A comprehensive pre-clinical treatment quality assurance program using unique spot patterns for proton pencil beam scanning FLASH radiotherapy.

BACKGROUND: Quality assurance (QA) for ultra-high dose rate (UHDR) irradiation is a crucial aspect in the emerging field of FLASH radiotherapy (FLASH-RT). This innovative treatment approach delivers radiation at UHDR, demanding careful adoption of QA protocols and procedures. A comprehensive understanding of beam properties and dosimetry consistency is vital to ensure the safe and effective delivery of FLASH-RT. PURPOSE: To develop a comprehensive pre-treatment QA program for cyclotron-based proton pencil beam scanning (PBS) FLASH-RT. Establish appropriate tolerances for QA items based on this study's outcomes and TG-224 recommendations. METHODS: A 250 MeV proton spot pattern was designed and implemented using UHDR with a 215nA nozzle beam current. The QA pattern that covers a central uniform field area, various spot spacings, spot delivery modes and scanning directions, and enabling the assessment of absolute, relative and temporal dosimetry QA parameters. A strip ionization chamber array (SICA) and an Advanced Markus chamber were utilized in conjunction with a 2 cm polyethylene slab and a range (R80) verification wedge. The data have been monitored for over 3 months. RESULTS: The relative dosimetries were compliant with TG-224. The variations of temporal dosimetry for scanning speed, spot dwell time, and spot transition time were within ± 1 mm/ms, ± 0.2 ms, and ± 0.2 ms, respectively. While the beam-to-beam absolute output on the same day reached up to 2.14%, the day-to-day variation was as high as 9.69%. High correlation between the absolute dose and dose rate fluctuations were identified. The dose rate of the central 5 × 5 cm2 field exhibited variations within 5% of the baseline value (155 Gy/s) during an experimental session. CONCLUSIONS: A comprehensive QA program for FLASH-RT was developed and effectively assesses the performance of a UHDR delivery system. Establishing tolerances to unify standards and offering direction for future advancements in the evolving FLASH-RT field.

Proton pencil beam scanning craniospinal irradiation (CSI) with a single posterior brain beam: Dosimetry and efficiency.

This study explores the feasibility and potential dosimetric and time efficiency benefit of proton Pencil Beam Scanning (PBS) craniospinal irradiation with a single posterior-anterior (SPA) brain field. The SPA approach was compared to our current clinical protocol using Bilateral Posterior Oblique brain fields (BPO). Ten consecutive patients were simulated in the head-first supine position on a long BOS frame and scanned using 3 mm CT slice thickness. A customized thermoplastic mask immobilized the patient's head, neck, and shoulders. A vac-lock was used to secure the legs. PBS proton plans were robustly optimized with 3mm setup errors and 3.5% range uncertainties in the Eclipse V15.6 treatment planning system (n = 12 scenarios). In order to achieve a smooth gradient dose match at the junction area, at least 5 cm overlap region was maintained between the segments and 5 mm uncertainty along the cranial-cauda direction was applied to each segment independently as additional robust optimization scenarios. The brain doses were planned by SPA or BPO fields. All spine segments were planned with a single PA field. Dosimetric differences between the BPO and SPA approaches were compared, and the treatment efficiency was analyzed according to timestamps of beam delivery. Results: The maximum brain dose increases to 111.1 ± 2.1% for SPA vs. 109.0 ± 1.7% for BPO (p < 0.01). The dose homogeneity index (D5/D95) in brain CTV was comparable between techniques (1.037 ± 0.010 for SPA and 1.033 ± 0.008 for BPO). Lens received lower maximum doses by 2.88 ± 1.58 Gy (RBE) (left) and 2.23 ± 1.37 Gy (RBE) (right) in the SPA plans (p < 0.01). No significant cochlea dose change was observed. SPA reduced the treatment time by more than 4 minutes on average and ranged from 2 to 10 minutes, depending on the beam waiting and allocation time. SPA is dosimetrically comparable to BPO, with reduced lens doses at the cost of slightly higher dose inhomogeneity and hot spots. Implementation of SPA is feasible and can help to improve the treatment efficiency of PBS CSI treatment.

Comparative Evaluation of Proton Therapy and Volumetric Modulated Arc Therapy for Brachial Plexus Sparing in the Comprehensive Reirradiation of High-Risk Recurrent Breast Cancer.

