A Melancon

A beam-specific planning target volume (PTV) design for proton therapy to account for setup and range uncertainties

PURPOSE To report a method for explicitly designing a planning target volume (PTV) for treatment planning and evaluation in heterogeneous media for passively scattered proton therapy and scanning beam proton therapy using single-field optimization (SFO). METHODS AND MATERIALS A beam-specific PTV (bsPTV) for proton beams was derived by ray-tracing and shifting ray lines to account for tissue misalignment in the presence of setup error or organ motion. Range uncertainties resulting from inaccuracies in computed tomography-based range estimation were calculated for proximal and distal surfaces of the target in the beam direction. The bsPTV was then constructed based on local heterogeneity. The bsPTV thus can be used directly as a planning target as if it were in photon therapy. To test the robustness of the bsPTV, we generated a single-field proton plan in a virtual phantom. Intentional setup and range errors were introduced. Dose coverage to the clinical target volume (CTV) under various simulation conditions was compared between plans designed based on the bsPTV and a conventional PTV. RESULTS The simulated treatment using the bsPTV design performed significantly better than the plan using the conventional PTV in maintaining dose coverage to the CTV. With conventional PTV plans, the minimum coverage to the CTV dropped from 99% to 67% in the presence of setup error, internal motion, and range uncertainty. However, plans using the bsPTV showed minimal drop of target coverage from 99% to 94%. CONCLUSIONS The conventional geometry-based PTV concept used in photon therapy does not work well for proton therapy. We investigated and validated a beam-specific PTV method for designing and evaluating proton plans.

Spot Scanning Proton Therapy for Malignancies of the Base of Skull: Treatment Planning, Acute Toxicities, and Preliminary Clinical Outcomes

PURPOSE To describe treatment planning techniques and early clinical outcomes in patients treated with spot scanning proton therapy for chordoma or chondrosarcoma of the skull base. METHODS AND MATERIALS From June 2010 through August 2011, 15 patients were treated with spot scanning proton therapy for chordoma (n=10) or chondrosarcoma (n=5) at a single institution. Toxicity was prospectively evaluated and scored weekly and at all follow-up visits according to Common Terminology Criteria for Adverse Events, version 3.0. Treatment planning techniques and dosimetric data were recorded and compared with those of passive scattering plans created with clinically applicable dose constraints. RESULTS Ten patients were treated with single-field-optimized scanning beam plans and 5 with multifield-optimized intensity modulated proton therapy. All but 2 patients received a simultaneous integrated boost as well. The mean prescribed radiation doses were 69.8 Gy (relative biological effectiveness [RBE]; range, 68-70 Gy [RBE]) for chordoma and 68.4 Gy (RBE) (range, 66-70) for chondrosarcoma. In comparison with passive scattering plans, spot scanning plans demonstrated improved high-dose conformality and sparing of temporal lobes and brainstem. Clinically, the most common acute toxicities included fatigue (grade 2 for 2 patients, grade 1 for 8 patients) and nausea (grade 2 for 2 patients, grade 1 for 6 patients). No toxicities of grades 3 to 5 were recorded. At a median follow-up time of 27 months (range, 13-42 months), 1 patient had experienced local recurrence and a second developed distant metastatic disease. Two patients had magnetic resonance imaging-documented temporal lobe changes, and a third patient developed facial numbness. No other subacute or late effects were recorded. CONCLUSIONS In comparison to passive scattering, treatment plans for spot scanning proton therapy displayed improved high-dose conformality. Clinically, the treatment was well tolerated, and with short-term follow-up, disease control rates and toxicity profiles were favorable.

Technical Note: A Monte Carlo study of magnetic‐field‐induced radiation dose effects in mice

