Maximum Dose Research Articles

8097 A Rare Case of a Renal Cell Carcinoma and Pheochromocytoma Collision Tumor

Abstract Disclosure: R. Daas: None. S. Logan: None. W. Sexton: None. V. Chumbalkar: None. M. McGettigan: None. C. Veloski: None. Background: Collision tumors are neoplasms comprised of two or more distinct tumors. A collision tumor consisting of a renal cell carcinoma and pheochromocytoma is extremely rare with less than five cases reported in the literature. Clinical Case: A 64-year-old male with a history of hypertension and type 2 diabetes presented with hematuria. The patient was on 4 anti-hypertensive medications at the time. He noted increased road rage, anxiety, tremors, and insomnia. A CT abdomen/pelvis revealed an exophytic 8.6 x 7.9 cm left upper pole renal mass and a 7.5 x 6.2 cm left adrenal mass. Contrast-enhanced MRI abdomen showed a left upper/interpolar renal mass with heterogenous peripheral enhancement, restricted diffusion, and areas of central necrosis along with a heterogenous, enhancing left adrenal mass with associated restricted diffusion and areas of cystic necrosis. Both masses had associated areas of hyperintense signal on T1 fat-suppressed MRI suggestive of hemorrhage. Lab work revealed ACTH 26.6 pg/mL (7.2-63.3), cortisol 13 ug/dL (3.7-19.4), aldosterone 23.1 ng/dL (4-31), renin 4 ng/mL/hr (0.5-4), dopamine 136 pmol/L (<240), epinephrine 121 pmol/L (<330), norepinephrine 23,666 pmol/L (1050-4800), plasma normetanephrines 12.3 nmol/L (0-0.89), plasma metanephrines <0.10 nmol/L (0-0.49), 24-hour urine normetanephrines 4,178 mcg (122-676) and 24-hour urine metanephrines 4,233mcg (224-832). The patient was treated with alpha blockade prior to left radical nephrectomy, left adrenalectomy and infrahilar paraaortic lymph node dissection. Despite aggressive preoperative alpha blockade with maximal doses of doxazosin, addition of metyrosine and other anti-hypertensives, he developed acute hypertension with adrenal mass manipulation during the procedure and then hypotension following removal. He was admitted to the ICU for management of hypotension with pressors and fluid resuscitation and did well. Post-operative labs showed plasma normetanephrines 0.98 nmol/L (0.00-0.89) and plasma metanephrines 0.11 nmol/L (0.00-0.49). Pathology revealed clear cell renal cell carcinoma (RCC) of the kidney. The adrenal gland showed 2 tumors; one consistent with pheochromocytoma and another intimately associated with the former consistent with metastatic RCC, morphology diagnostic of a collision tumor. Following surgical resection, the patient was referred for genetic testing, surveillance imaging and lab testing, and treated with pembrolizumab adjuvant therapy for stage IV RCC. Conclusion: Although collision tumors are rare, biochemical testing to rule out a pheochromocytoma must be performed for all indeterminate adrenal masses and presumed adrenal metastases of active malignancies. Presentation: 6/2/2024

7805 Adrenocortical Carcinoma - A Tertiary Center's Recent ∼10-Year Experience

Abstract Disclosure: E. Osher: None. K.M. Tordjman: None. Y. Sofer: None. N. Stern: None. J. Klausner: None. G. Lahat: None. N. Lubezky: None. Y. Goykhman: None. B. Sagie: None. G. Ravit: None. A. Asaf: None. K. Rivka: None. W. Ido: None. Y. Greenman: None. Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Prospective randomized controlled studies to evaluate the optimal treatment modalities are limited. Therefore, retrospective studies are needed. The aim of the study is to describe and summarize additional data and knowledge on treatment modalities in a tertiary medical center treating patients with ACC by a multidisciplinary expert team. Methods: A retrospective study. Results: The study cohort included 42 subjects (57% females), followed for a median of 26 (range 0.3-237) months. The mean age at diagnosis was 54±17 years; 60% of tumors were functioning, 57 % were cortisol-secreting, 41% were androgen-secreting, 12% aldosterone-secreting, and 45% were co-secreting. ENSAT stage at diagnosis was stage 1 in 19%, stage 2 in 26%, stage 3 in 24% and stage 4 in 29%. Eighty-eight % of patients underwent surgery; residual disease was in 21% post surgery. Treatment with mitotane was initiated in 62% of patients, reaching a mean maximal dose of 3.1 ±2 grams/day. Oncologic pharmacological treatment (Chemotherapy, TKI, Immunotherapy) and/or radiation were given in 50 % and 21%, respectively. In 14 /42 patients, genetic evaluation was done, in most cases, no target for treatment was found. 52% of patients died during follow-up; all cohort median time to death was 31(range 0.3-237) months. Time to death longer than 31 months was also seen in advanced disease stage 3- 3/9(33%) and stage 4-4/11(36%). Except association between mitotane and prolonged time to death (p=0.013), no other factors (age, gender, surgery, radiation, residual disease functional status), were associated with prolonged survival. Conclusions: ACC remains a rare disease with a poor prognosis. However, it is a heterogeneous disease, with some patients with advanced disease achieving more prolonged survival. Further characterization of these patients may improve our understanding of the biology and treatment of this rare disease. Presentation: 6/2/2024

