Comparing cone-beam CT intensity correction methods for dose recalculation in adaptive intensity-modulated photon and proton therapy for head and neck cancer.

BACKGROUND: Adaptive intensity-modulated photon and proton radiotherapy (IMRT and IMPT) of head and neck (H&N) cancer requires frequent three-dimensional (3D) dose calculation. We compared two approaches for dose recalculation on the basis of intensity-corrected cone-beam (CB) x-ray computed tomography (CT) images. MATERIAL AND METHODS: For nine H&N tumor patients, virtual CTs (vCT) were generated by deformable image registration of the planning CT (pCT) to the CBCT. The second intensity correction approach used population-based lookup tables for scaling CBCT intensities to the pCT HU range (CBCTLUT). IMRT and IMPT plans were generated with a commercial treatment planning system. Dose recalculations on vCT and CBCTLUT were analyzed using a (3%, 3 mm) gamma-index analysis and comparison of normal tissue and tumor dose/volume parameters. A replanning CT (rpCT) acquired within three days of the CBCT served as reference. Single field uniform dose (SFUD) proton plans were created and recalculated on vCT and CBCTLUT for proton range comparison. RESULTS: Dose/volume parameters showed minor differences between rpCT, vCT and CBCTLUT in IMRT, but clinically relevant deviations between CBCTLUT and rpCT in the spinal cord for IMPT. Gamma-index pass-rates were found increased for vCT with respect to CBCTLUT in IMPT (by up to 21 percentage points) and IMRT (by up to 9 percentage points) for most cases. The SFUD-based proton range assessment showed improved agreement of vCT and rpCT, with 88-99% of the depth dose profiles in beam's eye view agreeing within 3 mm. For CBCTLUT, only 80-94% of the profiles fulfilled this criterion. CONCLUSION: vCT and CBCTLUT are suitable options for dose recalculation in adaptive IMRT. In the scope of IMPT, the vCT approach is preferable.

Pulmonary magnetic resonance-guided online adaptive radiotherapy of locally advanced: the PUMA trial.

BACKGROUND: Patients with locally-advanced non-small-cell lung cancer (LA-NSCLC) are often ineligible for surgery, so that definitive chemoradiotherapy (CRT) represents the treatment of choice. Nevertheless, long-term tumor control is often not achieved. Intensification of radiotherapy (RT) to improve locoregional tumor control is limited by the detrimental effect of higher radiation exposure of thoracic organs-at-risk (OAR). This narrow therapeutic ratio may be expanded by exploiting the advantages of magnetic resonance (MR) linear accelerators, mainly the online adaptation of the treatment plan to the current anatomy based on daily acquired MR images. However, MR-guidance is both labor-intensive and increases treatment times, which raises the question of its clinical feasibility to treat LA-NSCLC. Therefore, the PUMA trial was designed as a prospective, multicenter phase I trial to demonstrate the clinical feasibility of MR-guided online adaptive RT in LA-NSCLC. METHODS: Thirty patients with LA-NSCLC in stage III A-C will be accrued at three German university hospitals to receive MR-guided online adaptive RT at two different MR-linac systems (MRIdian Linac®, View Ray Inc. and Elekta Unity®, Elekta AB) with concurrent chemotherapy. Conventionally fractioned RT with isotoxic dose escalation up to 70 Gy is applied. Online plan adaptation is performed once weekly or in case of major anatomical changes. Patients are followed-up by thoracic CT- and MR-imaging for 24 months after treatment. The primary endpoint is twofold: (1) successfully completed online adapted fractions, (2) on-table time. Main secondary endpoints include adaptation frequency, toxicity, local tumor control, progression-free and overall survival. DISCUSSION: PUMA aims to demonstrate the clinical feasibility of MR-guided online adaptive RT of LA-NSCLC. If successful, PUMA will be followed by a clinical phase II trial that further investigates the clinical benefits of this approach. Moreover, PUMA is part of a large multidisciplinary project to develop MR-guidance techniques. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05237453 .

