Prostate intra-fraction motion recorded by transperineal ultrasound.

Infra-fraction motion of the prostate was recorded during 3.423 fractions of image guided radiotherapy (IGRT) in 191 patients, 14 of which were treated by intensity modulated radiation therapy (IMRT), and 177 of which were treated by volumetric arc therapy (VMAT). The prostate was imaged by three-dimensional and time-resolved transperineal ultrasound (4D-US) of type Clarity by Elekta AB, Stockholm, Sweden. The prostate volume was registered and the prostate position (center of volume) was recorded at a frequency of 2.0 samples per second. This raw data set contains a total of 1.985.392 prostate and patient couch positions over a time span of 272 hours, 52 minutes and 34 seconds of life radiotherapy as exported by the instrument software. This data set has been used for the validation of models of prostate intra-fraction motion and for the estimation of the dosimetric impact of actual intra-fraction motion on treatment quality and side effects. We hope that this data set may be reused by other groups for similar purposes.

Planning CT Identifies Patients at Risk of High Prostate Intrafraction Motion.

Prostate motion (standard deviation, range of motion, and diffusion coefficient) was calculated from 4D ultrasound data of 1791 fractions of radiation therapy in N = 100 patients. The inner diameter of the lesser pelvis was obtained from transversal slices through the pubic symphysis in planning CTs. On the lateral and craniocaudal axes, motility increases significantly (t-test, p < 0.005) with the inner diameter of the lesser pelvis. A diameter of >106 mm (ca. 6th decile) is a good predictor for high prostate intrafraction motion (ca. 9th decile). The corresponding area under the receiver operator curve (AUROC) is 80% in the lateral direction, 68% to 80% in the craniocaudal direction, and 62% to 70% in the vertical direction. On the lateral x-axis, the proposed test is 100% sensitive and has a 100% negative predictive value for all three characteristics (standard deviation, range of motion, and diffusion coefficient). On the craniocaudal z-axis, the proposed test is 79% to 100% sensitive and reaches 95% to 100% negative predictive value. On the vertical axis, the proposed test still delivers 98% negative predictive value but is not particularly sensitive. Overall, the proposed predictor is able to help identify patients at risk of high prostate motion based on a single planning CT.

The ProMotion LMU dataset (2022 edition), prostate intra-fraction motion recorded by transperineal ultrasound.

Infra-fraction motion of the prostate was recorded during 2.385 fractions of image guided radiotherapy (IGRT) in 126 patients, 14 of which were treated by intensity modulated radiation therapy (IMRT), and 112 of which were treated by volumetric arc therapy (VMAT). The prostate was imaged by three-dimensional and time-resolved transperineal ultrasound (4D-US) of type Clarity by Elekta, Stockholm, Sweden. The prostate volume was registered and the prostate position (center of volume) was recorded at a frequency of 2.0 samples per second. This raw data set contains a total of 1.138.024 prostate and patient couch positions over a time span of 158 hours, 25 minutes and 50 seconds of life radiotherapy as exported by the instrument software. This data set has been used for the validation of models of prostate intra-fraction motion and for the estimation of the dosimetric impact of actual intra-fraction motion on treatment quality and side effects. We hope that this data set may be reused by other groups for similar purposes.

A Privacy-Preserving Log-Rank Test for the Kaplan-Meier Estimator With Secure Multiparty Computation: Algorithm Development and Validation.

