Evaluating optimal quality assurance and quality control conditions of activation measurements at the accelerator-based boron neutron capture therapy system employing a lithium target.

Evaluating neutron output is important to ensure proper dose delivery for patients in boron neutron capture therapy (BNCT). It requires efficient quality assurance (QA) and quality control (QC) while maintaining measurement accuracy. This study investigated the optimal measurement conditions for QA/QC of activation measurements using a high-purity germanium (HP-Ge) detector in an accelerator-based boron neutron capture therapy (AB-BNCT) system employing a lithium target. The QA/QC uncertainty of the activation measurement was evaluated based on counts, reproducibility, and standard radiation source uncertainties. Measurements in a polymethyl methacrylate (PMMA) cylindrical phantom using aluminum-manganese (Al-Mn) foils and aluminum-gold (Al-Au) foils and measurements in a water phantom using gold wire with and without cadmium cover were performed to determine the optimal measurement conditions. The QA/QC uncertainties of the activation measurements were 4.5% for Au and 4.6% for Mn. The optimum irradiation proton charge and measurement time were determined to be 36 C and 900 s for measurements in a PMMA cylindrical phantom, 7.0 C and 900 s for gold wire measurements in a water phantom, and 54 C and 900 s at 0-2.2 cm depth and 3,600 s at deeper depths for gold wire measurements with cadmium cover. Our results serve as a reference for determining measurement conditions when performing QA/QC of activation measurements using HP-Ge detectors at an AB-BNCT employing a lithium target.

Navigating cholestasis: identifying inborn errors of bile acid metabolism for precision diagnosis.

Inborn errors of bile acid metabolism (IEBAM) cause cholestasis during the neonatal period, and 8 types of IEBAM have been reported to date. IEBAM accounts for approximately 2% of cases of cholestasis of unknown cause. As only 10 patients have been identified in Japan, IEBAM presents diagnostic challenges due to the similarity of clinical symptoms with biliary atresia, thus necessitating precise differentiation to avoid unnecessary invasive procedures. Laboratory tests in IEBAM are characterized by normal γ-glutamyltransferase (GGT) and serum total bile acid (STBA) levels despite the presence of cholestasis; therefore, measuring STBA and GGT is essential to distinguishing biliary atresia from IEBAM. With suspected IEBAM, liquid chromatography-mass spectrometry (LC/MS) analysis of urinary bile acids is needed to optimize diagnostic and therapeutic efficacy and avoid open cholangiography and initiate treatment for primary bile acids such as cholic acid or chenodeoxycholic acid. This prospective report aims to increase awareness of IEBAM by highlighting the characteristics of general blood test and bile acid profiles from LC/MS analyses of blood, urine, and stool samples.

Genotype-Phenotype Correlations in Thirty Japanese Patients with Congenital Hypothyroidism Attributable to TG Defects.

CONTEXT: Thyroglobulin (Tg), encoded by TG, is essential for thyroid hormone synthesis. TG defects result in congenital hypothyroidism (CH). Most reported patients were born before the introduction of newborn screening (NBS). OBJECTIVE: We aimed to clarify the phenotypic features of patients with TG defects diagnosed and treated since the neonatal period. SUBJECTS AND METHODS: We screened 1061 patients with CH for thirteen CH-related genes and identified thirty patients with TG defects. One patient was diagnosed due to hypothyroidism-related symptoms and the rest were diagnosed via NBS. Patients were divided into two groups according to their genotypes, and clinical characteristics were compared. We evaluated the functionality of the seven missense variants using HEK293 cells. RESULTS: Twenty-seven rare TG variants were detected, including fifteen nonsense, three frameshift, two splice-site, and seven missense variants. Patients were divided into two groups: thirteen patients with biallelic truncating variants and seventeen patients with monoallelic/biallelic missense variants. Patients with missense variants were more likely to develop thyroid enlargement with TSH stimulation than patients with biallelic truncating variants. Patients with biallelic truncating variants invariably required full hormone replacement, whereas patients with missense variants required variable doses of levothyroxine. Loss of function of the seven missense variants was confirmed in vitro. CONCLUSION: To our knowledge, this is the largest investigation on the clinical presentation of TG defects diagnosed in the neonatal period. Patients with missense variants showed relatively mild hypothyroidism with compensative goiter. Patients with only truncating variants showed minimal or no compensative goiter and required full hormone replacement.

