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INTRODUCTION: Carbamazepine causes dose-dependent toxicity in overdose. Resources commonly state that severe toxicity occurs with ingestions >50 mg/kg without supporting evidence. We aimed to compare ingested dose with clinical toxicity. METHODS: This was a retrospective series of patients reportedly ingesting carbamazepine >2,000 mg referred to a clinical toxicology unit and state poisons information centre. Medical records were reviewed to extract patient demographics, ingestion details, clinical effects and management. Severe toxicity was defined as the presence of coma (Glasgow Coma Scale <9), seizure, or hypotension (systolic blood pressure <90 mmHg). RESULTS: There were 69 presentations in 42 patients with a median ingested carbamazepine dose of 113 mg/kg (IQR: 71-151 mg/kg). Coma occurred in 10 cases, eight having ingested >200 mg/kg and the remaining two ingesting 113 mg/kg and 151 mg/kg, respectively. Seizures occurred in four cases (lowest ingested dose 143 mg/kg). Hypotension occurred in five cases (lowest ingested dose 113 mg/kg). DISCUSSION: Severe carbamazepine toxicity did not occur with reported ingestions <100 mg/kg and was uncommon in ingestions <200 mg/kg. CONCLUSION: Severe toxicity was common in ingestions >200 mg/kg. Using the suggested threshold of severe toxicity of >50 mg/kg appeared overly conservative in this series.

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BACKGROUND: Focal laser ablation (FLA) serves as a targeted therapy for prostate cancer (PCa). Clinical studies have demonstrated significant variations in ablation volumes with consistent fiber configurations. Consequently, a prediction model is needed for the safe application of FLA in treating PCa. OBJECTIVE: This study aimed to evaluate the reproducibility of FLA-induced temperature profiles in controlled ex vivo experiments using clinical laser treatment protocols. Additionally, it sought to examine the effectiveness of the CEM43 model in predicting the zone of irreversible damage (ZID) and to compare these findings with outcomes derived from the Arrhenius model. METHODS: Freshly excised postmortem human prostate and porcine liver specimens were used for controlled ex vivo ablation. Tissues were secured in a Perspex sample holder for precise placement of the laser fiber and thermocouples. FLA was conducted with a 1064-nm Nd:YAG laser at 3 W in continuous-wave mode for 10 min. Pre- and post-FLA 3D T1-weighted 7 T MRI scans were obtained to assess the treatment area. Whole-mount hematoxylin and eosin histological slides were prepared and digitized. On histology, the ZID was defined as the total of vaporized, carbonized, and coagulated tissue. A 2D thermal development map was created from temperature data, using bi-cubic interpolation. The cumulative equivalent thermal isoeffect dose at 43°C in minutes (CEM43) model was applied to predict the ZID, with 240 equivalent minutes (240-CEM43) used as the damage threshold. Additionally, the Arrhenius thermal model was used for comparison of CEM43 results. Predicted ZIDs were compared to MRI and histology. RESULTS: FLA treatment was performed on ex vivo human prostate samples (n = 2) and porcine liver specimens (n = 5). For human prostate tissue, FLA did not result in an identifiable ZID upon histological macroscopic examination or a lesion on MRI. Ex vivo porcine liver samples showed a clearly demarcated oval-shaped hyperintense lesion surrounding the laser fiber tip on post-FLA MRI. The MRI lesion (range 1.6-2.1 cm2) corresponded with the shape and location of the ZID on histology, but was smaller (median 1.7 vs. 3.2, p = 0.02). Histological examination of porcine liver samples revealed ZIDs ranging from 2.1 to 4.1 cm2, whereas 240-CEM43-predicted ZIDs ranged from 3.3 to 3.8 cm2. Although the median 240-CEM43-predicted ZID was not significantly larger than the histology ZID (3.8 vs. 3.2 cm2, p = 0.22), it tended to overpredict the histological results in most experiments. The median Arrhenius-predicted ZID was similar to the histological ZID (3.2 vs. 3.2 cm2, p = 0.56), but varied in size when comparing individual experiments (range 2.5-3.2 cm2). CONCLUSION: FLA on ex vivo human prostate showed no thermal damage on histopathology or MRI. Ex vivo porcine liver FLA resulted in identifiable ZID on histology and lesions on MRI. 240-CEM43 generally overestimated the ZID and had less variability compared to histology. Results from the Arrhenius model were in better agreement with the histology findings, but still did not predict the individual FLA-induced histological thermal damage. Inter-experiment ZID variability underlines the need for developing a more comprehensive predictive dosimetry model for FLA in PCa treatment.

