Patient- versus physician-reported outcomes in prostate cancer patients receiving hypofractionated radiotherapy within a randomized controlled trial.

PURPOSE: The risk of developing acute radiotherapy(RT)-induced side effects may increase with hypofractionated RT. To detect treatment-related side effects, patient-reported outcomes (PROs) might be more reliable than physician-reported outcomes. Therefore, we tried to evaluate the rate of agreement between urinary and gastrointestinal (GI) side effects and the prevalence of side effects reported by patients and by physicians. METHODS: Data from a randomized controlled trial (RCT) comparing two hypofractionated RT schedules were used. Urinary (nocturia, incontinence, frequency, dysuria, and urgency) and GI (obstruction, diarrhea, vomiting, nausea, bloating, hemorragia, and incontinence) symptoms measured by the EORTC QLQ-C30 and PR-25 were used for PROs. The same symptoms were scored by the physician using the Common Terminology Criteria Adverse Events v4.0. Outcomes were reported at baseline, end of treatment, month 1, and month 3. PROs and physician-reported outcomes were converted in two categories (0 = no symptoms; 1 = symptoms of any severity) and were correlated using the kappa (κ) correlation statistics. Values below 0.40 were considered low agreement. In addition, the prevalence of symptoms was calculated. RESULTS: Data from 160 patients were used. The mean value for Cohen's κ was 0.31 (ranging between 0.04 and 0.55) and 0.23 (ranging between 0.04 and 0.47) for urinary and GI symptoms, respectively. Except for three symptoms at baseline, all symptoms reported by patients were higher than those reported by physicians. CONCLUSION: There is low agreement between symptoms reported by patients and physicians, with high rates of underreporting by the physician.

Computed chest radiography for total body irradiation: image quality and clinical feasibility.

Objective.In myeloablative total body irradiation (TBI), lung shielding blocks are used to reduce the dose to the lungs and hence decrease the risk of radiation pneumonitis. Some centers are still using mega-Volt (MV) imaging with dedicated silver halide-based films during simulation and treatment for lung delineation and position verification. However, the availability of these films has recently become an issue. This study examines the clinical performance of a computed radiography (CR) solution in comparison to radiographic films and potential improvement of image quality by filtering and post-processing.Approach.We compared BaFBrI-based CR plates to radiographic films. First, images of an aluminum block were analyzed to assess filter impact on scatter reduction. Secondly, a dedicated image quality phantom was used to assess signal linearity, signal-to-noise ratio (SNR), contrast and spatial resolution. Ultimately, a clinical performance study involving two impartial observers was conducted on an anthropomorphic chest phantom, employing visual grading analysis (VGA). Various filter materials and positions as well as post-processing were examined, and the workflow between CR and film was compared.Main results.CR images exhibited high SNR and linearity but demonstrated lower spatial and contrast resolution when compared to film. However, filtering improved contrast resolution and SNR, while positioning filters inside the cassette additionally enhanced sharpness. Image processing improved VGA scores, while additional filtering also resulted in higher spine visibility scores. CR shortened TBI simulation by over 10 minutes for one patient, alongside a dose reduction by order of 0.1 Gy.Significance.This study highlights potential advantages of shifting from conventional radiographic film to CR for TBI. Overall, CR with the incorporation of processing and filtering proves to be suitable for TBI chest imaging. When compared to radiographic film, CR offers advantages such as reduced simulation time and dose delivery, re-usability of image plates and digital workflow integration.

Peripheral blood lymphocytes differ in DNA damage response after exposure to X-rays with different physical properties.