Dried blood spot-based newborn screening for bile acid synthesis disorders, Zellweger spectrum disorder, and Niemann-Pick type C1 by detection of bile acid metabolites.

OBJECTIVE: To examine whether it is possible to screen for bile acid synthesis disorders (BASDs) including peroxisome biogenesis disorder 1a (PBD1A) and Niemann-Pick type C1 (NPC1) at the time of newborn mass screening by measuring the intermediary metabolites of bile acid (BA) synthesis. METHODS: Patients with 3ß-hydroxy-ΔSuchy et al. (2021)5-C27-steroid dehydrogenase/isomerase (HSD3B7) deficiency (n = 2), 3-oxo-ΔPandak and Kakiyama (n.d.)4-steroid 5ß-reductase (SRD5B1) deficiency (n = 1), oxysterol 7α-hydroxylase (CYP7B1) deficiency (n = 1), PBD1A (n = 1), and NPC1 (n = 2) with available dried blood spot (DBS) samples collected in the neonatal period were included. DBSs from healthy neonates at 4 days of age (n = 1055) were also collected for the control. Disease specific BAs were measured by newly optimized liquid chromatography-tandem mass spectrometry with short run cycle (5-min/run). The results were validated by comparing with those obtained by the conventional condition with longer run cycle (76-min/run). RESULTS: In healthy specimens, taurocholic acid and cholic acid were the two major BAs which constituted approximately 80% in the measured BAs. The disease marker BAs presented <10%. In BASDs, the following BAs were determined for the disease specific markers: Glyco/tauro 3ß,7α,12α-trihydroxy-5-cholenoic acid 3-sulfate for HSD3B7 deficiency (>70%); glyco/tauro 7α,12α-dihydroxy-3-oxo-4-cholenoic acid for SRD5B1 deficiency (54%); tauro 3ß-hydroxy-5-cholenoic acid 3-sulfate for CYP7B1 deficiency (94%); 3α,7α,12α-trihydroxy-5ß-cholestanoic acid for PBD1A (78%); and tauro 3ß,7ß-dihydroxy-5-cholenoic acid 3-sulfate for NPC1 (26%). *The % in the parenthesis indicates the portion found in the patient's specimen. CONCLUSIONS: Early postnatal screening for BASDs, PBD1A and NPC1 is feasible with the described DBS-based method by measuring disease specific BAs. The present method is a quick and affordable test for screening for these inherited diseases.

MucoUp® as a spacer in brachytherapy for uterine cervical cancer: A first-in-human experience.

We first used MucoUp®, a hyaluronic acid used in endoscopic resection, as a spacer in brachytherapy. In five cervical cancer patients, MucoUp® insertion increased a 90% dose of the high-risk CTV to over 80 Gy while decreasing the dose of organs at risk. No related adverse events were observed.

Dosimetric investigation of whole-brain radiotherapy with helical intensity modulated radiation therapy and volumetric modulated arc therapy for scalp sparing.

Objective: Intensity-modulated radiotherapy (IMRT) is a well-established radiotherapy technique for delivering radiation to cancer with high conformity while sparing the surrounding normal tissue. Two main purposes of this study are: (1) to investigate dose calculation accuracy of helical IMRT (HIMRT) and volumetric-modulated arc therapy (VMAT) on surface region and (2) to evaluate the dosimetric efficacy of HIMRT and VMAT for scalp-sparing in whole brain radiotherapy (WBRT). Methods: First, using a radiochromic film and water-equivalent phantom with three types of boluses (1, 3, 5 mm), calculation/measurement dose agreement at the surface region in the VMAT and HIMRT plans were examined. Then, HIMRT, 6MV-VMAT and 10MV-VMAT with scalp-sparing, and two conventional three-dimensional conformal radiotherapy plans (6MV-3DCRT and 10MV-3DCRT; as reference data) were created for 30 patients with brain metastasis (30 Gy/10 fractions). The mean dose to the scalp and the scalp volume receiving 24 and 30 Gy were compared. Results: The percentage dose differences between the calculation and measurement were within 7%, except for the HIMRT plan at a depth of 1 mm. The averaged mean scalp doses [Gy], V24Gy [%], and V30Gy [%] (1SD) for 6MV-3DCRT, 10MV-3DCRT, HIMRT, 6MV-VMAT, and 10MV-VMAT were [26.6 (1.1), 86.4 (7.3), 13.2 (4.2)], [25.4 (1.0), 77.8 (7.5), 13.2 (4.2)], [23.2 (1.5), 42.8 (19.2), 0.2 (0.5)], [23.6 (1.6), 47.5 (17.9), 1.2 (1.8)], and [22.7 (1.7), 36.4 (17.6), 0.7 (1.1)], respectively. Conclusion: Regarding the dose parameters, HIMRT achieved a lower scalp dose compared with 6MV-VMAT. However, the highest ability to reduce the mean scalp dose was showed in 10MV-VMAT. Advances in knowledge: Scalp-sparing WBRT using HIMRT or VMAT may prevent radiation-induced alopecia in patients with BM.