BACKGROUND: Patient data is considered particularly sensitive personal data. Privacy regulations strictly govern the use of patient data and restrict their exchange. However, medical research can benefit from multicentric studies in which patient data from different institutions are pooled and evaluated together. Thus, the goals of data utilization and data protection are in conflict. Secure multiparty computation (SMPC) solves this conflict because it allows direct computation on distributed proprietary data-held by different data owners-in a secure way without exchanging private data. OBJECTIVE: The objective of this work was to provide a proof-of-principle of secure and privacy-preserving multicentric computation by SMPC with real-patient data over the free internet. A privacy-preserving log-rank test for the Kaplan-Meier estimator was implemented and tested in both an experimental setting and a real-world setting between two university hospitals. METHODS: The domain of survival analysis is particularly relevant in clinical research. For the Kaplan-Meier estimator, we provided a secure version of the log-rank test. It was based on the SMPC realization SPDZ and implemented via the FRESCO framework in Java. The complexity of the algorithm was explored both for synthetic data and for real-patient data in a proof-of-principle over the internet between two clinical institutions located in Munich and Berlin, Germany. RESULTS: We obtained a functional realization of an SMPC-based log-rank evaluation. This implementation was assessed with respect to performance and scaling behavior. We showed that network latency strongly influences execution time of our solution. Furthermore, we identified a lower bound of 2 Mbit/s for the transmission rate that has to be fulfilled for unimpeded communication. In contrast, performance of the participating parties have comparatively low influence on execution speed, since the peer-side processing is parallelized and the computational time only constitutes 30% to 50% even with optimal network settings. In the real-world setting, our computation between three parties over the internet, processing 100 items each, took approximately 20 minutes. CONCLUSIONS: We showed that SMPC is applicable in the medical domain. A secure version of commonly used evaluation methods for clinical studies is possible with current implementations of SMPC. Furthermore, we infer that its application is practically feasible in terms of execution time.

Long-term outcome of stereotactic brachytherapy with temporary Iodine-125 seeds in patients with WHO grade II gliomas.

BACKGROUND: This long-term retrospective analysis aimed to investigate the outcome and toxicity profile of stereotactic brachytherapy (SBT) in selected low-grade gliomas WHO grade II (LGGII) in a large patient series. METHODS: This analysis comprised 106 consecutive patients who received SBT with temporary Iodine-125 seeds for histologically verified LGGII at the University of Munich between March 1997 and July 2011. Investigation included clinical characteristics, technical aspects of SBT, the application of other treatments, outcome analyses including malignization rates, and prognostic factors with special focus on molecular biomarkers. RESULTS: For the entire study population, the 5- and 10-years overall survival (OS) rates were 79% and 62%, respectively, with a median follow-up of 115.9 months. No prognostic factors could be identified. Interstitial radiotherapy was applied in 51 cases as first-line treatment with a median number of two seeds (range 1-5), and a median total implanted activity of 21.8 mCi (range 4.2-43.4). The reference dose average was 54.0 Gy. Five- and ten-years OS and progression-free survival rates after SBT were 72% and 43%, and 40% and 23%, respectively, with a median follow-up of 86.7 months. The procedure-related mortality rate was zero, although an overall complication rate of 16% was registered. Patients with complications had a significantly larger tumor volume (p = 0.029). CONCLUSION: SBT is a minimally invasive treatment modality with a favorable outcome and toxicity profile. It is both an alternative primary treatment method as well as an adjunct to open tumor resection in selected low-grade gliomas.

The ProMotion LMU dataset, prostate intra-fraction motion recorded by transperineal ultrasound.

Intra-fraction motion of the prostate was recorded during 721 fractions of image guided radiotherapy (IGRT) in 28 patients, 14 of which were treated by intensity modulated radiation therapy (IMRT), and 14 of which were treated by volumetric arc therapy (VMAT). The prostate was imaged by three-dimensional and time-resolved transperineal ultrasound (4D-US) of type Clarity by Elekta, Stockholm, Sweden. The prostate volume was registered and the prostate position (center of volume) was recorded at a frequency of 1.6 samples per second. This raw data set contains a total of 380.199 prostate and patient couch positions over a time span of 53 hours, 47 minutes and 29 seconds of life radiotherapy as exported by the instrument software. This data set has been used for the validation of models of prostate intra-fraction motion and for the estimation of the dosimetric impact of actual intra-fraction motion on treatment quality and side effects. We hope that this data set may be reused by other groups for similar purposes.

Dosimetric impact of intrafraction motion on boosts on intraprostatic lesions: a simulation based on actual motion data from real time ultrasound tracking.

