Patient Dose Research Articles

A Population Pharmacokinetic Study to Evaluate Doxorubicin Exposure Across All Age Groups.

The effect of age on doxorubicin pharmacokinetics remains inconclusive, especially in patients at the extremes of the age spectrum. We developed a population pharmacokinetic model to further investigate the impact of age on the pharmacokinetics of doxorubicin. A three-compartment model, incorporating allometric scaling was developed to describe doxorubicin pharmacokinetics across all ages. First, the effect of age in young patients was investigated, by adding a maturation function on clearance (CL), the central compartment (V1) and peripheral compartments (V2 and V3). Second, the impact of ageing was investigated by adding a maximal effect (Emax) function on CL, V1, V2, and V3. To investigate the overall impact of age on doxorubicin exposure, various simulations were conducted. A total of 168 patients (age: 0.11-90 years) with 555 doxorubicin samples were included. The maturation function was relevant for V1 and V2 (13.1 and 23.7L, respectively), leading to an increase in V1 and V2 with increasing age. In contrast, adding an Emax function only impacted V3 (1063L), resulting in a decrease of V3 with age. Simulations showed no clinically relevant difference in the exposure of doxorubicin between age groups. A population pharmacokinetic model with data across the age range showed that age predominantly affected volumes of distribution of the central and peripheral compartments. These effects were not considered to be clinically relevant based on performed simulations. This supports the use of currently used doxorubicin dosages of 1 mg/kg for infants and toddlers <10 kg and body surface area-based dosing for other patients.

Effect of crystalloidsolution co-loading infusion rate on the dose requirements of prophylactic phenylephrine for preventing hypotension following combined spinal-epidural anesthesia for cesarean delivery.

Intravenous fluid administration and prophylactic vasopressor infusion are the primary methods for preventing spinal anesthesia-induced hypotension during cesarean delivery. However, evidence regarding the impact of different volumes of crystalloid solution on the phenylephrine infusion dosage for preventing this hypotension remains inconclusive. This study aimed to determine the effect of two IV fluid infusion rates (10 or 20 mL/kg/h) on phenylephrine requirement for preventing spinal anesthesia-induced hypotension. Eighty healthy parturients undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled. Participants were randomly assigned to receive either 10 mL/kg/h (group 10) or 20 mL/kg/h (group 20) of lactated Ringer's solution. The first patient in each group received 0.5µg/kg/min of phenylephrine infusion immediately after intrathecal injection. The phenylephrine dose in subsequent patients was adjusted by increments or decrements of 0.05µg/kg/min based on the previous patient's response. The ED50 of phenylephrine infusion for preventing spinal-induced hypotension for cesarean delivery was estimated using a modified up-down sequential analysis, with probit analysis applied as a backup sensitivity analysis. The ED50 values for preventing spinal anesthesia-induced hypotension were 0.30µg/kg/min (95% CI, 0.29-0.32µg/kg/min) for group 10, and 0.19µg/kg/min (95% CI, 0.16-0.22µg/kg/min) for group 20, respectively. The estimated relative potency for phenylephrine in group 10 compared to group 20 was 1.52 (95%CI, 1.24-1.97), showing a significant difference in the ED50 values between the two groups. This study found that a higher crystalloid co-loading rate significantly reduces prophylactic phenylephrine requirement for preventing spinal anesthesia induced hypotension. https://www.chictr.org.cn/showproj.html?proj=125918 (Trial number: ChiCTR2100048002).

Ciprofloxacin Dosage Optimization in Cystic Fibrosis Through Therapeutic Drug Monitoring

