The effect of common dental fixtures on treatment planning and delivery for head and neck intensity modulated proton therapy.

PURPOSE: Proton treatment plan perturbation by common dental fixtures such as amalgams (Am) and porcelain-fused-to-metal (PFM) crowns has, to date, been uncharacterized. Previous studies have been conducted to determine the physical effect of these materials within the beam path for single spots, but their effects on complex treatment plans and clinical anatomy have not yet been quantified. The present manuscript aims to study the effect of Am and PFM fixtures on proton treatment planning in a clinical setting. METHODS: An anthropomorphic phantom with removable tongue, maxilla, and mandible modules was simulated on a clinical computed tomography (CT) scanner. Spare maxilla modules were modified to include either a 1.5 mm depth central groove occlusal amalgam (Am) or a porcelain-fused-to-metal (PFM) crown, implanted on the first right molar. Modified tongue modules were 3D printed to accommodate several axial or sagittal oriented pieces of EBT-3 film. Clinically representative spot-scanning proton plans were generated in Eclipse v.15.6 using the proton convolution superposition (PCS) algorithm v.15.6.06 using a multi-field optimization (MFO) technique with the goal of delivering a uniform 54 Gy dose to a clinical target volume (CTV) typical of a base-of-tongue (BoT) treatment. A typical geometric beam arrangement of two anterior oblique (AO) beams and a posterior beam was employed. Plans optimized without any material overrides were delivered to the phantom A) without implants; B) with Am fixture; or C) with PFM crown. Plans were also reoptimized and delivered with inclusion of material overrides to equate relative stopping power of the fixture with that of a previously measured result. RESULTS: Plans exhibit slightly greater dose weight towards AO beams. The optimizer accounted for inclusion of fixture overrides by increasing beam weights to the beam closest to the implant. Film measurements exhibited cold spots directly within the beam path through the fixture in plans with and without overridden materials. Cold spots were somewhat mitigated in plans including overridden materials in the structure set but were not entirely eliminated. Cold spots associated with Am and PFM fixtures were quantified at 17% and 14% for plans without overrides, respectively, and 11% and 9% with using Monte Carlo simulation. Compared with film measurements and Monte Carlo simulation, the treatment planning system underestimates the dose shadowing effect in plans including material overrides. CONCLUSIONS: Dental fixtures create a dose shadowing effect directly in line with the beam path through the material. This cold spot is partially mitigated by overriding the material to measured relative stopping powers. Due to uncertainties in modeling perturbation through the fixture, the magnitude of the cold spot is underestimated using the institutional TPS when compared to measurement and MC simulation.

Physical characterization of therapeutic proton delivery through common dental materials.

PURPOSE: Dental fixtures are commonplace in an aging, radiation treatment population. The current, local standard of practice in particle therapy is to employ treatment geometries to avoid delivery through implanted dental fixtures. The present study aims to observe the physical effect of delivering therapeutic proton beams through common dental fixture materials as prelude to an eventual goal of assessing the feasibility of using treatment geometries not specified for avoidance of oral implants. A sampling of common dental materials was selected based on prosthodontic consult and was evaluated in terms of relative stopping power and three-dimensional (3D) dose perturbation. METHODS: Amalgams, porcelain-fused-to-metal (PFM) crowns consisting of zirconia and non-noble base metals, and lithium disilicate implants were chosen for analysis. Theoretical stopping power (S) and mass stopping power (S/ρ) were calculated using the Stopping and Range of Ions in Matter (SRIM) application, basing stoichiometric compositions of each fixture on published materials data. S and S/ρ were calculated for a range of historically available compositions of amalgams from 1900 until the current era. The perturbance of S and S/ρ as a function of clinically relevant ranges of amalgam compositions for the modern era was analyzed. Water equivalent thickness (WET) and relative stopping power (Srel ) of each material was measured for a clinical spot-scanning proton beam with monoenergies of 159.9 and 228.8 MeV with a multi-layer ionization chamber (MLIC). Subsequently, 3D dose perturbation was assessed by delivering proton beams through a custom phantom designed to simulate both en-face and on-edge treatment geometries through the selected materials. A treatment plan mimicking the experimental delivery was constructed in the institutional treatment planning system and calculated using TOPAS-based Monte Carlo simulation (MCS). Experimental results were used to validate the MCS. Finally, treatment planning system (TPS) outputs were compared to MCS to determine the accuracy of the dose calculation model. RESULTS: Historical compositions of amalgams ranged in S from 44.8 to 42.9 MeV/cm, with the greatest deviation being observed for the 1900-1959 era. Deviation as a function of amalgam composition from the modern era was most sensitive to proportion of Hg, accounting for deviations up to -4.2% at the greatest clinically relevant concentration. S/ρ was not found to vary greatly between each porcelain and metal alloy material for PFM type crowns. Relative stopping powers ranged between 1.3 and 5.4 for all studied materials, suggesting substantial changes in proton range with respect to water. Film measurements of pristine spots confirm dose perturbance and shortening of proton range, with an upstream shift of each Bragg peak being observed directly behind the installed fixture. At high energies, cold spots were found in all cases directly behind each material feature with a medial fill-in of dose occurring distally. Qualitative agreement of spot perturbance was confirmed between film measurements and MCS. Finally, when comparing integrated depth doses (IDD) by summing over all axial directions, good agreement is observed between TPS and MCS. CONCLUSIONS: All dental materials studied substantially perturbed the dosimetry of pristine proton spots both in terms of WET/Srel as well as the spatial distribution of dose. Proton range was quantifiably shortened, and each dental material affected a cold spot directly behind the object with medial dose back-filling was observed distally. MCS and Eclipse dose calculations exhibited good agreement with measurements, suggesting that treatment planning without employing avoidance strategies may be possible with further investigation.