BACKGROUND: Intrafraction motion is particularly problematic in case of small target volumes and narrow margins. Here we simulate the dose coverage of intraprostatic lesions (IPL) by simultaneous integrated boosts (SIB). For this purpose, we use a large sample of actual intrafraction motion data. METHODS: Fifty-three h of intra-fraction motion of the prostate were recorded in real-time by 4D ultrasound (4DUS) during 720 fractions in 28 patients. We simulate spherical IPLs with 3, 5, and 7 mm radius and matching spherical SIBs with 0, 2, and 5 mm safety margins. The volumetric overlap between IPLs and SIBs is calculated. Dose volume histograms (DVH) are estimated by Monte Carlo simulation. RESULTS: On average, the distance of the prostate was 1.3 mm from its initial position over all fractions and patients. Average volumetric overlap was 73, 82, and 87% of IPL volume in case of 3, 5, and 7 mm IPLs and SIBs without safety margins. These improved to 95% or more in case of 2 mm safety margins and 98% or more in case of 5 mm safety margins. DVHs showed that 80% of the IPL volume received 60, 72, and 79% of maximum dose in case of 3, 5, and 7 mm IPLs and SIBs without safety margins. These improved to 94% or more given moderately sized safety margins of 2 mm. CONCLUSIONS: On average over all fractions and patients, the dose coverage would have been acceptable even for small target volumes such as IPLs of radius 3 to 7 mm and narrow fields. Moderate safety margins of 2 mm could have ensured a delivery of 90% or more of the SIB dose to the IPL. In this case, SIB volume would have been considerably larger than IPL volume, but still considerably smaller than the overall PTV of the prostate.

Shorter treatment times reduce the impact of intra-fractional motion : A real-time 4DUS study comparing VMAT vs. step-and-shoot IMRT for prostate cancer.

PURPOSE: To evaluate the impact of shorter treatment times on intra-fractional motion of the prostate during external beam radiotherapy. METHODS: 53 h of intra-fractional motion of the prostate were recorded in real-time by 4D ultrasound (4DUS) during 720 fractions in 28 patients, 14 of which whom treated with step-and-shoot intensity-modulated radiotherapy (IMRT) and 14 of whom were treated with volumetric arc therapy (VMAT). RESULTS: The average VMAT fraction was recorded for 2 min 43 s and was substantially shorter than the average step-and-shoot IMRT fraction at 6 min 13 s. Average radial displacement of the prostate per fraction was substantially and significantly reduced from 1.31 ± 1.28 mm (n = 357 step-and-shoot IMRT fractions) to 0.96 ± 1.04 mm (n = 363 VMAT fractions), p = 0.00004. Radial, vertical, and longitudinal root-mean-square (r. m. s.) error per fraction was reduced from 1.55 to 1.12 mm (-28%, p < 0.0001), from 1.16 to 0.77 mm (-34%, p < 0.0001), and from 0.79 to 0.56 mm (-29%, p = 0.0002), respectively. Lateral intra-fractional motion was generally small and did not differ significantly. The prostate remained during 95% of fraction time within 4.55 mm of the isocenter in case of step-and-shoot IMRT and within 2.45 mm in case of VMAT. The variance of displacements increased linearly with time, and the rate was the same for both step-and-shoot IMRT and VMAT patients. CONCLUSIONS: The position of the prostate changed less during shorter fractions, limiting fraction-average and end-of-fraction variance. This substantially and significantly reduced the impact of intra-fractional motion during shorter VMAT fractions as compared to longer step-and-shoot IMRT fractions.

Left-sided breast cancer and risks of secondary lung cancer and ischemic heart disease : Effects of modern radiotherapy techniques.

