Evaluation of measures related to dosimetric uncertainty of VMAT plans.

Dosimetric uncertainty is most often not included in the process of creating and selecting plans for treatment. Treatment planning and the physician's choice of treatment plan is instead often based only on evaluation of clinical goals of the calculated absorbed dose distribution. Estimation of the dosimetric uncertainty could potentially have impact in the process of comparing and selecting volumetric modulated arc therapy (VMAT) plans. In this study, different measures for estimation of dosimetric uncertainty based on treatment plan parameters for plans with similar dose distributions were evaluated. VMAT plans with similar dose distributions but with different treatment plan designs were created using three different optimization methods for each of ten patient cases (tonsil and prostate cancer). Two plans were optimized in Eclipse, one with and one without the use of aperture shape controller, and one plan was optimized in RayStation. The studied measures related to dosimetric uncertainty of treatment plans were aperture-based complexity metric analysis, investigation of modulation level of multi leaf collimator leaves, gantry speed and dose rate, quasi-3D measurements and evaluation of simulations of realistic delivery variations. The results showed that there can be variations in dosimetric uncertainty for treatment plans with similar dose distributions. Dosimetric uncertainty assessment could therefore have impact on the choice of plan to be used for treatment and lead to a decrease in the uncertainty level of the delivered absorbed dose distribution. This study showed that aperture shape complexity had a larger impact on dosimetric uncertainty compared to modulation level of MLC, gantry speed and dose rate.

Luminescent Iridium Complexes with a Sulfurated Bipyridine Ligand: PCET Thermochemistry of the Disulfide Unit and Photophysical Properties.

Molecular systems combining light harvesting and charge storage are receiving great attention in the context of, for example, artificial photosynthesis and solar fuel generation. As part of ongoing efforts to develop new concepts for photoinduced proton-coupled electron transfer (PCET) reactivities, we report a cyclometallated iridium(III) complex [Ir(ppy)2(S-Sbpy)](PF6) ([1]PF6) equipped with our previously developed sulfurated bipyridine ligand S-Sbpy. A new one-step synthetic protocol for S-Sbpy is developed, starting from commercially available 2,2'-bipyridine, which significantly facilitates the use of this ligand. [1]+ features a two-electron reduction with potential inversion (|E1| > |E2|) at moderate potentials (E1 = -1.12, E2 = -1.11 V versus. Fc+/0 at 253 K), leading to a dithiolate species [1]-. Protonation with weak acids allows for determination of pKa = 23.5 in MeCN for the S-H···S- unit of [1H]. The driving forces for both the H atom and the hydride transfer are calculated to be ∼60 kcal mol-1 and verified experimentally by reaction with a suitable H atom and a hydride acceptor, demonstrating the ability of [1]+ to serve as a versatile PCET reagent, albeit with limited thermal stability. In MeCN solution, an orange emission for [1]PF6 from a triplet-excited state was found. Density functional calculations and ultrafast absorption spectroscopy are used to give insight into the excited-state dynamics of the complex and suggest a significantly stretched S-S bond for the lowest triplet-state T1. The structural responsiveness of the disulfide unit is proposed to open an effective relaxation channel toward the ground state, explaining the unexpectedly short lifetime of [1]+. These insights as well as the quantitative ground-state thermochemistry data provide valuable information for the use of S-Sbpy-functionalized complexes and their disulfide-/dithiol-directed PCET reactivity.

Dosimetric effects of respiratory motion during stereotactic body radiation therapy of lung tumors.

BACKGROUND: Respiratory-induced lung tumor motion may affect the delivered dose in stereotactic body radiation therapy (SBRT). Previous studies are often based on phantom studies for one specific treatment technique. In this study, the dosimetric effect of tumor motion was quantified in real patient geometries for different modulated treatments and tumor motion amplitudes for lung-SBRT. MATERIAL AND METHODS: A simulation method using deformable image registrations and 4-dimensional computed tomographies (4DCT) was developed to assess the dosimetric effects of tumor motion. The method was evaluated with ionization chamber and Gafchromic film measurements in a thorax phantom and used to simulate the effect for 15 patients with lung tumors moving 7.3-27.4 mm. Four treatment plans with different complexities were created for each patient and the motion-induced dosimetric effect to the gross tumor volume (GTV) was simulated. The difference between the planned dose to the static tumor and the simulated delivered dose to the moving tumor was quantified for the near minimum (D98%), near maximum (D2%) and mean dose (Dmean) to the GTV as well as the largest observed local difference within the GTV (Maxdiff). RESULTS: No correlation was found between the dose differences and the tumor motion amplitude or plan complexity. However, the largest deviations were observed for tumors moving >15.0 mm. The simulated delivered dose was within 2.5% from the planned dose for D98% (tumors moving <15 mm) and within 3.3% (tumors moving >15 mm). The corresponding values were 1.7% vs. 6.4% (D2%); 1.7% vs. 2.4% (Dmean) and 8.9% vs. 35.2% (Maxdiff). Using less complex treatment techniques minimized Maxdiff for tumors moving >15.0 mm. CONCLUSION: The dosimetric effects of respiratory-induced motion during lung SBRT are patient and plan specific. The magnitude of the dosimetric effect cannot be assessed solely based upon tumor motion amplitude or plan complexity.

