Steven van de Water

Clinical introduction of Monte Carlo treatment planning: A different prescription dose for non-small cell lung cancer according to tumor location and size

PURPOSE To provide a prescription dose for Monte Carlo (MC) treatment planning in patients with non-small-cell lung cancer according to tumor size and location. METHODS Fifty-three stereotactic radiotherapy plans designed using the equivalent path-length (EPL) algorithm were re-calculated using MC. Plans were compared by the minimum dose to 95% of the PTV (D95), the heterogeneity index (HI) and the mean dose to organs at risk (OARs). Based on changes in D95, the prescription dose was converted from EPL to MC. Based on changes in HI, we examined the feasibility of MC prescription to plans re-calculated but not re-optimized with MC. RESULTS The MC fraction dose for peripheral tumors is 16-18 Gy depending on tumor size. For central tumors the MC dose was reduced less than for peripheral tumors. The HI decreased on average by 4-9% in peripheral tumors and 3-5% in central tumors. The mean dose to OARs was lower for MC than EPL, and correlated strongly (R(2)=0.98-0.99). CONCLUSION For the conversion from EPL to MC we recommend a separate prescription dose according to tumor size. MC optimization is not required if a HI > or = 70% is accepted. Dose constraints to OARs can be easily converted due to the high EPL-MC correlation.

Dose Uncertainties in IMPT for Oropharyngeal Cancer in the Presence of Anatomical, Range, and Setup Errors

PURPOSE Setup, range, and anatomical uncertainties influence the dose delivered with intensity modulated proton therapy (IMPT), but clinical quantification of these errors for oropharyngeal cancer is lacking. We quantified these factors and investigated treatment fidelity, that is, robustness, as influenced by adaptive planning and by applying more beam directions. METHODS AND MATERIALS We used an in-house treatment planning system with multicriteria optimization of pencil beam energies, directions, and weights to create treatment plans for 3-, 5-, and 7-beam directions for 10 oropharyngeal cancer patients. The dose prescription was a simultaneously integrated boost scheme, prescribing 66 Gy to primary tumor and positive neck levels (clinical target volume-66 Gy; CTV-66 Gy) and 54 Gy to elective neck levels (CTV-54 Gy). Doses were recalculated in 3700 simulations of setup, range, and anatomical uncertainties. Repeat computed tomography (CT) scans were used to evaluate an adaptive planning strategy using nonrigid registration for dose accumulation. RESULTS For the recalculated 3-beam plans including all treatment uncertainty sources, only 69% (CTV-66 Gy) and 88% (CTV-54 Gy) of the simulations had a dose received by 98% of the target volume (D98%) >95% of the prescription dose. Doses to organs at risk (OARs) showed considerable spread around planned values. Causes for major deviations were mixed. Adaptive planning based on repeat imaging positively affected dose delivery accuracy: in the presence of the other errors, percentages of treatments with D98% >95% increased to 96% (CTV-66 Gy) and 100% (CTV-54 Gy). Plans with more beam directions were not more robust. CONCLUSIONS For oropharyngeal cancer patients, treatment uncertainties can result in significant differences between planned and delivered IMPT doses. Given the mixed causes for major deviations, we advise repeat diagnostic CT scans during treatment, recalculation of the dose, and if required, adaptive planning to improve adequate IMPT dose delivery.

Stability of Markers Used for Real-Time Tumor Tracking After Percutaneous Intrapulmonary Placement