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Objective　 @#To obtain the peak skin dose (PSD) of patients with interventional cardiology procedures and toevaluate the risk of deterministic effects.@*Methods　 @# Gafchromic XR RV3 films were used in a Level A tertiary hospital inBeijing to measure the PSD of patients who underwent interventional cardiology procedures. The measurement focused onfour common types of procedures, including coronary angiography, percutaneous transluminal coronary angioplasty,cathet-er radiofrequency ablation, and congenital heart disease. The films were scanned by EPSON EXPRESSION 10000XL andanalyzed by FILM QA ProTM 2014 software.@*Results　 @#PSD was measured in 59 patients with interventional cardiologypro-cedures, including 23 with coronary angiography, 21 with percutaneous transluminal coronary angioplasty, 9 with catheterradiofrequency ablation, and 6 with congenital heart disease. The seven patients with PSD ≥ 2 Gy all underwentpercu-taneous transluminal coronary angioplasty, one with PSD > 3 Gy and six with PSD < 2 Gy.@*Conclusion　@# The PSD of somepatients with interventional cardiology surgery exceeded the dose threshold of deterministic effects recommended by theICRP 118. There is a risk of deterministic effects in interventional cardiology surgery, especially in patients withpercu-taneous transluminal coronary angioplasty.

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Objective.Ultra-high-dose-rate radiotherapy, referred to as FLASH therapy, has been demonstrated to reduce the damage of normal tissue as well as inhibiting tumor growth compared with conventional dose-rate radiotherapy. The transient hypoxia may be a vital explanation for sparing the normal tissue. The heterogeneity of oxygen distribution for different doses and dose rates in the different radiotherapy schemes are analyzed. With these results, the influence of doses and dose rates on cell survival are evaluated in this work.Approach.The two-dimensional reaction-diffusion equations are used to describe the heterogeneity of the oxygen distribution in capillaries and tissue. A modified linear quadratic model is employed to characterize the surviving fraction at different doses and dose rates.Main results.The reduction of the damage to the normal tissue can be observed if the doses exceeds a minimum dose threshold under the ultra-high-dose-rate radiation. Also, the surviving fraction exhibits the 'plateau effect' under the ultra-high dose rates radiation, which signifies that within a specific range of doses, the surviving fraction either exhibits minimal variation or increases with the dose. For a given dose, the surviving fraction increases with the dose rate until tending to a stable value, which means that the protection in normal tissue reaches saturation.Significance.The emergence of the 'plateau effect' allows delivering the higher doses while minimizing damage to normal tissue. It is necessary to develop appropriate program of doses and dose rates for different irradiated tissue to achieve more efficient protection.

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PURPOSE: The purpose of this study was to evaluate the treatment outcomes and toxicity profile of patients with early glottic cancer who underwent hypofractionated radiation therapy (RT) with 3.5 Gy per fraction. MATERIALS AND METHODS: A retrospective review was performed of the medical records of 35 patients with early stage (T1-2N0M0) glottic cancer who underwent definitive RT. The dose fractionation scheme was 59.5 Gy in 17 fractions. Posterior commissure was excluded from the clinical target volume (CTV) for 26 patients (74.3%) without glottic lesions close to this region. RESULTS: With a median follow-up of 16.23 months (range, 6.82 to 67.15 months), no local, regional, or distant recurrence was reported. Acute hoarseness (65.7%), mucositis (68.6%), radiation dermatitis (60.0%) was frequent. One patient (2.9%) reported grade 3 acute toxicity (mucositis) and there was no grade 4-5 acute toxicity. There was no grade ≥3 late toxicities; however, grade 1 late intermittent hoarseness was frequent (45.7%). The receiver operative characteristic analysis revealed that mean hypopharyngeal dose was predictive for acute grade ≥2 mucositis (area under the curve=0.9314; 95% confidence interval, 0.8524-1). The optimal threshold of mean hypopharyngeal dose for occurrence of acute grade ≥2 mucositis was 26.31 Gy, with a specificity and sensitivity of 83.3% and 88.2%, respectively. CONCLUSION: Hypofractionated RT with fraction size of 3.5 Gy for early glottic cancer is effective. The hypopharyngeal mean dose could predict the occurrence of grade ≥2 acute mucositis. The posterior commissure can be safely excluded from the CTV.