6537 Recurrent Graves Thyrotoxicosis After Prolonged Radioiodine-Induced Hypothyroidism

Abstract Disclosure: H.K. Deveaux: None. A. Gundeti: None. K. Mitrollari: None. A.P. Calimag: None. T. Yasmeen: None. Radioactive iodine (I-131) ablation (RAI) is one of the effective therapies for Graves’ disease (GD). Successful treatment is indicated by sustained, irreversible hypothyroidism requiring lifelong replacement for which recurrence of disease rarely develops. Recurrent hyperthyroidism is a rare development without apparent predisposition. Here, we describe a case of recurrent thyrotoxicosis after 36 years of RAI.70-year-old female PMH atrial fibrillation (AFib) on apixaban s/p cardioversion, HTN, HFpEF, Pulmonary HTN, and Graves’ Disease s/p RAI ablation 36 years ago with RAI-induced hypothyroidism. The patient was initially on levothyroxine for post-ablative hypothyroidism and stopped taking levothyroxine around 2019. NM scintigraphy done in 2019 showed an abnormal I-123 thyroid uptake and scan with the five-hour radioiodine thyroid uptake showed mildly hyperthyroid. On the thyroid scan, there is a note of a prominent pyramidal lobe with some thyroid gland asymmetry. In 2022, the patient was admitted for new-onset AFib and was noted to have subclinical hyperthyroidism with TSH 0.157, fT4 1.4, TrAb>40, and TSI 34.8. The patient was started on methimazole, which she stopped one month later. During this admission, the patient presented secondary to a mechanical fall and was found to be in AFib with a rapid ventricular rate. Her labs were significant for TSH<0.008 fT4 4.2, TrAb >40. Methimazole was restarted with maximal doses of diltiazem and metoprolol for rate control. Thyroid ultrasound demonstrated an enlarged, heterogeneous thyroid gland with increased vascularity and multiple bilateral TR3 thyroid nodules.Hyperthyroidism affects approximately 1.2% of the population. GD involves autoantibodies activating the thyrotropin receptor, increasing synthesis and release of thyroid hormone and is for 50-60% of cases with a 5-to-10-fold preference for females. RAI ablation is preferred, being inexpensive, with a cure rate approaching 100%. The incidence of transient hypothyroidism post-RAI varies from 9-17%. Retrospective studies have observed hyperthyroidism within the first 12 months post-RAI; however, some cases have seen a resurgence as late as 22 years later. Recurrent hyperthyroidism is an uncommon occurrence with various postulated aetiologies, such as inadequate dosing/incomplete ablation with residual cells remaining viable and regenerating in the setting of increased TSIiv, Marine-Lenhart syndrome (MLS), or an unclear mechanism associated with autoimmunity in the presence of TSI. Hyperthyroidism rarely recurs in GD after successful post-ablative treatment with RAI. Our case, while an uncommon presentation and underlying aetiology yet to be determined, illustrates the importance of continued surveillance, even after successful treatment.‌ Presentation: 6/3/2024

RTOG 0915-compliant patient specific QA for lung stereotactic body radiotherapy using the new PTW 1600SRS detector array

PurposeAn area of focus in radiotherapy is the treatment of oligometastatic lung cancer using highly conformal techniques such as SBRT, performed using VMAT that involves flattening filter free (FFF) beams. This study proposes a new calibration procedure for PTW Octavius 1600SRS detector array and was designed to also evaluate clinical and dosimetric aspects of a patient-specific quality assurance (PSQA) for lung SBRT patients. MethodsThe cohort consists of 20 patients, treated for lung metastases using SBRT with 50 Gy dose in 5 fractions (10 Gy/fr). The proposed calibration method uses only one calibration factor determined at maximum dose rate of 6MV FFF photon beam. The dosimetric accuracy of achieving a high dose gradient was analyzed using the RTOG 0915 protocol and was confirmed by PSQA procedures using the PTW Octavius 1600SRS detector. ResultsConformity index, gradient index, maximum dose at 2 cm and V20 parameters were evaluated with clinical favorable results, with only two plans with lesions situated in the inferior lobe exceeding the deviation allowed for the gradient index. Gamma passing rates using the new calibration method were 98.93% and 99.38% for different gamma criteria of 2 mm/2% and 1 mm/3%, respectively. ConclusionsThe proposed method for calibration using one calibration factor at maximum dose rate for the involved photon beam shows clinically acceptable gamma passing rates. Employing the RTOG 0915 protocol for lung SBRT treatment plan evaluation brings important dosimetric information about treatment plan quality and dose gradient fall-off which can be correlated with the results achieved during the pretreatment verification procedures.

