Intrafraction Imaging Can Replace the Midtreatment Cone Beam Tomography for Lung Stereotactic Ablative Radiation Therapy Patients for Increased Treatment Efficiency.

Purpose: To determine the feasibility of replacing the mid treatment cone beam computed tomography (MT CBCT) image with Intrafraction Imaging (IFI) acquired concurrently during dose delivery in lung Stereotactic Ablative Body Radiation therapy (SABR) patients, and thus improve treatment efficiency. Methods and Materials: A review of departmental imaging data was performed on ten lung SABR patients treated with dual arc volumetric modulated arc therapy (VMAT) on an Elekta Versa HD linear accelerator with XVI imaging software.IFI data was extracted and a database of the translational (TX, TY, TZ) and the rotational (RX, RY, RZ) position errors was created for retrospective comparison, with the values of the MT CBCT for the same patients, treated between March 2021 and March 2022 at our center. The data was evaluated for correlation between the values in all 6° of freedom. Results: The inter-class correlation (ICC) coefficient for Tx was 0.89 (95% CI, 0.80-0.94), Ty was 0.69 (95% CI, 0.49-0.82), Tz was 0.89 (95% CI, 0.82-0.95) in the translational planes, and Rx was 0.79 (95% CI, 0.65-0.88), Ry was 0.79 (95% CI, 0.65-0.88), and Rz was 0.91 (95% CI, 0.84-0.95) in rotational planes.The Bland-Altman (BA) statistics for Tx had a bias of -1.22 × 10-3, with an upper limit of agreement (UOA) of 0.07, and a lower limit of agreement (LOA) of -0.07, for Ty the bias was 0.01 (UOA: 0.18; LOA: -0.16), Tz bias was 2.6 × 10-3(UOA: 0.10; LOA: -0.09), Rx bias was 0.09 (UOA: 0.82; LOA: -0.64), Ry bias was -0.04 (UOA: 1.08; LOA: -1.16) and Rz was -0.03 (UOA: 0.44; LOA: -0.51). Conclusions: The ICC was excellent for Tx, Tz, Rx, y, z, and good for Ty. The data demonstrated promising correlation between IFI and MT CBCT values, and therefore supports the use of IFI for clinical decision making and improving treatment efficiency.

The first clinical implementation of real-time 6 degree-of-freedom image-guided radiotherapy for liver SABR patients.

PURPOSE: Multiple survey results have identified a demand for improved motion management for liver cancer IGRT. Until now, real-time IGRT for liver has been the domain of dedicated and expensive cancer radiotherapy systems. The purpose of this study was to clinically implement and characterise the performance of a novel real-time 6 degree-of-freedom (DoF) IGRT system, Kilovoltage Intrafraction Monitoring (KIM) for liver SABR patients. METHODS/MATERIALS: The KIM technology segmented gold fiducial markers in intra-fraction x-ray images as a surrogate for the liver tumour and converted the 2D segmented marker positions into a real-time 6DoF tumour position. Fifteen liver SABR patients were recruited and treated with KIM combined with external surrogate guidance at three radiotherapy centres in the TROG 17.03 LARK multi-institutional prospective clinical trial. Patients were either treated in breath-hold or in free breathing using the gating method. The KIM localisation accuracy and dosimetric accuracy achieved with KIM + external surrogate were measured and the results were compared to those with the estimated external surrogate alone. RESULTS: The KIM localisation accuracy was 0.2±0.9 mm (left-right), 0.3±0.6 mm (superior-inferior) and 1.2±0.8 mm (anterior-posterior) for translations and -0.1◦±0.8◦ (left-right), 0.6◦±1.2◦ (superior-inferior) and 0.1◦±0.9◦ (anterior-posterior) for rotations. The cumulative dose to the GTV with KIM + external surrogate was always within 5% of the plan. In 2 out of 15 patients, >5% dose error would have occurred to the GTV and an organ-at-risk with external surrogate alone. CONCLUSIONS: This work demonstrates that real-time 6DoF IGRT for liver can be implemented on standard radiotherapy systems to improve treatment accuracy and safety. The observations made during the treatments highlight the potential false assurance of using traditional external surrogates to assess tumour motion in patients and the need for ongoing improvement of IGRT technologies.

A predictive model for determining rectum and bladder dose constraints in prostate volumetric modulated arc therapy.

Generic dose-volume constraints of the rectum/bladder (R/B) are used in inverse planning to reduce doses to these organs for patients undergoing prostate radiotherapy. A retrospective study was undertaken to assess correlations between the overlap of the R/B with the planning target volume (PTV) and the dose received during planning to organs at risk (OARs). Data for 105 prostate cancer patients who had volumetric modulated arc therapy (VMAT) to the intact prostate and proximal seminal vesicles at Nepean Cancer Care Centre from 2011 to 2015 were analyzed. R/B volume, R/B-PTV overlap volume, and R/B-PTV overlap percent metrics were collected with VMAT planning objectives. Characteristics were evaluated for correlation with different planning outcomes. The percentage overlap between the R/B and PTV were highly correlated to the doses to the relevant OAR, with a coefficient of determination (R2) of 0.63 for the rectum volume percentage receiving more than 75 Gy (RV75Gy) and R2 of 0.91 for the bladder volume percentage receiving more than 70 Gy (BV70Gy). We identified a cut-off value of 10.14% (sensitivity 84.62%, specificity 80.43%) as predictive of RV75Gy < 10% and a cut-off of 7.95% (sensitivity 97.62%, specificity 92.06%) as predictive of BV70Gy < 15%. A 95% prediction interval assisted in identifying individualized R/B planning goals. The R/B-PTV percentage overlap has a high reliability in estimating sparing of the R/B. This prediction model can be used to improve planning efficiency and create customised automated OAR planning goals in prostate VMAT plans. By doing this, the radiation doses received by these OARs can be minimized.

