The multimorbidity problem involves the identification and mitigation of adverse interactions that occur when multiple computer interpretable guidelines are applied concurrently to develop a treatment plan for a patient diagnosed with multiple diseases. Solving this problem requires decision support approaches which are difficult to comprehend for physicians. As such, the rationale for treatment plans generated by these approaches needs to be provided.
OBJECTIVE: To develop an explainability component for an automated planning-based approach to the multimorbidity problem, and to assess the fidelity and interpretability of generated explanations using a clinical case study.
METHODS: The explainability component leverages the task-network model for representing computer interpretable guidelines. It generates post-hoc explanations composed of three aspects that answer why specific clinical actions are in a treatment plan, why specific revisions were applied, and how factors like medication cost, patient\'s adherence, etc. influence the selection of specific actions. The explainability component is implemented as part of MitPlan, where we revised our planning-based approach to support explainability. We developed an evaluation instrument based on the system causability scale and other vetted surveys to evaluate the fidelity and interpretability of its explanations using a two dimensional comparison study design.
RESULTS: The explainability component was implemented for MitPlan and tested in the context of a clinical case study. The fidelity and interpretability of the generated explanations were assessed using a physician-focused evaluation study involving 21 participants from two different specialties and two levels of experience. Results show that explanations provided by the explainability component in MitPlan are of acceptable fidelity and interpretability, and that the clinical justification of the actions in a treatment plan is important to physicians.
CONCLUSIONS: We created an explainability component that enriches an automated planning-based approach to solving the multimorbidity problem with meaningful explanations for actions in a treatment plan. This component relies on the task-network model to represent computer interpretable guidelines and as such can be ported to other approaches that also use the task-network model representation. Our evaluation study demonstrated that explanations that support a physician\'s understanding of the clinical reasons for the actions in a treatment plan are useful and important.

OBJECTIVE: To validate a fully-automated lexicographic optimization-planning system (mCycle, Elekta) for single-(SL) and multiple-(ML, up to 4 metastases) lesions in intracranial stereotactic radiosurgery (SRS, 21 Gy, single fraction).
METHODS: A pre-determined priority list, Wish-List (WL), represents a dialogue between planner and clinician, establishing strict constraints and pursuing objectives. In order to satisfy the clinical protocol without manual intervention, four patients were required to tweak and fine-tune each WL (SLp, MLp) for coplanar arcs. Thirty-five testing plans (20 SLp, 15 MLp) were automatically re-planned (mCP). Automatic and manual plans were compared including dose constraints, conformality, modulation complexity score (MCS), delivery time, and local gamma analysis (2%/2 mm). To ensure plan clinical acceptability, two radiation oncologists conducted an independent blind plan choice.
RESULTS: Each WL-tuning took 3 days. Estimated median manual plans and mCP calculation time were 8 and 3 h, respectively. Significant increases in SLp and MLp target coverage and conformity were registered. mCP showed a not significant and clinically acceptable higher median brain V12Gy. SLp registered a -5.8% MU decrease with comparable median delivery time (MP 2.0 min, mCP 1.9 min) while MLp showed a +9.8% MU increase and longer delivery time (MP 3.5 min, mCP 4.4 min). mCP MCS resulted significantly higher without affecting gamma passing rates. At blind choice, mCP were preferred in the majority of cases.
CONCLUSIONS: Lexicographic optimization produced acceptable SRS plans with coplanar arcs significantly reducing the overall planning time in cases with up to 4 brain metastases. These planning improvements suggest further investigations by setting high-quality non-coplanar arc plans as a reference.