Ultrafast photochemistry of a molybdenum carbonyl-nitrosyl complex with a triazacyclononane coligand.

Transition metal complexes capable of releasing small molecules such as carbon monoxide and nitric oxide upon photoactivation are versatile tools in various fields of chemistry and biology. In this work, we report on the ultrafast photochemistry of [Mo(CO)2(NO)(iPr3tacn)]PF6 (iPr3tacn = 1,4,7-triisopropyl-1,4,7-triazacyclononane), which was characterized under continuous illumination and with femtosecond UV-pump/UV-probe and UV-pump/MIR-probe spectroscopy, as well as with stationary calculations. The experimental and theoretical results demonstrate that while the photodissociation of one of the two CO ligands upon UV excitation can be inferred both on an ultrafast timescale as well as under exposure times of several minutes, no evidence of NO release is observed under the same conditions. The binding mode of the diatomic ligands is impacted by the electronic excitation, and transient intermediates are observed on a timescale of tens of picoseconds before CO is released from the coordination sphere. Furthermore, based on calculated potential energy scans, we suggest that photolysis of NO could be possible after a subsequent excitation of an electronically excited state with a second laser pulse, or by accessing low-lying excited states that otherwise cannot be directly excited by light.

Surface guided frameless positioning for lung stereotactic body radiation therapy.

BACKGROUND AND PURPOSE: When treating lung tumors with stereotactic body radiation therapy (SBRT), patient immobilization is of outmost importance. In this study, the intra-fractional shifts of the patient (based on bony anatomy) and the tumor (based on the visible target volume) are quantified, and the associated impact on the delivered dose is estimated for a frameless immobilization approach in combination with surface guided radiation therapy (SGRT) monitoring. METHODS: Cone beam computed tomographies (CBCT) were collected in free breathing prior and after each treatment for 25 patients with lung tumors, in total 137 fractions. The CBCT collected after each treatment was registered to the CBCT collected before each treatment with focus on bony anatomy to determine the shift of the patient, and with focus on the visible target volume to determine the shift of the tumor. Rigid registrations with 6 degrees of freedom were used. The patients were positioned in frameless immobilizations with their position and respiration continuously monitored by a commercial SGRT system. The patients were breathing freely within a preset gating window during treatment delivery. The beam was automatically interrupted if isocenter shifts >4 mm or breathing amplitudes outside the gating window were detected by the SGRT system. The time between the acquisition of the CBCTs was registered for each fraction to examine correlations between treatment time and patient shift. The impact of the observed shifts on the dose to organs at risk (OAR) and the gross tumor volume (GTV) was assessed. RESULTS: The shift of the patient in the CBCTs was ≤2 mm for 132/137 fractions in the vertical (vrt) and lateral (lat) directions, and 134/137 fractions in the longitudinal (lng) direction and ≤4 mm in 134/137 (vrt) and 137/137 (lat, lng) of the fractions. The shift of the tumor was ≤2 mm in 116/137 (vrt), 123/137 (lat) and 115/137 (lng) fractions and ≤4 mm in 136/137 (vrt), 137/137 (lat), and 135/137 (lng) fractions. The maximal observed shift in the evaluated CBCT data was 4.6 mm for the patient and 7.2 mm for the tumor. Rotations were ≤3.3ᵒ for all fractions and the mean/standard deviation were 0.2/1.0ᵒ (roll), 0.1/0.8ᵒ (yaw), and 0.3/1.0ᵒ (pitch). The SGRT system interrupted the beam due to intra-fractional isocenter shifts >4 mm for 21% of the fractions, but the patients always returned within tolerance without the need of repositioning. The maximal observed isocenter shift by the SGRT system during the beam holds was 8 mm. For the respiration monitoring, the beam was interrupted at least one time for 54% of the fractions. The visual tumor was within the planned internal target volume (ITV) for 136/137 fractions in the evaluated CBCT data collected at the end of each fraction. For the fraction where the tumor was outside the ITV, the D98% for the GTV decreased with 0.4 Gy. For the OARs, the difference between planned and estimated dose from the CBCT data (D2% or Dmean ) was ≤2.6% of the prescribed PTV dose. No correlation was found between treatment time and the magnitude of the patient shift. CONCLUSIONS: Using SGRT for motion management and respiration monitoring in combination with a frameless immobilization is a feasible approach for lung SBRT.