Purpose: Recurrent or new primary breast cancer requiring comprehensive regional nodal irradiation after prior radiation therapy (RT) to the supraclavicular area and upper axilla is challenging due to cumulative brachial plexus (BP) dose tolerance. We assessed BP dose sparing achieved with pencil beam scanning proton therapy (PBS-PT) and photon volumetric modulated arc therapy (VMAT). Methods and Materials: In an institutional review board-approved planning study, all patients with ipsilateral recurrent breast cancer treated with PBS-PT re-RT (PBT1) with at least partial BP overlap from prior photon RT were identified. Comparative VMAT plans (XRT1) using matched BP dose constraints were developed. A second pair of proton (PBT2) and VMAT (XRT2) plans using standardized target volumes were created, applying uniform prescription dose of 50.4 per 1.8 Gy and a maximum BP constraint <25 Gy. Incidence of brachial plexopathy was also assessed. Results: Ten consecutive patients were identified. Median time between RT courses was 48 months (15-276). Median first, second, and cumulative RT doses were 50.4 Gy (range, 42.6-60.0), 50.4 Gy relative biologic effectiveness (RBE) (45.0-64.4), and 102.4 Gy (RBE) (95.0-120.0), respectively. Median follow-up was 15 months (5-33) and 18 months for living patients (11-33) Mean BP max was 37.5 Gy (RBE) for PBT1 and 36.9 Gy for XRT1. Target volume coverage of V85% (volume receiving 85% of prescription dose), V90%, and V95% were numerically lower for XRT1 versus PBT1. Similarly, axilla I-III and supraclavicular area coverage were significantly higher for PBT2 than XRT2 at dose levels of V55%, V65%, V75%, V85%, and V95%. Only axilla I V55% did not reach significance (P = .06) favoring PBS-PT. Two patients with high cumulative BPmax (95.2 Gy [RBE], 101.6 Gy [RBE]) developed brachial plexopathy symptoms with ulnar nerve distribution neuropathy without pain or weakness (1 of 2 had symptom resolution after 6 months without intervention). Conclusions: PBS-PT improved BP sparing and target volume coverage versus VMAT. For patients requiring comprehensive re-RT for high-risk, nonmetastatic breast cancer recurrence with BP overlap and reasonable expectation for prolonged life expectancy, PBT may be the preferred treatment modality.

Case Report: Cumulative proton dose reconstruction using CBCT-based synthetic CT for interfraction metallic port variability in breast tissue expanders.

Introduction: Dose perturbation of spot-scanning proton beams passing through a dislocated metallic port (MP) of a breast tissue expander may degrade target dose coverage or deliver excess dose to the ipsilateral lung and heart. The feasibility of utilizing daily cone-beam computed tomography (CBCT)-based synthetic CTs (synCTs) for dose reconstruction was evaluated, and the fractional and cumulative dosimetric impact due to daily MP dislocation is reported. Methods: The synCT was generated by deforming the simulation CT to daily CBCT. The MP structure template was mapped onto all CTs on the basis of daily MP position. Proton treatment plans were generated with two and three fields on the planned CT (pCT, Plan A) and the first verification CT (vCT, Plan B), respectively, for a fractional dose of 1.8 Gy(RBE). Plan A and Plan B were used alternatively, as determined by the daily MP position. The reconstructed fractional doses were calculated with corresponding plans and synCTs, and the cumulative doses were summed with the rigid or deformed fractional doses on pCT and vCT. Results: The planned and reconstructed fractional dose demonstrated a low-dose socket around the planned MP position due to the use of field-specific targets (FSTs). Dose hot spots with >120% of the prescription due to MP dislocation were found behind the planned MP position on most reconstructed fractional doses. The reconstructed cumulative dose shows two low-dose sockets around the two planned MP positions reflecting the two plans used. The doses at the hot spots behind the planned MPs averaged out to 114% of the prescription. The cumulative D95% of the CTV_Chest Wall decreased by up to 2.4% and 4.0%, and the cumulative V20Gy(RBE) of the left lung decreased to 16.1% and 16.8% on pCT and vCT, respectively. The cumulative Dmean of the heart decreased to as low as 0.7 Gy(RBE) on pCT but increased to as high as 1.6 Gy(RBE) on vCT. Conclusion: The robustness of proton plans using FSTs around the magnet in the MP of the tissue expander can be improved by applying multiple fields and plans, which provides forgiveness of dose heterogeneity incurred from dislocation of high-Z materials in this single case.

Impact of respiratory motion on proton pencil beam scanning FLASH radiotherapy: anin silicoand phantom measurement study.

