Deep learning based linear energy transfer calculation for proton therapy.

Objective.This study aims to address the limitations of traditional methods for calculating linear energy transfer (LET), a critical component in assessing relative biological effectiveness (RBE). Currently, Monte Carlo (MC) simulation, the gold-standard for accuracy, is resource-intensive and slow for dose optimization, while the speedier analytical approximation has compromised accuracy. Our objective was to prototype a deep-learning-based model for calculating dose-averaged LET (LETd) using patient anatomy and dose-to-water (DW) data, facilitating real-time biological dose evaluation and LET optimization within proton treatment planning systems.Approach. 275 4-field prostate proton Stereotactic Body Radiotherapy plans were analyzed, rendering a total of 1100 fields. Those were randomly split into 880, 110, and 110 fields for training, validation, and testing. A 3D Cascaded UNet model, along with data processing and inference pipelines, was developed to generate patient-specific LETddistributions from CT images and DW. The accuracy of the LETdof the test dataset was evaluated against MC-generated ground truth through voxel-based mean absolute error (MAE) and gamma analysis.Main results.The proposed model accurately inferred LETddistributions for each proton field in the test dataset. A single-field LETdcalculation took around 100 ms with trained models running on a NVidia A100 GPU. The selected model yielded an average MAE of 0.94 ± 0.14 MeV cm-1and a gamma passing rate of 97.4% ± 1.3% when applied to the test dataset, with the largest discrepancy at the edge of fields where the dose gradient was the largest and counting statistics was the lowest.Significance.This study demonstrates that deep-learning-based models can efficiently calculate LETdwith high accuracy as a fast-forward approach. The model shows great potential to be utilized for optimizing the RBE of proton treatment plans. Future efforts will focus on enhancing the model's performance and evaluating its adaptability to different clinical scenarios.

Optimizing Gantry Breakpoint Angles in Proton Therapy: Enhancing Efficiency and Patient Experience.

Purpose: The breakpoint for a 360° radiotherapy gantry is typically positioned at 180°. This arbitrary setting has not been systematically evaluated for efficiency and may cause redundant gantry rotation and extended setup times. Our study aimed to identify an optimal gantry breakpoint angle for a full-gantry proton therapy system, with the goal of minimizing gantry movement. Materials and Methods: We analyzed 70 months of clinically delivered proton therapy plans (9152 plans, 131 883 fractions), categorizing them by treatment site and mapping the fields from a partial-gantry to full-gantry orientation. For each delivered fraction, we computed the minimum total gantry rotation angle as a function of gantry breakpoint position, which was varied between 0° and 360° in 1° steps. This analysis was performed separately within the entire plan cohort and individual treatment sites, both with and without the capability of over-rotating 10° past the breakpoint from either direction (20° overlap). The optimal gantry breakpoint was identified as one which resulted in a low average gantry rotation per fraction. Results: Considering mechanical constraints, 130° was identified as a reasonable balance between increased gantry-rotation efficiency and practical treatment considerations. With a 20° overlap, this selection reduced the average gantry rotation by 41.4° per fraction when compared to the standard 180° breakpoint. Disease site subgroups showed the following reduction in average gantry rotation: gastrointestinal 192.2°, thoracic 56.3°, pediatric 44.9°, genitourinary 19.9°, central nervous system 10.7°, breast 2.8°, and head and neck 0.1°. Conclusion: For a full-gantry system, a breakpoint of 130° generally outperforms the conventional 180° breakpoint. This reduction is particularly impactful for gastrointestinal, pediatric, and thoracic sites, which constitute a significant proportion of cases at our center. The adjusted breakpoint could potentially streamline patient delivery, alleviate mechanical wear, and enhance treatment precision by reducing the likelihood of patient movement during delivery.

Rotating Gantries Provide Individualized Beam Arrangements for Charged Particle Therapy.

PURPOSE: This study evaluates beam angles used to generate highly individualized proton therapy treatment plans for patients eligible for carbon ion radiotherapy (CIRT). METHODS AND MATERIALS: We retrospectively evaluated patients treated with pencil beam scanning intensity modulated proton therapy from 2015 to 2020 who had indications for CIRT. Patients were treated with a 190° rotating gantry with a robotic patient positioning system. Treatment plans were individualized to provide maximal prescription dose delivery to the tumor target volume while sparing organs at risk. The utilized beam angles were grouped, and anatomic sites with at least 10 different beam angles were sorted into histograms. RESULTS: A total of 467 patients with 484 plans and 1196 unique beam angles were evaluated and characterized by anatomic treatment site and the number of beam angles utilized. The most common beam angles used were 0° and 180°. A wide range of beam angles were used in treating almost all anatomic sites. Only esophageal cancers had a predominantly unimodal grouping of beam angles. Pancreas cancers showed a modest grouping of beam angles. CONCLUSIONS: The wide distribution of beam angles used to treat CIRT-eligible patients suggests that a rotating gantry is optimal to provide highly individualized beam arrangements.