Selective inhibition of HDAC class IIA as therapeutic intervention for KMT2A-rearranged acute lymphoblastic leukemia

KMT2A-rearranged acute lymphoblastic leukemia (ALL) is characterized by deregulation of the epigenome and shows susceptibility towards histone deacetylase (HDAC) inhibition. Most broad-spectrum HDAC inhibitors simultaneously target multiple human HDAC isoforms. Consequently, they often induce toxicity and especially in combination with other therapeutic agents. Therefore, more specifically targeting HDAC isoforms may represent a safer therapeutic strategy. Here we show that shRNA-mediated knock-down of the class IIA HDAC isoforms HDAC4, HDAC5, and HDAC7 results in apoptosis induction and cell cycle arrest in KMT2A-rearranged ALL cells. In concordance, the HDAC4/5 selective small molecule inhibitor LMK-235 effectively eradicates KMT2A-rearranged ALL cell lines as well as primary patient samples in vitro. However, using a xenograft mouse model of KMT2A-rearranged ALL we found that the maximum achievable dose of LMK-235 was insufficient to induce anti-leukemic effects in vivo. Similar results were obtained for the specific class IIA HDAC inhibitors MC1568 and TMP195. Finally, LMK-235 appeared to exert minimal anti-leukemic effects in vivo in combination with the BCL-2 inhibitor venetoclax, but not enough to prolong survival in treated mice. In conclusion, class IIA HDAC isoforms represent attractive therapeutic target in KMT2A-rearranged ALL, although clinical applications require the development of more stable and efficient specific HDAC inhibitors.

Preclinical Evaluation of 226Ac as a Theranostic Agent: Imaging, Dosimetry, and Therapy.

226Ac (t½ = 29.37 h) has been proposed as a theranostic radioisotope leveraging both its diagnostic γ-emissions and therapeutic α-emissions. 226Ac emits 158 and 230 keV γ-photons ideal for quantitative SPECT imaging and acts as an invivo generator of 4 high-energy α-particles. Because of these nuclear decay properties, 226Ac has potential to act as a standalone theranostic isotope. In this proof-of-concept study, we evaluated a preclinical 226Ac-radiopharmaceutical for its theranostic efficacy and present the first 226Ac-targeted α-therapy study. Methods: 226Ac was produced at TRIUMF and labeled with the chelator-peptide bioconjugate crown-TATE. [226Ac]Ac-crown-TATE was selected to target neuroendocrine tumors in male NRG mice bearing AR42J tumor xenografts for SPECT imaging, biodistribution, and therapy studies. A preclinical SPECT/CT scanner acquired quantitative images reconstructed from both the 158 and the 230 keV emissions. Mice in the biodistribution study were euthanized at 1, 3, 5, 24, and 48 h after injection, and internal radiation dosimetry was derived for the tumor and organs of interest to establish appropriate therapeutic activity levels. Mice in the therapy study were administered 125, 250, or 375 kBq treatments and were monitored for tumor size and body condition. Results: We present quantitative SPECT images of the invivo biodistribution of [226Ac]Ac-crown-TATE, which showed agreement with ex vivo measurements. Biodistribution studies demonstrated high uptake (>30%IA/g at 5 h after injection) and retention in the tumor, with an estimated mean absorbed dose coefficient of 222 mGy/kBq. [226Ac]Ac-crown-TATE treatments significantly extended the median survival from 7 d in the control groups to 16, 24, and 27 d in the 125, 250, and 375 kBq treatment groups, respectively. Survival was prolonged by slowing tumor growth, and no weight loss or toxicities were observed. Conclusion: This study highlights the theranostic potential of 226Ac as a standalone therapeutic isotope in addition to its demonstrated diagnostic capabilities to assess dosimetry in matched 225Ac-radiopharmaceuticals. Future studies will investigate maximum dose and toxicity to further explore the therapeutic potential of 226Ac-radiopharmaceuticals.

A detailed investigation on assessing the introduction of hybrid fibres in Geopolymer composites for pavement application

ABSTRACT Geopolymer concrete (GPC) has been widely researched as an emerging sustainable construction material. As GPC possesses excellent mechanical and durability properties, it is highly recommended for the construction of rigid pavements. However, the brittle nature of GPC limits its utilisation in heavy traffic roads, reducing its fatigue life. This study aims to minimise the brittleness of Pavement quality GPC (PQGPC) by adding hybrid fibres (steel fibre + polypropylene fibre). Fresh, hardened and durability properties of hybrid fibre-reinforced pavement quality geopolymer concrete (HGPC) under ambient curing have been analysed. In addition, the experimental study also compared the flexural fatigue life of PQGPC with that of the best HGPC mix. Both fibres were added in the same % (by volume) up to a maximum dosage of 1.25% each. Results show that workability decreases with increased fibre addition, but compressive and flexural strength increases with an increment in the quantity of fibres up to 1%. It was observed that the abrasion resistance and shrinkage resistance also increase with the inclusion of hybrid fibres in HGPC. Fatigue results prove that the fatigue life of HGPC-3 (with 2% hybrid fibres addition) mix under medium and heavy loads is 40% and 28%, higher than PQGPC.