A stochastic approach to estimate the uncertainty of dose mapping caused by uncertainties in b-spline registration.

PURPOSE: In fractionated radiation therapy, image guidance with daily tomographic imaging becomes more and more clinical routine. In principle, this allows for daily computation of the delivered dose and for accumulation of these daily dose distributions to determine the actually delivered total dose to the patient. However, uncertainties in the mapping of the images can translate into errors of the accumulated total dose, depending on the dose gradient. In this work, an approach to estimate the uncertainty of mapping between medical images is proposed that identifies areas bearing a significant risk of inaccurate dose accumulation. METHODS: This method accounts for the geometric uncertainty of image registration and the heterogeneity of the dose distribution, which is to be mapped. Its performance is demonstrated in context of dose mapping based on b-spline registration. It is based on evaluation of the sensitivity of dose mapping to variations of the b-spline coefficients combined with evaluation of the sensitivity of the registration metric with respect to the variations of the coefficients. It was evaluated based on patient data that was deformed based on a breathing model, where the ground truth of the deformation, and hence the actual true dose mapping error, is known. RESULTS: The proposed approach has the potential to distinguish areas of the image where dose mapping is likely to be accurate from other areas of the same image, where a larger uncertainty must be expected. CONCLUSIONS: An approach to identify areas where dose mapping is likely to be inaccurate was developed and implemented. This method was tested for dose mapping, but it may be applied in context of other mapping tasks as well.

A deep image-to-image network organ segmentation algorithm for radiation treatment planning: principles and evaluation.

BACKGROUND: We describe and evaluate a deep network algorithm which automatically contours organs at risk in the thorax and pelvis on computed tomography (CT) images for radiation treatment planning. METHODS: The algorithm identifies the region of interest (ROI) automatically by detecting anatomical landmarks around the specific organs using a deep reinforcement learning technique. The segmentation is restricted to this ROI and performed by a deep image-to-image network (DI2IN) based on a convolutional encoder-decoder architecture combined with multi-level feature concatenation. The algorithm is commercially available in the medical products "syngo.via RT Image Suite VB50" and "AI-Rad Companion Organs RT VA20" (Siemens Healthineers). For evaluation, thoracic CT images of 237 patients and pelvic CT images of 102 patients were manually contoured following the Radiation Therapy Oncology Group (RTOG) guidelines and compared to the DI2IN results using metrics for volume, overlap and distance, e.g., Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD95). The contours were also compared visually slice by slice. RESULTS: We observed high correlations between automatic and manual contours. The best results were obtained for the lungs (DSC 0.97, HD95 2.7 mm/2.9 mm for left/right lung), followed by heart (DSC 0.92, HD95 4.4 mm), bladder (DSC 0.88, HD95 6.7 mm) and rectum (DSC 0.79, HD95 10.8 mm). Visual inspection showed excellent agreements with some exceptions for heart and rectum. CONCLUSIONS: The DI2IN algorithm automatically generated contours for organs at risk close to those by a human expert, making the contouring step in radiation treatment planning simpler and faster. Few cases still required manual corrections, mainly for heart and rectum.

Statistical breathing curve sampling to quantify interplay effects of moving lung tumors in a 4D Monte Carlo dose calculation framework.

