Robustness and dosimetric verification of hippocampal-sparing craniospinal pencil beam scanning proton plans for pediatric medulloblastoma.

Background and Purpose: Hippocampal-sparing (HS) is a method that can potentially reduce late cognitive complications for pediatric medulloblastoma (MB) patients treated with craniospinal proton therapy (PT). The aim of this study was to investigate robustness and dosimetric plan verification of pencil beam scanning HS PT. Materials and Methods: HS and non-HS PT plans for the whole brain part of craniospinal treatment were created for 15 pediatric MB patients. A robust evaluation of the plans was performed. Plans were recalculated in a water phantom and measured field-by-field using an ion chamber detector at depths corresponding to the central part of hippocampi. All HS and non-HS fields were measured with the standard resolution of the detector and in addition 16 HS fields were measured with high resolution. Measured and planned dose distributions were compared using gamma evaluation. Results: The median mean hippocampus dose was reduced from 22.9 Gy (RBE) to 8.9 Gy (RBE), while keeping CTV V95% above 95 % for all nominal HS plans. HS plans were relatively robust regarding hippocampus mean dose, however, less robust regarding target coverage and maximum dose compared to non-HS plans. For standard resolution measurements, median pass rates were 99.7 % for HS and 99.5 % for non-HS plans (p < 0.001). For high-resolution measurements, median pass rates were 100 % in the hippocampus region and 98.2 % in the surrounding region. Conclusions: A substantial reduction of dose in the hippocampus region appeared feasible. Dosimetric accuracy of HS plans was comparable to non-HS plans and agreed well with planned dose distribution in the hippocampus region.

Consensus guide on CT-based prediction of stopping-power ratio using a Hounsfield look-up table for proton therapy.

BACKGROUND AND PURPOSE: Studies have shown large variations in stopping-power ratio (SPR) prediction from computed tomography (CT) across European proton centres. To standardise this process, a step-by-step guide on specifying a Hounsfield look-up table (HLUT) is presented here. MATERIALS AND METHODS: The HLUT specification process is divided into six steps: Phantom setup, CT acquisition, CT number extraction, SPR determination, HLUT specification, and HLUT validation. Appropriate CT phantoms have a head- and body-sized part, with tissue-equivalent inserts in regard to X-ray and proton interactions. CT numbers are extracted from a region-of-interest covering the inner 70% of each insert in-plane and several axial CT slices in scan direction. For optimal HLUT specification, the SPR of phantom inserts is measured in a proton beam and the SPR of tabulated human tissues is computed stoichiometrically at 100 MeV. Including both phantom inserts and tabulated human tissues increases HLUT stability. Piecewise linear regressions are performed between CT numbers and SPRs for four tissue groups (lung, adipose, soft tissue, and bone) and then connected with straight lines. Finally, a thorough but simple validation is performed. RESULTS: The best practices and individual challenges are explained comprehensively for each step. A well-defined strategy for specifying the connection points between the individual line segments of the HLUT is presented. The guide was tested exemplarily on three CT scanners from different vendors, proving its feasibility. CONCLUSION: The presented step-by-step guide for CT-based HLUT specification with recommendations and examples can contribute to reduce inter-centre variations in SPR prediction.

Experimental assessment of inter-centre variation in stopping-power and range prediction in particle therapy.

PURPOSE: Experimental assessment of inter-centre variation and absolute accuracy of stopping-power-ratio (SPR) prediction within 17 particle therapy centres of the European Particle Therapy Network. MATERIAL AND METHODS: A head and body phantom with seventeen tissue-equivalent materials were scanned consecutively at the participating centres using their individual clinical CT scan protocol and translated into SPR with their in-house CT-number-to-SPR conversion. Inter-centre variation and absolute accuracy in SPR prediction were quantified for three tissue groups: lung, soft tissues and bones. The integral effect on range prediction for typical clinical beams traversing different tissues was determined for representative beam paths for the treatment of primary brain tumours as well as lung and prostate cancer. RESULTS: An inter-centre variation in SPR prediction (2σ) of 8.7%, 6.3% and 1.5% relative to water was determined for bone, lung and soft-tissue surrogates in the head setup, respectively. Slightly smaller variations were observed in the body phantom (6.2%, 3.1%, 1.3%). This translated into inter-centre variation of integral range prediction (2σ) of 2.9%, 2.6% and 1.3% for typical beam paths of prostate-, lung- and primary brain-tumour treatments, respectively. The absolute error in range exceeded 2% in every fourth participating centre. The consideration of beam hardening and the execution of an independent HLUT validation had a positive effect, on average. CONCLUSION: The large inter-centre variations in SPR and range prediction justify the currently clinically used margins accounting for range uncertainty, which are of the same magnitude as the inter-centre variation. This study underlines the necessity of higher standardisation in CT-number-to-SPR conversion.