Analysis of early respiratory-related mortality after radiation therapy of non-small-cell lung cancer: feasibility of automatic data extraction for dose-response studies.

Purpose: To examine the feasibility of automatic data extraction from clinical radiation therapy (RT) databases at four hospitals to investigate the impact of mean lung dose (MLD) and age on the risk of early respiratory-related death and early overall death for patients treated with RT for non-small-cell lung cancer (NSCLC).Material and methods: We included adult patients with NSCLC receiving curatively intended RT between 2002 and 2017 at four hospitals. A script was developed to automatically extract RT-related data. The cause of death for patients deceased within 180 days of the start of RT was retrospectively assessed. Using logistic regression, the risks of respiratory-related death and of overall death within 90 and 180 days were investigated using MLD and age as variables.Results: Altogether, 1785 patients were included in the analysis of early overall mortality and 1655 of early respiratory-related mortality. The respiratory-related mortalities within 90 and 180 days were 0.9% (15/1655) and 3.6% (60/1655). The overall mortalities within 90 and 180 days were 2.5% (45/1785) and 10.6% (190/1785). Higher MLD and older age were associated with an increased risk of respiratory-related death within 180 days and overall death within 90 and 180 days (all p<.05). For example, the risk of respiratory-related death within 180 days and their 95% confidence interval for patients aged 65 and 75 years with MLDs of 20 Gy was according to our logistic model 3.8% (2.6-5.0%) and 7.7% (5.5-10%), respectively.Conclusions: Automatic data extraction was successfully used to pool data from four hospitals. MLD and age were associated with the risk of respiratory-related death within 180 days of the start of RT and with overall death within 90 and 180 days. A model quantifying the risk of respiratory-related death within 180 days was formulated.

Harmonization of proton treatment planning for head and neck cancer using pencil beam scanning: first report of the IPACS collaboration group.

Background and purpose: A collaborative network between proton therapy (PT) centres in Trento in Italy, Poland, Austria, Czech Republic and Sweden (IPACS) was founded to implement trials and harmonize PT. This is the first report of IPACS with the aim to show the level of harmonization that can be achieved for proton therapy planning of head and neck (sino-nasal) cancer.Methods: CT-data sets of five patients were included. During several face-to-face and online meetings, a common treatment planning protocol was developed. Each centre used its own treatment planning system (TPS) and planning approach with some restrictions specified in the treatment planning protocol. In addition, volumetric modulated arc therapy (VMAT) photon plans were created.Results: For CTV1, the average Dmedian was 59.3 ± 2.4 Gy(RBE) for protons and 58.8 ± 2.0 Gy(RBE) for VMAT (aim was 56 Gy(RBE)). For CTV2, the average Dmedian was 71.2 ± 1.0 Gy(RBE) for protons and 70.6 ± 0.4 Gy(RBE) for VMAT (aim was 70 Gy(RBE)). The average D2% for the spinal cord was 25.1 ± 8.5 Gy(RBE) for protons and 47.6 ± 1.4 Gy(RBE) for VMAT. The average D2% for chiasm was 46.5 ± 4.4 Gy(RBE) for protons and 50.8 ± 1.4 Gy(RBE) for VMAT, respectively. Robust evaluation was performed and showed the least robust plans for plans with a low number of beams.Discussion: In conclusion, several influences on harmonization were identified: adherence/interpretation to/of the protocol, available technology, experience in treatment planning and use of different beam arrangements. In future, all OARs that should be included in the optimization need to be specified in order to further harmonize treatment planning.

Systematic evaluation of lung tumor motion using four-dimensional computed tomography.