Background: Ciprofloxacin (CIP) is effective against many Gram-negative pathogens and penetrates well into respiratory secretions and pulmonary tissues, thus making it useful for treating respiratory infections in patients with cystic fibrosis (CF). Methods: A 13-year-old patient with severe CF and an acute respiratory exacerbation from multidrug-resistant Pseudomonas aeruginosa was treated with 700 mg of CIP every 8 hours. Bronchial secretions confirmed that P. aeruginosa was sensitive to high doses of CIP. Pharmacokinetic monitoring using 2 blood samples estimated the AUC24 at 50 hours*mg/L. This led to an increase in CIP dosage to 850 mg three time a day (TID), then to 1000 mg TID, and finally to 1200 mg every 6 hours. Results: CIP pharmacokinetics can vary significantly, particularly in patients with CF due to increased clearance, ultimately resulting in shorter half-lives and higher risks of therapeutic failure and resistance. Therapeutic drug monitoring helps when adjusting dosages to maintain effective blood concentrations. Conclusions: This case underscores the role of therapeutic drug monitoring in optimizing CIP dosing for patients with CF and highlights the necessity for close collaboration between clinicians and pharmacologists to ensure effective antibiotic exposure.

CTNI-81. PROPOSAL FOR A PHASE IB PILOT CLINICAL TRIAL TO STUDY SAFETY AND IMPROVING ANTI-NEOPLASTIC ADVERSE EFFECTS BY ADDITION OF NATURAL MARINE PRODUCT FUCOIDAN TO THE STANDARD THERAPY FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA (GBM)

Abstract INTRODUCTION GBM is the most aggressive primary brain tumor. Despite standard of care (SOC) with the Stupp protocol and tumor treating fields (TTFs), survival remains poor. In addition, SOC treatment is associated with 96% any adverse effects (AE) and 25% severe AEs (Chinot et al, NEJM 2014), which affects quality of life (QOL) and can lead to early treatment termination. Therefore, novel therapies are needed and minimization of chemoradiation-related AEs is crucial. Marine natural product, fucoidan, may have an important role in oncological management as tumor-directed therapy and as a protectant against chemoradiation-related AEs. Fucoidan is a seaweed-derived sulfated polysaccharide. Mounting evidence garnered from randomized clinical trials for colon, head and neck, and lung cancer patients suggests that fucoidan can improve certain AEs associated with chemoradiation. Furthermore, data gleaned from multiple studies have shown that fucoidan is tolerable with a good safety profile. HYPOTHESIS Fucoidan is safe in combination with chemoradiation and chemotherapy and improves treatment related AE profile. Fucoidan may improve survival outcome in GBM patients by augmenting cytotoxic effects, inhibiting angiogenesis, and improving the tolerability of SOC therapy. METHOD 12 newly diagnosed GBM patients will be enrolled. A Fucoidan-based product will be administered orally at the established dose for cancer patients daily with concurrent chemoradiation therapy and adjuvant chemotherapy over 6 months. Patients will be evaluated weekly to monthly for AEs and QOL scoring; laboratory and brain MRI monitoring will be performed per SOC guidelines. NK cell activity, proinflammatory cytokines, including interleukin (IL)-1β, will be measured. POTENTIAL OUTCOME This pilot study may establish a foundation for future larger randomized clinical trials to treat brain cancer more effectively by adding nature products.

CTNI-83. PROPOSAL FOR A PILOT PHASE 1B CLINICAL TRIAL WITH ADDITION OF NATURAL MARINE PRODUCT FUCOIDAN TO ANTI-NEOPLASTIC THERAPY FOR PATIENTS WITH RECURRENT GLIOBLASTOMA (RGBM) TO IMPROVE FATIGUE AND OTHER HEALTH-RELATED QUALITY OF LIFE (HRQOL) SYMPTOMS

