Robust Intensity-modulated Proton Therapy Research Articles

SISS-MCO: large scale sparsity-induced spot selection for fast and fully-automated robust multi-criteria optimisation of proton plans

Objective. Intensity modulated proton therapy (IMPT) is an emerging treatment modality for cancer. However, treatment planning for IMPT is labour-intensive and time-consuming. We have developed a novel approach for multi-criteria optimisation (MCO) of robust IMPT plans (SISS-MCO) that is fully automated and fast, and we compare it for head and neck, cervix, and prostate tumours to a previously published method for automated robust MCO (IPBR-MCO, van de Water 2013). Approach. In both auto-planning approaches, the applied automated MCO of spot weights was performed with wish-list driven prioritised optimisation (Breedveld 2012). In SISS-MCO, spot weight MCO was applied once for every patient after sparsity-induced spot selection (SISS) for pre-selection of the most relevant spots from a large input set of candidate spots. IPBR-MCO had several iterations of spot re-sampling, each followed by MCO of the weights of the current spots. Main results. Compared to the published IPBR-MCO, the novel SISS-MCO resulted in similar or slightly superior plan quality. Optimisation times were reduced by a factor of 6 i.e. from 287 to 47 min. Numbers of spots and energy layers in the final plans were similar. Significance. The novel SISS-MCO automatically generated high-quality robust IMPT plans. Compared to a published algorithm for automated robust IMPT planning, optimisation times were reduced on average by a factor of 6. Moreover, SISS-MCO is a large scale approach; this enables optimisation of more complex wish-lists, and novel research opportunities in proton therapy.

Validation of Fully Automated Robust Multicriterial Treatment Planning for Head and Neck Cancer IMPT

Our purpose was to compare robust intensity modulated proton therapy (IMPT) plans, automatically generated with wish-list-based multicriterial optimization as implemented in Erasmus-iCycle, with manually created robust clinical IMPT plans for patients with head and neck cancer. Thirty-three patients with head and neck cancer were retrospectively included. All patients were previously treated with a manually created IMPT plan with 7000 cGy dose prescription to the primary tumor (clinical target volume [CTV]7000) and 5425 cGy dose prescription to the bilateral elective volumes (CTV5425). Plans had a 4-beam field configuration and were generated with scenario-based robust optimization (21 scenarios, 3-mm setup error, and ±3% density uncertainty for the CTVs). Three clinical plans were used to configure the Erasmus-iCycle wish-list for automated generation of robust IMPT plans for the other 30 included patients, in line with clinical planning requirements. Automatically and manually generated IMPT plans were compared for (robust) target coverage, organ-at-risk (OAR) doses, and normal tissue complication probabilities (NTCP). No manual fine-tuning of automatically generated plans was performed. For all automatically generated plans, voxel-wise minimum D98% values for the CTVs were within clinical constraints and similar to manual plans. All investigated OAR parameters were favorable in the automatically generated plans (all P < .001). Median reductions in mean dose to OARs went up to 667 cGy for the inferior pharyngeal constrictor muscle, and median reductions in D0.03cm3 in serial OARs ranged up to 1795 cGy for the spinal cord surface. The observed lower mean dose in parallel OARs resulted in statistically significant lower NTCP for xerostomia (grade ≥2: 34.4% vs 38.0%; grade ≥3: 9.0% vs 10.2%) and dysphagia (grade ≥2: 11.8% vs 15.0%; grade ≥3: 1.8% vs 2.8%). Erasmus-iCycle was able to produce IMPT dose distributions fully automatically with similar (robust) target coverage and improved OAR doses and NTCPs compared with clinical manual planning, with negligible hands-on planning workload.

Dosimetric comparison of gantry and horizontal fixed-beam proton therapy treatment plans for base of skull chordoma.

Australia's first proton beam therapy (PBT) centre will house a fixed-beam room and two gantry rooms. As the only PBT facility in Australia for at least the short term, there is a need to efficiently allocate treatment appointments between the gantry and fixed-beam rooms. This planning study assesses the dosimetric differences between fixed-beam and gantry-based treatment plans for base of skull chordoma, one of the core indications likely to be referred for PBT in Australia. Retrospective gantry-based and fixed-beam treatment plans were generated for five patients with base of skull chordoma. Fixed-beam plans were generated with a conventional horizontal patient positioning system. Robust intensity modulated proton therapy (IMPT) optimisation and evaluation techniques were used for both delivery systems. Plans were designed to maximise target coverage while adhering to maximum dose constraints to neighbouring critical organs at risk. Robust target coverage and integral dose were found to be approximately equivalent for the gantry-based and fixed-beam plans. Doses to specific organs at risk could be reduced with the gantry-based geometry; however, the gantry-based plans did not exhibit a general decrease in doses to organs at risk. A fixed-beam treatment plan was found to be non-inferior to a gantry-based treatment plan for all base of skull patients included in the current study.