BACKGROUND: Respiratory-induced lung tumor motion may decrease robustness and outcome of radiation therapy (RT) if not accounted for. This study provides detailed information on the motion distribution of lung tumors for a group of 126 patients treated with stereotactic body RT. MATERIAL AND METHODS: Four-dimensional computed tomography scans were reviewed to assess lung tumor motion. The tumor motion was determined by the center of mass shift based on a rigid registration of the breathing phases containing the largest positional differences in the inferior-superior (IS), left-right (LR), and anterior-posterior (AP) directions. The patients were divided into subgroups depending on tumor diameter (φ < 2.0 cm, 2.0 ≤ φ ≤ 5.0 cm, φ > 5.0 cm) and tumor location within the lung (upper, middle, or lower lobe). The observed motion distributions were evaluated for each group separately to assess the dependence on tumor size and location. For each tumor size, the motion pattern in each direction (IS, LR, and AP) was analyzed for every tumor moving >5 mm. Sinusoidal trigonometric functions were fitted to the measured data using the least mean square method to determine which type of function best describes the motion pattern. Tumor volumes between 1.6 and 52.3 cm3 were evaluated. Mann-Whitney statistical tests were used for statistical analyses. RESULTS: The mean amplitude for the tumors in this study was 1.5 mm (LR), 2.5 mm (AP), and 6.9 mm (IS) while the maximum amplitude was 11.0 mm (LR), 9.0 mm (AP), and 53.0 mm (IS). In total, 95% of the tumors moved ≤20 mm in the IS direction, ≤3 mm in the LR direction, and ≤6 mm in the AP direction. The observed motion distributions showed no statistically significant correlation with tumor size or location within the lung except for motion in the IS direction, where the mean and maximum amplitudes significantly increased for tumors located in the middle and lower parts of the lung. The motion pattern of a tumor in any direction was best described using a squared trigonometric function of the type [Formula: see text], where A is the maximum amplitude of the motion in the current direction, t is the time of measurement, T is the total time of the breathing cycle and B is a constant used to synchronize the starting point of the breathing cycle. CONCLUSION: Lung tumor movements were generally larger in the IS direction and the motion amplitude in this direction increased for tumors located in the middle and lower parts of the lungs. Motions in LR or AP showed no such relation. Tumor size was not found to have any correlation with the motion amplitude in any direction. The motion pattern of a lung tumor in any direction is best described with a squared sinusoidal function independently of the tumor size or tumor location.

Jaw position uncertainty and adjacent fields in breast cancer radiotherapy.

Locoregional treatment of breast cancer involves adjacent, half blocked fields matched at isocenter. The objective of this work is to study the dosimetric effects of the uncertainties in jaw positioning for such a case, and how a treatment planning protocol including adjacent field overlap of 1 mm affects the dose distribution. A representative treatment plan, involving 6 and 15 photon beams, for a patient treated at our hospital is chosen. Monte Carlo method (EGSnrc/BEAMnrc) is used to simulate the treatment. Uncertainties in jaw positioning of ± 1 mm are addressed, which implies extremes in reality of 2 mm field gap/overlap when planning adjacent fields without overlap and 1 mm gap or 3 mm overlap for a planning protocol with 1 mm overlap. Dosimetric parameters for PTV, lung and body are analyzed. Treatment planning protocol with 1 mm overlap of the adjacent fields does not considerably counteract possible underdosage of the target in the case studied. PTV-V95% is for example reduced from 95% for perfectly aligned fields to 90% and 91% for 2 mm and 1 mm gap, respectively. However, the risk of overdosage in PTV and in healthy soft tissue is increased when following the protocol with 1 mm overlap. A 3 mm overlap compared to 2 mm overlap results in an increase in maximum dose to PTV, PTV-D2%, from 113% to 121%. V120% for 'Body-PTV' is also increased from 5 cm(3) to 14 cm(3). A treatment planning protocol with 1 mm overlap does not considerably improve the coverage of PTV in the case of erroneous jaw positions causing gap between fields, but increases the overdosage in PTV and doses to healthy tissue, in the case of overlapping fields, for the case investigated.

Impact of delivery variations on 3D dose distributions for volumetric modulated arc therapy plans of various complexity.

BACKGROUND: Delivery variations during radiotherapy can cause discrepancies between planned and delivered dose distribution. These variations could arise from random and systematic offsets in certain machine parameters or systematic offsets related to the calibration process of the treatment unit. PURPOSE: The aim of this study was to present a novel simulation-based methodology to evaluate realistic delivery variations in three dimensions (3D). Additionally, we investigated the dosimetric impact of delivery variations for volumetric modulated arc therapy (VMAT) plans for different treatment sites and complexities. METHODS: Twelve VMAT plans for different treatment sites (prostate-, head & neck-, lung-, and gynecological cancer) were selected. The clinical plan used for the treatment of each patient was reoptimized to create one plan with reduced complexity (i.e., simple plan) and one of higher complexity (i.e., complex plan). This resulted in a total of 36 plans. Delivery variations were simulated by randomly introducing offsets in multi-leaf collimator position, jaw position, gantry angle and collimator angle simultaneously. Twenty simulations were carried out for each of the 36 plans, yielding 720 simulated deliveries. To explore the impact of individual offsets, additional simulations were conducted for each type of offset separately. A 3D dose calculation was performed for each simulation using the same calculation engine as for the clinical plan. Two standard deviations (2SD) of dose were determined for every voxel for 3D-spatial evaluations. The dose variation in certain DVH metrics, that is, D2% and D98% for the clinical target volume and five different DVH metrics for selected organs at risk, was calculated for the twenty simulated deliveries of each plan. For comparison, the effect of delivery variations was assessed by conducting measurements with the Delta4 phantom. RESULTS: The volume of voxels with 2SD above 1% of the prescribed dose was consistently larger for the complex plans in comparison to their corresponding simple and clinical plans. 2SDs larger than 1% were in many cases, found to accumulate outside the planning target volume. For complex plans, regions with 2SDs larger than 1% were detected also inside the high dose region, exhibiting, on average, a size six times larger volume, than those observed in simple plans. Similar results were found for all treatment sites. Variation in the selected DVH metrics for the simulated deliveries was generally largest for the complex plans with few exceptions. When comparing the 2SD distribution of the measurements with the 2SD distribution from the simulations, the spatial information showed deviations outside the PTV in both simulations and measurements. However, the measured values were, on average, 35% higher for the prostate plans and 10% higher for the head & neck plans compared to the simulated values. CONCLUSIONS: The presented methodology effectively quantified and localized dose deviations due to delivery offsets. The 3D analysis provided information that was undetectable using the analysis based on DVH metrics. Dosimetric uncertainties due to delivery variations were prominent at the edge of the high-dose region irrespective of treatment site and plan complexity. Dosimetric uncertainties inside the high-dose region was more profound for plans of higher complexity.

