Dose Assessment Research Articles

Dosimetric impact of the respiratory motion of the liver dome in stereotactic body radiotherapy for spine metastasis: A planning study.

This study aimed to clarify the dosimetric impact of the respiratory motion of the liver on stereotactic body radiation therapy (SBRT) for spine metastasis and examine the utility of introducing beam avoidance (beam-off at specific gantry angles). A total of 112 consecutive patients who underwent SBRT for spine metastasis between 2018 and 2024 were examined. Overall, 15 patients who had lesions near the liver dome were included in this study. Retrospective treatment plans were generated using computed tomography (CT) images acquired during inhalation and exhalation to evaluate the dosimetric impact of respiratory motion of the liver. The dose difference (DD) and relative value (DD%) were evaluated using the dose-volume histogram (DVH) metrics, planning target volume Dmax, D95%, spinal cord D0.035 cc, and esophagus D2.5 cc. The magnitude of the liver movements was evaluated based on differences of liver size Lave at the isocentric axial plane between the inspiratory and expiratory CT images. The DD in almost all DVH metrics tended to increase when the liver moved away from the target during inhalation: For example, Mean a standard deviation (SD) DD in PTV D95% for the treatment plan incorporating beam avoidance and those without beam avoidance was 0.5 0.3 and 0.9 0.6Gy, respectively. The spinal cord D0.035 cc for those shows 0.4 0.2 and 0.7 0.7Gy, respectively. The treatment plans without beam avoidance also showed moderate or strong correlations between Lave and DD for almost all DVH metrics. No correlation was seen in the beam avoidance plan. The spinal cord D0.035 cc revealed approximately 1Gy or +4% in DD when Lave was < -4cm. Respiratory motion of the liver dome can cause substantial dosimetric discrepancies in the dose delivered to the spinal cord, although the extent depends on patient variables. Dose assessment should be performed for determining the appropriate means of respiratory management, such as breath-hold. Alternatively, beam avoidance effectively mitigates the impact.

Clinical impact of DVH uncertainties

Dose-volume histograms (DVH), along with dose and volume metrics, are central to radiotherapy planning. As such, errors have the potential to significantly impact the selection of appropriate treatment plans. Dose distributions that pass tests in one TPS may fail the same tests when transferred to another, even if using identical structures and dose grid information. This work shows the design and implementation of methods for assessing the accuracy of dose and volume computations performed by treatment planning systems (TPS), and other analytical tools. We demonstrate examples where differences in calculations between systems can change the assessment of a plan’s clinical acceptability. Our work also provides a more detailed DVH analysis of single targets than earlier published studies. This is relevant for SRS plans and small structure dose assessments. Very small structures are a particular problem because of their coarse digital representation, and the impact of this is thoroughly examined.Reference DVH curves were derived mathematically, based on Gaussian dose distributions centered on spherical structures. The structures and dose distributions were generated synthetically, and imported into RayStation, MasterPlan, and ProKnow. Corresponding DVHs were analytically derived and taken as ground truth references, for comparison with the commercial DVH calculations. Two commonly used dose metrics PCI and MGI were used to determine the limit of calculation accuracy for small structures. In addition, to measure the DVH differences between a larger range of commercial DVH calculators, the D95 metric from a set of real clinical plans was compared across both the 3 DVH calculators under test, and across a further six TPSs from other hospitals.We show that even slight deviations between the results of DVH calculators can lead to plan check failures, and we illustrate this with the commonly used D95 planning metric. We present clinical data across eight planning systems that highlight instances where plan checks would pass in one software and fail in another due to DVH calculation differences. For the smallest volumes tested, errors of up to 20% were observed in the DVHs. RayStation was tested down to a 3 mm radius sphere (≈0.1 cc) and this showed close to 10% error, reducing to 1% for 10 mm radius (≈4.0 cc) and 0.1% for 20 mm radius (≈33 cc). In clinical plans, the variation in D95 was up to 9% for the smallest volumes, and typically around 2% in the range 0.5 cc-20 cc, and 1% in 20 cc-70 cc, falling to <0.1% for large volumes. Paddick Conformity Index (PCI) and Modified Gradient Index (MGI) are commonly used plan quality indicators for very small volumes. For volumes ≈0.1 cc we observed errors of up to 40% in PCI, and up to 75% in MGI.Our study extends the range of tested DVH calculators in published work, and shows their performance over a wider range of volume sizes. We provide quantitative evidence of the critical need to test the accuracy of DVH calculators in the TPS before clinical use. This work is particularly relevant for both stereotactic plan evaluation and for assessment of small volume doses in published dose constraint recommendations. We demonstrate that significant errors can occur in DVHs for volumes less than 1 cc, even if the volumes themselves are calculated accurately. Even for large structures, deviations between the outputs of DVH calculators can lead to indicated or reported plan check failures if they do not include appropriate tolerances. We urge caution in the use of DVH metrics for these very small volumes and recommend that appropriate DVH uncertainty tolerances are set in organ dose constraints when using them to evaluate clinical plans.

