grand).Materials and methodsTwenty-five nasopharynx patients were studied using the Prowess Panther Treatment Planning System (Prowess Inc). The results were compared with the dose distribution obtained using 3D-CRT.ResultsRegarding tumor coverage and CI, JO-IMRT showed better results than 3D-CRT. The average doses received by the PTVs were quite similar: 72.1 ± 0.8 Gy by 3D-CRT and 72.5 ± 0.6 Gy by JO-IMRT plans (p > 0.05). The mean doses received by the parotid gland were 56.7 ± 0.7 Gy by 3D-CRT and 26.8 ± 0.3 Gy by JO-IMRT (p > 0.05). The HI and CI were 0.13 ± 0.01 and 0.14 ± 0.05 and (p > 0.05) by 3D-CRT and 0.83 ± 0.05 and 0.73 ± 0.10 by JO-IMRT (p < 0.05). The average TCP of PTV was 0.82 ± 0.08 by 3D-CRT and 0.92 ± 0.02 by JO-IMRT. Moreover, the NTCP of the parotid glands, brain stem, and spinal cord were lower using the JO-IMRT than 3D-CRT plans. In comparison to the 3D-CRT approach, the JO-IMRT technique was able to boost dose coverage to the PTV, improve the target's CI and HI, and spare the parotid glands. This suggests the power of the JO-IMRT over 3D-CRT in head-and-neck radiotherapy.     

Dosimetric and radiobiological comparison of TG-43 and Monte Carlo calculations in 192Ir breast brachytherapy applications

PurposeTo investigate the clinical significance of introducing model based dose calculation algorithms (MBDCAs) as an alternative to TG-43 in ¹⁹²Ir interstitial breast brachytherapy.Materials and methodsA 57 patient cohort was used in a retrospective comparison between TG-43 based dosimetry data exported from a treatment planning system and Monte Carlo (MC) dosimetry performed using MCNP v. 6.1 with plan and anatomy information in DICOM-RT format. Comparison was performed for the target, ipsilateral lung, heart, skin, breast and ribs, using dose distributions, dose-volume histograms (DVH) and plan quality indices clinically used for plan evaluation, as well as radiobiological parameters.ResultsTG-43 overestimation of target DVH parameters is statistically significant but small (less than 2% for the target coverage indices and 4% for homogeneity indices, on average). Significant dose differences (>5%) were observed close to the skin and at relatively large distances from the implant leading to a TG-43 dose overestimation for the organs at risk. These differences correspond to low dose regions (<50% of the prescribed dose), being less than 2% of the prescribed dose. Detected dosimetric differences did not induce clinically significant differences in calculated tumor control probabilities (mean absolute difference <0.2%) and normal tissue complication probabilities.ConclusionWhile TG-43 shows a statistically significant overestimation of most indices used for plan evaluation, differences are small and therefore not clinically significant. Improved MBDCA dosimetry could be important for re-irradiation, technique inter-comparison and/or the assessment of secondary cancer induction risk, where accurate dosimetry in the whole patient anatomy is of the essence.     

Image fusion analysis of volumetric changes after interstitial low-dose-rate iodine-125 irradiation of supratentorial low-grade gliomas

The aim of this study was to compare the volumes of tumor necrosis, reactive zone and edema with the three-dimensional dose distributions after brachytherapy treatments of gliomas. The investigation was performed an average of 14.2 months after low-dose-rate (125)I interstitial irradiation of 25 inoperable low-grade gliomas. The prescribed dose was 50-60 Gy to the tumor surface. Dose planning and image fusion were performed with the BrainLab-Target 1.19 software. In the CT/ MRI images, the "triple ring" (tumor necrosis, reactive ring and edema) developing after the interstitial irradiation of the brain tumors was examined. The images with the triple ring were fused with the planning images, and the isodose curves were superimposed on them. The volumes of the three regions were measured. The average dose at the necrosis border was determined from the isodose distribution. For quantitative assessment of the dose distributions, the dose nonuniformity ratio (DNR), homogeneity index (HI), coverage index (CI) and conformal index (COIN) were calculated. The relative volumes of the different parts of the triple ring after the interstitial irradiation compared to the reference dose volume were the following: necrosis, 40.9%, reactive zone, 47.1%, and edema, 367%. The tumor necrosis developed at 79.1 Gy on average. The average DNR, HI, CI and COIN were 0.45, 0.24, 0.94 and 0.57, respectively. The image fusion analysis of the volume of tumor necrosis, reactive ring and edema caused by interstitial irradiation and their correlation with the dose distribution provide valuable information for patient follow-up, treatment options, and effects and side effects of radio therapy.     