Abstract BACKGROUND Recurrent Glioblastoma (rGBM) has poor outcome with limited treatment options. rGBM causes significant fatigue and other health-related quality of life (HRQOL) symptoms secondary to tumor progression and anti-neoplastic therapies. More than 80% of brain tumor patients were found to experience fatigue during anti-neoplastic therapy and the incidence of cancer related fatigue may reach 89-94% among patients with rGBM. Therefore, improvement of fatigue and HRQOL in rGBM patients are crucial. Marine natural product, fucoidan, available as health supplement in the US, was found to play important roles in oncological management as supportive therapy against cancer and chemoradiation-related adverse effects and as a potential anti-neoplastic therapy. Fucoidan is a seaweed-derived sulfated polysaccharide. Data resulted from randomized clinical trials for colon, head and neck, and lung cancer patients suggest that fucoidan can improve cancer and chemotherapy or chemoradiation therapy related negative symptoms. In addition, Tachikawa et al. reported &amp;gt;50% tumor regression and increased natural killer (NK) cell activity in sarcoma-transplanted mice treated with Fucoidan. In Vitro anticancer investigation found that Fucoidan fractions clearly suppressed the growth of GBM U-251MG cancer cells. Multiple studies have also shown that fucoidan is tolerable with a good safety profile. METHOD 18 rGBM patients will be enrolled. Fucoidan based product will be administered orally at established dose for cancer patients daily with anti-neoplastic therapy over 6 months. Patients will be evaluated monthly for AEs and HRQOL score; laboratory and brain MRI monitoring will be performed per SOC guidelines. NK cell activity will be measured. POTENTIAL OUTCOME Fucoidan is safe and has good tolerability in combination with anti-neoplastic therapy for rGBM and improves fatigue and other HRQOL symptoms by ameliorating tumor progression and treatment related negative impact. Fucoidan may also improve survival in rGBM patients by improving the tolerability of anti-tumor therapy, augmenting cytotoxic effects, and inhibiting angiogenesis.

Heterotopic Osteotomy for Intrathecal Baclofen Test Dose Administration in a Pediatric Patient With Spinal Fusion: A Technical Note.

Intrathecal baclofen (ITB) pumps are used for the treatment of pediatric movement disorders that are rapidly progressive or do not respond to medical management. An ITB test dose is indicated in patients who have mixed tone, when the family remains unconvinced, or when insurance companies require it. Test doses are typically delivered by lumbar puncture; however, lumbar puncture in patients with heterotopic ossification of the lumbar vertebrae after a previous spinal fusion is not possible. To our knowledge, we present the first technical note describing a heterotopic osteotomy to access the subarachnoid space for a complex ITB test dose in a pediatric patient with a spinal fusion. We present a 14-year-old woman with spastic, dystonic quadriplegic cerebral palsy, neuromuscular scoliosis, and previous T3-pelvis posterior spinal fusion. She continued to have significant dystonia and spasticity despite maximal medical management and was offered ITB therapy. A complex ITB test dose through heterotopic osteotomy was performed with excellent clinical results, and the patient will ultimately receive an ITB pump. Heterotopic ossification following spinal fusion is not a contraindication to an ITB test dose. A heterotopic osteotomy is a feasible surgical approach to administer an ITB test dose in these pediatric patients.

Nanomaterial-Based Electrochemical Sensors for the Detection of Pharmaceutical Drugs

The rapidly increasing human population has led to new biological and environmental challenges. These challenges, in turn, have contributed to the rapid growth of the pharmaceutical sector. Quality control in pharmaceutical manufacturing and drug delivery necessitates portable, sensitive, precise, and cost-effective devices to monitor patient dosing and assess pharmaceutical hazards. This study highlights the attributes and applications of the current nanomaterial-based sensors for drug detection, emphasizing the potential of these devices to advance the detection of bioactive molecules, thereby promoting human health and environmental protection on a large scale. Electrochemical sensors, in particular, have become invaluable in bioimaging, electrochemical analysis, and drug delivery due to their high specificity, selectivity, and stability across cycles. This review focuses on recent advancements in electrochemical devices for healthcare applications, detailing their production, analytical performance, and clinical uses.

An integrated population pharmacokinetic model of febuxostat in pediatric patients with hyperuricemia including gout and adult population of healthy subjects and patients with renal dysfunction.