Association of Type 2 Deiodinase Thr92Ala Polymorphism with Pediatric Obesity in Japanese Children: A Case-Control Study.

Genetic factors play critical roles in the onset and progression of obesity. Brown adipose tissue (BAT) activity is also critical for adiposity. The objective of this study was to evaluate the prevalence and effects of BAT gene polymorphisms in pediatric obesity. This case-control study included 270 non-obese and 86 obese children. All participants underwent genotyping for type 2 deiodinase (DIO2) Thr92Ala (rs225014). The prevalence of the homozygous Ala/Ala allele of the DIO2 gene in the obese group was 15.1% versus 6.3% in the non-obese group, resulting in an odds ratio (OR) of 3.393 (p = 0.003). The results of this study indicate that the homozygous Ala/Ala allele of the DIO2 gene is associated with an increased risk of pediatric obesity and suggest that pediatric obesity might be suitable for assessing the association with gene polymorphisms related to BAT, especially DIO2 Thr92Ala.

Intracranial stereotactic radiotherapy in off-isocenter target with SyncTraX FX4.

PURPOSE: We investigated the localization accuracy of the off-isocenter targets using SyncTraX FX4, a new image registration device. METHODS: In a phantom study, we used a MultiMet-WL Cube with metal targets at different distances from the isocenter. Image registrations were performed with SyncTraX and cone-beam computed tomography (CBCT). Nineteen fields with different gantry, collimator, and couch angles were delivered to each target. Localization errors of the off-isocenter targets were then evaluated. In a clinical study, localization accuracy was evaluated for 32 patients. First, image registration was performed using SyncTraX, and the accuracy of patient positioning was evaluated using CBCT. Next, positioning corrections were performed for intracranial setup errors exceeding the threshold (0.5 mm/0.5°) in each field. Finally, total setup uncertainty was evaluated using CBCT. Differences in dosimetric errors from planned doses between no patient positioning corrections during treatment and positioning corrections with SyncTraX were also evaluated. RESULTS: In the phantom study, the positioning accuracy on targets up to 7 cm from the isocenter was within 1 mm. In the clinical practice, the localization accuracies of SyncTraX were 0.35 ± 0.39 mm, 0.30 ± 0.24 mm, and 0.03 ± 0.27 mm in the lateral, vertical, and longitudinal directions, respectively. Post-treatment setup errors were reduced by correcting intrafractional setup errors with SyncTraX during treatment. Positioning corrections with SyncTraX reduced the maximum dosimetric error from 1.6% to 1.0%. CONCLUSIONS: SyncTraX provides satisfactory localization accuracy for the off-isocenter targets within 7 cm. SyncTraX reduce dosimetric errors caused by intrafractional setup errors during treatment.

Brown adipose tissue-derived MaR2 contributes to cold-induced resolution of inflammation.

Obesity induces chronic inflammation resulting in insulin resistance and metabolic disorders. Cold exposure can improve insulin sensitivity in humans and rodents, but the mechanisms have not been fully elucidated. Here, we find that cold resolves obesity-induced inflammation and insulin resistance and improves glucose tolerance in diet-induced obese mice. The beneficial effects of cold exposure on improving obesity-induced inflammation and insulin resistance depend on brown adipose tissue (BAT) and liver. Using targeted liquid chromatography with tandem mass spectrometry, we discovered that cold and ß3-adrenergic stimulation promote BAT to produce maresin 2 (MaR2), a member of the specialized pro-resolving mediators of bioactive lipids that play a role in the resolution of inflammation. Notably, MaR2 reduces inflammation in obesity in part by targeting macrophages in the liver. Thus, BAT-derived MaR2 could contribute to the beneficial effects of BAT activation in resolving obesity-induced inflammation and may inform therapeutic approaches to combat obesity and its complications.