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Polysorbate 80 (PS80) functions as a dispersing agent or solubilizer in many pharmaceuticals, and as a stabilizer in biopharmaceuticals. Topical or parenteral administration of low doses of PS80 in biopharmaceuticals has been associated with mild allergic reactions, including local injection site reactions in humans. High doses of PS80, such as levels found in traditional Chinese herbal parenteral medicines, have been linked to systemic effects consistent with anaphylactoid-type reactions, which are characterized by the direct release of histamine from mast cells (degranulation). Nonclinical safety assessments of PS80 in vivo have mainly focused on canine model systems, a species established to be particularly sensitive to PS80. However, there is conflicting data about the dose and route of administration of PS80 required to elicit an anaphylactoid-type reaction in this model system. Therefore, studies using multiple dosing regimens in anesthetized and conscious dogs including a combination of cardiovascular data, clinical signs, and biomarkers of mast cell degranulation were conducted. An intravenous (IV) bolus of 1 mg/kg PS80 (0.25% w/v) elicited a positive anaphylactoid reaction including increased heart rate, hypotension, and clinical signs associated with anaphylactoid reactions (e.g., reddened muzzle). However, a full reaction was not observed with a subcutaneous (SC) injection of PS80 (0.25% w/v) up to 20 mg/kg and IV bolus or IV infusions up to 0.5 mg/kg. These data establish a threshold dose for eliciting an anaphylactoid reaction in canine which varies depending on the route of administration as well as the rate of PS80 infusion.

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Objective:To compare the effects of parameters, such as planning target volume (PTV), calculation grid size, and dose threshold, on the dosimetric verification result of three dosimetric verification systems ArcCHECK, SRS MapCHECK, and 3DMap for stereotactic body radiation therapy (SBRT).Methods:Based on the dosimetric verification result of the SBRT plans of 50 patients, this study compared the effects of PTV (<25 cm 3 and ≥25 cm 3), calculation grid size (1.0, 1.5, and 2.0 mm), and dose threshold (5%, 10%, and 15%) on the γ passing rates of the three dosimetric verification systems at five criteria, i. e., 3 mm/3%, 3 mm/2%, 3 mm/1%, 2 mm/3%, and 2 mm/2%. Results:The changes in PTV affected 3DMap more significantly. With an increase in PTV, the γ passing rates of 3DMap at the criteria of 3 mm/3%, 3 mm/2%, 2 mm/3%, and 2 mm/2% increased by 2.2%, 2.2%, 4.4%, and 4.7% ( t=-2.76, -2.17, -4.72, -3.86, P<0.05), respectively. The increase in the calculation grid from 1.0 mm to 1.5 mm had greater effect on MapCHECK, with the γ passing rates at the criteria of 3 mm/3%, 3 mm/2%, 3 mm/1%, 2 mm/3% and 2 mm/2% decreased by 0.7%, 1.1%, 1.7%, 0.9%, 1.5% ( t=-6.15, -6.23, -5.98, -5.11, -8.34, P<0.05), respectively. The increases in the calculation grid from 1.0 mm to 2.0 mm had greater impact on ArcCHECK, with the γ passing rates at the criteria of 3 mm/3%, 3 mm/2%, 3 mm/1%, 2 mm/3%, 2 mm/2% decreased by 1.0%, 1.7%, 2.4%, 1.7%, 2.7% ( t=-4.75, -7.3, -8.63, -7.11, -8.26, P<0.05), respectively. The increase in the dose threshold from 5% to 10% had greater impact on ArcCHECK, with the γ passing rates at the criteria of 3 mm/3%, 3 mm/2%, 2 mm/3% and 2 mm/2% decreased by 1.1%, 1.4%, 2.5%, and 3.0% ( t=5.20, 5.68, 8.17, 9.99, P<0.05), respectively. Moreover, the increase in the dose threshold from 5% to 15% had more impact on 3DMap, with the γ passing rates at the criteria of 3 mm/3%, 3 mm/2%, 2 mm/3%, and 2 mm/2% decreased by 1.6%, 1.7%, 2.8%, and 3.2% ( t=3.25, 2.98, 4.40, 4.21, P<0.05), respectively. Conclusions:Target volume, calculation grid, and dose threshold are influencing factors in the dosimetric verification of three dosimetric verification systems for SBRT. Therefore, the effects of these parameters should be considered for different verification systems in clinical applications.

