Potential Therapeutic Improvements in Prostate Cancer Treatment Using Pencil Beam Scanning Proton Therapy with LETd Optimization and Disease-Specific RBE Models.

PURPOSE: To demonstrate the feasibility of improving prostate cancer patient outcomes with PBS proton LETd optimization. METHODS: SFO, IPT-SIB, and LET-optimized plans were created for 12 patients, and generalized-tissue and disease-specific LET-dependent RBE models were applied. The mean LETd in several structures was determined and used to calculate mean RBEs. LETd- and dose-volume histograms (LVHs/DVHs) are shown. TODRs were defined based on clinical dose goals and compared between plans. The impact of robust perturbations on LETd, TODRs, and DVH spread was evaluated. RESULTS: LETd optimization achieved statistically significant increased target volume LETd of ~4 keV/µm compared to SFO and IPT-SIB LETd of ~2 keV/µm while mitigating OAR LETd increases. A disease-specific RBE model predicted target volume RBEs > 1.5 for LET-optimized plans, up to 18% higher than for SFO plans. LET-optimized target LVHs/DVHs showed a large increase not present in OARs. All RBE models showed a statistically significant increase in TODRs from SFO to IPT-SIB to LET-optimized plans. RBE = 1.1 does not accurately represent TODRs when using LETd optimization. Robust evaluations demonstrated a trade-off between increased mean target LETd and decreased DVH spread. CONCLUSION: The demonstration of improved TODRs provided via LETd optimization shows potential for improved patient outcomes.

Anatomical changes in the male pelvis between the supine and upright positions-A feasibility study for prostate treatments in the upright position.

Treating and imaging patients in the upright orientation is gaining acceptance in radiation oncology and radiology and has distinct advantages over the recumbent position. An IRB approved study to investigate the positions and orientations of the male pelvic organs between the supine and upright positions was conducted. The study comprised of scanning 15 male volunteers (aged 55-75 years) on a 0.6 T Fonar MRI scanner in the supine and upright positions with a full bladder and in the upright position with an empty bladder. The Pelvic study revealed that in the upright position the 1. Position and shape of the prostate are not impacted significantly by bladder fill. 2. Distance between the sacrum and the anterior bladder wall is significantly smaller. 3. Anterior-Posterior length and the bladder width is significantly larger. 4. Seminal vesicles are pushed down by the bladder. 5. Top of the penile bulb is further away from the apex of the prostate. These observed differences could positively impact upright prostate treatments by 1. Reducing the risk of small bowel approximating the treatment volume. 2. Prostate treatments can be done with a reduced focus on bladder fill. 3. Radiation beams for treating intermediate risk prostrate can be made smaller or a larger portion of the seminal vesicles can be treated with the same beam size than typically used for supine treatments. 4. Reducing the average dose to the penile bulb.

Fast MCsquare-Based Independent Dose Verification Platform for Pencil Beam Scanning Proton Therapy.

PURPOSE: To commission MCsquare (a multi-cores CPU-based dose calculation engine) for pencil beam scanning (PBS) proton therapy, integrate it into RayStation treatment plan system (TPS) to create a dedicated platform for fast independent dose verification. METHOD: A MCsquare-based independent dose verification platform (MC2InRS) was developed to realize automatic dose re-calculation for clinical use, including data preparation, dose calculation, 2D/3D gamma analysis. MCsquare was commissioned based on in-air lateral dose profiles, integrated depth dose, and the absolute dose of different beam energies for Proteus®ONE. MC2InRS was validated with measurement data using various targets and depths in a water phantom. This study also investigated 15 clinical cases to demonstrate the feasibility and effectiveness of MC2InRS platform in clinic practice. RESULTS: Between simulation and measurement, the distal range differences at 80% (R80) and 20% (R20) dose levels for each energy were below 0.05 mm, and 0.1 mm, respectively, and the absolute dose differences were below 0.5%. 29 out of 36 QA planes reached a 100% gamma passing rate (GPR) for 2%/2mm criteria, and a minimum of 98.3% gamma was obtained in water phantom between simulation and measurement. For the 15 clinical cases investigated, the average 2D GPR (2%/2mm) was 95.4%, 99.3% for MCsquare vs. measurement, MCsquare vs. TPS, respectively. The average 3D GPR (2%/2mm) was 98.9%, 95.3% for MCsquare vs. TPS in water, and computed tomography (CT), respectively. CONCLUSION: MC2InRS, a fast, independent dose verification platform, has been developed to perform dose verification with high accuracy and efficiency for Pencil Bream Scanning (PBS). Its potential to be applied in routine clinical practice has also been discussed.

