Intensity Modulated Proton Therapy Treatment Research Articles

Dosimetric Comparison Between Proton and Photon Radiation Therapies for Pediatric Neuroblastoma

PurposeThe aim of this study is to determine the most beneficial radiation treatment technique for pediatric patients with thoracic and abdominal neuroblastoma (NBL), through a dosimetric comparison between photon Volumetric Modulated Arc Therapy and proton Intensity-Modulated Proton Therapy treatment plans. Materials and MethodsA retrospective analysis was conducted on a multicentre case series of 19 patients with thoracic and/or abdominal NBL who underwent radiation therapy, following the recommendations of the European protocol for high-risk NBL (HR-NBL2/SIOPEN). The prescribed dose was 21.6 Gy in 12 fractions (1.8 Gy/fraction) delivered over the preoperative disease volume. The dose volume histograms were analyzed for each patient, and a Wilcoxon signed-rank test with a significance level of 0.01 was employed to assess statistical differences between the dosimetric parameters investigated. Two homogeneity indices (HI and newHI) were compared to evaluate the uniformity in dose, delivered to the adjacent vertebrae (VBs_Adj). ResultsBoth radiation techniques conform to the protocol regarding CTV/PTV coverage for every location. Proton therapy resulted in statistically significant dose sparing for the heart and lungs in supradiaphragmatic locations and for the contralateral kidney, liver, spleen, and bowel in subdiaphragmatic locations. For both techniques, sparing the non-adjacent vertebrae (VBs_NAdj) results more challenging, although promising results were obtained. Furthermore, the dose delivered to the VBs_Adj was not statistically different, in terms of homogeneity, for the 2 radiation techniques that both met the protocol’s requirements. ConclusionThis dosimetric analysis highlights the potential of protons to reduce radiation dose to healthy tissue. These findings apply to all the investigated patients, regardless of primary tumor location, making proton therapy a valuable option for the treatment of neuroblastoma. However, a multidisciplinary assessment of each case is essential to ensure the selection of the most effective and suitable treatment modality.

Feasibility and constraints of Bragg peak FLASH proton therapy treatment planning.

FLASH proton therapy (FLASH-PT) requires ultra-high dose rate (≥40 Gy/s) protons to be delivered in a short timescale whilst conforming to a patient-specific target. This study investigates the feasibility and constraints of Bragg peak FLASH-PT treatment planning, and compares the in silico results produced to plans for intensity modulated proton therapy (IMPT). Bragg peak FLASH-PT and IMPT treatment plans were generated for bone (n=3), brain (n=3), and lung (n=4) targets using the MIROpt research treatment planning system and the Conformal FLASH library developed by Applications SA from the open-source version of UCLouvain. FLASH-PT beams were simulated using monoenergetic spot-scanned protons traversing through a conformal energy modulator, a range shifter, and an aperture. A dose rate constraint of ≥ 40 Gy/s was included in each FLASH-PT plan optimisation. Space limitations in the FLASH-PT adapted beam nozzle imposed a maximum target width constraint, excluding 4 cases from the study. FLASH-PT plans did not satisfy the imposed target dose constraints (D95% ≥ 95% and D2%≤ 105%) but achieved clinically acceptable doses to organs at risk (OARs). IMPT plans adhered to all target and OAR dose constraints. FLASH-PT plans showed a reduction in both target homogeneity (p < 0.001) and dose conformity (non-significant) compared to IMPT. Without accounting for a sparing effect, IMPT plans were superior in target coverage, dose conformity, target homogeneity, and OAR sparing compared to FLASH-PT. Further research is warranted in treatment planning optimisation and beam delivery for clinical implementation of Bragg peak FLASH-PT.

Dosimetric impact of bone marrow sparing for robustly optimized IMPT for locally advanced cervical cancer

