Range Uncertainties Research Articles

Potential benefits of using radioactive ion beams for range margin reduction in carbon ion therapy

Sharp dose gradients and high biological effectiveness make ions such as 12C an ideal tool to treat deep-seated tumors, however, at the same time, sensitive to errors in the range prediction. Tumor safety margins mitigate these uncertainties, but during the irradiation they lead to unavoidable damage to the surrounding healthy tissue. To fully exploit the Bragg peak benefits, a large effort is put into establishing precise range verification methods. Despite positron emission tomography being widely in use for this purpose in 12C therapy, the low count rates, biological washout, and broad activity distribution still limit its precision. Instead, radioactive beams used directly for treatment would yield an improved signal and a closer match with the dose fall-off, potentially enabling precise in vivo beam range monitoring. We have performed a treatment planning study to estimate the possible impact of the reduced range uncertainties, enabled by radioactive 11C ions treatments, on sparing critical organs in tumor proximity. Compared to 12C treatments, (i) annihilation maps for 11C ions can reflect sub- millimeter shifts in dose distributions in the patient, (ii) outcomes of treatment planning with 11C significantly improve and (iii) less severe toxicities for serial and parallel critical organs can be expected.

JPSS-2 VIIRS Pre-Launch Reflective Solar Band Testing and Performance

The Visible Infrared Imaging Radiometer Suite (VIIRS) instruments on-board the Suomi National Polar-orbiting Partnership (S-NPP) and Joint Polar Satellite System (JPSS) spacecrafts 1 and 2 provides calibrated sensor data record (SDR) reflectance, radiance, and brightness temperatures for use in environment data record (EDR) products. The SDRs and EDRs are used in weather forecasting models, weather imagery and climate applications such as ocean color, sea surface temperature and active fires. The VIIRS has 22 bands covering a spectral range 0.4–12.4 µm with resolutions of 375 m and 750 m for imaging and moderate bands respectively on four focal planes. The bands are stratified into three different types based on the source of energy sensed by the bands. The reflective solar bands (RSBs) detect sunlight reflected from the Earth, thermal emissive bands (TEBs) sense emitted energy from the Earth and the day/night band (DNB) detects both solar and lunar reflected energy from the Earth. The SDR calibration uses a combination of pre-launch testing and the solar diffuser (SD), on-board calibrator blackbody (OBCBB) and space view (SV) on-orbit calibrator sources. The pre-launch testing transfers the National Institute of Standards and Technology (NIST) traceable calibration to the SD, for the RSB, and the OBCBB, for the TEB. Post-launch, the on-board calibrators track the changes in instrument response and adjust the SDR product as necessary to maintain the calibration. This paper will discuss the pre-launch radiometric calibration portion of the SDR calibration for the RSBs that includes the dynamic range, detector noise, calibration coefficients and radiometric uncertainties for JPSS-2 VIIRS.

Parameter range estimation and uncertainty analysis for high strain rate material response via model fusion

The dynamic stress–strain response of a material can be described by a number of different models of varying fidelity. However, an individual model’s ability to replicate the dynamic stress–strain response of a material can be hindered by experimental variability. Reification, an approach to fusing models and experimental data with inherent scatter, is presented. It is then used to determine the optimum parameters of the Johnson–Cook (JC) and Zerilli–Armstrong (ZA) models using a fusion of Split-Hopkinson Pressure Bar (SHPB) data and the JC and ZA models fit to the SHPB data using a traditional approach. The output of the fused model is a dataset that represents a “best-guess” sampling of the possible stress–strain response of a high strength steel. In the present work, the dynamic response of a newly developed steel, AF9628, is evaluated. Under the reification framework, the experimental variability and limitations of the mathematical model expressions are addressed by the optimized sampling of data and combined fitting process. The JC and ZA models are then re-fit to partitions of the fused dataset, which bound the responses of the traditionally fit JC and ZA models. The behavior of the re-fit models and the traditionally fit models are compared via a simulated Taylor anvil test.

Improvement of proton beam range uncertainty in breast treatment using tissue samples