Single Fraction Radiosurgical Tolerance of Brainstem, Trigeminal Nerve, and Meckel's Cave for Facial Numbness

IntroductionThe purpose of this article is to review toxicity outcomes for a series of patients treated with stereotactic radiosurgery (SRS) for trigeminal neuralgia, focusing on dose to the brainstem, trigeminal nerve, and Meckel's cave as possible explanatory variables for the development of the most common post-treatment neuropathy, facial numbness. MaterialsA retrospective review of 136 cases treated with Cyberknife radiosurgery for trigeminal neuralgia was performed. Dose was initially (cohort 1) prescribed to 57 to 64 Gy covering a 6mm cylindrical shaped target volume at least 2mm from the dorsal root entry zone (DREZ). Subsequently a deliberate change to isocentric treatment planning occurred, resulting in delivery of 85 Gy to a spherical target (cohort 2). Brainstem, trigeminal nerve, and Meckel's cave were contoured and a variety of dosimetric and clinical factors were analyzed for association with development of treatment related facial numbness. ResultsTreatment-related numbness occurred in 59/136 (43%) patients and did not differ between the treatment cohorts. Fifty-two patients experienced BNI grade II toxicity, and 7 patients experienced BNI grade III toxicity. Time to numbness was 16.0 months for cohort 1 and 10.4 months for cohort 2 (p=0.184). The median brainstem maximum dose was 26.1 Gy, ranging from 4.2 Gy to 57.3 Gy. Maximum dose to the trigeminal nerve was 85 Gy. Mean trigeminal nerve dose was 47.3 Gy. The median Meckel's cave maximum and mean doses were 26.0 Gy and 6.8 Gy, respectively. No definitive upper limit dose threshold was detected for the structures analyzed, but trends were noted for maximum trigeminal nerve dose of 85 Gy (p=0.083) and for prescription dose (p=0.057) and trigeminal nerve V40 (p=0.077) in the Type I subset. ConclusionsBrainstem, trigeminal nerve, and Meckel's cave tolerated doses within the range delivered. Discussion of the literature is provided to guide treatment planning and management.

Enhancing Delivery Efficiency on the MR-Linac: A Comprehensive Evaluation of Prostate SBRT using VMAT

PurposeLong treatment sessions are a limitation within MRIgART. This work aims for significantly enhancing the delivery efficiency on the MR-linac by introducing dedicated optimization and delivery techniques for VMAT. VMAT plan and delivery quality during MRIgART is compared to step-and-shoot IMRT for prostate SBRT. Methods and MaterialsTen prostate patients previously treated on a 1.5T MR-linac were retrospectively replanned to 36.25 Gy in five fractions using step-and-shoot IMRT and the clinical Hyperion optimizer within Monaco (Hyp-IMRT), the same optimizer with a VMAT technique (Hyp-VMAT), and a research-based optimizer with VMAT (OFL+PGD-VMAT). The plans were then adapted onto each daily MRI dataset using two different optimization strategies to evaluate the ATP workflow: “optimize weights” (IMRT-Weights and VMAT-Weights) and “optimize shapes” (IMRT-Shapes and VMAT-Shapes). Treatment efficiency was evaluated by measuring optimization time, delivery time, and total time (optimization + delivery). Plan quality was assessed by evaluating OAR sparing. Ten patient plans were measured using a modified linac control system to assess delivery accuracy via a gamma analysis (2%/2mm). Delivery efficiency was calculated as average dose rate divided by maximum dose rate. ResultsFor Hyp-VMAT and OFL+PGD-VMAT the total time was reduced by 124 ± 140 seconds (p = .020) and 459 ± 110 seconds (p < 0.001), respectively as compared to the clinical Hyp-IMRT group. Speed enhancements were also measured for ATP with reductions in total time of 404 ± 55 (p<0.001) for VMAT-Weights as compared to the clinical IMRT-Shapes group. Bladder and rectum DVH points were within 1.3 % or 0.8 cc for each group. All VMAT plans had gamma passing rates greater than 96 %. The delivery efficiency of VMAT plans was 89.7 ± 2.7 % compared to 50.0 ± 2.2 % for clinical IMRT. ConclusionsIncorporating VMAT into MRIgART will significantly reduce treatment session times while maintaining equivalent plan quality.

