The Role of Proton Therapy for Prostate Cancer in the Setting of Hip Prosthesis.

PURPOSE: Given that the current standard of proton therapy (PT) for prostate cancer is through bilateral beams, this modality is typically avoided when it comes to treatment of patients with hip prosthesis. The purpose of this study was to evaluate whether novel PT methods, i.e., anterior proton beams and proton arc therapy (PArc), could be feasible options to treat this patient subpopulation. We evaluate PT methods in the context of dosimetry and robustness and compare with standard of practice volumetric modulated arc therapy (VMAT) to explore any potential benefits. METHODS: Two PT and one VMAT treatment plans were retrospectively created for 10 patients who participated in a clinical trial with a weekly repeat CT (rCT) imaging component. All plans were robustly optimized and featured: (1) combination anterior oblique and lateral proton beams (AoL), (2) PArc, and (3) VMAT. All patients had hydrogel spacers in place, which enabled safe application of anterior proton beams. The planned dose was 70 Gy (RBE) to the entire prostate gland and 50 Gy (RBE) to the proximal seminal vesicles in 28 fractions. Along with plan dose-volume metrics, robustness to setup and interfractional variations were evaluated using the weekly rCT images. The linear energy transfer (LET)-weighted dose was evaluated for PArc plans to ensure urethra sparing given the typical high-LET region at the end of range. RESULTS: Both PT methods were dosimetrically feasible and provided reduction of some key OAR metrics compared to VMAT except for penile bulb, while providing equally good target coverage. Significant differences in median rectum V35 (22-25%), penile bulb Dmean (5 Gy), rectum V61 (2%), right femoral head Dmean (5 Gy), and bladder V39 (4%) were found between PT and VMAT. All plans were equally robust to variations. LET-weighted dose in urethra was equivalent to the physical dose for PArc plans and hence no added urethral toxicity was expected. CONCLUSIONS: PT for treatment of prostate cancer patients with hip prosthesis is feasible and equivalent or potentially superior to VMAT in quality in some cases. The choice of radiotherapy regimen can be personalized based on patient characteristics to achieve the best treatment outcome.

Evaluating the effect of setup uncertainty reduction and adaptation to geometric changes on normal tissue complication probability using online adaptive head and neck intensity modulated proton therapy.

Objective. To evaluate the impact of setup uncertainty reduction (SUR) and adaptation to geometrical changes (AGC) on normal tissue complication probability (NTCP) when using online adaptive head and neck intensity modulated proton therapy (IMPT).Approach.A cohort of ten retrospective head and neck cancer patients with daily scatter corrected cone-beam CT (CBCT) was studied. For each patient, two IMPT treatment plans were created: one with a 3 mm setup uncertainty robustness setting and one with no explicit setup robustness. Both plans were recalculated on the daily CBCT considering three scenarios: the robust plan without adaptation, the non-robust plan without adaptation and the non-robust plan with daily online adaptation. Online-adaptation was simulated using an in-house developed workflow based on GPU-accelerated Monte Carlo dose calculation and partial spot-intensity re-optimization. Dose distributions associated with each scenario were accumulated on the planning CT, where NTCP models for six toxicities were applied. NTCP values from each scenario were intercompared to quantify the reduction in toxicity risk induced by SUR alone, AGC alone and SUR and AGC combined. Finally, a decision tree was implemented to assess the clinical significance of the toxicity reduction associated with each mechanism.Main results. For most patients, clinically meaningful NTCP reductions were only achieved when SUR and AGC were performed together. In these conditions, total reductions in NTCP of up to 30.48 pp were obtained, with noticeable NTCP reductions for aspiration, dysphagia and xerostomia (mean reductions of 8.25, 5.42 and 5.12 pp respectively). While SUR had a generally larger impact than AGC on NTCP reductions, SUR alone did not induce clinically meaningful toxicity reductions in any patient, compared to only one for AGC alone.SignificanceOnline adaptive head and neck proton therapy can only yield clinically significant reductions in the risk of long-term side effects when combining the benefits of SUR and AGC.

Large anatomical changes in head-and-neck cancers - A dosimetric comparison of online and offline adaptive proton therapy.