Temporal relationship of sleep apnea and acromegaly: a nationwide study.

PURPOSE: Patients with acromegaly have an increased risk of sleep apnea, but reported prevalence rates vary largely. Here we aimed to evaluate the sleep apnea prevalence in a large national cohort of patients with acromegaly, to examine possible risk factors, and to assess the proportion of patients diagnosed with sleep apnea prior to acromegaly diagnosis. METHODS: Cross-sectional multicenter study of 259 Swedish patients with acromegaly. At patients' follow-up visits at the endocrine outpatient clinics of all seven university hospitals in Sweden, questionnaires were completed to assess previous sleep apnea diagnosis and treatment, cardiovascular diseases, smoking habits, anthropometric data, and S-IGF-1 levels. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale. Patients suspected to have undiagnosed sleep apnea were referred for sleep apnea investigations. RESULTS: Of the 259 participants, 75 (29%) were diagnosed with sleep apnea before the study start. In 43 (57%) of these patients, sleep apnea had been diagnosed before the diagnosis of acromegaly. After clinical assessment and sleep studies, sleep apnea was diagnosed in an additional 20 patients, yielding a total sleep apnea prevalence of 37%. Higher sleep apnea risk was associated with higher BMI, waist circumference, and index finger circumference. Sleep apnea was more frequent among patients with S-IGF-1 levels in the highest quartile. CONCLUSION: Sleep apnea is common among patients with acromegaly, and is often diagnosed prior to their acromegaly diagnosis. These results support early screening for sleep apnea in patients with acromegaly and awareness for acromegaly in patients with sleep apnea.

Evaluation of two commercial CT metal artifact reduction algorithms for use in proton radiotherapy treatment planning in the head and neck area.

PURPOSE: To evaluate two commercial CT metal artifact reduction (MAR) algorithms for use in proton treatment planning in the head and neck (H&N) area. METHODS: An anthropomorphic head phantom with removable metallic implants (dental fillings or neck implant) was CT-scanned to evaluate the O-MAR (Philips) and the iMAR (Siemens) algorithms. Reference images were acquired without any metallic implants in place. Water equivalent thickness (WET) was calculated for different path directions and compared between image sets. Images were also evaluated for use in proton treatment planning for parotid, tonsil, tongue base, and neck node targets. The beams were arranged so as to not traverse any metal prior to the target, enabling evaluation of the impact on dose calculation accuracy from artifacts surrounding the metal volume. Plans were compared based on γ analysis (1 mm distance-to-agreement/1% difference in local dose) and dose volume histogram metrics for targets and organs at risk (OARs). Visual grading evaluation of 30 dental implant patient MAR images was performed by three radiation oncologists. RESULTS: In the dental fillings images, ΔWET along a low-density streak was reduced from -17.0 to -4.3 mm with O-MAR and from -16.1 mm to -2.3 mm with iMAR, while for other directions the deviations were increased or approximately unchanged when the MAR algorithms were used. For the neck implant images, ΔWET was generally reduced with MAR but residual deviations remained (of up to -2.3 mm with O-MAR and of up to -1.5 mm with iMAR). The γ analysis comparing proton dose distributions for uncorrected/MAR plans and corresponding reference plans showed passing rates >98% of the voxels for all phantom plans. However, substantial dose differences were seen in areas of most severe artifacts (γ passing rates of down to 89% for some cases). MAR reduced the deviations in some cases, but not for all plans. For a single patient case dosimetrically evaluated, minor dose differences were seen between the uncorrected and MAR plans (γ passing rate approximately 97%). The visual grading of patient images showed that MAR significantly improved image quality (P < 0.001). CONCLUSIONS: O-MAR and iMAR significantly improved image quality in terms of anatomical visualization for target and OAR delineation in dental implant patient images. WET calculations along several directions, all outside the metallic regions, showed that both uncorrected and MAR images contained metal artifacts which could potentially lead to unacceptable errors in proton treatment planning. ΔWET was reduced by MAR in some areas, while increased or unchanged deviations were seen for other path directions. The proton treatment plans created for the phantom images showed overall acceptable dose distributions differences when compared to the reference cases, both for the uncorrected and MAR images. However, substantial dose distribution differences in the areas of most severe artifacts were seen for some plans, which were reduced by MAR in some cases but not all. In conclusion, MAR could be beneficial to use for proton treatment planning; however, case-by-case evaluations of the metal artifact-degraded images are always recommended.