Introduction: In radiology, low X-ray energies (<140 keV) are used to obtain an optimal image while in radiotherapy, higher X-ray energies (MeV) are used to eradicate tumor tissue. In radiation research, both these X-ray energies being used to extrapolate in vitro research to clinical practice. However, the energy deposition of X-rays depends on their energy spectrum, which might lead to changes in biological response. Therefore, this study compared the DNA damage response (DDR) in peripheral blood lymphocytes (PBLs) exposed to X-rays with varying beam quality, mean photon energy (MPE) and dose rate.Methods: The DDR was evaluated in peripheral blood lymphocytes (PBLs) by the É£-H2AX foci assay, the cytokinesis-block micronucleus assay and an SYTOX-based cell death assay, combined with specific cell death inhibitors. Cell cultures were irradiated with a 220 kV X-ray research cabinet (SARRP, X-Strahl) or a 6 MV X-ray linear accelerator (Elekta Synergy). Three main physical parameters were investigated: beam quality (V), MPE (eV) and dose rate (Gy/min). Additional copper (Cu) filtration caused variation in the MPE (78 keV, 94 keV, 118 keV) at SARRP; dose rates were varied by adjusting tube current for 220 kV X-rays (0.33-3 Gy/min) or water-phantom depth in the 6 MV set-up (3-6 Gy/min).Results: The induction of chromosomal damage and initial (30 min) DNA double-stranded breaks (DSBs) were significantly higher for 220 kV X-rays compared to 6 MV X-rays, while cell death induction was similar. Specific cell death inhibitors for apoptosis, necroptosis and ferroptosis were not capable of blocking cell death after irradiation using low or high-energy X-rays. Additional Cu filtration increased the MPE, which significantly decreased the amount of chromosomal damage and DSBs. Within the tested ranges no specific effects of dose rate variation were observed.Conclusion: The DDR in PBLs is influenced by the beam quality and MPE. This study reinforces the need for consideration and inclusion of all physical parameters in radiation-related studies.

Impact of proton therapy on the DNA damage induction and repair in hematopoietic stem and progenitor cells.

Proton therapy is of great interest to pediatric cancer patients because of its optimal depth dose distribution. In view of healthy tissue damage and the increased risk of secondary cancers, we investigated DNA damage induction and repair of radiosensitive hematopoietic stem and progenitor cells (HSPCs) exposed to therapeutic proton and photon irradiation due to their role in radiation-induced leukemia. Human CD34+ HSPCs were exposed to 6 MV X-rays, mid- and distal spread-out Bragg peak (SOBP) protons at doses ranging from 0.5 to 2 Gy. Persistent chromosomal damage was assessed with the micronucleus assay, while DNA damage induction and repair were analyzed with the γ-H2AX foci assay. No differences were found in induction and disappearance of γ-H2AX foci between 6 MV X-rays, mid- and distal SOBP protons at 1 Gy. A significantly higher number of micronuclei was found for distal SOBP protons compared to 6 MV X-rays and mid- SOBP protons at 0.5 and 1 Gy, while no significant differences in micronuclei were found at 2 Gy. In HSPCs, mid-SOBP protons are as damaging as conventional X-rays. Distal SOBP protons showed a higher number of micronuclei in HSPCs depending on the radiation dose, indicating possible changes of the in vivo biological response.

ARCHERY: a prospective observational study of artificial intelligence-based radiotherapy treatment planning for cervical, head and neck and prostate cancer - study protocol.

INTRODUCTION: Fifty per cent of patients with cancer require radiotherapy during their disease course, however, only 10%-40% of patients in low-income and middle-income countries (LMICs) have access to it. A shortfall in specialised workforce has been identified as the most significant barrier to expanding radiotherapy capacity. Artificial intelligence (AI)-based software has been developed to automate both the delineation of anatomical target structures and the definition of the position, size and shape of the radiation beams. Proposed advantages include improved treatment accuracy, as well as a reduction in the time (from weeks to minutes) and human resources needed to deliver radiotherapy. METHODS: ARCHERY is a non-randomised prospective study to evaluate the quality and economic impact of AI-based automated radiotherapy treatment planning for cervical, head and neck, and prostate cancers, which are endemic in LMICs, and for which radiotherapy is the primary curative treatment modality. The sample size of 990 patients (330 for each cancer type) has been calculated based on an estimated 95% treatment plan acceptability rate. Time and cost savings will be analysed as secondary outcome measures using the time-driven activity-based costing model. The 48-month study will take place in six public sector cancer hospitals in India (n=2), Jordan (n=1), Malaysia (n=1) and South Africa (n=2) to support implementation of the software in LMICs. ETHICS AND DISSEMINATION: The study has received ethical approval from University College London (UCL) and each of the six study sites. If the study objectives are met, the AI-based software will be offered as a not-for-profit web service to public sector state hospitals in LMICs to support expansion of high quality radiotherapy capacity, improving access to and affordability of this key modality of cancer cure and control. Public and policy engagement plans will involve patients as key partners.