PURPOSE: The interplay between respiratory tumor motion and dose application by intensity modulated radiotherapy (IMRT) techniques can potentially lead to undesirable and non-intuitive deviations from the planned dose distribution. We developed a 4D Monte Carlo (MC) dose recalculation framework featuring statistical breathing curve sampling, to precisely simulate the dose distribution for moving target volumes aiming at a comprehensive assessment of interplay effects. METHODS: We implemented a dose accumulation tool that enables dose recalculations of arbitrary breathing curves including the actual breathing curve of the patient. This MC dose recalculation framework is based on linac log-files, facilitating a high temporal resolution up to 0.1 s. By statistical analysis of 128 different breathing curves, interplay susceptibility of different treatment parameters was evaluated for an exemplary patient case. To facilitate prospective clinical application in the treatment planning stage, in which patient breathing curves or linac log-files are not available, we derived a log-file free version with breathing curves generated by a random walk approach. Interplay was quantified by standard deviations σ in D5%, D50% and D95%. RESULTS: Interplay induced dose deviations for single fractions were observed and evaluated for IMRT and volumetric arc therapy (σD95% up to 1.3 %) showing a decrease with higher fraction doses and an increase with higher MU rates. Interplay effects for conformal treatment techniques were negligible (σ<0.1%). The log-file free version and the random walk generated breathing curves yielded similar results (deviations in σ< 0.1 %) and can be used as substitutes for interplay assessment. CONCLUSION: It is feasible to combine statistically sampled breathing curves with MC dose calculations. The universality of the presented framework allows comprehensive assessment of interplay effects in retrospective and prospective clinically relevant scenarios.

Respiratory-induced prostate motion: characterization and quantification in dynamic MRI.

BACKGROUND AND PURPOSE: To investigate prostate movement during deep breathing and contraction of abdominal musculature by means of dynamic MRI and analyze implications for image-guided radiotherapy of prostate cancer. PATIENTS AND METHODS: A total of 43 patients and 8 healthy volunteers were examined with MRI. Images during deep respiration and during contraction of abdominal musculature (via a coughing maneuver) were obtained with dynamic two-dimensional (2D) balanced SSFP; 3 frames/s were obtained over an acquisition time of 15 s. Images were acquired in sagittal orientation to evaluate motion along both the craniocaudal (cc)-axis and anteroposterior (ap)-axis. Prostate motion was quantified semi-automatically using dedicated software tools. RESULTS: Respiratory induced mean cc-axis displacement of the prostate was 2.7 ± 1.9 (SD) mm (range, 0.5-10.6 mm) and mean ap-axis displacement 1.8 ± 1.0 (SD) mm (range, 0.3-10 mm). In 69% of the subjects, breathing-related prostate movements were found to be negligible (< 3 mm). The prostate displacement for abdominal contraction was significantly higher: mean cc-axis displacement was max. 8.4 ± 6.7 (SD) mm (range, 0.6-27 mm); mean anteroposterior movement was 8.3 ± 7.7 (SD) mm (range, 0.7-26 mm). CONCLUSION: Dynamic MRI is an excellent tool for noninvasive real-time imaging of prostate movement. Further investigations regarding possible applications in image-guided radiotherapy, e.g., for individualized planning and in integrated linac/MRI systems, are warranted.

IMRT reirradiation with concurrent cetuximab immunotherapy in recurrent head and neck cancer.

PURPOSE: In this retrospective investigation, the outcome and toxicity after reirradiation with concurrent cetuximab immunotherapy of recurrent head and neck cancer (HNC) in patients who had contraindications to platinum-based chemotherapy were analyzed. MATERIALS AND METHODS: Ten patients with locally advanced recurrent HNC were retrospectively evaluated. In 9 cases, histology was squamous cell carcinoma, in one case adenoid cystic carcinoma. External beam radiotherapy was part of the initial treatment in all cases. Reirradiation was carried out using step-and-shoot intensity-modulated radiotherapy (IMRT) with a median dose of 50.4 Gy. Cetuximab was applied as loading dose (400 mg/m(2)) 1 week prior to reirradiation and then weekly concurrently with radiotherapy (250 mg/m(2)). RESULTS: The median overall survival time after initiation of reirradiation was 7 months; the 1-year overall survival (OS) rate was 40%. Local failure was found in 3 patients, resulting in a 1-year local control (LC) rate of 61%. The 1-year locoregional control (LRC) rate was 44%, while the 1-year distant metastasis-free survival (DMFS) was 75%. Acute hematological toxicity was not observed in the group. Severe acute toxicity included one fatal infield arterial bleeding and one flap necrosis. Severe late toxicities were noted in 2 patients: fibrosis of the temporomandibular joint in 1 patient and stenosis of the cervical esophagus in another. CONCLUSIONS: IMRT reirradiation with concurrent cetuximab immunotherapy in recurrent HNC is feasible with acceptable acute toxicity. Further investigations are necessary to determine the clinical role of this therapy concept.