Inter-centre variability of CT-based stopping-power prediction in particle therapy: Survey-based evaluation.

BACKGROUND AND PURPOSE: Stopping-power ratios (SPRs) are used in particle therapy to calculate particle range in patients. The heuristic CT-to-SPR conversion (Hounsfield Look-Up-Table, HLUT), needed for treatment planning, depends on CT-scan and reconstruction parameters as well as the specific HLUT definition. To assess inter-centre differences in these parameters, we performed a survey-based qualitative evaluation, as a first step towards better standardisation of CT-based SPR derivation. MATERIALS AND METHODS: A questionnaire was sent to twelve particle therapy centres (ten from Europe and two from USA). It asked for details on CT scanners, image acquisition and reconstruction, definition of the HLUT, body-region specific HLUT selection, investigations of beam-hardening and experimental validations of the HLUT. Technological improvements were rated regarding their potential to improve SPR accuracy. RESULTS: Scan parameters and HLUT definition varied widely. Either the stoichiometric method (eight centres) or a tissue-substitute-only HLUT definition (three centres) was used. One centre combined both methods. The number of HLUT line segments varied widely between two and eleven. Nine centres had investigated influence of beam-hardening, often including patient-size dependence. Ten centres had validated their HLUT experimentally, with very different validation schemes. Most centres deemed dual-energy CT promising for improving SPR accuracy. CONCLUSIONS: Large inter-centre variability was found in implementation of CT scans, image reconstruction and especially in specification of the CT-to-SPR conversion. A future standardisation would reduce time-intensive institution-specific efforts and variations in treatment quality. Due to the interdependency of multiple parameters, no conclusion can be drawn on the derived SPR accuracy and its inter-centre variability.

Evaluation of a metal artifact reduction algorithm in CT studies used for proton radiotherapy treatment planning.

Metal objects in the body such as hip prostheses cause artifacts in CT images. When CT images degraded by artifacts are used for treatment planning of radiotherapy, the artifacts can yield inaccurate dose calculations and, for particle beams, erroneous penetration depths. A metal artifact reduction software (O-MAR) installed on a Philips Brilliance Big Bore CT has been tested for applications in treatment planning of proton radiotherapy. Hip prostheses mounted in a water phantom were used as test objects. Images without metal objects were acquired and used as reference data for the analysis of artifact-affected regions outside of the metal objects in both the O-MAR corrected and the uncorrected images. Water equivalent thicknesses (WET) based on proton stopping power data were calculated to quantify differences in the calculated proton beam penetration for the different image sets. The WET to a selected point of interest between the hip prostheses was calculated for several beam directions of clinical relevance. The results show that the calculated differences in WET relative to the reference case were decreased when the O-MAR algorithm was applied. WET differences up to 2.0 cm were seen in the uncorrected case while, for the O-MAR corrected case, the maximum difference was decreased to 0.4 cm. The O-MAR algorithm can significantly improve the accuracy in proton range calculations. However, there are some residual effects, and the use of proton beam directions along artifact streaks should only be used with caution and appropriate margins.

Out-of-field dose studies with an anthropomorphic phantom: comparison of X-rays and particle therapy treatments.

BACKGROUND AND PURPOSE: Characterization of the out-of-field dose profile following irradiation of the target with a 3D treatment plan delivered with modern techniques. METHODS: An anthropomorphic RANDO phantom was irradiated with a treatment plan designed for a simulated 5 × 2 × 5 cm(3) tumor volume located in the center of the head. The experiment was repeated with all most common radiation treatment types (photons, protons and carbon ions) and delivery techniques (Intensity Modulated Radiation Therapy, passive modulation and spot scanning). The measurements were performed with active diamond detector and passive thermoluminescence (TLD) detectors to investigate the out-of-field dose both inside and outside the phantom. RESULTS: The highest out-of-field dose values both on the surface and inside the phantom were measured during the treatment with 25 MV photons. In the proximity of the Planned Target Volume (PTV), the lowest lateral dose profile was observed for passively modulated protons mainly because of the presence of the collimator in combination with the chosen volume shape. In the far out-of-field region (above 100mm from the PTV), passively modulated ions were characterized by a less pronounced dose fall-off in comparison with scanned beams. Overall, the treatment with scanned carbon ions delivered the lowest dose outside the target volume. CONCLUSIONS: For the selected PTV, the use of the collimator in proton therapy drastically reduced the dose deposited by ions or photons nearby the tumor. Scanning modulation represents the optimal technique for achieving the highest dose reduction far-out-of-field.