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The aim of this study was to estimate brain radiation dose to the main operator during interventional radiology procedures. Occupational brain doses from 19 interventional procedures were measured using thermoluminiscent dosimeters and an anthropomorphic RANDO woman phantom simulating a main operator. Results show that, interventional radiologists may receive minimum and maximum brain doses per procedure of 0.01 mGy (left temporal cortex) and 0.08 mGy (temporal lobe cortex), respectively. A radiologist who works without movable shielding devices during procedures and has a typical workload (for example 500 procedures per year), might exceed the new dose threshold of 0.5 Gy for circulatory disease in the brain working 12.6 years of his career.

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X-rays have been the gold standard for diagnosis, evaluation, and management of spinal scoliosis for decades as other assessment methods are indirect, too expensive, or not practical in practice. The average scoliosis patient will receive 10 to 25 spinal X-rays over several years equating to a maximum estimated dose of 10 to 25 mGy. Some patients, those getting diagnosed at a younger age and receiving early and ongoing treatments, may receive up to 40 to 50 X-rays, approaching at most 50 mGy. There are concerns that repeated radiographs given to patients are carcinogenic. Some studies have used the linear no-threshold model to derive cancer-risk estimates; however, it is invalid for low-dose irradiation (ie, X-rays); these estimates are untrue. Other studies have calculated cancer-risk ratios from long-term health data of historic scoliosis cohorts. Since data indicate reduced cancer rates in a cohort receiving a total radiation dose between 50 and 300 mGy, it is unlikely that scoliosis patients would get cancer from repeated X-rays. Moreover, since the threshold for leukemia is about 1100 mGy, scoliosis patients will not likely develop cancers from spinal X-rays. Scoliosis patients likely have long-term health consequences, including cancers, from the actual disease entity itself and not from protracted X-ray radiation exposures that are essential and indeed safe.

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The objective of the present study was to investigate the association between thyroid gland-dosimetric parameters and hypothyroidism induced by intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma (NPC). A total of 52 patients with NPC treated in the Department of Radiation Oncology of The Affiliated Hospital of Xuzhou Medical University, from May 2008 to December 2016 were retrospectively enrolled in the present study and divided into two groups based on thyroid function: The euthyroid and hypothyroid groups. The association between hypothyroidism and clinical or dosimetric parameters were analyzed. Females had a significantly increased probability of suffering from radiation-induced hypothyroidism (RIHT), compared with males (P=0.010). The occurrence of RIHT was significantly negatively associated with thyroid volume prior to radiotherapy (P=0.048). Furthermore, the mean dose (Dmean) and V50 in the hypothyroidism group were significantly increased, compared with the euthyroidism group (P=0.017 and P=0.023, respectively). During the treatment optimization period, dose constraints associated with the thyroid gland demonstrated a significantly protective effect on thyroid function compared with the unconstrained group (P=0.034). According to the receiver operating characteristic curves, the threshold value was 5,160 cGy for Dmean and 54.5% for V50. The 3-year cumulative incidence of RIHT was 67.8% when the Dmean value was >5,160 cGy and 44.6% when the Dmean was <5,160 cGy (log rank test, P=0.036). Furthermore, the 3-year cumulative incidence was 66.1% when the V50 was >54.5%, and 29.9% when the V50 was <54.5% (log rank test, P=0.025). In conclusion, RIHT is associated with radiation dose, particularly with Dmean and V50 of the thyroid gland. Dose constraints associated with the thyroid gland significantly reduced the incidence of hypothyroidism compared with the unconstrained group.