New multileaf collimator with a leaf width of 5 mm improves plan quality compared to 10 mm in step-and-shoot IMRT of HNC using integrated boost procedure.

PURPOSE: To investigate whether a new multileaf collimator with a leaf width of 5 mm (MLC-5) over the entire field size of 40 x 40 cm(2) improves plan quality compared to a leaf width of 10 mm (MLC-10) in intensity-modulated radiotherapy (IMRT) with integrated boost for head and neck cancer. PATIENTS AND METHODS: A plan comparison was performed for ten patients with head and neck cancer. For each patient, seven plans were calculated: one plan with MLC-10 and nine beams, four plans with MLC-5 and nine beams (with different intensity levels and two-dimensional median filter sizes [2D-MFS]), and one seven-beam plan with MLC-5 and MLC-10, respectively. Isocenter, beam angles and planning constraints were not changed. Mean values of common plan parameters over all ten patients were estimated, and plan groups of MLC-5 and MLC-10 with nine and seven beams were compared. RESULTS: The use of MLC-5 led to a significantly higher conformity index and an improvement of the 90% coverage of PTV1 (planning target volume) and PTV2 compared with MLC-10. This was noted in the nine- and seven-beam plans. Within the nine-beam group with MLC-5, a reduction of the segment number by up to 25% at reduced intensity levels and for increased 2D-MFS did not markedly worsen plan quality. Interestingly, a seven-beam IMRT with MLC-5 was inferior to a nine-beam IMRT with MLC-5, but superior to a nine-beam IMRT with MLC-10. CONCLUSION: The use of an MLC-5 has significant advantages over an MLC-10 with respect to target coverage and protection of normal tissues in step-and-shoot IMRT of head and neck cancer.

Long-term survival of cancer patients compared to heart failure and stroke: a systematic review.

BACKGROUND: Cancer, heart failure and stroke are among the most common causes of death worldwide. Investigation of the prognostic impact of each disease is important, especially for a better understanding of competing risks. Aim of this study is to provide an overview of long term survival of cancer, heart failure and stroke patients based on the results of large population- and hospital-based studies. METHODS: Records for our study were identified by searches of Medline via Pubmed. We focused on observed and relative age- and sex-adjusted 5-year survival rates for cancer in general and for the four most common malignancies in developed countries, i.e. lung, breast, prostate and colorectal cancer, as well as for heart failure and stroke. RESULTS: Twenty studies were identified and included for analysis. Five-year observed survival was about 43% for all cancer entities, 40-68% for stroke and 26-52% for heart failure. Five-year age and sex adjusted relative survival was 50-57% for all cancer entities, about 50% for stroke and about 62% for heart failure. In regard to the four most common malignancies in developed countries 5-year relative survival was 12-18% for lung cancer, 73-89% for breast cancer, 50-99% for prostate cancer and about 43-63% for colorectal cancer. Trend analysis revealed a survival improvement over the last decades. CONCLUSIONS: The results indicate that long term survival and prognosis of cancer is not necessarily worse than that of heart failure and stroke. However, a comparison of the prognostic impact of the different diseases is limited, corroborating the necessity for further systematic investigation of competing risks.

Comparison of peripheral zone and central gland volume in patients undergoing intensity-modulated radiotherapy.