Ketorolac Dose Ceiling Effect for Pediatric Headache in the Emergency Department

OBJECTIVE This study sought to demonstrate a non-inferiority analgesic ceiling effect previously ­demonstrated within adults for pediatric patients receiving a maximum ketorolac dose of 15 mg. METHODS We conducted a retrospective cohort study of pediatric ED patients weighing at least 60 kg treated with 30 mg (pre-intervention) or 15 mg (post-intervention) intravenous (IV) ketorolac for headache. The primary outcome included patient-reported pain scores. Additional outcomes included demographic variables, adjunct medication use and adverse effects. Categorical data were evaluated using a χ2 test, and numerical data were evaluated using an ANOVA F test and Welch 2-sample t test. RESULTS The pre- and post-intervention groups included 216 and 62 patients, respectively. Overall demographics were similar between the groups (72.3% female, 49.3% White/Caucasian, mean age 15.5 years, mean weight 79.2 kg, and mean baseline 10-point pain score 7.5). Twelve (5.6%) in the pre-intervention group required rescue analgesic compared with 2 patients (3.2%) in the post-intervention group (p = 0.416). In the pre-intervention group, 198 patients (91.7%) received nausea medication compared with 52 patients (83.9%) in the post-intervention group (p = 0.087). Mean 10-point pain scores following ketorolac administration decreased by 3.9 in the pre-intervention group compared with 5.1 in the post-intervention group (p = &amp;lt; 0.001). Common (0.9%) or rare (0.9%) side effects were infrequent and only seen in the pre-intervention group patients. CONCLUSIONS Truncating the maximum intravenous ketorolac dose in pediatric patients at least 60 kg in weight to 15 mg compared with 30 mg results in effective analgesia in pediatric patients with headache. Future research could explore differences in admission rates, treatment of other indications, or treatment with multiple-dose regimens.

Development of learning-based predictive models for radiation-induced atrial fibrillation in non-small cell lung cancer patients by integrating patient-specific clinical, dosimetry, and diagnostic information

Background and purposeRadiotherapy (RT) in non-small cell lung cancer (NSCLC) can induce cardiac adverse events, including atrial fibrillation (AF), despite advanced RT. This study integrates patient-specific information to develop learning-based models to predict the incidence of AF following NSCLC chemoradiotherapy (CRT) and evaluates these models using institutional and external datasets. Materials and methodsInstitutional and external patient cohorts consisted of 321 and 187 NSCLC datasets who received definitive CRT, including 17 and 6 AF incidences, respectively. The network input had 159 features with clinical, dosimetry, and diagnostic. The class imbalance was mitigated by synthetic minority oversampling technique. To handle various types of input features, machine learning-based model adopted an intervention technique that chose one feature with the largest weight at each dosimetry sub-group in feature selection process, while deep learning-based model employed a hybrid architecture assigning different types of networks to corresponding input paths. Performance was assessed by area under the curve (AUC). The key features were investigated for the machine and deep learning-based models. ResultsThe hybrid deep learning model outperformed the machine learning-based algorithm in internal validation (AUC: 0.817 vs. 0.801) and produced more consistent performance in external validation (AUC: 0.806 vs. 0.776). Importantly, maximum dose to heart and sinoatrial node (SAN) were found to be the key features for both learning-based models in external and internal validations. ConclusionsThe learning-based predictive models showed consistent prediction performance across internal and external cohorts, identifying maximum heart and SAN dose as key features for the incidence of AF.

Comprehensive analysis of peripheral dose in electron beam therapy with a Varian TrueBeam Linac

ObjectiveTo investigate the characteristics of peripheral doses outside electron-beam applicators in Varian TrueBeam linacs. MethodPeripheral doses outside the electron applicator were measured for 6-, 9- and 12-MeV beams at the maximum dose depth (Dmax) for each energy source and at a source-to-surface distance of 100 cm. Measurements were performed using EBT3 films in solid water phantoms. The impact of field size on the penumbra width and peripheral doses was studied using various cutouts, including 3 cm × 3 cm, 6 cm × 6 cm, and 10 cm × 10 cm in a 10 cm × 10 cm applicator with the gantry and collimator at 0°. The influence of the applicator size was investigated using a circular cutout of 5 cm in diameter for various applicator sizes, including 6 cm × 6 cm, 10 cm × 10 cm, 15 cm × 15 cm, 20 × 20 cm, and 25 cm × 25 cm, at Dmax for each energy, while keeping the gantry and collimator angle at 0°. The measured dose profiles were compared with the Eclipse treatment planning system (TPS) predicted dose profiles. The effect of varying gantry angles (0°, 90°, and 270°) for a 3 cm × 3 cm cutout in a 10 cm × 10 cm applicator for each energy source and varying collimator angles (0°, 90°, and 270°) for a 10 cm × 10 cm field were investigated to determine their effects on the penumbra widths and peripheral doses. ResultsBoth the penumbra width and peripheral dose values increased with energy across different field sizes, gantry angles, collimator angles, and applicator sizes. Root Mean Square Deviation (RMSD) analysis indicated minimal differences between the measured profiles and TPS data. Peripheral doses remained below 5% of the maximum dose approximately 10–15 mm away from the field edges, suggesting the potential for implementing additional shielding where required. ConclusionsThis study highlights the importance of considering peripheral doses in electron radiotherapy. It is important to note the impact on healthy tissues beyond the treatment area to ensure patient safety and prevent the long-term side effects of treatment. These findings emphasize the necessity of implementing appropriate measures to minimize peripheral doses.