Dose comparison of robustly optimized intensity modulated proton therapy (IMPT) vs IMRT and VMAT photon plans for testicular seminoma

Background Patients with stage II seminoma have traditionally been treated with photons to the retroperitoneal and iliac space, which leads to a substantial dose bath to abdominal and pelvic organs at risk (OAR). As these patients are young and with excellent prognosis, reducing dose to OAR and thereby the risk of secondary cancer is of utmost importance. We compared IMPT to opposing IMRT fields and VMAT, assessing dose to OAR and both overall and organ-specific secondary cancer risk. Material and methods A comparative treatment planning study was conducted on planning CT-scans from ten patients with stage II seminoma, treated with photons to a ‘dog-leg’ field with doses ranging from 20 to 25 Gy and a 10 Gy sequential boost to the metastatic lymph node(s). Photon plans were either 3–4 field IMRT (Eclipse) or 1–2 arc VMAT (Pinnacle). Proton plans used robust (5 mm; 3.5%) IMPT (Eclipse), multi field optimization with 3 posterior fields supplemented by 2 anterior fields at the level of the iliac vessels. Thirty plans were generated. Mean doses to OARs were compared for IMRT vs IMPT and VMAT vs IMPT. The risk of secondary cancer was calculated according to the model described by Schneider, using excess absolute risk (EAR, per 10,000 persons per year) for body outline, stomach, duodenum, pancreas, bowel, bladder and spinal cord. Results Mean doses to all OARs were significantly lower with IMPT except similar kidney (IMRT) and spinal cord (VMAT) doses. The relative EAR for body outline was 0.59 for IMPT/IMRT (p < .05) and 0.33 for IMPT/VMAT (p < .05). Organ specific secondary cancer risk was also lower for IMPT except for pancreas and duodenum. Conclusion Proton therapy reduced radiation dose to OAR compared to both IMRT and VMAT plans, and potentially reduce the risk of secondary cancer both overall and for most OAR.

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.

Machine learning-based automatic proton therapy planning: impact of post-processing and dose-mimicking in plan robustness.

Automated treatment planning strategies are being widely implemented in clinical routine to reduce inter-planner variability, speed up the optimization process, and improve plan quality. This study aims to evaluate the feasibility and quality of intensity-modulated proton therapy (IMPT) plans generated with four different knowledge-based planning (KBP) pipelines fully integrated into a commercial treatment planning system (TPS). A data set containing 60 oropharyngeal cancer patients was split into 11 folds, each containing 47 patients for training, 5 patients for validation and 5 patients for testing. A dose prediction model was trained on each of the folds, resulting in a total of 11 models. Three patients were left out in order to assess if the differences introduced between models were significant. From voxel-based dose predictions, we analyze the two steps that follow the dose prediction: post-processing of the predicted dose and dose mimicking (DM). We focused on the effect of post-processing (PP) or no post-processing (NPP) combined with two different DM algorithms for optimization: the one available in the commercial TPS RayStation (RSM) and a simpler isodose-based mimicking (IBM). Using 55 test patients (5 test patients for each model), we evaluated the quality and robustness of the plans generated by the four proposed KBP pipelines (PP-RSM, PP-IBM, NPP-RSM, NPP-IBM). After robust evaluation, dose-volume histogram (DVH) metrics in nominal and worst-case scenarios were compared to those of the manually generated plans. Nominal doses from the four KBP pipelines showed promising results achieving comparable target coverage and improved dose to organs at risk (OARs) compared to the manual plans. However, too optimistic post-processing applied to the dose prediction (i.e. important decrease of the dose to the organs) compromised the robustness of the plans. Even though RSM seemed to partially compensate for the lack of robustness in the PP plans, still 65% of the patients did not achieve the expected robustness levels. NPP-RSM plans seemed to achieve the best trade-off between robustness and OAR sparing. PP and DM strategies are crucial steps to generate acceptable robust and deliverable IMPT plans from ML-predicted doses. Before the clinical implementation of any KBP pipeline, the PP and DM parameters predefined by the commercial TPS need to be modified accordingly with a comprehensive feedback loop in which the robustness of the final dose calculations is evaluated. With the right choice of PP and DM parameters, KBP strategies have the potential to generate IMPT plans within clinically acceptable levels comparable to plans manually generated by dosimetrists. This article is protected by copyright. All rights reserved.

Scatter correction of 4D cone beam computed tomography to detect dosimetric effects due to anatomical changes in proton therapy for lung cancer.

