Nominal Plan Research Articles

Robust IMPT and follow-up toxicity in skull base chordoma and chondrosarcoma-asingle-institution clinical experience.

Chordomas and chondrosarcomas of the skull base are rare, slowly growing malignant bone neoplasms. Despite their radioresistant properties, proton therapy has been successfully used as an adjunct to resection or as adefinitive treatment. Herewith, we present our experience with robustly optimized intensity-modulated proton therapy (IMPT) and related toxicities in skull base chordoma and chondrosarcoma patients treated at HollandPTC, Delft, the Netherlands. Clinical data, treatment plans, and acute toxicities of patients treated between July 2019 and August 2021 were reviewed. CT and 3.0T MRI scans for treatment planning were performed in supine position in athermoplastic mold. In total, 21dose optimization and 28dose evaluation scenarios were simulated. Acute toxicity was scored weekly before and during the treatment according to the CTCAE v4.0. Median follow-up was 35months (range 12-36months). Overall, 9chordoma and 3chondrosarcoma patients with 1-3 resections prior to IMPT were included; 4patients had titanium implants. Brainstem core and surface and spinal cord core and surface were used for nominal plan robust optimization in 11, 10, 8, and 7patients, respectively. Middle ear inflammation, dry mouth, radiation dermatitis, taste disorder, and/or alopecia of grades 1-3 were noted at the end of treatment among 6patients without similar complaints at inclusion; symptoms disappeared 3months following the treatment. Robustly optimized IMPT is clinically feasible as apostoperative treatment for skull base chordoma and chondrosarcoma patients. We observed acceptable early toxicities (grade1-3) that disappeared within the first 3months after irradiation.

Quantifying the Dosimetric Impact of Proton Range Uncertainties on RBE-Weighted Dose Distributions in Intensity-Modulated Proton Therapy for Bilateral Head and Neck Cancer.

In current clinical practice, intensity-modulated proton therapy (IMPT) head and neck cancer (HNC) plans are generated using a constant relative biological effectiveness (cRBE) of 1.1. The primary goal of this study was to explore the dosimetric impact of proton range uncertainties on RBE-weighted dose (RWD) distributions using a variable RBE (vRBE) model in the context of bilateral HNC IMPT plans. The current study included the computed tomography (CT) datasets of ten bilateral HNC patients who had undergone photon therapy. Each patient's plan was generated using three IMPT beams to deliver doses to the CTV_High and CTV_Low for doses of 70 Gy(RBE) and 54 Gy(RBE), respectively, in 35 fractions through a simultaneous integrated boost (SIB) technique. Each nominal plan calculated with a cRBE of 1.1 was subjected to the range uncertainties of ±3%. The McNamara vRBE model was used for RWD calculations. For each patient, the differences in dosimetric metrices between the RWD and nominal dose distributions were compared. The constrictor muscles, oral cavity, parotids, larynx, thyroid, and esophagus showed average differences in mean dose (Dmean) values up to 6.91 Gy(RBE), indicating the impact of proton range uncertainties on RWD distributions. Similarly, the brachial plexus, brain, brainstem, spinal cord, and mandible showed varying degrees of the average differences in maximum dose (Dmax) values (2.78-10.75 Gy(RBE)). The Dmean and Dmax to the CTV from RWD distributions were within ±2% of the dosimetric results in nominal plans. The consistent trend of higher mean and maximum doses to the OARs with the McNamara vRBE model compared to cRBE model highlighted the need for consideration of proton range uncertainties while evaluating OAR doses in bilateral HNC IMPT plans.

Software cost and effort estimation using dragonfly whale optimized multilayer perceptron neural network

This paper proposed a Constructive Rapid Application Development Model based Software Cost Estimation Technique (CORADMO based SCET) for accurate software cost estimation. The data requirements, cost drivers, constraints and priorities are given as an input to the Fuzzy Inference System (FIS). The processed output such as effort, time and cost for nominal plan, shortest schedule plan, and least cost plan are computed in the Fuzzy Inference System (FIS). Further to reduce the effort time and cost means, the output optimized by Dragon fly Whale Optimization (DWO)which provides the best estimated effort, time and cost as an output for software development. The proposed CORADMO based SCET model is evaluated by NASA 93 dataset using MATLAB. The performance of the CORADMO based SCET approach is assessed in terms of Mean Magnitude of Relative Error, Pred (25%), and Magnitude of Relative Error attains the values of 98.77%, 92.55%, and 93.45% respectively. Finally, the CORADMO based SCET model justifies the suitability of Dragon fly Whale Optimization with the proposed fuzzy logic.