The study objective was to validate febuxostat dosage and administration in pediatric patients with hyperuricemia including gout, using an integrated population pharmacokinetic (PopPK) analysis in the Japanese population. Integrated PopPK analysis of febuxostat used a nonlinear mixed-effects modeling (NONMEM) program on plasma febuxostat concentration data for 2611 samples from Japanese pediatric patients with hyperuricemia including gout (n = 29) and from adult subjects who are healthy or have renal dysfunction (n = 113). We described febuxostat pharmacokinetics using an integrated PopPK model applicable both to pediatric patients and to the adult population. The covariates of body weight and eGFR were identified for CL/F and the covariate of fasted/fed status for bioavailability. The range of steady-state exposures (Cmax,ss and AUCτ,ss) for 5, 10, 20, and 30 mg of febuxostat in fed pediatric patients weighing 20 to 40 kg was within that for 10, 20, 40, and 60 mg of febuxostat in fed pediatric patients and adults weighing 40 to 120 kg. Post hoc estimates of CL/F, adjusted by body weight, differed little between pediatric patients and the adult population in the renal function categories of normal, mild dysfunction, and moderate dysfunction. We successfully validated the febuxostat dose that provided the same level of exposure in pediatric patients as in the adult population: half the adult dose for pediatric patients weighing <40 kg and the full adult dose for pediatric patients weighing ≥40 kg. As in adults, the results support the use of febuxostat without dose adjustment in pediatric patients who have mild to moderate renal dysfunction.

Exogenous progesterone rescue in patients with low mid-luteal serum progesterone levels undergoing true natural vitrified-warmed blastocyst transfer.

To explore whether a 25mg subcutaneous progesterone daily rescue daily improves the reproductive outcomes in patients with low serum progesterone (P4) levels (7-10ng/mL), measured one day before true natural cycle (t-NC) frozen embryo transfer (FET). A cohort study of 192 women undergoing t-NC warmed blastocyst transfer. Patients were stratified into three different groups based on serum P4 levels on the FET-1day: patients who had serum P4 levels of 7-10ng/mL and underwent rescue progesterone administration (rescue group), patients with serum P4 levels of 7-10ng/mL without progesterone administration (non-rescue group), and patients with serum P4 > 10ng/mL on FET-1day (control group). The primary outcome was possible differences in live birth rate (LBR) between groups. The LBRs for the serum P4 7-10ng/mL without rescue, 7-10ng/mL with rescue, and > 10ng/mL (control) groups were 41%, 46%, and 52%, respectively (p = 0.61). The estimated adjusted probability of live birth for serum P4 7-10ng/mL without rescue, 7-10ng/mL with rescue, and > 10ng/mL (control) groups were also comparable: 43.5% (95% CI, 20.0-70.4%), 49.8% (95% CI, 28.1-71.6%), and 57.4% (95% CI, 44.0-69.8%), respectively. Serum P4 levels higher than 7ng/mL seem to secure LBRs in patients undergoing t-NC FET. A rescue policy consisting of a daily subcutaneous 25mg progesterone dose in patients with serum P4 levels 7-10ng/mL does not further enhance LBRs when compared to those patients with similar serum P4 levels without rescue.

Real-time measurement of radiation exposure in interventional radiologists during CT-guided intrathecal injections of nusinersen.

Some patients with spinal muscular atrophy and scoliosis require CT guidance during injections of nusinersen. The radiation applied to the operator in such procedures becomes an important issue in terms of staff health and safety. The aim of the study was to assess the operator's radiation exposure during CT-guided nusinersen injections in patients with spinal muscular atrophy and scoliosis. Consecutive 40 CT-guided nusinersen injections were analyzed in terms of operator's radiation exposure measured in real time. The median radiation dose measured under the physician's lead apron and patient dose in terms of DLP was 0.20 µSv and 31.90 mGy*cm respectively. The radiation doses were significantly higher (p = 0.047) in patients with spinal instrumentation. The results show that CT-guided nusinersen injection is a relatively safe procedure in terms of operator's radiation exposure. This can allow for interventional radiologists to perform more procedures without exceeding their annual dose limit.

RADIATION PATIENT AND WORKER DOSE APPLICATION (SI PADI)