PURPOSE Magnetic fields are known to alter radiation dose deposition. Before patients receive treatment using an MRI-linear accelerator (MRI-Linac), preclinical studies are needed to understand the biological consequences of magnetic-field-induced dose effects. In the present study, the authors sought to identify a beam energy and magnetic field strength combination suitable for preclinical murine experiments. METHODS Magnetic field dose effects were simulated in a mouse lung phantom using various beam energies (225 kVp, 350 kVp, 662 keV [Cs-137], 2 MV, and 1.25 MeV [Co-60]) and magnetic field strengths (0.75, 1.5, and 3 T). The resulting dose distributions were compared with those in a simulated human lung phantom irradiated with a 6 or 8 MV beam and orthogonal 1.5 T magnetic field. RESULTS In the human lung phantom, the authors observed a dose increase of 45% and 54% at the soft-tissue-to-lung interface and a dose decrease of 41% and 48% at the lung-to-soft-tissue interface for the 6 and 8 MV beams, respectively. In the mouse simulations, the magnetic fields had no measurable effect on the 225 or 350 kVp dose distribution. The dose increases with the Cs-137 beam for the 0.75, 1.5, and 3 T magnetic fields were 9%, 29%, and 42%, respectively. The dose decreases were 9%, 21%, and 37%. For the 2 MV beam, the dose increases were 16%, 33%, and 31% and the dose decreases were 9%, 19%, and 30%. For the Co-60 beam, the dose increases were 19%, 54%, and 44%, and the dose decreases were 19%, 42%, and 40%. CONCLUSIONS The magnetic field dose effects in the mouse phantom using a Cs-137, 3 T combination or a Co-60, 1.5 or 3 T combination most closely resemble those in simulated human treatments with a 6 MV, 1.5 T MRI-Linac. The effects with a Co-60, 1.5 T combination most closely resemble those in simulated human treatments with an 8 MV, 1.5 T MRI-Linac.

TU-H-CAMPUS-TeP2-01: A Comparison of Noninvasive Techniques to Assess Radiation-Induced Lung Damage in Mice

PURPOSE To evaluate the use of post-irradiation changes in respiratory rate and CBCT-based morphology as predictors of survival in mice. METHODS C57L/J mice underwent whole-thorax irradiation with a Co-60 beam to four different doses [0Gy (n=3), 9Gy (n=5), 11Gy (n=7), and 13Gy (n=5)] in order to induce varying levels of pneumonitis. Respiratory rate measurements, breath-hold CBCTs, and free-breathing CBCTs were acquired pre-irradiation and at six time points between two and seven months post-irradiation. For respiratory rate measurements, we developed a novel computer-vision-based technique. We recorded mice sleeping in standard laboratory cages with a 30 fps, 1080p webcam (Logitech C920). We calculated respiratory rate using corner detection and optical flow to track cyclical motion in the fur in the recorded video. Breath-hold and free-breathing CBCTs were acquired on the X-RAD225Cx system. For breathhold imaging, the mice were intubated and their breath was held at full-inhale for 20 seconds. Healthy lung tissue was delineated in the scans using auto-threshold contouring (0-0.7 g/cm3 ). The volume of healthy lung was measured in each of the scans. Next, lung density was measured in a 6-mm2 ROI in a fixed anatomic location in each of the scans. RESULTS Day-to-day variability in respiratory rate with our technique was 13%. All metrics except for breath-hold lung volume were correlated with survival: lung density on free-breathing (r=-0.7482,p<0.01) and breath-hold images (r=-0.5864,p<0.01), free-breathing lung volume (r=0.7179,p<0.01), and respiratory rate (r= 0.6953,p<0.01). Lung density on free-breathing scans was correlated with respiratory rate (r=0.7142,p<0.01) and lung density on breath-hold scans (r=0.5543,p<0.01). One significant practical hurdle in the CBCT measurements was that at least one lobe of the lung was collapsed in 36% of free-breathing scans and 45% of breath-hold scans. CONCLUSION Lung density and lung volume on free-breathing CBCTs and respiratory rate outperform breath-hold CBCT measurements as indicators for survival from radiation-induced pneumonitis. This work was partially funded by Elekta.

Radiopaque Resorbable Inferior Vena Cava Filter Infused with Gold Nanoparticles

Failure to remove a retrievable inferior vena cava (IVC) filter can cause severe complications with high treatment costs. Polydioxanone (PPDO) has been shown to be a good candidate material for resorbable IVC filters. However, PPDO is radioluscent under conventional imaging modalities. Thus, the positioning and integrity of these PPDO filters cannot be monitored by computed tomography (CT) or x-ray. Here we report the development of radiopaque PPDO IVC filters based on gold nanoparticles (AuNPs). Commercially available PPDO sutures were infused with AuNPs. Scanning electron microscopy analysis confirmed the presence of AuNP on the surface of PPDO. Micro-CT and x-ray images of the AuNP-infused PPDO sutures showed significant signal enhancement compared to untreated PPDO sutures. Elemental analysis showed that gold loading exceeded 2000 ppm. Tensile strength and in vitro cytotoxicity showed no significant difference between AuNP-infused and untreated PPDO. In a 10-week stability study, neither the gold content nor the radiopacity of the infused PPDO sutures significantly changed in the first 6 weeks. The increased attenuation of AuNP-infused PPDO sutures indicates their major advantage as a radiopaque resorbable filter material, as the radiopacity allows monitoring of the position and integrity of the filter, thereby increasing its safety and efficacy.