Purpose: This work evaluates an online adaptive (OA) workflow for head-and-neck (H&N) intensity-modulated proton therapy (IMPT) and compares it with full offline replanning (FOR) in patients with large anatomical changes. Methods: IMPT treatment plans are created retrospectively for a cohort of eight H&N cancer patients that previously required replanning during the course of treatment due to large anatomical changes. Daily cone-beam CTs (CBCT) are acquired and corrected for scatter, resulting in 253 analyzed fractions. To simulate the FOR workflow, nominal plans are created on the planning-CT and delivered until a repeated-CT is acquired; at this point, a new plan is created on the repeated-CT. To simulate the OA workflow, nominal plans are created on the planning-CT and adapted at each fraction using a simple beamlet weight-tuning technique. Dose distributions are calculated on the CBCTs with Monte Carlo for both delivery methods. The total treatment dose is accumulated on the planning-CT. Results: Daily OA improved target coverage compared to FOR despite using smaller target margins. In the high-risk CTV, the median D98 degradation was 1.1 % and 2.1 % for OA and FOR, respectively. In the low-risk CTV, the same metrics yield 1.3 % and 5.2 % for OA and FOR, respectively. Smaller setup margins of OA reduced the dose to all OARs, which was most relevant for the parotid glands. Conclusion: Daily OA can maintain prescription doses and constraints over the course of fractionated treatment, even in cases of large anatomical changes, reducing the necessity for manual replanning in H&N IMPT.

Optically stimulated luminescence dosimeters for simultaneous measurement of point dose and dose-weighted LET in an adaptive proton therapy workflow.

Purpose: To demonstrate the suitability of optically stimulated luminescence detectors (OSLDs) for accurate simultaneous measurement of the absolute point dose and dose-weighted linear energy transfer (LETD) in an anthropomorphic phantom for experimental validation of daily adaptive proton therapy. Methods: A clinically realistic intensity-modulated proton therapy (IMPT) treatment plan was created based on a CT of an anthropomorphic head-and-neck phantom made of tissue-equivalent material. The IMPT plan was optimized with three fields to deliver a uniform dose to the target volume covering the OSLDs. Different scenarios representing inter-fractional anatomical changes were created by modifying the phantom. An online adaptive proton therapy workflow was used to recover the daily dose distribution and account for the applied geometry changes. To validate the adaptive workflow, measurements were performed by irradiating Al2O3:C OSLDs inside the phantom. In addition to the measurements, retrospective Monte Carlo simulations were performed to compare the absolute dose and dose-averaged LET (LETD) delivered to the OSLDs. Results: The online adaptive proton therapy workflow was shown to recover significant degradation in dose conformity resulting from large anatomical and positioning deviations from the reference plan. The Monte Carlo simulations were in close agreement with the OSLD measurements, with an average relative error of 1.4% for doses and 3.2% for LETD. The use of OSLDs for LET determination allowed for a correction for the ionization quenched response. Conclusion: The OSLDs appear to be an excellent detector for simultaneously assessing dose and LET distributions in proton irradiation of an anthropomorphic phantom. The OSLDs can be cut to almost any size and shape, making them ideal for in-phantom measurements to probe the radiation quality and dose in a predefined region of interest. Although we have presented the results obtained in the experimental validation of an adaptive proton therapy workflow, the same approach can be generalized and used for a variety of clinical innovations and workflow developments that require accurate assessment of point dose and/or average LET.

Low-Dose Computed Tomography Scanning Protocols for Online Adaptive Proton Therapy of Head-and-Neck Cancers.

PURPOSE: To evaluate the suitability of low-dose CT protocols for online plan adaptation of head-and-neck patients. METHODS: We acquired CT scans of a head phantom with protocols corresponding to CT dose index volume CTDIvol in the range of 4.2-165.9 mGy. The highest value corresponds to the standard protocol used for CT simulations of 10 head-and-neck patients included in the study. The minimum value corresponds to the lowest achievable tube current of the GE Discovery RT scanner used for the study. For each patient and each low-dose protocol, the noise relative to the standard protocol, derived from phantom images, was applied to a virtual CT (vCT). The vCT was obtained from a daily CBCT scan corresponding to the fraction with the largest anatomical changes. We ran an established adaptive workflow twice for each low-dose protocol using a high-quality daily vCT and the corresponding low-dose synthetic vCT. For a relative comparison of the adaptation efficacy, two adapted plans were recalculated in the high-quality vCT and evaluated with the contours obtained through deformable registration of the planning CT. We also evaluated the accuracy of dose calculation in low-dose CT volumes using the standard CT protocol as reference. RESULTS: The maximum differences in D98 between low-dose protocols and the standard protocol for the high-risk and low-risk CTV were found to be 0.6% and 0.3%, respectively. The difference in OAR sparing was up to 3%. The Dice similarity coefficient between propagated contours obtained with low-dose and standard protocols was above 0.982. The mean 2%/2 mm gamma pass rate for the lowest-dose image, using the standard protocol as reference, was found to be 99.99%. CONCLUSION: The differences between low-dose protocols and the standard scanning protocol were marginal. Thus, low-dose CT protocols are suitable for online adaptive proton therapy of head-and-neck cancers. As such, considering scanning protocols used in our clinic, the imaging dose associated with online adaption of head-and-neck cancers treated with protons can be reduced by a factor of 40.