Medical procedures for diagnostic and therapeutic purposes currently use many sources of ionizing radiation. Monitoring patient and radiation worker doses is needed to keep the radiation dose received to a minimum. The purpose of the patient and radiation worker dose application is to facilitate the task of Medical Physicists in conducting patient and radiation worker dose audits so that they become faster and more effective. The patient and radiation worker dose application is made based on dose audits conducted by Medical Physicists by monitoring patient doses on CT Scan examinations using CT dose index volume (CTDIvol) and dose length product (DLP) parameters on CT Scans and patient doses of the Siemens Somatom 128 slice Cathlab using Dose Area Product (DAP) data on the Philips Azurion 7 C-Arm. Radiation worker dose audits are conducted using evaluation data from TLD badges, TLD eyes, and pocket dosimeters of radiation workers working at Karawang Regional Hospital. Data processing uses a spreadsheet program. The menus on the dashboard are combined with formulas so that the data automatically appears in tables, graphs, or special formats as needed. The radiation patient and worker dose information system (Si Padi) was successfully developed at Karawang Regional Hospital to realize efforts to optimize radiation protection and safety for patients and radiation workers. Keywords: patient dose, radiation worker dose, dose audit, CT dose index (CTDI), dose length product (DLP), dose area product (DAP), Si Padi application.

APPLICATION OF SIZE SPECIFIC DOSE ESTIMATE (SSDE) AS A LOCAL DIAGNOSTIC REFERENCE LEVEL IN HEAD CT SCAN EXAMINATION AT INDRIATI HOSPITAL SOLOBARU, DR. MOEWARDI HOSPITAL SURAKARTA, SLEMAN HOSPITAL, AND NATIONAL BRAIN CENTER HOSPITAL JAKARTA

CT scan is a modality that produces a higher radiation dose compared to other modalities in radiodiagnostic installations. The radiation dose received by patients from examinations with this CT scan device is expressed in the volume CT Dose Index (CTDIvol) and Dose Length Product (DLP), which are dose indicators from the Indonesian Diagnostic Reference Level (DRL) value regulated in the Decree of the Head of the Nuclear Energy Regulatory Agency (BAPETEN) nationally. However, the CTDIvol value is only an indicator of the output dose from the CT scan, and the DLP value is an indicator of the total dose during the examination, which is influenced by the length of the scan. Both do not represent the specific dose received by the patient because the patient's dose depends not only on the output dose but also on the patient's characteristics. The patient's dose, which includes the output dose and patient characteristics, is called the Size-Specific Dose Estimate (SSDE), which is used to estimate the dose received by the patient by including a correction factor depending on the patient's dimensions. This study aims to calculate the SSDE value in a CT Head examination with a standard protocol using the same type of device, namely a 128-slice CT scan in several hospitals. The values of CTDIvol and DLP patients are obtained from the dose report displayed on the CT scan monitor screen in the IndoseCT software. The patient samples studied were patients undergoing CT Head examinations from March 2023 to February 2024, with 100 patients in each hospital. The results of this study obtained local DRL values based on SSDE calculated at Indriati Hospital, Moewardi Hospital, Sleman Hospital, and the National Brain Center Hospital and then compared them with the national TPD values. Based on the SSDE value from Indriati Hospital, the TPD value was 30.26 mGy, Sleman Hospital was 39.5 mGy, Dr. Moewardi Hospital was 49.3 mGy, and RSPON was 51.7 mGy. The TPD value of CT Head examinations without contrast from each hospital was still below the national TPD value of 60 mGy. Keywords: CT scan, diagnostic reference level (DRL), local DRL, national DRL, Size-Specific Dose Estimate (SSDE), IndoseCT.

ESTIMATION OF PATIENT RADIATION DOSE WITH SIZE SPECIFIC DOSE ESTIMATE (SSDE) METHOD IN ABDOMEN CT-SCAN EXAMINATION AT SEMEN GRESIK HOSPITAL