Upgrade of the Hungarian PILLE-ISS onboard thermoluminescent system for the dose assessment during extravehicular activities

The paper presents results of on-ground (pre-flight) calibrations and flight tests (cross-calibration and in situ measurements) of the new, Modified PILLE-ISS Dosimeters with reduced shielding, developed for the radiation monitoring of astronauts during their extravehicular activity (EVA) on board the International Space Station (ISS). The smaller dimensions and weight of the modified thermoluminescent dosimeter allows ergonomic and safe use during EVA, when the dosimeter kit is worn in the outer pocket of a spacesuit. The special design of the detector housing makes it possible to estimate the dose to the astronaut's skin during EVA more accurately. Both pre-flight calibration with high-energy protons and on-board cross-calibration at ISS showed that the variability of the relative sensitivities does not exceed (5–10)% for any of the Modified PILLE-ISS Dosimeters. The additional dose received by astronauts during ISS EVAs in 2023 was in the range (0.37–0.75) mGy (in water) based on the measurements. The corresponding dose rate outside ISS is consistent with the previous readings of other dosimetric equipment installed on the outer surface of space station.

Depth Dose According to Depth during Cone Beam Computed Tomography Acquisition and Dose Assessment in the Orbital Area Using a Three-Dimensional Printer

Background: Cone beam computed tomography (CBCT) is essential for correcting and verifying patient position before radiation therapy. However, it poses additional radiation exposure during CBCT scans. Therefore, this study aimed to evaluate radiological safety for the human body through dose assessment for CBCT.Materials and Methods: For CBCT dose assessment, the depth dose was evaluated using a cheese phantom, and the dose in the orbital area was evaluated using a human body phantom self-fabricated with a three-dimensional printer.Results and Discussion: The evaluation of radiation doses revealed maximum doses of 14.14 mGy and minimum doses of 6.12 mGy for pelvic imaging conditions. For chest imaging conditions, the maximum doses were 4.82 mGy, and the minimum doses were 2.35 mGy. Head imaging conditions showed maximum doses of 1.46 mGy and minimum doses of 0.39 mGy. The eyeball doses using a human body phantom model averaged at 2.11 mGy on the left and 2.19 mGy on the right. The depth dose ranged between 0.39 mGy and 14.14 mGy, depending on the change in depth for each imaging mode, and the average dose in the orbit area using a human body phantom was 2.15 mGy.Conclusion: Based on the experimental results, CBCT did not significantly affect the radiation dose. However, it is important to maintain a minimal radiation dose to optimize radiation protection following the as low as reasonable achievable principle.

Radiation Research Society Journal-based Historical Review of the Use of Biomarkers for Radiation Dose and Injury Assessment: Acute Health Effects Predictions.

A multiple-parameter based approach using radiation-induced clinical signs and symptoms, hematology changes, cytogenetic chromosomal aberrations, and molecular biomarkers changes after radiation exposure is used for biodosimetry-based dose assessment. In the current article, relevant milestones from Radiation Research are documented that forms the basis of the current consensus approach for diagnostics after radiation exposure. For example, in 1962 the use of cytogenetic chromosomal aberration using the lymphocyte metaphase spread dicentric assay for biodosimetry applications was first published in Radiation Research. This assay is now complimented using other cytogenetic chromosomal aberration assays (i.e., chromosomal translocations, cytokinesis-blocked micronuclei, premature chromosome condensation, γ-H2AX foci, etc.). Changes in blood cell counts represent an early-phase biomarker for radiation exposures. Molecular biomarker changes have evolved to include panels of organ-specific plasma proteomic and blood-based gene expression biomarkers for radiation dose assessment. Maturation of these assays are shown by efforts for automated processing and scoring, development of point-of-care diagnostics devices, service laboratories inter-comparison exercises, and applications for dose and injury assessments in radiation accidents. An alternative and complementary approach has been advocated with the focus to de-emphasize "dose" and instead focus on predicting acute or delayed health effects. The same biomarkers used for dose estimation (e.g., lymphocyte counts) can be used to directly predict the later developing severity degree of acute health effects without performing dose estimation as an additional or intermediate step. This review illustrates contributing steps toward these developments published in Radiation Research.