Comparison of plan quality and robustness using VMAT and IMRT for breast cancer

Abstract To evaluate the plan quality and robustness of volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) for breast cancer, 50 patients, including 25 patients who received radiotherapy after breast-conserving surgery (BCR) and 25 patients who received postmastectomy radiotherapy (PRT), were selected for this study. Nominal VMAT and IMRT plans were generated for each patient on Eclipse treatment planning system (version 15.6). The dosimetric metrics, dose distribution, gamma passing rate, and delivery time were compared. In addition, 12 uncertainty plans with plan isocenter uncertainty and CT density uncertainty were recalculated based on the nominal plans for each patient. The dose volume histogram (DVH) band width (DVHBW) was adopted to quantify the plan robustness of the nominal plans for the perturbed scenarios in this study. For BCR, the dosimetric metrics except planning target volume (PTV) conformal index (CI) and ipsilateral lung V 5 were not statistically different for IMRT and VMAT plans. PTV CI of VMAT plans was better than that of IMRT plans (VMAT: 0.923 ± 0.024, IMRT: 0.855 ± 0.032, p = 0.003). The ipsilateral lung V 5 of VMAT plan was higher than that of IMRT plan (VMAT: 42.4% ± 2.8%, IMRT: 40.5% ± 4.0%, p = 0.045). The VMAT plans save more than 1.20 min compared to the IMRT plans (VMAT: 0.87 min, IMRT: 2.08 min, p < 0.001). The gamma passing rates of VMAT plans were better than those of IMRT plans (3 mm/3%, VMAT: 99.7% ± 0.2%, IMRT: 99.4% ± 0.4%, p < 0.001; 2 mm/2%, VMAT: 97.2% ± 1.0%, IMRT: 96.9% ± 0.6%, p = 0.108). For PRT, the dosimetric metrics of VMAT plans, including PTV D mean, homogeneity index (HI), CI, and D max of spinal cord, were significantly better than those of IMRT plans. The VMAT plans save more than 45% time compared with IMRT plans (VMAT: 1.54 min, IMRT: 2.81 min, p < 0.001). The difference in gamma passing rates between VMAT plans and IMRT plans was not statistically significant. For the plan robustness, the DVHBW of VMAT plans and IMRT plans for BCR were 2.09% ± 0.23% and 2.98% ± 0.40%, respectively (p < 0.05). For PRT, the DVHBW of VMAT plans was significantly better than those of IMRT plans (VMAT: 3.05% ± 0.26%, IMRT: 3.57% ± 0.27%, p < 0.05). The results show that the dosimetric metrics of VMAT plans were comparable to those of IMRT plans. More importantly, the VMAT plans had excited dose distribution and fast execution efficiency. The plan robustness of VMAT plans were superior.

Real-time schedule adjustments for conflict-free vehicle routing

Conflict-Free Vehicle Routing Problems (CFVRPs) arise in manufacturing, transportation and logistics applications where Automated Guided Vehicles (AGVs) are utilized to move pallets and containers. A peculiar feature of these problems is that collision avoidance among vehicles must be considered explicitly. To make things more complex, the uncertainty affecting both travel times and machine ready times often results in vehicle delays or anticipations that require real-time modifications to the fleet nominal plan. In this paper, the determination of such modifications (schedule adjustment problem in CFVRPs) is modeled as a sequential decision problem for which we develop a tailored fast exact algorithm suitable for any objective function that is non-decreasing in the arrival times. Computational results show that optimal solutions can be found within at most 3.3 milliseconds for instances with up to 300 vehicles with improvements of various performance measures up to 74% compared to state-of-the-art solution algorithms.