Background and purposeTo investigate the trade-off between bone marrow sparing (BMS) and dose to organs at risk (OARs) for intensity modulated proton therapy (IMPT) for women with locally advanced cervical cancer (LACC). Materials and methodsTwenty LACC patients were retrospectively included. IMPT plans were created for each patient using automated treatment planning. These plans progressively reduced bone marrow mean doses by steps of 1 GyRBE, while constraining target coverage and conformality. The relation between bone marrow dose and bladder, small bowel, rectum, and sigmoid doses was evaluated. ResultsA total of 140 IMPT plans were created. Plans without BMS had an average [range] bone marrow mean dose of 17.3 [14.7–21.6] GyRBE , which reduced to 12.0 [10.0–14.0] GyRBE with maximum BMS. The mean OAR dose [range] increased modestly for 1 GyRBE BMS: 0.2 [0.0 – 0.6] GyRBE for bladder, 0.3 [-0.2 – 0.7] GyRBE for rectum, 0.4 [0.1 – 0.8] GyRBE for small bowel, and 0.2 [-0.2 – 0.4] GyRBE for sigmoid. Moreover, for maximum BMS, mean OAR doses [range] escalated by 3.3 [0.1 – 6.7] GyRBE for bladder, 5.8 [1.8 – 12.4] GyRBE for rectum, 3.9 [1.6 – 5.9] GyRBE for small bowel, and 2.7 [0.6 – 5.9] GyRBE for sigmoid. ConclusionAchieving 1 GyRBE BMS for IMPT is feasible for LACC patients with limited dosimetric impact on other OARs. While further bone marrow dose reduction is possible for some patients, it may increase OAR doses substantially for others. Hence, we recommend a personalized approach when introducing BMS into clinical IMPT treatment planning to carefully assess individual patient benefits and risks.

FLASH radiotherapy sparing effect on the circulating lymphocytes in pencil beam scanning proton therapy: impact of hypofractionation and dose rate

Purpose. The sparing effect of ultra-high dose rate (FLASH) radiotherapy has been reported, but its potential to mitigate depletion of circulating blood and lymphocytes (CL) has not been investigated in pencil-beam scanning-based (PBS) proton therapy, which could potentially reduce the risk of radiation-induced lymphopenia. Material and methods. A time-dependent framework was used to score the dose to the CL during the course of radiotherapy. For brain patients, cerebral vasculatures were semi-automatic segmented from 3T MR-angiography data. A dynamic beam delivery system was developed capable of simulating spatially varying instantaneous dose rates of PBS treatment plans, and which is based on realistic beam delivery parameters that are available clinically. We simulated single and different hypofractionated PBS intensity modulated proton therapy (IMPT) FLASH schemes using 600 nA beam current along with conventionally fractionated IMPT treatment plan at 2 nA beam current. The dosimetric impact of treatment schemes on CL was quantified, and we also evaluated the depletion in subsets of CL based on their radiosensitivity. Results. The proton FLASH sparing effect on CL was observed. In single-fraction PBS FLASH, just 1.5% of peripheral blood was irradiated, whereas hypofractionated FLASH irradiated 7.3% of peripheral blood. In contrast, conventional fractionated IMPT exposed 42.4% of peripheral blood to radiation. PBS FLASH reduced the depletion rate of CL by 69.2% when compared to conventional fractionated IMPT. Conclusion. Our dosimetric blood flow model provides quantitative measures of the PBS FLASH sparing effect on the CL in radiotherapy for brain cancer. FLASH Single treatment fraction offers superior CL sparing when compared to hypofractionated FLASH and conventional IMPT, supporting assumptions about reducing risks of lymphopenia compared to proton therapy at conventional dose rates. The results also indicate that faster conformal FLASH delivery, such as passive patient-specific energy modulation, may further enhance the sparing of the immune system.

Treatment planning comparison for head and neck cancer between photon, proton, and combined proton–photon therapy – From a fixed beam line to an arc

Background and purposeThis study investigates whether combined proton–photon therapy (CPPT) improves treatment plan quality compared to single-modality intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) for head and neck cancer (HNC) patients. Different proton beam arrangements for CPPT and IMPT are compared, which could be of specific interest concerning potential future upright-positioned treatments. Furthermore, it is evaluated if CPPT benefits remain under inter-fractional anatomical changes for HNC treatments. Material and methodsFive HNC patients with a planning CT and multiple (4–7) repeated CTs were studied. CPPT with simultaneously optimized photon and proton fluence, single-modality IMPT, and IMRT treatment plans were optimized on the planning CT and then recalculated and reoptimized on each repeated CT. For CPPT and IMPT, plans with different degrees of freedom for the proton beams were optimized. Fixed horizontal proton beam line (FHB), gantry-like, and arc-like plans were compared. ResultsThe target coverage for CPPT without adaptation is insufficient (average V95%=88.4 %), while adapted plans can recover the initial treatment plan quality for target (average V95%=95.5 %) and organs-at-risk. CPPT with increased proton beam flexibility increases plan quality and reduces normal tissue complication probability of Xerostomia and Dysphagia. On average, Xerostomia NTCP reductions compared to IMRT are −2.7 %/-3.4 %/-5.0 % for CPPT FHB/CPPT Gantry/CPPT Arc. The differences for IMPT FHB/IMPT Gantry/IMPT Arc are + 0.8 %/-0.9 %/-4.3 %. ConclusionCPPT for HNC needs adaptive treatments. Increasing proton beam flexibility in CPPT, either by using a gantry or an upright-positioned patient, improves treatment plan quality. However, the photon component is substantially reduced, therefore, the balance between improved plan quality and costs must be further determined.

