Total Dose Research Articles

Construction of a realistic voxel phantom of the Japanese red fox (Vulpes vulpes japonica) based on MRI imaging and estimation of its background external radiation dose rate from environmental radionuclides

Abstract In this study, we selected the Japanese red fox (Vulpes vulpes japonica) as a representative mid-size mammal from the forests near the spent nuclear fuel reprocessing plant at Rokkasho. A fox voxel phantom was constructed based on magnetic resonance imaging of a female red fox caught in Rokkasho. This phantom consisted of 264 × 321 × 383 voxels (each voxel size: 0.78 × 0.78 × 2 mm) with internal organs. The external radiation dose rate to the voxel phantom by beta and gamma rays from environmental radionuclides was estimated using a Monte Carlo code (EGS4 and UCPIXEL). We estimated the dose rates to the phantom on the ground and in an average fox burrow in the Rokkasho forest, which were 11 and 27 nGy h−1, respectively. Assuming that the animal on the ground was irradiated by cosmic rays of 27 nGy h−1, the total external dose rate was evaluated to be 38 nGy h−1. Based on the assumption that the fox lives on the ground for 12 h and in the burrow for 12 h, the dose rate was estimated to be 33 nGy h−1.

Assessment of annual effective doses from indoor radon and thoron in Doi Lo, Chiang Mai, Thailand

Abstract This study aimed to determine the annual effective dose resulting from radon and thoron progeny inhalation. The levels of radon, thoron, and progeny were assessed in residences situated in the Doi Lo region of Chiang Mai, Thailand. Indoor radon and thoron concentrations were detected using passive discriminative detectors. Using a progeny deposition rate detector, this study evaluates radon and thoron progeny [equilibrium-equivalent radon concentration (EERC) for radon and equilibrium-equivalent thoron concentration (EETC) for thoron]. Data were collected from 44 dwellings between March and May 2020. The results found that indoor radon concentrations ranged from 17 to 118 Bq m−3, while thoron concentrations ranged from 12 to 72 Bq m−3. The radon progeny (EERC) ranged from 4 to 173 Bq m−3, whereas thoron progeny (EETC) ranged from 1 to 15 Bq m−3. The total annual effective dose received from radon and thoron progeny inhalation varied from 0.5 to 5 mSv y−1.

Radiation dose estimation for indoor radon, thoron and their progenies using a stochastic method—a small-scale survey in Wuhan, China

Abstract Passive radon monitors with CR-39s are widely used in major epidemiological surveys. However, the conventional CR-39 track density determining strategy makes it difficult to accurately estimate the concentration because of the heterogeneity of tracks on CR-39s. This study introduced a stochastic method, Latin hypercube sampling, to improve the track density determining strategy and provide the probability distribution of 222Rn concentration and equilibrium equivalent thoron concentration. The first 222Rn and 220Rn discriminated survey was conducted in Wuhan, China, in 2018 using RADUET® and deposition-based passive 220Rn progeny monitors and applying the stochastic method to the measurement. The results indicate that the stochastic method could decrease the effects of the track heterogeneity on the CR-39s and provide reliable results. The 220Rn progeny contributed more than 40% of the total inhalation dose in the survey, which cannot be ignored in urban family dwellings.

Oocyte maturity rate is an age-independent predictor of blastocyst development and euploidy rates: a multicenter retrospective study

Research Question Can oocyte maturity rate predict blastocyst development and euploidy rates independently of patient age? Design A multicenter retrospective study including 1547 consecutive women undergoing first in-vitro fertilization cycle of oocyte retrieval-intracytoplasmic sperm injection with preimplantation genetic testing for aneuploidy (IVF/ICSI/PGT-A). Both centers used the same PGT lab for PGT-A testing. Oocyte maturity rate as a predictor for cycle outcomes of blastocyst development and euploidy rates was analyzed by Poisson regression model, after controlling for other known confounders. Results Oocyte maturity rate is positively correlated with blastocyst development rate and euploidy rate after controlling for patient age at cycle start, BMI, AMH levels, total FSH dosage, number of days of ovarian stimulation, and peak estradiol level (p<0.01). Conclusion This study demonstrated that oocyte maturity rate can predict blastocyst development and euploidy rates independently of other confounding factors including patient age. This finding suggests that oocyte maturity rate may serve as an important biomarker for oocyte quality. This can be used by physicians to evaluate and improve the efficacy of ovarian stimulation regimens for IVF. This may further enhance artificial intelligence (AI) capabilities in optimizing ovarian stimulation protocols and outcomes of Assisted Reproductive Technologies (ART).