PURPOSE To determine the stability of markers used for real-time tumor tracking after percutaneous intrapulmonary placement. METHODS AND MATERIALS A total of 42 patients with 44 lesions, 111 markers, and ≥2 repeat computed tomography (CT) scans were studied. The tumor on the repeat CT scans was registered with the tumor on the planning CT scan. Next, the three-dimensional marker coordinates were determined on the planning CT scan and repeat CT scans. Marker stability was analyzed by the displacement of the markers and the displacement of the center of mass (COM) of the marker configurations. In addition, we assessed the reliability of using the intermarker distance as a check for displacements in the COM of the marker configurations. RESULTS The median marker displacement was 1.3 mm (range, 0.1-53.6). The marker displacement was >5 mm in 12% of the markers and >10 mm in 5% of the markers. The causes of marker displacement >5 mm included marker migration (2 of 13) and target volume changes (5 of 13). Nonsynchronous tumor and marker movement during breathing might have been responsible for the displacements >5 mm in the other 6 of 13 markers. The median displacement in the COM of the marker configurations was 1.0 mm (range, 0.1-23.3). Displacements in the COM of the marker configurations of ≥2.0 mm were detected by changes in the intermarker distance of >1.5 mm in 96% of the treatment fractions. CONCLUSION The median marker displacement was small (1.3 mm). Nevertheless, displacements >5 mm occurred in 12% of the markers. Therefore, we recommend the implantation of multiple markers because multiple markers will enable a quick and reliable check of marker displacement by determining the change in the intermarker distance. A displacement in the COM of the marker configuration of ≥2.0 mm was almost always detected (96%) by a change in the distance between the markers of >1.5 mm. This enabled the displaced marker to be disabled, such that tumor localization was not compromised.

Intrafraction Prostate Translations and Rotations During Hypofractionated Robotic Radiation Surgery: Dosimetric Impact of Correction Strategies and Margins

PURPOSE To investigate the dosimetric impact of intrafraction prostate motion and the effect of robot correction strategies for hypofractionated CyberKnife treatments with a simultaneously integrated boost. METHODS AND MATERIALS A total of 548 real-time prostate motion tracks from 17 patients were available for dosimetric simulations of CyberKnife treatments, in which various correction strategies were included. Fixed time intervals between imaging/correction (15, 60, 180, and 360 seconds) were simulated, as well as adaptive timing (ie, the time interval reduced from 60 to 15 seconds in case prostate motion exceeded 3 mm or 2° in consecutive images). The simulated extent of robot corrections was also varied: no corrections, translational corrections only, and translational corrections combined with rotational corrections up to 5°, 10°, and perfect rotational correction. The correction strategies were evaluated for treatment plans with a 0-mm or 3-mm margin around the clinical target volume (CTV). We recorded CTV coverage (V100%) and dose-volume parameters of the peripheral zone (boost), rectum, bladder, and urethra. RESULTS Planned dose parameters were increasingly preserved with larger extents of robot corrections. A time interval between corrections of 60 to 180 seconds provided optimal preservation of CTV coverage. To achieve 98% CTV coverage in 98% of the treatments, translational and rotational corrections up to 10° were required for the 0-mm margin plans, whereas translational and rotational corrections up to 5° were required for the 3-mm margin plans. Rectum and bladder were spared considerably better in the 0-mm margin plans. Adaptive timing did not improve delivered dose. CONCLUSIONS Intrafraction prostate motion substantially affected the delivered dose but was compensated for effectively by robot corrections using a time interval of 60 to 180 seconds. A 0-mm margin required larger extents of additional rotational corrections than a 3-mm margin but resulted in lower doses to rectum and bladder.

Shortening treatment time in robotic radiosurgery using a novel node reduction technique