A Novel Analytic Method of Automatically Assessing Beamline Geometric Range Variations for CBCT-Guided Intensity-Modulated Proton Therapy (IMPT) for Localized Prostate Cancer

A novel image-processing analytics software was introduced to quantitatively assess the beamline geometric range variations for proton spots around the planning target in daily CBCT-guided prostate IMPT. Three hundred eighty-seven consecutive full-CBCT alignment images of 11 localized prostate cancer IMPT cases were retrospectively analyzed to quantify the range variations of proton beamlines using a home-grown software. Each patient treatment comprises two proton scanning beams. All cases had a history of a plan revision with a re-simulated CT set. With this novel method the patient body surfaces are reconstructed by generating triangle mesh surfaces using a python Delaunay tessellation method. A python ray casting algorithm is utilized to determine the surface offset of the aligned CBCT relative to the planning CT. The proton beamlines are extrapolated from all the beam spots within 10 mm-enlarged planning target volume. The maximal geometric range variation was used to score the selected percentile of the included beamlines of the beam. The accuracy of this analytic software was satisfactorily validated prior to its application to this retrospective investigation. In practice, the proton range uncertainties are routinely estimated from their geometric range variations measured on a setup CBCT. The computation or processing time is about 60 seconds for each CBCT - planning CT analysis on a prostate IMPT positioning. The geometric range variations in the 95th percentile beamlines of 774 fractional beams or 387 aligned CBCT images are 3.29 ± 1.43 mm. As tabulated in table-1, worsened beam range variations of setup CBCTs were reduced by 2.60 ± 0.30 mm in the succeeding 2 fractions post using re-simulated setups. In this serial, an averaged 1.41 ± 0.10 mm range variation reduction was seen by re-simulation throughout the course. The geometric range variations of beamlines in prostate IMPT were comprehensively analyzed, for the first time, using a novel analytic software based on aligned daily CBCTs. The results of this study suggest that the re-simulated setups can be an effective way to reduce beamline range variations for localized prostate IMPT. Incorporation of this process for other IMPT treatment sites, as well as a Gamma-indexed analysis will be added in our immediate future research.

Improving Interfraction Robustness for IMPT Treatment Planning for Lung Cancer Using Multiple-CT Incorporated Robust Optimization

Dose deterioration due to motion-induced density variation is a major concern in intensity-modulated proton therapy (IMPT) for lung cancer. Robust optimization is capable to address the intrafraction motion issue but not the interfraction variation. This study aims to investigate the potential of a new robust optimization technique of IMPT in mitigating the interfraction variation of lung cancer patients. Two optimization techniques were used to create an IMPT plan for a lung cancer case, one was conventional robust optimization (ROcon) considering the perturbation of 3 mm setup uncertainty and 3.5% range uncertainty, and the other was multiple-CT incorporated robust optimization (ROmul) considering one more perturbation quantified using the end-of-inhalation-phase (T0) and end-of-exhalation-phase (T50) CTs. The ROcon plan was optimized on the average-intensity-projection (AIP) planning CT (pCT), and the ROmul plan was optimized on the AIP, T0, and T50 pCTs. The dose prescription was 40 Gy (RBE) in 5 fractions. The patient underwent a verification 4DCT (vCT) scan on six successive days. Both plans were recalculated on the T0 pCT, T50 pCT, and AIP vCT. The dose to the target and organ at risk of the ROcon and ROmul plans on pCT and vCT were compared. Compared with the ROcon plan, the ROmul plan reduced the deviation of target coverage by greater than 50% in presence of intrafraction motion (ROmul:0.38-0.88%, ROcon:1.90-2.23%) and interfraction variation (ROmul: 0.62-1.63% vs ROcon:0.50-2.75%) while meeting the dose criteria on the planning AIP CT. As for the dose to the organ at risk, the ROmul plan had a slightly high lung V20 (0.3%) than did the ROcon plan on the AIP pCT. The deviations in lung V20 of the ROmul plan (mean 0.15%) on the vCTs were similar to that of the ROcon plan (mean 0.17%). This study indicates that dose variation of an IMPT plan can be reduced in presence of interfraction variation along the treatment course by combining conventional robust optimization and novel multiple-CT optimization using only the planning CT.