The treatment of moving tumor entities is expected to have superior clinical outcomes, using image-guided adaptive intensity-modulated proton therapy (IMPT). For 21 lung cancer patients, IMPT dose calculations were performed on scatter-corrected 4D cone beam CTs (4DCBCTcor ) to evaluate their potential for triggering treatment adaptation. Additional dose calculations were performed on corresponding planning 4DCTs and day-of-treatment 4D virtual CTs (4DvCTs). A 4DCBCT correction workflow, previously validated on a phantom, generates 4DvCT (CT-to-CBCT deformable registration) and 4DCBCTcor images (projection-based correction using 4DvCT as a prior) with 10 phase bins, using day-of-treatment free-breathing CBCT projections and planning 4DCT images as input. Using a research planning system, robust IMPT plans administering eight fractions of 7.5 Gy were created on a free-breathing planning CT (pCT) contoured by a physician. The internal target volume (ITV) was overridden with muscle tissue. Robustness settings for range and setup uncertainties were 3% and 6 mm, and a Monte Carlo dose engine was used. On every phase of planning 4DCT, day-of-treatment 4DvCT, and 4DCBCTcor , the dose was recalculated. For evaluation, image analysis as well as dose analysis were performed using mean error (ME) and mean absolute error (MAE) analysis, dose-volume histogram (DVH) parameters, and 2%/2-mm gamma pass rate analysis. Action levels (1.6% ITV D98 and 90% gamma pass rate) based on our previous phantom validation study were set to determine which patients had a loss of dosimetriccoverage. Quality enhancements of 4DvCT and 4DCBCTcor over 4DCBCT were observed. ITV D98% and bronchi D2% had its largest agreement for 4DCBCTcor -4DvCT, and the largest gamma pass rates (>94%, median 98%) were found for 4DCBCTcor -4DvCT. Deviations were larger and gamma pass rates were smaller for 4DvCT-4DCT and 4DCBCTcor -4DCT. For five patients, deviations were larger than the action levels, suggesting substantial anatomical changes between pCT and CBCT projectionsacquisition. This retrospective study shows the feasibility of daily proton dose calculation on 4DCBCTcor for lung tumor patients. The applied method is of clinical interest as it generates up-to-date in-room images, accounting for breathing motion and anatomical changes. This information could be used to triggerreplanning.

Deformed dose restoration to account for tumor deformation and position changes for adaptive proton therapy.

Online adaptation during intensity-modulated proton therapy (IMPT) can minimize the effect of inter-fractional anatomical changes, but remains challenging because of the complex workflow. One approach for fast and automated online IMPT adaptation is dose restoration, which restores the initial dose distribution on the updated anatomy. However, this method may fail in cases where tumor deformation or position changes occur. To develop a fast and robust IMPT online adaptation method named "deformed dose restoration (DDR)" that can adjust for inter-fractional tumor deformation and position changes. THE DDR METHOD COMPRISES TWO STEPS: : (1) calculation of the deformed dose distribution, and (2) restoration of the deformed dose distribution. First, the deformable image registration (DIR) between the initial clinical target volume (CTV) and the new CTV were performed to calculate the vector field. To ensure robustness for setup and range uncertainty and the ability to restore the deformed dose distribution, an expanded CTV-based registration to maintain the dose gradient outside the CTV was developed. The deformed dose distribution was obtained by applying the vector field to the initial dose distribution. Then, the voxel-by-voxel dose difference optimization was performed to calculate beam parameters that restore the deformed dose distribution on the updated anatomy. The optimization function was the sum of total dose differences and dose differences of each field to restore the initial dose overlap of each field. This method only requires target contouring, which eliminates the need for organs at risk (OARs) contouring. Six clinical cases wherein the tumor deformation and/or position changed on repeated CTs were selected. DDR feasibility was evaluated by comparing the results with those from three other strategies, namely, not adapted (continuing the initial plan), adapted by previous dose restoration, and fully optimized. In all cases, continuing the initial plan was largely distorted on the repeated CTs and the dose-volume histogram (DVH) metrics for the target were reduced due to the tumor deformation or position changes. On the other hand, DDR improved DVH metrics for the target to the same level as the initial dose distribution. Dose increase was seen for some OARs because tumor growth had reduced the relative distance between CTVs and OARs. Robustness evaluation for setup and range uncertainty (3 mm/3.5%) showed that deviation in DVH-bandwidth for CTV D95% from the initial plan was 0.4 ± 0.5% (Mean ± S.D.) for DDR. The calculation time was 8.1 ± 6.4 min. An online adaptation algorithm was developed that improved the treatment quality for inter-fractional anatomical changes and retained robustness for intra-fractional setup and range uncertainty. The main advantage of this method is that it only requires target contouring alone and saves the time for OARs contouring. The fast and robust adaptation method for tumor deformation and position changes described here can reduce the need for offline adaptation and improve treatment efficiency. This article is protected by copyright. All rights reserved.

