Fast and accurate deformable contour propagation for intra-fraction adaptive magnetic resonance-guided prostate radiotherapy.

To facilitate full intra-fraction adaptive MR-guided radiotherapy, accurate contour propagation is needed. We aimed to assess the clinical usability of intra-fraction propagated contours by a deformable image registration algorithm in ten prostate cancer patients. Two observers judged the contours on need for manual adaptation and feasibility of adapting contours within 3 min. CTV and bladder contours needed none or only minor editing in most cases (≥ 97%), whereas rectum contours needed more extensive editing in 12-23%. Nevertheless, adaptation times were < 3 min for ≥ 93% of the cases. This paves the way for exploring adaptive workflows using intra-fraction deformable contour propagation.

On-line daily plan optimization combined with a virtual couch shift procedure to address intrafraction motion in prostate magnetic resonance guided radiotherapy.

BACKGROUND AND PURPOSE: In daily adaptive magnetic resonance (MR)-guided radiotherapy, plans are adapted based on the patient's daily anatomy. During this adaptation phase, prostate intrafraction motion (IM) can occur. The aim of this study was to investigate the efficacy of always applying a subsequent virtual couch shift (VCS) to counter IM that occurred during the daily contour and plan adaption (CPa) procedure. MATERIAL AND METHODS: One hundred fifty patients with low and intermediate risk prostate cancer were treated with 5x7.25 Gy fractions on a 1.5 T MR-Linac. In each fraction, contour adaptation and dose re-optimization was performed using the session's first MR-scan. IM that occurred here was countered using two methods. One patient group had selective VCS (sVCS) applied if the CTV reached outside the PTV on a second MR acquired during plan optimization. The other group had always VCS (aVCS) applied for any prostate shift greater than 1 mm. Remaining IM during beam delivery was determined using 3D cine-MR. RESULTS: Percentage of fractions where a VCS was applied was 28% (sVCS) vs 78% (aVCS). Always applying VCS significantly reduced influences of systematic prostate IM. Population random and systematic median values in all translations directions were lower for the aVCS than sVCS group, but not for the population random cranial-caudal direction. CONCLUSION: Applying VCS after daily CPa reduced impact of systematic prostate drift in especially the posterior and caudal translation direction. However, due to the continuous and stochastical nature of prostate IM, margin reduction below 4 mm requires fast intrafraction plan adaption methods.

Anorectal dose-effect relations for late gastrointestinal toxicity following external beam radiotherapy for prostate cancer in the FLAME trial.

BACKGROUND AND PURPOSE: The phase III FLAME trial (NCT01168479) showed an increase in five-year biochemical disease-free survival, with no significant increase in toxicity when adding a focal boost to external beam radiotherapy (EBRT) for localized prostate cancer [Kerkmeijer et al. JCO 2021]. The aim of this study was to investigate the association between delivered radiation dose to the anorectum and gastrointestinal (GI) toxicity (grade ≥2). MATERIAL AND METHODS: All patients in the FLAME trial were analyzed, irrespective of treatment arm. The dose-effect relation of the anorectal dose parameters (D2cm3 and D50%) and GI toxicity grade ≥2 in four years of follow-up was assessed using a mixed model analysis for repeated measurements, adjusted for age, cardiovascular disease, diabetes mellitus, T-stage, baseline toxicity grade ≥1, hormonal therapy and institute. RESULTS: A dose-effect relation for D2cm3 and D50% was observed with adjusted odds ratios of 1.17 (95% CI 1.13-1.21, p < 0.0001) and 1.20 (95% CI 1.14-1.25, p < 0.0001) for GI toxicity, respectively. CONCLUSION: Although there was no difference in toxicity between study arms, a higher radiation dose to the anorectum was associated with a statistically significant increase in GI toxicity following EBRT for prostate cancer. This dose-effect relation was present for both large and small anorectal volumes. Therefore, further increase in dose to the anorectum should be weighed against the benefit of focal dose escalation for prostate cancer.

Development and internal validation of multivariable prediction models for biochemical failure after MRI-guided focal salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer.