Intrafraction stability using full head mask for brain stereotactic radiotherapy.

PURPOSE: We investigated the immobilization accuracy of a new type of thermoplastic mask-the Double Shell Positioning System (DSPS)-in terms of geometry and dose delivery. METHODS: Thirty-one consecutive patients with 1-5 brain metastases treated with stereotactic radiotherapy (SRT) were selected and divided into two groups. Patients were divided into two groups. One group of patients was immobilized by the DSPS (n = 9). Another group of patients was immobilized by a combination of the DSPS and a mouthpiece (n = 22). Patient repositioning was performed with cone beam computed tomography (CBCT) and six-degree of freedom couch. Additionally, CBCT images were acquired before and after treatment. Registration errors were analyzed with off-line review. The inter- and intrafractional setup errors, and planning target volume (PTV) margin were also calculated. Delivered doses were calculated by shifting the isocenter according to inter- and intrafractional setup errors. Dose differences of GTV D99% were compared between planned and delivered doses against the modified PTV margin of 1 mm. RESULTS: Interfractional setup errors associated with the mouthpiece group were significantly smaller than the translation errors in another group (p = 0.03). Intrafractional setup errors for the two groups were almost the same in all directions. PTV margins were 0.89 mm, 0.75 mm, and 0.90 mm for the DSPS combined with the mouthpiece in lateral, vertical, and longitudinal directions, respectively. Similarly, PTV margins were 1.20 mm, 0.72 mm, and 1.37 mm for the DSPS in the lateral, vertical, and longitudinal directions, respectively. Dose differences between planned and delivered doses were small enough to be within 1% for both groups. CONCLUSIONS: The geometric and dosimetric assessments revealed that the DSPS provides sufficient immobilization accuracy. Higher accuracy can be expected when the immobilization is combined with the use of a mouthpiece.

Investigation of clinical target volume segmentation for whole breast irradiation using three-dimensional convolutional neural networks with gradient-weighted class activation mapping.

This study aims to implement three-dimensional convolutional neural networks (3D-CNN) for clinical target volume (CTV) segmentation for whole breast irradiation and investigate the focus of 3D-CNNs during decision-making using gradient-weighted class activation mapping (Grad-CAM). A 3D-UNet CNN was adopted to conduct automatic segmentation of the CTV for breast cancer. The 3D-UNet was trained using three datasets of left-, right-, and both left- and right-sided breast cancer patients. Segmentation accuracy was evaluated using the Dice similarity coefficient (DSC). Grad-CAM was applied to trained CNNs. The DSCs for the datasets of the left-, right-, and both left- and right-sided breasts were on an average 0.88, 0.89, and 0.85, respectively. The Grad-CAM heatmaps showed that the 3D-UNet used for segmentation determined the CTV region from the target-side breast tissue and by referring to the opposite-side breast. Although the size of the dataset was limited, DSC ≥ 0.85 was achieved for the segmentation of breast CTV using the 3D-UNet. Grad-CAM indicates the applicable scope and limitations of using a CNN by indicating the focus of such networks during decision-making.

Trajectory log analysis and cone-beam CT-based daily dose calculation to investigate the dosimetric accuracy of intensity-modulated radiotherapy for gynecologic cancer.

This study evaluated unexpected dosimetric errors caused by machine control accuracy, patient setup errors, and patient weight changes/internal organ deformations. Trajectory log files for 13 gynecologic plans with seven- or nine-beam dynamic multileaf collimator (MLC) intensity-modulated radiation therapy (IMRT), and differences between expected and actual MLC positions and MUs were evaluated. Effects of patient setup errors on dosimetry were estimated by in-house software. To simulate residual patient setup errors after image-guided patient repositioning, planned dose distributions were recalculated (blurred dose) after the positions were randomly moved in three dimensions 0-2 mm (translation) and 0°-2° (rotation) 28 times per patient. Differences between planned and blurred doses in the clinical target volume (CTV) D98% and D2% were evaluated. Daily delivered doses were calculated from cone-beam computed tomography by the Hounsfield unit-to-density conversion method. Fractional and accumulated dose differences between original plans and actual delivery were evaluated by CTV D98% and D2% . The significance of accumulated doses was tested by the paired t test. Trajectory log file analysis showed that MLC positional errors were -0.01 ± 0.02 mm and MU delivery errors were 0.10 ± 0.10 MU. Differences in CTV D98% and D2% were <0.5% for simulated patient setup errors. Differences in CTV D98% and D2% were 2.4% or less between the fractional planned and delivered doses, but were 1.7% or less for the accumulated dose. Dosimetric errors were primarily caused by patient weight changes and internal organ deformation in gynecologic radiation therapy.

FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis.

Uncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue (BAT). Using high-throughput library screening of secreted peptides, we identify two fibroblast growth factors (FGF), FGF6 and FGF9, as potent inducers of UCP1 expression in adipocytes and preadipocytes. Surprisingly, this occurs through a mechanism independent of adipogenesis and involves FGF receptor-3 (FGFR3), prostaglandin-E2 and interaction between estrogen receptor-related alpha, flightless-1 (FLII) and leucine-rich-repeat-(in FLII)-interacting-protein-1 as a regulatory complex for UCP1 transcription. Physiologically, FGF6/9 expression in adipose is upregulated by exercise and cold in mice, and FGF9/FGFR3 expression in human neck fat is significantly associated with UCP1 expression. Loss of FGF9 impairs BAT thermogenesis. In vivo administration of FGF9 increases UCP1 expression and thermogenic capacity. Thus, FGF6 and FGF9 are adipokines that can regulate UCP1 through a transcriptional network that is dissociated from brown adipogenesis, and act to modulate systemic energy metabolism.

Aging-associated impairment in metabolic compensation by subcutaneous adipose tissue promotes diet-induced fatty liver disease in mice.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome, and its progression is associated with aging-associated impairment in metabolic homeostasis. Recently, energy metabolism in adipose tissue has been the subject of renewed interest, because significant energy expenditure can be induced in cells derived from white adipose tissue progenitors, in addition to brown adipose tissue (BAT). Here we evaluated whether aging-associated change in various adipose tissue depots affects the progression of NAFLD. METHODS: Six-week-old male C57BL/6NCrSlc mice were fed control chow (C) or high-fat diet (60% fat; HF) for 12 or 24 weeks (12w/C, 12w/HF, 24w/C and 24w/HF groups, respectively) or switched from C to HF diet at 18 weeks of age (24w/C/HF group) and fed for a further 24 weeks. Some 24w/HF mice received a subcutaneous transplantation of adipose progenitors (106 cells/mouse) from young donor mice. Basal energy expenditure, glucose tolerance, and liver and adipose tissue histology were then evaluated. In addition, features of senescence and the capacity of adipose progenitors to "brown" were compared in mice of various ages. RESULTS: 12w/HF mice demonstrated compensation in the forms of hypertrophy of interscapular classical BAT and the appearance of subcutaneous beige adipocytes, consistent with improved metabolic homeostasis. In contrast, 24w/HF and 24w/C/HF mice developed obesity, glucose intolerance, and severe NAFLD, with accelerated senescence and loss of adipose progenitors in subcutaneous fat tissues. Recruitment of adipose progenitors ameliorated these findings in 24w/HF mice. CONCLUSION: Impaired metabolic compensation in adipose tissue resulted in the progression of NAFLD, which was associated with aging-related deterioration in adipose progenitors. A new approach targeting adipose tissue progenitors might represent a potential strategy for the prevention of NAFLD.

12-Lipoxygenase Regulates Cold Adaptation and Glucose Metabolism by Producing the Omega-3 Lipid 12-HEPE from Brown Fat.

Distinct oxygenases and their oxylipin products have been shown to participate in thermogenesis by mediating physiological adaptations required to sustain body temperature. Since the role of the lipoxygenase (LOX) family in cold adaptation remains elusive, we aimed to investigate whether, and how, LOX activity is required for cold adaptation and to identify LOX-derived lipid mediators that could serve as putative cold mimetics with therapeutic potential to combat diabetes. By utilizing mass-spectrometry-based lipidomics in mice and humans, we demonstrated that cold and ß3-adrenergic stimulation could promote the biosynthesis and release of 12-LOX metabolites from brown adipose tissue (BAT). Moreover, 12-LOX ablation in mouse brown adipocytes impaired glucose uptake and metabolism, resulting in blunted adaptation to the cold in vivo. The cold-induced 12-LOX product 12-HEPE was found to be a batokine that improves glucose metabolism by promoting glucose uptake into adipocytes and skeletal muscle through activation of an insulin-like intracellular signaling pathway.