Bilateral erector spinae plane block on opioid-sparing effect in upper abdominal surgery: study protocol for a bi-center prospective randomized controlled trial

Abstract Background Erector spinae plane block (ESPB) is a promising technique for effective analgesia. It is still uncertain if ESPB offers the same opioid-sparing effect as thoracic paravertebral block (PVB) in midline incision for upper abdominal surgery. Methods The study is a prospective, bi-center, randomized, controlled, non-inferior trial. One hundred fifty-eight patients scheduled for upper abdominal surgery will be randomly assigned to receive bilateral ESPB or PVB before surgery. The primary outcome will be the equivalent cumulative analgesia dosage of sufentanil during the surgery, which is defined as the total dosage of sufentanil from anesthesia induction to tracheal extubation. The main secondary outcomes include postoperative complications and the quality of recovery-15 score at 24 h, 48 h, and 30 days after surgery. Discussion This study will assess the opioid-sparing efficacy of ESPB and PVB, complications, and the quality of recovery of two blocks. Trial registration ChiCTR2300073030 (https://www.chictr.org.cn/). Registered on 30 June 2023.

Efficacy of palliative hemostatic radiotherapy for tumor bleeding and pain relief in locally advanced pelvic gynecological malignancies

Abstract Purpose The appearance of symptomatic tumor-related vaginal bleeding and pain in advanced incurable cancer patients with pelvic gynecological malignancies remains a therapeutic challenge in oncological treatment. The aim of our analysis was to evaluate the efficacy and safety of palliative hemostatic radiotherapy. Methods We retrospectively identified patients who had received palliative hemostatic radiotherapy (RT) at our institution between 2011 and 2023 and evaluated acute toxicity, local control, cessation of bleeding, and pain relief. Results In total, 40 patients with a median planning target volume of 804 cm3 were treated with a median total dose of 39 Gy in 13 fractions, resulting in 6‑month and 1‑year local control rates of 66.9 and 60.8%, respectively. No higher-grade (>grade III) acute RT-induced toxicity appeared. Complete cessation of bleeding was achieved in 80.0% of all patients after a median of 16 days and pain relief was documented in 60.9% at first follow-up. 37.5% of the women required a blood transfusion and 25% an additional tamponade with local hemostatic agents. Successful stopping of bleeding was significantly less frequent in patients receiving anticoagulation concurrently with radiation and in the case of infield re-irradiation. Patients with a higher total RT dose had cessation of bleeding significantly more often, with a cut-off value of at least EQD2 (α/β = 10) = 36 Gy. The applied RT technique and planning target volume had no significant influence on the occurrence of bleeding cessation. Conclusion Palliative hemostatic radiotherapy for locally advanced pelvic gynecological malignancies is safe and effective in achieving high control rates of hemostasis in tumor bleeding and pain relief.

Impact of Body Mass Index on the Outcomes of Cryoballoon Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation

Background: Atrial fibrillation (AF) is prevalent among obese patients, and cryoballoon ablation (CBA) is an effective strategy for the rhythm control of AF. The impact of body mass index (BMI) on the clinical outcomes of CBA for AF is not fully explored. Methods: 85 consecutive patients with paroxysmal AF were enrolled and were categorized into three groups as per their BMI: normal weight (BMI 18.5–25 kg/m2), overweight (BMI 25–30 kg/m2), and obese patients (BMI > 30 kg/m2). The primary study endpoint was a late (12 month) recurrence of AF. Early recurrence of AF, symptom improvement, and procedural outcomes were some key secondary outcomes. Results: 20 patients had normal weight, 35 were overweight, and 30 were obese. Obese patients featured a higher prevalence of diabetes mellitus, heavier exposure to smoking, and worse baseline symptoms (as assessed through EHRA class at admission and 12 months before CBA) compared to overweight and normal weight patients. Both late and early (<3 months) AF recurrence rates were comparable across the three groups. Of note, obese patients showed greater improvement in their symptoms post-CBA, defined as improvement by at least one EHRA class, compared to normal weight patients; this might be explained by improved diastolic function. Total procedure time and dose area product were significantly increased in obese patients. The multivariate logistic regression analysis indicated that early AF recurrence and the duration of hypertension are independent predictors of late AF recurrence. Conclusion: CBA is effective in overweight and obese patients with paroxysmal AF. Procedure time and radiation exposure are increased in obese patients undergoing CBA.

Prone positioning is associated with increased insulin requirements in mechanically ventilated patients with COVID-19

AbstractStress hyperglycaemia is common in critical illness. We have previously observed that increasing severity of respiratory failure in patients with severe COVID-19 is associated with increased insulin demand. Given previously reported direct effects of hypoxia on insulin action, we reasoned that rapid improvements in oxygenation following prone positioning may improve insulin sensitivity and increase risk of hypoglycaemia. A retrospective multi-centre service evaluation comparing blood glucose and insulin administration in patients with COVID-19 pneumonitis receiving prone mechanical ventilation, comparing the 16 h pre-prone and 16 h post-prone time periods. 155 patients were included in this analysis. Oxygenation improved significantly following prone positioning (change in SpO2/FIO2 per hour prone: 3.01 ± 0.14, P < 0.0001). Glycaemic control was similar during the supine and prone study periods, and there were no hypoglycaemic events in the prone study period. Prone positioning was associated with an unexpected modest but significant increase in insulin requirements (mean difference in total insulin dose (IU): 8.32 ± 2.14, P < 0.001) that was robust to several sensitivity analyses, and could not be explained by changes in carbohydrate intake. We did not observe an increased rate of hypoglycaemia during prone ventilation and the adequacy of glycaemic control was comparable during the supine and prone study periods. Unexpectedly, prone ventilation was associated with an increase in insulin requirements despite significant improvement in hypoxaemia. Our findings support the safety of prone ventilation with respect to glycaemic control and identify a novel relationship between ventilation position and insulin requirements in critical illness.

De‐intensification of basal‐bolus therapy by replacing prandial insulin with once‐weekly subcutaneous semaglutide in individuals with well‐controlled type 2 diabetes: A single‐centre, open‐label randomised trial (TRANSITION‐T2D)

AbstractAimsThe study aims to examine the outcome of replacement of prandial insulin with once‐weekly subcutaneous semaglutide in people with type 2 diabetes reasonably controlled on multiple daily insulin injections (MDI).Materials and MethodsThis single‐centre, randomised, open‐label trial enrolled a statistically predetermined sample of 60 adults with HbA1c ≤7.5% (58 mmol/mol) receiving MDI, with a total daily dose (TDD) ≤120 units/day. Participants were assigned 2:1 to subcutaneous semaglutide 1.0 mg plus insulin degludec, or to continue MDI. The primary outcome was percentage of subjects maintaining HbA1c ≤7.5% (58 mmol/mol) at Week 26.ResultsAt Week 26, 90% of semaglutide and 75% of MDI subjects maintained HbA1c ≤7.5% (≤58 mmol/mol) (p = 0.18). Mean changes (95% CI) in HbA1c, weight and percentage body weight for semaglutide versus MDI, respectively, were −0.5% (−0.7, −0.3) versus 0.0% (−0.3, 0.3; p = 0.009); −8.9 kg (−9.9, −7.8) versus 1.5 kg (−0.1, 3.1; p < 0.001); and −8.6% (−9.6, −7.6) versus 1.4% (0.0, 2.8; p < 0.001). Insulin TDD decreased 56.0% (−62.3, −49.7) with semaglutide and increased 6.7% (−2.5, 16.0) with MDI (p < 0.001). Among semaglutide subjects, 58% reduced insulin TDD > 50%, 97.5% stopped prandial insulin and 45% lost >10% body weight. Participant treatment satisfaction scores trended higher with semaglutide. Hypoglycaemia frequency was similar between groups.ConclusionsIn people with type 2 diabetes well controlled (HbA1c ≤7.5% [≤58 mmol/mol]) on MDI ≤120 units/day, replacing multiple daily injections of prandial insulin with once‐weekly subcutaneous semaglutide can maintain and even improve HbA1c, lower body weight and lessen the burden of management.