Detailed analysis of dose difference in using water as tissue-equivalent material in 252Cf brachytherapy

AimThe purpose of this study is to analyse how small variations in the elemental composition of soft tissue lead to differences in dose distributions from a ²⁵²Cf brachytherapy source and to determine the error percentage in using water as a tissue-equivalent material.BackgroundWater is normally used as a tissue-equivalent phantom material in radiotherapy dosimetry.Materials and methodsNeutron energy spectra, neutron and gamma-ray dose rate distributions were calculated for a ²⁵²Cf AT source located at the center of a spherical phantom filled with various types of tissue compositions: adipose, brain, muscle, International Commission on Radiation Units and Measurements (ICRU) report No. 44 9-component soft tissue and water, using Monte Carlo simulation.ResultsThe obtained results showed differences between total dose rates in various tissues relative to water varying between zero and 4.94%. The contributions of neutron and total gamma ray doses to these differences are, on average, 81% and 19%, respectively. It was found that the dose differences between various soft tissues and water depend not only on the soft tissue composition, but also on the beam type emitted from the ²⁵²Cf source and the distance from the source.ConclusionAssuming water as a tissue-equivalent material, although leads to overestimation of dose rate (except in the case of adipose tissue), is acceptable and suitable for use in ²⁵²Cf brachytherapy treatment planning systems based on the recommendation by the ICRU that the uncertainties in dose delivery in radiotherapy should be lower than 5%.     

Dosimetric verification of a high dose rate brachytherapy treatment planning system in homogeneous and heterogeneous media

ObjectivesTo verify the dosimetric accuracy of treatment plans in high dose rate (HDR) brachytherapy by using Gafchromic EBT2 film and to demonstrate the adequacy of dose calculations of a commercial treatment planning system (TPS) in a heterogeneous medium.MethodsAbsorbed doses at chosen points in anatomically different tissue equivalent phantoms were measured using Gafchromic EBT2 film. In one case, tandem ovoid brachytherapy was performed in a homogeneous cervix phantom, whereas in the other, organ heterogeneities were introduced in a phantom to replicate the upper thorax for esophageal brachytherapy treatment. A commercially available TPS was used to perform treatment planning in each case and the EBT2 films were irradiated with the HDR Ir-192 brachytherapy source.ResultsFilm measurements in the cervix phantom were found to agree with the TPS calculated values within 3% in the clinically relevant volume. In the thorax phantom, the presence of surrounding heterogeneities was not seen to affect the dose distribution in the volume being treated, whereas, a little dose perturbation was observed at the lung surface. Doses to the spinal cord and to the sternum bone were overestimated and underestimated by 14.6% and 16.5% respectively by the TPS relative to the film measurements. At the trachea wall facing the esophagus, a dose reduction of 10% was noticed in the measurements.ConclusionsThe dose calculation accuracy of the TPS was confirmed in homogeneous medium, whereas, it was proved inadequate to produce correct dosimetric results in conditions of tissue heterogeneity.     

Comparison of planned and measured rectal dose in-vivo during high dose rate Cobalt-60 brachytherapy of cervical cancer

Cobalt-60 (Co-60) is a relatively new source for the application of high-dose rate (HDR) brachytherapy. Radiation dose to the rectum is often a limiting factor in achieving the full prescribed dose to the target during brachytherapy of cervical cancer. The aim of this study was to measure radiation doses to the rectum in-vivo during HDR Co-60 brachytherapy. A total of eleven HDR brachytherapy treatments of cervical cancer were recruited in this study. A series of diodes incorporated in a rectal probe was inserted into the patient's rectum during each brachytherapy procedure. Real-time measured rectal doses were compared to calculated doses by the treatment planning system (TPS). The differences between calculated and measured dose ranged from 8.5% to 41.2%. This corresponds to absolute dose differences ranging from 0.3 Gy to 1.5 Gy. A linear relationship was observed between calculated and measured doses with linear regression R² value of 0.88, indicating close association between the measured and calculated doses. In general, absorbed doses for the rectum as calculated by TPS were observed to be higher than the doses measured using the diode probe. In-vivo dosimetry is an important quality assurance method for HDR brachytherapy of cervical cancer. It provides information that can contribute to the reduction of errors and discrepancies in dose delivery. Our study has shown that in-vivo dosimetry is feasible and can be performed to estimate the dose to the rectum during HDR brachytherapy using Co-60.     