CT-Scan abdomen is an examination to see the anatomy and pathology of the abdominal organs, and the scanning image results are in the form of three-dimensional axial images of the body. The radiation dose released from the CT-Scan examination is more significant than other radiology modalities. Therefore, it is very important to estimate the patient's dose accurately. Computed Tomography Dose Index (CTDIvol) and Dose Length Product (DLP) are dose parameters used in CT-Scan to describe the dose value received by the patient. However, these parameters are the output of the CT-Scan, not as the dose received by the patient. The Size Specific Dose Estimate (SSDE) method based on AAPM Report No. 204 is used to determine the estimated dose received by the CT-Scan Abdomen patient. Calculations are done manually and with IndoseCT software. The data used are secondary data of 60 patients, namely 21 females and 39 males, who were on the CT-Scan Abdomen examination without contrast from the Instalasi Radiologi Rumah Sakit Semen Gresik. The SSDE value is obtained from the multiplication between the conversion factor and CTDIvol, where the conversion factor is an effective diameter function. The analysis examined the error value in manual calculations and IndoseCT software in men and women, the relationship between effective diameter and scanning radiation output (CTDIvol), and dose estimation estimates (SSDE). The difference in SSDE values between manual calculations and IndoseCT software was insignificant. The highest error value in women was 3% and 3.2% in men. Meanwhile, the relationship between effective diameter (Deff) and scanning radiation output (CTDIvol) and dose estimation estimates (SSDE) showed that the correlation between effective diameter (Deff) and CTDIvol showed a stronger correlation, namely with R2 around 0.7 in women and men, compared to the correlation between effective diameter (Deff) and SSDE with R2 around 0.03 in women and 0.2 in men. Keywords: CT-Scan, Abdomen, Size Specific Dose Estimate (SSDE).

DETERMINATION OF DIAGNOSTIC REFERENCE LEVEL (DRL) AND STUDY OF EXPOSURE PARAMETER SELECTION IN HEAD AND ABDOMEN CT SCAN AT BANGIL REGIONAL HOSPITAL

A study has been conducted to determine the local diagnostic reference level (DRL) value of CT scans at Bangil Regional Hospital. The determination and calculation of the DRL value are based on the measurement of the patient's dose, namely using the CT scan examination results in the form of CTDIVol values and DLP values. The DRL value is determined from the CTDIVol and DLP data distribution in quartile 3. Patient dose data uses a Toshiba 16-slice CT scan and a Canon 160-slice CT scan. Seven hundred twenty data were obtained, distinguished by 680 adults and 40 children. The local DRL value at Bangil Regional Hospital for CT scans of the Head without contrast for the adult group CTDIVol 47.5 mGy and DLP 1162 mGy.cm. CT scans of the Head with contrast for the adult group CTDIVol 47.22 mGy and DLP 2784.38 mGy.cm. DRL on CT scan Abdomen without contrast adult age group at Bangil Hospital CTDIVol 3.7 mGy and DLP 179.9 mGy.cm. CT scan of Abdomen with contrast CTDIVol 3.9 mGy and DLP 774.92 mGy.cm. When compared to the National DRL value, this value is still below the National DRL value. However, the nature of DRL is dynamic, so each period is expected to be lower. Efforts should focus on achieving lower DRL values by considering the selection of parameters and the skills of radiographers that influence the dose administered to patients. Values that exceed the DRL value are evaluated using the choice of parameters. Factors that affect the DRL value include kV, mAs, rotation time, pitch, iterative reconstruction, and number of phases. The parameters used in CT scans at Bangil Hospital must be adjusted to provide optimal doses to patients. Keywords: diagnostic reference level (DRL), dose length product (DLP), CT dose index (CTDI), CT Head, CT Abdomen, dose delivery parameters.

DETERMINATION OF DOSE REFERENCE LEVELS AT BENDAN PEKALONGAN REGIONAL HOSPITAL FOR INTERNAL DOSE AUDIT AS AN EFFORT TO OPTIMIZE RADIATION PROTECTION FOR PATIENTS

Unnecessary exposure is less of a concern because it is considered not to cause injury to patients. Radiation protection optimization is carried out for patients to reduce unnecessary exposure. Following BAPETEN Regulation No. 4 of 2020 Article 46, permit holders are required to implement radiation protection optimization [1]. This study aimed to obtain the local dose reference level (TPD) value through an internal dose audit to optimize patient radiation protection. This optimization is carried out in several steps, including conducting an internal dose audit, determining the local TPD, and evaluating the examination. This study is expected to motivate documentation of radiation parameters to obtain sufficient data for analysis. The method used in this study is a literature study through related references and X-ray radiation output data to calculate the dose in the form of incident air kerma (INAK) and entrance surface air kerma (ESAK). The results showed that the local INAK TPD value was 52% below the national TPD, and the local ESAK TPD value was 57% below the national TPD. The expected local TPD value is a TPD value that is lower than the national TPD value. This indicates that the imaging protocol at RSUD Bendan has been well-optimized. However, there are still several types of examinations where the local TPD value exceeds the national TPD, indicating the need to review further the imaging techniques and protocols used. The influence of body weight and radiological image diagnosis was analyzed as a basis for further optimization. Thus, the determination of this local TPD can be an essential reference in efforts to improve patient safety and optimize radiation protection in health facilities. Keywords: radiation protection optimization of patient, Dose Reference Level (DRL), patient dose.

