A review on fetal dose in Radiotherapy: A historical to contemporary perspective.

This paper aims to review on fetal dose in radiotherapy and extends and updates on a previous work1 to include proton therapy. Out-of-field doses, which are the doses received by regions outside of the treatment field, are unavoidable regardless of the treatment modalities used during radiotherapy. In the case of pregnant patients, fetal dose is a major concern as it has long been recognized that fetuses exposed to radiation have a higher probability of suffering from adverse effects such as anatomical malformations and even fetal death, especially when the 0.1Gy threshold is exceeded. In spite of the low occurrence of cancer during pregnancy, the radiotherapy team should be equipped with the necessary knowledge to deal with fetal dose. This is crucial so as to ensure that the fetus is adequately protected while not compromising the patient treatment outcomes. In this review paper, various aspects of fetal dose will be discussed ranging from biological, clinical to the physics aspects. Other than fetal dose resulting from conventional photon therapy, this paper will also extend the discussion to modern treatment modalities and techniques, namely proton therapy and image-guided radiotherapy, all of which have seen a significant increase in use in current radiotherapy. This review is expected to provide readers with a comprehensive understanding of fetal dose in radiotherapy, and to be fully aware of the steps to be taken in providing radiotherapy for pregnant patients.

A software tool for organ-specific second cancer risk assessment from exposure to therapeutic doses.

The aim of this study was the development of a software tool (SCRcalc) for the automatic estimation of the patient- and organ-specific cancer risk due to radiotherapy. SCRcalc was developed using the Python 3.8.7 programming language. It incorporates equations and parameters of mechanistic models for the calculation of the organ equivalent dose (OED), the excess absolute risk (EA R) and the lifetime attributable risk (LA R) of carcinogenesis for various organs due to radiotherapy. Data from differential dose-volume histograms, as defined by a treatment planning system, could be automatically inserted into the program. Eighteen different cancer risk estimates for various organs were performed of patients subjected to radiation therapy with conventional and modulated techniques. These software estimates were compared with manual calculations. SCRcalc was developed as a standalone executable program without any dependencies. It enables direct estimations of the OED and LAR for various organs at risk. An important aspect of the software is that it does not require pre-processing of the DVH data. No differences were found between the SCRcalc results and those derived from manual calculations. The newly developed software offers the possibility to medical physicists and radiation oncologists to directly estimate the probability of radiotherapy-induced secondary malignancies for various organs at risk.

Extraocular Muscle Volumetry for Assessment of Thyroid Eye Disease.

BACKGROUND: In this study we evaluate the diagnostic accuracy of extraocular muscle volumetry in detecting thyroid eye disease and to compare the results with simple measurements of maximal medial rectus (MR) diameter. METHODS: Cross-sectional study that included 47 eyes of 47 patients with thyroid eye disease and 47 healthy controls. Patients underwent slitlamp examination and imaging consisting of computed tomography scans. Image segmentation and volume measurements were performed by 2 independent researchers. Intraobserver and interobserver reliability testing was also conducted. RESULTS: Total extraocular muscle volume was 7.31 ± 1.88 cm3 and medial volume was 2.38 ± 0.73 cm3 in the study group. In this group, the maximum measured diameter of the MR was 6.67 ± 0.35 mm. MR volume was statistically associated with maximum MR diameter (r = 9.78; P < 0.001). Both MR volume and maximum MR diameter measurements showed good predictive efficacy as shown using receiver operator characteristic curve analysis. CONCLUSIONS: Complications of thyroid eye disease are often sight threatening, and timely diagnosis is crucial for the management of the entity and its sequelae. The results of this study imply that simple measurements of maximum MR diameter are sensitive enough to establish diagnosis.

Orbital volume measurements from magnetic resonance images using the techniques of manual planimetry and stereology.