Objective. To investigate the effects of respiratory motion on the delivered dose in the context of proton pencil beam scanning (PBS) transmission FLASH radiotherapy (FLASH-RT) by simulation and phantom measurements.Approach. An in-house simulation code was employed to performin silicosimulation of 2D dose distributions for clinically relevant proton PBS transmission FLASH-RT treatments. A moving simulation grid was introduced to investigate the impacts of various respiratory motion and treatment delivery parameters on the dynamic PBS dose delivery. A strip-ionization chamber array detector and an IROC motion platform were employed to perform phantom measurements of the 2D dose distribution for treatment fields similar to those used for simulation.Main results. Clinically relevant respiratory motion and treatment delivery parameters resulted in degradation of the delivered dose compared to the static delivery as translation and distortion. Simulation showed that the gamma passing rates (2 mm/2% criterion) and target coverage could drop below 50% and 80%, respectively, for certain scenarios if no mitigation strategy was used. The gamma passing rates and target coverage could be restored to more than 95% and 98%, respectively, for short beams delivered at the maximal inhalation or exhalation phase. The simulation results were qualitatively confirmed in phantom measurements with the motion platform.Significance. Respiratory motion could cause dose quality degradation in a clinically relevant proton PBS transmission FLASH-RT treatment if no mitigation strategy is employed, or if an adequate margin is not given to the target. Besides breath-hold, gated delivery can be an alternative motion management strategy to ensure high consistency of the delivered dose while maintaining minimal dose to the surrounding normal tissues. To the best of our knowledge, this is the first study on motion impacts in the context of proton transmission FLASH radiotherapy.

The Applications and Pitfalls of Cone-Beam Computed Tomography-Based Synthetic Computed Tomography for Adaptive Evaluation in Pencil-Beam Scanning Proton Therapy.

PURPOSE: The study evaluates the efficacy of cone-beam computed tomography (CBCT)-based synthetic CTs (sCT) as a potential alternative to verification CT (vCT) for enhanced treatment monitoring and early adaptation in proton therapy. METHODS: Seven common treatment sites were studied. Two sets of sCT per case were generated: direct-deformed (DD) sCT and image-correction (IC) sCT. The image qualities and dosimetric impact of the sCT were compared to the same-day vCT. RESULTS: The sCT agreed with vCT in regions of homogeneous tissues such as the brain and breast; however, notable discrepancies were observed in the thorax and abdomen. The sCT outliers existed for DD sCT when there was an anatomy change and for IC sCT in low-density regions. The target coverage exhibited less than a 5% variance in most DD and IC sCT cases when compared to vCT. The Dmax of serial organ-at-risk (OAR) in sCT plans shows greater deviation from vCT than small-volume dose metrics (D0.1cc). The parallel OAR volumetric and mean doses remained consistent, with average deviations below 1.5%. CONCLUSION: The use of sCT enables precise treatment and prompt early adaptation for proton therapy. The quality assurance of sCT is mandatory in the early stage of clinical implementation.

Implementation of novel measurement-based patient-specific QA for pencil beam scanning proton FLASH radiotherapy.

BACKGROUND: Several studies have shown pencil beam scanning (PBS) proton therapy is a feasible and safe modality to deliver conformal and ultra-high dose rate (UHDR) FLASH radiation therapy. However, it would be challenging and burdensome to conduct the quality assurance (QA) of the dose rate along with conventional patient-specific QA (psQA). PURPOSE: To demonstrate a novel measurement-based psQA program for UHDR PBS proton transmission FLASH radiotherapy (FLASH-RT) using a high spatiotemporal resolution 2D strip ionization chamber array (SICA). METHODS: The SICA is a newly designed open-air strip-segmented parallel plate ionization chamber, which is capable of measuring spot position and profile through 2 mm-spacing-strip electrodes at a 20 kHz sampling rate (50 µs per event) and has been characterized to exhibit excellent dose and dose rate linearity under UHDR conditions. A SICA-based delivery log was collected for each irradiation containing the measured position, size, dwell time, and delivered MU for each planned spot. Such spot-level information was compared with the corresponding quantities in the treatment planning system (TPS). The dose and dose rate distributions were reconstructed on patient CT using the measured SICA log and compared to the planned values in volume histograms and 3D gamma analysis. Furthermore, the 2D dose and dose rate measurements were compared with the TPS calculations of the same depth. In addition, simulations using different machine-delivery uncertainties were performed, and QA tolerances were deduced. RESULTS: A transmission proton plan of 250 MeV for a lung lesion was planned and measured in a dedicated ProBeam research beamline (Varian Medical System) with a nozzle beam current between 100 to 215 nA. The worst gamma passing rates for dose and dose rate of the 2D SICA measurements (four fields) compared to TPS prediction (3%/3 mm criterion) were 96.6% and 98.8%, respectively, whereas the SICA-log reconstructed 3D dose distribution achieved a gamma passing rate of 99.1% (2%/2 mm criterion) compared to TPS. The deviations between SICA measured log, and TPS were within 0.3 ms for spot dwell time with a mean difference of 0.069 ± 0.11 s, within 0.2 mm for spot position with a mean difference of -0.016 ± 0.03 mm in the x-direction, and -0.036 ± 0.059 mm in the y-direction, and within 3% for delivered spot MUs. Volume histogram metric of dose (D95) and dose rate (V40Gy/s ) showed minimal differences, within less than 1%. CONCLUSIONS: This work is the first to describe and validate an all-in-one measurement-based psQA framework that can fulfill the goals of validating the dose rate accuracy in addition to dosimetric accuracy for proton PBS transmission FLASH-RT. The successful implementation of this novel QA program can provide future clinical practice with more confidence in the FLASH application.