Proton Whole-Lung Irradiation: Initial Report of Outcomes.

PURPOSE: Whole-lung irradiation is typically used in pediatric patients to decrease the risk of future lung metastases, but radiation dose to normal tissue is associated with long-term risks. Proton whole-lung irradiation (PWLI) provides an opportunity to decrease radiation dose to normal tissue and potentially decrease late toxicity. METHODS AND MATERIALS: This retrospective study included patients treated with spot-scanning PWLI at a single institution. Toxicity and oncologic outcomes were reviewed. Intensity modulated radiation therapy (IMRT) plans were created prospectively or retrospectively for dosimetric comparisons. Simple paired t tests were performed to assess differences between IMRT and PWLI dosimetric parameters. RESULTS: Twelve patients treated with PWLI were included in this study. Median age was 15 years (range, 3-34). Most (75%) had Ewing sarcoma. Most (92%) received 15 Gy in 10 fractions PWLI, and 3 (25%) received a focal pulmonary boost. Median follow-up was 16.5 months (range, 0-40.4 months). At last follow-up, 1 patient died of disease, while 11 were still alive (7 without disease, 4 with ongoing disease). During and immediately after treatment, 5 patients developed fatigue, 2 patients developed cough, and 1 patient developed nausea. Each treatment-related adverse event was Common Terminology Criteria for Adverse Events (version 5.0) grade 1 and resolved within 3 weeks of treatment completion. No patients have experienced clinical or radiographic pneumonitis or evidence of clinically apparent cardiac toxicity. Compared with IMRT plans, PWLI decreased mean dose to the heart, coronary artery, cardiac valve, left ventricle, aorta, breast, esophagus, kidney, liver, pancreas, thyroid, stomach, and spleen (all P < .001), without sacrificing target coverage. CONCLUSIONS: PWLI is feasible to deliver, decreases dose to normal tissue compared with IMRT, and appears to be well-tolerated. PWLI provides potential for decreased late toxicity and merits further investigation.

New School Technology Meets Old School Technique: Intensity Modulated Proton Therapy and Laparoscopic Pelvic Sling Facilitate Safe and Efficacious Treatment of Pelvic Sarcoma.

Purpose: Small bowel tolerance may be dose-limiting in the management of some pelvic and abdominal malignancies with curative-intent radiation therapy. Multiple techniques previously have been attempted to exclude the small bowel from the radiation field, including the surgical insertion of an absorbable mesh to serve as a temporary pelvic sling. This case highlights a clinically meaningful application of this technique with modern radiation therapy. Methods and Materials: A patient with locally invasive, unresectable high-grade sarcoma of the right pelvic vasculature was evaluated for definitive radiation therapy. The tumor immediately abutted the small bowel. The patient underwent laparoscopic placement of a mesh sling to retract the abutting small bowel and subsequently completed intensity modulated proton therapy. Results: The patient tolerated the mesh insertion procedure and radiation therapy well with no significant toxic effects. The combination approach achieved excellent dose metrics, and the patient has no evidence of progression 14 months out from treatment. Conclusions: The combination of mesh as a pelvic sling and proton radiation therapy enabled the application of a curative dose of radiation therapy and should be considered for patients in need of curative-intent radiation when the bowel is in close proximity to the target.

Nuclear Fragmentation Imaging for Carbon-Ion Radiation Therapy Monitoring: an In Silico Study.