Radiation dose assessments for generic nuclear power plants part I: Routine operation

The main task of the site evaluation report for nuclear installation concerning nuclear safety is the protection of the public and environment from the radiological consequences of radioactive releases in both cases of normal operation and accident conditions. The atmosphere is the most important pathway to be considered in the assessment of the environmental impact of radioactive materials released from nuclear facilities. The present study is a comprehensive investigation of environmental assessments for the dose calculation model resulting from routine operation NPPs of 1000 Mw (e). The procedure consists of different parts, beginning with the manipulation of collected meteorological data such as wind speed and direction, temperature, incoming solar radiation and utilizing a set of empirical formulae for evaluating night solar radiation emitted from the ground, and then evaluating hourly stability classes and joint frequency distribution of winds by developing code. The dilution factor was evaluated using computer code (XOQDOQ code). Finally, the radiation dose assessments resulting from the routine operation of NPPs were calculated. The processes are adapted with IAEA recommendations documents, safety guides, and ICRP recommendations. The results reveal that there is no detectable value that affects the people surrounding the site nor the environmental area concerning low population zone or exclusion area.

Assessment of cone-beam CT technical image quality indicators and radiation dose for optimal STL model used in visual surgical planning.

The aim of this study was to identify cone-beam computed tomography (CBCT) protocols that offer an optimal balance between effective dose (ED) and 3D model for orthognathic virtual surgery planning, using CT as a reference, and to assess whether such protocols can be defined based on technical image quality metrics. Eleven CBCT (VISO G7, Planmeca Oy, Helsinki, Finland) scan protocols were selected out of 32 candidate protocols, based on ED and technical image quality measurements. Next, an anthropomorphic RANDO SK150 phantom was scanned using these 11 CBCT protocols and 2 CT scanners for bone quantity assessments. The resulting DICOM (Digital Imaging and Communications in Medicine) files were converted into Standard Tessellation Language (STL) models that were used for bone volume and area measurements in the predefined orbital region to assess the validity of each CBCT protocol for virtual surgical planning. The highest CBCT bone volume and area of the STL models were obtained using normal dose protocol (F2) and ultra-low dose protocol (J13), which resulted in 48% and 96% of the mean STL bone volume and 48% and 95% of the bone area measured on CT scanners, respectively. The normal dose CBCT protocol "F2" offered optimal bone area and volume balance for STL. The optimal CBCT protocol can be defined using contrast-to-noise ratio and modulation transfer function values that were similar to those of the reference CT scanners'. CBCT scanners with selected protocols can offer a viable alternative to CT scanners for acquiring STL models for virtual surgical planning at a lower effective dose.

Assessment of peripheral dose as a function of distance and depth from cobalt-60 beam in water phantom using TLD-100

BackgroundInnovations in cancer treatment have contributed to the improved survival rate of cancer patients. The cancer survival rates have been growing and nearly two third of those survivors have been exposed to clinical radiation during their treatment. The study of long-term radiation effects, especially secondary cancer induction, has become increasingly important. An accurate assessment of out-of-field/peripheral dose (PDs) is necessary to estimate the risk of second cancer after radiotherapy and the damage to the organs at risk surrounding the planning target volume. This study was designed to measure the PDs as a function of dose, distances, and depths from Telecobalt-60 (Co-60) beam in water phantom using thermoluminescent dosimeter-100 (TLD-100).MethodsThe PDs were measured for Co-60 beam at specified depths of 0 cm (surface), 5 cm, 10 cm, and 15 cm outside the radiation beam at distances of 5, 10, and 13 cm away from the radiation field edge using TLD-100 (G1 cards) as detectors. These calibrated cards were placed on the acrylic disc in circular tracks. The radiation dose of 2000 mGy of Co-60 beam was applied inside 10 × 10 cm2 field size at constant source to surface distance (SSD) of 80 cm.ResultsThe results showed maximum and minimum PDs at surface and 5 cm depth respectively at all distances from the radiation field edge. Dose distributions out of the field edge with respect to distance were isotropic. The decrease in PDs at 5 cm depth was due to dominant forward scattering of Co-60 gamma rays. The increase in PDs beyond 5 cm depth was due to increase in the irradiated volume, increase in penumbra, increase in source to axis distance (SAD), and increase in field size due to inverse square factor.ConclusionIt is concluded that the PDs depends upon depth and distance from the radiation field edge. All the measurements show PDs in the homogenous medium (water); therefore, it estimates absorbed dose to the organ at risk (OAR) adjacent to cancer tissues/planning target volume (PTV). It is suggested that PDs can be minimized by using the SAD technique, as this technique controls sources of scattered radiation like inverse square factor and effect of penumbra up-to some extent.

