PURPOSE: To investigate positional uncertainty and its correlation with clinical parameters in spine stereotactic body radiotherapy (SBRT) using thermoplastic mask (TM) immobilization. MATERIALS AND METHODS: A total of 21 patients who underwent spine SBRT for cervical or upper thoracic spinal lesions were retrospectively analyzed. All patients were treated with image guidance using cone beam computed tomography (CBCT) and 4 degrees-of-freedom (DoF) positional correction. Initial, pre-treatment, and post-treatment CBCTs were analyzed. Setup error (SE), pre-treatment residual error (preRE), post-treatment residual error (postRE), intrafraction motion before treatment (IM1), and intrafraction motion during treatment (IM2) were determined from 6 DoF manual rigid registration. RESULTS: The three-dimensional (3D) magnitudes of translational uncertainties (mean ± 2 standard deviation) were 3.7±3.5 mm (SE), 0.9±0.9 mm (preRE), 1.2±1.5 mm (postRE), 1.4±2.4 mm (IM1), and 0.9±1.0 mm (IM2), and average angular differences were 1.1°±1.2° (SE), 0.9°±1.1° (preRE), 0.9°±1.1° (postRE), 0.6°±0.9° (IM1), and 0.5°±0.5° (IM2). The 3D magnitude of SE, preRE, postRE, IM1, and IM2 exceeded 2 mm in 18, 0, 3, 3, and 1 patients, respectively. No association were found between all positional uncertainties and body mass index, pain score, and treatment location (p > 0.05, Mann-Whitney test). There was a tendency of intrafraction motion to increase with overall treatment time; however, the correlation was not statistically significant (p > 0.05, Spearman rank correlation test). CONCLUSION: In spine SBRT using TM immobilization, CBCT and 4 DoF alignment correction, a minimum residual translational uncertainty was 2 mm. Shortening overall treatment time and 6 DoF positional correction may further reduce positional uncertainties.
Body Mass Index ; Cone-Beam Computed Tomography ; Humans ; Immobilization ; Masks ; Neoplasm Metastasis ; Radiosurgery ; Radiotherapy ; Retrospective Studies ; Spine ; Uncertainty

Purpose: Exogenous epidermal growth factor (EGF) causes apoptosis in EGF receptor (EGFR)–overexpressing cell lines. The apoptosis-inducing factors could be a therapeutic target. We aimed to determine the mechanism of EGF-induced apoptosis using a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-based knockout screen. Materials and Methods: Two-vector system of the human genome-scale CRISPR knockout library v2 was used to target 19,050 genes using 123,411 single guide RNAs (sgRNAs). Recombinant human EGF (100 nM) or distilled water four times was administered to the experimental and control groups, respectively. The read counts of each sgRNA obtained from next-generation sequencing were analyzed using the edgeR algorithm. We used another EGFR-overexpressing cell line (A549) and short hairpin RNAs (shRNAs) targeting five EGF-resistance genes for validation. DUSP1 expression in A431, A549, and HEK293FT cells was calculated using reverse transcription–quantitative polymerase chain reaction. Results: We found 77 enriched and 189 depleted genes in the experimental group using the CRISPR-based knockout screen and identified the top five EGF-resistance genes: DDX20, LHFP, REPS1, DUSP1,<.i> and KRTAP10-12. Transfecting shRNAs targeting these genes into A549 cells significantly increased the surviving fractions after EGF treatment, compared with those observed in the control shRNA-transfected cells. The expression ratio of DUSP1 (inhibits ERK signaling) increased in A431 and A549 cells after EGF treatment. However, DUSP1 expression remained unchanged in HEK293FT cells after EGF treatment. Conclusion The CRISPR-based knockout screen revealed 266 genes possibly responsible for EGF-induced apoptosis. DUSP1 might be a critical component of EGF-induced apoptosis and a novel target for EGFR-overexpressing cancers.

PURPOSE: Idoxifene is currently entering phase II clinical trials for the treatment of advanced breast cancer. The radiolabeled idoxifene using 123I provides an opportunity for clinical pharmacology with single photon emission computed tomography (SPECT). The purpose of this study was to prepare radiolabeled idoxifene using 123I and to determine its cell uptake of breast cancer cell line. MATERIALS AND METHODS: With a view to evaluating new anticancer drugs, we are investigating the novel antiestrogen pyrrolidino- 4-iodotamoxifen (idoxifene). [123I]Idoxifene has been prepared in no-carrier-added form using a tributyl stannylated precursor which has been synthesized by means of (2-chloroethoxy)benzene with (+/-)-2- phenylbutanoic acid on the basis of previously reported standard methods. The biodistribution and dynamic behavior of the compound were investigated using the comparative breast cancer cell line, MCF-7 (estrogen receptor-positive) and MDA-MB-468 (non-estrogen receptor). RESULTS AND CONCLUSION: Acylation of (2-chloroethoxy)benzene with (+/-)-2-phenylbutanoic acid gave the versatile ketone (81%) which reacted with 1,4-diiodobenzene to give triphenylethylene as a mixture of E and Z geometric isomers, which were separated by the recrystallization in ethanol. The E-isomer was treated with pyrrolidine to give idoxifene (67%). In order to incorporate radioactive iodine into the 4-position, the 4-stannylated precursor was prepared (30%). The yield of radioiodination was 90-92% with a high radiochemical purity greater than 98%. The ratio of tumor uptake of the breast cancer cell line between MCF-7 and MDA-MB-468 was about 1.7.
Acylation ; Breast Neoplasms* ; Breast* ; Cell Line ; Estrogen Receptor Modulators ; Ethanol ; Iodine ; Pharmacology, Clinical ; Tomography, Emission-Computed, Single-Photon