Pencil beam scanning proton therapy for mediastinal lymphomas in deep inspiration breath-hold: a retrospective assessment of plan robustness.

The aim of this study was to evaluate pencil beam scanning (PBS) proton therapy (PT) in deep inspiration breath-hold (DIBH) for mediastinal lymphoma patients, by retrospectively evaluating plan robustness to the clinical target volume (CTV) and organs at risk (OARs) on repeated CT images acquired throughout treatment. Methods: Sixteen mediastinal lymphoma patients treated with PBS-PT in DIBH were included. Treatment plans (TPs) were robustly optimized on the CTV (7 mm/4.5%). Repeated verification CTs (vCT) were acquired during the treatment course, resulting in 52 images for the entire patient cohort. The CTV and OARs were transferred from the planning CT to the vCTs with deformable image registration and the TPs were recalculated on the vCTs. Target coverage and OAR doses at the vCTs were compared to the nominal plan. Deviation in lung volume was also calculated. The TPs demonstrated high robust target coverage throughout treatment with D98%,CTV deviations within 2% for 14 patients and above the desired requirement of 95% for 49/52 vCTs. However, two patients did not achieve a robust dose to CTV due to poor DIBH reproducibility, with D98%,CTV at 78 and 93% respectively, and replanning was performed for one patient. Adequate OAR sparing was achieved for all patients. Total lung volume variation was below 10% for 39/52 vCTs. PBS PT in DIBH is generally a robust technique for treatment of mediastinal lymphomas. However, closely monitoring the DIBH-reproducibility during treatment is important to avoid underdosing CTV and achieve sufficient dose-sparing of the OARs.

A retrospective study on the investigation of potential dosimetric benefits of online adaptive proton therapy for head and neck cancer.

Proton therapy is sensitive to anatomical changes, often occurring in head-and-neck (HN) cancer patients. Although multiple studies have proposed online adaptive proton therapy (APT), there is still a concern in the radiotherapy community about the necessity of online APT. We have performed a retrospective study to investigate the potential dosimetric benefits of online APT for HN patients relative to the current offline APT. Our retrospective study has a patient cohort of 10 cases. To mimic online APT, we re-evaluated the dose of the in-use treatment plan on patients' actual treatment anatomy captured by cone-beam CT (CBCT) for each fraction and performed a templated-based automatic replanning if needed, assuming that these were performed online before treatment delivery. Cumulative dose of the simulated online APT course was calculated and compared with that of the actual offline APT course and the designed plan dose of the initial treatment plan (referred to as nominal plan). The ProKnow scoring system was employed and adapted for our study to quantify the actual quality of both courses against our planning goals. The average score of the nominal plans over the 10 cases is 41.0, while those of the actual offline APT course and our simulated online course is 25.8 and 37.5, respectively. Compared to the offline APT course, our online course improved dose quality for all cases, with the score improvement ranging from 0.4 to 26.9 and an average improvement of 11.7. The results of our retrospective study have demonstrated that online APT can better address anatomical changes for HN cancer patients than the current offline replanning practice. The advanced artificial intelligence based automatic replanning technology presents a promising avenue for extending potential benefits of online APT.

Comparing Efficacy Between Robust and PTV Margin-based Optimizations for Interfractional Anatomical Variations in Prostate Tomotherapy.

Interfractional anatomical variations cause considerable differences between planned and actual radiotherapy doses. This study aimed to investigate the efficacy of robust and planning target volume (PTV) margin-based optimizations for the anatomical variations in helical tomotherapy for prostate cancer. Ten patients underwent treatment-planning kilovolt computed tomography (kVCT) and daily megavolt computed tomography (MVCT). Two types of nominal plans, with a prescription of 60 Gy/20 fractions, were created using robust and PTV margin-based optimizations on kVCT for each patient. Subsequently, the daily estimated doses were recalculated using nominal plans, and all available MVCTs modified the daily patient-setup errors. Due to the difference in dose calculation accuracy between kVCT and MVCT, three scenarios with dose corrections of 1, 2, and 3% were considered in the recalculation process. The dosimetric metrics, including target coverage with the prescription dose, Paddick's conformity index, homogeneity index, and mean dose to the rectum, were analyzed. A dosimetric comparison of the nominal plans demonstrated that the robust plans had better dose conformity, lower target coverage, and dose homogeneity than the PTV plans. In the daily estimated doses of any dose-corrected scenario, the target coverage and dose sparing to the rectum in the robust plans were significantly higher than those in the PTV plans, whereas dose conformity and homogeneity were identical to those of the nominal case. Robust optimization is recommended as it accounts for anatomical variations during treatment regarding target coverage in helical tomotherapy plans for prostate cancer.