A radiobiological model for the relative biological effectiveness of high-dose-rate 252Cf brachytherapy

While there is significant clinical experience using both low- and high-dose-rate 252Cf brachytherapy, there are minimal data regarding values for the neutron relative biological effectiveness (RBE) with both modalities. The aim of this research was to derive a radiobiological model for 252Cf neutron RBE and to compare these results with neutron RBE values used clinically in Russia. The linear-quadratic (LQ) model was used as the basis to characterize cell survival after irradiation, with identical cell killing rates (S(N) = S(gamma)) between 252Cf neutrons and photons used for derivation of RBE. Using this equality, a relationship among neutron dose and LQ radiobiological parameter (i.e., alpha(N), beta(N), alpha(gamma), beta(gamma)) was obtained without the need to specify the photon dose. These results were used to derive the 252Cf neutron RBE, which was then compared with Russian neutron RBE values. The 252Cf neutron RBE was determined after incorporating the LQ radiobiological parameters obtained from cell survival studies with fast neutrons and teletherapy photons. For single-fraction high-dose-rate neutron doses of 0.5, 1.0, 1.5 and 2.0 Gy, the total biologically equivalent doses were 1.8, 3.4, 4.7 and 6.0 RBE Gy with 252Cf neutron RBE values of 3.2, 2.9, 2.7 and 2.5, respectively. Using clinical data for late-responding reactions from 252Cf, Russian investigators created an empirical model that predicted high-dose-rate 252Cf neutron RBE values ranging from 3.6 to 2.9 for similar doses and fractionation schemes and observed that 252Cf neutron RBE increases with the number of treatment fractions. Using these relationships, our results were in general concordance with high-dose-rate 252Cf RBE values obtained from Russian clinical experience.     

Analysis of primate head irradiation with 55-MeV protons.

The distribution of the dose to the head of a primate phantom due to 55-MeV proton irradiation was calculated using a clinical radiotherapy treatment planning system, with anatomic definition through computerized tomography scans. Dose profiles, isodose distributions, and differential and integral dose-volume histograms are used to describe the probable proton dose to the brain of rhesus monkeys, irradiated over two decades ago, in which brain tumors have now developed. The dose analysis shows that 59% of the brain received a dose in excess of the reference surface dose, and that portions of the brain received doses greater than 300% of the reference surface dose. The regions of high dose are illustrated in isodose distributions. This information may be useful in evaluating potential tumor induction following radiation exposure.     

Optimized matching of film dosimetry with calculated doses for IMRT quality assurance

We develop a new method with a global optimization for registering films to calculate doses for intensity-modulated radiation therapy (IMRT) and intensity-modulated radiosurgery (IMRS) quality assurance (QA). Both absolute point dosimetry and two-dimensional (2D) film dosimetry are performed through the IMRT and IMRS using Clinac 21EX's 120 millenium MLC and BrainLab's micro-MLC, respectively. The measured and calculated dose distributions are superimposed by coincidence of their origins, followed by comparison of the point doses at all matched positions. Then, with the optimization algorithm the setup error of the dosimeter is corrected. An example of IMRT cases shows that the average percentage showing 3% of dose difference for 10 patients has been reduced from 19% to 9%, before and after optimization and weight, respectively. Similar results are obtained for IMRS. This method dramatically reduces the difference between measured and calculated dose distributions in all cases investigated.     

Dosimetric analysis of Tomotherapy-based intracranial stereotactic radiosurgery of brain metastasis

PurposeThis paper analyzes Tomotherapy-based intracranial stereotactic radiosurgery (HTSRS) of brain metastasis targeting two end-points: 1) evaluation of dose homogeneity, conformity and gradient scores for single and multiple lesions and 2) assay of dosimetric criticality of completion of HTSRS procedures.Methods42 treatment plans of 33 patients (53 brain lesions) treated with HTSRS were analyzed. Dose to healthy brain, homogeneity, conformity and gradient indexes were evaluated for each lesion. Influence of Field Length and multiple lesions cross-talk effect were assessed. Treatment interruption and completion was investigated using radiochromic films in order to examine the delivered dose and its robustness to patient intrafraction movement.ResultsThe average dose homogeneity index was 1.04 ± 0.02 (SD). Average dose conformity and gradient score indexes were 1.4 ± 0.2 and 50 ± 14 respectively. We found a strong correlation of the dose to healthy brain and conformity and gradient indexes with target(s) volume for which analytical functions were obtained. Field Length and cross-talk effect were significantly correlated with poor gradient scores, but were found not to affect dose conformity.ConclusionsHomogeneity and conformity of HTSRS plans achieved excellent scores, while dose falloff and dose to healthy brain were slightly larger when compared with non-coplanar SRS techniques. Care should be given if treating large (>3 cc) or multiple near in-plane lesions in order to reduce dose to healthy brain. Analysis of interrupted treatments suggests splitting HTSRS treatments in two consecutive fractions in order to prevent target miss and overdosage due to patient intrafraction movement.     