Long-Term Investigation (1968–2023) of 137Cs in Apples

Due to the consequences of nuclear and/or radiological accidents in the past (Chernobyl, Fukushima, etc.), and potential future events of that kind, the constant monitoring of environmental radioactivity is important. There are different pathways of the transfer of radionuclides from environment to humans (ingestion, inhalation and external). Food ingestion greatly contributes to the total effective dose; hence, it is of great importance to investigate exposure to radionuclides through food. This paper presents the results of a long-term investigation of 137Cs activity concentration in apples in northwestern Croatia for the period 1968–2023. The highest 137Cs activity concentration in apples was measured in 1986, decreasing exponentially ever since. The Fukushima-Daiichi accident in 2011 did not cause a significant increase in 137Cs activity concentration, although the presence of the consequent fallout was detected via the appearance of 134Cs in some parts of the environment. The observed residence time for 137Cs in apples was estimated to be 4.5 and 3.9 years for the pre-Chernobyl and post-Chernobyl periods, respectively. The correlation between 137Cs in fallout and apples is very good, the correlation coefficients being 0.99, which indicates that fallout is the main source of contamination. The estimated effective dose received by adult members of the Croatian public due to intake of radiocaesium from apples over the overall observed period is 6.4 µSv. Therefore, the consumption of apples was not a critical pathway for the transfer of radiocaesium to humans.

Abstract 4136654: Urine Output Response to a Furosemide Infusion is Associated with Acute Kidney Injury in Infants Following Cardiac Surgery

Background: Acute kidney injury (AKI) following cardiac surgery in infants is common and associated with longer mechanical ventilation times and length of stay. Prior studies have shown that a lack of responsiveness to bolus dose furosemide has been associated with increased incidence of AKI. However, these studies have excluded patients on continuous furosemide infusions who are often younger, more hemodynamically unstable, and at higher risk for AKI. Hypothesis: Decreased urine output after initiation of a furosemide infusion predicts development of AKI. Methods: A retrospective cohort study of infants (<1 year of age) was conducted who underwent cardiac surgery requiring cardiopulmonary bypass from 2020-2023 and were on a furosemide infusion post-operatively. The primary outcome was post-operative AKI as defined using KDIGO (Kidney Disease: Improving Global Outcomes) guidelines. A furosemide response score (FRS) was calculated using the total urine output divided by the total dose of furosemide administered over a given time. Univariate and multivariate analyses were performed, and receiver operating characteristic curves used to determine the discriminatory ability of the FRS with regards to the primary outcome. Results: A total of 155 infants (median age at surgery 9 days) were included. Overall, 77% of infants met definition for the primary outcome of AKI; 32% stage 1, 30% stage 2, and 15% stage 3. Lower FRS at 4, 10, and 24 hours after infusion initiation were associated with AKI development (p<0.0001). Younger age, smaller weight at surgery, lack of pre-operative feedings, pre-operative inotropic use and higher surgical complexity were also associated with a higher risk of AKI. An FRS (mL/mg/kg) cutoff of <11.3 at 4 hours, <25.5 at 10 hours, and <55.3 at 24 hours had good discriminatory ability (area under the curve 0.7-0.75) in predicting AKI stage 2 or 3 (p<0.001). Controlling for the significant univariate variables listed above, the FRS cutoffs remained an independent risk factor for the development of AKI stage 2 or 3, (p<0.01) and were significantly associated with longer mechanical ventilation days and length of stay. Conclusion: Lack of responsiveness to a furosemide infusion (as measured by urine output corrected for dose of furosemide) is associated with the development of AKI in a high-risk cohort of infants. These novel findings may be helpful to predict those at risk and allow for further investigations for modifiable risk factors.