BACKGROUND AND PURPOSE: Magnetic resonance-guided focal salvage high-dose-rate brachytherapy (FS-HDR-BT) for radiorecurrent prostate cancer (PCa) shows low toxicity rates. However, biochemical failure (BF) after treatment occurs frequently. We developed two prediction models for BF (Phoenix definition) with the aim of enhancing patient counselling before FS-HDR-BT and during follow-up. MATERIALS AND METHODS: A prospective cohort of 150 radiorecurrent PCa patients treated with FS-HDR-BT between 2013 and 2020 was used for model development and internal validation. Multivariable Cox Proportional Hazards regression was applied. For model 1, only pre-salvage variables were included as candidate predictors. For model 2, additional (post-)salvage characteristics were tested. After calibration, nomograms and webtools were constructed. Finally, three risk groups were identified. RESULTS: Sixty-one patients (41%) experienced BF. At baseline (model 1), age, gross tumour volume, pre-salvage PSA, and pre-salvage PSA doubling time (PSADT) were predictive of BF. During follow-up (model 2), age, pre-salvage PSA and PSADT, seminal vesicle involvement, post-salvage time to PSA nadir, and percentage PSA reduction were predictive of BF. The adjusted C-statistics were 0.73 (95% CI: 0.66-0.81) and 0.84 (95% CI: 0.78-0.90), respectively, with acceptable calibration. Estimated 2-year biochemical disease-free survival for the low-, intermediate-, and high-risk groups were 84%, 70%, and 31% (model 1), and 100%, 71%, and 5% (model 2). CONCLUSION: Two models are provided for prediction of BF in patients with radiorecurrent PCa treated with FS-HDR-BT. Based on pre- and post-salvage characteristics, we are able to identify patients with a high risk of BF. These findings can aid patient counselling for FS-HDR-BT.

Evaluation of daily online contour adaptation by radiation therapists for prostate cancer treatment on an MRI-guided linear accelerator.

BACKGROUND AND PURPOSE: Magnetic resonance (MR)-guided linear accelerator (MR-Linac) systems have changed radiotherapy workflows. The addition of daily online contour adaptation allows for higher precision treatment, but also increases the workload of those involved. We train radiation therapists (RTTs) to perform daily online contour adaptation for MR-Linac treatment of prostate cancer (PCa) patients. The purpose of this study was to evaluate these prostate contours by performing an interfraction and interobserver analysis. MATERIALS AND METHODS: Clinical target volume (CTV) contours generated online by RTTs from 30 low-intermediate risk PCa patients, treated with 5x7.25 Gy, were used. Two physicians (Observers) judged the RTTs contours and performed adaptations when necessary. Interfraction relative volume differences between the first and the subsequent fractions were calculated for the RTTs, Observer 1, and Observer 2. Additionally, interobserver dice's similarity coefficient (DSC) for fraction 2-5 was calculated with the RTTs- and physician-adapted contours. Clinical acceptability of the RTTs contours was judged by a third observer. RESULTS: Mean (SD) online contour adaptation time was 12.6 (±3.8) minutes and overall median (interquartile range [IQR]) relative volume difference was 9.3% (4.4-13.0). Adaptations by the observers were mostly performed at the apex and base of the prostate. Median (IQR) interobserver DSC between RTTs and Observer 1, RTTs and Observer 2, and Observer 1 and 2 was 0.99 (0.98-1.00), 1.00 (0.98-1.00), and 1.00 (0.99-1.00), respectively. Contours were acceptable for clinical use in 113 (94.2%) fractions. Dose-volume histogram (DVH) analysis showed significant CTV underdosage for one of the seven identified outliers. CONCLUSION: Daily online contour adaptation by RTTs is clinically feasible for MR-Linac treatment of PCa.

Delivered dose quantification in prostate radiotherapy using online 3D cine imaging and treatment log files on a combined 1.5T magnetic resonance imaging and linear accelerator system.