BACKGROUND AND PURPOSE: The shrinking effect of androgen deprivation therapy (ADT) and radiotherapy (RT) on prostate gland volume is a known clinical finding. Until now, it is not known which part of the prostate shrinks more. We examined patients with and without ADT undergoing intensity-modulated RT (IMRT) and performed 3-dimensional measurements of the peripheral zone (PZ) and central gland (CG) with magnetic resonance imaging (MRI). METHODS AND MATERIALS: Prostate gland volumes of PZ and CG between planning MRI and first available follow-up MRI were retrospectively determined in 44 patients with localized prostate carcinoma. A total of 24 patients had ADT with a median time interval of 5 months (range, 1.5-24 months). Median time interval between both MRI time points was 132 days (range, 104-224 days). Two observers performed PZ and CG delineation in consensus using planimetry. Volume changes over time were determined and compared. RESULTS: Patients who had ADT showed smaller prostate volume in the first MRI (mean [SD], 32 [16.7] mL), which was still present after IMRT (28.1 [16.7] mL). Patients who had no ADT started with 44.6 (16.9) mL and showed 37.5 (13.9) mL after IMRT. Shrinking effect in PZ was significantly larger than in CG for all patients (-18.3% vs -6.3%, P < 0.05). CONCLUSIONS: Because, typically, most tumors are located in PZ and this area also shows the largest shrinkage effect after IMRT, this should be taken into account for planning purposes. Notably, there are only minor differences in the relative shrinking effects between patients with and without ADT, although they start with different volumes.

Dosimetric Impact of the Positional Imaging Frequency for Hypofractionated Prostate Radiotherapy - A Voxel-by-Voxel Analysis.

BACKGROUND: To investigate deviations between planned and applied treatment doses for hypofractionated prostate radiotherapy and to quantify dosimetric accuracy in dependence of the image guidance frequency. METHODS: Daily diagnostic in-room CTs were carried out in 10 patients in treatment position as image guidance for hypofractionated prostate radiotherapy. Fraction doses were mapped to the planning CTs and recalculated, and applied doses were accumulated voxel-wise using deformable registration. Non-daily imaging schedules were simulated by deriving position correction vectors from individual scans and used to rigidly register the following scans until the next repositioning before dose recalculation and accumulation. Planned and applied doses were compared regarding dose-volume indices and TCP and NTCP values in dependence of the imaging and repositioning frequency. RESULTS: Daily image-guided repositioning was associated with only negligible deviations of analyzed dose-volume parameters and conformity/homogeneity indices for the prostate, bladder and rectum. Average CTV T did not significantly deviate from the plan values, and rectum NTCPs were highly comparable, while bladder NTCPs were reduced. For non-daily image-guided repositioning, there were significant deviations in the high-dose range from the planned values. Similarly, CTV dose conformity and homogeneity were reduced. While TCPs and rectal NTCPs did not significantly deteriorate for non-daily repositioning, bladder NTCPs appeared falsely diminished in dependence of the imaging frequency. CONCLUSION: Using voxel-by-voxel dose accumulation, we showed for the first time that daily image-guided repositioning resulted in only negligible dosimetric deviations for hypofractionated prostate radiotherapy. Regarding dosimetric aberrations for non-daily imaging, daily imaging is required to adequately deliver treatment.

Real-time 4DMRI-based internal target volume definition for moving lung tumors.