Measuring Spatial Radiation Dose Distribution During Abdominal Computed Tomography Scanning with Optically Stimulated Luminescence Dosimeters

PurposeAs the proportion of medical radiation exposure increases, the exposure dose has received increasing attention. When performing interventional radiological diagnosis, examiners are often exposed to radiation. Therefore, patients and medical personnel are exposed to higher amounts of radiation dose. Accordingly, we used optically stimulated luminescence dosimeters (OSLDs) to measure the ambient air kerma during abdominal CT scanning to observe the spatial distribution of the doses.MethodsAn abdominal CT scan under a voltage of 120 kVp was performed, and OSLDs were used for the measurement. The measurement range extended from the examination couch that serves as the center point to the walls and was divided into four areas. The OSLD measurements were undertaken at three different heights (i.e., 85, 140, and 150 cm from the floor) for spatial dose detection. The OSLDs were fixed up to lines at the three height levels. Each dosimetry point was 50 cm apart. In addition, the surface incident doses of the prosthesis's mammary gland, liver, and gonad were estimated.ResultsAccording to the spatial dose distribution at the three different heights, the maximum dose and minimum dose in front of the bore were 0.194 ± 0.008 and 0.006 ± 0.001 mGy, respectively; 2 m away from the bore, the dose reduced to 9% of the maximum dose. The surface incident doses of the mammary gland, liver, and gonad were 1.321 ± 0.121, 13.083 ± 0.642, and 13.441 ± 0.658 mGy, respectively.ConclusionThe spatial dose distribution revealed that the dose was the highest at the height of 140 cm and in front of the bore. The dose on the left side was higher than that on the right side. In addition, the dose was inversely proportional to the square of the distance. If the examiners must perform interventional radiological diagnosis during CT scanning, they should put on radiation protection equipment and stand behind the bore to minimize the radiation exposure.

Radiotherapy Dose Accumulation Routine (RADAR)- A novel dose accumulation script with built-in uncertainty

PurposeTo incorporate uncertainty into dose accumulation for reirradiation. MethodsThe RADAR script for the Eclipse treatment planning system (Varian Medical Systems, Palo Alto, CA) is described and the voxel-wise ellipsoid search algorithm is introduced as a means of incorporating uncertainty. RADAR is first demonstrated on a test patient reirradiated to the spine illustrating the effect of the uncertainty algorithm. A summary of initial evaluation testing by 11 users, each of whom ran a separate spine reirradiation case, follows. Finally, RADAR run times are reported for different conditions. ResultsIn the demonstration case in which a 3mm ellipsoid search was used, maximum RADAR 2 Gy equivalent (EQD2) accumulated spinal cord dose increased from 7244 cGy to 12689 cGy because the ellipsoid search pulled dose from closer to the adjacent target structure. When the ellipsoid search was restricted to voxels within the spinal cord, the maximum accumulated cord dose was reduced to 6523 cGy and did not exceed the sum of the maximum EQD2 spinal cord doses of the individual plans (6730 cGy). In the evaluation cases, the RADAR EQD2 maximum dose for the spinal cord increased an average of 31.6% with uncertainty applied compared to a conventional dose accumulation and decreased an average of 16.7% compared to a conventional dose accumulation when the uncertainty calculation was restricted to voxels within the spinal cord. RADAR run times depend on the number of plans being added and the type of uncertainty being used. ConclusionRADAR offers a novel way to directly account for uncertainty in dose accumulation by means of a voxel-wise ellipsoid search algorithm. EQD2 dose accumulation with and without dose discounts is also available.

Verification of mean dose in a tumor using 3D-printed tumor-model scintillators in anthropomorphic phantoms and a spherical phantom

To enhance treatment outcomes of radiotherapy, accurate verification of dosimetric parameters such as the mean, minimum, and maximum doses is essential. This study aimed to measure the mean absorbed dose in a tumor-shaped target and compare the results with the calculated value of the treatment planning system. Tumor model scintillators (TMSs) mimicking brain tumors were fabricated with a commercial 3D printer based on stereolithography files of tumors. The TMSs were irradiated following treatment plans made with the Leksell Gamma Plan® (Elekta AB, Stockholm, Sweden), and the mean dose in each TMS was measured three times and compared with the calculated value. Eleven TMSs were set at the center of a spherical solid water phantom. Two additional TMSs were fabricated according to images of vestibular schwannomas and were set at the tumor location in head model phantoms following each patient's head shape. The mean relative differences between the measured and calculated mean doses were less than one percent. This method provides an independent parameter for evaluating the accuracy of the treatment planning system.