BACKGROUND AND PURPOSE: Monitoring the intrafraction motion and its impact on the planned dose distribution is of crucial importance in radiotherapy. In this work we quantify the delivered dose for the first prostate patients treated on a combined 1.5T Magnetic Resonance Imaging (MRI) and linear accelerator system in our clinic based on online 3D cine-MR and treatment log files. MATERIALS AND METHODS: A prostate intrafraction motion trace was obtained with a soft-tissue based rigid registration method with six degrees of freedom from 3D cine-MR dynamics with a temporal resolution of 8.5-16.9 s. For each fraction, all dynamics were also registered to the daily MR image used during the online treatment planning, enabling the mapping to this reference point. Moreover, each fraction's treatment log file was used to extract the timestamped machine parameters during delivery and assign it to the appropriate dynamic volume. These partial plans to dynamic volume combinations were calculated and summed to yield the delivered fraction dose. The planned and delivered dose distributions were compared among all patients for a total of 100 fractions. RESULTS: The clinical target volume underwent on average a decrease of 2.2% ± 2.9% in terms of D99% coverage while bladder V62Gy was increased by 1.6% ± 2.3% and rectum V62Gy decreased by 0.2% ± 2.2%. CONCLUSIONS: The first MR-linac dose reconstruction results based on prostate tracking from intrafraction 3D cine-MR and treatment log files are presented. Such a pipeline is essential for online adaptation especially as we progress to MRI-guided extremely hypofractionated treatments.

Focal salvage treatment for radiorecurrent prostate cancer: A magnetic resonance-guided stereotactic body radiotherapy versus high-dose-rate brachytherapy planning study.

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI)-guided focal salvage high-dose-rate brachytherapy (FS-HDR-BT) is one of the treatment options for radiorecurrent localized prostate cancer. However, due to the invasive nature of the treatment, not all patients are eligible. Magnetic resonance linear accelerator (MR-Linac) systems open up new treatment possibilities and could potentially replace FS-HDR-BT treatment. We conducted a planning study to investigate the feasibility of delivering a single 19 Gy dose to the recurrent lesion using a 1.5 Tesla MR-Linac system. MATERIALS AND METHODS: Thirty patients who underwent FS-HDR-BT were included. The clinical target volume (CTV) encompassed the visible lesion plus a 5 mm margin. Treatment plans were created for a 1.5 Tesla MR-Linac system using a 1 mm planning target volume (PTV) margin. A dose of 19 Gy was prescribed to ≥ 95% of the PTV. In case this target could not be reached, i.e. when organs-at-risk (OAR) constraints were violated, a dose of ≥ 17 Gy to ≥ 90% of the PTV was accepted. MR-Linac plans were compared to clinical FS-HDR-BT plans. RESULTS: Target dose coverage was achieved in 14/30 (47%) FS-HDR-BT plans and 17/30 (57%) MR-Linac plans, with comparable median D95% and D90%. In FS-HDR-BT plans, a larger volume reached ≥ 150% of the prescribed dose. Urethra D10%, rectum D1cm3, and rectum D2cm3 were lower in the FS-HDR-BT plans, while bladder dose was comparable for both modalities. CONCLUSION: Single fraction treatment of recurrent prostate cancer lesions may be feasible using stereotactic body radiotherapy (SBRT) on a MR-Linac system.

Quantitative MRI Changes During Weekly Ultra-Hypofractionated Prostate Cancer Radiotherapy With Integrated Boost.

Purpose: Quantitative MRI reflects tissue characteristics. As possible changes during radiotherapy may lead to treatment adaptation based on response, we here assessed if such changes during treatment can be detected. Methods and Materials: In the hypoFLAME trial patients received ultra-hypofractionated prostate radiotherapy with an integrated boost to the tumor in 5 weekly fractions. We analyzed T2 and ADC maps of 47 patients that were acquired in MRI exams prior to and during radiotherapy, and performed rigid registrations based on the prostate contour on anatomical T2-weighted images. We analyzed median T2 and ADC values in three regions of interest (ROIs): the central gland (CG), peripheral zone (PZ), and tumor. We analyzed T2 and ADC changes during treatment and compared patients with and without hormonal therapy. We tested changes during treatment for statistical significance with Wilcoxon signed rank tests. Using confidence intervals as recommended from test-retest measurements, we identified persistent T2 and ADC changes during treatment. Results: In the CG, median T2 and ADC values significantly decreased 12 and 8%, respectively, in patients that received hormonal therapy, while in the PZ these values decreased 17 and 18%. In the tumor no statistically significant change was observed. In patients that did not receive hormonal therapy, median ADC values in the tumor increased with 20%, while in the CG and PZ no changes were observed. Persistent T2 changes in the tumor were found in 2 out of 24 patients, while none of the 47 patients had persistent ADC changes. Conclusions: Weekly quantitative MRI could identify statistically significant ADC changes in the tumor in patients without hormonal therapy. On a patient level few persistent T2 changes in the tumor were observed. Long-term follow-up is required to relate the persistent T2 and ADC changes to outcome and evaluate the applicability of quantitative MRI for response based treatment adaptation.