PURPOSE: In photon radiotherapy, respiratory-induced target motion can be accounted for by internal target volumes (ITV) or mid-ventilation target volumes (midV) defined on the basis of four-dimensional computed tomography (4D-CT). Intrinsic limitations of these approaches can result in target volumes that are not representative for the gross tumor volume (GTV) motion over the course of treatment. To address these limitations, we propose a novel patient-specific ITV definition method based on real-time 4D magnetic resonance imaging (rt-4DMRI). METHODS: Three lung cancer patients underwent weekly rt-4DMRI scans. A total of 24 datasets were included in this retrospective study. The GTV was contoured on breath-hold MR images and propagated to all rt-4DMRI images by deformable image registration. Different targets were created for the first (reference) imaging sessions: ITVs encompassing all GTV positions over the complete (ITV 80 s ) or partial acquisition time ( ITV 10 s ), ITVs including only voxels with a GTV probability-of-presence (POP) of at least 5% ( ITV 5 % ) or 10% ( ITV 10 % ), and the mid-ventilation GTV position. Reference planning target volumes ( PTV r ) were created by adding margins around the ITVs and midV target volumes. The geometrical overlap of the PTV r with ITV n 5 % from the six to eight subsequent imaging sessions on days n was quantified in terms of the Dice similarity coefficient (DSC), sensitivity [SE: ( PTV r ∩ ITV n 5 % )/ ITV n 5 % ] and precision [PRE: ( PTV r ∩ ITV n 5 % )/ PTV r ] as surrogates for target coverage and normal tissue sparing. RESULTS: Patient-specific analysis yielded a high variance of the overlap values of PTV r 10 s , when different periods within the reference imaging session were sampled. The mid-ventilation-based PTVs were smaller than the ITV-based PTVs. While the SE was high for patients with small breathing pattern variations, changes of the median breathing amplitudes in different imaging sessions led to inferior SE values for the mid-ventilation PTV for one patient. In contrast, PTV r 5 % and PTV r 10 % showed higher SE values with a higher robustness against interfractional changes, at the cost of larger target volumes. CONCLUSIONS: The results indicate that rt-4DMRI could be valuable for the definition of target volumes based on the GTV POP to achieve a higher robustness against interfractional changes than feasible with today's 4D-CT-based target definition concepts.

Changes of prostate gland volume with and without androgen deprivation after intensity modulated radiotherapy - A follow-up study.

BACKGROUND AND PURPOSE: The shrinking effect of androgen deprivation therapy (ADT) on prostate volume is a known finding, but data on volume changes during radiotherapy are inconsistent. We examined patients with and without ADT undergoing intensity modulated radiotherapy (IMRT) and performed follow-up examinations to study volume changes before and after radiotherapy. METHODS AND MATERIALS: Prostate volumes between planning magnetic resonance imaging (MRI) and last available follow-up MRI were retrospectively determined in 39 patients. Median time interval between first and last MRI was 233days (range 126-813). Two observers performed volume measurements in consensus and were blind to the timing of MRI. Volume changes over MRI were determined using the ellipsoid formula. Data of patients with and without ADT were compared by a linear mixed model. RESULTS: Of 39 patients, 22 had ADT with a median duration of 5months (range 1-24). ADT patients showed lower prostate volume throughout the study period (-28% to 38%). Although individual shrinking effect was highly variable, patients treated with IMRT but without ADT showed a significantly larger volume reduction (26.1%) than patients with ADT (12.9%, p<0.05). CONCLUSIONS: Patients undergoing IMRT show definite prostate shrinkage. The rate is slowed down after 6months in both groups, whereas the volume reduction is significantly larger in patients without ADT. Nevertheless there is no adding effect of ADT+IMRT vs. IMRT alone.

Catch me if you can--the use of image guidance in the radiotherapy of an unusual case of esophageal cancer.

BACKGROUND: Despite maximum therapy the prognosis of esophageal carcinoma still remains extremely poor. New treatment strategies including improved radiation therapy techniques promise better outcome by improving local control through precise dose delivery due to higher conformality. CASE REPORT: A 62-year-old patient with locally advanced carcinoma of the gastroesophageal junction underwent definitive radiochemotherapy with intensity-modulated radiation therapy (IMRT). On positioning control with the in-room CT, the distal esophagus, and hence the tumor, was found to be highly mobile exhibiting changes in position of up to 4 cm from fraction to fraction. RESULTS: IMRT plans were created for various positions establishing a plan library to choose from as appropriate. CT scans were performed prior to each treatment fraction to clarify esophagus position in order to choose the adequate treatment plan. CONCLUSION: Image guidance was crucial in this unusual case of esophageal carcinoma. Without the information from position control CTs, the tumor would have received only about half the prescribed dose due to variations in position. For this specific case, in-room CT scans are probably superior to kilo- or megavoltage CTs due to the higher soft-tissue contrast enabling detection of positioning variation of the organ and offering the possibility to use the CT for treatment planning.