External Beam Radiotherapy for Malignant Central Airway Obstruction in a Remote Rural Patient: A Case Study

Introduction: Malignant central airway obstruction (MCAO) is a challenging therapeutic scenario, caused by tumour burden which limits airflow within the large airways. Squamous cell carcinoma (SCC) of the lung accounts for 50% of MCAO seen in the setting of non-small cell lung cancer. Here, we present the challenging case of a 63-year-old Indigenous Australian Female rom a remote rural community with background history of metastatic SCC of presumed pulmonary origin, who presented with a 1-week history of dyspnoea, stridor, and hoarse voice. Case Presentation: A CT chest and neck demonstrated a superior mediastinal mass compressing the trachea to a narrowest diameter of 3 mm. The patient was stabilised in her local health centre, then transferred to our tertiary care facility for further evaluation and management. This stenotic lesion was not amenable to bronchoscopic or surgical intervention but was instead treated successfully with a short course of external beam radiotherapy, to total dose of 25Gy delivered over 10 fractions. The patient had almost complete resolution of respiratory symptoms with no significant radiotherapy related toxicity. Conclusion: Here, we discuss a challenging case of MCAO in a remote rural Australian patient and demonstrate the utility of external beam radiotherapy in this setting. We also discuss aspects of cancer related healthcare disparities which exist for Indigenous Australians. In doing so, we wish to highlight the need for improved cancer healthcare for such communities.

RADT-11. FACTORS ASSOCIATED WITH LOCAL FAILURE AFTER STEREOTACTIC RADIATION TO THE SURGICAL BED OF BREAST CANCER PATIENTS WITH A SINGLE BRAIN METASTASIS

Abstract BACKGROUND Metastatic breast cancer is the second most common cancer associated with brain metastases (BCBM). In our study we evaluated variables that influence local control in this breast cancer patients with a single BCBM who underwent surgical resection and stereotactic radiation to resection cavity. METHODS After ethics approval, we conducted a retrospective review of the medical records of BCBM patients treated with stereotactic radiation for BCBM between 2011 to 2022. Only breast cancer patients with a single BCBM who underwent surgical resection and stereotactic radiation to the surgical cavity were included. Clinical and dosimetric variables were analyzed to evaluate their impact on local control. Statistical analysis included descriptive analyses. X2 test was used for categorical variables. Total dose, dose per fraction, biologically effective dose (BED), and planning target volumes were analyzed as both continuous and categorical variables at different thresholds. A binary regression model was applied to study variables shown to impact local control. RESULTS A total of 62 patients included local control was 70.9% at 12 months. HER-2 disease, luminal-B, size of BCBM, time from craniotomy, total dose, inclusion of corridor, and non-cystic lesion were significant for local control. CONCLUSION Our data supports previous publications about the importance of tumor bed delineation, dose and fractionation, and time from craniotomy as factors associated with better local control. Our study shows that the role of BCBM subtype and new systemic therapies in contributing to local and intracranial control should be further explored.

Increasing the effectiveness of total-skin electron beam therapy by reducing the manifestations of radiation dermatitis in patients with primary lymphomas. A comparative randomized prospective study