Interplay Effect of Splenic Motion for Total Lymphoid Irradiation in Pediatric Proton Therapy.

(1) Background: The most significant cause of an unacceptable deviation from the planned dose during respiratory motion is the interplay effect. We examined the correlation between the magnitude of splenic motion and its impact on plan quality for total lymphoid irradiation (TLI); (2) Methods: Static and 4D CT images from ten patients were used for interplay effect simulations. Patients' original plans were optimized based on the average CT extracted from the 4D CT and planned with two posterior beams using scenario-based optimization (±3 mm of setup and ±3% of range uncertainty) and gradient matching at the level of mid-spleen. Dynamically accumulated 4D doses (interplay effect dose) were calculated based on the time-dependent delivery sequence of radiation fluence across all phases of the 4D CT. Dose volume parameters for each simulated treatment delivery were evaluated for plan quality; (3) Results: Peak-to-peak splenic motion (≤12 mm) was measured from the 4D CT of ten patients. Interplay effect simulations revealed that the ITV coverage of the spleen remained within the protocol tolerance for splenic motion, ≤8 mm. The D100% coverage for ITV spleen decreased from 95.0% (nominal plan) to 89.3% with 10 mm and 87.2% with 12 mm of splenic motion; (4) Conclusions: 4D plan evaluation and robust optimization may overcome problems associated with respiratory motion in proton TLI treatments. Patient-specific respiratory motion evaluations are essential to confirming adequate dosimetric coverage when proton therapy is utilized.

The first investigation of spot-scanning proton arc (SPArc) delivery time and accuracy with different delivery tolerance window settings

Objective. To investigate the impact of various delivery tolerance window settings on the treatment delivery time and dosimetric accuracy of spot-scanning proton arc (SPArc) therapy. Approach. SPArc plans were generated for three representative disease sites (brain, lung, and liver cancer) with an angle sampling frequency of 2.5°. An in-house dynamic arc controller was used to simulate the arc treatment delivery with various tolerance windows (±0.25, ±0.5, ±1, and ±1.25°). The controller generates virtual logfiles during the arc delivery simulation, such as gantry speed, acceleration and deceleration, spot position, and delivery sequence, similar to machine logfiles. The virtual logfile was then imported to the treatment planning system to reconstruct the delivered dose distribution and compare it to the initial SPArc nominal plan. A three-dimensional gamma index was used to quantitatively assess delivery accuracy. Total treatment delivery time and relative lost time (dynamic arc delivery time—fix beam delivery time)/fix beam delivery time) were reported. Main Results. The 3D gamma passing rate (GPR) was greater than 99% for all cases when using 3%/3 mm and 2%/2 mm criteria and the GPR (1%/1 mm criteria) degraded as the tolerance window opens. The total delivery time for dynamic arc delivery increased with the decreasing delivery tolerance window length. The average delivery time and the relative lost time (%) were 630 ± 212 s (253% ± 68%), 322 ± 101 s (81% ± 31%), 225 ± 60 s (27% ± 16%), 196 ± 41 s (11% ± 6%), 187 ± 29 s (6% ± 1%) for tolerance windows ±0.25, ±0.5, ±1, and ±1.25° respectively. Significance. The study quantitatively analyzed the dynamic SPArc delivery time and accuracy with different delivery tolerance window settings, which offer a critical reference in the future SPArc plan optimization and delivery controller design.