High-Precision Radiosurgical Dose Delivery by Interlaced Microbeam Arrays of High-Flux Low-Energy Synchrotron X-Rays

Microbeam Radiation Therapy (MRT) is a preclinical form of radiosurgery dedicated to brain tumor treatment. It uses micrometer-wide synchrotron-generated X-ray beams on the basis of spatial beam fractionation. Due to the radioresistance of normal brain vasculature to MRT, a continuous blood supply can be maintained which would in part explain the surprising tolerance of normal tissues to very high radiation doses (hundreds of Gy). Based on this well described normal tissue sparing effect of microplanar beams, we developed a new irradiation geometry which allows the delivery of a high uniform dose deposition at a given brain target whereas surrounding normal tissues are irradiated by well tolerated parallel microbeams only. Normal rat brains were exposed to 4 focally interlaced arrays of 10 microplanar beams (52 µm wide, spaced 200 µm on-center, 50 to 350 keV in energy range), targeted from 4 different ports, with a peak entrance dose of 200Gy each, to deliver an homogenous dose to a target volume of 7 mm³ in the caudate nucleus. Magnetic resonance imaging follow-up of rats showed a highly localized increase in blood vessel permeability, starting 1 week after irradiation. Contrast agent diffusion was confined to the target volume and was still observed 1 month after irradiation, along with histopathological changes, including damaged blood vessels. No changes in vessel permeability were detected in the normal brain tissue surrounding the target. The interlacing radiation-induced reduction of spontaneous seizures of epileptic rats illustrated the potential pre-clinical applications of this new irradiation geometry. Finally, Monte Carlo simulations performed on a human-sized head phantom suggested that synchrotron photons can be used for human radiosurgical applications. Our data show that interlaced microbeam irradiation allows a high homogeneous dose deposition in a brain target and leads to a confined tissue necrosis while sparing surrounding tissues. The use of synchrotron-generated X-rays enables delivery of high doses for destruction of small focal regions in human brains, with sharper dose fall-offs than those described in any other conventional radiation therapy.     

Application of Monte Carlo calculations for validation of a treatment planning system in high dose rate brachytherapy

AimThe accuracy of treatment planning systems is of vital importance in treatment outcomes in brachytherapy. In the current study the accuracy of dose calculations of a high dose rate (HDR) brachytherapy treatment planning system (TPS) was validated using the Monte Carlo method.Materials and methodsThree ⁶⁰Co sources of the GZP6 afterloading brachytherapy system were modelled using MCNP4C Monte Carlo (MC) code. The dose distribution around all the sources was calculated by MC and a dedicated treatment planning system. The results of both methods were compared.ResultsThere was good agreement (<2%) between TPS and MC calculated dose distributions except at a point near the sources (<1 cm) and beyond the tip of the sources.ConclusionsOur study confirmed the accuracy of TPS calculated dose distributions for clinical use in HDR brachytherapy.     

Influence of multi-leaf collimator leaf width in radiosurgery via volumetric modulated arc therapy and 3D dynamic conformal arc therapy

PurposeTo study the influence of Multileaf Collimator (MLC) leaf width in radiosurgery treatment planning for Volumetric Modulated Arc Therapy (VMAT) and 3D Dynamic Conformal Arc Therapy (3D-DCA).Material and methods16 patients with solitary brain metastases treated with radiosurgery via the non-coplanar VMAT were replanned for the 3D-DCA. For each planning technique two MLC leaf width sizes were utilized, i.e. 5 mm and 2.5 mm. These treatment plans were compared using dosimetric indices (conformity, gradient and mean dose for brain tissue) and the normal tissue complication probability (NTCP).ResultsAn improvement in planning quality for VMAT was observed versus 3D-DCA for any MLC leaf width, mainly with regards to dose conformity and to a lesser extent regards dose gradient. No significant difference was observed for any of both techniques using smaller leaf width. However, dose gradient was improved in favor of the 2.5 mm MLC for either of both techniques (15% VMAT and 10% 3D-DCA); being noticeable for lesions smaller than 10 cm³. Nonetheless, the NTCP index was not significantly affected by variations in the dose gradient index.ConclusionsThis, our present study, suggests that the use of an MLC leaf width of 2.5 mm via the noncoplanar VMAT and 3D-DCA techniques provides improvement in terms of dose gradient for small volumes, over those results obtained with an MLC leaf width of 5 mm. The 3D-DCA does also benefit from MLC leaf widths of a smaller size, mainly in terms of conformity.     