Prediction of proton stopping power ratios using dual-energy CT basis material decomposition.

BACKGROUND: Proton radiotherapy treatment plans are currently restricted by the range uncertainties originating from the stopping power ratio (SPR) prediction based on single-energy computed tomography (SECT). Various studies have shown that multi-energy CT (MECT) can reduce the range uncertainties due to medical implant materials and age-related variations in tissue composition. None of these has directly applied the basis material density (MD) images produced by projection-based MECT systems for SPR prediction. PURPOSE: To present and evaluate a novel proton SPR prediction method based on MD images from dual-energy CT (DECT), which could reduce the range uncertainties currently associated with proton radiotherapy. METHODS: A theoretical basis material decomposition into water and iodine material densities was performed for various pediatric and adult human reference tissues, as well as other non-tissue materials, by minimizing the root-mean-square relative attenuation error in the energy interval from 40 to 140 keV. A model (here called MD-SPR) mapping predicted MDs to theoretically calculated reference SPRs was created with locally weighted scatterplot smoothing (LOWESS) data-fitting. The goodness of fit of the MD-SPR model was evaluated for the included reference tissues. MD images of two electron density phantoms, combined to form a head- and an abdomen-sized phantom setup, were acquired with a clinical projection-based fast-kV switching DECT scanner. The MD images were compared to the theoretically predicted MDs of the tissue surrogates and other non-tissue materials in the phantoms, as well as used for input to the MD-SPR model for generation of SPR images. The SPR images were subsequently compared to theoretical reference SPRs of the materials in the phantoms, as well as to SPR images from a commercial algorithm (DirectSPR, Siemens Healthineers, Forchheim, Germany) using image-based consecutive scan DECT for the same phantom setups. RESULTS: The predicted SPRs of the tissue surrogates were similar for MD-SPR and DirectSPR, where the adipose and bone tissue surrogates were within 1% difference to the reference SPRs, while other non-adipose soft tissue surrogates (breast, brain, liver, muscle) were all underestimated by between -0.7% and -1.8%. The SPRs of the non-tissue materials (polymethyl methacrylate (PMMA), polyether ether ketone (PEEK), graphite and Teflon) were within 2.8% for MD-SPR images, compared to 6.8% for DirectSPR. CONCLUSIONS: The MD-SPR model performed similar compared to other published methods for the human reference tissues. The SPR prediction for tissue surrogates was similar to DirectSPR and showed potential to improve SPR prediction for non-tissue materials.

Influence of different dose calculation algorithms on the estimate of NTCP for lung complications.

Due to limitations and uncertainties in dose calculation algorithms, different algorithms can predict different dose distributions and dose-volume histograms for the same treatment. This can be a problem when estimating the normal tissue complication probability (NTCP) for patient-specific dose distributions. Published NTCP model parameters are often derived for a different dose calculation algorithm than the one used to calculate the actual dose distribution. The use of algorithm-specific NTCP model parameters can prevent errors caused by differences in dose calculation algorithms. The objective of this work was to determine how to change the NTCP model parameters for lung complications derived for a simple correction-based pencil beam dose calculation algorithm, in order to make them valid for three other common dose calculation algorithms. NTCP was calculated with the relative seriality (RS) and Lyman-Kutcher-Burman (LKB) models. The four dose calculation algorithms used were the pencil beam (PB) and collapsed cone (CC) algorithms employed by Oncentra, and the pencil beam convolution (PBC) and anisotropic analytical algorithm (AAA) employed by Eclipse. Original model parameters for lung complications were taken from four published studies on different grades of pneumonitis, and new algorithm-specific NTCP model parameters were determined. The difference between original and new model parameters was presented in relation to the reported model parameter uncertainties. Three different types of treatments were considered in the study: tangential and locoregional breast cancer treatment and lung cancer treatment. Changing the algorithm without the derivation of new model parameters caused changes in the NTCP value of up to 10 percentage points for the cases studied. Furthermore, the error introduced could be of the same magnitude as the confidence intervals of the calculated NTCP values. The new NTCP model parameters were tabulated as the algorithm was varied from PB to PBC, AAA, or CC. Moving from the PB to the PBC algorithm did not require new model parameters; however, moving from PB to AAA or CC did require a change in the NTCP model parameters, with CC requiring the largest change. It was shown that the new model parameters for a given algorithm are different for the different treatment types.