Clinical commissioning of intensity-modulated proton therapy systems: Report of AAPM Task Group 185.

Proton therapy is an expanding radiotherapy modality in the United States and worldwide. With the number of proton therapy centers treating patients increasing, so does the need for consistent, high-quality clinical commissioning practices. Clinical commissioning encompasses the entire proton therapy system's multiple components, including the treatment delivery system, the patient positioning system, and the image-guided radiotherapy components. Also included in the commissioning process are the x-ray computed tomography scanner calibration for proton stopping power, the radiotherapy treatment planning system, and corresponding portions of the treatment management system. This commissioning report focuses exclusively on intensity-modulated scanning systems, presenting details of how to perform the commissioning of the proton therapy and ancillary systems, including the required proton beam measurements, treatment planning system dose modeling, and the equipment needed.

Development of an isocentric rotating chair positioner to treat patients of head and neck cancer at upright seated position with multiple nonplanar fields in a fixed carbon-ion beamline.

PURPOSE: An isocentric rotating chair for a positioner was developed as a nongantry solution to provide multiple nonplanar radiation fields with a maximum tilt of 20 ∘ for treating head and neck cancer patients at an upright seated position in a fixed carbon-ion beamline. METHODS: The preclinical validation of the chair was present for this study funded by a grant through the Shanghai Proton and Heavy Ion Center (SPHIC) in Shanghai, China. The chair was installed in SPHIC. A concept of parallel kinematic was adopted to build the chair. Three movement subunits of the chair are a Stewart hexapod platform and two modules for three-dimensional translation and 360 ∘ rotation. This chair can position patients with a tilt up to 20 ∘ over a continuous 360 ∘ rotation. Any weak structures within each subunit were investigated by industrial static/dynamic simulations of used materials. After manufactured subunits were assembled in a factory, a series of executed six degree-of-freedom (DoF) displacements were measured by using a laser-based dynamic tracking system (LDTS) for the initial validation. Deviations between measured and required displacements, referred to as displacement deviation, were used to evaluate the displacement accuracy of the chair. After satisfying the initial validation in the factory, the chair was disassembled and installed in our treatment room. The displacement accuracy of the chair was revalidated by using the LDTS. Then, an integration validation of the chair was conducted to position a head phantom by using our image-guided radiotherapy (IGRT) system. Because the positioning accuracy of our IGRT system achieved a clinical tolerance of 1.0 mm and 1.0 ∘ only for a pitch/roll of <5 ∘ , the integration validation was conducted on 36 planned fields with a 5 ∘ tilt evenly over 360 ∘ rotation. RESULTS: To fulfill the general purpose of positioner, the chair allows the execution of any displacement over a cubic treatment volume with a length of 500 mm. Materials selected by simulations met required strengths under all circumstances of the clinical usage. The displacement accuracy of the chair satisfied the tolerance of 0.3 mm in-translation and 0.3 ∘ in-rotation during the initial validation in the factory. After the chair was installed in our institute, a linear displacement deviation of +/-0.6 mm was observed over +/-200 mm displacements in horizontal X/Y axes. After correcting the linear deviation, the displacement deviations of the chair for horizontal and vertical X/Y/Z axes were within 0.5 mm and 0.5 ∘ for its revalidation. During the integration validation, the displacement deviation of the chair was 0.8 mm and 0.6 ∘ when positioning a head phantom for the 36 fields with a 5 ∘ tilt. CONCLUSIONS: The chair achieved the required clinical tolerance for the clinical application. The tilt angle was limited to within 5 ∘ to treat patients through a specific treatment workflow with a proper daily quality assurance program during a clinical trial, started in May 2019. An integration validation with a 20 ∘ tilt will be conducted in the near future to realize the full potential of the isocentric rotating chair.