Comparing Predicted Toxicities between Hypofractionated Proton and Photon Radiotherapy of Liver Cancer Patients with Different Adaptive Schemes.

With the availability of MRI linacs, online adaptive intensity modulated radiotherapy (IMRT) has become a treatment option for liver cancer patients, often combined with hypofractionation. Intensity modulated proton therapy (IMPT) has the potential to reduce the dose to healthy tissue, but it is particularly sensitive to changes in the beam path and might therefore benefit from online adaptation. This study compares the normal tissue complication probabilities (NTCPs) for liver and duodenal toxicity for adaptive and non-adaptive IMRT and IMPT treatments of liver cancer patients. Adaptive and non-adaptive IMRT and IMPT plans were optimized to 50 Gy (RBE = 1.1 for IMPT) in five fractions for 10 liver cancer patients, using the original MRI linac images and physician-drawn structures. Three liver NTCP models were used to predict radiation-induced liver disease, an increase in albumin-bilirubin level, and a Child-Pugh score increase of more than 2. Additionally, three duodenal NTCP models were used to predict gastric bleeding, gastrointestinal (GI) toxicity with grades >3, and duodenal toxicity grades 2-4. NTCPs were calculated for adaptive and non-adaptive IMRT and IMPT treatments. In general, IMRT showed higher NTCP values than IMPT and the differences were often significant. However, the differences between adaptive and non-adaptive treatment schemes were not significant, indicating that the NTCP benefit of adaptive treatment regimens is expected to be smaller than the expected difference between IMRT and IMPT.

Applicator-guided proton therapy versus multichannel brachytherapy for vaginal vault irradiation.

To dosimetrically compare applicator-guided intensity-modulated proton therapy(IMPT) and multichannel brachytherapy (MC-BRT) for vaginal vault irradiation(VVI) with special focus on dose to organs at risk (OARs) and normal tissues. Ten patients with uterine confined endometrial cancer who received adjuvant vaginal cuff brachytherapy were included in this study. For each patient an additional IMPT treatment plan was created using the same computed tomography dataset and contours segmented for MC-BRT plans. Clinical target volume (CTV) was defined as the proximal 3.5 cm of the vagina including the entire thickness of vaginal wall. Planning target volume for IMPT plans was generated from the CTV with an addition isotropic 3 mm margin. OARs included rectum, bladder, sigmoid, small bowel and femoral heads. The prescribed dose was 21 Gy in 3 fractions. For simplicity, all doses were expressed in Gy and a constant relative biological effectiveness of 1.1 was used for IMPT plans. Plan comparison was performed using dose-volume histogram and treatment planning parameters. A significant improvement of the D98% coverage for CTV was reached by the applicator-guided IMPT plans (p < 0.01). IMPT also provided a dose reduction in all OARs except for femoral heads due to the lateral beam direction, especially significant reduction of V5Gy, D2cc, D0.1 cc, Dmean, V95% values for the rectum and Dmean, D0.1 cc to bladder, sigmoid, small bowel. Additionally, IMPT plans showed a significant reduction of integral dose to normal tissue with respect to MC-BRT (221.5 cGy.L vs. 653.6 cGy.L, p < 0.01). Applicator-guided IMPT has the potential for improving plan quality in VVI while maintaining the high conformity afforded by the state-of-the-art intracavitary brachytherapy.

ScatterNet for projection-based 4D cone-beam computed tomography intensity correction of lung cancer patients.

Background and purpose: In radiotherapy, dose calculations based on 4D cone beam CTs (4DCBCTs) require image intensity corrections. This retrospective study compared the dose calculation accuracy of a deep learning, projection-based scatter correction workflow (ScatterNet), to slower workflows: conventional 4D projection-based scatter correction (CBCTcor) and a deformable image registration (DIR)-based method (4DvCT). Materials and methods: For 26 lung cancer patients, planning CTs (pCTs), 4DCTs and CBCT projections were available. ScatterNet was trained with pairs of raw and corrected CBCT projections. Corrected projections from ScatterNet and the conventional workflow were reconstructed using MA-ROOSTER, yielding 4DCBCTSN and 4DCBCTcor. The 4DvCT was generated by 4DCT to 4DCBCT DIR, as part of the 4DCBCTcor workflow. Robust intensity modulated proton therapy treatment plans were created on free-breathing pCTs. 4DCBCTSN was compared to 4DCBCTcor and the 4DvCT in terms of image quality and dose calculation accuracy (dose-volume-histogram parameters and / gamma analysis). Results: 4DCBCTSN resulted in an average mean absolute error of and when compared to 4DCBCTcor and 4DvCT respectively. High agreement was observed in targets with median dose differences of (4DCBCTSN-4DCBCTcor) and (4DCBCTSN-4DvCT). The gamma analysis showed high average / pass rates of for both 4DCBCTSN vs. 4DCBCTcor and 4DCBCTSN vs. 4DvCT. Conclusions: Accurate 4D dose calculations are feasible for lung cancer patients using ScatterNet for 4DCBCT correction. Average scatter correction times could be reduced from (4DCBCTcor) to , showing the clinical suitability of the proposed deep learning-based method.