Commissioning a 250 MeV research beamline for proton FLASH radiotherapy preclinical experiments.

BACKGROUND: The potential reduction of normal tissue toxicities during FLASH radiotherapy (FLASH-RT) has inspired many efforts to investigate its underlying mechanism and to translate it into the clinic. Such investigations require experimental platforms of FLASH-RT capabilities. PURPOSE: To commission and characterize a 250 MeV proton research beamline with a saturated nozzle monitor ionization chamber for proton FLASH-RT small animal experiments. METHODS: A 2D strip ionization chamber array (SICA) with high spatiotemporal resolution was used to measure spot dwell times under various beam currents and to quantify dose rates for various field sizes. An Advanced Markus chamber and a Faraday cup were irradiated with spot-scanned uniform fields and nozzle currents from 50 to 215 nA to investigate dose scaling relations. The SICA detector was set up upstream to establish a correlation between SICA signal and delivered dose at isocenter to serve as an in vivo dosimeter and monitor the delivered dose rate. Two off-the-shelf brass blocks were used as apertures to shape the dose laterally. Dose profiles in 2D were measured with an amorphous silicon detector array at a low current of 2 nA and validated with Gafchromic films EBT-XD at high currents of up to 215 nA. RESULTS: Spot dwell times become asymptotically constant as a function of the requested beam current at the nozzle of greater than 30 nA due to the saturation of monitor ionization chamber (MIC). With a saturated nozzle MIC, the delivered dose is always greater than the planned dose, but the desired dose can be achieved by scaling the MU of the field. The delivered doses exhibit excellent linearity with R 2 > 0.99 ${R^2} > 0.99$ with respect to MU, beam current, and the product of MU and beam current. If the total number of spots is less than 100 at a nozzle current of 215 nA, a field-averaged dose rate greater than 40 Gy/s can be achieved. The SICA-based in vivo dosimetry system achieved excellent estimates of the delivered dose with an average (maximum) deviation of 0.02 Gy (0.05 Gy) over a range of delivered doses from 3 to 44 Gy. Using brass aperture blocks reduced the 80%-20% penumbra by 64% from 7.55 to 2.75 mm. The 2D dose profiles measured by the Phoenix detector at 2 nA and the EBT-XD film at 215 nA showed great agreement, with a gamma passing rate of 95.99% using 1 mm/2% criterion. CONCLUSION: A 250 MeV proton research beamline was successfully commissioned and characterized. Challenges due to the saturated monitor ionization chamber were mitigated by scaling MU and using an in vivo dosimetry system. A simple aperture system was designed and validated to provide sharp dose fall-off for small animal experiments. This experience can serve as a foundation for other centers interested in implementing FLASH radiotherapy preclinical research, especially those equipped with a similar saturated MIC.

Use of single-energy proton pencil beam scanning Bragg peak for intensity-modulated proton therapy FLASH treatment planning in liver-hypofractionated radiation therapy.