Purpose: This article presents an in vivo imaging technique based on nuclear fragmentation of carbon ions in irradiated tissues for potential real-time monitoring of carbon-ion radiation therapy (CIRT) treatment delivery and quality assurance purposes in clinical settings. Materials and Methods: A proof-of-concept imaging and monitoring system (IMS) was devised to implement the technique. Monte Carlo simulations were performed for a prospective pencil-beam scanning CIRT nozzle. The development IMS benchmark considered a 5×5-cm2 pixelated charged-particle detector stack positioned downstream from a target phantom and list-mode data acquisition. The abundance and production origins, that is, vertices, of the detected fragments were studied. Fragment trajectories were approximated by straight lines and a beam back-projection algorithm was built to reconstruct the vertices. The spatial distribution of the vertices was then used to determine plan relevant markers. Results: The IMS technique was applied for a simulated CIRT case, a primary brain tumor. Four treatment plan monitoring markers were conclusively recovered: a depth dose distribution correlated profile, ion beam range, treatment target boundaries, and the beam spot position. Promising millimeter-scale (3-mm, ≤10% uncertainty) beam range and submillimeter (≤0.6-mm precision for shifts <3 cm) beam spot position verification accuracies were obtained for typical therapeutic energies between 150 and 290 MeV/u. Conclusions: This work demonstrated a viable online monitoring technique for CIRT treatment delivery. The method's strong advantage is that it requires few signal inputs (position and timing), which can be simultaneously acquired with readily available technology. Future investigations will probe the technique's applicability to motion-sensitive organ sites and patient tissue heterogeneities. In-beam measurements with candidate detector-acquisition systems are ultimately essential to validate the IMS benchmark performance and subsequent deployment in the clinic.

Intensity Modulated Proton Therapy for Hepatocellular Carcinoma: Initial Clinical Experience.

PURPOSE: Our purpose was to assess the safety and efficacy of intensity modulated proton therapy (IMPT) for the treatment of hepatocellular carcinoma (HCC). METHODS AND MATERIALS: A retrospective review was conducted on all patients who were treated with IMPT for HCC with curative intent from June 2015 to December 2018. All patients had fiducials placed before treatment. Inverse treatment planning used robust optimization with 2 to 3 beams. The majority of patients were treated in 15 fractions (n = 30, 81%, 52.5-67.5 Gy, relative biological effectiveness), whereas the remainder were treated in 5 fractions (n = 7, 19%, 37.5-50 Gy, relative biological effectiveness). Daily image guidance consisted of orthogonal kilovoltage x-rays and use of a 6° of freedom robotic couch. Outcomes (local control, progression free survival, and overall survival) were determined using Kaplan-Meier methods. RESULTS: Thirty-seven patients were included. The median follow-up for living patients was 21 months (Q1-Q3, 17-30 months). Pretreatment Child-Pugh score was A5-6 in 70% of patients and B7-9 in 30% of patients. Nineteen patients had prior liver directed therapy for HCC before IMPT. Eight patients (22%) required a replan during treatment, most commonly due to inadequate clinical target volume coverage. One patient (3%) experienced a grade 3 acute toxicity (pain) with no recorded grade 4 or 5 toxicities. An increase in Child-Pugh score by ≥ 2 within 3 months of treatment was observed in 6 patients (16%). At 1 year, local control was 94%, intrahepatic control was 54%, progression free survival was 35%, and overall survival was 78%. CONCLUSIONS: IMPT is safe and feasible for treatment of HCC.

Optimization of motion management parameters in a synchrotron-based spot scanning system.

PURPOSE: To quantify the effects of combining layer-based repainting and respiratory gating as a strategy to mitigate the dosimetric degradation caused by the interplay effect between a moving target and dynamic spot-scanning proton delivery. METHODS: An analytic routine modeled three-dimensional dose distributions of pencil-beam proton plans delivered to a moving target. Spot positions and weights were established for a single field to deliver 100 cGy to a static, 15-cm deep, 3-cm radius spherical clinical target volume with a 1-cm isotropic internal target volume expansion. The interplay effect was studied by modeling proton delivery from a clinical synchrotron-based spot scanning system and respiratory target motion, patterned from surrogate patient breathing traces. Motion both parallel and orthogonal to the beam scanning direction was investigated. Repainting was modeled using a layer-based technique. For each of 13 patient breathing traces, the dose from 20 distinct delivery schemes (combinations of four gate window amplitudes and five repainting techniques) was computed. Delivery strategies were inter-compared based on target coverage, dose homogeneity, high dose spillage, and delivery time. RESULTS: Notable degradation and variability in plan quality were observed for ungated delivery. Decreasing the gate window reduced this variability and improved plan quality at the expense of longer delivery times. Dose deviations were substantially greater for motion orthogonal to the scan direction when compared with parallel motion. Repainting coupled with gating was effective at partially restoring dosimetric coverage at only a fraction of the delivery time increase associated with very small gate windows alone. Trends for orthogonal motion were similar, but more complicated, due to the increased severity of the interplay. CONCLUSIONS: Layer-based repainting helps suppress the interplay effect from intra-gate motion, with only a modest penalty in delivery time. The magnitude of the improvement in target coverage is strongly influenced by individual patient breathing patterns and the tumor motion trajectory.