Automated Robust Planning for IMPT in Oropharyngeal Cancer Patients Using Machine Learning

The aim of this study was to evaluate an automated treatment planning method for robustly optimized intensity modulated proton therapy (IMPT) plans for oropharyngeal carcinoma patients and to compare the results with manually optimized robust IMPT plans. An atlas regression forest based machine learning (ML) model for dose prediction was trained on CT scans, contours and dose distributions of robust IMPT plans of 88 oropharyngeal cancer patients (OCP). The ML model was combined with a robust voxel and dose volume histogram based dose mimicking optimization algorithm for 21 perturbed scenarios to generate a machine deliverable plan from the predicted dose distribution. Machine learning optimization (MLO) configuration was performed using a cross-validation approach with 3 × 8 tuning patients and comprised of adjustments to the mimicking optimization, to generate higher quality MLO plans. Independent testing of the MLO algorithm was performed with another 25 patients. Plan quality of clinical and MLO plans was evaluated by the clinical target volume (D98% voxel-wise minimum dose >94%), organ at risk (OAR) doses and the normal tissue complication probability (NTCP) (sum (Σ) of grade-2 and grade-3 dysphagia and xerostomia). Adequate robust target coverage was achieved in 24/25 clinical plans and in 23/25 MLO plans in the primary clinical target volume (CTV). In the elective CTV, 22/25 clinical plans and 24/25 MLO plans passed the robust target coverage evaluation threshold. The MLO average Σgrade 2 and Σgrade 3 NTCPs were comparable to the clinical plans (Σgrade 2 NTCPs: clinical 47.5% vs MLO 48.4%, Σgrade 3 NTCPs: clinical 11.9% vs MLO 12.3%). Significant increases in OAR average doses in MLO plans were found in the pharynx constrictor muscles (163 cGy, p=0.002) and cervical esophagus (265 cGy, p=0.002). The MLO plans were created within 45 min. This study showed that automated MLO planning is able to generate robustly optimized MLO plans with quality comparable to clinical plans in OCP.

Target Volume Coverage and Organ at Risk Doses for Left-sided Whole-breast Irradiation With or Without Internal Mammary Chain Irradiation: A Comparison Between Three Techniques Representing the Past and the Present

AimsThe 15-year results of the EORTC 229922-10925 phase III trial showed a significant reduction in breast cancer mortality and breast cancer recurrences after internal mammary chain (IMC) and medio-supraclavicular irradiation. Unexpectedly, cardiac death was not increased, and the incidence of cardiac events did not differ between left- and right-sided cases, although target volume coverages and organ at risk doses were unknown. Therefore, a planning study was carried out comparing the past and the present, to eventually enable, thereafter, an increased therapeutic ratio of IMC irradiation. Materials and methodsA planning study was carried out on target volume coverage and organ at risk doses for whole-breast irradiation (WBI) ± IMC comparing the results between two-dimensional radiotherapy (free-breathing), hybrid intensity-modulated radiotherapy (IMRT; breath-hold) and robust intensity-modulated proton therapy (IMPT; free-breathing) for 10 left-sided breast cancer cases. Two-dimensional radiotherapy consisted of two tangential wedged photon breast fields and mixed electron/photon beams for the IMC. Hybrid IMRT included two tangential photon breast fields (70%) complemented with IMRT (30%). IMPT plans were created using multi-field robust optimisation (5 mm set-up and 3% range uncertainties) with two (WBI) or three (WBI + IMC) beams. ResultsTarget volume dose objectives were met for hybrid IMRT and IMPT. For two-dimensional radiotherapy, target coverage was 97% and 83% for breast and IMC, respectively. The mean heart dose for WBI only was <2 Gy for all techniques. For WBI + IMC, heart doses (mean heart dose, mean left anterior descending region, volume of the heart receiving 5 Gy (V5) were significantly higher for two-dimensional radiotherapy when compared with contemporary techniques. The V5 left anterior descending region reduced from 100% (two-dimensional radiotherapy) to 70% and 20% for hybrid IMRT and IMPT, respectively. Conclusion: Contemporary radiotherapy techniques result in improved target volume coverage and significantly decreased heart doses for WBI + IMC radiotherapy. Hence, nowadays an increased therapeutic ratio of elective IMC irradiation may be anticipated.