PURPOSE: Modern breast cancer radiotherapy techniques, such as respiratory-gated radiotherapy in deep-inspiration breath-hold (DIBH) or volumetric-modulated arc radiotherapy (VMAT) have been shown to reduce the high dose exposure of the heart in left-sided breast cancer. The aim of the present study was to comparatively estimate the excess relative and absolute risks of radiation-induced secondary lung cancer and ischemic heart disease for different modern radiotherapy techniques. METHODS: Four different treatment plans were generated for ten computed tomography data sets of patients with left-sided breast cancer, using either three-dimensional conformal radiotherapy (3D-CRT) or VMAT, in free-breathing (FB) or DIBH. Dose-volume histograms were used for organ equivalent dose (OED) calculations using linear, linear-exponential, and plateau models for the lung. A linear model was applied to estimate the long-term risk of ischemic heart disease as motivated by epidemiologic data. Excess relative risk (ERR) and 10-year excess absolute risk (EAR) for radiation-induced secondary lung cancer and ischemic heart disease were estimated for different representative baseline risks. RESULTS: The DIBH maneuver resulted in a significant reduction of the ERR and estimated 10-year excess absolute risk for major coronary events compared to FB in 3D-CRT plans (p = 0.04). In VMAT plans, the mean predicted risk reduction through DIBH was less pronounced and not statistically significant (p = 0.44). The risk of radiation-induced secondary lung cancer was mainly influenced by the radiotherapy technique, with no beneficial effect through DIBH. VMAT plans correlated with an increase in 10-year EAR for radiation-induced lung cancer as compared to 3D-CRT plans (DIBH p = 0.007; FB p = 0.005, respectively). However, the EARs were affected more strongly by nonradiation-associated risk factors, such as smoking, as compared to the choice of treatment technique. CONCLUSION: The results indicate that 3D-CRT plans in DIBH pose the lowest risk for both major coronary events and secondary lung cancer.

Correction to: Left-sided breast cancer and risks of secondary lung cancer and ischemic heart disease-Effects of modern radiotherapy techniques.

Correction to: Strahlenther Onkol 2017 https://doi.org/10.1007/s00066-017-1213-y Unfortunately, during copy editing, the titles of Fig. 2a and 2b were removed.The correct Fig. 2a and 2b are shown below. The original article has been corrected ….

Temozolomide during radiotherapy of glioblastoma multiforme : Daily administration improves survival.

BACKGROUND: Temozolomide-(TMZ)-based chemoradiotherapy defines the current gold standard for the treatment of newly diagnosed glioblastoma. Data regarding the influence of TMZ dose density during chemoradiotherapy are currently not available. We retrospectively compared outcomes in patients receiving no TMZ, TMZ during radiotherapy on radiotherapy days only, and TMZ constantly 7 days a week. PATIENTS AND METHODS: From 2002-2012, a total of 432 patients with newly diagnosed glioblastoma received radiotherapy in our department: 118 patients had radiotherapy alone, 210 had chemoradiotherapy with TMZ (75 mg/m2) daily (7/7), and 104 with TMZ only on radiotherapy days (5/7). Radiotherapy was applied to a total dose of 60 Gy. RESULTS: Median survival after radiotherapy alone was 9.1 months, compared to 12.6 months with 5/7-TMZ and to 15.7 months with 7/7-TMZ. The 1­year survival rates were 33, 52, and 64%, respectively. Kaplan-Meier analysis showed a significant improvement of TMZ-7/7 vs. 5/7 (p = 0.01 by the log-rank test), while 5/7-TMZ was still superior to no TMZ at all (p = 0.02). Multivariate Cox regression showed a significant influence of TMZ regimen (p = 0.009) on hazard rate (+58% between groups) even in the presence of confounding factors age, sex, resection status, and radiotherapy dose concept. CONCLUSION: Our results confirm the findings of the EORTC/NCIC trial. It seems that also a reduced TMZ scheme can at first prolong the survival of glioblastoma patients, but not as much as the daily administration.

Prefraction displacement and intrafraction drift of the prostate due to perineal ultrasound probe pressure.

OBJECTIVE: In image-guided EBRT of the prostate, transperineal ultrasound (US) probes exert pressure on the perineum both during planning and treatment. Through tissue deformation and relaxation, this causes target and risk organ displacement and drift. In this study, prefraction shift and intrafraction drift of the prostate are quantified during robotic transperineal 4DUS. METHODS: The position of the prostate was recorded for different positions of the probe before treatment in 10 patients (16 series of measurements). During treatment (15 patients, 273 fractions), intrafraction motion of the prostate was tracked (total of 27 h and 24 min) with the transperineal probe in place. RESULTS: Per 1 mm shift of the US probe in the cranial direction, a displacement of the prostate by 0.42 ± 0.09 mm in the cranial direction was detected. The relationship was found to be linear (R² = 0.97) and highly significant (p < 0.0001). After initial contact of the probe and the perineum (no pressure), a shift of the probe of about 5-10 mm was typically necessary to achieve good image quality, corresponding to a shift of the prostate of about 2-4 mm in the cranial direction. Tissue compression and prostate displacement were well visible. During treatment, the prostate drifted at an average rate of 0.075 mm/min in the cranial direction (p = 0.0014). CONCLUSION: The pressure applied by a perineal US probe has a quantitatively similar impact on prostate displacement as transabdominal pressure. Shifts are predominantly in the cranial direction (typically 2-4 mm) with some component in the anterior direction (typically <1 mm). Slight probe pressure can improve image quality, but excessive probe pressure can distort the surrounding anatomy and potentially move risk organs closer to the high-dose area.