OBJECTIVE: This study aimed to develop and validate algorithms for automating intensity modulated radiation therapy (IMRT) planning in breast cancer patients, with a focus on patient anatomical characteristics.
METHODS: We retrospectively selected 400 breast cancer patients without lymph node involvement for automated treatment planning. Automation was achieved using the Eclipse Scripting Application Programming Interface (ESAPI) integrated into the Eclipse Treatment Planning System. We employed three beam insertion geometries and three optimization strategies, resulting in 3600 plans, each delivering a 40.05 Gy dose in 15 fractions. Gantry angles in the tangent fields were selected based on a criterion involving the minimum intersection area between the Planning Target Volume (PTV) and the ipsilateral lung in the Beam\'s Eye View projection. ESAPI was also used to gather patient anatomical data, serving as input for Random Forest models to select the optimal plan. The Random Forest classification considered both beam insertion geometry and optimization strategy. Dosimetric data were evaluated in accordance with the Radiation Therapy Oncology Group (RTOG) 1005 protocol.
RESULTS: Overall, all approaches generated high-quality plans, with approximately 94% meeting the acceptable dose criteria for organs at risk and/or target coverage as defined by RTOG guidelines. Average automated plan generation time ranged from 6 min and 37 s to 9 min and 22 s, with the mean time increasing with additional fields. The Random Forest approach did not successfully enable automatic planning strategy selection. Instead, our automated planning system allows users to choose from the tested geometry and strategy options.
CONCLUSIONS: Although our attempt to correlate patient anatomical features with planning strategy using machine learning tools was unsuccessful, the resulting dosimetric outcomes proved satisfactory. Our algorithm consistently produced high-quality plans, offering significant time and efficiency advantages.

UNASSIGNED: The lack of dedicated tools in commercial planning systems currently restricts efficient review and planning for re-irradiation. The aim of this study was to develop an automated re-irradiation planning framework based on cumulative doses.
UNASSIGNED: We performed a retrospective study of 14 patients who received spine SBRT re-irradiation near a previously irradiated treatment site. A fully-automated workflow, DART (Dose Accumulation-based Re-irradiation Tool), was implemented within Eclipse by leveraging a combination of a dose accumulation script and a proprietary automated optimization algorithm. First, we converted the prior treatment dose into equivalent dose in 2 Gy fractions (EQD2) and mapped it to the current anatomy, utilizing deformable image registration. Subsequently, the intersection of EQD2 isodose lines with relevant organs at risk defines a series of optimization structures. During plan optimization, the residual allowable dose at a specified tissue tolerance was treated as a hard constraint.
UNASSIGNED: All DART plans met institutional physical and cumulative constraints and passed plan checks by qualified medical physicists. DART demonstrated significant improvements in target coverage over clinical plans, with an average increase in PTV D99% and V100% of 2.3 Gy [range -0.3-7.7 Gy] and 3.4 % [range -0.4 %-7.6 %] (p < 0.01, paired t-test), respectively. Moreover, high-dose spillage (>105 %) outside the PTV was reduced by up to 7 cm3. The homogeneity index for DART plans was improved by 19 % (p < 0.001).
UNASSIGNED: DART provides a powerful framework to achieve more tailored re-irradiation plans by accounting for dose distributions from the previous treatments. The superior plan quality could improve the therapeutic ratio for re-irradiation patients.

Objective.Automated Stereotactic Radiosurgery (SRS) planning solutions improve clinical efficiency and reduce treatment plan variability. Available commercial solutions employ a template-based strategy that may not be optimal for all SRS patients. This study compares a novel beam angle optimized Volumetric Modulated Arc Therapy (VMAT) planning solution for multi-metastatic SRS to the commercial solution HyperArc.Approach.Stereotactic Optimized Automated Radiotherapy (SOAR) performs automated plan creation by combining collision prediction, beam angle optimization, and dose optimization to produce individualized high-quality SRS plans using Eclipse Scripting. In this retrospective study 50 patients were planned using SOAR and HyperArc. Assessed dose metrics included the Conformity Index (CI), Gradient Index (GI), and doses to organs-at-risk. Complexity metrics evaluated the modulation, gantry speed, and dose rate complexity. Plan dosimetric quality, and complexity were compared using double-sided Wilcoxon signed rank tests (α= 0.05) adjusted for multiple comparisons.Main Results.The median target CI was 0.82 with SOAR and 0.79 with HyperArc (p < .001). Median GI was 1.85 for SOAR and 1.68 for HyperArc (p < .001). The median V12Gy normal brain volume for SOAR and HyperArc were 7.76 cm3and 7.47 cm3respectively. Median doses to the eyes, lens, optic nerves, and optic chiasm were statistically significant favoring SOAR. The SOAR algorithm scored lower for all complexity metrics assessed.Significance.In-house developed automated planning solutions are a viable alternative to commercial solutions. SOAR designs high-quality patient-specific SRS plans with a greater degree of versatility than template-based methods.