PURPOSE: The transmission proton FLASH technique delivers high doses to the normal tissue distal to the target, which is less conformal compared to the Bragg peak technique. To investigate FLASH radiotherapy (RT) planning using single-energy Bragg peak beams with a similar beam arrangement as clinical intensity-modulated proton therapy (IMPT) in a liver stereotactic body radiation therapy (SBRT) and to characterize the plan quality, dose sparing of organs-at-risk (OARs), and FLASH dose rate percentage. MATERIALS AND METHODS: An in-house platform was developed to enable inverse IMPT-FLASH planning using single-energy Bragg peaks. A universal range shifter and range compensators were utilized to effectively align the Bragg peak to the distal edge of the target. Two different minimum MU settings of 400 and 800 MU/spot (Bragg-400 MU and Bragg-800 MU) plans were investigated on 10 consecutive hepatocellular carcinoma patients previously treated by IMPT-SBRT to evaluate the FLASH dose and dose rate coverage for OARs. The IMPT-FLASH using single-energy Bragg peaks delivered 50 Gy in five fractions with similar or identical beam arrangement to the clinical IMPT-SBRT plans. NRG GI003 dose constraint metrics were used. Three dose rate calculation methods, including average dose rate (ADR), dose threshold dose rate (DTDR), and dose-ADR (DADR), were all studied. RESULTS: The novel spot map optimization can fulfill the inverse planning using single-energy Bragg peaks. All the Bragg peak FLASH plans achieved similar results for the liver-gross tumor volume (GTV) Dmean and heart D 0.5 c m 3 ${D_{0.5\,{\rm{c}}{{\rm{m}}^3}}}$ , compared to SBRT-IMPT. The Bragg-800 MU plans resulted in 18.3% higher clinical target volume (CTV) D 2 c m 3 ${D_{2\,{\rm{c}}{{\rm{m}}^{\rm{3}}}}}$ compared with SBRT (p < 0.05), and no significant difference was found between Bragg-400 MU and SBRT plans. For the CTV Dmax , SBRT plans resulted in 10.3% (p < 0.01) less than Bragg-400 MU plans and 16.6% (p < 0.01) less than Bragg-800 MU plans. The Bragg-800 MU plans generally achieved higher ADR, DADR, and DTDR dose rates than Bragg-400 MU plans, and DADR mostly led to the highest V40 Gy/s compared to other dose rate calculation methods, whereas ADR led to the lowest. The lower dose rate portions in certain OARs are related to the lower dose deposited due to the farther distances from targets, especially in the penumbra of the beams. CONCLUSION: Single-energy Bragg peak IMPT-FLASH plans eliminate the exit dose in normal tissues, maintaining comparable dose metrics to the conventional IMPT-SBRT plans, while achieving a sufficient FLASH dose rate for liver cancers. This study demonstrates the feasibility of and sufficiently high dose rate when applying the Bragg peak FLASH treatment for a liver cancer hypofractionated FLASH therapy. The advancement of this novel method has the potential to optimize treatment for liver cancer patients.

A 2D strip ionization chamber array with high spatiotemporal resolution for proton pencil beam scanning FLASH radiotherapy.

PURPOSE: Experimental measurements of two-dimensional (2D) dose rate distributions in proton pencil beam scanning (PBS) FLASH radiation therapy (RT) are currently lacking. In this study, we characterize a newly designed 2D strip-segmented ionization chamber array (SICA) with high spatial and temporal resolution and demonstrate its applications in a modern proton PBS delivery system at both conventional and ultrahigh dose rates. METHODS: A dedicated research beamline of the Varian ProBeam system was employed to deliver a 250-MeV proton PBS beam with nozzle currents up to 215 nA. In the research and clinical beamlines, the spatial, temporal, and dosimetric performances of the SICA were characterized and compared with measurements using parallel-plate ion chambers (IBA PPC05 and PTW Advanced Markus chamber), a 2D scintillator camera (IBA Lynx), Gafchromic films (EBT-XD), and a Faraday cup. A novel reconstruction approach was proposed to enable the measurement of 2D dose and dose rate distributions using such a strip-type detector. RESULTS: The SICA demonstrated a position accuracy of 0.12 ± 0.02 mm at a 20-kHz sampling rate (50 µs per event) and a linearity of R2  > 0.99 for both dose and dose rate with nozzle beam currents ranging from 1 to 215 nA. The 2D dose comparison to the film measurement resulted in a gamma passing rate of 99.8% (2 mm/2%). A measurement-based proton PBS 2D FLASH dose rate distribution was compared to simulation results and showed a gamma passing rate of 97.3% (2 mm/2%). CONCLUSIONS: The newly designed SICA demonstrated excellent spatial, temporal, and dosimetric performances and is well suited for commissioning, quality assurance, and a wide range of clinical applications in proton PBS clinical and FLASH-RT.

Experience of micromultileaf collimator linear accelerator based single fraction stereotactic radiosurgery: tumor dose inhomogeneity, conformity, and dose fall off.