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

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

Dose Planning Evaluation of Intensity-Modulated Proton Therapy (IMPT) Technique Based on In-House Dynamic Thorax Phantom

One of the drawbacks of the Intensity Modulated Radiation Therapy (IMRT) technique is that the absorbed dose in healthy tissue is relatively high. Proton beam has characteristics that can compensate for these drawbacks. The Bragg peak characteristic of a proton beam allows the administration of high radiation doses to the target organ only. Non-Small Cell Lung Cancer (NSCLC) cases are located in the vicinity of many vital organs, so radiation doses that exceed a certain limit will have a significant impact on these organs. Proton is a heavy particle that exhibits interaction patterns with tissue heterogeneity that differ from that of photon. This study aims to determine the distribution of proton beam planning doses in the NSCLC cases with the Intensity Modulated Proton Therapy (IMPT) technique and compare its effectiveness with the IMRT technique. Treatment planning was done by using TPS Eclipse on the water phantom and on the in-house thorax dynamic phantom. The water phantom planning parameters used are one field at 0° and three fields at 45°, 135°, and 225°. In this study, a single, sum, and multiple field techniques on the in-house thorax dynamic phantom were used. The evaluation was performed by calculating Conformity Index (CI), Homogeneity Index (HI), and Gradient Index (GI) parameters for each treatment planning. As a result, a bit of difference in the CI the HI values are shown between IMPT and IMRT planning. The GI values of IMPT planning are in the range between 4.15-4.53, while the GI value of IMRT is 7.89. The histogram results of the planar dose distribution show that the IMPT treatment planning provides fewer off-target organ doses than the IMRT planning. Evaluation was also carried out on the IMPT treatment planning of target organs in five areas of interest and four OAR positions. The evaluation results were then compared with the IMRT measurement data. As a result, the value of the point doses at the target organ did not differ significantly. However, the absorbed dose with the IMPT technique at four OAR positions is nearly zero, which had a large difference compared to the IMRT technique.

Radiation Exposure of Cardiac Conduction Nodes During Breast Proton Therapy.

The exposition of cardiac conduction system during breast radiation therapy has never been studied, despite the increasing use of intensity-modulated radiation therapy, which exposes larger volume to low-dose bath. We evaluated conduction node exposure during breast irradiation with volumetric modulated arc therapy and estimated the potential dosimetric benefit with intensity-modulated proton therapy. Atrioventricular (AVN) and sinoatrial (SAN) nodes were retrospectively delineated according to published guidelines on the simulation computed tomography scans of 12 breast cancer patients having undergone conserving surgery and adjuvant locoregional volumetric modulated arc therapy. Intensity-modulated proton therapy treatment was replanned on the simulation computed tomography scans for all breast cancer patients. Mean and maximum doses delivered to the SAN and the AVN were retrieved and compared. Correlation coefficients were calculated between doses to the SAN or the AVN and the whole heart. Average mean doses delivered to the SAN and AVN were 2.8 and 2.3 Gy, respectively, for left-sided irradiation and 9.6 and 3.6 Gy, respectively, for right-sided irradiation. Average maximum doses to the SAN and AVN were 3.5 Gy and 2.8 Gy, respectively, for left-sided irradiation and 13.1 and 4.6 Gy, respectively, for right-sided irradiation. Intensity-modulated proton therapy significantly reduced mean and maximum doses to the SAN and AVN. Correlations between doses to the SAN or AVN and whole heart were usually significant. SAN and AVN can be substantially exposed during breast volumetric modulated arc therapy, especially for right-sided irradiation. Cardiotoxicity studies evaluating conduction node exposure might define dose constraints and criteria for additional cardiac-sparing techniques, such as respiratory techniques or proton therapy, which could benefit patients with underlying rhythmic or conduction disorders.