INTRODUCTION: Current volume measurement techniques, for the orbit, are time-consuming and involve complex assessments, which prevents their routine clinical use. In this study, we evaluate the applicability and efficacy of stereology and planimetry in orbital volume measurements using magnetic resonance imaging (MRI). MATERIALS AND METHODS: Prospective imaging study using MRI. Sheep craniums and human subjects were evaluated. Water-filling measurements were performed in animal skulls, as the standard validation technique. Planimetry and stereology techniques were used in each dataset. Intraobserver and interobserver reliability testing were applied. RESULTS: In stereology customization, 1/6 systematic sampling scheme was determined as optimal with acceptable coefficient of error (3.09%) and low measurement time (1.2 min). In sheep craniums, the mean volume measured by water displacement, planimetry, and stereology was 17.81 ± 0.59 cm3, 18.53 ± 0.24 cm3, and 19.19 ± 0.17 cm3, respectively. Planimetric and stereological methods were highly correlated (r = 0.94; P ≈ 0.001). The mean difference of the orbital volume using planimetry and stereology was 0.316 ± 0.168 cm3. In human subjects, using stereology, the mean orbital volume was found to be 19.62 ± 0.2 cm3 with a CE of 3.91 ± 0.15%. CONCLUSIONS: The optimized stereological method was found superior to manual planimetry in terms of user effort and time spent. Stereology sampling of 1/6 was successfully applied in human subjects and showed strong correlation with manual planimetry. However, optimized stereological method tended to overestimate the orbital volume by about 1 cc, a considerable limitation to be taken in clinical practice.

Ex vivo orbital volumetry using stereology and CT imaging: A comparison with manual planimetry.

OBJECTIVES: To evaluate the applicability of stereology and planimetry in orbital volume measurements using computed tomography (CT) and to compare the results between the two measurements. METHODS: Experimental study using sheep craniums for CT imaging. Water filling measurements were performed, as the validation technique. Quantification techniques were also evaluated in five human subjects. To examine the proportion of agreement among measurements, we tested intra- and inter-observer agreement. RESULTS: For stereology customization, a 1/8 systematic sampling scheme was considered as optimal; this resulted in a low coefficient of error (2.59 %) and low measurement time (1.9 mins). In sheep craniums, mean volume measured by water displacement, planimetry and stereology was 17.81 ± 0.59 cm3, 17.87 ± 0.68 cm3 and 17.54 ± 0.49 cm3, respectively. Total volumes, obtained by stereology, were highly correlated with the water-filling method (r=0.893; p = 0.001) and a paired t-test showed significant difference between methods (t=3.047; p = 0.014). Planimetry results displayed a high correlation with the water-filling method (r=0.957; p ≈ 0.001) but no statistically significant difference was found (p = 0.154). Mean difference using planimetry and stereology was 0.332 ± 0.322 cm3. In human subjects, using stereology, the estimated volume ranged between 18.57 cm3 and 19.27 cm3, and the mean orbital volume was 19.05 ± 0.50 cm3 with CE=3.75 ± 0.16 %. Mean measure time was 2.1 ± 0.1 mins. CONCLUSIONS: Stereological measurements were superior to manual planimetry in terms of user effort and time spent. Stereology sampling of 1/8 was successfully applied in human subjects and yielded a strong correlation with manual planimetry. KEY POINTS: • Stereology can be applied to measure the orbital volume using computed tomography. • Stereological measurements display high correlation with gold standard planimetry and combine low coefficient of error (2.59%) with low measurement time (1.9 min). • Stereology is superior in terms of user effort and time spent.

Quantification of effective orbital volume and its association with axial length of the eye. A 3D-MRI study.

Objective: To measure the effective orbital volume (EOV) from magnetic resonance images, and investigate its relationship with axial length (AL) in those parameters. Methods: Cross-sectional, 3D-MRI study. 54 eyes of 54 patients (25 males) were included in this work. Patient weight, height and head circumference were also measured. Orbital and eyeball volumes were calculated after image segmentation. The difference between those values volume was assessed, estimating the EOV for each eye. Results: Mean eyeball volume was 7.83 ± 2.27 mm3, mean orbital volume 26.81 ± 0.59 mm3 and EOV 21.64 ± 0.19 mm3. The orbital volume was significantly higher in the male group (Wilcoxon signed-rank tests Z=-1.51, p<0.001; Z=-3.57, p<0.001 respectively). EOV was significantly correlated with AL in both males (r=-0.71, p<0.001) and females (r=-0.73, p<0.001), whereas it was also significantly associated with patient height (r=0.261, p=0.03). Associations between EOV and other age, axial and anthropometric characteristics were not statistically significant. Conclusions: Findings of this study could be of valuable importance in various clinical situations in which quantification of orbital volume is needed, such as orbital decompression in Graves' orbitopathy, volume restoration in orbital fractures or other orbital reconstructive surgery. In surgical interventions, clinical relationships should be carefully taken under consideration to avoid iatrogenic injury. Abbreviations: EOV = Effective orbital volume, AL = Axial length, ROI = Region of interest.