Fetal dose assessment in a pregnant patient with brain tumor: A comparative study of proton PBS and 3DCRT/VMAT radiation therapy techniques.

The treatment of brain tumors in pregnant patients poses challenges, as the out-of-field dose exposure to the fetus can potentially be harmful. A pregnant patient with prior radiation treatment was presented with a brain tumor at our clinic. This work reports on our pre-treatment study that compared fetal dose exposure between intensity-modulated proton therapy (IMPT) using pencil beam scanning (PBS) and conventional photon 3D conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT), and the subsequent pregnant patient's radiation treatment. Pre-treatment measurements of clinical plans, 3DCRT, VMAT, and IMPT, were conducted on a phantom. Measurements were performed using a device capable of neutron detections, closely following AAPM guidelines, TG158. For photon measurements, fetus shielding was utilized. On patient treatment days, which was determined to be proton treatment, shielding was used only during daily imaging for patient setup. Additionally, an in vivo measurement was conducted on the patient. Measurements showed that IMPT delivered the lowest fetal dose, considering both photon and neutron out-of-field doses to the fetus, even when shielding was implemented for photon measurements. Additionally, the proton plans demonstrated superior treatment for the mother, a reirradiation case. The patient was treated with proton therapy, and the baby was subsequently delivered at full term with no complications. This case study supports previous clinical findings and advocates for the expanded use of proton therapy in this patient population.

The Comparison of Surface Dose in Vivo Dosimetry Using 3D-CRT and IMRT Technique on Breast Cancer Case

The aim of this study is to verify the adequacy of the surface radiation dose calculated by the Treatment Planning System (TPS) using 3DCRT and IMRT technique with the dose measured by the TLD-100, referring to the report of the American Association of Physicists in Medicine Task Group No.219 (AAPM-TG No.219). This research process began with annealing the TLD-100 at the Research Center for Safety Technology Metrology and Nuclear Quality of the National Innovation Research Agency (PRTKMMR-BRIN), followed by scanning the TLD-100 on the surface of the phantom plate using a CT simulator. In addition, the TLD-100 was calibrated with different radiation doses (0; 20; 50; 80; 100; 150; 200; 250; 370) cGy. Verification of the surface radiation dose was performed by calculating the TPS surface dose by Patient Specific Quality Assurance (PSQA) and comparing it with the dose measured by the TLD-100. The result is Radiation techniques such as IMRT are more conformal than 3D-CRT because they precisely control dose intensity, making the TLD dose in IMRT closer to TPS. Differences in detector types such as TLD also affect the results of radiation dose measurements. Continuous assessment of patient dose is important for the safety of radiation therapy.

United States Navy nuclear accident dosimetry program: History and Current Status

Federal Regulations of the United States require that installations possessing sufficient quantities of fissile material to potentially constitute a critical mass, such that the excessive exposure of individuals to radiation from a nuclear accident is possible, shall provide appropriate nuclear accident dosimetry. The American National Standard ANSl/HPS N13.3–2013 Dosimetry for Criticality Accidents provides technical, quality assurance, and performance requirements for nuclear accident dosimeters (NAD). In 2023 the U.S. Navy operated 82 nuclear-powered ships, with the fleet being composed of 11 aircraft carriers, 68 submarines, having a total number of 98 reactors. Since 1968 the U.S. Navy has used fixed nuclear accident dosimeters (FNAD) mounted to the bulkheads surrounding naval nuclear propulsion reactors. Since 1968 the US Navy has used two nuclear accident criticality dosimeters. The first Navy accident dosimeter DT-518/PD was introduced in 1968. It was developed by the Naval Radiological Defense Laboratory in San Francisco, California under leadership of Eugene Tochilin. This dosimeter contains two indium foils for quick dose assessments using shipboard gamma instruments available on nuclear powered vessels and two sulfur pellets/LiF TLD-700 powder for final dose determination at the Naval Dosimetry Center. The newest Navy NAD is the DT-723/PD, which contains indium foil, gold foil, cadmium shielded gold foil, sulfur pellet and a LiF TLD-700 chip. This paper provides a brief description of the measurement procedures, results of the testing of both NADs and comparison of their performance.