Impact of delineation errors on the estimated organ at risk dose and of dose errors on the normal tissue complication probability model.

BACKGROUND: Normal tissue complication probability (NTCP) models are often based on doses retrieved from delineated volumes. For retrospective dose-response studies focusing on organs that have not been delineated historically, automatic segmentation might be considered. However, automatic segmentation risks generating considerable delineation errors and knowledge regarding how these errors impact the estimated organ dose is important. Furthermore, organ-at-risk (OAR) dose uncertainties cannot be eliminated and might affect the resulting NTCP model. Therefore, it is also of interest to study how OAR dose errors impact the NTCP modeling results. PURPOSE: To investigate how random delineation errors of the proximal bronchial tree, heart, and esophagus impact the estimated OAR dose, and to investigate how random errors in the doses used for dose-response modeling affect the estimated NTCPs. METHODS: We investigated the impact of random delineation errors on the estimated OAR dose using the treatment plans of 39 patients treated with conventionally fractionated radiation therapy of non-small-cell lung cancer. Study-specific reference structures were defined by manually contouring the proximal bronchial tree, heart and esophagus. For each patient and organ, 120 reshaped structures were created by introducing random shifts and margins to the entire reference structure. The mean and near-maximum dose to the reference and reshaped structures were compared. In a separate investigation, the impact of random dose errors on the NTCP model was studied performing dose-response modeling with study sets containing treatment outcomes and OAR doses with and without introduced errors. Universal patient populations with defined population risks, dose-response relationships and distributions of OAR doses were used as ground truth. From such a universal population, we randomly sampled data sets consisting of OAR dose and treatment outcome into reference populations. Study sets of different sizes were created by repeatedly introducing errors to the OAR doses of each reference population. The NTCP models generated with dose errors were compared to the reference NTCP model of the corresponding reference population. RESULTS: A total of 14 040 reshaped structures with random delineation errors were created. The delineation errors resulted in systematic mean dose errors of less than 1% of the prescribed dose (PD). Mean dose differences above 15% of PD and near-maximum doses differences above 25% of PD were observed for 211 and 457 reshaped structures, respectively. Introducing random errors to OAR doses used for dose-response modeling resulted in systematic underestimations of the median NTCP. For all investigated scenarios, the median differences in NTCP were within 0.1 percentage points (p.p.) when comparing different study sizes. CONCLUSIONS: Introducing random delineation errors to the proximal bronchial tree, heart and esophagus resulted in mean dose and near-maximum dose differences above 15% and 25% of PD, respectively. We did not observe an association between the dose level and the magnitude of the dose errors. For the scenarios investigated in this study, introducing random errors to OAR doses used for dose-response modeling resulted in systematic underestimations of the median NTCP for reference risks higher than the universal population risk. The median NTCP underestimation was similar for different study sizes, all within 0.1 p.p.

The holistic effects of medical cannabis compared to opioids on pain experience in Finnish patients with chronic pain.

BACKGROUND: Medical cannabis (MC) is increasingly used for chronic pain, but it is unclear how it aids in pain management. Previous literature suggests that MC could holistically alter the pain experience instead of only targeting pain intensity. However, this hypothesis has not been previously systematically tested. METHOD: A retrospective internet survey was used in a sample of Finnish chronic pain patients (40 MC users and 161 opioid users). The patients evaluated statements describing positive and negative phenomenological effects of the medicine. The two groups were propensity score matched to control for possible confounding factors. RESULTS: Exploratory factor analysis revealed three experience factors: Negative Side Effects, Positive Holistic Effects, and Positive Emotional Effects. The MC group (matched n = 39) received higher scores than the opioid group (matched n = 39) in Positive Emotional Effects with large effect size (Rank-Biserial Correlation RBC = .71, p < .001), and in Holistic Positive Effects with medium effect size (RBC = .47, p < .001), with no difference in Negative Side Effects (p = .13). MC and opioids were perceived as equally efficacious in reducing pain intensity. Ratings of individual statements were exploratively examined in a post hoc analysis. CONCLUSION: MC and opioids were perceived to be equally efficacious in reducing pain intensity, but MC additionally positively affected broader pain-related factors such as emotion, functionality, and overall sense of wellbeing. This supports the hypothesis that MC alleviates pain through holistically altering the pain experience.