Towards optimal stopping in radiation therapy.

A typical fractionated radiotherapy (RT) course is a long and arduous process, demanding significant financial, physical, and mental commitments from patients. Each additional session of RT significantly increases the physical and psychological burden on patients and leads to higher radiation exposure in organs-at-risk (OAR), while, in some cases, the therapeutic benefits might not be high enough to justify the risks. Today, through technological advancements in molecular biology, imaging, and genetics more information is gathered about individual patient response before, during, and after the treatment. we highlight some of the ways that mathematical tools can help assess treatment efficacy on the fly, adapt the treatment plan based on individual biological response, and optimally stop the treatment, if necessary. We term this "Optimal Stopping in RT (OSRT)", after a similar concept in the fields of dynamic programming and Markov decision processes. In short, OSRT can dynamically determine "whether, when and how" to stop the treatment to improve therapeutic ratios.

Feasibility of 4DCBCT-based proton dose calculation: An ex vivo porcine lung phantom study.

Inter-fractional variations of breathing pattern and patient anatomy introduce dose uncertainties in proton therapy. One approach to monitor these variations is to utilize the cone-beam computed tomography (CT, CBCT) scans routinely taken for patient positioning, reconstruct them as 4DCBCTs, and generate 'virtual CTs' (vCTs), combining the accurate CT numbers of the diagnostic 4DCT and the geometry of the daily 4DCBCT by using deformable image registration (DIR). In this study different algorithms for 4DCBCT reconstruction and DIR were evaluated. For this purpose, CBCT scans of a moving ex vivo porcine lung phantom with 663 and 2350 projections respectively were acquired, accompanied by an additional 4DCT as reference. The CBCT projections were sorted in 10 phase bins with the Amsterdam-shroud method and reconstructed phase-by-phase using first a FDK reconstruction from the Reconstruction Toolkit (RTK) and again an iterative reconstruction algorithm implemented in the Gadgetron Toolkit. The resulting 4DCBCTs were corrected by DIR of the corresponding 4DCT phases, using both a morphons algorithm from REGGUI and a b-spline deformation from Plastimatch. The resulting 4DvCTs were compared to the 4DCT by visual inspection and by calculating water equivalent thickness (WET) maps from the phantom's surface to the distal edge of a target from various angles. The optimized procedure was successfully repeated with mismatched input phases and on a clinical patient dataset. Proton treatment plans were simulated on the 4DvCTs and the dose distributions compared to the reference based on the 4DCT via gamma pass rate analysis. A combination of iterative reconstruction and morphons DIR yielded the most accurate 4DvCTs, with median WET differences under 2mm and 3%/3mm gamma pass rates per phase between 89% and 99%. These results suggest that image correction of iteratively reconstructed 4DCBCTs with a morphons DIR of the planning CT may yield sufficiently accurate 4DvCTs for daily time resolved proton dose calculations.

Dose-guided patient positioning in proton radiotherapy using multicriteria-optimization.