Qualitative analysis of physico-chemical parameters of packaged drinking water commercially available in India

ABSTRACT The demand for packaged drinking water is increasing day by day, so it is necessary that the quality of this water must be monitored. Our present study focuses on the determination of the concentration of minerals and trace elements present in commercialised packaged drinking water sold out in various regions of India. In total, we have analysed 41 brands. The different treatments through which this water has passed as claimed by the manufacturers are also mentioned. The average value of the total dissolved solids in these waters is found to be 101.1 mg L−1. The content of anions and cations present in water is represented by box and whisker plots. Bottled water samples are also analysed for the radioactive element uranium, which is observed in the range of &amp;lt;0.1 to 9.2 μg L−1 with a mean concentration of 1.6 μg L−1. The radiation dose assessment for various age groups has been calculated due to the ingestion of uranium present in the water.

Present and new operational quantities evaluated from photon spectrum measurements at workplaces in the research reactor and accelerator facility at the JAEA

The International Commission on Radiation Units and Measurements (ICRU) has proposed to change the definitions of the operational quantities used for the area and individual monitoring of external exposure in ICRU Report 95. Since introducing new operational quantities into the radiation monitoring may affect the dose assessment using the present personal dosimeters, precise assessments of the influence on monitoring are necessary by characterizing the energy spectrum in the workplace and the energy dependency of the dosimeters to be used. This study measured photon spectra using a NaI(Tl) scintillation detector or a LaBr3(Ce) scintillation detector at the Japan Research Reactor No. 3 (JRR-3) and Japan Proton Accelerator Research Complex (J-PARC) workplaces at the Japan Atomic Energy Agency (JAEA). The photon energy spectra were obtained by unfolding the pulse height distributions measured at each workplace. The present and new operational quantities were then evaluated and compared using the spectra measured at the workplaces.In JRR-3, the photon energy spectra were measured at the workplaces in the reactor room and thermal neutron beam hall while the reactor was operated. The ambient dose equivalent rates H˙*(10) at the workplaces were 0.2 μSv·h−1 – 13 μSv·h−1. High energy gamma-rays of 6–7 MeV from 16N were observed near the fuel failure detection system in the reactor room. Those of 7–8 MeV produced by the thermal neutron capture of iron were observed in the reactor room and the beam hall. In J-PARC, the photon energy spectra were measured at the workplaces in the beam tunnel of the 3 GeV synchrotron beam ring five days after the operation. The ambient dose equivalent rates H˙*(10) at the workplaces were 35 μSv·h−1 –430 μSv·h−1.It was found that the new personal doses, Hp, were 10%–20% smaller than the present personal dose equivalents, Hp(10), at the workplaces.