Safety and Usefulness of Intracoronary Acetylcholine 200 μg Into the Left Coronary Artery as Vasoreactivity Testing: Comparisons With Intracoronary Acetylcholine Maximum 100 μg.

We retrospectively analyzed the usefulness and safety of intracoronary acetylcholine (ACh) 200 μg into the left coronary artery (LCA) as vasoreactivity testing compared with intracoronary ACh 100 μg. We recruited 1433 patients who had angina-like chest pain and intracoronary ACh testing in the LCA, including 1234 patients with a maximum ACh 100 μg and 199 patients with a maximum ACh 200 μg. ACh was injected in incremental doses of 20/50/100/200 μg into the LCA. Positive spasm was defined as ≥ 90% stenosis, usual chest pain, and ischemic electrocardiogram (ECG) changes. The incidence of coronary constriction ≥ 90%, usual chest pain, and ischemic ECG changes with a maximum ACh of 100 μg was markedly higher than that with a maximum ACh of 200 μg. The frequency of unusual chest pain in patients with a maximum ACh of 200 μg was higher than that in those with a maximum ACh of 100 μg (13% vs. 3%, p < 0.001). In patients with rest angina, positive spasm of maximum ACh 100 μg was significantly higher than that of maximum ACh 200 μg, whereas there was no difference regarding positive spasm in patients with atypical chest pain between the two ACh doses. Major complications (1.38% vs. 1.51%, p = 0.8565) and the occurrence of paroxysmal atrial fibrillation (1.81% vs. 2.63%, p = 0.6307) during ACh testing in the LCA were not different between the two maximum ACH doses. Intracoronary ACh 200 μg into the LCA is clinically useful and safe for vasoreactivity testing when intracoronary ACh 100 μg dose not provoke spasms.

Previously unrecognized and potentially consequential challenges facing Hsp90 inhibitors in cancer clinical trials.

Targeting the heat shock protein-90 (Hsp90)chaperone machinery in various cancers with 200 monotherapyor combined-therapy clinical trials since 1999 has not yielded any success of food and drug administration approval. Blames for the failures were unanimously directed at the Hsp90 inhibitorsortumors or both. However, analyses of recent cellular and genetic studies together with the Hsp90 data from the Human Protein Atlas database suggest that the vast variations in Hsp90 expression among different organs in patients might have been the actual cause. It is evident now that Hsp90β is the root of dose-limiting toxicity (DLT), whereas Hsp90α is a buffer of penetrated Hsp90 inhibitors. The more Hsp90α, the safer Hsp90β, and the lower DLT are for the host. Unfortunately, the dramatic variations of Hsp90, from total absence in theeye, muscle, pancreas, and heart to abundance in reproduction organs, lung, liver, and gastrointestinal track, would cause the selection of any fair toxicity biomarker and an effective maximum tolerable dose (MTD) of Hsp90 inhibitor extremely challenging. In theory, a safe MTD for the organs with high Hsp90 could harm the organs with low Hsp90. In reverse, a safe MTD for organs with low or undetectable Hsp90 would have little impact on the tumors, whose cells exhibit average 3-7% Hsp90 over the average 2-3% Hsp90 in normal cells. Moreover, not all tumor cell lines tested follow the "inhibitor binding-client protein degradation" paradigm. It is likely why the oral Hsp90 inhibitor TAS-116 (Pimitespib), which bypasses blood circulation and other organs, showed some beneficiary efficacy by conveniently hitting tumors along the gastrointestinal track. The critical question is what the next step will be for the Hsp90 chaperone as a cancer therapeutic target.

Variation in Opioid Agonist Dosing in Clinical Trials by Race and Ethnicity

Racial and ethnic disparities in access to treatment and quality of treatment for opioid use disorder (OUD) have been identified in usual care settings. In contrast, disparities in treatment quality within clinical trials are relatively unexamined. To estimate racial and ethnic differences in the dose of opioid agonist treatment for OUD in the first 4 weeks of treatment in clinical trials. This cohort study performed analysis of the methadone and buprenorphine treatment arms of 3 trials conducted by the National Institute on Drug Abuse Clinical Trials Network between May 2006, and January 31, 2017, at multiple Clinical Trials Network sites across the US. Trial participants who were randomized to and initiated buprenorphine or methadone treatment and who identified as Hispanic, non-Hispanic Black, or non-Hispanic White were included in the present study. Data were analyzed from November 1, 2023, to August 5, 2024. Combined race and ethnicity as self-classified by the patient at trial enrollment. The maximum daily dose of buprenorphine or methadone received in each week for the first 4 weeks of treatment. The mean dose and the percentage of patients receiving a higher dose (buprenorphine ≥16 mg and methadone ≥60 mg) were compared across race and ethnicity groups. A total of 1748 patients (1263 who initiated buprenorphine and 485 who initiated methadone treatment) were included in the analysis (1168 [66.8%] male; median age, 33 [IQR, 26-45] years). Of these, 138 patients (7.9%) identified as Black, 273 (15.6%) as Hispanic, and 1337 (76.5%) as White. In week 4, Black patients received buprenorphine doses 2.5 (95% CI -4.6 to -0.5) mg lower and methadone doses 16.7 (95% CI, -30.7 to -2.7) mg lower compared with White patients, after standardizing by age and sex. In week 4, the percentage of patients receiving a higher dose of medication (buprenorphine ≥16 mg; methadone ≥60 mg) was 16.9 (95% CI, -31.9 to -1.9) points lower for Black patients compared with White patients. Hispanic and White patients received similar buprenorphine doses; Hispanic patients received lower methadone doses than White patients. In this cohort study of data from 3 clinical trials, White patients generally received higher doses of medication than Black patients. Future research is needed to understand the mechanisms of and interventions to reduce disparities in OUD treatment quality and how such disparities impact generalizability of trial results.