PURPOSE: Sharp dose fall off outside a tumor is essential for high dose single fraction stereotactic radiosurgery (SRS) plans. This study explores the relationship among tumor dose inhomogeneity, conformity, and dose fall off in normal tissues for micromultileaf collimator (mMLC) linear accelerator (LINAC) based cranial SRS plans. METHODS: Between January 2007 and July 2009, 65 patients with single cranial lesions were treated with LINAC-based SRS. Among them, tumors had maximum diameters < or = 20 mm: 31; between 20 and 30 mm: 21; and > 30 mm: 13. All patients were treated with 6 MV photons on a Trilogy linear accelerator (Varian Medical Systems, Palo Alto, CA) with a tertiary m3 high-resolution mMLC (Brainlab, Feldkirchen, Germany), using either noncoplanar conformal fixed fields or dynamic conformal arcs. The authors also created retrospective study plans with identical beam arrangement as the treated plan but with different tumor dose inhomogeneity by varying the beam margins around the planning target volume (PTV). All retrospective study plans were normalized so that the minimum PTV dose was the prescription dose (PD). Isocenter dose, mean PTV dose, RTOG conformity index (CI), RTOG homogeneity index (HI), dose gradient index R50-R100 (defined as the difference between equivalent sphere radius of 50% isodose volume and prescription isodose volume), and normal tissue volume (as a ratio to PTV volume) receiving 50% prescription dose (NTV50) were calculated. RESULTS: HI was inversely related to the beam margins around the PTV. CI had a "V" shaped relationship with HI, reaching a minimum when HI was approximately 1.3. Isocenter dose and mean PTV dose (as percentage of PD) increased linearly with HI. R50-R100 and NTV50 initially declined with HI and then reached a plateau when HI was approximately 1.3. These trends also held when tumors were grouped according to their maximum diameters. The smallest tumor group (maximum diameters < or = 20 mm) had the most HI dependence for dose fall off. For treated plans, CI averaged 2.55 +/- 0.79 with HI 1.23 +/- 0.06; the average R50-R100 was 0.41 +/- 0.08, 0.55 +/- 0.10, and 0.65 +/- 0.09 cm, respectively, for tumors < or = 20 mm, between 20 and 30 mm, and > 30 mm. CONCLUSIONS: Tumor dose inhomogeneity can be used as an important and convenient parameter to evaluate mMLC LINAC-based SRS plans. Sharp dose fall off in the normal tissue is achieved with sufficiently high tumor dose inhomogeneity. By adjusting beam margins, a homogeneity index of approximately 1.3 would provide best conformity for the authors' SRS system.

A Beam-Specific Optimization Target Volume for Stereotactic Proton Pencil Beam Scanning Therapy for Locally Advanced Pancreatic Cancer.

PURPOSE: We investigate two margin-based schemes for optimization target volumes (OTV), both isotropic expansion (2 mm) and beam-specific OTV, to account for uncertainties due to the setup errors and range uncertainties in pancreatic stereotactic pencil beam scanning (PBS) proton therapy. Also, as 2-mm being one of the extreme sizes of margin, we also study whether the plan quality of 2-mm uniform expansion could be comparable to other plan schemes. METHODS AND MATERIALS: We developed 2 schemes for OTV: (1) a uniform expansion of 2 mm (OTV2mm) for setup uncertainty and (2) a water equivalent thickness-based, beam-specific expansion (OTVWET) on beam direction and 2 mm expansion laterally. Six LAPC patients were planned with a prescribed dose of 33 Gy (RBE) in 5 fractions. Robustness optimization (RO) plans on gross tumor volumes, with setup uncertainties of 2 mm and range uncertainties of 3.5%, were implemented as a benchmark. RESULTS: All 3 optimization schemes achieved decent target coverage with no significant difference. The OTV2mm plans show superior organ at risk (OAR) sparing, especially for proximal duodenum. However, OTV2mm plans demonstrate severe susceptibility to range and setup uncertainties with a passing rate of 19% of the plans meeting the goal of 95% volume covered by the prescribed dose. The proposed dose spread function analysis shows no significant difference. CONCLUSIONS: The use of OTVWET mimics a union volume for all scenarios in robust optimization but saves optimization time noticeably. The beam-specific margin can be attractive to online adaptive stereotactic body proton therapy owing to the efficiency of the plan optimization.

Retrospective analysis of reduced energy switching and room switching times on throughput efficiency of a multi-room proton therapy center.

OBJECTIVE: To quantify how a control software upgrade changed beam delivery times and impacted efficiency and capacity of a multiroom proton therapy center. METHODS: A four-room center treating approximately 90 patients/day, treating for approximately 7 years with optimized operations, underwent a software upgrade which reduced room and energy switching times from approximately 30 to 20 s and approximately 4 s to ~0.5 s, respectively. The center uses radio-frequency identification data to track patient treatments and has software which links this to beam delivery data extracted from the treatment log server. Two 4-month periods, with comparable patient volume, representing periods before and after the software change, were retrospectively analyzed. RESULTS: A total of 16,168 and 17,102 fields were analyzed. For bilateral head and neck and prostate patients, the beam waiting time was reduced by nearly a factor of 3 and the beam delivery times were reduced by nearly a factor of 2.5. Room switching times were reduced more modestly. Gantry capacity has increased from approximately 30 patients to 40-45 patients in a 16-h daily operation. CONCLUSIONS: Many proton centers are striving for increased efficiencies. We demonstrated that reductions in energy and room switching time can significantly increase center capacity. Greater potential for further gains would come from improvements in setup and imaging efficiency. ADVANCES IN KNOWLEDGE: This paper provides detailed measured data on the effect on treatment times resulting from reducing energy and room switching times under controlled conditions. It helps validate the models of previous investigations to establish treatment capacity of a proton therapy center.