Handle With Care: The Anterior Hip Capsule Plays a Key Role in Daily Hip Performance.

Background: Passive energy storage and return has long been recognized as one of the central mechanisms for minimizing the energy cost needed for terrestrial locomotion. Although the iliofemoral ligament (IFL) is the strongest ligament in the body, its potential role in energy-efficient walking remains unexplored. Purpose: To identify the contribution of the IFL to the amount of work performed by the hip muscles for normal, straight-level walking. Study Design: Controlled laboratory study. Methods: Straight-level walking of 50 healthy and injury-free adults was simulated using the AnyBody Modeling System. For each participant, the bone morphology and soft tissue properties were nonuniformly scaled. The superior and inferior parts of the IFL were represented by 2 springs each, and a linear force-strain relation was defined. A parameter study was conducted to account for the uncertainty surrounding the mechanical properties of the IFL. The work required from the gluteus, quadriceps, iliopsoas, and sartorius with and without inclusion of the IFL was calculated. Analysis of variance with subsequent post hoc paired t test was used to test the significance of IFL presence on the required mechanical work. Results: During walking, the strain in the IFL reached a median of 18.7% (95% CI, 8.0%-26.5%), with the largest values obtained at toe-off. With the IFL undamaged and fully operational, the effort required by the hip flexor muscles was reduced by a median of 54% (99% CI, 45%-62%) for the iliopsoas and by a median of 41% (99% CI, 27%-54%) for the sartorius muscles. The inclusion of the IFL did not significantly alter the work required by the gluteus and the quadriceps. Conclusion: The findings emphasized the key role the IFL plays in hip flexion by working synergistically with the hip musculature. Clinical Relevance: The importance of the contribution of the IFL to the hip flexors warrants careful handling and repair of these ligaments in cases of surgery and structural damage.

Dose-volume-based evaluation of convolutional neural network-based auto-segmentation of thoracic organs at risk.

Background and purpose: The geometrical accuracy of auto-segmentation using convolutional neural networks (CNNs) has been demonstrated. This study aimed to investigate the dose-volume impact of differences between automatic and manual OARs for locally advanced (LA) and peripherally located early-stage (ES) non-small cell lung cancer (NSCLC). Material and methods: A single CNN was created for automatic delineation of the heart, lungs, main left and right bronchus, esophagus, spinal cord and trachea using 55/10/40 patients for training/validation/testing. Dice score coefficient (DSC) and 95th percentile Hausdorff distance (HD95) were used for geometrical analysis. A new treatment plan based on the auto-segmented OARs was created for each test patient using 3D for ES-NSCLC (SBRT, 3-8 fractions) and IMRT for LA-NSCLC (24-35 fractions). The correlation between geometrical metrics and dose-volume differences was investigated. Results: The average (±1 SD) DSC and HD95 were 0.82 ± 0.07 and 16.2 ± 22.4 mm, while the average dose-volume differences were 0.5 ± 1.5 Gy (ES) and 1.5 ± 2.8 Gy (LA). The geometrical metrics did not correlate with the observed dose-volume differences (average Pearson for DSC: -0.27 ± 0.18 (ES) and -0.09 ± 0.12 (LA); HD95: 0.1 ± 0.3 mm (ES) and 0.2 ± 0.2 mm (LA)). Conclusions: After post-processing, manual adjustments of automatic contours are only needed for clinically relevant OARs situated close to the tumor or within an entry or exit beam e.g., the heart and the esophagus for LA-NSCLC and the bronchi for ES-NSCLC. The lungs do not need to be checked further in detail.

Automated Instead of Manual Treatment Planning? A Plan Comparison Based on Dose-Volume Statistics and Clinical Preference.