Comparison of photon volumetric modulated arc therapy, intensity-modulated proton therapy, and intensity-modulated carbon ion therapy for delivery of hypo-fractionated thoracic radiotherapy.

PURPOSE: The aim of the present study was to compare the dose distribution generated from photon volumetric modulated arc therapy (VMAT), intensity modulated proton therapy (IMPT), and intensity modulated carbon ion therapy (IMCIT) in the delivery of hypo-fractionated thoracic radiotherapy. METHODS AND MATERIALS: Ten selected patients who underwent thoracic particle therapy between 2015 and 2016 were re-planned to receive a relative biological effectiveness (RBE) weighted dose of 60 Gy (i.e., GyE) in 15 fractions delivered with VMAT, IMPT, or IMCIT with the same optimization criteria. Treatment plans were then compared. RESULTS: There were no significant differences in target volume dose coverage or dose conformity, except improved D95 was found with IMCIT compared with VMAT (p = 0.01), and IMCIT was significantly better than IMPT in all target volume dose parameters. Particle therapy led to more prominent lung sparing at low doses, and this result was most prominent with IMCIT (p < 0.05). Improved sparing of other thoracic organs at risk (OARs) was observed with particle therapy, and IMCIT further lowered the D1cc and D5cc for major blood vessels, as compared with IMPT (p = 0.01). CONCLUSION: Although it was comparable to VMAT, IMCIT led to significantly better tumor target dose coverage and conformity than did IMPT. Particle therapy, compared with VMAT, improved thoracic OAR sparing. IMCIT, compared with IMPT, may further improve normal lung and major blood vessel sparing under limited respiratory motion.

Validation of dosimetric field matching accuracy from proton therapy using a robotic patient positioning system.

Large area, shallow fields are well suited to proton therapy. However, due to beam production limitations, such volumes typically require multiple matched fields. This is problematic due to the relatively narrow beam penumbra at shallow depths compared to electron and photon beams. Therefore, highly accurate dose planning and delivery is required. As the dose delivery includes shifting the patient for matched fields, accuracy at the 1-2 millimeter level in patient positioning is also required. This study investigates the dosimetric accuracy of such proton field matching by an innovative robotic patient positioner system (RPPS). The dosimetric comparisons were made between treatment planning system calculations, radiographic film and ionization chamber measurements. The results indicated good agreement amongst the methods and suggest that proton field matching by a RPPS is accurate and efficient.

Cine-magnetic resonance imaging assessment of intrafraction motion for prostate cancer patients supine or prone with and without a rectal balloon.

PURPOSE: Determine prostate intrafraction motion with Cine-magnetic resonance imaging (MRI) and deformable registration. METHODS: A total of 68 cine-MRI studies were done in 17 different series with 4 scans per series in 7 patients. In without rectal balloon (WORB) scans, 100 mL of water was infused in the rectum. Each series consisted of supine and prone, with a rectal balloon (WRB) and WORB. Each scan was performed over 4 minutes. Automatic deformable registration software developed by View Ray, Inc., Cleveland, Ohio was employed to segment the prostate for each cine-MRI image. A time-based analysis was done for the different positions and the use of the rectal balloon. RESULTS: The variation/standard deviation of the prostate position during 240 seconds was: supine WRB: 0.55 mm, WORB: 1.2 mm, and prone WRB: 1.48 mm, WORB: 2.15 mm (P < 0.001). A strong relationship was observed between time and prostate motion. For the initial 120 s the standard deviation was smaller than for the second 120 s supine WRB 0.54 mm versus 1.37 mm; supine WORB 0.61 mm versus 1.70 mm; prone WRB 0.85 mm versus 1.85 mm; and prone WORB 1.60 mm versus 2.56 mm. The probabilities for prostate staying within +/-2 mm to its initial position are: 94.8% supine WRB; 91.5% supine WORB; 92.3% prone WRB; 79.2% prone WORB. CONCLUSIONS: Intrafraction prostate motion was found dependent on time, patient position, and the use of a rectal balloon. Relatively stable positions can be obtained for 4 minutes or less especially in the supine position with a rectal balloon.