Doubling of water intake increases daytime blood pressure and reduces vertigo in healthy subjects.

We studied the effect of increased water intake on ambulatory blood pressure (BP) in healthy individuals. Blood pressure was recorded after 2 weeks of either regular (RWI) or extra water intake (EWI, an additional 30 ml water/kg body weight per day) in 20 healthy subjects (10 males, 10 females). The extra water intake (RWI: 1.7 ± 0.59 l, EWI: 3.7 ± 0.84 l, respectively, p < 0.0001, i.e., an increase of 2 liters) induced an increase in mean arterial daytime BP from 89.0 ± 5.5 mmHg during RWI to 91.4 ± 6.4 mmHg during the EWI phase (p = 0.005), while night-time BP was unchanged by the intervention. The visual-analogue-scale (VAS, maximum score of 10) score corresponding to the statement "I often experience vertigo" was 3.1 ± 2.6 during RWI and decreased to 2.1 ± 2. 1 during EWI phase (p = 0.008). In conclusion,two liters of extra water intake for 2 weeks significantly increased daytime blood pressure and reduced a sense of vertigo in healthy individuals.

Portal dose image verification: the collapsed cone superposition method applied with different electronic portal imaging devices.

Two different commercial electronic portal imaging devices (EPIDs), one based on a liquid ion chamber matrix and the other based on a fluoroscopic CCD camera, were used to acquire readings that, through a calibration procedure, provided images proportional to the absolute dose to a virtual water slab located at the EPID plane. The transformation of the matrix ion chamber image into a portal dose image (PDI) was based on a published relationship between dose rate and ionization current. For the fluoroscopic CCD-camera-based system, the transformation was based on a deconvolution with a radial light scatter kernel. Local response variations were corrected in the images from both systems using open field fluence maps. The acquired PDIs were compared with PDIs calculated with the collapsed cone superposition method for a three-dimensional detector model in water equivalent buildup material. The calculation model was based on the beam modelling and geometrical description of the treatment unit and energy used for treatment planning in a kernel-based system. The validity of the calculation method was evaluated for several field shapes and thicknesses of patient phantoms for the matrix ion chamber at 6 MV x-rays and for the camera-based EPID at 6 and 15 MV x-rays. The agreement between predicted and measured PDIs was evaluated with dose comparisons at points of interest and gamma index calculations. The average area failing the passing criteria in dose and position deviation was analysed to validate the performance of the method. For the matrix ion chamber on average an area less than 1% fails the passing criteria of 3 mm and 3%. For the camera-based EPID, the average area is 7% and 1% for 6 and 15 MV, respectively. The overall agreement centrally in the fields was 0.1 +/- 1.6% (1 sd) for the camera-based EPID and -0.1 +/- 1.6% (1 sd) for the matrix ion chamber. Thus, an absolute dose calibrated EPID could validate the delivered dose to the patient by comparing a calculated and a measured PDI.

Portal dose image verification: formalism and application of the collapsed cone superposition method.

A formalism tailored for portal dose image verification is proposed to facilitate the comparison of calculated and measured portal dose distributions. Each portal image is converted into a dose proportional image and normalized to the reference beam calibration dose per monitor unit. The calculated or measured dose to a detector phantom is accordingly normalized so as to enable direct comparison. The collapsed cone kernel superposition method is adapted and evaluated for calculation of portal dose distributions in a water-equivalent detector phantom through comparisons with Monte Carlo calculations and with measurements. The deviation compared with Monte Carlo calculations for 6 and 15 MV was between +0.9% (the 0.9 quantile) and -2.1% (the 0.1 quantile) for a range of investigated geometries. Collapsed cone calculations compared with measurements for clinical fields agreed within [-1.9%, +2.4%] for 15 MV and [-0.9%, +3.2%] for 6 MV for the 0.1 and 0.9 quantiles, respectively. Hence, the absolute portal dose to a detector phantom could be calculated and verified well within the present accuracy requirements for clinical dose calculations.