Glycemia control after total pancreatoduodenectomy

Aim. To study the features of correction of carbohydrate metabolism disorders and nutritional deficiency in patients after total pancreatoduodenectomy; to develop a unified protocol for managing patients after total pancreatoduodenectomy. Materials and methods. From 2007 to 2022, 62 patients underwent total pancreatoduodenectomy in the Hepatopancreatic Surgery Unit of the Botkin Hospital. The patients were divided into two groups, comparable in terms of basic parameters. The first group included patients (n = 32) who underwent “classical” total pancreatoduodenectomy with gastric resection and splenectomy. The second group consisted of patients (n = 30) who underwent total pancreatoduodenectomy in the modification of Botkin Hospital. In the perioperative period, patients of both groups were examined for carbohydrate metabolism with the selection and assessment of the average daily dose of short-acting and long-acting insulin, assessment of enzyme and protein deficiency with the selection of enzyme replacement therapy and nutritional support. For a more accurate assessment of carbohydrate metabolism disorders, all patients underwent continuous monitoring of the level of glycemia intraoperatively and in the early postoperative period (FreeStyle Libre flash monitoring system, Abbott). The glycated hemoglobin level was assessed on day 90 and body mass index – on days 30, 60 and 90 after surgery. Results. The mean level of glycemia in patients after total pancreatoduodenectomy in the modification of the Botkin Hospital accounted for 8.0 mmol/l and the variability (daily fluctuations in glycemia) comprised 39 %, which was significantly lower compared to the group of “classical” total pancreatoduodenectomy with 7.6 mmol/l and 48 %, respectively. Seven patients (21.9 %) after total pancreatoduodenectomy in the modification of the Botkin Hospital experienced a severe hypoglycemic episode, while a similar severe hypoglycemic episode was noted in 25 patients (80.6 %) after pancreatectomy in its “classical” variant, of which 18 patients (60 %) required hospitalization in the endocrinology unit in order to correct the sugar-lowering therapy. In turn, only three patients (9.4 %) after total pancreatoduodenectomy modified by the Botkin Hospital required hospitalization due to severe hypoglycemia. The mean level of glycated hemoglobin in patients of the first and second groups on day 90 accounted for 7.2 % and 7.7 %, respectively (p = 0.789). The average body mass index on day 90 after surgery was higher in the group of organ-preserving total pancreatoduodenectomy: 24 kg/m2, compared to the “classical” pancreatectomy with 21.2 kg/m2 (p = 0.001). The daily dose of both short-acting and long-acting insulin was higher in the organ-preserving total pancreatoduodenectomy group of 17.4 ± 5.6 U/day and 12 ± 4.6 U/day, respectively, compared to the group of “classical” total pancreatoduodenectomy of 13.8 ± 4.6 U/day and 10.8 ± 2.7 U/day, respectively. This can be attributed to the faster normalization of the patient's body weight and the preserved function of physiological digestion due to the pylorus-preserving variant of total pancreatoduodenectomy. Conclusion. Management of patients after total pancreatoduodenectomy is claimed to be an extremely complex task that requires a multidisciplinary approach involving surgeons, intensivists, endocrinologists and gastroenterologists at all stages of patient management. Organ-preserving modification of total pancreatoduodenectomy with preservation of the stomach, spleen and splenic vessels in the modification of the Botkin Hospital improves treatment results and simplifies the selection of insulin therapy for this group of patients.

How Much Radiation Are Women in Saudi Arabia Receiving from Mammography? A Review

This review compiles and assesses data from recent studies on mammographic radiation doses in Saudi Arabia, aiming to evaluate mean glandular dose (MGD) exposure during mammography and its implications in breast cancer risk. The reviewed studies spanned from 2019 to 2023 and included a range of sample sizes and institutional settings, with patients’ ages from 27 to 85 years. Considerations such as the number of mammographic views and compressed breast thickness were examined. The studies reported average MGDs below the National Diagnostic Reference Level set by the Saudi Food and Drug Authority. However, limitations were noted regarding sample size selection and incomplete data on all mammographic projections. Despite these limitations, the findings highlight the need for continued assessment of patient doses to optimize mammography practices and address the absence of quality standardization acts in Saudi Arabia. These insights are critical for governing authorities to ensure that effective patient dose monitoring occurs regularly and that the establishment of minimum quality standards for breast cancer screening is intact.

Dendrimer-enhanced (DEP) SN38 (DEP irinotecan) in patients (pts) with advanced solid tumors: A phase 1/2 trial.