Objective. Proton therapy after breast-conserving surgery (BCS) can substantially reduce the dose to lung and cardiac structures. However, these dosimetric benefits are subject to beam range uncertainty in patient. The conversion of the CT-Hounsfield unit (HU) into relative stopping power (RSP) is the primary contribution to range uncertainty. Hence, an accurate HU-RSP conversion is essential. Approach. Real tissue samples, including muscle and adipose, were prepared. The water equivalent path length (WEPL) of these samples was measured under homogeneous conditions using a 12-diode detector array of our time-resolved in vivo range verification system (IRVS). The HU-RSP conversion was improved using the measured WEPL and HU for adipose tissue. The measured WEPL values were compared with the treatment planning calculation results based on the stoichiometric CT-HU calibration technique. The effect was investigated for both with and without adipose tissue in HU-RSP conversion. Main results. The IRVS was calibrated based on the solid water phantom. The relative differences in WEPL (RSP) between measurements and calculations for muscle, adipose, and water was −1.19% (−0.75%), −4.25%(−4%), and −0.23%(−0.07%), respectively. Based on the improved HU-RSP conversion, the relative differences in WEPL was reduced to −0.97%(−0.62%), −1.50%(−1.46%), and −0.22% (0.00%), respectively. Significance. The WEPL deviation of adipose tissue is larger than the testing limit of 3.5% for beam range robustness in current clinical practice. However, the improved HU-RSP conversion reduced this deviation. The main component of breast tissue is adipose. Hence, the proton treatment of BCS can be undershooting if no proper measures are taken against this specific uncertainty.

Carbon-Ion Therapy Patient-Specific QA: Preliminary Results Derived Using 3D Polymer Gel Dosimetry in Anthropomorphic Inhomogeneous Geometry

<h3>Purpose/Objective(s)</h3> Improved conformity in carbon-ion radiation therapy (CIRT) with respect to photon RT comes at the cost of a potential reduced delivery robustness due to patient setup uncertainties, approximations in dose calculations and carbon-ion range uncertainties. This work presents preliminary results of a study aiming to address these challenges using 3D polymer gel dosimetry in anthropomorphic and inhomogeneous geometry. <h3>Materials/Methods</h3> All irradiations were performed at a synchrotron facility, in one of the treatment rooms equipped with a horizontal fixed beam line and pencil beam scanning (PBS) modality. For basic dosimetric characterization, carbon pristine Bragg peaks (BP) (ranges 30, 70, 90 mm in water) and a spread-out BP (SOBP) (range 115 mm and modulation 40 mm) were delivered on a cylindrical PMMA container filled with VIPAR polymer gel. An anthropomorphic phantom equipped with a cylindrical polymer gel insert was used for the irradiation of a pseudo-clinical CIRT plan, following all the steps of the standard clinical workflow, from simulation CT to irradiation. Two contralateral beams were optimized with a TPS (v.8b) to deliver 15 Gy (RBE) on a target located approximately at the center of the brain, in proximity of critical OARs such as brainstem and optical pathways. The phantom was then MRI scanned post-irradiation to retrieve the irradiated brain volume in 3D. The measured irradiated volume was compared against corresponding TPS derived data. <h3>Results</h3> Carbon-ion range was spatially verified with an accuracy of < 1 mm. For both the pristine BP and the SOBP irradiations. A significant deviation of the polymer gels' response on high-LET has been observed, as expected from previous studies with proton irradiations. For the pseudo-clinical treatment plan, a qualitative comparison between doses measured in polymer gels, against the corresponding TPS calculations, revealed a satisfying geometric accuracy of dose delivery in 3D, thus showing a high 3D geometrical accuracy of dose delivery in a typical standard clinical workflow. <h3>Conclusion</h3> In this work, we showed that patient-specific 3D polymer gel dosimetry is applicable to CIRT, as a valid tool to evaluate dosimetric and spatial plan accuracy in the clinical environment. As expected, the LET dependence of polymer gel's response, especially in the high-LET region, poses severe limitations for accurate dose measurements. Nevertheless, the proposed methodology is a promising efficient and safe clinical way for verifying such a complex RT technique.

Can Proton Linear Accelerator Beams and Minibeams Achieve Superior Plan Quality over Cyclotron-Generated Proton Beams and Photons in the Treatment of Multiple Brain Metastases?