EFFECTIVE DOSE ANALYSIS IN ABDOMEN AP EXAMINATION PATIENTS WITH CALDOSE_X VERSION 5.0

This study evaluates radiation dose exposure during diagnostic radiology procedures using X-rays and their potential risks, including cancer, to optimize radiation safety through the CALDose_X software that calculates the absorbed organ dose, effective dose, and cancer risk, according to the lowest possible achievable (ALARA) principle. This study used a quantitative experimental design to evaluate the impact of filter thickness variations on Entrance Surface Air Kerma (ESAK) and effective dose by analyzing data from 54 patients undergoing AP Abdominal X-ray examinations. The results showed that the effective dose to the abdominal organs varied with exposure factors and Focus to Detector Distance (FDD), where the colon wall had the highest sensitivity with doses ranging from 0.030 mSv to 0.126 mSv, followed by the stomach and pancreas. Increasing kV, mAs, and FDD increased the effective dose, emphasizing the importance of careful dose management. This study concluded that exposure factors and FDD affect the effective dose received by the abdominal organs, with recommendations to monitor patient doses, revise national diagnostic reference levels, and establish standard protocols with health authorities. Keywords: CALDose_X, X-ray Exposure Factor, patient dose, ESAK, Effective Dose, Abdomen AP.

Pharmacometric and statistical considerations for dose optimization.

The probability of target attainment (PTA) is a common metric in drug dose optimization, but it requires a specific known target concentration threshold. Such target thresholds are not always available for some treatments, and patient and disease groups, particularly when treating children. This study performed pharmacokinetic and pharmacokinetic-pharmacodynamic (PKPD) simulations to explore different statistical approaches for determining the optimal dose for unknown PK and PKPD targets. To determine an optimal dose, PK and PKPD outcomes in typical patients with a standard adult dosing regimen were simulated and set as the reference profile, and compared to simulated outcomes for different dosing regimens in the population of interest. Statistical distances between the empirical cumulative distribution functions of the outcomes from all possible dosing regimens were calculated and compared to the reference profile. An optimal dose for known PK and PKPD target outcomes was selected to maintain the outcome above the assigned target, while optimal dosing in a population of interest with an unknown target was selected to generate equivalent PK and PKPD outcomes as the typical population. All of the dose optimization methods with commonly used PK and PKPD models and covariates were implemented as an open source freely available Shiny web-application. The developed pharmacometric method for dose optimization in populations with known and unknown target levels were robust and reproducible, and the implementation of a freely accessible Shiny web-application ensures widespread use and could be a useful tool for dose optimization in populations of interest.

OPTIMIZATION OF RADIATION PROTECTION IN PATIENTS THROUGH IMPLEMENTATION OF LOCAL DIAGNOSTIC REFERENCE LEVEL (DRL) IN PANORAMIC DENTAL EXAMINATION IN RADIOLOGY INSTALLATION OF PROF. DR. MARGONO SOEKARJO HOSPITAL