Proton radiotherapy (PT) requires accurate target alignment before each treatment fraction, ideally utilizing 3D in-room X-ray computed tomography (CT) imaging. Typically, the optimal patient position is determined based on anatomical landmarks or implanted markers. In the presence of non-rigid anatomical changes, however, the planning scenario cannot be exactly reproduced and positioning should rather aim at finding the optimal position in terms of the actually applied dose. In this work, dose-guided patient alignment, implemented as multicriterial optimization (MCO) problem, was investigated in the scope of intensity-modulated and double-scattered PT (IMPT and DSPT) for the first time. A method for automatically determining the optimal patient position with respect to pre-defined clinical goals was implemented. Linear dose interpolation was used to access a continuous space of potential patient shifts. Fourteen head and neck (H&N) and eight prostate cancer patients with up to five repeated CTs were included. Dose interpolation accuracy was evaluated and the potential dosimetric advantages of dose-guided over bony-anatomy-based patient alignment investigated by comparison of clinically relevant target and organ-at-risk (OAR) dose-volume histogram (DVH) parameters. Dose interpolation was found sufficiently accurate with average pass-rates of 90% and 99% for an exemplary H&N and prostate patient, respectively, using a 2% dose-difference criterion. Compared to bony-anatomy-based alignment, the main impact of automated MCO-based dose-guided positioning was a reduced dose to the serial OARs (spinal cord and brain stem) for the H&N cohort. For the prostate cohort, under-dosage of the target structures could be efficiently diminished. Limitations of dose-guided positioning were mainly found in reducing target over-dosage due to weight loss for H&N patients, which might require adaptation of the treatment plan. Since labor-intense online quality-assurance is not required for dose-guided patient positioning, it might, nevertheless, be considered an interesting alternative to full online re-planning for initially mitigating the effects of anatomical changes.

Evaluating target coverage and normal tissue sparing in the adjuvant radiotherapy of malignant pleural mesothelioma: helical tomotherapy compared with step-and-shoot IMRT.

PURPOSE: To evaluate the potential of helical tomotherapy in the adjuvant treatment of malignant pleural mesothelioma and compare target homogeneity, conformity and normal tissue dose with step-and-shoot intensity-modulated radiotherapy. METHODS AND MATERIALS: Ten patients with malignant pleural mesothelioma who had undergone neoadjuvant chemotherapy with cisplatin and permetrexed followed by extrapleural pneumonectomy (EPP) were treated in our department with 54 Gy to the hemithorax delivered by step-and-shoot IMRT. A planning comparison was performed by creating radiation plans for helical tomotherapy. The different plans were compared by analysing target homogeneity using the homogeneity indices HI(max) and HI(min) and target conformity by using the conformity index CI(95). To assess target coverage and normal tissue sparing TV(90), TV(95) and mean and maximum doses were compared. RESULTS: Both modalities achieved excellent dose distributions while sparing organs at risk. Target coverage and homogeneity could be increased significantly with helical tomotherapy compared with step-and-shoot IMRT. Mean dose to the contralateral lung could be lowered beyond 5 Gy. CONCLUSIONS: Our planning study showed that helical tomotherapy is an excellent option for the adjuvant intensity-modulated radiotherapy of MPM. It is capable of improving target coverage and homogeneity.

On the role of modeling parameters in IMRT plan optimization.

The formulation of optimization problems in intensity-modulated radiotherapy (IMRT) planning comprises the choice of various values such as function-specific parameters or constraint bounds. In current inverse planning programs that yield a single treatment plan for each optimization, it is often unclear how strongly these modeling parameters affect the resulting plan. This work investigates the mathematical concepts of elasticity and sensitivity to deal with this problem. An artificial planning case with a horse-shoe formed target with different opening angles surrounding a circular risk structure is studied. As evaluation functions the generalized equivalent uniform dose (EUD) and the average underdosage below and average overdosage beyond certain dose thresholds are used. A single IMRT plan is calculated for an exemplary parameter configuration. The elasticity and sensitivity of each parameter are then calculated without re-optimization, and the results are numerically verified. The results show the following. (1) elasticity can quantify the influence of a modeling parameter on the optimization result in terms of how strongly the objective function value varies under modifications of the parameter value. It also can describe how strongly the geometry of the involved planning structures affects the optimization result. (2) Based on the current parameter settings and corresponding treatment plan, sensitivity analysis can predict the optimization result for modified parameter values without re-optimization, and it can estimate the value intervals in which such predictions are valid. In conclusion, elasticity and sensitivity can provide helpful tools in inverse IMRT planning to identify the most critical parameters of an individual planning problem and to modify their values in an appropriate way.