Prevalence of splenic infarction developed during acute pancreatitis is extremely rare. However, we recently experienced a case of 42-year-old woman who developed splenic infarction during acute alcoholic pancreatitis. There were sustained subjective symptoms and no resolution of image despite of conservative management, so we performed angiography to confirm whether vascular lesion existed or not. We found the significant celiac artery stenosis due to compression by median arcuate ligament and no visible thrombus. We report an unusual case of splenic infarction developed during acute recurrent pancreatitis possibly related with celiac artery stenosis.
Adult ; Angiography ; Celiac Artery* ; Constriction, Pathologic* ; Female ; Humans ; Ligaments ; Pancreatitis* ; Pancreatitis, Alcoholic ; Prevalence ; Splenic Infarction* ; Thrombosis

OBJECTIVES: Due to the heterogeneous receptor distribution and changes of receptor status over time, the biochemical measurement of estrogen receptor status of biopsy specimens is not sufficient to diagnose breast cancer. As a result, I-123 labeled estradiols have been applied for the diagnosis. The purpose of this study was to develop a suitable radioligand for imaging estrogen receptor-positive human breast tumors. METHODS: Among the various estradiol derivatives, 17alpha-[123I]iodovinyl estradiol ([123I]IVE) has been prepared from 17alpha-ethynyl estradiol. Labeling of E-17alpha-[123I]iodovinyl estradiol (E-[123I]IVE) was carried out using peracetic acid with [123I]NaI and Z-[123I]IVE labelling was archived using chloamine- T/HCl solution with [123I]NaI. Labeling yield was determined by silica thin-layer chromatography (TLC) and radiochemical purity was measured by high performance liquid chromatography (HPLC). The biodistribution of E-[123I]IVE was measured in immature female rats at 60 min, 120 min and 300 min after injection. RESULTS: The labeling yield of two isomers was 92% and 94% (E-[123I]IVE and Z-[123I]IVE, respectively). The radiochemical purity was more than 98% after purification. The highest uptake was observed at 120 min in uterus (3.11% ID/g for E-[123I]IVE). CONCLUSION: These results suggest the possibility of using E-[123I]IVE as an imaging agent for the evaluation of the presence of estrogen receptor in patients with breast cancer.
Animals ; Biopsy ; Breast Neoplasms ; Chromatography, Liquid ; Chromatography, Thin Layer ; Diagnosis ; Estradiol* ; Estrogens ; Female ; Humans ; Peracetic Acid ; Rats ; Silicon Dioxide ; Uterus

OBJECTIVE: To investigate a diagnostic value of ultrasonography in carpal tunnel syndrome (CTS) patients and to evaluate a correlation of sonographic measurements with the degree of electrodiagnostic abnormalities and clinical severity. METHODS: Two-hundred-forty-six symptomatic hands in 135 patients and 30 asymptomatic hands in 19 healthy individuals as control group were included. In ultrasonographic study, we measured the cross-sectional area (CSA) and flattening ratio (FR) of the median nerve at the pisiform as well as palmar bowing (PB) of the flexor retinaculum. Sensitivity and specificity of ultrasonographic measurements were evaluated and ultrasonographic data from the symptomatic and control hands were compared to the grade of electrodiagnostic and clinical severity. RESULTS: The mean CSA was 13.7+/-4.2 mm2 in symptomatic hands and 7.9+/-1.3 mm2 in asymptomatic hands. The mean FR was 4.2+/-1.0 in symptomatic hands and 3.4+/-0.4 in asymptomatic hands. The mean PB was 3.5+/-0.5 mm in symptomatic hands and 2.6+/-0.3 mm in asymptomatic hands. Statistical analysis showed differences of the mean CSA, FR and PB between groups were significant. A cut-off value of 10 mm2 for the mean CSA was found to be the upper limit for normal value. Both the mean CSA and PB are correlated with the grade of electrophysiological abnormalities and clinical severity, respectively. CONCLUSION: Ultrasographic measurement of the CSA and PB is helpful to diagnose CTS as a non-invasive and an alternative modality for the evaluation of CTS. In addition, ultrasonography also provides a reliable correlation with the grade of electrodiagnostic abnormalities and clinical severity.
Carpal Tunnel Syndrome* ; Diagnosis* ; Hand ; Humans ; Median Nerve ; Reference Values ; Sensitivity and Specificity ; Ultrasonography*