3014 Background: Dendrimer nanoparticles enable prolonged cytotoxic drug targeting to tumors. DEP SN38 is a water-soluble version of SN38, the active metabolite of irinotecan, attached to a dendrimer, so avoiding usual metabolic pathways of conventional irinotecan (c-IRI). This phase 1/2 (P1/2) trial evaluated safety, tolerability and efficacy of DEP SN38 in pts with advanced solid tumors, including colorectal (CRC), platinum-resistant high-grade serous ovarian (HGSOC) and breast (BC). Methods: Pts who had exhausted standard therapy were enrolled in dose assessment (P1)/dose expansion (P2) cohorts of DEP SN38 given IV 3-weekly (Q3W) or Q2W alone or in combination with 5-fluorouracil &amp; leucovorin (5FU/LV combo). Efficacy was evaluated by RECIST 1.1 and serum tumor markers. (EudraCT 2019-001318-40). Results: 114 pts were enrolled. The Q3W Recommended Dose (RD) was 12.5 mg/m2 SN38 with dose limiting toxicity (DLT) in 1/7 pts (grade (G) 4 neutropenia &gt; 7d). The Q2W RD was 12.5 mg/m2 for SN38 alone or with 5FU/LV. DEP SN38 was well-tolerated for all dose regimens with mostly mild/moderate (G1/2) treatment-related adverse events (TRAEs) &amp; no new events compared with c-IRI. TRAEs in ≥ 10% pts included neutropenia, thrombocytopenia, anemia, fatigue, nausea, vomiting, diarrhea, constipation and alopecia. Of734 DEP SN38 cycles only 1 event of G3 diarrhea (0.9% pts) and no cholinergic symptoms have been observed, contrasting with c-IRI (~20% &amp; 47% pts respectively). G3 nausea (1.8% pts) and vomiting (0.9% pts) occurred less frequently than with c-IRI (both ~10% pts). Febrile neutropenia was the DLT at 15 mg/m2 Q2W monotherapy (2/6 pts), with neutropenia otherwise essentially uneventful and managed with G-CSF. 38 CRC pts received DEP SN38 monotherapy (31 evaluable) and 17 received the 5FU/LV combo (14 evaluable). CRC pts had a mean 4 prior lines with 97% receiving ≥ 1 c-IRI containing line. The disease control rate (DCR) in monotherapy was 48% (stable disease (SD) up to 72 wks). The 5FU/LV combo cohort DCR was 85.7%, the objective response rate (ORR) was 14.3%, with disease control observed for at least 35 wks. Several CRC pts continue combo treatment. 23 HGSOC pts with a mean of 6 prior lines received DEP SN38 monotherapy (18 evaluable). The DCR for Q2W was 100% with 33.3% ORR, and 72% DCR for all HGSOC pts. 3 pts have PRs for at least 36 wks; with 1 pt achieving complete tumor &amp; ascites resolution. Reduced CA-125 of up to 98% was observed in 75% pts. Several HGSOC pts continue DEP SN38 treatment. 8 BC pts with a mean of 7 prior lines received DEP SN38 monotherapy Q3W (5 evaluable). The DCR was 100% with SD up to 72 wks. Conclusions: DEP SN38 shows promising clinical utility with encouraging antitumor activity including prolonged disease control &amp; durable PRs in heavily pre-treated CRC, HGSOC &amp; BC pts. DEP SN38 is well-tolerated with significantly fewer severe gastrointestinal TRAEs compared to c-IRI, &amp; warrants further clinical assessment. Clinical trial information: 2019-001318-40 .

Multidisciplinary consensus on the use of hydroxychloroquine in patients with systemic lupus erythematosus

BackgroundHydroxychloroquine (HCQ) is the first-line treatment for systemic lupus erythematosus (SLE); however, there is heterogeneity in its clinical use. This consensus aims to bridge the gap in SLE treatment by providing practical and valuable recommendations for health professionals. MethodsThe methodology used is based on a systematic literature review and a nominal group technique (NGT). A ten-member scientific committee formulated eight clinically relevant questions. First, a systematic review was conducted to identify the available evidence, which the scientific committee evaluated to developed recommendations based on their expertise, achieving consensus through NGT. Results1673 titles and abstracts were screened, and 43 studies were included for meeting the inclusion criteria. The scientific committee established 11 recommendations for HCQ use in initiation, maintenance, and monitoring, considering benefits and potential adverse effects of HCQ. Unanimous agreement was achieved on all recommendations. ConclusionsThe available evidence supports HCQ's effectiveness and safety for SLE. Individualized assessment of the initial HCQ dose is important, especially in situations requiring dose reduction or discontinuation. This risk–benefit assessment, specifically focusing on the balance between retinal toxicity and the risk of SLE relapse, should guide decisions regarding medication withdrawal, considering disease activity, risk factors, and HCQ potential benefits. Close monitoring is essential for optimal disease management and minimize potential risks, such as QT prolongation or retinal toxicity.

Results from 2023 interlaboratory comparison in Southeast and East Asia on OSL personal dosimeter performance in photon fields

The intercomparison of personal dose equivalent (Hp(10)) among nine economies was carried out at 27 Individual Monitoring Service (IMS) Laboratories in Southeast and East Asia in 2023. In this programme, a whole-body dose assessment from Cs-137 and N-80 X-rays with two different incident beam angles (0 deg and 30 deg) was performed using an Optically Stimulated Luminescence (OSL) dosimeter. The trumpet curve recommended by IAEA GSG-7 was used as the criterion of acceptance value. The results showed that 95% of all data were within the acceptable value, with 13 items of data from two laboratories being unacceptable. After the intercomparison programme was concluded, these two laboratories implemented system improvement, including reader performance checks, calibration, configuration adjustment, and dose evaluation method enhancement. The results after improvement fell within the acceptable limit, indicating successful system enhancement. This study contributes to the harmonisation of individual monitoring service laboratories in Southeast and East Asia, ensuring that measurement results are traceable to the International System of Units (SI). Each laboratory fulfils the performance standard requirements to ensure the validity of the results for the individual monitoring service laboratory. Moreover, the complementary study induced by this exercise indicates the necessity of the intercomparison programme and successful outcome of the system improvement.