Off-nominal transfer analysis for NASA’s solar cruiser mission

In this work, off-nominal trajectory design options for NASA’s sail-based Solar Cruiser mission are examined. A novel method for constructing bounded trajectories about a periodic reference orbit is used to parameterize insertion into the target sub-L1 halo orbit. The nominal mission plan of reaching the sub-L1 halo orbit under purely sail power is then examined for a range of projected launch vehicle dispersions. Results indicate that cold (underburn) injections less than −0.2 m/s are incapable of arriving at the nominal sub-L1 mission orbit. However, hot (overburn) injections are shown to be much more robust to the nominal mission plan than the low-energy trajectories. The resilience of the overburn cases compared to the underburn cases reveals that the mission would significantly benefit from additional launch vehicle hyperbolic excess energy to ensure mission requirements are satisfied.

Is Robust Optimization Essential When Planning Pencil Beam Scanned Proton Therapy for Intracranial Lesions?

Creating intensity modulated proton therapy (IMPT) plans usually involves a robust optimization step to account for uncertainties in proton range and positioning instead of using the PTV margins typically seen in photon IMRT planning. Because robust optimization adds significant planning time per iteration, and proton planning typically involves many iterations to obtain an optimal plan, this project evaluates whether a PTV approach can be used to more efficiently create plans for intracranial lesions by comparing plan quality from both approaches to determine if they produce equivalent plans. Five patients with intracranial lesions treated with IMPT at our center were randomly chosen for this study. 3-4 beams were used to treat CTVs ranging between 46 and 246 cc. Patients were treated on a Mevion S250i single-vault proton machine with Hyperscan. Static blocks (7mm conformed to the CTV) were used for all cases and plans were created in a treatment planning system using robustness criteria of 3mm (position uncertainty) and 3.5% (range uncertainty). For each patient, the CTV was uniformly grown by 3 mm to create a PTV. The optimization criteria used in the clinical plan were used as baseline to create two plans - one using robust optimization for CTV coverage and one without robust optimization for PTV coverage. A script was used to time two otherwise identical optimization runs. All plans were normalized so that the prescription was delivered to 95% of the CTV. The plan was robustly evaluated under conditions of 3.5% range uncertainty and 2mm positional uncertainty. For each nominal plan, the CTV dose heterogeneity and conformity as well as the following dose metrics were collected: CTV D99% and D98%, Normal Brain V100%, V90%, V80%, V50% as well as overall plan Dmax (to 0.03cc). For each plan, the minimum CTV D99 and maximum Brain Dmax were also collected for the robust evaluation scenarios. All collected metrics were compared between the robust CTV-based and non-robust PTV-based plans using paired t-tests with 5% significance. For the five cases investigated here, all dosimetric metrics investigated were not significantly different between the CTV-based and PTV-based plans except for the plan maximum dose (CTV-based: 104.6% Rx - 110.0% Rx, PTV-based: 105.6% Rx-110.6% Rx, p = 0.029). The optimization times were also significantly different, averaging 1532 s for CTV-based plans versus 252 s for the PTV-based plans (p = 0.004). For the plans investigated here, non-robust PTV planning approach creates plans of very similar quality to a robust CTV-based plan, while having significantly shorter planning times.

Plan robustness evaluation strategies in whole-pelvic proton therapy for high-risk prostate cancer patients within a randomised clinical trial

Background Inter-fractional anatomical changes challenge robust delivery of whole-pelvic proton therapy for high-risk prostate cancer. Pre-treatment robust evaluation (PRE) takes uncertainties in isocenter shifts and distal beam edge in treatment plans into account. Using weekly control computed tomography scans (cCTs), the aim of this study was to evaluate the PRE strategy by comparing to an off-line during-treatment robust evaluation (DRE) while also assessing plan robustness with respect to protocol planning constraints. Material and methods Treatment plans and cCTs from ten patients included in the pilot phase of the PROstate PROTON Trial 1 were analysed. Treatment planning followed protocol guidelines with 78 Gy to the primary clinical target volume (CTVp) and 56 Gy to the elective target (CTVe) in 39 fractions. Recalculations of the treatment plans were performed for a total of 64 cCTs and dose/volume measures corresponding to clinical constraints were evaluated for this DRE against the simulated scenario interval from the PRE. Results Of the 64 cCTs, 59 showed DRE CTVp measures within the robustness range from the PRE; this was also the case for 39 of the cCTs for the CTVe measures. However, DRE CTVe coverage was still within constraints for 57 of the 64 cCTs. DRE dose/volume measures for CTVp fulfilled target coverage constraints in 59 of 64 cCTs. All DRE measures for the rectum, bladder, and bowel were inside the PRE range in 63, 39, and 31 cCTs, respectively. Conclusion The PRE strategy predicted the DRE scenarios for CTVp and rectum. CTVe, bladder, and bowel showed more complex anatomical variations than simulated by the PRE isocenter shift. Both original and recalculated nominal treatment plans showed robust treatment delivery in terms of target coverage.