<h3>Purpose/Objective(s)</h3> To compare plan quality and delivery timing among photon Volumetric Arc Therapy (VMAT), Intensity-Modulated Proton Therapy using cyclotron-generated proton beams (CPB), linear accelerator proton beams (LPB), and linear accelerator proton minibeams (LPMB). <h3>Materials/Methods</h3> Thirty-five brain lesions from twenty patients were planned using CPBs and compared against LPBs and LPMBs and VMAT. All proton plans were optimized with multi-field optimization technique using the Monte Carlo algorithm. Benchmarked on the photon plans, dose coverage to each lesion for each proton plan was set to 99% of the GTV receiving the prescription (Rx) dose for all plans. Conformity index (CI), gradient index (GI), V_12Gy, V_4.5Gy and mean dose of the brain were compared. To achieve similar PTV dose coverage to photons, ±2 mm setup uncertainty and ±2% range uncertainty were included in robust evaluation using V_100%Rx > 95% of the GTV for proton plans. Additionally, the plan delivery timing was assessed based on the proton modalities' energy switching and spot scanning times. <h3>Results</h3> All metrics of CI, GI, V_12Gy, V_4.5Gy, and mean brain dose for VMAT photon and three different proton plans are listed in Table 1. When compared to CPB generated plans, CI and GI were significantly better for the LPB and LPMB plans with a mean CI of 1.7 ± 0.5, 1.57 ± 0.4, and 1.4 ± 0.6 and a mean GI of 4.64 ± 1.48, 3.7 ± 1.1 and 2.8 ± 0.7, respectively. In comparison, mean CI and GI from photon VMAT plans were 2 ± 1.2, 4.7 ± 1.4. All proton plans achieved better V_4.5Gy than photon VMAT plans. LPBs reduced the mean brain dose by 17% compared to the CPB plans, and LPMB plans reduced the mean brain dose by 44%. While all plans had V_100%Rx of the GTV > 99% in the nominal scenario, in the voxel-wise worst scenario, 97.1%, 92.8% and 84.2% of the lesions had V_100%Rx > 95% for CPB, LPB, and LPMB, respectively, and in the worst-case scenario, 97.1%, 94.3% and 78.6% of the plans showed V_100%Rx > 95% among all lesions. The LPB energy switching time (5 ms) enables a rapid beam delivery, 58% faster on average than for CPB plans. LPMB beam delivery time can be further reduced by spot reduction planning (SRP) with equal plan quality. <h3>Conclusion</h3> We successfully quantified plan quality and evaluated robustness for CPBs, LPBs and LPMBs for brain metastases. The LPB and LPMB stand as an excellent alternative to CPB therapy and can significantly increase the preservation of normal tissue while ensuring fast delivery time.

Ultrahypofractionated Adjuvant Proton Therapy for Localized Stage Breast Cancer: Early Toxicity Report

<h3>Purpose/Objective(s)</h3> To report early toxicity and dosimetry data in breast cancer patients treated with ultrahypofractionated proton therapy (Ultra-HF-PT). <h3>Materials/Methods</h3> Patients with localized breast cancer (Tis-T2, N0) who required postoperative whole-breast radiotherapy were eligible. The prescribed dose was 26 Gy in 5 daily fractions ± single fraction 5,2 Gy boost. Treatment planning was performed with 1 or 2 anterior fields (0°±40°) using multi-field optimization. Robust optimization was performed on the CTV structure with a 3- mm setup uncertainty and a 3.5% range uncertainty. For 69% of patients with left-sided cancer deep inspiration breath hold technique (DIBH) was used. The target coverage was defined as V_100%>98% (>98% of volume receiving 100% of the prescribed dose). Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3-month intervals thereafter. Toxicity was scored using CTCAE ver. 5.0. <h3>Results</h3> From July 2020 to November 2021, 63 patients were treated with intensity-modulated proton therapy. Median follow-up was 9 months (2 to 18). During radiotherapy Grade 1 and 2 dermatitis occurred in 45 (71%) and 4 (6%) patients respectively. After the end of treatment Grade 1 or 2 dermatitis occurred in all patients, resolving in 4 weeks. Mean dose to the left anterior descending coronary artery (LAD) was 1,28 Gy (0,12-8,2) for left-sided breast cancer patients. Mean ipsilateral lung dose was 2,66 Gy (0,55-5,8). Compared to free breathing DIBH significantly reduced mean dose to the heart (0,4 to 0,1 Gy, p=0,03) and LAD (2,5 to 1,2 Gy, p=0,03) in patients with left-sided cancer. <h3>Conclusion</h3> Limited data exists demonstrating the clinical benefit of proton radiotherapy (PRT) in breast cancer. This study is the first report of clinical data for Ultra-HF-PT in patients with localized breast cancer. Treatment was well tolerated, with acceptable rates of skin toxicity, providing low dose to normal tissue without compromising target coverage. Dose reduction to organs at risk might translate into the reduction of late toxicities.

Verification Studies Confirm Reproducibility of Post-Hysterectomy Pelvic Proton Radiotherapy