One of the principles of radiation protection is optimization. Optimization is done to make the dose received as low as reasonably achievable (ALARA) by considering economic and social factors. Implementation of radiation protection optimization can be done with dose management through the Local Diagnostic Reference Level (DRL). In recent years, the Nuclear Energy Regulatory Agency (BAPETEN) has set the Indonesian DRL value for several X-ray modalities, including dental panoramic. This study was motivated by panoramic patient dose audit data using the auto mode exposure factor, which operators often use. The method for determining the manual mode exposure factor is carried out by comparing the image quality of the current variations of 6.3 mA, 8 mA, 10 mA, 13 mA, and 16 mA with a fixed voltage of 66 kV and a time of 14.1 seconds. The local DRL value was obtained by comparing the dental panoramic auto mode measurements with manual mode using certain exposure factors according to the recommendations in the initial study using a head phantom. This study used 100 patient data with adult human criteria aged over 15. The results obtained from the initial study and questionnaires in manual mode were the values that had the highest CNR and SNR at a current variation of 10 mA. The exposure factor was then used to collect patient data. The local DRL value obtained for auto mode was 83.35 mGy cm2; in manual mode, it was 57.7 mGy cm2. Manual mode exposure factors in dental panoramic examinations affected the implementation of local DRL values with a decrease of 30.77% from auto mode. The use of manual mode in dental panoramic examinations significantly reduces the radiation dose received by patients, so the use of manual mode is one of the steps to optimize radiation protection. Keywords: Diagnostic Reference Level (DRL), optimization of radiation protection in patients, dental panoramic.

OPTIMIZATION OF EXPOSURE FACTORS WITH VARIATION OF FILTER THICKNESS ON DOSE VALUES AND RADIOGRAPHIC IMAGE QUALITY IN PELVIS EXAMINATION

This study examines the impact of varying X-ray tube voltage (kV) and filter thickness on patient radiation dose and image quality in radiographic procedures. It aims to optimize exposure factors to minimize patient dose while maintaining diagnostic image quality, contributing to safer and more efficient radiological practices. This quantitative experimental study investigates the impact of varying filter thickness and tube voltage on patient radiation dose. Using X-ray equipment, dosimeters, and phantoms, measurements of Incident Air Kerma (INAK) and Entrance Surface Air Kerma (ESAK) and effective dose are taken, followed by image quality assessments to optimize exposure factors while maintaining diagnostic efficacy. The study demonstrated that increasing filter thickness decreases both INAK and ESAK values, with the most significant dose reduction occurring at 2 mm thickness. Optimal image quality and effective dose reduction were observed with the 1 mm filter at 80 kV, reducing the dose by 14.3% to 20% while maintaining good spatial resolution and contrast. The study concludes that using a 1 mm aluminum filter with 80 kV significantly reduces the effective dose while maintaining image quality. It is recommended that hospitals adopt additional filters, conduct further research with different materials, and optimize exposure factors. Training for radiology technicians on these practices is essential to enhance patient safety and image quality. Keywords: X-ray Equipment, Entrance Surface Air Kerma, Effective Dose, Image Quality.

A randomized trial of early cardiotoxicity in breast cancer patients receiving postoperative IMRT with or without serial cardiac dose constraints.

Optimal cardiac dose constraints in breast cancer (BC) patients undergoing postoperative intensity-modulated radiation therapy (IMRT) are unclear, although as low as possible is recommended. This trial proposes serial cardiac dose constraint to optimize cardiac safety. Postoperative BC patients eligible for anthracycline/taxanes-based chemotherapy or HER2-targeted therapy were randomized to cardiac safety arm with prespecified mean heart dose (MHD) (≤6 Gy), V30 (≤20%), and V10 (≤50%) constraints, or to a control arm with in-house protocol (mainly MHD ≤8 Gy). The primary endpoint was cumulative incidence of newly onset cardiac events within 1-year post-RT. An exploratory analysis examined the relationship between whole heart dose metrics and those of substructures. Of 199 participants, 93 were in the cardiac safety and 106 in the control arm. The cardiac safety group showed lower MHD, V10, and V30. The 1-year cardiac event incidence was slightly lower in the cardiac safety group (19.4%) compared to controls (24.9%). The LVEF and diastolic dysfunction rates were 0% and 5.4% in the study arm, and 1.9% and 8.8% in the control arm, respectively. The LAD, LV, and RV received the highest doses for left-sided patients. For right-sided patients, RA, RCA, and RV were most irradiated. The MHD, V10, and Dmax of heart significantly correlated with all substructure doses in either laterality. Our study supports the early cardiac safety profile using IMRT in BC patients receiving cardiac-toxic systemic therapy, with serial cardiac dose constraints. Combined constraints on MHD and dose-volume parameters are representative of the cardiac substructure dose.