The effect of variations in CT scan protocol on femoral finite element failure load assessment using phantomless calibration.

Recently, it was shown that fracture risk assessment in patients with femoral bone metastases using Finite Element (FE) modeling can be performed using a calibration phantom or air-fat-muscle calibration and that non-patient-specific calibration was less favorable. The purpose of this study was to investigate if phantomless calibration can be used instead of phantom calibration when different CT protocols are used. Differences in effect of CT protocols on Hounsfield units (HU), calculated bone mineral density (BMD) and FE failure loads between phantom and two methods of phantomless calibrations were studied. Five human cadaver lower limbs were scanned atop a calibration phantom according to a standard scanning protocol and seven additional commonly deviating protocols including current, peak kilovoltage (kVp), slice thickness, rotation time, field of view, reconstruction kernel, and reconstruction algorithm. The HUs of the scans were calibrated to BMD (in mg/cm3) using the calibration phantom as well as using air-fat-muscle and non-patient-specific calibration, resulting in three models for each scan. FE models were created, and failure loads were calculated by simulating an axial load on the femur. HU, calculated BMD and failure load of all protocols were compared between the three calibration methods. The different protocols showed little variation in HU, BMD and failure load. However, compared to phantom calibration, changing the kVp resulted in a relatively large decrease of approximately 10% in mean HU and BMD of the trabecular and cortical region of interest (ROI), resulting in a 13.8% and 13.4% lower failure load when air-fat-muscle and non-patient-specific calibrations were used, respectively. In conclusion, while we observed significant correlations between air-fat-muscle calibration and phantom calibration as well as between non-patient-specific calibration and phantom calibration, our sample size was too small to prove that either of these calibration approaches was superior. Further studies are necessary to test whether air-fat-muscle or non-patient-specific calibration could replace phantom calibration in case of different scanning protocols.

Early clinical experience with a total body irradiation technique using field-in-field beams and on-line image guidance.

BACKGROUND AND PURPOSE: Total body irradiation (TBI) is a treatment used in the conditioning of patients prior to hematopoietic stem cell transplantation. We developed an extended-distance TBI technique using a conventional linac with multi-leaf collimator to deliver a homogeneous dose, and spare critical organs. MATERIALS AND METHODS: Patients were treated either in lateral recumbent or in supine position depending on the dose level. A conventional linac was used with the patient midline at 350 cm from the beam source. A series of beams was prepared manually using a 3D treatment planning system (TPS) aiming to improve dose homogeneity, spare the organs at risk and facilitate accurate patient positioning. An optimized dose calculation model for extended-distance treatments was developed using phantom measurements. During treatment, in-vivo dosimetry was performed using electronic dosimeters, and accurate positioning was verified using a mobile megavoltage imager. We analyzed dose volume histogram parameters for 19 patients, and in-vivo measurements for 46 delivered treatment fractions. RESULTS: Optimization of the dose calculation model for TBI improved dose calculation by 2.1% at the beam axis, and 17% at the field edge. Treatment planning dose objectives and constraints were met for 16 of 19 patients. Results of in-vivo dosimetry were within the set limitations (±10%) with mean deviations of 3.7% posterior of the lungs and 0.6% for the abdomen. CONCLUSIONS: We developed a TBI treatment technique using a conventional linac and TPS that can reliably be used in the conditioning regimen of patients prior to stem cell transplantation.

Implementation of state-of-the-art (chemo)radiation for advanced cervix cancer in the Netherlands: A quality improvement program.

PURPOSE: To report on the "Dutch Quality Improvement Project" regarding external beam (EBRT) and brachytherapy (BT) contouring and treatment planning for locally advanced cervical cancer (LACC). MATERIAL AND METHODS: Two rounds of three workshops were organized. Data from two patients with LACC were made available for homework exercises. Contouring and treatment planning was asked for according to the EMBRACE-II protocol. The submissions were analysed and the results were addressed during the workshops. RESULTS: Almost all invited centres participated. EBRT contouring guidelines were followed within acceptable range, with major effort needed with regard to the ITV concept. BT contouring was of good quality, with especially small discrepancies for centres already participating in EMBRACE.EBRT treatment planning results improved between workshops with more centres being able to fulfil the planning aims. Guidance was especially necessary to improve the coverage probability planning for affected nodes.For BT planning prioritizing between target coverage and OAR sparing improved over time; the variation in dose to vaginal points remained considerable, as did variation in loading patterns and spatial dose distribution.The project was highly appreciated by all participants. CONCLUSION: Homework and workshop activities provide a suitable platform for discussion, exchange of experience and improvement of quality and conformity. Due to this project, radiotherapy for LACC can be administered with better and more comparable quality throughout the Netherlands.

Image Guided Brachytherapy for Cancer of the Nasal Vestibule: Local Control and Cosmesis.

PURPOSE: To evaluate the efficacy of modern image guided brachytherapy for squamous cell carcinoma of the nasal vestibule, to explore tumor volume as a prognostic factor for local and regional recurrence, and to assess patient satisfaction with nasal function and appearance after treatment. METHODS AND MATERIALS: In a retrospective analysis, we reviewed the medical records of 102 patients with Wang T1-T2 nasal vestibule cancer treated at a single institution with brachytherapy as the sole treatment. Median follow-up time was 42 months (range, 3-210 months). A patient satisfaction study using the validated Nasal Appearance and Function Evaluation Questionnaire was conducted among 42 patients more than 1 year after treatment. A statistically significant cutoff point for tumor volume as a prognostic factor of local control was established using Youden's index method. RESULTS: Seventy-seven of 102 patients were treated with interstitial implants, and 25 patients were treated by an intracavitary mould technique. The 5-year control rates were 95%, 91%, and 83% for local, regional, and locoregional control, respectively. Tumor volume ≥2.3 cm3 resulted in worse 3-year regional control compared to tumor volume <2.3 cm3 (62% vs 96%; P = .01). Ultimate regional control after salvage treatment was 96%, with no significant difference observed between subgroups by tumor volume (92% for ≥2.3 cm3 vs 96% for <2.3 cm3; P = .57). Three patients with regional failure developed distant metastases. Five-year disease-specific survival and overall survival were 94% and 74%, respectively. Patient-assessed cosmetic and functional satisfaction were both rated high (mean 3.7 and 4.0 of 5, respectively). CONCLUSION: We report the largest cohort to date treated with brachytherapy as the sole treatment for nasal vestibule carcinoma. Brachytherapy offers excellent local control for Wang T1-T2 tumors with high patient satisfaction. Tumor volume is an adequate predictive factor for patients at risk of regional recurrence, but ultimate control rates after salvage treatment are high. Therefore, we do not recommend elective treatment of the neck.

Direct observation of chaperone-induced changes in a protein folding pathway.

How chaperone interactions affect protein folding pathways is a central problem in biology. With the use of optical tweezers and all-atom molecular dynamics simulations, we studied the effect of chaperone SecB on the folding and unfolding pathways of maltose binding protein (MBP) at the single-molecule level. In the absence of SecB, we find that the MBP polypeptide first collapses into a molten globulelike compacted state and then folds into a stable core structure onto which several alpha helices are finally wrapped. Interactions with SecB completely prevent stable tertiary contacts in the core structure but have no detectable effect on the folding of the external alpha helices. It appears that SecB only binds to the extended or molten globulelike structure and retains MBP in this latter state. Thus during MBP translocation, no energy is required to disrupt stable tertiary interactions.