<h3>Purpose/Objective(s)</h3> Post-hysterectomy radiotherapy (RT) is associated with urinary, gastrointestinal, and hematologic toxicity. Concern for organ and target motion has limited exploration of proton RT as a tool to reduce toxicity. Attention to planning and treatment delivery is paramount given sensitivity of protons to small changes in soft tissue in the beam path. We sought to evaluate the consistency of target coverage and organ at risk (OAR) sparing in post-hysterectomy proton RT. <h3>Materials/Methods</h3> The first 10 patients treated with proton RT on an institutional prospective non-randomized trial of proton post-hysterectomy RT for endometrial cancer were included. CT simulation was performed with pelvic immobilization and a rectal balloon, which was also used for treatment. Full and empty bladder and IV contrast scans were obtained. Clinical target volumes (CTV) included the vaginal cuff, proximal 3 cm of vagina, and pelvic lymph nodes to the level of L4/L5. Prescription was 45 Gy (relative biological effectiveness (RBE) 1.1) in 25 fractions. Planning was multi-field optimization with two posterior oblique beams and a posterior beam. Plans were evaluated for robustness to ensure CTV coverage in worst case scenarios of ±5 mm isocenter shifts in x, y, and z directions and ±5% range uncertainty. A variable RBE calculation assuming a linear relationship between RBE and linear energy transfer was used to evaluate for target coverage and increased RBE within OARs. If needed, the plan was modified to limit hot spots without compromising coverage in the calculation with uniform 1.1 RBE. Patients underwent weekly CT-on-rails verification scans. Target coverage and dose to OARs were assessed at each verification and replanning was done if target coverage or OAR constraints did not meet original planning objectives. <h3>Results</h3> The first patient on the study required replan after first verification due to excess air in the rectum at simulation and verification, resulting in rectum V30Gy 90% and V40Gy 81%. After replan, subsequent verifications met objectives. Subsequent patients were planned with air in the rectum or bowel accounted for by evaluation of plans with air overridden to HU = -300 to -450 and HU = 0. Target coverage met acceptable planning parameters in all cases (Table 1). There was no statistical difference in bladder mean, V30Gy, and V45Gy; sigmoid V45Gy; rectum mean, V30Gy, and V40Gy; and small bowel V40% and V45Gy. All patients were successfully treated with protons for all planned fractions. <h3>Conclusion</h3> Proton post-hysterectomy pelvic RT with robust optimization is feasible, reproducible, and associated with appropriate target coverage and acceptable dose to organs at risk as assessed with weekly verification scans.

Retrospective Analysis of Replan Frequency and Causes in Esophageal Cancer Patients Treated with Spot Scanned Proton Therapy

<h3>Purpose/Objective(s)</h3> For patients with esophageal cancer treated with intensity-modulated proton therapy (IMPT) at our institution, weekly verification CT scans are obtained to ensure that the plan is still acceptable. If unacceptable deviations from the intended dose are observed, replanning is performed. This study aims to investigate the frequency and causes of replans to determine the appropriate frequency of performing verification scans. <h3>Materials/Methods</h3> Data from a cohort of 205 esophageal cancer patients treated with IMPT between 2015 and 2020 were retrospectively analyzed. Patients were typically positioned head first supine with arms up in a vacuum immobilization device, and a four-dimensional CT (4DCT) simulation scan was obtained. The typical prescription was 50 Gy in 25 fractions over 5 weeks, with contours delineated as per consensus guidelines. For tumor motion ≤ 10 mm, patients were treated free-breathing with isolayer repainting, while for motion > 10 mm, gating was also added. Two posterior oblique beams were typically used, and single field optimization was performed. Robust optimization was utilized with 5-mm translational perturbations and 3% range uncertainty, with dose evaluation, also performed on the extreme respiratory phases. Weekly 4DCT verification scans in treatment position were acquired. Rigid image registration to the original planning CT image set was performed, and the care team reviewed the recalculated dose distributions to determine the need for replan. CTV (V95%) % was selected as a metric to compare the difference in target volume dose between verification scans that did [CTV_replan (V95%) %], versus did not [CTV_no-replan (V95%) %], lead to a replan. <h3>Results</h3> The primary tumor location was upper/middle esophagus (16%) or lower/gastroesophageal junction (83%). 21 patients (10%) required replanning, including 3 patients with 2 replans. Replans occurred during the 1^st (20%), 2^nd (33%), 3^rd (20%), or 4^th (25%) weeks of treatment. Primary reasons for replanning were a superior shift of the diaphragm baseline position affecting the range of the beams entering near this interface (46%), changes in tumor size or position (17%), new or resolving pleural effusion affecting the range of beams (13%), changes in stomach filling affecting the target geometry (13%), and patient setup reproducibility issues (13%). The average value of CTV_no-replan (V95%) % = 98% ± 3% vs. CTV_replan (V95%) % = 96% ± 1%. The modest size of this difference suggests that other factors, including poor fidelity of rigid CTV contours, also contribute to clinical decision-making. <h3>Conclusion</h3> In this large cohort of patients with esophageal cancer treated with robustly planned IMPT, the rate of adaptive replanning was 10% and resulted from 5 discrete changes as described above. Every other week frequency of verification scans should be considered.