Patient organ doses from megavoltage computed tomography delivery with a helical tomotherapy unit using a general treatment planning system.

The purpose of this study was to quantify actual patient organ doses from megavoltage computed tomography (MVCT) using an MVCT beam model of a helical tomotherapy unit in a general treatment planning system (TPS). Dosimetric parameters (percentage depth dose, lateral beam profile, and longitudinal beam profile) of the MVCT beam were measured using Gafchromic EBT3 films (ISP Corporation, Wayne, NJ, USA) and used for beam modeling in a Pinnacle3 TPS (Philips, Amsterdam, Netherlands); this TPS is widely used with linear accelerators. The created beam model was adjusted and validated by assessing point doses in a cylindrical phantom in static and helical beam plans with fine, normal and coarse pitches. Maximum doses delivered to important organs from MVCT delivery for five clinical cases were calculated using the created beam model. The difference (average ± one standard deviation for all evaluation points) between calculated and measured doses was -0.69 ± 1.20% in the static beam plan. In the helical beam plan, the differences were 1.83 ± 2.65%, 1.35 ± 5.94% and -0.66 ± 8.48% for fine, normal and coarse pitches, respectively. The average maximum additional dose to important organs from MVCT in clinical cases was 0.82% of the prescribed dose. In conclusion, we investigated a method for quantifying patient organ dose from MVCT delivery on helical tomotherapy using an MVCT beam model in a general TPS. This technique enables estimation of the patient-specific organ dose from MVCT delivery, without the need for additional equipment.

High-fat diet accelerates extreme obesity with hyperphagia in female heterozygous Mecp2-null mice.

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutation of the methyl-CpG-binding protein 2 (MECP2) gene. Although RTT has been associated with obesity, the underlying mechanism has not yet been elucidated. In this study, female heterozygous Mecp2-null mice (Mecp2+/- mice), a model of RTT, were fed a normal chow diet or high-fat diet (HFD), and the changes in molecular signaling pathways were investigated. Specifically, we examined the expression of genes related to the hypothalamus and dopamine reward circuitry, which represent a central network of feeding behavior control. In particular, dopamine reward circuitry has been shown to regulate hedonic feeding behavior, and its disruption is associated with HFD-related changes in palatability. The Mecp2+/- mice that were fed the normal chow showed normal body weight and food consumption, whereas those fed the HFD showed extreme obesity with hyperphagia, an increase of body fat mass, glucose intolerance, and insulin resistance compared with wild-type mice fed the HFD (WT-HFD mice). The main cause of obesity in Mecp2+/--HFD mice was a remarkable increase in calorie intake, with no difference in oxygen consumption or locomotor activity. Agouti-related peptide mRNA and protein levels were increased, whereas proopiomelanocortin mRNA and protein levels were reduced in Mecp2+/--HFD mice with hyperleptinemia, which play an essential role in appetite and satiety in the hypothalamus. The conditioned place preference test revealed that Mecp2+/- mice preferred the HFD. Tyrosine hydroxylase and dopamine transporter mRNA levels in the ventral tegmental area, and dopamine receptor and dopamine- and cAMP-regulated phosphoprotein mRNA levels in the nucleus accumbens were significantly lower in Mecp2+/--HFD mice than those of WT-HFD mice. Thus, HFD feeding induced dysregulation of food intake in the hypothalamus and dopamine reward circuitry, and accelerated the development of extreme obesity associated with addiction-like eating behavior in Mecp2+/- mice.

Output factor determination based on Monte Carlo simulation for small cone field in 10-MV photon beam.

The difficulty of measuring output factor (OPF) in a small field has been frequently discussed in recent publications. This study is aimed to determine the OPF in a small field using 10-MV photon beam and stereotactic conical collimator (cone). The OPF was measured by two diode detectors (SFD, EDGE detector) and one micro-ion chamber (PinPoint 3D chamber) in a water phantom. A Monte Carlo simulation using simplified detector model was performed to obtain the correction factor for the detector measurements. About 12% OPF difference was observed in the measurement at the smallest field (7.5 mm diameter) for EDGE detector and PinPoint 3D chamber. By applying the Monte Carlo-based correction factor to the measurement, the maximum discrepancy among the three detectors was reduced to within 3%. The results indicate that determination of OPF in a small field should be carefully performed. Especially, detector choice and appropriate correction factor application are very important in this regard.