Goal Recognition is the task of discerning the intended goal that an agent aims to achieve, given a set of goal hypotheses, a domain model, and a sequence of observations (i.e., a sample of the plan executed in the environment). Existing approaches assume that goal hypotheses comprise a single conjunctive formula over a single final state and that the environment dynamics are deterministic, preventing the recognition of temporally extended goals in more complex settings. In this paper, we expand goal recognition to temporally extended goals in Fully Observable Non-Deterministic (fond) planning domain models, focusing on goals on finite traces expressed in Linear Temporal Logic (ltlf) and Pure-Past Linear Temporal Logic (ppltl). We develop the first approach capable of recognizing goals in such settings and evaluate it using different ltlf and ppltl goals over six fond planning domain models. Empirical results show that our approach is accurate in recognizing temporally extended goals in different recognition settings.

BACKGROUND: This study aimed to evaluate an a-priori multicriteria plan optimization algorithm (mCycle) for locally advanced breast cancer radiation therapy (RT) by comparing automatically generated VMAT (Volumetric Modulated Arc Therapy) plans (AP-VMAT) with manual clinical Helical Tomotherapy (HT) plans.
METHODS: The study included 25 patients who received postoperative RT using HT. The patient cohort had diverse target selections, including both left and right breast/chest wall (CW) and III-IV node, with or without internal mammary node (IMN) and Simultaneous Integrated Boost (SIB). The Planning Target Volume (PTV) was obtained by applying a 5 mm isotropic expansion to the CTV (Clinical Target Volume), with a 5 mm clip from the skin. Comparisons of dosimetric parameters and delivery/planning times were conducted. Dosimetric verification of the AP-VMAT plans was performed.
RESULTS: The study showed statistically significant improvements in AP-VMAT plans compared to HT for OARs (Organs At Risk) mean dose, except for the heart and ipsilateral lung. No significant differences in V95% were observed for PTV breast/CW and PTV III-IV, while increased coverage (higher V95%) was seen for PTV IMN in AP-VMAT plans. HT plans exhibited smaller values of PTV V105% for breast/CW and III-IV, with no differences in PTV IMN and boost. HT had an average (± standard deviation) delivery time of (17 ± 8) minutes, while AP-VMAT took (3 ± 1) minutes. The average γ passing rate for AP-VMAT plans was 97%±1%. Planning times reduced from an average of 6 h for HT to about 2 min for AP-VMAT.
CONCLUSIONS: Comparing AP-VMAT plans with clinical HT plans showed similar or improved quality. The implementation of mCycle demonstrated successful automation of the planning process for VMAT treatment of locally advanced breast cancer, significantly reducing workload.

OBJECTIVE: Knowledge-based planning (KBP) aims to automate and standardize treatment planning. New KBP users are faced with many questions: How much does model size matter, and are multiple models needed to accommodate specific physician preferences? In this study, six head-and-neck KBP models were trained to address these questions.
METHODS: The six models differed in training size and plan composition: The KBPFull (n = 203 plans), KBP101 (n = 101), KBP50 (n = 50), and KBP25 (n = 25) were trained with plans from two head-and-neck physicians. KBPA and KBPB each contained n = 101 plans from only one physician, respectively. An independent set of 39 patients treated to 6000-7000 cGy by a third physician was re-planned with all KBP models for validation. Standard head-and-neck dosimetric parameters were used to compare resulting plans. KBPFull plans were compared to the clinical plans to evaluate overall model quality. Additionally, clinical and KBPFull plans were presented to another physician for blind review. Dosimetric comparison of KBPFull against KBP101 , KBP50 , and KBP25 investigated the effect of model size. Finally, KBPA versus KBPB tested whether training KBP models on plans from one physician only influences the resulting output. Dosimetric differences were tested for significance using a paired t-test (p < 0.05).
RESULTS: Compared to manual plans, KBPFull significantly increased PTV Low D95% and left parotid mean dose but decreased dose cochlea, constrictors, and larynx. The physician preferred the KBPFull plan over the manual plan in 20/39 cases. Dosimetric differences between KBPFull , KBP101 , KBP50 , and KBP25 plans did not exceed 187 cGy on aggregate, except for the cochlea. Further, average differences between KBPA and KBPB were below 110 cGy.
CONCLUSIONS: Overall, all models were shown to produce high-quality plans. Differences between model outputs were small compared to the prescription. This indicates only small improvements when increasing model size and minimal influence of the physician when choosing treatment plans for training head-and-neck KBP models.