Proton Beam Therapy for Pancreas Cancer: PTCOG Consensus Recommendations for Simulation, Treatment Planning and Treatment Delivery

<h3>Purpose/Objective(s)</h3> The proximity of gastrointestinal (GI) luminal organs-at-risk (OAR) poses a challenge to radiotherapy (RT) for pancreas cancer (PC). Proton beam therapy (PBT) may reduce toxicities compared to photon therapy by avoiding radiation exposure to large volumes of the abdomen while enabling safe dose escalation. The purpose of this study is to create recommendations for the safe treatment of PC with PBT. <h3>Materials/Methods</h3> The Particle Therapy Co-Operative Group (PTCOG) Gastrointestinal Subcommittee consisting of radiation oncologists and medical physicists with extensive clinical experience using PBT for GI cancers developed expert consensus recommendations for PC describing simulation, treatment planning, and treatment delivery through their collective experience and systematic review of the literature. <h3>Results</h3> The following general recommendations were established: <i>Simulation</i>: Indexed immobilization is recommended to reduce patient setup variability. Patients should be supine with arms above the head. Additional imaging such as PET/CT and/or MRI should be considered for target delineation. Contrast CT is recommended but should be performed subsequent to the planning CT at simulation to avoid the need to override Hounsfield Units. Dual-energy CT should be used, if available, to reduce CT-related proton range uncertainties. Motion management strategies are imperative, including 4DCT for motion accounting and breath-hold, or other techniques for motion mitigation. Patients should also have an empty stomach. <i>Treatment planning</i>: Beam angle selection is critical. Posterior and lateral beam angles are preferred to minimize the dosimetric impact of variable anatomy such as bowel. Robust optimization should be used for pencil beam scanning (PBS) techniques. When treating with PBS, single-field optimization (SFO) is often preferrable to increase robustness. If OAR constraints cannot be met with SFO, then multi-field optimization may be used. Higher linear energy transfer (LET) at the end of range should be considered in the context of sparing distal OARs. Increased beam angle separation should be used to reduce skin dose and mitigate the impact of higher LET. <i>Treatment delivery</i>: Volumetric image guidance, where available, should be used daily. Verification CT scans should be acquired <i>ad-hoc</i> as deemed necessary, or at least every other week, to assess the dosimetric impact of changes in anatomy, such as weight changes and variation in bowel gas and gastric filling. Adaptive re-planning should be performed as required. <h3>Conclusion</h3> The PTCOG Gastrointestinal Subcommittee has developed PBT expert consensus recommendations for PC. These recommendations enable PBT facilities to develop protocols for safe dose escalation studies.

Coupling life cycle assessment and global sensitivity analysis to evaluate the uncertainty and key processes associated with carbon footprint of rice production in Eastern China.

An accurate and objective evaluation of the carbon footprint of rice production is crucial for mitigating greenhouse gas (GHG) emissions from global food production. Sensitivity and uncertainty analysis of the carbon footprint evaluation model can help improve the efficiency and credibility of the evaluation. In this study, we combined a farm-scaled model consisting of widely used carbon footprint evaluation methods with a typical East Asian rice production system comprising two fertilization strategies. Furthermore, we used Morris and Sobol' global sensitivity analysis methods to evaluate the sensitivity and uncertainty of the carbon footprint model. Results showed that the carbon footprint evaluation model exhibits a certain nonlinearity, and it is the most sensitive to model parameters related to CH4 emission estimation, including EFc (baseline emission factor for continuously flooded fields without organic amendments), SFw (scaling factor to account for the differences in water regime during the cultivation period), and t (cultivation period of rice), but is not sensitive to activity data and its emission factors. The main sensitivity parameters of the model obtained using the two global sensitivity methods were essentially identical. Uncertainty analysis showed that the carbon footprint of organic rice production was 1271.7 ± 388.5kg CO2eq t-1 year-1 (95% confidence interval was 663.9-2175.8 kg CO2eq t-1 year-1), which was significantly higher than that of conventional rice production (926.0 ± 213.6kg CO2eq t-1 year-1, 95% confidence interval 582.5-1429.7kg CO2eq t-1 year-1) (p<0.0001). The carbon footprint for organic rice had a wider range and greater uncertainty, mainly due to the greater impact of CH4 emissions (79.8% for organic rice versus 53.8% for conventional rice). EFc , t, Y, and SFw contributed the most to the uncertainty of carbon footprint of the two rice production modes, wherein their correlation coefficients were between 0.34 and 0.55 (p<0.01). The analytical framework presented in this study provides insights into future on-farm advice related to GHG mitigation of rice production.

Validation of a deep learning-based material estimation model for Monte Carlo dose calculation in proton therapy