Dosimetric evaluation of MR-derived synthetic-CTs for MR-only proton treatment planning.

PURPOSE: To evaluate proton dose calculation accuracy of optimized pencil beam scanning (PBS) plans on MR-derived synthetic-CTs for prostate patients. MATERIAL AND METHODS: Ten patient datasets with both a CT and an MRI were planned with opposed lateral proton beams optimized to single field uniform dose under an IRB-approved study. The proton plans were created on CT datasets generated by a commercial synthetic CT-based software called MRCAT (MR for Calculating ATtenuation) routinely used in our clinic for photon-based MR-only planning. A standard prescription of 79.2 Gy (RBE) and 68.4 Gy (RBE) was used for intact prostate and prostate bed cases, respectively. Proton plans were first generated and optimized using the MRCAT synthetic-CT (syn-CT), and then recalculated on the planning CT rigidly aligned with the syn-CT (aligned-CT) and a deformed planning CT (deformed-CT), which was deformed to match outer contour between syn-CT and aligned-CT. The same beam arrangement, total MUs, MUs/spot, spot positions were used to recalculate dose on deformed-CT and aligned-CT without renormalization. DVH analysis was performed on aligned-CT, deformed-CT, and syn-CT to compare D98%, V100%, V95% for PTV, PTVeval, and GTV as well as V70Gy, V50Gy for OARs. RESULTS: The relative percentage dose difference between syn-CT and deformed-CT, were (0.17 ± 0.33 %) for PTVeval D98% and (0.07 ± 0.1 %) for CTV D98%. Rectum V70Gy, V50Gy, and Bladder V70Gy were (2.76 ± 4.01 %), (11.6 ± 11.2 %), and (3.41 ± 2.86 %), respectively for the syn-CT, and (3.23 ± 3.63 %), (11.3 ± 8.18 %), and (3.29 ± 2.76 %), respectively for the deformed-CT, and (1.37 ± 1.84 %), (8.48 ± 6.67 %), and (4.91 ± 3.65 %), respectively for aligned-CT. CONCLUSION: Dosimetric analysis shows that MR-only proton planning is feasible using syn-CT based on current clinical margins that account for a range uncertainty.

Image guidance in radiation oncology treatment planning: the role of imaging technologies on the planning process.

Radiation therapy has evolved from 2-dimensional (2D) to 3-dimensional (3D) treatments and, more recently, to intensity-modulated radiation therapy and image-guided radiation therapy. Improvements in imaging have enabled improvements in targeting and treatment. As computer-processing power has improved during the past few decades, it has facilitated developments in both imaging and treatment. The historical role of imaging from 2D to image-guided radiation therapy is reviewed here. Examples of imaging technologies such as positron emission tomography and magnetic resonance imaging are provided. The role of these imaging technologies, organ motion management approaches and their potential impacts on radiation therapy are described.

Monte Carlo calculation of the mass stopping power of EBT3 and EBT-XD films for protons for energy ranges of 50-400 MeV.

OBJECTIVE: The goal of the present study was to calculate the continuous slowing down approximation (CDSA) ranges and derive mass stopping power for EBT3 and EBT-XD films for therapeutic protons energy ranges of 50-400 MeV. METHODS: The MCNPX and TRansport of Ions in Matter (TRIM) Monte Carlo codes were used in this study. Utilizing the published International Commission on Radiation Units and Measurement 49 data for the water mass stopping power and CSDA ranges, the mass stopping powers of EBT3 and EBT-XD films were derived using the approximation proposed by Newhauser and Zhang in 2009. RESULTS: The calculated CSDA ranges by MCNPX and TRIM in water were first benchmarked to International Commission on Radiation Units and Measurement 49 published data for water, and found to be within 1% with a 1.4-mm maximum difference. The calculated CSDA values in EBT3 film, compared with the measured CSDA ranges in the EBT3 film, were within 2% of the calculated values with a 3-mm maximum difference. The MCNPX and TRIM results for CSDA ranges agreed with each other to within 2.7% for EBT3 film and 4.4% for EBT-XD film. The overall uncertainties of the MCNPX and TRIM-derived CSDA ranges were 3% and 1.3%, respectively. CONCLUSION: The mass stopping powers for Gafchromic EBT3 and EBT-XD films were derived.