Individual lymph nodes: "See it and Zap it".

BACKGROUND AND PURPOSE: With magnetic resonance imaging (MRI)-guided radiotherapy systems such as the 1.5T MR-linac the daily anatomy can be visualized before, during and after radiation delivery. With these treatment systems, seeing metastatic nodes with MRI and zapping them with stereotactic body radiotherapy (SBRT) comes into reach. The purpose of this study is to investigate different online treatment planning strategies and to determine the planning target volume (PTV) margin needed for adequate target coverage when treating lymph node oligometastases with SBRT on the 1.5T MR-linac. MATERIALS AND METHODS: Ten patients were treated for single pelvic or para-aortic lymph node metastases on the 1.5T MR-linac with a prescribed dose of 5x7Gy with a 3 mm isotropic GTV- PTV margin. Based on the daily MRI and actual contours, a completely new treatment plan was generated for each session (adapt to shape, ATS). These were compared with plans optimized on pre-treatment CT contours after correcting for the online target position (adapt to position, ATP). At the end of each treatment session, a post-radiation delivery MRI was acquired on which the GTV was delineated to evaluate the GTV coverage and PTV margins. RESULTS: The median PTV V35Gy was 99.9% [90.7-100%] for the clinically delivered ATS plans compared to 93.6% [76.3-99.7%] when using ATP. The median GTV V35Gy during radiotherapy delivery was 100% [98-100%] on the online planning and post-delivery MRIs for ATS and 100% [93.9-100%] for ATP, respectively. The applied 3 mm isotropic PTV margin is considered adequate. CONCLUSION: For pelvic and para-aortic metastatic lymph nodes, online MRI-guided adaptive treatment planning results in adequate PTV and GTV coverage when taking the actual patient anatomy into account (ATS). Generally, GTV coverage remained adequate throughout the treatment session for both adaptive planning strategies. "Seeing and zapping" metastatic lymph nodes comes within reach for MRI-guided SBRT.

Adaptive radiotherapy: The Elekta Unity MR-linac concept.

BACKGROUND AND PURPOSE: The promise of the MR-linac is that one can visualize all anatomical changes during the course of radiotherapy and hence adapt the treatment plan in order to always have the optimal treatment. Yet, there is a trade-off to be made between the time spent for adapting the treatment plan against the dosimetric gain. In this work, the various daily plan adaptation methods will be presented and applied on a variety of tumour sites. The aim is to provide an insight in the behavior of the state-of-the-art 1.5 T MRI guided on-line adaptive radiotherapy methods. MATERIALS AND METHODS: To explore the different available plan adaptation workflows and methods, we have simulated online plan adaptation for five cases with varying levels of inter-fraction motion, regions of interest and target sizes: prostate, rectum, esophagus and lymph node oligometastases (single and multiple target). The plans were evaluated based on the clinical dose constraints and the optimization time was measured. RESULTS: The time needed for plan adaptation ranged between 17 and 485 s. More advanced plan adaptation methods generally resulted in more plans that met the clinical dose criteria. Violations were often caused by insufficient PTV coverage or, for the multiple lymph node case, a too high dose to OAR in the vicinity of the PTV. With full online replanning it was possible to create plans that met all clinical dose constraints for all cases. CONCLUSION: Daily full online replanning is the most robust adaptive planning method for Unity. It is feasible for specific sites in clinically acceptable times. Faster methods are available, but before applying these, the specific use cases should be explored dosimetrically.

Planning feasibility of extremely hypofractionated prostate radiotherapy on a 1.5 T magnetic resonance imaging guided linear accelerator.