Objective. Computed tomography (CT) to material property conversion dominates proton range uncertainty, impacting the quality of proton treatment planning. Physics-based and machine learning-based methods have been investigated to leverage dual-energy CT (DECT) to predict proton ranges. Recent development includes physics-informed deep learning (DL) for material property inference. This paper aims to develop a framework to validate Monte Carlo dose calculation (MCDC) using CT-based material characterization models. Approach. The proposed framework includes two experiments to validate in vivo dose and water equivalent thickness (WET) distributions using anthropomorphic and porcine phantoms. Phantoms were irradiated using anteroposterior proton beams, and the exit doses and residual ranges were measured by MatriXX PT and a multi-layer strip ionization chamber. Two pre-trained conventional and physics-informed residual networks (RN/PRN) were used for mass density inference from DECT. Additional two heuristic material conversion models using single-energy CT (SECT) and DECT were implemented for comparisons. The gamma index was used for dose comparisons with criteria of 3%/3 mm (10% dose threshold). Main results. The phantom study showed that MCDC with PRN achieved mean gamma passing rates of 95.9% and 97.8% for the anthropomorphic and porcine phantoms. The rates were 86.0% and 79.7% for MCDC with the empirical DECT model. WET analyses indicated that the mean WET variations between measurement and simulation were −1.66 mm, −2.48 mm, and −0.06 mm for MCDC using a Hounsfield look-up table with SECT and empirical and PRN models with DECT. Validation experiments indicated that MCDC with PRN achieved consistent dose and WET distributions with measurement. Significance. The proposed framework can be used to identify the optimal CT-based material characterization model for MCDC to improve proton range uncertainty. The framework can systematically verify the accuracy of proton treatment planning, and it can potentially be implemented in the treatment room to be instrumental in online adaptive treatment planning.

JPSS-1 VIIRS Prelaunch Reflective Solar Band Testing and Performance

The Visible Infrared Imaging Radiometer Suite (VIIRS) instruments on board both the Suomi National Polar-orbiting Partnership (S-NPP) and the first Joint Polar Satellite System (JPSS-1) spacecraft provides calibrated reflectance, radiance, and brightness temperature products for weather and climate applications. It has 22 bands with resolutions of 375 and 750 m for imaging and moderate bands, respectively, on 4 focal planes covering a spectral range of 400–12,490 nm. The bands are stratified into reflective solar bands (RSBs), thermal emissive bands (TEBs), and the Day/Night Band (DNB). VIIRS has three on-board calibration sectors: the solar diffuser (SD), on-board calibrator blackbody (OBCBB), and space view (SV). The on-board calibrator targets are used to track on-orbit degradation and background offset drift. Extensive prelaunch radiometric testing of the RSB, TEB, and DNB detector’s radiometric sensitivity and noise was performed for both S-NPP and JPSS-1 VIIRS. The combination of prelaunch testing and on-orbit calibrators is used to produce calibrated sensor data record (SDR) reflectance, radiance, and brightness temperatures for use in environmental data record (EDR) products. This paper will discuss the prelaunch radiometric calibration activities for the RSBs only and includes the dynamic range, calibration coefficients, detector noise, and radiometric uncertainties for JPSS-1 VIIRS.

Validation of prompt gamma-ray spectroscopy for proton range verification in tissue-mimicking and porcine samples

Objective. Proton therapy of cancer improves dose conformality to the target and sparing of surrounding healthy tissues compared to conventional photon treatments. However, proton therapy’s advantage could be even larger if proton range uncertainties were reduced. Sources of range uncertainties include computed tomography treatment planning images and variations in patient anatomy and setup. To reduce range uncertainties, we have developed a system for real-time in vivo range monitoring. The system is based on spectroscopy of prompt gamma-rays emitted through proton-nuclear interactions during irradiation. We validated the performance of our prompt gamma-ray spectroscopy detector prototype using tissue-mimicking and porcine samples. Approach. Measurements were performed in water, four tissue-mimicking samples (spongiosa, muscle, adipose tissue, and cortical bone), and two porcine samples (liver and brain). A dose of 0.9 Gy was delivered to a target at a depth of 12.5–17.5 cm. Multi-layer ionization chamber measurements were performed to determine stopping power ratios relative to water and ground truth proton ranges. Ground truth elemental compositions were determined using combustion analysis. Proton ranges and elemental compositions measured using prompt gamma-ray spectroscopy were compared to the ground truth. Main results. For all samples, the mean measured range over all pencil-beam spots differed from the ground truth by less than 1.2 mm. The mean standard deviation was 0.9 mm (range: 0.4–1.6 mm). The mean difference between ground truth and measured elemental compositions was 0.06 (range: 0.00 to 0.12 ). Significance. We verified the performance of our prompt gamma-ray spectroscopy detector prototype for proton range verification using tissue-mimicking and porcine samples. Measured proton ranges and elemental sample compositions were in good agreement with the ground truth. These measurements confirm the system’s reliability for a variety of tissues and bridge the gap between previously-reported experiments and ongoing in vivo patient measurements.

