Epidemiological profile and clinico-pathological features of pediatric gynecological cancers at Moi Teaching & Referral Hospital, Kenya

Background: The main pediatric (0–18 years) gynecologic cancers include stromal carcinomas (juvenile granulosa cell tumors and Sertoli-Leydig cell tumors), genital rhabdomyosarcomas and ovarian germ cell. Outcomes depend on time of diagnosis, stage, tumor type and treatment which can have long-term effects on the reproductive career of these patients. This study seeks to analyze the trends in clinical-pathologic presentation, treatment and outcomes in the cases seen at our facility. This is the first paper identifying these cancers published from sub-Saharan Africa. Method: Retrospective review of clinico-pathologic profiles and treatment outcomes of pediatric gynecologic oncology patients managed at MTRH between 2010 and 2020. Data was abstracted from gynecologic oncology database and medical charts. Results: Records of 40 patients were analyzed. Most, (92.5%, 37/40) of the patients were between 10 and 18 years. Ovarian germ cell tumors were the leading histological diagnosis in 72.5% (29/40) of the patients; with dysgerminomas being the commonest subtype seen in 12 of the 37 patients (32.4%). The patients received platinum-based chemotherapy in 70% of cases (28/40). There were 14 deaths among the 40 patients (35%) Conclusion: Surgery remains the main stay of treatment and fertility-sparing surgery with or without adjuvant platinum-based chemotherapy are the standard of care with excellent prognosis following early detection and treatment initiation. LMICs face several challenges in access to quality care and that affects survival of these patients. Due to its commonality, ovarian germ cell cancers warrant a high index of suspicion amongst primary care providers attending to adnexal masses in this age group

An international multi-center investigation on the accuracy of radionuclide calibrators in nuclear medicine theragnostics

Background: Personalized molecular radiotherapy based on theragnostics requires accurate quantification of the amount of radiopharmaceutical activity administered to patients both in diagnostic and therapeutic applications. This international multi-center study aims to investigate the clinical measurement accuracy of radionuclide calibrators for 7 radionuclides used in theragnostics: 99mTc, 111In, 123I, 124I, 131I, 177Lu, and 90Y. Methods: In total, 32 radionuclide calibrators from 8 hospitals located in the Netherlands, Belgium, and Germany were tested. For each radio

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer

Dual-energy X-ray absorptiometry of lumbar vertebrae: Relative contribution of body and posterior elements and accuracy in relation with neutron activation analysis

The bone mineral content of 34 lumbar vertebrae obtained from ten cadavers (three men, seven women; age 61-88 years) was measured using a pulsed source dual-energy X-ray absorptiometry (DEXA) apparatus. Scanning was performed in the frontal projection and was repeated on the vertebral bodies obtained after removal of the posterior elements of the vertebrae. Subsequently a nondestructive neutron activation analysis (NAA) was performed. The mineral content of the vertebral bodies was found to represent (mean, SEM) 53.0% (1.9%) of the content of the whole vertebrae. The mineral content of the vertebral bodies assessed with NAA (BMC NAA) and with DEXA (BMC DEXA) showed a high correlation: BMC NAAA = (1.016 × BMC DEXA) + 0.990 r = 0.949 (p < 0.001). We conclude that the mineral content of lumbar vertebral bodies can be accurately measured in vitro in a water environment by DEXA and that the mean contribution of the posterior elements of the vertebra to the calcium hydroxyapatite content of whole vertebrae measured in the frontal projection is as high as 47.0%. © 1992.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Is there value to sub-specialty training in sub-Saharan Africa?

Over the past three decades, Africa has focused on combatting infectious diseases, such as tuberculosis, malaria, and HIV/ AIDS. As treatment strategies for infectious diseases have improved over time, life expectancy has increased, shifting the burden to chronic diseases, such as cancer. The WHO has now identified non-communicable diseases, including cancer, as the new epidemic in sub-Saharan Africa1. Cancer incidence and mortality are increasing rapidly in low and middle-income countries (LMIC) as compared to high-income countries. By 2020, it is predicted that 70% of all new cancers worldwide will occur in LMIC2. In 2012 850 000 new cancers were diagnosed in Africa, and over one million new cancers are predicted on the continent by 20202–4. Developing effective strategies to prevent, detect and treat this growing number of cancer cases poses a great challenge. There is an ongoing lack of resources, and little awareness of the need among policymakers and the general public. In addition, there is a severe shortage of health care personnel in sub-Sharan Africa5–7. With limited resources and a growing need to treat complex malignancies, is it feasible for LMIC to train subspecialists in oncology

Quality control of micro-computed tomography systems

The rapid proliferation of micro-computed tomography (micro-CT) scanners in preclinical small animal studies has created a need for a method on scanner performance evaluation and scan parameter optimisation. The purpose of this study was to investigate the performance of the scanner with a dedicated micro-CT phantom. The phantom was developed with different independent sections that allow for measurement of major scanner characteristics such as uniformity, linearity, contrast response, dosimetry and resolution. The results of a thorough investigation are discussed

Size of cortical bone and relationship to bone mineral density assessed by quantitative computed tomography image segmentation