BACKGROUND AND PURPOSE: Recently, intermediate and high-risk prostate cancer patients have been treated in a multicenter phase II trial with extremely hypofractionated prostate radiotherapy (hypo-FLAME trial). The purpose of the current study was to investigate whether a 1.5 T magnetic resonance imaging guided linear accelerator (MRI-linac) could achieve complex dose distributions of a quality similar to conventional linac state-of-the-art prostate treatments. MATERIALS AND METHODS: The clinically delivered treatment plans of 20 hypo-FLAME patients (volumetric modulated arc therapy, 10 MV, 5 mm leaf width) were included. Prescribed dose to the prostate was 5 × 7 Gy, with a focal tumor boost up to 5 × 10 Gy. MRI-linac treatment plans (intensity modulated radiotherapy, 7 MV, 7 mm leaf width, fixed collimator angle and 1.5 T magnetic field) were calculated. Dose distributions were compared. RESULTS: In both conventional and MRI-linac treatment plans, the V35Gy to the whole prostate was >99% in all patients. Mean dose to the gross tumor volume was 45 Gy for conventional and 44 Gy for MRI-linac plans, respectively. Organ at risk doses were met in the majority of plans, except for a rectal V35Gy constraint, which was exceeded in one patient, by 1 cc, for both modalities. The bladder V32Gy and V28Gy constraints were exceeded in two and one patient respectively, for both modalities. CONCLUSION: Planning of stereotactic radiotherapy with focal ablative boosting in prostate cancer on a high field MRI-linac is feasible with the current MRI-linac properties, without deterioration of plan quality compared to conventional treatments.

Evaluation of gold fiducial marker manual localisation for magnetic resonance-only prostate radiotherapy.

BACKGROUND: The use of intraprostatic gold fiducial markers (FMs) ensures highly accurate and precise image-guided radiation therapy for patients diagnosed with prostate cancer thanks to the ease of localising FMs on photon-based imaging, like Computed Tomography (CT) images. Recently, Magnetic Resonance (MR)-only radiotherapy has been proposed to simplify the workflow and reduce possible systematic uncertainties. A critical, determining factor in the accuracy of such an MR-only simulation will be accurate FM localisation using solely MR images. PURPOSE: The aim of this study is to evaluate the performances of manual MR-based FM localisation within a clinical environment. METHODS: We designed a study in which 5 clinically involved radiation therapy technicians (RTTs) independently localised the gold FMs implanted in 16 prostate cancer patients in two scenarios: employing a single MR sequence or a combination of sequences. Inter-observer precision and accuracy were assessed for the two scenarios for localisation in terms of 95% limit of agreement on single FMs (LoA)/ centre of mass (LoA CM) and inter-marker distances (IDs), respectively. RESULTS: The number of precisely located FMs (LoA <2 mm) increased from 38/48 to 45/48 FMs when localisation was performed using multiple sequences instead of single one. When performing localisation on multiple sequences, imprecise localisation of the FMs (3/48 FMs) occurred for 1/3 implanted FMs in three different patients. In terms of precision, we obtained LoA CM within 0.25 mm in all directions over the precisely located FMs. In terms of accuracy, IDs difference of manual MR-based localisation versus CT-based localisation was on average (±1 STD) 0.6 ±0.6 mm. CONCLUSIONS: For both the investigated scenarios, the results indicate that when FM classification was correct, the precision and accuracy are high and comparable to CT-based FM localisation. We found that use of multiple sequences led to better localisation performances compared with the use of single sequence. However, we observed that, due to the presence of calcification and motion, the risk of mislocated patient positioning is still too high to allow the sole use of manual FM localisation. Finally, strategies to possibly overcome the current challenges were proposed.

Evaluation of an automatic MR-based gold fiducial marker localisation method for MR-only prostate radiotherapy.