Abstract P1-10-16: Cardiac conduction system exposure with modern radiotherapy techniques for breast cancer irradiation

Abstract Introduction: Exposition of cardiac conduction system during breast radiotherapy has never been studied, despite increasing use of intensity modulated radiotherapy which expose larger volume to low dose bath. We evaluated conduction node exposure during breast irradiation with volumetric modulated arctherapy (VMAT) and estimated the potential dosimetric benefit with intensity modulated protontherapy (IMPT). Materials and methods: Atrioventricular (AVN) and sinoatrial (SAN) nodes were retrospectively delineated according to published guidelines on the simulation CT scans of twelve breast cancer patients having undergone conserving surgery and adjuvant locoregional VMAT. IMPT treatment was re-planned on the simulation CT scans for all breast cancer patients. Mean and maximum doses to the SAN and the AVN were retrieved and compared. Correlation coefficients were calculated between doses to the SAN or the AVN and to the whole heart. Results: Average mean doses to the SAN and to the AVN were 2.8 Gy and 2.3 Gy respectively for left-sided irradiation and 9.6 Gy and 3.6 Gy respectively for right-sided irradiation. Average maximum doses to the SAN and to the AVN were 3.5 Gy and 2.8 Gy respectively for left-sided irradiation and 13.1 Gy and 4.6 Gy respectively for right-sided irradiation. IMPT significantly reduces doses to conduction nodes. Correlations between doses to the SAN or the AVN and the whole heart were usually significant. Conclusion: SAN and AVN can be substantially exposed during breast VMAT, especially for right-sided irradiation. Cardiotoxicity studies evaluating conduction node exposure might define dose constraints and criteria for additional cardiac sparing techniques, such as respiratory techniques or proton therapy, which could be beneficial to patients with underlying rhythmic or conduction disorders. Citation Format: Pierre Loap, Farid Goudjil, Ludovic De Marzi, Vincent Servois, Krassen Kirov, Alain Fourquet, Youlia M. Kirova. Cardiac conduction system exposure with modern radiotherapy techniques for breast cancer irradiation [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-16.

Spot delivery error predictions for intensity modulated proton therapy using robustness analysis with machine learning.

The purpose of this work is to assess the robustness of treatment plans when spot delivery errors were predicted with a machine learning (ML) model for intensity modulated proton therapy (IMPT). Over 6000 machine log files from delivered IMPT treatment plans were included in this study. From these log files, over 4.1 106 delivered proton spots were used to train the ML model. The presented model was tested and used to predict the spot position as well as the monitor units (MU) per spot, based on the original planning parameters. Two patient plans (one accelerated partial breast irradiation [APBI] and one ependymoma) were recalculated with the predicted spot position/MUs by the ML model and then were re-analyzed for robustness. Plans with ML predicted spots were less robust than the original clinical plans. In the APBI plan, dosimetric changes to the left lung and heart were not clinically relevant. In the ependymoma plan, the hot spot in the brainstem decreased and the hot spot in the cervical cord increased. Despite these differences, after robustness analysis, both ML spot delivery error plans resulted in >95% of the CTV receiving >95% of the prescription dose. The presented workflow has the potential benefit of including realistic spots information for plan quality checks in IMPT. This work demonstrates that in the two example plans, the plans were still robust when accounting for spot delivery errors as predicted by the ML model.

Spot scanning proton arc therapy reduces toxicity in oropharyngeal cancer patients.