Background. One of the main adverse events that significantly reduce the quality of life of patients and limit the total focal dose is radiation-induced skin reactions (RISR). Their timely diagnosis, prevention, and treatment remain urgent tasks of modern radiotherapy. Aim. To improve the effectiveness of total skin irradiation (TSI) in patients with primary skin lymphomas by reducing the clinical manifestations of RISR by using additional therapy with a hydrogel containing active components with vasoprotective and anti-inflammatory action. Materials and methods. A comparative randomized prospective study was conducted, including data from 52 patients who received electron TSI by conventional fractionation at a total focal dose of 14 to 30 Gy for primary cutaneous lymphomas at the Granov Russian Research Center of Radiology and Surgical Technologies from September 2021 to January 2024. Before the first TSI session, during treatment and 2 weeks after the end of radiation therapy, all patients underwent assessment for RISR, quantitative assessment of various degrees of severity of radiodermatitis using instrumental methods and assessment scales; for the observation group, a therapeutic regimen for the prevention and treatment of RISR was used, including a hydrogel with troxerutin (2%) and trolamine (0.07%), and in the control group, basic skin care using moisturizers. Results. Analysis of the physiological parameters of the skin showed statistically significant differences between the study groups: patients of the study group (group I; 30 subjects receiving the above-mentioned therapeutic regimen) compared with the control group (group II; 28 subjects who did not receive specific treatment for radiodermatitis) reported significantly lower rates of erythema (386±12.3 and 572±14.4; p=0.005), transepidermal water loss (25±0.3 and 38±0.4 g/m2/h; p0.001) and a decrease in peak endothelial-dependent vasodilation of microvasculature and blood flow in the skin. A lower proportion of severe radiodermatitis (86.3 and 73.3%; p0.05) and a statistically significant difference in the subjective quality of life scores by the 29-point Skindex-29 scale by an average of 22.2% were also found. Conclusion. A comparative analysis of the quantitative indicators of radiodermatitis in the study group and the control group showed that the topical application of the hydrocolloid gel containing troxerutin and trolamine reduces the clinical manifestations of RISR concerning objectively measured physiological parameters of the skin and blood flow parameters of the microvasculature measured by high-frequency ultrasound, thus improving the quality of life of patients during and after the course of radiation therapy.

NCOG-04. MEMORY TRACT SPARING USING DIFFUSE TENSOR IMAGING IN RADIATION PLANNING OF PRIMARY BRAIN TUMORS

Abstract INTRODUCTION Radiation therapy (RT) is a critical treatment modality for both primary and metastatic brain tumors, yet approximately 30% of patients experience cognitive decline post-radiotherapy. This cognitive toxicity is linked to low radiation doses affecting neural stem cells in the hippocampal dentate gyrus. Hippocampal Avoidance (HA)-Whole Brain Radiotherapy (WBRT) combined with Memantine has shown promising outcomes in preserving cognitive function and quality of life (QOL) in patients with brain metastases, suggesting it should be the standard of care for those with good performance status and no hippocampal metastases. METHODS We conducted a prospective trial approved by the IRB (SMC0307-23), including patients aged 18 and above with primary brain tumors post-resection or biopsy. Exclusion criteria included multifocal glioma crossing to the other hemisphere. RT was delivered to a total dose of 60Gy in 30 fractions with concomitant TMZ. Diffusion tensor imaging (DTI) was performed to map hippocampal-associated white matter tracts. Memory fiber tracts and hippocampi were contoured and integrated into RT planning using Eclipse treatment planning software. Dosimetric analyses compared two plans: one with memory fiber constraints and one without. RESULTS Twelve patients with low-grade gliomas were included, with successful contouring of memory fibers and hippocampi. VMAT treatment plans met dose constraints for memory fibers, with an average mean dose of 10.1 Gy. The average MoCA score before RT was 27.1 and 26.4 at six months post-treatment, with a p-value of 0.07. Excluding one patient, the scores were 27.1 and 26.6, respectively (p=0.13). CONCLUSION MRI planning using DTI for memory fiber detection and incorporation into RT planning via VMAT techniques enables hippocampal and associated white fiber sparing, potentially preserving cognitive function. Preliminary cognitive data are promising, supporting the need for further validation in a larger cohort.

SURG-43. PATTERNS OF FAILURE FOLLOWING REIRRADIATION WITH GAMMA KNIFE STEREOTACTIC RADIOSURGERY FOR RECURRENT HIGH-GRADE GLIOMAS