An MR-only radiotherapy planning (RTP) workflow would reduce the cost, radiation exposure and uncertainties introduced by CT-MRI registrations. In the case of prostate treatment, one of the remaining challenges currently holding back the implementation of an RTP workflow is the MR-based localisation of intraprostatic gold fiducial markers (FMs), which is crucial for accurate patient positioning. Currently, MR-based FM localisation is clinically performed manually. This is sub-optimal, as manual interaction increases the workload. Attempts to perform automatic FM detection often rely on being able to detect signal voids induced by the FMs in magnitude images. However, signal voids may not always be sufficiently specific, hampering accurate and robust automatic FM localisation. Here, we present an approach that aims at automatic MR-based FM localisation. This method is based on template matching using a library of simulated complex-valued templates, and exploiting the behaviour of the complex MR signal in the vicinity of the FM. Clinical evaluation was performed on seventeen prostate cancer patients undergoing external beam radiotherapy treatment. Automatic MR-based FM localisation was compared to manual MR-based and semi-automatic CT-based localisation (the current gold standard) in terms of detection rate and the spatial accuracy and precision of localisation. The proposed method correctly detected all three FMs in 15/17 patients. The spatial accuracy (mean) and precision (STD) were 0.9 mm and 0.5 mm respectively, which is below the voxel size of [Formula: see text] mm3 and comparable to MR-based manual localisation. FM localisation failed (3/51 FMs) in the presence of bleeding or calcifications in the direct vicinity of the FM. The method was found to be spatially accurate and precise, which is essential for clinical use. To overcome any missed detection, we envision the use of the proposed method along with verification by an observer. This will result in a semi-automatic workflow facilitating the introduction of an MR-only workflow.

Automated daily breath hold stability measurements by real-time imaging in radiotherapy of breast cancer.

BACKGROUND AND PURPOSE: Breath hold is increasingly used for cardiac sparing in left-sided breast cancer irradiation. We have developed a fast automated method to verify breath hold stability in each treatment fraction. MATERIAL AND METHODS: We evaluated 504 patients treated with breath hold. Moderate deep inspiration breath hold was audio-guided. Medial and lateral large tangential field segments were delivered in a single breath hold and movieloops of these fields were acquired with an EPID. The thoracic wall position was automatically detected in each frame and the full range of thoracic wall motion (RTWM) was determined. If the RTWM >4mm more than 3 times, the patient was excluded from breath hold treatment if further coaching did not yield improvement. RESULTS: Unstable breath hold was observed in 2.8% of the patients. However, this frequency dropped from 9.5% in the first 6months to 1.6% in the subsequent 16months. The 97% of patients with proper breath hold showed excellent stability: the average RTWM was 0.9±0.5mm. The reproducibility of the breath hold depth was confirmed by (1) the small difference between the thoracic wall positions in the medial and lateral fields within one fraction and (2) the setup errors of breath hold patients showed no significant differences with those of right-sided breast patients. CONCLUSIONS: We have developed and clinically applied an imaging tool to automatically determine stability of breath holds in each treatment fraction during beam delivery.

Emerging Role of MRI for Radiation Treatment Planning in Lung Cancer.

Magnetic resonance imaging (MRI) provides excellent soft-tissue contrast and allows for specific scanning sequences to optimize differentiation between various tissue types and properties. Moreover, it offers the potential for real-time motion imaging. This makes magnetic resonance imaging an ideal candidate imaging modality for radiation treatment planning in lung cancer. Although the number of clinical research protocols for the application of magnetic resonance imaging for lung cancer treatment is increasing (www.clinicaltrials.gov) and the magnetic resonance imaging sequences are becoming faster, there are still some technical challenges. This review describes the opportunities and challenges of magnetic resonance imaging for radiation treatment planning in lung cancer.

How does imaging frequency and soft tissue motion affect the PTV margin size in partial breast and boost radiotherapy?