A phase 1/2, open-label, multicenter trial investigating the safety, tolerability, and preliminary antineoplastic activity of IPH6501, a first-in-class NK cell engager, in patients with relapsed and/or refractory CD20-expressing non-Hodgkin lymphoma.

TPS7095 Background: The therapeutic landscape for relapsed and/or refractory B-cell non-Hodgkin lymphoma (B-NHL) is evolving to include targeted T-cell based immunotherapies. However, there remains an unmet medical need for patients who are refractory to, relapsing from, or are ineligible for these therapies. Leveraging natural killer (NK) cells emerges as a promising strategy, as demonstrated in a Phase 1 study with IPH6101/SAR’579 in R/R AML (Stein, ASCO 2023; Bajel, ASH 2023), and offers a novel approach that could complement or provide an alternative to T-cell therapies. IPH6501 is a first-in-class tetraspecific antibody-based NK cell engager that simultaneously targets the CD16a and NKp46 receptors on NK cells and CD20 on B-NHL cells. It also includes an engineered IL-2 variant designed with mutations to avoid binding to CD25 (IL-2Rα), limiting Treg activation and potential IL-2 related side effects, whilst inducing NK proliferation. In preclinical animal models, IPH6501 boosted NK cell proliferation and activation, and CD20+ target cell elimination in peripheral blood and tissues, at well-tolerated doses. In samples obtained from R/R B-NHL patients, IPH6501 demonstrated greater killing efficacy compared to a CD3xCD20 T-cell engager, and yet lower cytokine secretion, suggesting a potentially safer profile. Methods: This is a global first-in-human, multicenter, open-label Phase 1/2 study to evaluate the safety profile (DLTs and MTD), tolerability according to NCI-CTCAE v5.0 and to determine the RP2D of IPH6501 for patients with B-NHL (NCT06088654). Secondary objectives are to characterize the pharmacokinetic profile and evaluate the immunogenicity of IPH6501. Eligible subjects are aged ≥18 years with advanced, histologically confirmed, CD20+ B-NHL with an ECOG PS ≤2, and without established alternative therapy. Subjects must have received ≥2 prior systemic therapies which may have included astem cell transplant or CAR-T cell therapy. The Phase 1 part of the study will consist of a dose escalation part which will follow a3+3 design to determine the MTD or the highest dose to be tested as defined in protocol if the MTD has not been reached, and a dose assessment part to randomize ≥2 dose levels to determine the RP2D. The Phase 2 part will enroll one or more cohorts of selected B-cell NHL subtypes to be determined at a later stage. Up to 184 subjects will be enrolled, and the study is open in the United States, Australia and Europe. Clinical trial information: NCT06088654 .

Commissioning of the first hospital-based PET radiopharmaceutical cyclotron in Greece: personnel dose assessment

The role of 18F–fluoro–deoxy–glucose in positron emission tomography (PET) imaging is well established in diagnosis and management of cancer patients. Installations of on-site self-shielded mini cyclotrons are increasing. The Dose on Demand Biomarker Generator BG-75 was installed at Metaxa Cancer Hospital, Greece, in May 2021 and is the first hospital-based PET radiopharmaceutical cyclotron in the country. Personnel expected external exposure was established during commissioning; internal exposure is not expected. Personnel dose was estimated with two methods: survey meter measurements in various locations combined with the time spent in each location, and direct measurement using electronic personal dosemeters. Gamma and neutron radiation readings outside the cyclotron vault were at background levels. Inside the cyclotron vault, the highest recorded radiation readings by the target were 18 μSv h−1 for both gammas and neutrons with cyclotron in operational mode; at one meter, the values were 5 μSv h−1 and 4 μSv h−1, respectively. The annual expected whole body dose per cyclotron operator is 0.6 mSv, and the respective extremity dose 16 mSv. The annual expected whole body and extremity dose for the radiochemist is 0.3 mSv and 25 mSv, respectively. The respective annual dose estimates for the medical physicists are < 1 mSv. The expected personnel doses are well below the regulatory limits and local as low as reasonably achievable (ALARA) levels. With experience and a robust ALARA program, personnel exposure could be further reduced.