PURPOSE: Automated planning aims to speed up treatment planning and improve plan quality. We compared manual planning with automated planning for lung stereotactic body radiation therapy based on dose-volume histogram statistics and clinical preference. METHODS AND MATERIALS: Manual and automated intensity modulated radiation therapy plans were generated for 56 patients by use of software developed in-house and Pinnacle 9.10 Auto-Planning, respectively. Optimization times were measured in 10 patients, and the impact of the automated plan (AP) on the total treatment cost was estimated. For the remaining 46 patients, each plan was checked against our clinical objectives, and a pair-wise dose-volume histogram comparison was performed. Three experienced radiation oncologists evaluated each plan and indicated their preference. RESULTS: APs reduced the average optimization time by 77.3% but only affected the total treatment cost by 3.6%. Three APs and 0 manual plans failed our clinical objectives, and 13 APs and 9 manual plans showed a minor deviation. APs significantly reduced D2% (2% of the volume receives a dose of at least D2%) for the spinal cord, esophagus, heart, aorta, and main stem bronchus (P < .05) while preserving target coverage. The radiation oncologists found >75% of the APs clinically acceptable without any further fine-tuning. CONCLUSIONS: APs may help to create satisfactory treatment plans quickly and effectively. Because critical appraisal by qualified professionals remains necessary, there is no such thing as "fully automated" planning yet.

4 Weeks Versus 5 Weeks of Hypofractionated High-dose Radiation Therapy as Primary Therapy for Prostate Cancer: Interim Safety Analysis of a Randomized Phase 3 Trial.

PURPOSE: Hypofractionated radiation therapy (HFRT) for localized prostate cancer is safe and effective. The question that remains is which hypofractionation schedule to implement. We compared 2 different HFRT regimens in the present study. METHODS AND MATERIALS: From June 2013 to July 2016, 160 patients with prostate cancer were randomly assigned (1:1), within this single-center phase III trial, to 56 Gy (16 fractions of 3.5 Gy; arm A) or 67 Gy (25 fractions of 2.68 Gy; arm B). Randomization was performed using computer-generated permuted blocks, stratified by previous transurethral resection of the prostate and the presence of a dominant intraprostatic lesion. Treatment allocation was not masked, and the clinicians were not blinded. The primary endpoint was acute gastrointestinal (GI) toxicity, assessed using the Common Terminology Criteria for Adverse Events, version 4.0, and Radiation Therapy Oncology Group toxicity scale. An interim analysis of acute toxicity was planned at 160 patients to prove the safety of both treatment regimens. If ≥22 of 72 patients had grade ≥2 GI toxicity, the study arm would be rejected. The study is registered at ClinicalTrials.gov (NCT01921803). RESULTS: In arm A, 20 patients (26%) and 1 patient (1%) developed acute grade 2 and grade 3 GI toxicity. In arm B, 16 patients (20%) reported acute grade 2 GI toxicity. In arm A, 42 (55%) and 5 (6%) patients developed acute grade 2 and grade 3 urinary toxicity. In arm B, 40 (49%) and 7 (9%) patients reported acute grade 2 and grade 3 urinary toxicity. Toxicity peaked during radiation therapy and resolved in the months after radiation therapy. CONCLUSIONS: With acute grade ≥2 GI toxicity reported in 21 of 77 patients in arm A and 16 of 82 patients in arm B, both treatment arms can be considered safe.

Evaluation of uncertainty-based stopping criteria for monte carlo calculations of intensity-modulated radiotherapy and arc therapy patient dose distributions.