Integrating Structure Propagation Uncertainties in the Optimization of Online Adaptive Proton Therapy Plans.

Currently, adaptive strategies require time- and resource-intensive manual structure corrections. This study compares different strategies: optimization without manual structure correction, adaptation with physician-drawn structures, and no adaptation. Strategies were compared for 16 patients with pancreas, liver, and head and neck (HN) cancer with 1-5 repeated images during treatment: 'reference adaptation', with structures drawn by a physician; 'single-DIR adaptation', using a single set of deformably propagated structures; 'multi-DIR adaptation', using robust planning with multiple deformed structure sets; 'conservative adaptation', using the intersection and union of all deformed structures; 'probabilistic adaptation', using the probability of a voxel belonging to the structure in the optimization weight; and 'no adaptation'. Plans were evaluated using reference structures and compared using a scoring system. The reference adaptation with physician-drawn structures performed best, and no adaptation performed the worst. For pancreas and liver patients, adaptation with a single DIR improved the plan quality over no adaptation. For HN patients, integrating structure uncertainties brought an additional benefit. If resources for manual structure corrections would prevent online adaptation, manual correction could be replaced by a fast 'plausibility check', and plans could be adapted with correction-free adaptation strategies. Including structure uncertainties in the optimization has the potential to make online adaptation more automatable.

MOQUI: an open-source GPU-based Monte Carlo code for proton dose calculation with efficient data structure.

Objective.Monte Carlo (MC) codes are increasingly used for accurate radiotherapy dose calculation. In proton therapy, the accuracy of the dose calculation algorithm is expected to have a more significant impact than in photon therapy due to the depth-dose characteristics of proton beams. However, MC simulations come at a considerable computational cost to achieve statistically sufficient accuracy. There have been efforts to improve computational efficiency while maintaining sufficient accuracy. Among those, parallelizing particle transportation using graphic processing units (GPU) achieved significant improvements. Contrary to the central processing unit, a GPU has limited memory capacity and is not expandable. It is therefore challenging to score quantities with large dimensions requiring extensive memory. The objective of this study is to develop an open-source GPU-based MC package capable of scoring those quantities.Approach.We employed a hash-table, one of the key-value pair data structures, to efficiently utilize the limited memory of the GPU and score the quantities requiring a large amount of memory. With the hash table, only voxels interacting with particles will occupy memory, and we can search the data efficiently to determine their address. The hash-table was integrated with a novel GPU-based MC code, moqui.Main results.The developed code was validated against an MC code widely used in proton therapy, TOPAS, with homogeneous and heterogeneous phantoms. We also compared the dose calculation results of clinical treatment plans. The developed code agreed with TOPAS within 2%, except for the fall-off and regions, and the gamma pass rates of the results were >99% for all cases with a 2 mm/2% criteria.Significance.We can score dose-influence matrix and dose-rate on a GPU for a 3-field H&N case with 10 GB of memory using moqui, which would require more than 100 GB of memory with the conventionally used array data structure.

CO oxidation by Pt2/Fe3O4: Metastable dimer and support configurations facilitate lattice oxygen extraction.

Heterogeneous catalysts based on subnanometer metal clusters often exhibit strongly size-dependent properties, and the addition or removal of a single atom can make all the difference. Identifying the most active species and deciphering the reaction mechanism is extremely difficult, however, because it is often not clear how the catalyst evolves in operando. Here, we use a combination of atomically resolved scanning probe microscopies, spectroscopic techniques, and density functional theory (DFT)-based calculations to study CO oxidation by a model Pt/Fe3O4(001) "single-atom" catalyst. We demonstrate that (PtCO)2 dimers, formed dynamically through the agglomeration of mobile Pt-carbonyl species, catalyze a reaction involving the oxide support to form CO2. Pt2 dimers produce one CO2 molecule before falling apart into two adatoms, releasing the second CO. Olattice extraction only becomes facile when both the Pt-dimer and the Fe3O4 support can access metastable configurations, suggesting that substantial, concerted rearrangements of both cluster and support must be considered for reactions occurring at elevated temperature.