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BACKGROUND: With radiotherapy having entered the era of image guidance, or image-guided radiation therapy (IGRT), imaging procedures are routinely performed for patient positioning and target localization. The imaging dose delivered may result in excessive dose to sensitive organs and potentially increase the chance of secondary cancers and, therefore, needs to be managed. AIMS: This task group was charged with: a) providing an overview on imaging dose, including megavoltage electronic portal imaging (MV EPI), kilovoltage digital radiography (kV DR), Tomotherapy MV-CT, megavoltage cone-beam CT (MV-CBCT) and kilovoltage cone-beam CT (kV-CBCT), and b) providing general guidelines for commissioning dose calculation methods and managing imaging dose to patients. MATERIALS & METHODS: We briefly review the dose to radiotherapy (RT) patients resulting from different image guidance procedures and list typical organ doses resulting from MV and kV image acquisition procedures. RESULTS: We provide recommendations for managing the imaging dose, including different methods for its calculation, and techniques for reducing it. The recommended threshold beyond which imaging dose should be considered in the treatment planning process is 5% of the therapeutic target dose. DISCUSSION: Although the imaging dose resulting from current kV acquisition procedures is generally below this threshold, the ALARA principle should always be applied in practice. Medical physicists should make radiation oncologists aware of the imaging doses delivered to patients under their care. CONCLUSION: Balancing ALARA with the requirement for effective target localization requires that imaging dose be managed based on the consideration of weighing risks and benefits to the patient.

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OBJECTIVE Laser interstitial thermal therapy (LITT), sometimes referred to as "stereotactic laser ablation," has demonstrated utility in a subset of high-risk surgical patients with difficult to access (DTA) intracranial neoplasms. However, the treatment of tumors larger than 10 cm3 is associated with suboptimal outcomes and morbidity. This may limit the utility of LITT in dealing with precisely those large or deep tumors that are most difficult to treat with conventional approaches. Recently, several groups have reported on minimally invasive transsulcal approaches utilizing tubular retracting systems. However, these approaches have been primarily used for intraventricular or paraventricular lesions, and subtotal resections have been reported for intraparenchymal lesions. Here, the authors describe a combined approach of LITT followed by minimally invasive transsulcal resection for large and DTA tumors. METHODS The authors retrospectively reviewed the results of LITT immediately followed by minimally invasive, transsulcal, transportal resection in 10 consecutive patients with unilateral, DTA malignant tumors > 10 cm3. The patients, 5 males and 5 females, had a median age of 65 years. Eight patients had glioblastoma multiforme (GBM), 1 had a previously treated GBM with radiation necrosis, and 1 had a melanoma brain metastasis. The median tumor volume treated was 38.0 cm3. RESULTS The median tumor volume treated to the yellow thermal dose threshold (TDT) line was 83% (range 76%-92%), the median tumor volume treated to the blue TDT line was 73% (range 60%-87%), and the median extent of resection was 93% (range 84%-100%). Two patients suffered mild postoperative neurological deficits, one transiently. Four patients have died since this analysis and 6 remain alive. Median progression-free survival was 280 days, and median overall survival was 482 days. CONCLUSIONS Laser interstitial thermal therapy followed by minimally invasive transsulcal resection, reported here for the first time, is a novel option for patients with large, DTA, malignant brain neoplasms. There were no unexpected neurological complications in this series, and operative characteristics improved as surgeon experience increased. Further studies are needed to elucidate any differences in survival or quality of life metrics.

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Adaptive responses to low doses of low LET radiation occur in all organisms thus far examined, from single cell lower eukaryotes to mammals. These responses reduce the deleterious consequences of DNA damaging events, including radiation-induced or spontaneous cancer and non-cancer diseases in mice. The adaptive response in mammalian cells and mammals operates within a certain window that can be defined by upper and lower dose thresholds, typically between about 1 and 100 mGy for a single low dose rate exposure. However, these thresholds for protection are not a fixed function of total dose, but also vary with dose rate, additional radiation or non-radiation stressors, tissue type and p53 functional status. Exposures above the upper threshold are generally detrimental, while exposures below the lower threshold may or may not increase either cancer or non-cancer disease risk.