Estimation of Morphological Characteristics in Asymmetrical Myopic Posterior Staphyloma using Optical Coherence Tomography.

PURPOSE: Posterior staphyloma is an ocular complication associated with high myopia and reflects degenerative changes on the sclera. Its morphology is associated with chorioretinal atrophy and myopic maculopathy. The purpose of this study was to validate the efficacy of optical coherence tomography (OCT) in providing a simple estimation of the staphyloma pattern. MATERIALS AND METHODS: Observational case-series study of high myopic patients with posterior staphylomas. Patients were examined using the star scan pattern OCT in different radial planes. Three-dimensional (3D) magnetic resonance tomography was also performed to visualize the anatomical characteristics of the posterior pole. 3D-segmentation and curvature analysis were also performed. RESULTS: Eight patients were totally enrolled in this pilot study. Our study pool consisted of 2 wide macular staphylomas, 2 narrow macular staphylomas, and 4 barrel-shaped staphylomas. Our preliminary results revealed that patients displayed mirror-image distortion in the steeper staphyloma axis. In the barrel-shaped subtype, no image distortion was displayed in any plane. CONCLUSION: We estimated the axis of the smaller base curvature by noting the distortion pattern in the different radial axis. The recognition of pathologic axial myopia is important since there is a risk of permanent vision loss from vision to threatening sequelae.

Calculation of organ doses from breast cancer radiotherapy: a Monte Carlo study.

The current study aimed to: a) utilize Monte Carlo simulation methods for the assessment of radiation doses imparted to all organs at risk to develop secondary radiation induced cancer, for patients undergoing radiotherapy for breast cancer; and b) evaluate the effect of breast size on dose to organs outside the irradiation field. A simulated linear accelerator model was generated. The in-field accuracy of the simulated photon beam properties was verified against percentage depth dose (PDD) and dose profile measurements on an actual water phantom. Off-axis dose calculations were verified with thermoluminescent dosimetry (TLD) measurements on a humanoid physical phantom. An anthropomorphic mathematical phantom was used to simulate breast cancer radiotherapy with medial and lateral fields. The effect of breast size on the calculated organ dose was investigated. Local differences between measured and calculated PDDs and dose profiles did not exceed 2% for the points at depths beyond the depth of maximum dose and the plateau region of the profile, respectively. For the penumbral regions of the dose profiles, the distance to agreement (DTA) did not exceed 2 mm. The mean difference between calculated out-of-field doses and TLD measurements was 11.4% ± 5.9%. The calculated doses to peripheral organs ranged from 2.32 cGy up to 161.41 cGy depending on breast size and thus the field dimensions applied, as well as the proximity of the organs to the primary beam. An increase to the therapeutic field area by 50% to account for the large breast led to a mean organ dose elevation by up to 85.2% for lateral exposure. The contralateral breast dose ranged between 1.4% and 1.6% of the prescribed dose to the tumor. Breast size affects dose deposition substantially.

Dependence of computed tomography volume measurements upon section thickness: an application to human dry skulls.