CT-on-Rails Versus In-Room CBCT for Online Daily Adaptive Proton Therapy of Head-and-Neck Cancers.

PURPOSE: To compare the efficacy of CT-on-rails versus in-room CBCT for daily adaptive proton therapy. METHODS: We analyzed a cohort of ten head-and-neck patients with daily CBCT and corresponding virtual CT images. The necessity of moving the patient after a CT scan is the most significant difference in the adaptation workflow, leading to an increased treatment execution uncertainty σ. It is a combination of the isocenter-matching σi and random patient movements induced by the couch motion σm. The former is assumed to never exceed 1 mm. For the latter, we studied three different scenarios with σm = 1, 2, and 3 mm. Accordingly, to mimic the adaptation workflow with CT-on-rails, we introduced random offsets after Monte-Carlo-based adaptation but before delivery of the adapted plan. RESULTS: There were no significant differences in accumulated dose-volume histograms and dose distributions for σm = 1 and 2 mm. Offsets with σm = 3 mm resulted in underdosage to CTV and hot spots of considerable volume. CONCLUSION: Since σm typically does not exceed 2 mm for in-room CT, there is no clinically significant dosimetric difference between the two modalities for online adaptive therapy of head-and-neck patients. Therefore, in-room CT-on-rails can be considered a good alternative to CBCT for adaptive proton therapy.

Pre- and post-treatment image-based dosimetry in90Y-microsphere radioembolization using the TOPAS Monte Carlo toolkit.

Objective. To evaluate the pre-treatment and post-treatment imaging-based dosimetry of patients treated with 90Y-microspheres, including accurate estimations of dose to tumor, healthy liver and lung. To do so, the Monte Carlo (MC) TOPAS platform is in this work extended towards its utilization in radionuclide therapy.Approach. Five patients treated at the Massachusetts General Hospital were selected for this study. All patients had data for both pre-treatment SPECT-CT imaging using 99mTc-MAA as a surrogate of the 90Y-microspheres treatment and SPECT-CT imaging immediately after the 90Y activity administration. Pre- and post-treatment doses were computed with TOPAS using the SPECT images to localize the source positions and the CT images to account for tissue inhomoegeneities. We compared our results with analytical calculations following the voxel-based MIRD scheme.Main results. TOPAS results largely agreed with the MIRD-based calculations in soft tissue regions: the average difference in mean dose to the liver was 0.14 Gy GBq-1(2.6%). However, dose distributions in the lung differed considerably: absolute differences in mean doses to the lung ranged from 1.2 to 6.3 Gy GBq-1and relative differences from 153% to 231%. We also found large differences in the intra-hepatic dose distributions between pre- and post-treatment imaging, but only limited differences in the pulmonary dose.Significance. Doses to lung were found to be higher using TOPAS with respect to analytical calculations which may significantly underestimate dose to the lung, suggesting the use of MC methods for 90Y dosimetry. According to our results, pre-treatment imaging may still be representative of dose to lung in these treatments.

Throughput of an IEEE 802.11 Wireless Network in the Presence of Wireless Audio Transmission: A Laboratory Analysis.

Wireless networks, including IEEE 802.11-based or Wi-Fi networks, are inexpensive and easy to install and therefore serve as useful connectivity alternatives in areas lacking wired-network infrastructure. However, IEEE 802.11 networks may not always provide the seamless connectivity and minimal throughput required for Industry 4.0 communications because of their susceptibility to interference from other devices operating in the unlicensed "Industrial, Scientific, and Medical" frequency band. Here we analyzed how a wireless audio transmitter operating on this band influences the throughput of an IEEE 802.11 b/g/n network under laboratory conditions. Wireless audio transmission reduced mean throughput by 85%, rendering the IEEE 802.11 b/g/n network nearly unusable. Our analysis suggests that in order for IEEE 802.11 wireless networks to support Industrial 4.0 applications, attention should be paid to the physical layer as well as the data or upper layers, and critical services should not transmit on the 2.4 GHz band. These findings may contribute to understanding and managing IEEE 802.11 wireless networks in various Industry 4.0 contexts.

Anatomic changes in head and neck intensity-modulated proton therapy: Comparison between robust optimization and online adaptation.