PURPOSE: This study investigates (i) the effect of verification protocols on treatment accuracy and PTV margins for partial breast and boost breast radiotherapy with short fractionation schema (15 fractions), (ii) the effect of deformation of the excision cavity (EC) on PTV margin size, (iii) the imaging dose required to achieve specific PTV margins. METHODS AND MATERIALS: Verification images using implanted EC markers were studied in 36 patients. Target motion was estimated for a 15 fraction partial breast regimen using imaging protocols based on on-line and off-line motion correction strategies (No Action Level (NAL) and the extended NAL (eNAL) protocols). Target motion was used to estimate a PTV margin for each protocol. To evaluate treatment errors due to deformation of the excision cavity, individual marker positions were obtained from 11 patients. The mean clip displacement and daily variation in clip position during radiotherapy were determined and the contribution of these errors to PTV margin calculated. Published imaging dose data were used to estimate total dose for each protocol. Finally the number of images required to obtain a specific PTV margin was evaluated and hence, the relationship between PTV margins and imaging dose was investigated. RESULTS: The PTV margin required to account for excision cavity motion, varied between 10.2 and 2.4mm depending on the correction strategy used. Average clip movement was 0.8mm and average variation in clip position during treatment was 0.4mm. The contribution to PTV margin from deformation was estimated to be small, less than 0.2mm for both off-line and on-line correction protocols. CONCLUSION: A boost or partial breast PTV margin of ∼10 mm, is possible with zero imaging dose and workload, however, patients receiving boost radiotherapy may benefit from a margin reduction of ∼4 mm with imaging doses from 0.4cGy to 25cGy using an eNAL protocol. PTV margin contributions from deformation errors are likely to be small in comparison to other sources of error, i.e., set up or delineation.

Software-controlled, highly automated intrafraction prostate motion correction with intrafraction stereographic targeting: System description and clinical results.

PURPOSE: A new system for software-controlled, highly automated correction of intrafraction prostate motion," intrafraction stereographic targeting" (iSGT), is described and evaluated. METHODS: At our institute, daily prostate positioning is routinely performed at the start of treatment beam using stereographic targeting (SGT). iSGT was implemented by extension of the SGT software to facilitate fast and accurate intrafraction motion corrections with minimal user interaction. iSGT entails megavoltage (MV) image acquisitions with the first segment of selected IMRT beams, automatic registration of implanted markers, followed by remote couch repositioning to correct for intrafraction motion above a predefined threshold, prior to delivery of the remaining segments. For a group of 120 patients, iSGT with corrections for two nearly lateral beams was evaluated in terms of workload and impact on effective intrafraction displacements in the sagittal plane. RESULTS: SDs of systematic (Σ) and random (σ) displacements relative to the planning CT measured directly after initial SGT setup correction were <0.5 and <0.8 mm, respectively. Without iSGT corrections, effective Σ and σ for the 11-min treatments would increase to Σ(eff) < 1.1 mm and σ(eff) < 1.2 mm. With the iSGT procedure with an action level of 4 mm, effective positioning errors were reduced to Σ(eff) < 0.8 mm and σ(eff) < 1.0 mm, with 23.1% of all fractions requiring a correction. Computer simulations demonstrated that with an action level of 2 mm, the errors would have been reduced to Σ(eff) < 0.6 mm and σ(eff) < 0.7 mm, requiring corrections in 82.4% of the fractions. Because iSGT is highly automated, the extra time added by iSGT is <30 s if a correction is required. CONCLUSIONS: Without increasing imaging dose, iSGT successfully reduces intrafraction prostate motion with minimal workload and increase in fraction time. An action level of 2 mm is recommended.

IMRT for image-guided single vocal cord irradiation.

PURPOSE: We have been developing an image-guided single vocal cord irradiation technique to treat patients with stage T1a glottic carcinoma. In the present study, we compared the dose coverage to the affected vocal cord and the dose delivered to the organs at risk using conventional, intensity-modulated radiotherapy (IMRT) coplanar, and IMRT non-coplanar techniques. METHODS AND MATERIALS: For 10 patients, conventional treatment plans using two laterally opposed wedged 6-MV photon beams were calculated in XiO (Elekta-CMS treatment planning system). An in-house IMRT/beam angle optimization algorithm was used to obtain the coplanar and non-coplanar optimized beam angles. Using these angles, the IMRT plans were generated in Monaco (IMRT treatment planning system, Elekta-CMS) with the implemented Monte Carlo dose calculation algorithm. The organs at risk included the contralateral vocal cord, arytenoids, swallowing muscles, carotid arteries, and spinal cord. The prescription dose was 66 Gy in 33 fractions. RESULTS: For the conventional plans and coplanar and non-coplanar IMRT plans, the population-averaged mean dose ± standard deviation to the planning target volume was 67 ± 1 Gy. The contralateral vocal cord dose was reduced from 66 ± 1 Gy in the conventional plans to 39 ± 8 Gy and 36 ± 6 Gy in the coplanar and non-coplanar IMRT plans, respectively. IMRT consistently reduced the doses to the other organs at risk. CONCLUSIONS: Single vocal cord irradiation with IMRT resulted in good target coverage and provided significant sparing of the critical structures. This has the potential to improve the quality-of-life outcomes after RT and maintain the same local control rates.