Proton arc technology has recently shown dosimetric gains for various treatment indications. The increased number of beams and energy layers (ELs) in proton arc plans, increases the degrees of freedom in plan optimization and thereby flexibility to spare dose in organs at risk (OARs). A relationship exists between dosimetric plan quality, delivery efficiency, the number of ELs -and beams in a proton arcplan. This work aims to investigate the effect of the number of beams and ELs in a proton arc plan, on toxicity and delivery time for oropharyngeal cancer patients (OPC) selected for intensity modulated proton therapy (IMPT) based on the Dutch model-basedapproach. The EL reduction algorithm iteratively selects ELs from beams equidistantly spaced over a 360° arc. The beams in the final plan may contain multiple ELs, making them suited for static delivery on the studied treatment machine. The produced plans can therefore be called "step and shoot" proton arc plans. The number of beams and ELs were varied to determine the relationship with the planning cost function value, normal tissue complication probability (NTCP) and delivery time. Proton arc plans with robust target coverage and optimal energy layer reduction (ELR) settings to reduce NTCP, were generated for 10 OPC patients. Proton arc plans were compared to clinical volumetric modulated arc therapy (VMAT) and IMPT plans in terms of integral dose, OAR dose, NTCP for xerostomia and dysphagia and delivery time. Furthermore, dose-weighted average linear energy transfer (LETd ) distributions were compared between the IMPT and proton arc plans. A dry run delivery of a plan containing 20 beams and 360 ELs was performed to evaluate delivery time andaccuracy. We found 360 ELs distributed over 30 beams generated proton arc plans with near minimal expected plan toxicity. Relative to corresponding IMPT and VMAT plans, an average reduction of 21 ± 3% and 58 ± 10% in integral dose was observed. D was reduced most in the pharyngeal constrictor muscle (PCM) medius structure, with on average 9.0 ± 4.2 Gy(RBE) (p = 0.0002) compared to the clinical IMPT plans. The average NTCP for grade≥2 and grade≥3 xerostomia at 6 months after treatment significantly decreased with 4.7 ± 1.8% (p = 0.002) and 1.7 ± 0.8% (p = 0.002), respectively, while the average NTCP for grade≥2 and grade≥3 dysphagia decreased with 4.4 ± 2.9% (p = 0.002) and 0.9 ± 0.4% (p = 0.002), respectively, increasing the benefit of protons relative to VMAT. For a "step and shoot" proton arc delivery with auto beam sequencing the estimated delivery time is 11 min, similar to the delivery time of a 6-field IMPT treatment. Gamma analysis between the planned and delivered dose distribution resulted in a 99.99% pass rate using 1mm/1% dose difference/distance to agreement criteria. "Step and shoot" proton arc demonstrates potential to further reduce toxicity compared to IMPT and VMAT in OPC treatment. By employing 360 ELs and 30 beams in the proposed ELR method, delivery time can reach clinically acceptable levels without compromising plan toxicity when automatic beam sequencing isavailable.

Advanced pencil beam scanning Bragg peak FLASH-RT delivery technique can enhance lung cancer planning treatment outcomes compared to conventional multiple-energy proton PBS techniques

To investigate the dosimetric characteristics between an advanced proton pencil beam scanning (PBS) Bragg peak FLASH technique and conventional PBS planning technique in lung tumors. To evaluate the "FLASHness" of single-field in a multiple-field delivery scheme for a hypofractionation regimen and move a step forward to clinical application. Single-energy PBS Bragg peak FLASH treatment plans were optimized based on a novel Bragg peak tracking technique to enable Bragg peaks to stop at the distal edge of the target. Inverse treatment planning using multiple-field optimization (MFO) can achieve sufficient FLASH dose rate and intensity-modulated proton therapy (IMPT)-equivalent dosimetric quality. The dose rate of organs-at-risk (OARs) and the target were calculated under FLASH machine parameters. A group of 10 consecutive lung SBRT patients was optimized to 34Gy/fraction using a standard treatment of PBS technique with multiple energy layers as references to the Bragg peak plans. The dosimetric quality was compared between Bragg peak FLASH and conventional plans based on RTOG0915 dose metrics. FLASH dose rate ratios (V40Gy/s) were calculated as a metric of the FLASH-sparing effect. For higher dose thresholds, the Bragg peak plans achieved greater V40Gy/s FLASH coverage for all major OARs. The V40Gy/s was close to 100% for all OARs when the dose thresholds were>5Gy for full plan and single beam evaluations. The less "FLASHness" region was associated with a low dose distribution, mainly occurring in the PBS field penumbra region. The conventional IMPT treatment plans yielded slightly superior target dose uniformity with a D2%(%) of 108.02% versus that of Bragg peak 300 MU plans of 111.81% (p<0.01) and that of Bragg peak 1200 MU plans of 115.95% (p<0.01). No significant difference in dose metrics was found between Bragg peak and IMPT treatment plans for the spinal cord, esophagus, heart, or lung-GTV (all p>0.05). Hypofractionated lung Bragg peak plans can maintain comparable plan quality to conventional PBS while achieving sufficient FLASH dose rate coverage for major OARs for each field under the multiple-field delivery scheme. The novel Bragg peak FLASH technique has the potential to enhance lung cancer planning treatment outcomes compared to standard PBS treatment techniques.

Proceedings to the 7th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA)

Proceedings to the 7th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA)

Dosimetric comparison of intensity modulated radiotherapy and intensity modulated proton therapy in the treatment of recurrent nasopharyngeal carcinoma.