Clinical Implementation of a Proton Dose Verification System Utilizing a GPU Accelerated Monte Carlo Engine.

PURPOSE: To develop a clinical infrastructure that allows for routine Monte Carlo dose calculation verification of spot scanning proton treatment plans and includes a simple biological model to aid in normal tissue protection. MATERIALS AND METHODS: A graphical processing unit accelerated Monte Carlo dose engine was used as the calculation engine for dose verification on spot scanning proton plans. An infrastructure was built around this engine that allows for seamless exporting of treatment plans from the treatment planning system and importing of dose distribution from the Monte Carlo calculation via DICOM (digital imaging and communications in medicine). An easy-to-use Web-based interface was developed so that the application could be run from any computer. In addition to the standard relative biological effectiveness = 1.1 for proton therapy, a simple linear equation dependent on dose-weighted linear energy transfer was included. This was used to help detect possible high biological dose in critical structures. RESULTS: More than 270 patients were treated at our proton center in the first year of operation. Because most plans underwent multiple iterations before final approval, more than 1000 plans have been run through the system from multiple users with minimal downtime. The average time from plan export to importing of the Monte Carlo doses was less than 15 minutes. Treatment plans have been modified based on the nominal Monte Carlo dose or the biological dose. CONCLUSION: Monte Carlo dose calculation verification of spot scanning proton treatment plans is feasible in a clinical environment. The 3-dimensional dose verification, particularly near heterogeneities, has resulted in plan modifications. The biological dose data provides actionable feedback for end of range effects, especially in pediatric patients.

Radiation binary targeted therapy for HER-2 positive breast cancers: assumptions, theoretical assessment and future directions.

A novel radiation targeted therapy is investigated for HER-2 positive breast cancers. The proposed concept combines two known approaches, but never used together for the treatment of advanced, relapsed or metastasized HER-2 positive breast cancers. The proposed radiation binary targeted concept is based on the anti HER-2 monoclonal antibodies (MABs) that would be used as vehicles to transport the nontoxic agent to cancer cells. The anti HER-2 MABs have been successful in targeting HER-2 positive breast cancers with high affinity. The proposed concept would utilize a neutral nontoxic boron-10 predicting that anti HER-2 MABs would assure its selective delivery to cancer cells. MABs against HER-2 have been a widely researched strategy in the clinical setting. The most promising antibody is Trastuzumab (Herceptin). Targeting HER-2 with the MAB Trastuzumab has been proven to be a successful strategy in inducing tumour regression and improving patient survival. Unfortunately, these tumours become resistant and afflicted women succumb to breast cancer. In the proposed concept, when the tumour region is loaded with boron-10 it is irradiated with neutrons (treatment used for head and neck cancers, melanoma and glioblastoma for over 40 years in Japan and Europe). The irradiation process takes less than an hour producing minimal side effects. This paper summarizes our recent theoretical assessments of radiation binary targeted therapy for HER-2 positive breast cancers on: the effective drug delivery mechanism, the numerical model to evaluate the targeted radiation delivery and the survey study to find the neutron facility in the world that might be capable of producing the radiation effect as needed. A novel method of drug delivery utilizing Trastuzumab is described, followed by the description of a computational Monte Carlo based breast model used to determine radiation dose distributions. The total flux and neutron energy spectra of five currently available neutron irradiation treatment facilities are examined for this application. The tumour boron concentrations and tumour to healthy tissue concentration ratios required to deliver 50 Gy-Eq to the tumour without exceeding 18 Gy-Eq in the skin are determined, as well as the associated therapeutic ratios. Discussion is provided to address the future research direction for assessing the feasibility of the proposed concept.