Dosimetric impact of intrafraction motion for compensator-based proton therapy of lung cancer.

Compensator-based proton therapy of lung cancer using an un-gated treatment while allowing the patient to breathe freely requires a compensator design that ensures tumor coverage throughout respiration. Our investigation had two purposes: one is to investigate the dosimetric impact when a composite compensator correction is applied, or is not, and the other one is to evaluate the significance of using different respiratory phases as the reference computed tomography (CT) for treatment planning dose calculations. A 4D-CT-based phantom study and a real patient treatment planning study were performed. A 3D MIP dataset generated over all phases of the acquired 4D-CT scans was adopted to design the field-specific composite aperture and compensator. In the phantom study, the MIP-based compensator design plan named plan D was compared to the other three plans, in which average intensity projection (AIP) images in conjunction with the composite target volume contour copied from the MIP images were used. Relative electron densities within the target envelope were assigned either to original values from the AIP image dataset (plan A) or to predetermined values, 0.8 (plan B) and 0.9 (plan C). In the patient study, the dosimetric impact of a compensator design based on the MIP images (plan ITV(MIP)) was compared to designs based on end-of-inhale (EOI) (plan ITV(EOI)) and middle-of-exhale (MOE) CT images (plan ITV(MOE)). The dose distributions were recalculated for each phase. Throughout the ten phases, it shows that D(GTV)(min) changed slightly from 86% to 89% (SD = 0.9%) of prescribed dose (PD) in the MIP plan, while varying greatly from 10% to 79% (SD = 26.7%) in plan A, 17% to 73% (SD = 22.5%) in plan B and 53% to 73% (SD = 6.8%) in plan C. The same trend was observed for D(GTV)(mean) and V95 with less amplitude. In the MIP-based plan ITV(MIP), D(GTV)(mean) was almost identically equal to 95% in each phase (SD = 0.5%). The patient study verified that the MIP approach increased the minimum value of D99 of the clinical target volume (CTV) by 58.8% compared to plan ITV(EOI) and 12.9% compared to plan ITV(MOE). Minimum values of D99 were 37.60%, 83.50% and 96.40% for plan ITV(EOI), plan ITV(MOE) and plan ITV(MIP), respectively. Standard deviations of D99 were significantly decreased (SD = 0.5%) in the MIP plan as compared to plan ITV(EOI) (SD = 18.9%) or plan ITV(MOE) (SD = 4.0%). These studies demonstrate that the use of MIP images to design the patient-specific composite compensators provide superior and consistent tumor coverage throughout the entire respiratory cycle whilst maintaining a low average normal lung dose. The additional benefit of the MIP-based design approach is that the dose calculation can be implemented on any single phase as long as it uses the aperture and compensator optimized from the MIP images. This also reduces the requirement for contouring on all breathing phases down to just one.

Patient-specific margins for proton therapy of lung.

Lung cancer treatment presents a greater treatment planning and treatment delivery challenge in proton beam therapy compared to conventional photon therapy due to the proton beam's energy deposition sensitivity to the breathing-induced dynamic tissue density variations along the beam path. Four-dimensional computed tomography (4D-CT) has been defined as the explicit inclusion of temporal changes of tumor and normal organ mobility into an image series. It allows more accurate delineation of lung cancer target volumes by suppression of any breathing motion artifacts present in the CT images. It also allows analysis of the tumor's 3D spatial movement within a breathing phase cycle. The motivation for this study was to investigate dosimetric errors caused by lung tumor motion in order to find an optimal method of design for patient compensators and apertures for a passive scattering beam delivery system and treatment of the patient under free breathing conditions. In this study, the maximum intensity projection (MIP) method was compared to patient-specific internal margin designs based on a single breathing phase at the end-of inhale (EOI) or middle-of-exhale (MOE). It was found that MIP method provides superior tumor dose distribution compared to patient-specific internal margin designs derived from 4D-CT.