Estimation of intracranial volume (ICV) using computed tomography (CT) scans has previously been described. However, we were not able to identify a gold standard study that analyzed the effect of section thickness on the estimation of ICV. Therefore, we conducted the present study, scanning five dry skulls in the coronal and axial planes using a multislice CT machine (Toshiba TSX-101A, Aquilion 16 Slice, Tochigi, Japan). Consecutive sections of variable thicknesses of 2, 3, 5, 7, and 10 mm, respectively, were used to estimate ICV by means of the planimetry method of the Cavalieri principle. All estimations were done by the same observer. However, the estimated volumes did not concur with the actual volumes of the skulls as determined by the fluid displacement technique (P < 0.05). In fact, results revealed that the section thicknesses created over- or under-projection effects for the estimated volumes. The results were analyzed to reveal the deviation principles of the estimates based on section thickness. Prediction formulas were calculated to estimate the deviation percentage of the ICV depending on section thickness and section plane. Ultimately, the results showed that the effect of section thickness on ICV estimates could not be overlooked, but that the values obtained could be corrected using the proposed prediction formulas presented in this study.

Radiation dose to laterally transposed ovaries during external beam radiotherapy for cervical cancer.

The purpose of this study was to estimate the radiation dose to laterally transposed ovaries from external beam radiotherapy for cervical cancer. Dose measurements were performed in a modified humanoid phantom using a 6 MV photon beam. The dependence of the ovarian dose upon the field size, the distance from the primary irradiation field and the presence of wedges or gonadal shielding was determined. For a tumor dose of 45 Gy, ovarian dose was 0.88-8.51 Gy depending on the field size employed and the location of the transposed ovary in respect to the treatment field. Positioning of 7 cm thick shielding reduced the dose to ovary by less than 19%. The use of wedges increased the ovarian dose by a factor up to 1.5. Accurate radiographic localization of the ovaries allows the use of the presented dosimetric results to obtain a reasonable prediction of the ovarian dose.

Phase I/II trial of external irradiation plus medium-dose brachytherapy given concurrently to liposomal doxorubicin and cisplatin for advanced uterine cervix carcinoma.

BACKGROUND AND PURPOSE: Although the standard of care for patients with locally advanced uterine cervix carcinoma is cisplatin-(CDDP-)based chemotherapy and irradiation (RT), the optimal regimen remains to be elucidated. A phase I/II study was conducted to evaluate the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of liposomal doxorubicin (Caelyx) combined with CDDP and RT for cervical cancer. PATIENTS AND METHODS: 24 patients with stage IIB-IVA were enrolled (Table 1). They all received external RT (up to 50.4 Gy) and two medium-dose rate (MDR) brachytherapy implants (20 Gy each at point A). The Caelyx starting dose of 7 mg/m2/week was increased in 5-mg/m2 increments to two levels. The standard dose of CDDP was 20-25 mg/m2/week. RESULTS: Concurrent chemoradiation (CCRT) sequelae and the DLTs (grade 3 myelotoxicity and grade 3 proctitis in five patients treated at the 17 mg/m2/week Caelyx dose level) are shown in Tables 2, 3, 4, and 5. After a median follow-up time of 17.2 months (range 4-36 months), four patients had died, 15 showed no evidence of progressive disease, and five (20.8%, 95% confidence interval [CI]: 12.5-29.1%) were alive with relapse (Figure 1). There were seven complete (29.1%, 95% CI: 19.8-38.4%) and 17 partial clinical responses (95% CI: 61.1-80.1%). The median progression-free survival was 10.4 months. Causes of death were local regional failure with or without paraaortic node relapse combined with distant metastases (Table 6). CONCLUSION: The MTD of Caelyx given concurrently with CDDP and RT was determined at the 12 mg/m2/week dose level. The above CCRT schema is a well-tolerated regimen, easy to administer in ambulatory patients, and results appear promising.

Stereology versus planimetry to estimate the volume of malignant liver lesions on MR imaging.

Liver tumor volume measurements are clinically useful in patients undergoing cancer treatment. The techniques of planimetry and stereology were applied for this purpose on magnetic resonance (MR) imaging. Fifty-eight malignant liver lesions were depicted on MR images in 20 consecutive patients. The volume of all lesions was estimated using stereology technique, based on point counting. Stereological tumor volume estimations were compared with those determined by manual planimetry. The repeatability of both techniques was assessed. Tumor volumes estimated by the two techniques were highly correlated (r = 0.98, p < 0.0001). The 95% limits of agreement showed that the stereological volume estimations may differ from the planimetric assessments by less than 23%. Both techniques presented comparable intra- and interobserver variability. The planimetry was 1.5 times faster than the stereology. Both volumetric techniques may provide reliable and reproducible liver tumor volume estimations. The planimetry may be the method of choice because of its superior speed.