RATIONALE AND OBJECTIVES. The accuracy of the measurement of the size of cortical bone on computed tomography (CT) images of human vertebrae was evaluated using an automated contour detection and segmentation procedure. METHODS. Forty human lumbar vertebrae were scanned using 8-mm slices and an automated detection for definition of trabecular and cortical region of interest. The vertebrae were embedded in a polyester resin and 8-mm-thick midvertebral specimens were excised using a diamond circular saw. Contact radiographs of these specimens were performed and, after photograph magnification, the cortical area was measured using computerized planimetry. RESULTS. Cortical area measured on CT images was highly correlated with the area measured by planimetry on the specimens (r =.91; P <.001) with, however, a systematic overestimation. A significant relationship was found between density and width of the cortex (r =.56; P <.001). CONCLUSIONS. Computed tomography is able to assess the size of cortical bone in human vertebrae, but a threshold detection algorithm, as used in the current study, is not adequate to obtain the precise anatomic dimensions. © 1993, J.B. Lippincott Company.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Mineral content of vertebral trabecular bone: Accuracy of dual energy quantitative computed tomography evaluated against neutron activation analysis and flame atomic absorption spectrometry

The goal of this study was to evaluate the accuracy of preprocessing dual energy quantitative computed tomography (QCT) for assessment of trabecular bone mineral content (BMC) in lumbar vertebrae. The BMC of 49 lumbar vertebrae taken from 16 cadavers was measured using dual energy QCT with advanced software and hardware capabilities, including an automated definition of the trabecular region of interest (ROI). The midvertebral part of each vertebral body was embedded in a polyester resin and, subsequently, an experimental ROI was cut out using a Scanjet image transmission procedure and a computer-assisted milling machine in order to mimic the ROI defined on QCT. After low temperature ashing, the experimental ROIs reduced to a bone powder were submitted to either nondestructive neutron activation analysis (n = 49) or to flame atomic absorption spectrometry (n = 45). BMC obtained with neutron activation analysis was closely related (r = 0.896) to that derived from atomic absorption spectrometry, taken as the gold standard, with, however, a slight overestimation. BMC values measured by QCT were highly correlated with those assessed using the two reference methods, all correlation coefficients being > 0.841. The standard errors of the estimate ranged 47.4-58.9 mg calcium hydroxyapatite in the regressions of BMC obtained with reference methods against BMC assessed by single energy QCT, 47.1-51.9 in the regressions involving dual energy QCT. We conclude that the trabecular BMC of lumbar vertebrae can be accurately measured by QCT and that the superiority in accuracy of dual energy is moderate, which is possibly a characteristic of the preprocessing method. © 1994.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

First steps towards online Personal Dosimetry Using Computational Methods in Interventional Radiology: operator’s position tracking and simulation input generation

peer reviewedInterventional radiologists/cardiologists are repeatedly exposed to low radiation doses which makes them the group of the highest occupational exposure and put them at high risk of stochastic effects. Routine monitoring of staff is usually performed by means of passive dosimeters. However, current personal dosimeters are subject to large uncertainties, especially in non-homogeneous fields, like those found in interventional cardiology (IC). Within the PODIUM (Personal Online DosImetry Using computational Methods) research project, a user-friendly tool was developed based on MCNP code to calculate doses to the staff in IC. The application uses both the data of motion tracking system to generate the position of the operator and the data from the Radiation Dose Structure Report (RDSR) from the imaging device to generate time-dependent parameters of the radiation source. The results of the first clinical validation of the system show a difference of about 50% between simulated Hp(10) with MCNP and measured Hp(10) with electronic personal dosimeter worn above the lead apron.Introduction With this work we present an innovative system for calculating occupational doses, as it is now being developed within the PODIUM (Personal Online DosImetry Using computational Methods) project. Individual monitoring of workers is essential to follow up regulatory dose limits and to apply the ALARA principle. However, current personal dosimeters are subject to large uncertainties, especially in non-homogeneous fields, like those found interventional radiology/cardiology. Workers in these fields also need to wear several dosimeters (extremity, eye lens, above/below apron), which causes practical problems. As the capabilities of computational methods are increasing exponentially, it will become feasible to use pure computations to calculate doses in place of physical dosimeters. Methods In our concept system, operational and protection quantities are calculated by fast Monte Carlo methods. Our dose calculation accounts for the real radiation field (including fluence, energy and angular distributions) and for the relative position of different body parts of the worker. The real movements of exposed workers are captured using depth cameras. This information is translated to a flexible anthropomorphic phantom, and then in Monte-Carlo simulations. For the moment this is done off-line, after the procedure is finished, and the parameters of the procedure are collected. Results For validating our system, we performed tests in interventional radiology (IR) rooms. In total, we followed 15 procedures in Cath-labs at UZ-VUB and CHU- Liège. An accurate analysis of the staff position was performed, and as a first step, we compared simulated Hp(10) and measured Hp(10) with electronic personal dosimeter (EPD) during an angiography procedure for some of these procedures. The results showed good agreement between the calculated doses and the ones measured by the EPD dosimeter. Conclusions With this work, we show that simulating worker doses based on tracking systems and flexible phantoms is possible. This method has big advantages in interventional radiology workplaces where the fields are non-homogeneous and doses to staff can be relatively high. This method can also help in ALARA applications and for education and training.PODIUM: Personal Online DosImetry Using computational Method