PURPOSE: To formulate uncertainty-based stopping criteria for Monte Carlo (MC) calculations of intensity-modulated radiotherapy and intensity-modulated arc therapy patient dose distributions and evaluate their influence on MC simulation times and dose characteristics. METHODS AND MATERIALS: For each structure of interest, stopping criteria were formulated as follows: sigma(rel) or=95% of the voxels, where sigma(rel) represents the relative statistical uncertainty on the estimated dose, D. The tolerated uncertainty (sigma(rel,tol)) was 2%. The dose limit (D(lim)) equaled the planning target volume (PTV) prescription dose or a dose value related to the organ at risk (OAR) planning constraints. An intensity-modulated radiotherapy-lung, intensity-modulated radiotherapy-ethmoid sinus, and intensity-modulated arc therapy-rectum patient case were studied. The PTV-stopping criteria-based calculations were compared with the PTV+OAR-stopping criteria-based calculations. RESULTS: The MC dose distributions complied with the PTV-stopping criteria after 14% (lung), 21% (ethmoid), and 12% (rectum) of the simulation times of a 100 million histories reference calculation, and increased to 29%, 44%, and 51%, respectively, by the addition of the OAR-stopping criteria. Dose-volume histograms corresponding to the PTV-stopping criteria, PTV+OAR-stopping criteria, and reference dose calculations were indiscernible. The median local dose differences between the PTV-stopping criteria and the reference calculations amounted to 1.4% (lung), 2.1% (ethmoid), and 2.5% (rectum). CONCLUSIONS: For the patient cases studied, the MC calculations using PTV-stopping criteria only allowed accurate treatment plan evaluation. The proposed stopping criteria provided a flexible tool to assist MC patient dose calculations. The structures of interest and appropriate values of sigma(rel,tol) and D(lim) should be selected for each patient individually according to the clinical treatment planning goals.

Positron emission tomography-guided, focal-dose escalation using intensity-modulated radiotherapy for head and neck cancer.

PURPOSE: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. METHODS AND MATERIALS: A Phase I clinical trial was designed to escalate the dose limited to the [(18)-F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy. RESULTS: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p = n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted (18)F-FDG-PET-delineated region. CONCLUSIONS: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.

Comparison of 6 MV and 18 MV photons for IMRT treatment of lung cancer.

BACKGROUND AND PURPOSE: To compare 6 MV and 18 MV photon intensity modulated radiotherapy (IMRT) for non-small cell lung cancer. MATERIALS AND METHODS: Doses for a cohort of 10 patients, typical for our department, were computed with a commercially available convolution/superposition (CS) algorithm. Final dose computation was also performed with a dedicated IMRT Monte Carlo dose engine (MCDE). RESULTS: CS plans showed higher D(95%) (Gy) for the GTV (68.13 vs 67.36, p=0.004) and CTV (67.23 vs 66.87, p=0.028) with 18 than with 6 MV photons. MCDE computations demonstrated higher doses with 6 MV than 18 MV in D(95%) for the PTV (64.62 vs 63.64, p=0.009), PTV(optim) (65.48 vs 64.83, p=0.014) and CTV (66.22 vs 65.64, p=0.027). Dose inhomogeneity was lower with 18 than with 6 MV photons for GTV (0.08 vs 0.09, p=0.007) and CTV (0.10 vs 0.11, p=0.045) in CS but not MCDE plans. 6 MV photons significantly (D(33%); p=0.045) spared the esophagus in MCDE plans. Observed dose differences between lower and higher energy IMRT plans were dependent on the individual patient. CONCLUSIONS: Selection of photon energy depends on priority ranking of endpoints and individual patients. In the absence of highly accurate dose computation algorithms such as CS and MCDE, 6 MV photons may be the prudent choice.

Conversion of CT numbers into tissue parameters for Monte Carlo dose calculations: a multi-centre study.

The conversion of computed tomography (CT) numbers into material composition and mass density data influences the accuracy of patient dose calculations in Monte Carlo treatment planning (MCTP). The aim of our work was to develop a CT conversion scheme by performing a stoichiometric CT calibration. Fourteen dosimetrically equivalent tissue subsets (bins), of which ten bone bins, were created. After validating the proposed CT conversion scheme on phantoms, it was compared to a conventional five bin scheme with only one bone bin. This resulted in dose distributions D(14) and D(5) for nine clinical patient cases in a European multi-centre study. The observed local relative differences in dose to medium were mostly smaller than 5%. The dose-volume histograms of both targets and organs at risk were comparable, although within bony structures D(14) was found to be slightly but systematically higher than D(5). Converting dose to medium to dose to water (D(14) to D(14wat) and D(5) to D(5wat)) resulted in larger local differences as D(5wat) became up to 10% higher than D(14wat). In conclusion, multiple bone bins need to be introduced when Monte Carlo (MC) calculations of patient dose distributions are converted to dose to water.