Comparison of prostate positioning guided by three-dimensional transperineal ultrasound and cone beam CT.

OBJECTIVE: The accuracy of a transperineal three-dimensional ultrasound system (3DUS) was assessed for prostate positioning and compared to fiducial- and bone-based positioning in kV cone beam computed tomography (CBCT) during definitive radiotherapy of prostate cancer. METHODS: Each of the 7 patients had three fiducial markers implanted into the prostate before treatment. Prostate positioning was simultaneously measured by 3DUS and CBCT before each fraction. In total, 177 pairs of 3DUS and CBCT scans were collected. Bone-match and seed-match were performed for each CBCT. Using seed-match as a reference, the accuracy of 3DUS and bone-match was evaluated. Systematic and random errors as well as optimal setup margins were calculated for 3DUS and bone-match. RESULTS: The discrepancy between 3DUS and seed-match in CBCT (average ± standard deviation) was 0.0 ± 1.7 mm laterally, 0.2 ± 2.0 mm longitudinally, and 0.3 ± 1.7 mm vertically. Using seed-match as a reference, systematic errors for 3DUS were 1.2 mm, 1.1 mm, and 0.9 mm; and random errors were 1.4 mm, 1.8 mm, and 1.6 mm, on lateral, longitudinal, and vertical axes, respectively. By analogy, the difference of bone-match to seed-match was 0.1 ± 1.1 mm laterally, 1.3 ± 3.8 mm longitudinally, and 1.3 ± 4.5 mm vertically. Systematic errors were 0.5 mm, 2.2 mm, and 2.6 mm; and random errors were 1.0 mm, 3.1 mm, and 3.9 mm on lateral, longitudinal, and vertical axes, respectively. The accuracy of 3DUS was significantly higher than that of bone-match on longitudinal and vertical axes, but not on the lateral axis. CONCLUSION: Image-guided radiotherapy of prostate cancer based on transperineal 3DUS was feasible, with overall small discrepancy to seed-match in CBCT in this retrospective study. Compared to bone-match, transperineal 3DUS achieved higher accuracy on longitudinal and vertical axes.

In the linear quadratic model, the Poisson approximation and the Zaider-Minerbo formula agree on the ranking of tumor control probabilities, up to a critical cell birth rate.

PURPOSE: To provide a rule for the agreement or disagreement of the Poisson approximation (PA) and the Zaider-Minerbo formula (ZM) on the ranking of treatment alternatives in terms of tumor control probability (TCP) in the linear quadratic model. MATERIALS AND METHODS: A general criterion involving a critical cell birth rate was formally derived. For demonstration, the criterion was applied to a distinct radiobiological model of fast growing head and neck tumors and a respective range of 22 conventional and nonconventional head and neck schedules. RESULTS: There is a critical cell birth rate bcrit below which PA and ZM agree on which one out of two alternative treatment schemes with single-cell survival curves S'(t) and S''(t) offers better TCP: [Formula: see text] For cell birth rates b above this critical cell birth rate, PA and ZM disagree if and only if b >bcrit > 0. In case of the exemplary head and neck schedules, out of 231 possible combinations, only 16 or 7% were found where PA and ZM disagreed. In all 231 cases the prediction of the criterion was numerically confirmed, and cell birth rates at crossovers between schedules matched the calculated critical cell birth rates. CONCLUSIONS: TCP estimated by PA and ZM almost never numerically coincide. Still, in many cases both formulas at least agree about which one out of two alternative fractionation schemes offers better TCP. In case of fast growing tumors featuring a high cell birth rate, however, ZM may suggest a re-evaluation of treatment options.