PO-1507 Dose comparison of clinical robust intensity modulated proton therapy plans for testicular seminoma

PO-1507 Dose comparison of clinical robust intensity modulated proton therapy plans for testicular seminoma

Substantial Sparing of Organs at Risk with Modern Proton Therapy in Lung Cancer, but Altered Breathing Patterns Can Jeopardize Target Coverage.

Simple SummaryTreatment of locally advanced non-small cell lung cancer (LA-NSCLC) is a fine balance between toxicity and cure. Modern proton therapy might offer a more gentle radiation treatment compared to state-of-the-art photon radiotherapy, but is also more susceptible to the influence of breathing motion and anatomical changes. In this study, the influence of such uncertainties on treatment delivery was thoroughly investigated. Modern proton therapy did indeed show potential to reduce the risk of toxicity for the heart and lungs. This potential was maintained under the influence of anatomical and delivery uncertainties. However, changes in breathing motion jeopardized the target dose distribution in a subset of patients. We therefore recommend imaging at onset or early in treatment to recognize these patients and adapt the treatment.Enhancing treatment of locally advanced non-small cell lung cancer (LA-NSCLC) by using pencil beam scanning proton therapy (PBS-PT) is attractive, but little knowledge exists on the effects of uncertainties occurring between the planning (Plan) and the start of treatment (Start). In this prospective simulation study, we investigated the clinical potential for PBS-PT under the influence of such uncertainties. Imaging with 4DCT at Plan and Start was carried out for 15 patients that received state-of-the-art intensity-modulated radiotherapy (IMRT). Three PBS-PT plans were created per patient: 3D robust single-field uniform dose (SFUD), 3D robust intensity-modulated proton therapy (IMPT), and 4D robust IMPT (4DIMPT). These were exposed to setup and range uncertainties and breathing motion at Plan, and changes in breathing motion and anatomy at Start. Target coverage and dose-volume parameters relevant for toxicity were compared. The organ at risk sparing at Plan was greatest with IMPT, followed by 4DIMPT, SFUD and IMRT, and persisted at Start. All plans met the preset criteria for target robustness at Plan. At Start, three patients had a lack of CTV coverage with PBS-PT. In conclusion, the clinical potential for heart and lung toxicity reduction with PBS-PT was substantial and persistent. Altered breathing patterns between Plan and Start jeopardized target coverage for all PBS-PT techniques.

Single-institution clinical experience using robust intensity modulated proton therapy in chordoma and chondrosarcoma of the mobile spine and sacrum: Feasibility and need for plan adaptation

BackgroundDue to its specific physical characteristics, proton irradiation is especially suited for irradiation of chordomas and chondrosarcoma in the axial skeleton. Robust plan optimization renders the proton beam therapy more predictable upon individual setup errors. Reported experience with the planning and delivery of robustly optimized plans in chordoma and chondrosarcoma of the mobile spine and sacrum, is limited. In this study, we report on the clinical use of robustly optimized, intensity modulated proton beam therapy in these patients. MethodsWe retrospectively reviewed patient, treatment and acute toxicity data of all patients with chordoma and chondrosarcoma of the mobile spine and sacrum, treated between 1 April 2019 and 1 April 2020 at our institute. Anatomy changes during treatment were evaluated by weekly cone-beam CTs (CBCT), supplemented by scheduled control-CTs or ad-hoc control-CTs. Acute toxicity was scored weekly during treatment and at 3 months after therapy according to CTCAE 4.0. Results17 chordoma and 3 chondrosarcoma patients were included. Coverage of the high dose clinical target volume was 99.8% (range 56.1–100%) in the nominal and 80.9% (range 14.3–99.6%) in the voxel-wise minimum dose distribution. Treatment plan adaptation was needed in 5 out of 22 (22.7%) plans. Reasons for plan adaptation were either reduced tumor coverage or increased dose to the OAR. ConclusionsRobustly optimized intensity modulated proton beam therapy for chordoma and chondrosarcoma of the mobile spine is feasible. Plan adaptations due to anatomical changes were required in approximately 23 percent of treatment courses.

Small Non-Rigid Variations Can Assist Robust IMPT Plan Selection for Head and Neck Patients