Low-dose CT allows for accurate proton therapy dose calculation and plan optimization

Objective. Protons offer a more conformal dose delivery compared to photons, yet they are sensitive to anatomical changes over the course of treatment. To minimize range uncertainties due to anatomical variations, a new CT acquisition at every treatment session would be paramount to enable daily dose calculation and subsequent plan adaptation. However, the series of CT scans results in an additional accumulated patient dose. Reducing CT radiation dose and thereby decreasing the potential risk of radiation exposure to patients is desirable, however, lowering the CT dose results in a lower signal-to-noise ratio and therefore in a reduced quality image. We hypothesized that the signal-to-noise ratio provided by conventional CT protocols is higher than needed for proton dose distribution estimation. In this study, we aim to investigate the effect of CT imaging dose reduction on proton therapy dose calculations and plan optimization. Approach. To verify our hypothesis, a CT dose reduction simulation tool has been developed and validated to simulate lower-dose CT scans from an existing standard-dose scan. The simulated lower-dose CTs were then used for proton dose calculation and plan optimization and the results were compared with those of the standard-dose scan. The same strategy was adopted to investigate the effect of CT dose reduction on water equivalent thickness (WET) calculation to quantify CT noise accumulation during integration along the beam. Main results. The similarity between the dose distributions acquired from the low-dose and standard-dose CTs was evaluated by the dose-volume histogram and the 3D Gamma analysis. The results on an anthropomorphic head phantom and three patient cases indicate that CT imaging dose reduction up to 90% does not have a significant effect on proton dose calculation and plan optimization. The relative error was employed to evaluate the similarity between WET maps and was found to be less than 1% after reducing the CT imaging dose by 90%. Significance. The results suggest the possibility of using low-dose CT for proton therapy dose estimation, since the dose distributions acquired from the standard-dose and low-dose CTs are clinically equivalent.

Assessment of IMPT versus VMAT plans using different uncertainty scenarios for prostate cancer

BackgroundTo assess the impact of systematic setup and range uncertainties for robustly optimized (RO) intensity modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans in patients with localized prostate cancer.MethodsTwenty-six localized prostate patients previously treated with VMAT (CTV to PTV expansion of 3-5 mm) were re-planned with RO-IMPT with 3 mm and 5 mm geometrical uncertainties coupled with 3% range uncertainties. Robust evaluations (RE) accounting for the geometrical uncertainties of 3 and 5 mm were evaluated for the IMPT and VMAT plans. Clinical target volume (CTV), anorectum, and bladder dose metrics were analyzed between the nominal plans and their uncertainty perturbations.ResultsWith geometric uncertainties of 5 mm and accounting for potential inter-fractional perturbations, RO-IMPT provided statistically significant (p < 0.05) sparing at intermediate doses (V4000cGy) to the anorectum and bladder and high dose sparring (V8000cGy) to the bladder compared to VMAT. Decreasing the RO and RE parameters to 3 mm improved IMPT sparing over VMAT at all OAR dose levels investigated while maintaining equivalent coverage to the CTV.ConclusionsFor localized prostate treatments, if geometric uncertainties can be maintained at or below 3 mm, RO-IMPT provides clear dosimetric advantages in anorectum and bladder sparing compared to VMAT. This advantage remains even under uncertainty scenarios. As geometric uncertainties increase to 5 mm, RO-IMPT still provides dosimetric advantages, but to a smaller magnitude.

In-vivo range verification analysis with in-beam PET data for patients treated with proton therapy at CNAO.

Morphological changes that may arise through a treatment course are probably one of the most significant sources of range uncertainty in proton therapy. Non-invasive in-vivo treatment monitoring is useful to increase treatment quality. The INSIDE in-beam Positron Emission Tomography (PET) scanner performs in-vivo range monitoring in proton and carbon therapy treatments at the National Center of Oncological Hadrontherapy (CNAO). It is currently in a clinical trial (ID: NCT03662373) and has acquired in-beam PET data during the treatment of various patients. In this work we analyze the in-beam PET (IB-PET) data of eight patients treated with proton therapy at CNAO. The goal of the analysis is twofold. First, we assess the level of experimental fluctuations in inter-fractional range differences (sensitivity) of the INSIDE PET system by studying patients without morphological changes. Second, we use the obtained results to see whether we can observe anomalously large range variations in patients where morphological changes have occurred. The sensitivity of the INSIDE IB-PET scanner was quantified as the standard deviation of the range difference distributions observed for six patients that did not show morphological changes. Inter-fractional range variations with respect to a reference distribution were estimated using the Most-Likely-Shift (MLS) method. To establish the efficacy of this method, we made a comparison with the Beam’s Eye View (BEV) method. For patients showing no morphological changes in the control CT the average range variation standard deviation was found to be 2.5 mm with the MLS method and 2.3 mm with the BEV method. On the other hand, for patients where some small anatomical changes occurred, we found larger standard deviation values. In these patients we evaluated where anomalous range differences were found and compared them with the CT. We found that the identified regions were mostly in agreement with the morphological changes seen in the CT scan.