Dosimetric impact of a CT metal artefact suppression algorithm for proton, electron and photon therapies.

Accurate dose calculation is essential to precision radiation treatment planning and this accuracy depends upon anatomic and tissue electron density information. Modern treatment planning inhomogeneity corrections use x-ray CT images and calibrated scales of tissue CT number to electron density to provide this information. The presence of metal in the volume scanned by an x-ray CT scanner causes metal induced image artefacts that influence CT numbers and thereby introduce errors in the radiation dose distribution calculated. This paper investigates the dosimetric improvement achieved by a previously proposed x-ray CT metal artefact suppression technique when the suppressed images of a patient with bilateral hip prostheses are used in commercial treatment planning systems for proton, electron or photon therapies. For all these beam types, this clinical image and treatment planning study reveals that the target may be severely underdosed if a metal artefact-contaminated image is used for dose calculations instead of the artefact suppressed one. Of the three beam types studied, the metal artefact suppression is most important for proton therapy dose calculations, intermediate for electron therapy and least important for x-ray therapy but still significant. The study of a water phantom having a metal rod simulating a hip prosthesis indicates that CT numbers generated after image processing for metal artefact suppression are accurate and thus dose calculations based on the metal artefact suppressed images will be of high fidelity.

Cosmetic outcome and incidence of infection with the MammoSite breast brachytherapy applicator.

We present our results regarding the cosmetic outcome achieved and the rate of infection using the MammoSite breast brachytherapy applicator to treat patients with partial breast irradiation. In addition, factors associated with cosmetic outcome and infection are analyzed. The study population consisted of 30 patients with early stage breast cancer treated using the MammoSite device from October 28, 2002, to February 13, 2004. Cosmetic outcome was analyzed for its association with the following parameters: volume of the balloon, balloon-to-skin distance, maximal skin point dose per fraction, V100 (percent of volume that received 100% of the prescription dose), V150 (percent of volume that received 150% of the prescription dose), and V200 (percent of volume that received 200% of the prescription dose). The occurrence of infection at the time of treatment and during follow-up was also recorded. At a median follow-up of 13 months (range 1-16 months), 53.3% of the patients (16/30) were reported to have an excellent cosmetic outcome and 40.0% (12/30) had a good cosmetic outcome. Excellent cosmetic outcome was associated with a greater mean balloon-to-skin distance compared to those who achieved a good cosmetic outcome (1.5 cm versus 1.2 cm) (p = 0.164). The mean V100, V150, and V200 of those in the excellent cosmetic outcome group were 92.1%, 34.5%, and 7.6% versus 93.0%, 34.7%, and 7.6% in the good cosmetic outcome group (p = 0.642, 0.926, and 0.853), The mean balloon volumes were 47.7 cm3 and 56.9 cm3, respectively (p = 0.063) in the excellent and good outcome groups. The mean maximal skin doses per fraction in the excellent and good outcome groups were 354.8 cGy and 422.3 cGy (p = 0.286), respectively. Infection occurred in 13.3% of the patients (4/30). An excellent or good cosmetic outcome was achieved in 93.3% of patients and infection occurred in 13.3% of patients treated with the MammoSite breast brachytherapy applicator. Excellent cosmetic outcome was associated with a greater balloon-to-skin distance, lower maximal skin dose per fraction, and smaller mean balloon volume; however, the results did not reach statistical significance.

Performance of magnetic field-guided navigation system for interventional neurosurgical and cardiac procedures.

A hospital-based magnetic guidance system (MGS) was installed to assist a physician in navigating catheters and guide wires during interventional cardiac and neurosurgical procedures. The objective of this study is to examine the performance of this magnetic field-guided navigation system. Our results show that the system's radiological imaging components produce images with quality similar to that produced by other modern fluoroscopic devices. The system's magnetic navigation components also deflect the wire and catheter tips toward the intended direction. The physician, however, will have to oversteer the wire or catheter when defining the steering angle during the procedure. The MGS could be clinically useful in device navigation deflection and vessel access.