Interfraction anatomical variability increases dosimetric discrepancy during delivery of intensity-modulated proton therapy (IMPT). Small non-rigid variations (sNRVs) such as neck extension, spinal flexion, jaw and shoulder position occur during IMPT for head & neck cancer. We assess dosimetric discrepancies caused by sNRVs and suggest a population-based model to incorporate sNRVs into robust evaluation of IMPT plans.A total of 20 nasopharynx and 15 oropharynx radiotherapy patients were retrospectively analyzed, each with weekly CT scans. Anatomical variations during the first week of treatment are predominately due to sNRV, when progressive changes (weight-loss, tumor shrinkage) are less significant. Using deformable image registration, we obtained deformations between week 0/week 1 of treatment for all 35 patients, creating a distribution of possible sNRVs. The deformations from this distribution are then applied to the planning CT of two patients. Patient 1 has a laterally located gross tumor volume (GTV), patient 2 has a central GTV, both with bilateral low-risk clinical target volume (CTV). For both patients, IMPT plans using 3-field, 4-field, and 5-field beam arrangements were generated (nominal dose) and dose was forward calculated on the 35 deformed CT images representing the possible sNRV dose (n = 210) to assess dose degradation. Dose-volume histogram (DVH) bandwidths for sNRV doses were calculated per patient and beam arrangement to evaluate the robustness of the nominal plans with respect to the sNRVs.Among both patients (210 scenarios), we observe a maximum difference to the nominal dose of: 7% degradation of CTV D95, increase in parotid Dmean 10.6 Gy (RBE), increase in brainstem Dmax 14.8 Gy (RBE), increase in chiasm Dmax 18 Gy (RBE), increase in larynx Dmean15 Gy (RBE). For both patients, the 4-field plan shows the narrowest bandwidth and thus best robustness against sNRV in terms of CTV coverage (tab 1). For patient 1, the 4-field plan appears most robust in terms of organ at risk dose. For patient 2, the 3-field plan shows the best parotid sparing while dose metrics for brainstem and chiasm are similar for all beam arrangements.We demonstrate that sNRVs can substantially degrade the dose to the target volume and increase OAR doses. Including the influence of sNRVs during robust evaluation may assist in plan selection, providing information on clinical uncertainties additional to the conventional rigid isocenter shift and CT number uncertainty.

Towards the clinical implementation of intensity-modulated proton therapy for thoracic indications with moderate motion: Robust optimised plan evaluation by means of patient and machine specific information

PurposeCompared to volumetric modulated arc therapy (VMAT), clinical benefits are anticipated when treating thoracic tumours with intensity-modulated proton therapy (IMPT). However, the current concern of plan robustness as a result of motion hampers its wide clinical implementation. To define an optimal protocol to treat lung and oesophageal cancers, we present a comprehensive evaluation of IMPT planning strategies, based on patient 4DCTs and machine log files. Materials and methodsFor ten lung and ten oesophageal cancer patients, a planning 4DCT and weekly repeated 4DCTs were collected. For these twenty patients, the CTV volume and motion were assessed based on the 4DCTs. In addition to clinical VMAT plans, layered rescanned 3D and 4D robust optimised IMPT plans (IMPT_3D and IMPT_4D respectively) were generated, and approved clinically, for all patients. The IMPT plans were then delivered in dry runs at our proton facility to obtain log files, and subsequently evaluated through our 4D robustness evaluation method (4DREM). With this method, for each evaluated plan, fourteen 4D accumulated scenario doses were obtained, representing 14 possible fractionated treatment courses. ResultsFrom VMAT to IMPT_3D, nominal Dmean(lungs-GTV) decreased 2.75 ± 0.56 GyRBE and 3.76 ± 0.92 GyRBE over all lung and oesophageal cancer patients, respectively. A more pronounced reduction was verified for Dmean(heart): 5.38 ± 7.36 GyRBE (lung cases) and 9.51 ± 2.25 GyRBE (oesophagus cases). Target coverage robustness of IMPT_3D was sufficient for 18/20 patients. Averaged dose in critical structures over all 4DREM scenarios changed only slightly for both IMPT_3D and IMPT_4D. Relative to IMPT_3D, no gain in IMPT_4D was observed. ConclusionThe dosimetric superiority of IMPT over VMAT has been established. For most thoracic tumours, our IMPT_3D planning protocol showed to be robust and clinically suitable. Nevertheless, accurate patient positioning and adapting to anatomical variations over the course of treatment remain compulsory.

A Retrospective Study of Bowel and Rectum Air Effect on Dose Coverage in Prostate, Colon, Gynecologic and Embryonal Rhabdomyosarcoma Tumors Treated With Robust Intensity-Modulated Proton Therapy