Anatomic variation and dosimetric consequences of neoadjuvant hormone therapy before radiation therapy for prostate cancer

PURPOSE To characterize anatomic variation during neoadjuvant androgen deprivation (NAD) and determine a treatment planning strategy to maintain acceptable normal tissue dose while treating potential microscopic disease in the original (pre-NAD) tumor bed. METHODS AND MATERIALS We retrospectively examined the effects of treating the post-NAD anatomy with plans derived before and after NAD in a group of 44 patients enrolled in an institutional review board-approved protocol. An 8-field intensity modulated radiation therapy (IMRT) treatment plan was generated on anatomy both before and after NAD for the first 35 patients. The pre-NAD treatment plan was applied to the post-NAD anatomy to evaluate the effect of complete pre-NAD tumor bed treatment on normal tissue sparing, and the post-NAD treatment plan was applied to the pre-NAD anatomy to investigate whether microscopic disease might go untreated in the location of the pre-NAD tumor bed. RESULTS The prostate decreased in volume by an average of about 14 cm(3) (24.3%) and was correlated with NAD duration (P = .002). The prostate center of volume systematically shifted in the inferior direction (mean = 1.4 mm, P = .005) and inferior shift was correlated with absolute volume reduction of the prostate (P = .044) in a multivariate model containing rectal and bladder volume change and initial prostate volume. Pre-NAD treatment planning resulted in a significant increase in the bladder volume (P < .01) but little increase in the rectal volume treated to all dose levels. Post-NAD treatment planning resulted in decreased treatment of the prostate and seminal vesicles (on the pre-NAD anatomy) at the prescribed and 95% isodose levels (prostate: P = .033 and 0.025; seminal vesicles: P < .001). CONCLUSIONS Anisotropic volume reduction of the prostate was found during NAD and correlated with NAD duration. Post-NAD based treatment planning can minimize excess bladder and rectal dose.

SU‐HH‐BRB‐11: Range Adaptive Proton Therapy for Prostate Cancer

Purpose: The rapid distal falloff of a proton beam allows for sparing of normal tissues distal to target organs. However proton beams that aim directly towards critical structures are avoided due to concerns of range uncertainties, such as CT number conversion and anatomy variations. We propose to eliminate range uncertainty and enable prostate treatment with a single anterior beam by detecting the protons range at the prostate‐rectal interface and adaptively adjusting the range in vivo and in real‐time. Materials and Methods: A prototype device, consisting of an endorectal liquid scintillation detector and dual‐inverted lucite wedges for range compensation, was designed to test the feasibility and accuracy of the technique. Liquid scintillation filled volume was fitted with optical fiber and placed inside the rectum of an anthropomorphic pelvic phantom. Photodiode‐generated current signal was generated as a function of proton beam depth, and the spatial resolution of this technique was calculated by relating the variance in detecting proton spills to the penetration depth. The relative water‐equivalent thickness of the wedges was measured in a water phantom and prospectively tested to determine the accuracy of range corrections. Treatment simulation studies were performed to test the potential dosimetric benefit in sparing the rectum.Results: The spatial resolution of the detector in phantom measurement was 0.5 mm. The precision of the range correction was 0.04 mm. The residual margin to ensure CTV coverage was 1.1 mm. The composite distal margin for 95% treatment confidence was 2.4 mm. Planning studies based on a previously estimated 2mm margin on 27 patients showed a rectal sparing up to 51% at 70Gy and 57% at 40Gy relative to IMRT and bilateral proton treatment. Conclusion: We demonstrated the feasibility of our design. Use of this technique allows for proton treatment using a single anterior beam, significantly reducing the rectal dose.

SU‐GG‐T‐470: Improving Rectal Sparing with a Single Anterior Proton Beam: A Planning Study

Purpose: To demonstrate the potential dosimetric advantage of an anterior proton beam for treatment of prostate cancer patients utilizing the Bragg peak for rectal sparing. Methods to detect the anterior proton beam at depth are being investigated to eliminate the large distal planning margin, enabling abrupt dose falloff at the anterior rectal wall rather than the relatively shallow falloff of the lateral beam penumbra with conventional lateral beam arrangement. Method and Materials: 27 consecutive prostate cancer patients treated with proton therapy were enrolled in a planning study to compare standard IMRT and bi‐lateral protontreatments with a single anterior proton beam treatment. Dose‐population histograms were generated comparing target coverage and normal tissue sparing of all critical structures between the treatment groups. Results: The anterior beam treatment significantly spared the anterior rectal wall more than the IMRT and bilateral beam treatments at the 70 Gy (12.3% vs 19.2% and 19.2%), 60 Gy (15.7% vs 23.8% and 24.3%), 45 Gy (19.4% vs 30.1% and 29.6%), and 30 Gy dose levels (22.7% vs 39.9% and 34.2%). Bladder wall dose was greater in the anterior beam treatment than IMRT and bilateral beam treatments at the 70 Gy (14.1% vs 11.2% and 12.8%), 60 Gy (22.5% vs 13.7% and 16.2%), 45 Gy (29.0% vs 17.9% and 19.8%), and 30 Gy dose levels (32.6% vs 25.1% and 23.1%). No dose was delivered to the femoral heads with the anterior beam treatment while the IMRT and bilateral treatments delivered a mean dose of 17.0 Gy and 25.1 Gy to the femoral heads respectively. Conclusion: With the implementation of in vivo proton beam detection, anterior proton beam treatment of prostate is a possible treatment alternative, sparing dose to the rectum and femoral heads at the cost of a small increase in bladder dose.