Abstract Re-irradiation with stereotactic radiosurgery (SRS) is an increasingly used treatment for recurrent high-grade glioma (HGG). We analyzed the patterns of failure and outcomes of salvage Gamma Knife SRS for recurrent HGG to better identify which patients would most benefit. We reviewed all patients who received SRS for recurrent HGG from January 2008 to May 2020. Pattern of failure was defined by the distance of recurrence from the SRS isodose line as follows: in-field local, marginal local, regional local, and distant failure. Overall survival (OS), progression-free survival (PFS), and local-failure free survival (LFS) were estimated using Kaplan-Meier methods, and regression model analysis was performed to analyze clinical predictors of failure. A total of 146 patients with HGG underwent SRS treatment to 410 target lesions. The median target volume was 3.3 cm3 and median total dose was 18 Gy. Sixty-one (41.8%) patients developed progression following SRS. PFS at 6 and 12 months were 65.8% and 37.3% respectively. Median OS was 12.4 months from salvage SRS. There were 113 (79.5%) local failures (53.1% in-field, 45.1% marginal, and 1.8% regional), 2 (1.4%) distant, and 27 (19%) concomitant local and distant failures. LFS at 6 and 12 months was 82.9% and 66.6%, respectively. Non-white race (HR = 0.37), SRS dose ≥ 20 Gy (HR = 0.34), age < 60 years (HR = 0.43), and KPS ≥ 70 (HR = 0.44) were associated with longer time to local failure. Non-white race (HR = 5.55) and SRS dose ≥ 20 Gy (HR = 5.62) were associated with more distant failure. No grade 4 or 5 toxicity was observed. In conclusion, the dominant pattern of failure remains local and in-field despite conformal dose distribution with SRS and infiltrative tumor histology. This supports the role of reirradiation with SRS in well selected patients with recurrent HGG.

Safety and Tolerability of a Shorter Agalsidase Beta Infusion Time in Patients with Classic or Later-Onset Fabry Disease

Background: The multisystem manifestations of Fabry disease can create major challenges in patient care. Although enzyme replacement therapy with recombinant agalsidase beta has demonstrated clinical benefits, the standard fortnightly, multi-hour infusion regimen imposes a substantial burden on patients. Methods: We assessed the safety and feasibility of shortening the agalsidase beta infusion time to 90 min in adult patients with classic or later-onset Fabry disease in the absence of premedication. A total of 39 consecutive adult patients (agalsidase-naïve: n = 7; with significant comorbidities: n = 15) with no recent infusion-associated reactions underwent a total of 85 agalsidase beta infusions in our tertiary reference centre for lysosomal diseases. Each infusion was administered at a constant rate (between 0.78 and 1.17 mg/min, depending on the total dose administered). Results: No adverse events of any type (including discomfort and infusion-associated reactions) were reported during or after infusions. The patients’ vital signs and physical examination remained stable, and patients’ satisfaction was high. Conclusions: Our results suggest that shortening the agalsidase beta infusion time to 90 min is safe and feasible in stably treated adult patients with Fabry disease and no recent infusion-associated reactions.

INNV-25. POST-OPERATIVE LOW DOSE VERSUS STANDARD DOSE DEXAMETHASONE FOR MANAGEMENT OF CEREBRAL EDEMA: A RANDOMIZED, DOUBLE-BLINDED FEASIBILITY STUDY IN PATIENTS WITH PRIMARY OR METASTATIC BRAIN TUMORS UNDERGOING CRANIOTOMY FOR TUMOR RESECTION

Abstract INTRODUCTION Although dexamethasone is effective for controlling cerebral edema during the peri-operative period, its immunosuppressive properties can inhibit responses to immunotherapy. We hypothesized that patients with mild to moderate cerebral edema could be safely managed post-operatively with lower doses of dexamethasone. METHODS Eligible patients with brain tumors who had less than 10 mm of midline shift on their pre-operative brain MRIs were randomized 1:1 to the standard or low dose dexamethasone arm, each tapering double blinded through post-op day 8. The double blind was maintained using equivalent volumes for IV doses and capsules containing dexamethasone or placebo. By post-op day 9, participants received the same dose of dexamethasone and continued tapering to off by day 14. Additional doses of dexamethasone were allowed if needed, based on specified symptom criteria. Lack of feasibility was defined as a participant requiring 18 mg or more of dexamethasone in addition to the planned total dose of dexamethasone (low dose: 49 mg; standard dose: 112 mg). Brain MRIs were performed on post-operative days 1, 3, and 8 to evaluate changes in cerebral edema. Manual segmentation and computer-assisted techniques were used to quantitatively measure cerebral edema volume. RESULTS Twenty-six patients were randomized and treated within tumor type strata (primary versus metastatic), of which 25 were evaluable. None of the participants on the low dose dexamethasone arm met the criteria for lack of feasibility. The quantitative assessment of differences in cerebral edema between the arms is ongoing and will be presented. CONCLUSIONS Administration of lower doses of dexamethasone post-operatively to brain tumor patients with mild to moderate cerebral edema is feasible. Treatment with lower doses of dexamethasone post-operatively should be considered in this patient population when peri-operative administration of immunotherapy is planned.