Characterization of Photon Intensity Modulated Radiation Therapy Robustness in Patients With Prostate Cancer as a Proposed Benchmark for Proton Therapy Robustness Evaluation

Robustness evaluation is increasingly used in particle therapy planning to assess clinical target volume (CTV) coverage in the setting of setup and range uncertainty. However, no clear standard exists as to an acceptable degree of plan robustness. The aim of this study is to quantify x-ray robustness parameters, as this could inform proton planning when held to a similar standard. Consecutive patients with prostate adenocarcinoma treated with definitive x-irradiation to the prostate alone at a single institution in 2019 were retrospectively reviewed. CTV to planned target volume (PTV) margins of 7 mm in all directions, except 4 mm posteriorly, were used in the main cohort. Plans were normalized to PTV V100% ≥ 95%. Patient setup errors were simulated by shifting the isocenter relative to the patient in each of the cardinal directions. The magnitude of each shift equaled the magnitude of the CTV to PTV expansion in that direction. Range uncertainty was set to 0%. A total of 27 patients were evaluated. The mean (SD) nominal plan CTV V100% was 99.6% (1.1%). The mean (SD) worst-case shift CTV V100% was 97.2% (2.8%). The mean (SD) nominal and worst-case CTV V95% were 100% (0%) and 99.7% (0.5%), respectively. A worst-case CTV V100% > 90% and a worst-case CTV V95% > 99% were achieved in over 95% of plans. The mean (SD) nominal and worst-case rectal V70 Gy were 2.37 cc (1.00 cc) and 11.60 cc (3.16 cc), respectively. The mean (SD) nominal and worst-case bladder V60 Gy were 7.8% (4.8%) and 14.5% (9.3%), respectively. Paired 2-tailed t tests comparing the nominal to worst-case dose-volume histograms were significant for each dosimetric parameter (P < .01). X-ray planning uses PTV margins to inherently provide robustness to patient setup errors. Although the prostate remains well covered in various setup uncertainty scenarios, organs at risk routinely exceeded nominal treatment plan institutional constraints in the worst-case scenarios. Robustness metrics obtained from x-ray plans could serve as a benchmark for proton therapy robust optimization and evaluation.

Assessment of residual geometrical errors of clinical target volumes and their impact on dose accumulation for head and neck radiotherapy

PurposeTo assess the residual geometrical errors (dr) and their impact on the clinical target volumes (CTV) dose coverage for head and neck cancer (HNC) proton therapy patients. MethodsWe analysed 28 HNC patients treated with 70 Gy (RBE) and 54.25 Gy (RBE) to the therapeutic CTV70 and prophylactic CTV54.25, respectively. Daily cone beam CTs were converted to high quality synthetic CTs (sCTs). The CTVs from the nominal CT were propagated to the corresponding sCTs using a hybrid deformable image registration (propagated CTVs) in RayStation 11B. For 11 patients, all propagated CTVs were reviewed by our HNC radiation oncologist (physician corrected CTVs).The residual geometrical error dr was quantified as a function of the daily CTVs volume overlap with the nominal plan CTV. The errors dr(propagated CTVs) and dr(physician corrected CTVs) and the difference in dice similarity coefficients (ΔDSC) were determined. Using clinical plans, dose coverage and the tumor control probability (TCP) for the nominal, accumulated and voxel-wise minimum scenarios were determined. ResultsThe difference in the residual geometrical error dr (propagated CTVs – physician corrected CTVs) and mean DSC (|ΔDSC|mean) were minor: Δdr(CTV70) = 0.16 mm, Δdr(CTV54.25) = 0.26 mm, |ΔDSC|mean < 0.9%. For all 28 patients, dr(CTV70) = 1.91 mm and dr(CTV54.25) = 1.90 mm. However, CTV54.25 above and below the cricoid cartilage differed substantially (1.00 mm c.f. 3.93 mm). The CTV54.25 coverage below the cricoid was then almost always lower, although the TCP of the accumulated dose was higher than the TCP of the voxel-wise minimum dose. ConclusionsSetup uncertainty setting of 2 mm is possible. The feasibility of using propagated CTVs for error determination is demonstrated.