PURPOSE The fraction duration of robotic radiosurgery treatments can be reduced by generating more time-efficient treatment plans with a reduced number of node positions, beams, and monitor units (MUs). Node positions are preprogramed locations where the robot can position the focal spot of the x-ray beam. As the time needed for the robot to travel between node positions takes up a large part of the treatment time, the aim of this study was to develop and evaluate a node reduction technique in order to reduce the treatment time per fraction for robotic radiosurgery. METHODS Node reduction was integrated into the inverse planning algorithm, developed in-house for the robotic radiosurgery modality. It involved repeated inverse optimization, each iteration excluding low-contribution node positions from the planning and resampling new candidate beams from the remaining node positions. Node reduction was performed until the exclusion of a single node position caused a constraint violation, after which the shortest treatment plan was selected retrospectively. Treatment plans were generated with and without node reduction for two lung cases of different complexity, one oropharyngeal case and one prostate case. Plan quality was assessed using the number of node positions, beams and MUs, and the estimated treatment time per fraction. All treatment plans had to fulfill all clinical dose constraints. Extra constraints were added to maintain the low-dose conformality and restrict skin doses during node reduction. RESULTS Node reduction resulted in 12 residual node positions, on average (reduction by 77%), at the cost of an increase in the number of beams and total MUs of 28% and 9%, respectively. Overall fraction durations (excluding patient setup) were shortened by 25% (range of 18%-40%), on average. Dose distributions changed only little and dose in low-dose regions was effectively restricted by the additional constraints. CONCLUSIONS The fraction duration of robotic radiosurgery treatments can be reduced considerably by node reduction with minimal changes in dosimetrical plan quality. Additional constraints are required to guarantee low-dose conformality and to avoid unacceptable skin dose.

Fast and accurate sensitivity analysis of IMPT treatment plans using Polynomial Chaos Expansion

The highly conformal planned dose distribution achievable in intensity modulated proton therapy (IMPT) can severely be compromised by uncertainties in patient setup and proton range. While several robust optimization approaches have been presented to address this issue, appropriate methods to accurately estimate the robustness of treatment plans are still lacking. To fill this gap we present Polynomial Chaos Expansion (PCE) techniques which are easily applicable and create a meta-model of the dose engine by approximating the dose in every voxel with multidimensional polynomials. This Polynomial Chaos (PC) model can be built in an automated fashion relatively cheaply and subsequently it can be used to perform comprehensive robustness analysis. We adapted PC to provide among others the expected dose, the dose variance, accurate probability distribution of dose-volume histogram (DVH) metrics (e.g. minimum tumor or maximum organ dose), exact bandwidths of DVHs, and to separate the effects of random and systematic errors. We present the outcome of our verification experiments based on 6 head-and-neck (HN) patients, and exemplify the usefulness of PCE by comparing a robust and a non-robust treatment plan for a selected HN case. The results suggest that PCE is highly valuable for both research and clinical applications.

The impact of treatment accuracy on proton therapy patient selection for oropharyngeal cancer patients

BACKGROUND AND PURPOSE The impact of treatment accuracy on NTCP-based patient selection for proton therapy is currently unknown. This study investigates this impact for oropharyngeal cancer patients. MATERIALS AND METHODS Data of 78 patients was used to automatically generate treatment plans for a simultaneously integrated boost prescribing 70 GyRBE/54.25 GyRBE in 35 fractions. IMRT treatment plans were generated with three different margins; intensity modulated proton therapy (IMPT) plans for five different setup and range robustness settings. Four NTCP models were evaluated. Patients were selected for proton therapy if NTCP reduction was ≥10% or ≥5% for grade II or III complications, respectively. RESULTS The degree of robustness had little impact on patient selection for tube feeding dependence, while the margin had. For other complications the impact of the robustness setting was noticeably higher. For high-precision IMRT (3 mm margin) and high-precision IMPT (3 mm setup/3% range error), most patients were selected for proton therapy based on problems swallowing solid food (51.3%) followed by tube feeding dependence (37.2%), decreased parotid flow (29.5%), and patient-rated xerostomia (7.7%). CONCLUSIONS Treatment accuracy has a significant impact on the number of patients selected for proton therapy. Therefore, it cannot be ignored in estimating the number of patients for proton therapy.

Which cervical and endometrial cancer patients will benefit most from intensity-modulated proton therapy?

In this dosimetric comparison study it was shown that IMPT with robust planning reduces dose to surrounding organs in cervical and endometrial cancer treatment compared with IMRT. Especially for the para-aortic region, clinically relevant dose reductions were obtained for kidneys, spinal cord and bowel, justifying the use of proton therapy for this indication.