For pelvis patients treated with intensity-modulated proton therapy (IMPT), robust treatment plans were made by using 3 CT sets: the planning CT (pCT) set and 2 virtual CT sets that were copies of pCT but where the fillings of bowels and rectum were overridden to be either air or muscle. The hypothesis is that assessment on the air volume during patient setup is still necessary for IMPT with such robust plans. The endpoints are the mean change of CTV dose D99 and mean CTV dose D99. The assessment is assumed to be necessary if the mean change of D99 of the CTV >3% and the mean of D99 of the CTV <95%. Data from 17 cancer patients (11 prostate, 3 gynecologic, 2 colon, and 1 embryonal rhabdomyosarcoma) with pCT and weekly or biweekly scanned quality assurance CTs (QACTs; 82 QACT scans total) were studied. Air in bowels and rectum traversed by proton pencil beams was contoured. The targets in the pCT were mapped to the QACTs by deformable image registration, and the dose in QACTs was calculated with original beamline data. Dose coverage (D99 and D95) and correlations between dose coverage and changes in air volume were analyzed. The significance of the correlation was analyzed by t test. For a majority of the treatment course, the air volume during treatment was larger than that during pCT scanning. The mean (stdev) change of air volume in beam path was 0.1(0.3), 2.4(1.2) and 11.2(3.6) cc for the air in rectum, small- and large-bowels respectively. For the relative change of dose, the mean changes of D99 in QACTs were within 3% of those in the pCT for all prostate and colon cases but >5% in 2 of the 3 gynecologic cases and >3% in the embryonal rhabdomyosarcoma case. Of these 3 cases with mean change of D99 >3%, air volume was the main cause in 2, where the locations of air in the pCT and some QACTs were different, and the air was on the path of multiple beams. These resulted in accumulated dose deviation. Mean changes of D95 were systematically less than those of D99, and only in one gynecologic case the change was >3%. In the QACTs of the boost plans for those prostate bed cases, the air in bowels and rectum was not in the lateral beam paths, and the mean change of D99 andD95 was <1.5% and <0.5% respectively. Correlations were of medium strength between change in air volume and change in D99 and D95, because other anatomic changes such as patient body shape, weight, bladder filling, and femoral bone rotation also contributed to dose deviation. The correlation was statistically significant. For the absolute change of dose, increases in air volume change reduced target dose coverage in QACTs. In these 17 cases, only 2 had CTV D99 < 95% of prescription dose (Dx) and D95 < 95% of Dx in the original plan, but 5 had means of D99 < 95% of Dx and 2 had D95 < 95% of Dx in QACTs. The effect of air volume on target dose coverage is significant in treatment plans using 3 CT sets, particularly when the air is traversed by multiple beams. We suggest contouring the air and beam path in pCT and using the contours to assess patient preparation and setup.

Evaluation of plan quality and robustness of IMPT and helical IMRT for cervical cancer

BackgroundBoth plan quality and robustness were investigated through comparing some dosimetric metrics between intensity modulated proton therapy (IMPT) and helical tomotherapy based intensity modulated radiotherapy (IMRT) for cervical cancer.MethodsBoth a spot-scanning robust (SRO) IMPT plan and a helical tomotherapy robust (TRO) IMRT plan were generated for each of 18 patients. In order to evaluate the quality of nominal plans without dose perturbations, planning scores (PS) on clinical target volume (CTV) and five organs at risk (OARs) based on clinical experience, and normal tissue complication probabilities (NTCP) of rectum and sigmoid were calculated based on Lyman-Kutcher-Burman (LKB) model. Dose volume histogram bands width (DVHBW) were calculated in 28 perturbed scenarios to evaluate plan robustness.ResultsCompared with TRO, the average scores of SRO nominal plans were higher in target metrics [V46.8Gy, V50Gy, Conformity and Homogeneity](16.5 vs. 15.1), and in OARs metrics (60.9 vs. 53.3), including bladder [V35,V45, Dmean,D2cc], rectum [V40,V45,D2cc,Dmax], bowel [V35,V40,V45, Dmax], sigmoid [V40,Dmax] and femoral heads [V30,Dmax]. Meanwhile, NTCP calculation showed that the toxicities of rectum and sigmoid in SRO were lower than those in TRO (rectum: 2.8% vs. 4.8%, p < 0.05; sigmoid: 5.2% vs. 5.7%, p < 0.05). DVHBW in target coverage for the SRO plan was smaller than that for the TRO plan (0.6% vs. 2.1%), which means that the SRO plan generated a more robust plan in target.ConclusionBetter CTV coverage and OAR Sparing were obtained in SRO nominal plan. Based on NTCP calculation, SRO was expected to allow a small reduction in rectal toxicity. Furthermore, SRO generated a more robust plan in CTV target coverage.

Quantification of plan robustness against different uncertainty sources for classical and anatomical robust optimized treatment plans in head and neck cancer proton therapy.