An online adaptive plan library approach for intensity modulated proton therapy for head and neck cancer

Background and purposeIn intensity modulated proton therapy (IMPT), the impact of setup errors and anatomical changes is commonly mitigated by robust optimization with population-based setup robustness (SR) settings and offline replanning. In this study we propose and evaluate an alternative approach based on daily plan selection from patient-specific pre-treatment established plan libraries (PLs). Clinical implementation of the PL strategy would be rather straightforward compared to daily online re-planning. Materials and methodsFor 15 head-and-neck cancer patients, the planning CT was used to generate a PL with 5 plans, robustly optimized for increasing SR: 0, 1, 2, 3, 5 mm, and 3% range robustness. Repeat CTs (rCTs) and realistic setup and range uncertainty distributions were used for simulation of treatment courses for the PL approach, treatments with fixed SR (fSR3) and a trigger-based offline adaptive schedule for 3 mm SR (fSR3OfA). Daily plan selection in the PL approach was based only on recomputed dose to the CTV on the rCT. ResultsCompared to using fSR3 and fSR3OfA, the risk of xerostomia grade ≥ II & III and dysphagia ≥ grade III were significantly reduced with the PL. For 6/15 patients the risk of xerostomia and/or dysphagia ≥ grade II could be reduced by > 2% by using PL. For the other patients, adherence to target coverage constraints was often improved. fSR3OfA resulted in significantly improved coverage compared to PL for selected patients. ConclusionThe proposed PL approach resulted in overall reduced NTCPs compared to fSR3 and fSR3OfA at limited cost in target coverage.

Depth dose measurements in water for 11C and 10C beams with therapy relevant energies

Owing to the favorable depth-dose distribution and the radiobiological properties of heavy ion radiation, ion beam therapy shows an improved success/toxicity ratio compared to conventional radiotherapy. The sharp dose gradients and very high doses in the Bragg peak region, which represent the larger physical advantage of ion beam therapy, make it also extremely sensitive to range uncertainties. The use of β+-radioactive ion beams would be ideal for simultaneous treatment and accurate online range monitoring through PET imaging. Since all the unfragmented primary ions are potentially contributing to the PET signal, these beams offer an improved image quality while preserving the physical and radiobiological advantages of the stable counterparts. The challenging production of radioactive ion beams and the difficulties in reaching high intensities, have discouraged their clinical application. In this context, the project Biomedical Applications of Radioactive ion Beams (BARB) started at GSI (Helmholtzzentrum für Schwerionenforschung GmbH) with the main goal to assess the technical feasibility and investigate possible advantages of radioactive ion beams on the pre-clinical level. During the first experimental campaign 11C and 10C beams were produced and isotopically separated with the FRagment Separator (FRS) at GSI. The β+-radioactive ion beams were produced with a beam purity of 99% for all the beam investigated (except one case where it was 94%) and intensities potentially sufficient to treat a small animal tumors within few minutes of irradiation time, ∼106 particle per spill for the 10C and ∼107 particle per spill for the 11C beam, respectively. The impact of different ion optical parameters on the depth dose distribution was studied with a precision water column system. In this work, the measured depth dose distributions are presented together with results from Monte Carlo simulations using the FLUKA software.

The role of multiple anatomical scenarios in plan optimization for carbon ion radiotherapy of pancreatic cancer

Purpose /objectiveTo quantify benefits of robust optimization on multiple 4DCT acquisitions combined with off-line treatment adaptation for neoadjuvant carbon ion therapy (CIRT) of pancreatic cancer. Material/methodsFor 10 previously treated patients, 4DCTs were acquired around −15 (CTPlan), −5 (RE1), −1 (RE2) and +6 (RE3) days from RT start. Treatment plans were newly optimized to a dose prescription of 38.4 Gy(RBE) (8 fractions) with a constraint of 38 Gy(RBE) to 1% of the gastrointestinal organs at risk volume (D1%). Three strategies were tested: (A) robust optimization on CTPlan maximum exhale (0Ex) with 3 mm set-up, 3% range uncertainty, including 30%-inhale; (B) addition of the RE1-0Ex scenario; (C) plan recalculation at each REi and adaptation (RPi) according to deviation thresholds from clinical goals. The cumulative variation of target coverage and GI-OARs doses was evaluated. Duodenum contours of all 4DCTs of each patient were registered on CTPlan-0Ex. The capacity of pre-RT acquisitions to predict duodenum position was investigated by computing the intersection of contours at CTplan, RE1, or their union, with respect to subsequent 4DCTs and the CTV, coupled with increasing margin. Results(A) No recalculation exceeded the D1% constraint. (B) The inclusion of RE1-0Ex in the optimization problem improved inter-fraction robustness on a patient-specific basis, but was non-significant on average. (C) Half of the plans would be re-optimized to recover target coverage and/or minimize duodenum dose, at least once. A significant difference was observed between pre-RT duodenum contours when intersecting subsequent contours, either with a margin expansion. ConclusionAnatomical variations highlighted at multiple REi proved that a fast and efficient online adaptation is essential to optimize treatment quality of CIRT for pancreatic cancer.