Patient-Specific QA of Spot-Scanning Proton Beams using Radiochromic Film.

Radiochromic film for spot-scanning QA provides high spatial resolution and efficiency gains from one-shot irradiation for multiple depths. However, calibration can be a tedious procedure which may limit widespread use. Moreover, since there may be an energy dependence, which manifests as a depth dependence, this may require additional measurements for each patient. We present a one-scan protocol to simplify the procedure. A calibration using an EBT3 film, exposed by a 6-level step-wedge plan on a Proteus®PLUS proton system (IBA, Belgium), was performed at depths of 18, 20, 24cm using Plastic Water® (CIRS, Norfolk, VA). The calibration doses ranged from 65-250 cGy(RBE) (relative biological effectiveness) for proton energies of 170-200 MeV. A clinical prostate+nodes plan was used for validation. The planar doses at selected depths were measured with EBT3 films and analyzed using One-scan protocol (one-scan digitization of QA film and at least one film exposed to a known dose). The gamma passing rates, dose-difference maps, and profiles of 2D planar doses measured with EBT3 film and IBA MatriXX-PT, versus the RayStation TPS calculations were analyzed and compared. The EBT3 film measurement results matched well with the TPS calculation data with an average passing rate of ~95% for 2%/2mm and slightly lower passing rates were obtained from an ion chamber array detector. We were able to demonstrate that the use of a proton step-wedge provided clinically acceptable results and minimized variations between film-scanner orientation, inter-scan, and scanning conditions. Furthermore, for relative dosimetry (calibration is not done at the time of experiment) it could be derived from no more than two films exposed to known doses (one could be zero) for rescaling the master calibration curve at each depth. The sensitivity of the calibration to depth variations has been explored. One-scan protocol results appear to be comparable to that of the ion chamber array detector. The use of a proton step-wedge for calibration of EBT3 film potentially increases efficiency in patient-specific QA of proton beams.

Technical Note: Spot characteristic stability for proton pencil beam scanning.

PURPOSE: The spot characteristics for proton pencil beam scanning (PBS) were measured and analyzed over a 16 month period, which included one major site configuration update and six cyclotron interventions. The results provide a reference to establish the quality assurance (QA) frequency and tolerance for proton pencil beam scanning. METHODS: A simple treatment plan was generated to produce an asymmetric 9-spot pattern distributed throughout a field of 16 × 18 cm for each of 18 proton energies (100.0-226.0 MeV). The delivered fluence distribution in air was measured using a phosphor screen based CCD camera at three planes perpendicular to the beam line axis (x-ray imaging isocenter and up/down stream 15.0 cm). The measured fluence distributions for each energy were analyzed using in-house programs which calculated the spot sizes and positional deviations of the Gaussian shaped spots. RESULTS: Compared to the spot characteristic data installed into the treatment planning system, the 16-month averaged deviations of the measured spot sizes at the isocenter plane were 2.30% and 1.38% in the IEC gantry x and y directions, respectively. The maximum deviation was 12.87% while the minimum deviation was 0.003%, both at the upstream plane. After the collinearity of the proton and x-ray imaging system isocenters was optimized, the positional deviations of the spots were all within 1.5 mm for all three planes. During the site configuration update, spot positions were found to deviate by 6 mm until the tuning parameters file was properly restored. CONCLUSIONS: For this beam delivery system, it is recommended to perform a spot size and position check at least monthly and any time after a database update or cyclotron intervention occurs. A spot size deviation tolerance of <15% can be easily met with this delivery system. Deviations of spot positions were <2 mm at any plane up/down stream 15 cm from the isocenter.

Condensation of supersaturated n-butanol vapor on charged/neutral nanoparticles of D-mannose and L-rhamnose.

The effects of size, charge, and solubility on the condensation of supersaturated n-butanol vapor on monodisperse nanoparticles of D-mannose and L-rhamnose are investigated in a flow cloud chamber. The dependence of the critical supersaturation S(cr) on particle size in the range from 30 to 90 nm is determined experimentally. The results show that the experimental S(cr) decreases with increasing particle size and solubility, qualitatively in agreement with the prediction by the Volmer theory of nucleation on soluble particles and by the Kohler theory, but quantitatively smaller than both theoretical predictions. The condensation of supersaturated vapor on singly positive/negative charged particles with diameters of 30, 60, and 90 nm is examined, and no obvious charge effect and sign preference are observed.