BACKGROUND: To investigate the capability of a not-yet commercially available fully automated lexicographic optimization (LO) planning algorithm, called mCycle (Elekta AB, Stockholm, Sweden), to further improve the plan quality of an already-validated Wish List (WL) pushing on the organs-at-risk (OAR) sparing without compromising target coverage and plan delivery accuracy.
METHODS: Twenty-four mono-institutional consecutive cervical cancer Volumetric-Modulated Arc Therapy (VMAT) plans delivered between November 2019 and April 2022 (50 Gy/25 fractions) have been retrospectively selected. In mCycle the LO planning algorithm was combined with the a-priori multi-criterial optimization (MCO). Two versions of WL have been defined to reproduce manual plans (WL01), and to improve the OAR sparing without affecting minimum target coverage and plan delivery accuracy (WL02). Robust WLs have been tuned using a subset of 4 randomly selected patients. The remaining plans have been automatically re-planned by using the designed WLs. Manual plans (MP) and mCycle plans (mCP01 and mCP02) were compared in terms of dose distributions, complexity, delivery accuracy, and clinical acceptability. Two senior physicians independently performed a blind clinical evaluation, ranking the three competing plans. Furthermore, a previous defined global quality index has been used to gather into a single score the plan quality evaluation.
RESULTS: The WL tweaking requests 5 and 3 working days for the WL01 and the WL02, respectively. The re-planning took in both cases 3 working days. mCP01 best performed in terms of target coverage (PTV V95% (%): MP 98.0 [95.6-99.3], mCP01 99.2 [89.7-99.9], mCP02 96.9 [89.4-99.5]), while mCP02 showed a large OAR sparing improvement, especially in the rectum parameters (e.g., Rectum D50% (Gy): MP 41.7 [30.2-47.0], mCP01 40.3 [31.4-45.8], mCP02 32.6 [26.9-42.6]). An increase in plan complexity has been registered in mCPs without affecting plan delivery accuracy. In the blind comparisons, all automated plans were considered clinically acceptable, and mCPs were preferred over MP in 90% of cases. Globally, automated plans registered a plan quality score at least comparable to MP.
CONCLUSIONS: This study showed the flexibility of the Lexicographic approach in creating more demanding Wish Lists able to potentially minimize toxicities in RT plans.

UNASSIGNED: The association between dose to selected bladder and rectum symptom-related sub-regions (SRS) and late toxicity after prostate cancer radiotherapy has been evidenced by voxel-wise analyses. The aim of the current study was to explore the feasibility of combining knowledge-based (KB) and multi-criteria optimization (MCO) to spare SRSs without compromising planning target volume (PTV) dose delivery, including pelvic-node irradiation.
UNASSIGNED: Forty-five previously treated patients (74.2 Gy/28fr) were selected and SRSs (in the bladder, associated with late dysuria/hematuria/retention; in the rectum, associated with bleeding) were generated using deformable registration. A KB model was used to obtain clinically suitable plans (KB-plan). KB-plans were further optimized using MCO, aiming to reduce dose to the SRSs while safeguarding target dose coverage, homogeneity and avoiding worsening dose volume histograms of the whole bladder, rectum and other organs at risk. The resulting MCO-generated plans were examined to identify the best-compromise plan (KB + MCO-plan).
UNASSIGNED: The mean SRS dose decreased in almost all patients for each SRS. D1% also decreased in the large majority, less frequently for dysuria/bleeding SRS. Mean differences were statistically significant (p < 0.05) and ranged between 1.3 and 2.2 Gy with maximum reduction of mean dose up to 3-5 Gy for the four SRSs. The better sparing of SRSs was obtained without compromising PTVs coverage.
UNASSIGNED: Selectively sparing SRSs without compromising PTV coverage is feasible and has the potential to reduce toxicities in prostate cancer radiotherapy. Further investigation to better quantify the expected risk reduction of late toxicities is warranted.