Stereoscopic X-ray imaging, cone beam CT, and couch positioning in stereotactic radiotherapy of intracranial tumors: preliminary results from a cross-modality pilot installation.

BACKGROUND: To assess the accuracy and precision of a fully integrated pilot installation of stereoscopic X-ray imaging and kV-CBCT for automatic couch positioning in stereotactic radiotherapy of intracranial tumors. Positioning errors as detected by stereoscopic X-ray imaging are compared to those by kV-CBCT (i.e. the accuracy of the new method is verified by the established method), and repeated X-ray images are compared (i.e. the precision of new method is determined intra-modally). METHODS: Preliminary results are reported from a study with 32 patients with intracranial tumors. Patients were treated with stereotactic radiotherapy guided by stereoscopic X-ray imaging and kV-CBCT. Patient positioning was automatically corrected by a robotic couch. Cross-modal discrepancies in position detection were measured (N = 42). Intra-modal improvements after correction and re-verification by stereoscopic X-ray imaging were measured (N = 70). The accuracy and precision of stereoscopic X-ray imaging and the accuracy and precision of CBCT were confirmed in phantom measurements (N = 12 shifts of a ball bearing phantom, N = 24 shifts of a head phantom). RESULTS: After correction based on stereoscopic X-ray imaging 95% of residual mean errors were below 0.4, 0.4, 0.5, and 0.7 mm (lateral, longitudinal, vertical, radial, respectively). Stereoscopic X-ray imaging and CBCT were in close agreement with an average discrepancy of 0.1, 0.5, 0.3 and 0.8 mm, respectively. 95% of discrepancies were below 0.8, 1.2, 1.0, and 1.4 mm, respectively. After correction and re-verification by stereoscopic X-ray imaging, the remaining intra-modal residual error was consistent with zero (p = 0.31, p = 0.48, p = 0.81 in lateral, longitudinal, and vertical direction; p-values from two-tailed t-test). The inherent technical accuracy and precision of stereoscopic X-ray imaging and the accuracy and precision of CBCT were found to be of the order of 0.1 mm in controlled phantom settings. CONCLUSIONS: In a routine clinical setting, both stereoscopic X-ray imaging and CBCT were able to reduce positioning errors by an order of magnitude. The end-to-end precision of the system, measured from the discrepancy (mean) between ExacTrac and CBCT, in a clinical setting seems to be about 0.8 mm radially, including couch positioning. The precision (measured from repeatability of ExacTrac, intra-modal) was found to be about 0.7 mm radially in a clinical setting.

Intra-fraction motion of the prostate is not increased by patient couch shifts.

BACKGROUND: During a fraction of external beam radiotherapy for prostate cancer, a mismatch between target volume and dose coverage may accumulate over time due to intra-fraction motion. One way to remove the residual error is to perform a couch shift in opposite direction. In principle, such couch shifts could cause secondary displacements of the patient and prostate. Hence it is interesting to investigate if couch shifts might amplify intra-fraction motion. FINDINGS: Intra-fraction motion of the prostate and patient couch position were simultaneously recorded during 359 fractions in 15 patients. During this time, a total of 22 couch shifts of up to 31.5 mm along different axes were recorded. Prostate position and couch position were plotted before, during and after each couch shift. There was no visible impact of couch shifts on prostate motion. The standard deviation of prostate position was calculated before, during and after each couch shift. The standard deviation did not significantly increase during couch shifts (by 3 % on average, p = 0.88) and even slightly decreased after a couch shift (by 37 % on average; p = 0.02). CONCLUSIONS: Shifts of the patient couch did not adversely affect the motion of the prostate relative to the patient couch. Hence, shifts of the patient couch may be a viable way to correct the position of the prostate relative to the dose distribution.

Excellent local control and survival after postoperative or definitive radiation therapy for sarcomas of the head and neck.