Classical robust optimization (cRO) in intensity-modulated proton therapy (IMPT) considers isocenter position and particle range uncertainties; anatomical robust optimization (aRO) aims to consider additional non-rigid positioning variations. This work compares the influence of different uncertainty sources on the robustness of cRO and aRO IMPT plans for head and neck squamous cell carcinoma (HNSCC). Two IMPT plans were optimized for 20 HNSCC patients who received weekly control CTs (cCT): cRO, using solely the planning CT, and aRO, including 2 additional cCTs. The robustness of the plans in terms of clinical target volume (CTV) coverage and organ at risk (OAR) sparing was analyzed considering stepwise the influence of (1) non-rigid anatomical variations given by the weekly cCT, (2) with fraction-wise added rigid random setup errors and (3) additional systematic proton range uncertainties. cRO plans presented significantly higher nominal CTV coverage but are outperformed by aRO plans when considering non-rigid anatomical variations only, as cRO and aRO plans presented a median target coverage (D98%) decrease for the low-risk/high-risk CTV of 1.8/1.1 percentage points (pp) and -0.2 pp/-0.3 pp, respectively. Setup and range uncertainties had larger influence on cRO CTV coverage, but led to similar OAR dose changes in both plans. Considering all error sources, 10/2 cRO/aRO patients missed the CTV coverage and a limited number exceeded some OAR constraints in both plans. Non-rigid anatomical variations are mainly responsible for critical target coverage loss of cRO plans, whereas the aRO approach was robust against such variations. Both plans provide similar robustness of OAR parameters. The influence of different uncertainty sources was quantified for robust IMPT HNSCC plans.

Organ sparing potential and inter-fraction robustness of adaptive intensity modulated proton therapy for lung cancer

Background: The aim of this study was to compare adaptive intensity modulated proton therapy (IMPT) robustness and organ sparing capabilities with that of adaptive volumetric arc photon therapy (VMAT).Material and methods: Eighteen lung cancer patients underwent a planning 4DCT (p4DCT) and 5 weekly repeated 4DCT (r4DCT) scans. Target volumes and organs at risk were manually delineated on the three-dimensional (3D) average scans of the p4DCT (av_p4DCT) and of the r4DCT scans (av_r4DCT). Planning target volume (PTV)-based VMAT plans and internal clinical target volume (ICTV)-based robust IMPT plans were optimized in 3D on the av_p4DCT and re-calculated on the av_r4DCTs. Re-planning on av_r4DCTs was performed when indicated and accumulated doses were evaluated on the av_p4DCT.Results: Adaptive VMAT and IMPT resulted in adequate ICTV coverage on av_r4DCT in all patients and adequate accumulated-dose ICTV coverage on av_p4DCT in 17/18 patients (due to a shrinking target in one patient). More frequent re-planning was needed for IMPT than for VMAT. The average mean heart dose reduction with IMPT compared with VMAT was 4.6 Gy (p = .001) and it was >5 Gy for five patients (6, 7, 8, 15, and 22 Gy). The average mean lung dose reduction was 3.2 Gy (p < .001). Significant reductions in heart and lung V5 Gy were observed with IMPT.Conclusion: Robust-planned IMPT required re-planning more often than VMAT but resulted in similar accumulated ICTV coverage. With IMPT, heart and lung mean dose values and low dose regions were significantly reduced. Substantial cardiac sparing was obtained in a subgroup of five patients (28%).

Multiple-CT optimization: An adaptive optimization method to account for anatomical changes in intensity-modulated proton therapy for head and neck cancers

PurposeWe aimed to determine whether multiple-CT (MCT) optimization of intensity-modulated proton therapy (IMPT) could improve plan robustness to anatomical changes and therefore reduce the additional need for adaptive planning. Methods and materialsTen patients with head and neck cancer who underwent IMPT were included in this retrospective study. Each patient had primary planning CT (PCT), a first adaptive planning CT (ACT1), and a second adaptive planning CT (ACT2). Selective robust IMPT plans were generated using each CT data set (PCT, ACT1, and ACT2). Moreover, a MCT optimized plan was generated using the PCT and ACT1 data sets together. Dose distributions optimized using each of the four plans (PCT, ACT1, ACT2, and MCT plans) were re-calculated on ACT2 data. The doses to the target and to organs at risk were compared between optimization strategies. ResultsMCT plans for all patients met all target dose and organs-at-risk criteria for all three CT data sets. Target dose and organs-at-risk dose for PCT and ACT1 plans re-calculated on ACT2 data set were compromised, indicating the need for adaptive planning on ACT2 if PCT or ACT1 plans were used. The D98% of CTV1 and CTV3 of MCT plan re-calculated on ACT2 were both above the coverage criteria. The CTV2 coverage of the MCT plan re-calculated on ACT2 was worse than ACT2 plan. The MCT plan re-calculated on ACT2 data set had lower chiasm, esophagus, and larynx doses than did PCT, ACT1, or ACT2 plans re-calculated on ACT2 data set. ConclusionsMCT optimization can improve plan robustness toward anatomical change and may reduce the number of plan adaptation for head and neck cancers.