Clinical implementation of respiratory-gated spot-scanning proton therapy: An efficiency analysis of active motion management.

PURPOSE: The aim of this work is to describe the clinical implementation of respiratory-gated spot-scanning proton therapy (SSPT) for the treatment of thoracic and abdominal moving targets. The experience of our institution is summarized, from initial acceptance and commissioning tests to the development of standard clinical operating procedures for simulation, motion assessment, motion mitigation, treatment planning, and gated SSPT treatment delivery. MATERIALS AND METHODS: A custom respiratory gating interface incorporating the Real-Time Position Management System (RPM, Varian Medical Systems, Inc., Palo Alto, CA, USA) was developed in-house for our synchrotron-based delivery system. To assess gating performance, a motion phantom and radiochromic films were used to compare gated vs nongated delivery. Site-specific treatment planning protocols and conservative motion cutoffs were developed, allowing for free-breathing (FB), breath-holding (BH), or phase-gating (Ph-G). Room usage efficiency of BH and Ph-G treatments was retrospectively evaluated using beam delivery data retrieved from our record and verify system and DICOM files from patient-specific quality assurance (QA) procedures. RESULTS: More than 70 patients were treated using active motion management between the launch of our motion mitigation program in October 2015 and the end date of data collection of this study in January 2018. During acceptance procedures, we found that overall system latency is clinically-suitable for Ph-G. Regarding room usage efficiency, the average number of energy layers delivered per minute was <10 for Ph-G, 10-15 for BH and ≥15 for FB, making Ph-G the slowest treatment modality. When comparing to continuous delivery measured during pretreatment QA procedures, the median values of BH treatment time were extended from 6.6 to 9.3 min (+48%). Ph-G treatments were extended from 7.3 to 13.0 min (+82%). CONCLUSIONS: Active motion management has been crucial to the overall success of our SSPT program. Nevertheless, our conservative approach has come with an efficiency cost that is more noticeable in Ph-G treatments and should be considered in decision-making.

Automation of routine elements for spot-scanning proton patient-specific quality assurance.

PURPOSE: At our institution, all proton patient plans undergo patient-specific quality assurance (PSQA) prior to treatment delivery. For intensity-modulated proton beam therapy, quality assurance is complex and time consuming, and it may involve multiple measurements per field. We reviewed our PSQA workflow and identified the steps that could be automated and developed solutions to improve efficiency. METHODS: We used the treatment planning system's (TPS) capability to support C# scripts to develop an Eclipse scripting application programming interface (ESAPI) script and automate the preparation of the verification phantom plan for measurements. A local area network (LAN) connection between our measurement equipment and shared database was established to facilitate equipment control, measurement data transfer, and storage. To improve the analysis of the measurement data, a Python script was developed to automatically perform a 2D-3D γ-index analysis comparing measurements in the plane of a two-dimensional detector array with TPS predictions in a water phantom for each acquired measurement. RESULTS: Device connection via LAN granted immediate access to the plan and measurement information for downstream analysis using an online software suite. Automated scripts applied to verification plans reduced time from preparation steps by at least 50%; time reduction from automating γ-index analysis was even more pronounced, dropping by a factor of 10. On average, we observed an overall time savings of 55% in completion of the PSQA per patient plan. CONCLUSIONS: The automation of the routine tasks in the PSQA workflow significantly reduced the time required per patient, reduced user fatigue, and frees up system users from routine and repetitive workflow steps allowing increased focus on evaluating key quality metrics.

A Monte-Carlo-based and GPU-accelerated 4D-dose calculator for a pencil beam scanning proton therapy system.