[18F]fluoro-deoxy-glucose positron emission tomography ([18F]FDG-PET) voxel intensity-based intensity-modulated radiation therapy (IMRT) for head and neck cancer.

BACKGROUND AND PURPOSE: Focused dose escalation may improve local control in head and neck cancer. Planning results of [(18)F]fluoro-deoxy-glucose positron emission tomography ([(18)F]FDG-PET) voxel intensity-based intensity-modulated radiation therapy (IMRT) were compared with those of PET contour-based IMRT. PATIENTS AND METHODS: PET contour-based IMRT aims to deliver a homogeneous boost dose to a PET-based subvolume of the planning target volume (PTV), called PTV(PET). The present PET voxel intensity-based planning study aims to prescribe the boost dose directly as a function of PET voxel intensity values, while leaving the dose distribution outside the PTV unchanged. Two escalation steps (2.5 and 3 Gy/fraction) were performed for 15 patients. RESULTS: PTV(PET) was irradiated with a homogeneous dose in the contour-based approach. In the voxel intensity-based approach, one or more sharp dose peaks were created inside the PTV, following the distribution of PET voxel intensity values. CONCLUSIONS: While PET voxel intensity-based IMRT had a large effect on the dose distribution within the PTV, only small effects were observed on the dose distribution outside this PTV and on the dose delivered to the organs at risk. Therefore both methods are alternatives for boosting subvolumes inside a selected PTV.

Comparison of dose-volume histograms of IMRT treatment plans for ethmoid sinus cancer computed by advanced treatment planning systems including Monte Carlo.

BACKGROUND AND PURPOSE: To recompute clinical intensity-modulated treatment plans for ethmoid sinus cancer and to compare quantitatively the dose-volume histograms (DVHs) of the planning target volume (PTV) and the optic organs at risk. MATERIAL AND METHODS: Ten step-and-shoot intensity-modulated treatment plans were enrolled in this study. Large natural and surgical air cavities challenged the calculation systems. Each optimized treatment plan was recalculated by two superposition convolution (TMS and Pinnacle) and a Monte Carlo system (MCDE). To compare the resulting DVHs, a one-way ANOVA for repeated measurements was performed and multiple pairwise comparisons were made. RESULTS: The tails of the PTV-DVHs were significantly higher for the Monte Carlo system. The DVHs of the critical organs displayed some statistically but not always clinically significant differences. For the individual patients, the three planning systems sometimes reproduced clinically discrepant DVHs that were not significantly different when averaged over all patients. CONCLUSIONS: Dose to air cavities contains computational uncertainty. As this dose is clinically irrelevant and optimizing it is meaningless, we recommended extracting the air from the PTV when constructing the PTV-DVH. The planning systems considered reproduce DVHs that are significantly different, especially in the tail region of PTV-DVHs.

Accuracy of patient dose calculation for lung IMRT: A comparison of Monte Carlo, convolution/superposition, and pencil beam computations.