Plan quality assessment in clinical practice: Results of the 2020 ESTRO survey on plan complexity and robustness.

PURPOSE: Plan complexity and robustness are two essential aspects of treatment plan quality but there is a great variability in their management in clinical practice. This study reports the results of the 2020 ESTRO survey on plan complexity and robustness to identify needs and guide future discussions and consensus. METHODS: A survey was distributed online to ESTRO members. Plan complexity was defined as the modulation of machine parameters and increased uncertainty in dose calculation and delivery. Robustness was defined as a dose distribution's sensitivity towards errors stemming from treatment uncertainties, patient setup, or anatomical changes. RESULTS: A total of 126 radiotherapy centres from 33 countries participated, 95 of them (75%) from Europe and Central Asia. The majority controlled and evaluated plan complexity using monitor units (56 centres) and aperture shapes (38 centres). To control robustness, 98 (97% of question responses) photon and 5 (50%) proton centres used PTV margins for plan optimization while 75 (94%) and 5 (50%), respectively, used margins for plan evaluation. Seventeen (21%) photon and 8 (80%) proton centres used robust optimisation, while 10 (13%) and 8 (80%), respectively, used robust evaluation. Primary uncertainties considered were patient setup (photons and protons) and range calculation uncertainties (protons). Participants expressed the need for improved commercial tools to control and evaluate plan complexity and robustness. CONCLUSION: Clinical implementation of methods to control and evaluate plan complexity and robustness is very heterogeneous. Better tools are needed to manage complexity and robustness in treatment planning systems. International guidelines may promote harmonization.

Edge area metric complexity scoring of volumetric modulated arc therapy plans.

BACKGROUND AND PURPOSE: Aperture-based complexity metrics have been suggested as a method to score complexity of volumetric modulated arc therapy (VMAT) plans. The purpose of this study was to evaluate the edge area metric (EAM) for clinical VMAT plans on a control point and treatment plan level. MATERIALS AND METHODS: EAM on a control point level was evaluated based on film measurements of 18 static beam openings originating from VMAT plans. EAM on a treatment plan level (arithmetic mean value of EAM scores for control points) was evaluated based on measurements with the Delta4® for 200 VMAT plans for four different treatment sites: pelvic, thorax, head and neck, and prostate. Measurements were compared to calculations and dose difference and gamma pass rates were evaluated. RESULTS: EAM scores on a control point level correlated with Pearson's r-values of -0.96 and -0.77 to dose difference and gamma pass rates, respectively. The prostate plans had the highest average EAM score. A connection between smaller PTVs and higher EAM scores was found. No correlation between the evaluation result and EAM on a plan level was found. CONCLUSIONS: EAM on a control point level was shown to correlate to the difference between measured and calculated 2D dose distributions of clinical VMAT beam openings. No correlation was found for EAM on a plan level for clinical treatment plans.

Renography with a semiautomated algorithm for diuretic decision 7 min postradiopharmaceutical administration: a feasibility study.

OBJECTIVE: The F+10 method for diuretic renography (diuretics given 10 min after the radiopharmaceutical) could be a time-conserving method. This method involves a 30-min dynamic acquisition where diuretics are administered only when necessary by the Nuclear Medicine technologist performing the examination. The purpose of this study was to assess the method's performance and to discover the optimal threshold of residual activity for a diuretic administration 7 min into the F+10 renography by reprocessing raw data from prior performed examinations with 20-min acquisitions without diuretics. METHODS: Retrospectively, raw data from 320 original examinations of adult patients performed from 2013 to 2015 were reprocessed into 7-min series and categorized as requiring diuretic or not. The diuretic decisions made by an expert panel were used as a reference. A receiver-operating characteristic curve was drawn to assess the optimal cutoff value for the residual renal activity. Sensitivity, specificity, positive and negative predictive values, as well as the Youden J index were calculated. RESULT: The experts classified 50% (160 examinations) as in need of diuretics. The receiver-operating characteristic curve demonstrated the theoretical optimal cutoff value at 7 min to be 94% of maximum activity (sensitivity 0.93, specificity 0.81, Youden J index 0.73). A clinically acceptable threshold is suggested to be 85% (sensitivity 0.99, specificity 0.59, Youden J index 0.58). CONCLUSION: Tc-mercaptoacetyltriglycine renography with the F+10 method and the threshold 85% for diuretic decision 7 min into the renography is a feasible and acceptable method in clinical practice.