Day-to-day reproducibility of prostate intrafraction motion assessed by multiple kV and MV imaging of implanted markers during treatment.

PURPOSE: When one is performing online setup correction for prostate positioning displacements prior to daily dose delivery, intrafraction motion can become a limiting factor to prostate targeting accuracy. The aim of this study was to quantify and characterize prostate intrafraction motion assessed by multiple kilovoltage (kV) and megavoltage (MV) imaging of implanted markers during treatment in a large patient group. METHODS AND MATERIALS: Intrafraction motion in the sagittal plane was studied by retrospective analysis of displacements of implanted gold markers on (nearly) lateral kV and MV images obtained at various time points during the treatment fractions (mean, 27 per patient) in 108 consecutive patients. The effective prostate motion in a fraction was defined as the time-weighted mean displacement. RESULTS: Prostate displacements in the sagittal plane increased during the fraction (mean, 0.2 ± 0.2 mm/min). Forty percent of patients had a systematic (i.e., appearing in all fractions) effective displacement in the sagittal plane greater than 2 mm. Observed effective population mean-of-means (µeff) +/- systematic (Σeff) intrafraction motion (µ(eff) ± Σ(eff)) was 0.9 ± 1.1 mm and 0.6 ± 1.0 mm for the anterior-posterior and superior inferior directions, respectively. Corresponding random motion (σ(eff)) was 1.2 mm and 1.1 mm. Mean effective prostate motion in the first 5 fractions was predictive for mean effective displacement in the remaining fractions (p < 0.001). CONCLUSION: For a large subgroup of patients, the systematic component of intrafraction prostate motion was substantial. Intrafraction motion correction prior to each beam delivery or offline corrections could likely be beneficial for the subgroup of patients with significant motion. The systematic component is well predicted by measurements in the initial fractions.

Margin evaluation in the presence of deformation, rotation, and translation in prostate and entire seminal vesicle irradiation with daily marker-based setup corrections.

PURPOSE: To develop a method for margin evaluation accounting for all measured displacements during treatment of prostate cancer. METHODS AND MATERIALS: For 21 patients treated with stereographic targeting marker-based online translation corrections, dose distributions with varying margins and gradients were created. Sets of possible cumulative delivered dose distributions were simulated by moving voxels and accumulating dose per voxel. Voxel motion was simulated consistent with measured distributions of systematic and random displacements due to stereographic targeting inaccuracies, deformation, rotation, and intrafraction motion. The method of simulation maintained measured correlation of voxel motions due to organ deformation. RESULTS: For the clinical target volume including prostate and seminal vesicles (SV), the probability that some part receives <95% of the prescribed dose, the changes in minimum dose, and volume receiving 95% of prescription dose compared with planning were 80.5% ± 19.2%, 9.0 ± 6.8 Gy, and 3.0% ± 3.7%, respectively, for the smallest studied margins (3 mm prostate, 5 mm SV) and steepest dose gradients. Corresponding values for largest margins (5 mm prostate, 8 mm SV) with a clinical intensity-modulated radiotherapy dose distribution were 46.5% ± 34.7%, 6.7 ± 5.8 Gy, and 1.6% ± 2.3%. For prostate-only clinical target volume, the values were 51.8% ± 17.7%, 3.3 ± 1.6 Gy, and 0.6% ± 0.5% with the smallest margins and 5.2% ± 7.4%, 1.8 ± 0.9 Gy, and 0.1% ± 0.1% for the largest margins. Addition of three-dimensional rotation corrections only improved these values slightly. All rectal planning constraints were met in the actual reconstructed doses for all studied margins. CONCLUSION: We developed a system for margin validation in the presence of deformations. In our population, a 5-mm margin provided sufficient dosimetric coverage for the prostate. In contrast, an 8-mm SV margin was still insufficient owing to deformations. Addition of three-dimensional rotation corrections was of minor influence.