To compare the dosimetric performance of Intensity Modulated Proton Therapy (IMPT) and Intensity Modulated Radiotherapy (IMRT) in terms of target volume coverage and sparing of neurological organs-at-risk (OARs) in salvaging recurrent nasopharyngeal carcinoma (rNPC). The maximum dose to the internal carotid artery (ICA) and nasopharyngeal (NP) mucosa, which are associated with potential carotid blowout and massive epistaxis, were also evaluated. IMRT and IMPT treatment plans were created for twenty patients with locally advanced rNPC. Planning Target Volume (PTV) was used to account for the setup and spatial error/uncertainty in the IMRT planning. Robust optimization on Clinical Target Volume (CTV) coverage with consideration of range and setup uncertainty was employed to produce two IMPT plans with 3-field and 4-field arrangements. The planning objective was to deliver 60 Gy to the PTV (IMRT) and CTV (IMPT) without exceeding the maximum lifetime cumulative Biologically Effective Dose (BED) of the neurological OARs (applied to the Planning organs-at-risk volume). The target dose coverage as well as the maximum dose to the neurological OARs, ICA, and NP mucosa were compared. Compared with IMRT, 3-field IMPT achieved better coverage to GTV V100% (83.3% vs. 73.2%, P <0.01) and CTV V100% (80.5% vs. 72.4%, P <0.01), and lower maximum dose to the critical OARs including the spinal cord (19.2 Gy vs. 22.3 Gy, P <0.01), brainstem (30.0 Gy vs. 32.3 Gy, P <0.01) and optic chiasm (6.6 Gy vs. 9.8 Gy, P <0.01). The additional beam with the 4-fields IMPT plans further improved the target coverage from the 3-field IMPT (CTV V98%: 85.3% vs. 82.4%, P <0.01) with similar OAR sparing. However, the target dose was highly non-uniform with both IMPT plans, leading to a significantly higher maximum dose to the ICA (∼68 Gy vs. 62.6 Gy, P <0.01) and NP mucosa (∼72 Gy vs. 62.8 Gy, P <0.01) than IMRT. IMPT demonstrated some dosimetric advantage over IMRT in treating rNPC. However, IMPT could also result in very high dose hot spots in the target volume. Careful consideration of the ICA and NP mucosal complications is recommended when applying IMPT on rNPC patients.

Evaluation of Cardiac Conduction System Exposure with Breast Volumetric Modulated Arc Therapy and Intensity Modulated Proton Therapy

Conduction disorders and arrhythmias are reported radiation-induced adverse events. Exposition of cardiac conduction system during breast radiotherapy has never been studied, despite increasing use of intensity modulated radiotherapy which expose larger volumes to low dose bath. We evaluated conduction node exposure during breast irradiation with volumetric modulated arc therapy (VMAT) and estimated the potential dosimetric benefit with intensity modulated proton therapy (IMPT).Atrioventricular (AVN) and sinoatrial (SAN) nodes were retrospectively delineated according to published guidelines on the simulation CT scans of twelve breast cancer patients having undergone conserving surgery and adjuvant locoregional VMAT. According to these guidelines, the SAN was delineated by a 2 cm-diameter sphere, tangent to the external wall of the right atrium, centered at the height of the ascending aorta origin and the AVN was delineated by a 2 cm-diameter sphere centered at the junction between the four cardiac chambers, 1 cm above the last slice where the left atrium is visible. IMPT treatment was re-planned on the simulation CT scans for left-sided breast cancer patients. Mean and maximum doses to the SAN and the AVN were retrieved and compared.Average mean doses to the SAN and to the AVN were 2.8 Gy and 2.3 Gy respectively for left-sided irradiation and 9.6 Gy and 3.6 Gy respectively for right-sided irradiation. Average maximum doses to the SAN and to the AVN were 3.5 Gy and 2.8 Gy respectively for left-sided irradiation and 13.1 Gy and 4.6 Gy respectively for right-sided irradiation. There were no significant differences between mean and maximum dose to the AVN and to the whole heart between right- and left-sided irradiations, while the SAN was significantly more exposed for right-sided irradiation. For left-sided breast cancer patients, IMPT significantly reduces mean dose to the SAN from 2.8 Gy to 0.0 Gy and to the AVN from 2.3 Gy to 0 Gy, and maximum dose to the SAN from 3.5 Gy to 0.2 Gy and to the AVN from 2.8 Gy to 0 Gy (P < 0.01).SAN and AVN can be substantially exposed during breast VMAT, especially for right-sided irradiation, while IMPT delivers virtually no dose to the SAN or the AVN. Cardiotoxicity studies evaluating conduction node exposure might define dose constraints and criteria for additional cardiac sparing techniques, such as respiratory techniques or proton therapy, which could be beneficial to patients with underlying rhythmic or conduction disorders.