The accuracy of dose computation within the lungs depends strongly on the performance of the calculation algorithm in regions of electronic disequilibrium that arise near tissue inhomogeneities with large density variations. There is a lack of data evaluating the performance of highly developed analytical dose calculation algorithms compared to Monte Carlo computations in a clinical setting. We compared full Monte Carlo calculations (performed by our Monte Carlo dose engine MCDE) with two different commercial convolution/superposition (CS) implementations (Pinnacle-CS and Helax-TMS's collapsed cone model Helax-CC) and one pencil beam algorithm (Helax-TMS's pencil beam model Helax-PB) for 10 intensity modulated radiation therapy (IMRT) lung cancer patients. Treatment plans were created for two photon beam qualities (6 and 18 MV). For each dose calculation algorithm, patient, and beam quality, the following set of clinically relevant dose-volume values was reported: (i) minimal, median, and maximal dose (Dmin, D50, and Dmax) for the gross tumor and planning target volumes (GTV and PTV); (ii) the volume of the lungs (excluding the GTV) receiving at least 20 and 30 Gy (V20 and V30) and the mean lung dose; (iii) the 33rd percentile dose (D33) and Dmax delivered to the heart and the expanded esophagus; and (iv) Dmax for the expanded spinal cord. Statistical analysis was performed by means of one-way analysis of variance for repeated measurements and Tukey pairwise comparison of means. Pinnacle-CS showed an excellent agreement with MCDE within the target structures, whereas the best correspondence for the organs at risk (OARs) was found between Helax-CC and MCDE. Results from Helax-PB were unsatisfying for both targets and OARs. Additionally, individual patient results were analyzed. Within the target structures, deviations above 5% were found in one patient for the comparison of MCDE and Helax-CC, while all differences between MCDE and Pinnacle-CS were below 5%. For both Pinnacle-CS and Helax-CC, deviations from MCDE above 5% were found within the OARs: within the lungs for two (6 MV) and six (18 MV) patients for Pinnacle-CS, and within other OARs for two patients for Helax-CC (for Dmax of the heart and D33 of the expanded esophagus) but only for 6 MV. For one patient, all four algorithms were used to recompute the dose after replacing all computed tomography voxels within the patient's skin contour by water. This made all differences above 5% between MCDE and the other dose calculation algorithms disappear. Thus, the observed deviations mainly arose from differences in particle transport modeling within the lungs, and the commissioning of the algorithms was adequately performed (or the commissioning was less important for this type of treatment). In conclusion, not one pair of the dose calculation algorithms we investigated could provide results that were consistent within 5% for all 10 patients for the set of clinically relevant dose-volume indices studied. As the results from both CS algorithms differed significantly, care should be taken when evaluating treatment plans as the choice of dose calculation algorithm may influence clinical results. Full Monte Carlo provides a great benchmarking tool for evaluating the performance of other algorithms for patient dose computations.

Implementation of biologically conformal radiation therapy (BCRT) in an algorithmic segmentation-based inverse planning approach.

The development of new biological imaging technologies offers the opportunity to further individualize radiotherapy. Biologically conformal radiation therapy (BCRT) implies the use of the spatial distribution of one or more radiobiological parameters to guide the IMRT dose prescription. Our aim was to implement BCRT in an algorithmic segmentation-based planning approach. A biology-based segmentation tool was developed to generate initial beam segments that reflect the biological signal intensity pattern. The weights and shapes of the initial segments are optimized by means of an objective function that minimizes the root mean square deviation between the actual and intended dose values within the PTV. As proof of principle, [(18)F]FDG-PET-guided BCRT plans for two different levels of dose escalation were created for an oropharyngeal cancer patient. Both plans proved to be dosimetrically feasible without violating the planning constraints for the expanded spinal cord and the contralateral parotid gland as organs at risk. The obtained biological conformity was better for the first (2.5 Gy per fraction) than for the second (3 Gy per fraction) dose escalation level.

In search of the economic sustainability of Hadron therapy: the real cost of setting up and operating a Hadron facility.

PURPOSE: To determine the treatment cost and required reimbursement for a new hadron therapy facility, considering different technical solutions and financing methods. METHODS AND MATERIALS: The 3 technical solutions analyzed are a carbon only (COC), proton only (POC), and combined (CC) center, each operating 2 treatment rooms and assumed to function at full capacity. A business model defines the required reimbursement and analyzes the financial implications of setting up a facility over time; activity-based costing (ABC) calculates the treatment costs per type of patient for a center in a steady state of operation. Both models compare a private, full-cost approach with public sponsoring, only taking into account operational costs. RESULTS: Yearly operational costs range between €10.0M (M = million) for a publicly sponsored POC to €24.8M for a CC with private financing. Disregarding inflation, the average treatment cost calculated with ABC (COC: €29,450; POC: €46,342; CC: €46,443 for private financing; respectively €16,059, €28,296, and €23,956 for public sponsoring) is slightly lower than the required reimbursement based on the business model (between €51,200 in a privately funded POC and €18,400 in COC with public sponsoring). Reimbursement for privately financed centers is very sensitive to a delay in commissioning and to the interest rate. Higher throughput and hypofractionation have a positive impact on the treatment costs. CONCLUSIONS: Both calculation methods are valid and complementary. The financially most attractive option of a publicly sponsored COC should be balanced to the clinical necessities and the sociopolitical context.