Surface optimization technique for MammoSite breast brachytherapy applicator.

PURPOSE: We present a technique to optimize the dwell times and positions of a high-dose-rate (192)Ir source using the MammoSite breast brachytherapy applicator. The surface optimization method used multiple dwell positions and optimization points to conform the 100% isodose line to the surface of the planning target volume (PTV). METHODS AND MATERIALS: The study population consisted of 20 patients treated using the MammoSite device between October 2002 and February 2004. Treatment was delivered in 10 fractions of 3.4 Gy/fraction, twice daily, with a minimum of 6 h between fractions. The treatment of each patient was planned using three optimization techniques. The dosimetric characteristics of the single-point, six-point, and surface optimization techniques were compared. RESULTS: The surface optimization technique increased the PTV coverage compared with the single- and six-point methods (mean percentage of PTV receiving 100% of the prescription dose was 94%, 85%, and 91%, respectively). The surface method, single-point, and six-point method had a mean dose homogeneity index of 0.62, 0.68, and 0.63 and a mean full width at half maximum value of 189, 190, and 192 cGy/fraction, respectively. CONCLUSION: The surface technique provided greater coverage of the PTV than did the single- and six-point methods. Using the FWHM method, the surface, single-, and six-point techniques resulted in equivalent dose homogeneity.

Treatment volume and dose optimization of MammoSite breast brachytherapy applicator.

PURPOSE: Limited information has been reported on the dosimetry achieved with the MammoSite breast brachytherapy applicator. We present our results regarding the volume of treatment and a comparison of a single prescription point, single dwell position optimization technique with a six prescription point, multiple dwell position method. METHODS AND MATERIALS: Between October 14, 2002 and February 28, 2003, 21 patients with early-stage breast cancer were treated using the MammoSite device. The treatment was delivered in 10 fractions of 3.4 Gy/fraction, b.i.d., with a minimum of 6 hours between the daily fractions. CT of the lumpectomy cavity was obtained both with and without the inflated balloon. A planning target volume was constructed using a three-dimensional planning system. A three-dimensional expansion of the balloon surface was performed using the chest wall and skin as limiting structures. The volume of the inflated balloon was removed from this volume, and the volume of tissue treated in each patient was determined. A sequential expansion in 1-mm increments around the empty lumpectomy cavity was performed until the closest equivalent volume to the planning target volume was obtained. The treatment for the patients in this study was planned using both a single prescription point, single dwell position optimization technique and a six-prescription point, multiple dwell position technique. The single prescription point method has been described in a previous publication. The six-prescription point method used six points placed 1 cm from the balloon surface. Four points are in a plane transverse to the balloon axis perpendicular to the axis of the catheter, and two points are placed along the axis of the catheter. The prescription points along the catheter axis are used to compensate for the decreased dose coverage owing to anisotropy dose distribution of the source. The Nucletron HDR Plato Brachytherapy planning system was used to optimize the source positions and dwell times. RESULTS: The volume of breast tissue treated by the MammoSite device was equal to the volume encompassed by a mean 1.6-cm (SD, 0.1) margin around the empty lumpectomy cavity. Compared with the single prescription point optimization method, the six prescription point method provided better dose coverage, with a mean percentage of volume receiving 90% of the prescription dose of 97.2% (SD = 2.1) vs. 89.5% (SD = 4.6) for the single-point method. The mean percentage of volume receiving 100% of the prescription dose was 88.9% (SD = 3.3) for the six-point method vs. 77.6% (SD = 6.1) for the single-point method. However, compared with the single-point method, the six-point optimization method resulted in treatment that was less uniform, with a mean dose homogeneity index of 0.62 (SD =.07) vs. 0.66 (SD =.08) for the single-point method. CONCLUSION: The volume of normal breast tissue treated by the MammoSite device is comparable to other methods of interstitial brachytherapy that treat a 1-2-cm margin of tissue around the excision cavity. The six-prescription point, multiple dwell position method improved dose coverage with a slight decrease in dose homogeneity. The six-point method offers greater reliability of dose coverage compared with the single-point method by providing an increased number of reference points.