Radiation dose and cancer risk to children undergoing skull radiography.

BACKGROUND: Limited data exist in the literature concerning the patient-effective dose from paediatric skull radiography. No information has been provided regarding organ doses, patient dose during PA skull projection, risk of cancer induction and dose to comforters, i.e. individuals supporting children during exposure. OBJECTIVE: To estimate patient-effective dose, organ doses, lifetime cancer mortality risk to children and radiation dose to comforters associated with skull radiography. MATERIALS AND METHODS: Data were collected from 136 paediatric examinations, including AP, PA and lateral skull radiographs. Entrance-surface dose (ESD) and dose to comforters were measured using thermoluminescent dosimeters. Patients were divided into the following age groups: 0.5-2, 3-7, 8-12 and 13-18 years. The patient-effective dose and corresponding organ doses were calculated using data from the NRPB and Monte Carlo techniques. The risk for fatal cancer induction was assessed using appropriate risk coefficients. RESULTS: For AP, PA and lateral skull radiography, effective dose ranges were 8.8-25.4, 8.2-27.3 and 8.4-22.7 microSv respectively, depending upon the age of the child. For each skull projection, the organs receiving doses above 10 microGy are presented. The number of fatal cancers was found to be less than or equal to 2 per 1 million children undergoing a skull radiograph. The mean radiation dose absorbed by the hands of comforters was 13.4 microGy. CONCLUSIONS: The current study provides detailed tabular and graphical data on ESD, effective dose, organ doses and lifetime cancer mortality risk to children associated with AP, PA and lateral skull projections at all patient ages.

Influence of initial electron beam parameters on Monte Carlo calculated absorbed dose distributions for radiotherapy photon beams.

Our aim in the present study was to investigate the effects of initial electron beam characteristics on Monte Carlo calculated absorbed dose distribution for a linac 6 MV photon beam. Moreover, the range of values of these parameters was derived, so that the resulted differences between measured and calculated doses were less than 1%. Mean energy, radial intensity distribution and energy spread of the initial electron beam, were studied. The method is based on absorbed dose comparisons of measured and calculated depth-dose and dose-profile curves. All comparisons were performed at 10.0 cm depth, in the umbral region for dose-profile and for depths past maximum for depth-dose curves. Depth-dose and dose-profile curves were considerably affected by the mean energy of electron beam, with dose profiles to be more sensitive on that parameter. The depth-dose curves were unaffected by the radial intensity of electron beam. In contrast, dose-profile curves were affected by the radial intensity of initial electron beam for a large field size. No influence was observed in dose-profile or depth-dose curves with respect to energy spread variations of electron beam. Conclusively, simulating the radiation source of a photon beam, two of the examined parameters (mean energy and radial intensity) of the electron beam should be tuned accurately, so that the resulting absorbed doses are within acceptable precision. The suggested method of evaluating these crucial but often poorly specified parameters may be of value in the Monte Carlo simulation of linear accelerator photon beams.

Stereological estimation of total intracranial volume on CT images.

This study aims to investigate the possibility of generating stereological estimations of total intracranial volume (TIV) on CT scans. The study group included 16 consecutive patients referred for a cranial CT examination. The TIV was estimated using the stereological point counting technique. Volume measurements were optimized by systematically sampling CT sections and by defining an optimum spacing between test points of the grid. The intraobserver and interobserver variability of the optimized volumetric technique was determined. Stereological TIV estimations were compared with the respective planimetric measurements. The application of a test grid with a point spacing of 2.4 cm on 6-8 systematically sampled CT sections provided TIV estimations with a coefficient of error of less than 5%. The intraobserver and interobserver coefficient of variation values were found to be 2.4 and 4.0%, respectively. The 95% limits of agreement between stereological and planimetric TIV measurements were equal to -91.4 and 103.4 cm3. The mean time (+/- SD) needed to obtain stereological TIV estimations was 2.9 +/- 0.6 min. The application of the optimized stereological technique on CT scans enables the efficient estimation of TIV.