What is plan quality in radiotherapy? The importance of evaluating dose metrics, complexity, and robustness of treatment plans.

Plan evaluation is a key step in the radiotherapy treatment workflow. Central to this step is the assessment of treatment plan quality. Hence, it is important to agree on what we mean by plan quality and to be fully aware of which parameters it depends on. We understand plan quality in radiotherapy as the clinical suitability of the delivered dose distribution that can be realistically expected from a treatment plan. Plan quality is commonly assessed by evaluating the dose distribution calculated by the treatment planning system (TPS). Evaluating the 3D dose distribution is not easy, however; it is hard to fully evaluate its spatial characteristics and we still lack the knowledge for personalising the prediction of the clinical outcome based on individual patient characteristics. This advocates for standardisation and systematic collection of clinical data and outcomes after radiotherapy. Additionally, the calculated dose distribution is not exactly the dose delivered to the patient due to uncertainties in the dose calculation and the treatment delivery, including variations in the patient set-up and anatomy. Consequently, plan quality also depends on the robustness and complexity of the treatment plan. We believe that future work and consensus on the best metrics for quality indices are required. Better tools are needed in TPSs for the evaluation of dose distributions, for the robust evaluation and optimisation of treatment plans, and for controlling and reporting plan complexity. Implementation of such tools and a better understanding of these concepts will facilitate the handling of these characteristics in clinical practice and be helpful to increase the overall quality of treatment plans in radiotherapy.

Evaluation of deformable image registration accuracy for CT images of the thorax region.

PURPOSE: Evaluate the performance of three commercial deformable image registration (DIR) solutions on computed tomography (CT) image-series of the thorax. METHODS: DIRs were performed on CT image-series of a thorax phantom with tumor inserts and on six 4-dimensional patient CT image-series of the thorax. The center of mass shift (CMS), dice similarity coefficient (DSC) and dose-volume-histogram (DVH) parameters were used to evaluate the accuracy. Dose calculations on deformed patient images were compared to calculations on un-deformed images for the gross tumor volume (GTV) (Dmean, D98%), lung (V20Gy, V12Gy), heart and spinal cord (D2%). RESULTS: Phantom structures with constant volume and shifts ≤30 mm were reproduced with visually acceptable accuracy (DSC ≥ 0.91, CMS ≤ 0.9 mm) for all software solutions. Deformations including volume changes were less accurate with 9/12 DIRs considered visually unacceptable. In patients, organs were reproduced with DSC ≥ 0.83. GTV shifts ≤1.6 cm were reproduced with visually acceptable accuracy by all software while larger shifts resulted in failures for at least one of the software. In total, the best software succeeded in 18/25 DIRs while the worst succeeded in 12/25 DIRs. Visually acceptable DIRs resulted in deviations ≤3.0% of the prescribed dose and ≤3.6% of the total structure volume in the evaluated DVH-parameters. CONCLUSIONS: The take home message from the results of this study is the importance to have a visually acceptable registration. DSC and CMS are not predictive of the associated dose deviation. Visually acceptable DIRs implied dose deviations ≤3.0%.

Structure delineation in the presence of metal - A comparative phantom study using single and dual-energy computed tomography with and without metal artefact reduction.

BACKGROUND AND PURPOSE: Metal artefacts in computed tomography (CT) images impairs structure delineation. These artefacts can potentially be reduced with dual-energy CT (DECT) with or without using metal artefact reduction (MAR). The purpose was to investigate how structure delineation in DECT with or without MAR and single-energy CT (SECT) images were affected by metals. MATERIALS AND METHODS: A phantom with known irregular structures was developed. Reference structures were determined from a low-noise scan without metal. Bilateral hip prostheses were simulated with steel or titanium inserts. The phantom was scanned with SECT and fast-kV switching DECT with optional MAR. Four radiation oncologists delineated the structures in two phantom set-ups. Delineated structures were evaluated with Dice similarity coefficient (DSC) and Hausdorff distance relative to the reference structures. RESULTS: With titanium inserts, more structures were detected for non-MAR DECT compared to SECT while the same or less were detected with steel inserts. MAR improved delineation in DECT images. For steel inserts, three structures in the region of artefacts, were delineated by at least two oncologists with MAR-DECT compared to none with non-MAR DECT or SECT. The highest values of DSC for MAR-DECT were 0.69, 0.81 and 0.77 for those structures. CONCLUSIONS: Delineation was improved with non-MAR DECT compared to SECT, especially for titanium inserts. A larger improvement was seen with the use of MAR for both steel and titanium inserts. The improvement was dependent on the location of the structure relative to the inserts, and the structure contrast relative to the background.