PURPOSE: The presence of respiratory motion during radiation treatment leads to degradation of the expected dose distribution, both for target coverage and healthy tissue sparing, particularly for techniques like pencil beam scanning proton therapy which have dynamic delivery systems. While tools exist to estimate this degraded four-dimensional (4D) dose, they typically have one or more deficiencies such as not including the particular effects from a dynamic delivery, using analytical dose calculations, and/or using nonphysical dose-accumulation methods. This work presents a clinically useful 4D-dose calculator that addresses each of these shortcomings. METHODS: To quickly compute the 4D dose, the three main tasks of the calculator were run on graphics processing units (GPUs). These tasks were (a) simulating the delivery of the plan using measured delivery parameters to distribute the plan amongst 4DCT phases characterizing the patient breathing, (b) using an in-house Monte Carlo simulation (MC) dose calculator to determine the dose delivered to each breathing phase, and (c) accumulating the doses from the various breathing phases onto a single phase for evaluation. The accumulation was performed by individually transferring the energy and mass of dose-grid subvoxels, a technique that models the transfer of dose in a more physically realistic manner. The calculator was run on three test cases, with lung, esophagus, and liver targets, respectively, to assess the various uncertainties in the beam delivery simulation as well as to characterize the dose-accumulation technique. RESULTS: Four-dimensional doses were successfully computed for the three test cases with computation times ranging from 4-6 min on a server with eight NVIDIA Titan X graphics cards; the most time-consuming component was the MC dose engine. The subvoxel-based dose-accumulation technique produced stable 4D-dose distributions at subvoxel scales of 0.5-1.0 mm without impairing the total computation time. The uncertainties in the beam delivery simulation led to moderate variations of the dose-volume histograms for these cases; the variations were reduced by implementing repainting or phase-gating motion mitigation techniques in the calculator. CONCLUSIONS: A MC-based and GPU-accelerated 4D-dose calculator was developed to estimate the effects of respiratory motion on pencil beam scanning proton therapy treatments. After future validation, the calculator could be used to assess treatment plans and its quick runtime would make it easily usable in a future 4D-robust optimization system.

Investigating the dosimetric impact of seed location uncertainties in Collaborative Ocular Melanoma Study-based eye plaques.

PURPOSE: To quantify the dosimetric effects of random and systematic seed position uncertainties in Collaborative Ocular Melanoma Study-based eye plaques. METHODS AND MATERIALS: An eye plaque dose calculation routine was created using Task Group 43 formalism. A variety of clinical configurations were simulated, including two seed models: (125)I and (103)Pd, three eye plaque sizes, and eight plaque/eye orientations. Dose was calculated at four ocular anatomic sites and three central axis plaque depths. Random seed positional uncertainty was modeled by adding Gaussian random displacements, in one of three seed-motion degrees of freedom, to each seed's nominal coordinate. Distributions of dosimetric outcomes were obtained and fitted after 10(6) randomizations. Similar analysis was performed for deterministic, systematic shifts of the plaque along the eye surface and radially from the globe center. RESULTS: Random seed placement uncertainties of 0.2-mm root mean square (RMS) (amplitude) produce dose changes that are typically <4% for each degree of freedom (95% confidence interval). Systematic seed placement uncertainties are generally greater than random uncertainty 95% confidence intervals (factor of 0.72-2.15), with the relative magnitudes depending on plaque size and location of interest. Eye plaque dosimetry is most sensitive to seed movement toward the center of the eye. Dosimetric uncertainty also increases with increasing dose gradients, which are typically greatest near the inner sclera, with smaller plaques, and with lower energy radionuclides (e.g., (103)Pd). CONCLUSIONS: Dosimetric uncertainties due to the random seed positional displacements anticipated in the clinic are expected to be <4% for each degree of freedom in most circumstances.

Stereotactic body radiotherapy for primary and metastatic liver tumors - the Mayo Clinic experience.

INTRODUCTION: To better understand the efficacy of liver SBRT we reviewed our prospectively collected institutional SBRT database. METHODS: Between May 2008 and March 2013, 80 patients with 104 liver lesions received SBRT. The Kaplan-Meier method estimated local control (LC), overall survival (OS). Cox proportional hazards regression models identified factors associated with LC and OS. RESULTS: The median follow-up for living patients was 38.6 months. Patients had primary (n=17) or metastatic (n=63) tumors. The median tumor size was 2.7 cm (range, 0.6-14.0). The 1 and 4 year rates of LC were 89.4% and 88%, respectively. Colorectal (CRC) metastasis was associated with lower rates of LC (p=0.013). OS at 1 and 4 years was 78% and 25%, respectively. Patients with CRC metastases had higher rates of OS (p=0.03). The occurrence of severe acute and late toxicity was 3.8% and 6.3%, respectively. CONCLUSIONS: SBRT should be studied in prospective clinical trials compared with other liver-directed treatment modalities.