Bilateral Ultrasound-Guided Erector Spinae Plane Block for Management of Acute Postoperative Surgical Pain After Pediatric Cardiac Surgeries Through a Midline Sternotomy.

Ultrasound (US) guided erector spinae plane block (ESPB) is a safe and effective technique in providing perioperative pain management in pediatrics with a high success rate. Was to compare the efficacy of bilateral ultrasound-guided erector spinae plane block for management of acute postoperative surgical pain after pediatric cardiac surgeries through a midline sternotomy. One hundred patients aged 4-12 years were randomly assigned into two groups, both groups received general anesthesia followed by bilateral sham erector spinae plane block at the level of T6 transverse process using 0.4 ml/kg normal saline on each side in the control group (group C) or bilateral ultrasound-guided erector spinae plane block at the level of T6 transverse process using 0.4 ml/kg ropivacaine 0.2% with a maximum dose of 2 mg/kg mixed with adrenaline 2 mcg/ml in erector spinae plane block group (group E). The postoperative pain scores were evaluated immediately post-extubation, at 1 hour, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours after extubation, total consumption of intraoperative fentanyl and time to first rescue analgesic administration were also recorded. There was a statistically high significant delay in the group E (314.72 ± 45.94) compared with the group C (36.7 ± 7.22) as regards to the mean (SD) of the time of the rescue analgesia (P < 0.001) (with 95% CI), moreover; the number of rescue analgesic was significantly higher in the group C compared with the group E (P < 0.001) (with 95% CI) and the mean (SD) of total intraoperative and postoperative levels fentanyl requirements in the group C were significantly higher compared with the group E (6.47 ± 0.98 and 5.09 ± 0.83) (with 95% CI) in group C versus (4.69 ± 0.71 and 2.31 ± 0.66) (with 95% CI) in group E respectively (P < 0.001) (with 95% CI). Ultrasound-guided bilateral ESPB with ropivacaine and adrenaline delays the postoperative need of analgesia and reduces postoperative fentanyl consumption at 24 h in pediatric patients undergoing cardiac surgery through midline sternotomy.

Efficacy and Safety of Adding Empagliflozin to Liraglutide on Renal Function in Patients with Advanced-Stage Type 2 Diabetic Kidney Disease: A Randomized Controlled Trial.

The aim of this study was to investigate the additional effects of empagliflozin on liraglutide in patients with advanced-stage type 2 diabetic kidney disease. Forty-one patients were randomly assigned (1:1) to treatment with liraglutide alone during the first 6 months and subsequent treatment with liraglutide plus empagliflozin during the next 6 months (liraglutide plus empagliflozin group) (n = 20) or treatment with liraglutide alone for 12 months (liraglutide group) (n = 21). Liraglutide was administered subcutaneously once daily at a starting dose of 0.3 mg/day and up-titrated weekly by 0.3 mg to a maximum dose of 0.9 mg/day. Empagliflozin was administered orally at a dose of 10 mg once daily. The primary outcome was the change in renal function (estimated glomerular filtration rate) during the latter 6 months. Secondary outcomes were changes in body weight, systolic blood pressure, hemoglobin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, uric acid, blood glucose, hemoglobin A1c, and urine protein creatinine ratio during the latter 6 months. Empagliflozin significantly increased the hemoglobin concentration (from 12.9 ± 1.9 to 13.7 ± 1.9 g/dL; p<0.05) and decreased body weight (from 66.1 ± 12.9 to 64.5 ± 12.6 kg; p<0.05). No significant differences were observed between the groups for estimated glomerular filtration rate, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, uric acid, blood glucose, hemoglobin A1c, and urine protein creatinine ratio. Empagliflozin increased hemoglobin concentration and decreased body weight in patients with advanced-stage type 2 diabetic kidney disease who received liraglutide. However, empagliflozin did not provide short-term benefits with regard to renal function decline, urinary protein excretion, or glycemic control in these patients.