The influence of daily imaging and target margin reduction on secondary cancer risk in image-guided and adaptive proton therapy

Objective. Image-guided and adaptive proton therapy rely on daily CBCT or CT imaging, which increases radiation dose and radiation-induced cancer risk. Online adaptation however also reduces setup uncertainty, and the additional risk might be compensated by reducing the setup robustness margin. This work developed a framework to investigate how much this robustness margin should be reduced to offset the secondary cancer risk from additional imaging dose and applied it to proton therapy for head-and-neck cancer.Approach. For five patients with head-and-neck cancer, voxel-wise CT and CBCT imaging doses were estimated with Monte Carlo radiation transport simulations, calibrated with air and PMMA phantom measurements. The total dose of several image-guided and adaptive treatments protocols was calculated by summing the planning CT dose, daily and weekly CBCT or CT dose, and therapy dose, robustly optimized with setup margins between 0 and 4 mm. These were compared to a reference protocol with 4 mm setup margin without daily imaging. All plans further used 3% range robustness. Organ-wise excess absolute risk (EAR) of cancer was calculated with three models to determine at which setup margin the total EAR of image-guided and adaptive treatment protocols was equal to the total EAR of the reference.Results. The difference between the simulated and measured CT and CBCT doses was within 10%. Using the Monte Carlo models, we found that a 1 mm setup margin reduction was sufficient for most patients, treatment protocols, and cancer risk models to compensate the additional risk imposed by daily and weekly imaging. For some protocols, even a smaller reduction sufficed, depending on the imaging frequency and type. The risk reduction by reducing the margin was mainly due to reducing the risk for carcinomas in the brain and, for some patients, the oral cavity.Significance. Our framework allows to compare an increased imaging dose with the reduced treatment dose from margin reductions in terms of radiation-induced cancer risk. It is extendable to different treatment sites, modalities, and imaging protocols, in clinic-specific or even patient-specific assessments.

Radiotherapy Effects on Airway Management in Patients with Nasopharyngeal Cancer

Background: At present, there is a paucity of data in the literature pertaining to the impact of radiotherapy (RT) on the success of tracheal intubation in patients with nasopharyngeal cancer (NPC). The aim of this study is to investigate the frequency of difficult tracheal intubation in patients with NPC following RT. Methods: Patients with NPC who underwent RT followed by surgery between 2012 and April 2024 at the University Hospital Heidelberg were retrospectively analyzed. Results: Twenty-three patients, predominantly males (73.9%) with a mean age of 52.9 years, were enrolled. Overall, 65.2% of the patients had an American Society of Anesthesiologists (ASA) class of III. The mean total laryngeal dose was 53.5 Gy for the main and boost plan, and the maximum total laryngeal dose was 66.61 Gy. Direct laryngoscopy was performed in 69.6% of cases, followed by 26.1% videolaryngoscopy, and 4.2% required fiberoptic intubation. In total, 47.8% of the patients had a Cormack/Lehane grade of I, followed by 43.5% with grade II and 8.7% with grade III. Overall, 87% of patients were successfully intubated on the first attempt. Conclusions: It has been demonstrated by previous studies that RT has the potential to enhance complications and difficulties encountered during airway management. While the results must be interpreted with caution, our study provides no evidence of severe impairment in advanced airway management in patients with nasopharyngeal cancer who have undergone radiotherapy.