Radiotherapy of Hodgkin's disease in early pregnancy: embryo dose measurements.

BACKGROUND AND PURPOSE: Limited information exists on the possibility of pregnant women undergoing radiotherapy for Hodgkin's disease in early pregnancy. The purpose of this study was to measure embryo dose resulting from treatment of supra-diaphragmatic Hodgkin's disease at the first trimester of gestation. MATERIALS AND METHODS: A humanoid phantom was used to simulate pregnancy at the first trimester of gestation. Embryo dose, was measured using three different field sizes that may be applied for local field irradiation in each of the regions of neck, axilla, neck-mediastinum and for mantle treatment. A shielding device consisting of 5 cm of lead was used to reduce the embryo dose. Dose measurements were carried out using thermoluminescent dosimeters. Phantom exposures were made with a 6 MV photon beam. RESULTS: Local field irradiation in the regions of neck or axilla always resulted in embryo doses below 10 cGy. For local field irradiation in the region of neck-mediastinum and for mantle treatment, the radiation dose to a shielded embryo was 2.8-18.6 and 4.2-24.5 cGy depending upon the distance from the field isocenter and the field size used, respectively. The corresponding dose for an unshielded embryo exceeded 10 cGy. All the above embryo doses were obtained for a tumor dose of 40 Gy. CONCLUSIONS: Local field irradiation in the regions of neck or axilla may be safely performed even without uterus shielding. For local field irradiation in the region of neck-mediastinum and for mantle radiotherapy, the extent of the irradiated area, the distance separating the embryo from the field isocenter and the tumor dose are the factors, determining whether the radiation dose to a shielded embryo may possibly be reduced below 10 cGy.

Radiation dose to conceptus resulting from tangential breast irradiation.

PURPOSE: To estimate the radiation dose to the conceptus resulting from tangential breast irradiation. METHODS AND MATERIALS: Conceptus radiation doses were measured in anthropomorphic phantoms simulating the geometry of a pregnant woman at the first, second, and third trimesters of gestation. Medial and lateral field irradiations were generated using a 6-MV X-ray beam. Dose measurements were performed with thermoluminescent dosimeters. RESULTS: For a treatment course delivering 50 Gy to the tumor, conceptus dose at the first trimester of gestation was found to be 2.1-7.6 cGy, depending on the field size used and the distance between conceptus and primary irradiation field. The corresponding dose ranges to the conceptus during the second and third trimesters of gestation were 2.2-24.6 cGy and 2.2-58.6 cGy, respectively. Dose data and formulas are presented to estimate conceptus dose for individual patients undergoing breast radiotherapy during the entire pregnancy. CONCLUSIONS: This study may be of value in the management of pregnant women needing tangential breast irradiation, because it provides the required information to estimate conceptus dose.

Comparison of two volumetric techniques for estimating liver volume using magnetic resonance imaging.

PURPOSE: To compare the conventional technique of manual planimetry with the point counting technique for estimating liver volume from magnetic resonance imaging (MRI) data. MATERIALS AND METHODS: This study comprised abdominal MR examinations of 38 consecutive patients. Evaluation of the images showed that liver size appeared normal in 27 patients and increased in 11. Liver volume was estimated using the techniques of planimetry and point counting. Both techniques were used in combination with the Cavalieri method of modern design stereology. A systematic slice sampling procedure was performed to estimate liver volumes using both volumetric techniques. The point counting technique was optimized by altering the point spacing of the grid. The agreement between the two techniques was found. Measurement repeatability of both volumetric techniques was also evaluated. RESULTS: Both techniques allowed the same degree of optimization through the procedure of systematic section sampling. The application of a point spacing of 2.5 cm reduced the time measurement by a factor of 3.5 in relation with the time needed with planimetry. An excellent agreement was observed between the two volumetric techniques with mean differences (+/-SD) of 2.4 +/- 41.6 cm(3) and 8.5 +/- 49.8 cm(3) for the patients presenting normal and increased liver sizes, respectively. Both techniques were highly reproducible. CONCLUSION: The point counting technique could be considered a more efficient approach than planimetry for estimating liver volume from MRI, due to its speed and simplicity.