BACKGROUND: To report our results with postoperative or definitive radiation therapy in head and neck sarcomas. METHODS: We performed a retrospective analysis of 26 patients suffering from head and neck sarcomas, who received postoperative or definitive radiation therapy between 2003 and 2012. Median age was 64 years (19-88) and 69 % were male. Tumor locations were skull (including skin) in 31 %, paranasal sinus/orbita in 27 % and neck (including pharynx/larynx) in 42 %. Median tumor size was 4.6 cm (1-12 cm). 22 patients (85 %) presented in primary situation. Stage at presentation (UICC 7(th) for soft tissue sarcomas) was as follows: Ia:4 %, IIa:50 %, IIb:15 %, III:31 %. All except one patient suffered from high grade lesions (G2/3 FNCLCC), predominantly angiosarcoma (35 %), MFH (19 %) and synovial sarcoma (15 %). Surgery was performed in 21 pts (81 %), resulting in free margins in 10 (38 %), microscopically positive margins in 6 (23 %) and gross residual disease in 5 (19 %). Median dose to the primary tumor region was 66Gy (45-72Gy) in conventional fractionation, using 3D-CRT in 65 %, IMRT in 27 % and electrons in 8 %. 50 % of the patients also received sequential chemotherapy. RESULTS: Median follow up was 39 months (8-136). We observed three local recurrences, transferring into estimated 3- and 5-year local control rates of 86 %. One additional patient failed distantly, resulting in 3- and 5-year freedom from treatment failure rates of 82 %. Four patients have deceased, transferring into 3- and 5-year overall survival rates of 88 % and 82 %, respectively. Only two of the four deaths were sarcoma related. Maximum acute toxicity (CTCAE 3.0) was grade 1 in 27 % of the patients, grade 2 in 50 % and grade 3 in 23 %. Severe acute toxicity was mainly represented by mucositis and dysphagia. Maximum late toxicity was grade 1 in 31 %, grade 2 in 15 % and grade 3 in 19 % of the patients. Severe late toxicity included skin ulceration (n = 1), dysphagia with persistent tube dependency (n = 1), persistent sinusitis (n = 1) and hearing loss (n = 2). CONCLUSION: Excellent local control and overall survival rates can be achieved with postoperative or definitive radiation therapy with acceptable acute and late toxicities in patients suffering from sarcomas of the head and neck region.

Surface refraction of sound waves affects calibration of three-dimensional ultrasound.

BACKGROUND: Three-dimensional ultrasound (3D-US) is used in planning and treatment during external beam radiotherapy. The accuracy of the technique depends not only on the achievable image quality in clinical routine, but also on technical limitations of achievable precision during calibration. Refraction of ultrasound waves is a known source for geometric distortion, but such an effect was not expected in homogenous calibration phantoms. However, in this paper we demonstrate that the discontinuity of the refraction index at the phantom surface may affect the calibration unless the ultrasound probe is perfectly perpendicular to the phantom. METHODS: A calibration phantom was repeatedly scanned with a 3D-US system (Elekta Clarity) by three independent observers. The ultrasound probe was moved horizontally at a fixed angle in the sagittal plane. The resulting wedge shaped volume between probe and phantom was filled with water to couple in the ultrasound waves. Because the speed of sound in water was smaller than the speed of sound in Zerdine, the main component of the phantom, the angle of the ultrasound waves inside the phantom increased. This caused an apparent shift in the calibration features which was recorded as a function of the impeding angle. To confirm the magnitude and temperature dependence, the experiment was repeated by two of the observers with a mixture of ice and water at 0 °C and with thermalized tap water at 21 °C room temperature. RESULTS: During the first series of measurements, a linear dependency of the displacements dx of the calibration features on the angle α of the ultrasound probe was observed. The three observers recorded significantly nonzero (p < 0.0001) and very consistent slopes of dx/dα of 0.12, 0.12, and 0.13 mm/°, respectively.. At 0 °C water temperature, the slope increased to 0.18 ± 0.04 mm/°. This matched the prediction of Snell's law of 0.185 mm/° for a speed of sound of 1,402 m/s at the melting point of ice. At 21 °C, slopes of 0.11 and 0.12 mm/° were recorded in agreement with the first experiment at about room temperature. The difference to the theoretical expectation of 0.07 mm/° was not significant (p = 0.09). CONCLUSIONS: The surface refraction of sound waves my affect the calibration of three-dimensional ultrasound. The temperature dependence of the effect rules out alternative explanations for the observed shifts in calibration. At room temperature and for a structure that is 10 cm below the water-phantom interface, a tilt of the ultrasound probe of 10° may result in a position reading that is off by more than half a millimeter. Such errors are of the order of other relevant errors typically encountered during the calibration of a 3D-US system. Hence, care must be taken not to tilt the ultrasound probe during calibration.