Plan evaluation indices: A journey of evolution

AimA systemic review and analysis of evolution journey of indices, such as conformity index (CI), homogeneity index (HI) and gradient index (GI), described in the literature.BackgroundModern radiotherapy techniques like VMAT, SRS and SBRT produce highly conformal plans and provide better critical structure and normal tissue sparing. These treatment techniques can generate a number of competitive plans for the same patients with different dose distributions. Therefore, indices like CI, HI and GI serve as complementary tools in addition to visual slice by slice isodose verification while plan evaluation. Reliability and accuracy of these indices have been tested in the past and found shortcomings and benefits when compared to one another.Material and methodsPotentially relevant studies published after 1993 were identified through a pubmed and web of science search using words “conformity index”, “Homogeneity index”, “Gradient index”,” Stereotactic radiosurgery”,” stereotactic Body radiotherapy” “complexity metrics” and “plan evaluation index”. Combinations of words “plan evaluation index conformity index” were also searched as were bibliographies of downloaded papers.Results and conclusionsMathematical definitions of plan evaluation indices modified with time. CI definitions presented by various authors tested at their own and could not be generalized. Those mathematical definitions of CI which take into account OAR sparing grant more confidence in plan evaluation. Gradient index emerged as a significant plan evaluation index in addition to CI whereas homogeneity index losing its credibility. Biological index base plan evaluation is becoming popular and may replace or alter the role of dosimetrical indices.     

The effect of altered fractionation schedule on the spinal cord response: radiobiological considerations

Increased fractionation spares late reacting normal tissues more than acute reacting normal tissues. A linear quadratic model is valid from large dose per fraction down to dose per fraction of 2 Gy. Experimental studies on animals and clinical studies on the spinal cord tolerance have shown incidences of myelopathy at doses lower than 50 Gy. The α/β value of the linear quadratic model have been lower for low doses per fraction, indicating a sparing effect of altered fractionation for spinal cord myelitis. Animal data, clinical and radiobiological explanations suggest limitation of the radiobiological models. Further data suggest that one must not assume the spinal cord to have a greater tolerance at doses per fraction below the conventional dose per fraction of 2 Gy.     

Radiation dose to the fetus during CyberKnife radiosurgery for a brain tumor in pregnancy

PurposePregnancy during radiosurgery is extremely rare in clinical practice. We report fetal dose results during CyberKnife radiosurgery for a brain tumor in pregnancy.Methods and materialsA 26 year old pregnant woman with a rapidly growing deep-seated grade-III glioma was treated during the third trimester of gestation using CyberKnife. Ultrasound imaging was used to determine the position of the embryo prior to treatment. A dose of 1400 cGy was prescribed aiming to control tumor growth until delivery of the child. Prior to radiosurgery, the treatment was simulated on an anthropomorphic phantom. Radiation dose to the embryo was measured using a Farmer chamber and EBT3 films.ResultsFetal doses of 4.4 cGy and 4.1 cGy were measured for the embryo's head and legs, lying at 56 cm and 72 cm from the isocenter, respectively, using the Farmer chamber situated at 8.5 cm depth beneath the phantom surface. Dose results of 4.4 cGy, 3.5 cGy and 2.0 cGy were measured with the films situated at depths of 6.5 cm, 9.5 cm and 14.5 cm, respectively. An average dose of 4.2 cGy to the fetus was derived from the above values. A corresponding dose of 3.2 cGy was also calculated based on results obtained using EBT3 films situated upon the patient skin.ConclusionsThe measured fetal doses are below the threshold of 10 cGy for congenital malformations, mental and growth retardation effects. The radiogenic cancer risk to the live-born embryo was estimated less than 0.3% over the normal incidence. The treatment was administered successfully, allowing the patient to deliver a healthy child.