Development and Validation of Online Personal Dosimetry Application Using Computational Method for Interventional Cardiology

Introduction Interventional cardiologists are often occupationally exposed to low radiation doses which put them at risk of stochastic radiation induced detriments. Therefore, individual monitoring of medical staff is essential to follow up regulatory dose limits and to apply the ALARA principle. However, current personal dosimeters are subject to large uncertainties, especially in non-homogeneous fields, like those found interventional radiology/cardiology. In these workplaces, medical staff should wear several dosimeters (extremity, eye lens, above/below apron) for a proper monitoring. However, the use of multiple dosimeters is unpractical, and in some cases it could hinder the work of the physicians (like in the case of finger dosimeters). As the capabilities of computational methods are increasing exponentially, it will become feasible to use pure computations to calculate doses in place of physical dosimeters. With this work, we present the current state of development of an innovative tool for calculating occupational doses using Monte-Carlo methods. The system is being developed within the PODIUM (Personal Online DosImetry Using computational Methods) research project. Materials & Methods In typical interventional radiology/cardiology scenarios, operators are exposed to non-homogeneous scatter radiation field coming from the body of the patient. The anisotropy is higher while working close by to the patient for performing manipulations. The two main inputs to our computational dosimetry system are: a) the spatiotemporal distribution of the scattered radiation field, including its intensity, its energy and its angular distributions; b) the relative position and pose of the operator in the scatter field. 1. Radiation field parameters. The scatter radiation is dependent on a number of factors such as: primary beam intensity, beam projection angle and patient thickness. Acquiring information about the primary beam and the patient can help reproducing the scatter field computationally. Imaging parameters includes kVp, filtration, collimation and beam projection are used to simulate the primary beam and its scattered field in Monte-Carlo simulations. At this stage, such information is obtained from a summary dose report after each procedure. The measured dose-area product (DAP) value allows to normalize the simulated relative doses (eV/g per particle) to the equivalent absolute dose units. 2. Operator motion tracking. The main input to compute doses to operators is the position and pose of the body of the operator relative to the X-ray beam and to the patient. Our system provides an indoor tracking system for tracking the position and the posture of the workers. The system is constituted by a Microsoft Kinect v2 Time-Of-Flight (TOF) camera and by an acquisition software package. The body skeleton information provided by the tracking system is then used to position a phantom. At the current stage, the system represents a proof-of-concept and calculations are done off-line, after the procedure is finished, and the parameters of the procedure are collected. For validating our system, we performed tests in two interventional radiology (IR) rooms. In total, we followed 15 procedures in Cath-labs at UZ-VUB and CHU- ULiège hospitals. The Monte Carlo N-particle code (MCNPX 2.7) code [1] is used in our method for modelling and dosimetry calculations. The body skeleton information of the main operator provided by the tracking system is used to estimate the position of a dosimeter on the chest level in the simulations. Results An accurate analysis of the staff position was performed, and as a first step, we compared simulated Hp(10) with MCNP and measured Hp(10) with electronic personal dosimeter (EPD) Mk2.3 from Thermo Fisher Scientific worn above the lead apron during an angiography procedure for some of these procedures. The results showed good agreement with less than 5% difference between the calculated doses and the ones measured by the EPD dosimeter. The differences found in our simulations are easily explained by the uncertainties of the EPD dosemeter. In fact, the study performed by Clairand et al. [2] showed that the EPD Mk2.3 has a variation on the response within 30-40% due to the energy and angular response with the effect of the pulse frequency of the x-ray beam in interventional radiology fields. In addition, simulations provided extra information about the eye lens dose Hp(3) to the operator during one procedure which shows the high spread of the ratio Hp(3)/Hp(10) between 0.48 to 1.75 for different beam projections due to field inhomogeneity. Conclusions and future work With this work, we show that simulating worker doses based on tracking systems and flexible phantoms in Monte-Carlo codes is possible. This method has big advantages in interventional radiology workplaces where the radiation fields are non-homogeneous and doses to staff can be relatively high. This method can also help for the application of the ALARA principle and for education and training of medical staff. For the future, we will transfer the skeletal data to the Realistic Anthropomorphic Flexible computational phantom [3] in Monte-Carlo simulation to calculate organ doses. References [1] D.B. Pelowitz, Ed., "MCNPX User’s Manual Version 2.7.0" LA-CP-11-00438 (2011). [2] Clairand et al. “Use of active personal dosemeters in interventional radiology and cardiology: Tests in laboratory conditions and recommendations - ORAMED project”, Radiation Measurements, Volume 46, Issue 11, (2011). [3] Lombardo et al. “Development and validation of the realistic anthropomorphic flexible (RAF) phantom”, Health Physics, 114:489–499, 05 (2018). Acknowledgements This project is funded by the CONCERT - European Joint Programme for the Integration of Radiation Protection Research 2014-2018 under grant agreement No. 662287.PODIUM: Personal Online DosImetry Using computational Method