A comparative assessment of prostate positioning guided by three-dimensional ultrasound and cone beam CT.

BACKGROUND: The accuracy of the Elekta Clarity™ three-dimensional ultrasound system (3DUS) was assessed for prostate positioning and compared to seed- and bone-based positioning in kilo-voltage cone-beam computed tomography (CBCT) during a definitive radiotherapy. METHODS: The prostate positioning of 6 patients, with fiducial markers implanted into the prostate, was controlled by 3DUS and CBCT. In total, 78 ultrasound scans were performed trans-abdominally and compared to bone-matches and seed-matches in CBCT scans. Setup errors detected by the different modalities were compared. Systematic and random errors were analysed, and optimal setup margins were calculated. RESULTS: The discrepancy between 3DUS and seed-match in CBCT was -0.2 ± 2.7 mm laterally, -1.9 ± 2.3 mm longitudinally and 0.0 ± 3.0 mm vertically and significant only in longitudinal direction. Using seed-match as reference, systematic errors of 3DUS were 1.3 mm laterally, 0.8 mm longitudinally and 1.4 mm vertically, and random errors were 2.5 mm laterally, 2.3 mm longitudinally, and 2.7 mm vertically. No significant difference could be detected for 3DUS in comparison to bone-match in CBCT. CONCLUSIONS: 3DUS is feasible for image guidance for patients with prostate cancer and appears comparable to CBCT based image guidance in the retrospective study. While 3DUS offers some distinct advantages such as no need of invasive fiducial implantation and avoidance of extra radiation, its disadvantages include the operator dependence of the technique and dependence on sufficient bladder filling. Further study of 3DUS for image guidance in a large patient cohort is warranted.

Linearity of patient positioning detection : a phantom study of skin markers, cone beam computed tomography, and 3D ultrasound.

BACKGROUND: Three-dimensional ultrasound (3D-US) is a modality complementary to kilovoltage cone beam computed tomography (kV-CBCT) and skin markers for patient positioning detection. This study compares the linearity of evaluations based on measurements using a modern 3D-US system (Elekta Clarity®; Elekta, Stockholm, Sweden), a kV-CBCT system (Elekta iView®), and skin markers. MATERIALS AND METHODS: An investigator deliberately displaced a multimodal phantom by up to ± 30 mm along different axes. The following data points were acquired: 27 along the lateral axis, 29 along the longitudinal axis, 27 along the vertical axis, and 27 along the space diagonal. At each of these 110 positions, the displacements according to skin' markers were recorded and scans were performed using both 3D-US and kV-CBCT. Shifts were detected by matching bony anatomy or soft tissue density to a reference planning CT in the case of kV-CBCT and for 3D-US, by matching ultrasound volume data to a reference planning volume. A consensus value was calculated from the average of the four modalities. With respect to this consensus value, the linearity (offset and regression coefficient, i.e., slope), average offset, systematic error, and random error of all four modalities were calculated for each axis. RESULTS: Linearity was similar for all four modalities, with regression coefficients between 0.994 and 1.012, and all offsets below 1 mm. The systematic errors of skin markers and 3D-US were higher than for kV-CBCT, but random errors were similar. In particular, 3D-US demonstrated an average offset of 0.36 mm to the right, 0.08 mm inferiorly, and 0.15 mm anteriorly; the systematic error was 0.36 mm laterally, 0.35 mm longitudinally, and 0.22 mm vertically; the random error was 0.15 mm laterally, 0.30 mm longitudinally, and 0.12 mm vertically. A total of 109 out of 110 (99 %) 3D-US measurements were within 1 mm of the consensus value on either axis. CONCLUSION: The linearity of 3D-US was no worse than that of skin markers or kV-CBCT. Average offsets, systematic errors, and random errors were all below 1 mm. Optimal margins in the order of 1 mm could be achieved in the controlled laboratory setting of this phantom study.