BACKGROUND/PURPOSE: Setup variations and anatomical changes can severely affect the quality of head and neck intensity-modulated proton therapy (IMPT) treatments. The impact of these changes can be alleviated by increasing the plan's robustness a priori, or by adapting the plan online. This work compares these approaches in the context of head and neck IMPT. MATERIALS/METHODS: A representative cohort of 10 head and neck squamous cell carcinoma (HNSCC) patients with daily cone-beam computed tomography (CBCT) was evaluated. For each patient, three IMPT plans were created: 1- a classical robust optimization (cRO) plan optimized on the planning CT, 2- an anatomical robust optimization (aRO) plan additionally including the two first daily CBCTs and 3- a plan optimized without robustness constraints, but online-adapted (OA) daily, using a constrained spot intensity re-optimization technique only. RESULTS: The cumulative dose following OA fulfilled the clinical objective of both the high-risk and low-risk clinical target volumes (CTV) coverage in all 10 patients, compared to 8 for aRO and 4 for cRO. aRO did not significantly increase the dose to most organs at risk compared to cRO, although the integral dose was higher. OA significantly reduced the integral dose to healthy tissues compared to both robust methods, while providing equivalent or superior target coverage. CONCLUSION: Using a simple spot intensity re-optimization, daily OA can achieve superior target coverage and lower dose to organs at risk than robust optimization methods.

Comparison of weekly and daily online adaptation for head and neck intensity-modulated proton therapy.

The high conformality of intensity-modulated proton therapy (IMPT) dose distributions causes treatment plans to be sensitive to geometrical changes during the course of a fractionated treatment. This can be addressed using adaptive proton therapy (APT). One important question in APT is the frequency of adaptations performed during a fractionated treatment, which is related to the question whether plan adaptation has to be done online or offline. The purpose of this work is to investigate the impact of weekly and daily online IMPT plan adaptation on the treatment quality for head and neck patients. A cohort of ten head and neck patients with daily acquired cone-beam CT (CBCT) images was evaluated retrospectively. Dose tracking of the IMPT treatment was performed for three scenarios: base plan with no adaptation (BP), weekly online adaptation (OAW), and daily online adaptation (OAD). Both adaptation schemes used an in-house developed online APT workflow, performing Monte Carlo dose calculations on scatter-corrected CBCTs. IMPT plan adaptation was achieved by only tuning the weights of a subset of beamlets, based on deformable image registration from the planning CT to each CBCT. Although OADmitigated random delivery errors more effectively than OAWon a fraction per fraction basis, both OAWand OADachieved the clinical goals for all ten patients, while BP failed for six cases. In the high-risk CTV, accumulated values ofD98%ranged between 97.15% and 99.73% of the prescription dose for OAD, with a median of 98.07%. For OAW, values between 95.02% and 99.26% were obtained, with a median of 97.61% of the prescription dose. Otherwise, the dose to most organs at risk was similar for all three scenarios. Globally, our results suggest that OAWcould be used as an alternative approach to OADfor most patients in order to reduce the clinical workload.

Deep Learning model for markerless tracking in spinal SBRT.

Stereotactic Body Radiation Therapy (SBRT), alternatively termed Stereotactic ABlative Radiotherapy (SABR) or Stereotactic RadioSurgery (SRS), delivers high dose with a sub-millimeter accuracy. It requires meticulous precautions on positioning, as sharp dose gradients near critical neighboring structures (e.g. the spinal cord for spinal tumor treatment) are an important clinical objective to avoid complications such as radiation myelopathy, compression fractures, or radiculopathy. To allow for dose escalation within the target without compromising the dose to critical structures, proper immobilization needs to be combined with (internal) motion monitoring. Metallic fiducials, as applied in prostate, liver or pancreas treatments, are not suitable in clinical practice for spine SBRT. However, the latest advances in Deep Learning (DL) allow for fast localization of the vertebrae as landmarks. Acquiring projection images during treatment delivery allows for instant 2D position verification as well as sequential (delayed) 3D position verification when incorporated in a Digital TomoSynthesis (DTS) or Cone Beam Computed Tomography (CBCT). Upgrading to an instant 3D position verification system could be envisioned with a stereoscopic kilovoltage (kV) imaging setup. This paper describes a fast DL landmark detection model for vertebra (trained in-house) and evaluates its accuracy to detect 2D motion of the vertebrae with the help of projection images acquired during treatment. The introduced motion consists of both translational and rotational variations, which are detected by the DL model with a sub-millimeter accuracy.