Recovering feasibility in real-time conflict-free vehicle routing

Conflict-Free Vehicle Routing Problems (CF-VRPs) arise in manufacturing, transportation and logistics facilities where Automated Guided Vehicles (AGVs) are utilized to move loads. Unlike Vehicle Routing Problems arising in distribution management, CF-VRPs explicitly consider the limited capacity of the arcs of the guide path network to avoid collisions among vehicles. AGV applications have two peculiar features. First, the uncertainty affecting both travel times and machine ready times may result in vehicle delays or anticipations with respect to the fleet nominal plan. Second, the relatively high vehicle speed (in the order of one or two meters per second) requires vehicle plans to be revised in a very short amount of time (usually few milliseconds) in order to avoid collisions. In this paper we present fast exact algorithms to recover plan feasibility in real-time. In particular, we identify two corrective actions that can be implemented in real-time and formulate the problem as a linear program with the aim to optimize four common performance measures (total vehicle delay, total weighted delay, maximum route duration and total lateness). Moreover, we develop tailored algorithms which, tested on randomly generated instances of various sizes, prove to be three orders of magnitude faster than using off-the-shelf solvers.

PTV-based VMAT vs. robust IMPT for head-and-neck cancer: A probabilistic uncertainty analysis of clinical plan evaluation with the Dutch model-based selection

Background and purposeIn the Netherlands, head-and-neck cancer (HNC) patients are referred for proton therapy (PT) through model-based selection (MBS). However, treatment errors may compromise adequate CTV dose. Our aims are: (i) to derive probabilistic plan evaluation metrics on the CTV consistent with clinical metrics; (ii) to evaluate plan consistency between photon (VMAT) and proton (IMPT) planning in terms of CTV dose iso-effectiveness and (iii) to assess the robustness of the OAR doses and of the risk toxicities involved in the MBS. Materials and methodsSixty HNC plans (30 IMPT/30 VMAT) were included. A robustness evaluation with 100,000 treatment scenarios per plan was performed using Polynomial Chaos Expansion (PCE). PCE was applied to determine scenario distributions of clinically relevant dosimetric parameters, which were compared between the 2 modalities. Finally, PCE-based probabilistic dose parameters were derived and compared to clinical PTV-based photon and voxel-wise proton evaluation metrics. ResultsProbabilistic dose to near-minimum volume v = 99.8% for the CTV correlated best with clinical PTV-D98% and VWmin-D98%,CTV doses for VMAT and IMPT respectively. IMPT showed slightly higher nominal CTV doses, with an average increase of 0.8 GyRBE in the median of the D99.8%,CTV distribution. Most patients qualified for IMPT through the dysphagia grade II model, for which an average NTCP gain of 10.5 percentages points (%-point) was found. For all complications, uncertainties resulted in moderate NTCP spreads lower than 3 p.p. on average for both modalities. ConclusionDespite the differences between photon and proton planning, the comparison between PTV-based VMAT and robust IMPT is consistent. Treatment errors had a moderate impact on NTCPs, showing that the nominal plans are a good estimator to qualify patients for PT.