In vivo imaging of radiopaque resorbable inferior vena cava filter infused with gold nanoparticles

Radiopaque resorbable inferior vena cava filter (IVCF) were developed to offer a less expensive alternative to assessing filter integrity in preventing pulmonary embolism for the recommended prophylactic period and then simply vanishes without intervention. In this study, we determined the efficacy of gold nanoparticle (AuNP)-infused poly-p-dioxanone (PPDO) as an IVCF in a swine model. Infusion into PPDO loaded 1.14±0.08 % AuNP by weight as determined by elemental analysis. The infusion did not alter PPDO’s mechanical strength nor crystallinity (Kruskal−Wallis one-way ANOVA, p<0.05). There was no cytotoxicity observed (one-way ANOVA, p<0.05) when tested against RF24 and MRC5 cells. Gold content in PPDO was maintained at ~2000 ppm during the 6-week incubation in PBS at 37oC. As a proof-of-concept, two pigs were deployed with IVCF, one with AuNP-PPDO and the other without coating. Results show that the stent ring of AuNP-PPDO was highly visible even in the presence of iodine-based contrast agent and after clot introduction, but not of the uncoated IVCF. Autopsy at two weeks post-implantation showed AuNP-PPDO filter was endothelialized onto the IVC wall, and no sign of filter migration was observed. The induced clot was also still trapped within the AuNP-PPDO IVCF. As a conclusion, we successfully fabricated AuNP-infused PPDO IVCF that is radiopaque, has robust mechanical strength, biocompatible, and can be imaged effectively in vivo. This suggests the efficacy of this novel, radiopaque, absorbable IVCF for monitoring its position and integrity over time, thus increasing the safety and efficacy of deep vein thrombosis treatment.

TH‐CD‐BRA‐01: BEST IN PHYSICS (THERAPY): ‐Field‐Induced Dose Effects in a Mouse Lung Phantom: Monte Carlo and Experimental Assessments

PURPOSE To simulate and measure magnetic-field-induced radiation dose effects in a mouse lung phantom. This data will be used to support pre-clinical experiments related to MRI-guided radiation therapy systems. METHODS A mouse lung phantom was constructed out of 1.5×1.5×2.0-cm3 lung-equivalent material (0.3 g/cm3 ) surrounded by a 0.6-cm solid water shell. EBT3 film was inserted into the phantom and the phantom was placed between the poles of an H-frame electromagnet. The phantom was irradiated with a cobalt-60 beam (1.25 MeV) with the electromagnet set to various magnetic field strengths (0T, 0.35T, 0.9T, and 1.5T). These magnetic field strengths correspond to the range of field strengths seen in MRI-guided radiation therapy systems. Dose increases at the solid-water-to-lung-interface and dose decreases at the lung-to-solid-water interface were compared with results of Monte Carlo simulations performed with MCNP6. RESULTS The measured dose to lung at the solid-water-to-lung interface increased by 0%, 16%, and 29% with application of the 0.35T, 0.9T, and 1.5T magnetic fields, respectively. The dose to lung at the lung-to-solid-water interface decreased by 4%, 18%, and 24% with application of the 0.35T, 0.9T, and 1.5T magnetic fields, respectively. Monte Carlo simulations showed dose increases of 0%, 16%, and 31% and dose decreases of 4%, 16%, and 25%. CONCLUSION Only small dose perturbations were observed at the lung-solid-water interfaces for the 0.35T case, while more substantial dose perturbations were observed for the 0.9T and 1.5T cases. There is good agreement between the Monte Carlo calculations and the experimental measurements (within 2%). These measurements will aid in designing pre-clinical studies which investigate the potential biological effects of radiation therapy in the presence of a strong magnetic field. This work was partially funded by Elekta.