Purpose: The value of the genomic profiling by targeted gene-sequencing on radiation therapy response prediction was evaluated through integrated analysis including clinical information. Radiation response prediction model was constructed based on the analyzed findings. Materials and Methods: Patients who had the tumor sequenced using institutional cancer panel after informed consent and received radiotherapy for the measurable disease served as the target cohort. Patients with irradiated tumor locally controlled for more than 6 months after radiotherapy were defined as the durable local control (DLC) group, otherwise, non-durable local control (NDLC) group. Significant genomic factors and domain knowledge were used to develop the Bayesian Network model to predict radiotherapy response. Results: Altogether, 88 patients were collected for analysis. Of those, 41 (43.6%) and 47 (54.4%) patients were classified as the NDLC and DLC group, respectively. Somatic mutations of NOTCH2 and BCL were enriched in the NDLC group, whereas, mutations of CHEK2, MSH2, and NOTCH1 were more frequently found in the DLC group. Altered DNA repair pathway was associated with better local failure–free survival (hazard ratio, 0.40; 95% confidence interval, 0.19 to 0.86; p=0.014). Smoking somatic signature was found more frequently in the DLC group. Area under the receiver operating characteristic curve of the Bayesian network model predicting probability of 6-month local control was 0.83. Conclusion Durable radiation response was associated with alterations of DNA repair pathway and smoking somatic signature. Bayesian network model could provide helpful insights for high precision radiotherapy. However, these findings should be verified in prospective cohort for further individualization.

Radiation-induced cavernous malformations (RICMs) are rare but significant late complications of highdose radiation therapy, particularly in young survivors of brain tumors. This report presents two cases of RICMs following aggressive multimodal treatment, including surgery, chemotherapy, and radiation therapy. Case 1 was a 22-year-old male patient with medulloblastoma treated with craniospinal irradiation, tumor bed boost, and tandem autologous peripheral blood stem cell transplantation. Approximately 8 years after treatment completion, routine follow-up imaging revealed a small focal hemorrhage in the right cerebellum, consistent with an RICM. The lesion was asymptomatic and managed conservatively with regular imaging, showing spontaneous resolution over time, with a significant size reduction noted 9 years post-treatment. Case 2 describes a 32-year-old male with an intracranial germinoma treated with whole-ventricular irradiation. Three years after treatment, the patient developed a symptomatic hemorrhagic RICM near a pre-existing developmental venous anomaly. Surgical resection and Gamma Knife Surgery stabilized the lesion; however, residual symptoms, including tremors and gait disturbances, persisted, affecting the patient’s daily activities. These cases illustrate the diverse clinical courses of RICMs, ranging from spontaneous resolution to the necessity of surgical intervention, and emphasize the importance of long-term surveillance and tailored management strategies for late-onset complications.

Radiation-induced cavernous malformations (RICMs) are rare but significant late complications of highdose radiation therapy, particularly in young survivors of brain tumors. This report presents two cases of RICMs following aggressive multimodal treatment, including surgery, chemotherapy, and radiation therapy. Case 1 was a 22-year-old male patient with medulloblastoma treated with craniospinal irradiation, tumor bed boost, and tandem autologous peripheral blood stem cell transplantation. Approximately 8 years after treatment completion, routine follow-up imaging revealed a small focal hemorrhage in the right cerebellum, consistent with an RICM. The lesion was asymptomatic and managed conservatively with regular imaging, showing spontaneous resolution over time, with a significant size reduction noted 9 years post-treatment. Case 2 describes a 32-year-old male with an intracranial germinoma treated with whole-ventricular irradiation. Three years after treatment, the patient developed a symptomatic hemorrhagic RICM near a pre-existing developmental venous anomaly. Surgical resection and Gamma Knife Surgery stabilized the lesion; however, residual symptoms, including tremors and gait disturbances, persisted, affecting the patient’s daily activities. These cases illustrate the diverse clinical courses of RICMs, ranging from spontaneous resolution to the necessity of surgical intervention, and emphasize the importance of long-term surveillance and tailored management strategies for late-onset complications.

Radiation-induced cavernous malformations (RICMs) are rare but significant late complications of highdose radiation therapy, particularly in young survivors of brain tumors. This report presents two cases of RICMs following aggressive multimodal treatment, including surgery, chemotherapy, and radiation therapy. Case 1 was a 22-year-old male patient with medulloblastoma treated with craniospinal irradiation, tumor bed boost, and tandem autologous peripheral blood stem cell transplantation. Approximately 8 years after treatment completion, routine follow-up imaging revealed a small focal hemorrhage in the right cerebellum, consistent with an RICM. The lesion was asymptomatic and managed conservatively with regular imaging, showing spontaneous resolution over time, with a significant size reduction noted 9 years post-treatment. Case 2 describes a 32-year-old male with an intracranial germinoma treated with whole-ventricular irradiation. Three years after treatment, the patient developed a symptomatic hemorrhagic RICM near a pre-existing developmental venous anomaly. Surgical resection and Gamma Knife Surgery stabilized the lesion; however, residual symptoms, including tremors and gait disturbances, persisted, affecting the patient’s daily activities. These cases illustrate the diverse clinical courses of RICMs, ranging from spontaneous resolution to the necessity of surgical intervention, and emphasize the importance of long-term surveillance and tailored management strategies for late-onset complications.