Being certain about uncertainties: a robust evaluation method for high-dose-rate prostate brachytherapy treatment plans including the combination of uncertainties

In high-dose-rate (HDR) prostate brachytherapy the combined effect of uncertainties cause a range of possible dose distributions deviating from the nominal plan, and which are not considered during treatment plan evaluation. This could lead to dosimetric misses for critical structures and overdosing of organs at risk. A robust evaluation method to assess the combination of uncertainties during plan evaluation is presented and demonstrated on one HDR prostate ultrasound treatment plan retrospectively. A range of uncertainty scenarios are simulated by changing six parameters in the nominal plan and calculating the corresponding dose distribution. Two methods are employed to change the parameters, a probabilistic approach using random number sampling to evaluate the likelihood of variation in dose distributions, and a combination of the most extreme possible values to access the worst-case dosimetric outcomes. One thousand probabilistic scenarios were run on the single treatment plan with 43.2% of scenarios passing seven of the eight clinical objectives. The prostate D90 had a standard deviation of 4.4%, with the worst case decreasing the dose by up to 27.2%. The urethra D10 was up to 29.3% higher than planned in the worst case. All DVH metrics in the probabilistic scenarios were found to be within acceptable clinical constraints for the plan under statistical tests for significance. The clinical significance of the results from the robust evaluation method presented on any individual treatment plan needs to be compared in the context of a historical data set that contains patient outcomes with robustness analysis data to ascertain a baseline acceptance.

Large anatomical changes in head-and-neck cancers – A dosimetric comparison of online and offline adaptive proton therapy

PurposeThis work evaluates an online adaptive (OA) workflow for head-and-neck (H&N) intensity-modulated proton therapy (IMPT) and compares it with full offline replanning (FOR) in patients with large anatomical changes. MethodsIMPT treatment plans are created retrospectively for a cohort of eight H&N cancer patients that previously required replanning during the course of treatment due to large anatomical changes. Daily cone-beam CTs (CBCT) are acquired and corrected for scatter, resulting in 253 analyzed fractions. To simulate the FOR workflow, nominal plans are created on the planning-CT and delivered until a repeated-CT is acquired; at this point, a new plan is created on the repeated-CT. To simulate the OA workflow, nominal plans are created on the planning-CT and adapted at each fraction using a simple beamlet weight-tuning technique. Dose distributions are calculated on the CBCTs with Monte Carlo for both delivery methods. The total treatment dose is accumulated on the planning-CT. ResultsDaily OA improved target coverage compared to FOR despite using smaller target margins. In the high-risk CTV, the median D98 degradation was 1.1 % and 2.1 % for OA and FOR, respectively. In the low-risk CTV, the same metrics yield 1.3 % and 5.2 % for OA and FOR, respectively. Smaller setup margins of OA reduced the dose to all OARs, which was most relevant for the parotid glands. ConclusionDaily OA can maintain prescription doses and constraints over the course of fractionated treatment, even in cases of large anatomical changes, reducing the necessity for manual replanning in H&N IMPT.

Uncertainty guidance in proton therapy planning visualization

We investigate uncertainty guidance mechanisms to support proton therapy (PT) planning visualization. Uncertainties in the PT workflow pose significant challenges for navigating treatment plan data and selecting the most optimal plan among alternatives. Although guidance techniques have not yet been applied to PT planning scenarios, they have successfully supported sense- and decision-making processes in other contexts. We hypothesize that augmenting PT uncertainty visualization with guidance may influence the intended users’ perceived confidence and provide new insights. To this end, we follow an iterative co-design process with domain experts to develop a visualization dashboard enhanced with distinct level-of-detail uncertainty guidance mechanisms. Our approach classifies uncertainty guidance into two dimensions: degree of intrusiveness and detail-orientation. Our dashboard supports the comparison of multiple treatment plans (i.e., nominal plans with their translational variations) while accounting for multiple uncertainty factors. We subsequently evaluate the designed and developed strategies by assessing perceived confidence and effectiveness during a sense- and decision-making process. Our findings indicate that uncertainty guidance in PT planning visualization does not necessarily impact the perceived confidence of the users in the process. Nonetheless, it provides new insights and raises uncertainty awareness during treatment plan selection. This observation was particularly evident for users with longer experience in PT planning.