Bioequivalence between two human insulin analogs in Chinese population: Glulisine and Lispro.

Intensive insulin therapy for diabetic patients has been demonstrated as an appropriate treatment. Regular fast-acting insulin can hardly mimic the efficiency of endogenous meal-activated insulin secretion. Glulisine is a new rapid-acting insulin analog for mealtime insulin supplementation. We compared the pharmacokinetics and pharmacodynamics end points between the two rapid-acting insulin analogs Glulisine and Lispro. Twenty healthy adult males age ranging from 22 to 32 years were included in a randomized, open-label, cross contrast research. Two long duration hyperinsulinemic euglycemic clamp tests, one with Glulisine and the other with Lispro, were conducted on two separate days for all the participants. The two rapid-acting insulin analogs were administrated randomly to each participant. Glucose infusion rate (GIR) began to increase 20 min after injection in both Glulisine and Lispro groups. GIR increased sharply during the first 150 min and reached a peak at 6.23 ± 1.35 mg/(kg min) in the Glulisine group and 6.02 ± 1.27 mg/(kg min) in the Lispro group. It returned to the initial level at hour 5. The Area Under Curve (AUC(0-clamp end)) in Glulisine and Lispro groups were 1455.04 ± 381.88 mg/kg and 1356.25 ± 287.30 mg/kg (P > 0.05), respectively. However, AUC(0-1h) between the two groups showed significant difference, with Glulisine showed greater AUC(0-1h) in the first hour after injection. Other parameters showed no significant difference between the two groups. Insulin analogs Glulisine and Lispro were proved to have equivalent pharmacokinetic and pharmacodynamic parameters when administered to healthy Chinese adults, but with Glulisine showing greater AUC(0-1h) after injection.

Positive correlations of liver enzymes with metabolic syndrome including insulin resistance in newly diagnosed type 2 diabetes mellitus.

It has long been proposed that elevation of liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (GGT) may be associated with insulin resistance (IR). In the present study, we aimed to investigate the association of the above mentioned liver enzymes with IR by using hyperinsulinemic euglycemic clamp, as well as their relationship with individual component of metabolic syndrome (MetS) in 95 newly diagnosed type 2 diabetes (T2DM) Chinese patients. All the diagnosed patients did not use drugs for treatment of diabetes or dyslipidemia previously and were divided into IR and non-IR groups. The results showed that IR group had significantly higher ALT, AST, and GGT (P<0.01, P<0.01, and P<0.05, respectively) compared with non-IR group. According to the individual MetS component, ALT and AST were significantly increased in patients with high blood pressure compared with those without (both P<0.001); ALT and GGT were increased in patients with high triglyceride (P<0.05 and P<0.01); AST was increased in patients with central obesity (P<0.05). In correlation analysis, a significant association was found between the three liver enzymes and clamp insulin sensitivity index (all P<0.001). In the linear regression analysis, ALT was the determinant of clamp ISI, independent of age, sex, BMI, and fasting and OGTT 2 h plasma glucose (P<0.0001). In conclusion, liver enzymes, especially ALT, were significantly associated with IR according to direct clamp assessment, which were independent of the traditional risk factors in diabetic patients; and individual liver enzymes may have different relationship with individual component of MetS.

Improving insulin resistance with traditional Chinese medicine in type 2 diabetic patients.

Some clinical studies and animal researches have evaluated the efficacy of Traditional Chinese Medicine (TCM) and compared its effects with placebo or other antidiabetic drugs. TCM involves three particular plants, as an antidiabetic drug. Our present research planned to evaluate the efficacy of TCM on insulin sensitivity and other related metabolic factors in type 2 diabetic patients. There were 43 newly diagnosed type 2 diabetic patients enrolled in this study, who did not use any antidiabetic drugs before. They were randomly assigned into TCM and placebo groups, administrated with TCM and placebo, respectively. Glucose disposal rate, fasting plasma glucose, postprandial plasma glucose, glycated hemoglobin, and other metabolic components were assessed at baseline and end point. Glucose disposal rate increased from 5.12 +/- 2.20 to 6.37 +/- 3.51 mg kg(-1) min(-1) in the TCM group, ANCOVA analysis showed that glucose disposal rate in the TCM group was significantly improved as compared to that in the placebo group (P < 0.05). Other metabolic related components such as fasting plasma glucose, postprandial plasma glucose, glycated hemoglobin, systolic blood pressure, diastolic blood pressure, body mass index, retinol binding protein 4 were improved in TCM group, but no statistical differences was detected between the two groups. No severe side effect was found in TCM group. TCM can ameliorate insulin resistance in type 2 diabetes and it is safe and effective in newly diagnosed diabetic patients.