Sealing Wax and Bottles in Bags-A Paradigm Shift in Refined Olive Oil Packaging: Preliminary Results.

Generally, olive oil possesses natural protection against oxidation due to antioxidant compounds such as phenols and tocopherols. However, in the case of refined olive oil, the refining process unavoidably reduces the presence of these compounds. Considering these considerations, the objective of this study was to address the issues related to the "tightness" of the cap used for packaging oil in SALOV, aiming to extend the product's shelf life. The oil under investigation was packaged in 250 mL transparent glass bottles, each filled with either argon or air. Subsequently, the samples were divided into three groups: one group sealed with a conventional screw cap, another covered with a special protective bag, and a third one sealed with a wax cover directly on the cap. The storage period varied, during which the atmospheric conditions were monitored daily through both destructive and non-destructive analyses. The preliminary results indicate that alternative preservation techniques, such as the use of argon, sealing wax, and protective bags, can effectively enhance the shelf life of the oil and maintain its quality (reduce oxidation, preserve phenolic compounds, and reduce the degradation of pigments). Further research and development in this area could lead to the production of high-quality extra virgin olive oils with extended shelf life and improved sensory and nutritional properties.

Improving knowledge-based treatment planning for lung cancer radiotherapy with automatic multi-criteria optimized training plans.

BACKGROUND: Knowledge-based planning (KBP) is a method for automated radiotherapy treatment planning where appropriate optimization objectives for new patients are predicted based on a library of training plans. KBP can save time and improve organ at-risk sparing and inter-patient consistency compared to manual planning, but its performance depends on the quality of the training plans. We used another system for automated planning, which generates multi-criteria optimized (MCO) plans based on a wish list, to create training plans for the KBP model, to allow seamless integration of knowledge from a new system into clinical routine. Model performance was compared for KBP models trained with manually created and automatic MCO treatment plans. MATERIAL AND METHODS: Two RapidPlan models with the same 30 locally advanced non-small cell lung cancer patients included were created, one containing manually created clinical plans (RP_CLIN) and one containing fully automatic multi-criteria optimized plans (RP_MCO). For 15 validation patients, model performance was compared in terms of dose-volume parameters and normal tissue complication probabilities, and an oncologist performed a blind comparison of the clinical (CLIN), RP_CLIN, and RP_MCO plans. RESULTS: The heart and esophagus doses were lower for RP_MCO compared to RP_CLIN, resulting in an average reduction in the risk of 2-year mortality by 0.9 percentage points and the risk of acute esophageal toxicity by 1.6 percentage points with RP_MCO. The oncologist preferred the RP_MCO plan for 8 patients and the CLIN plan for 7 patients, while the RP_CLIN plan was not preferred for any patients. CONCLUSION: RP_MCO improved OAR sparing compared to RP_CLIN and was selected for implementation in the clinic. Training a KBP model with clinical plans may lead to suboptimal output plans, and making an extra effort to optimize the library plans in the KBP model creation phase can improve the plan quality for many future patients.

Machine Learning for Predicting Clinician Evaluation of Treatment Plans for Left-Sided Whole Breast Radiation Therapy.

Purpose: The objective of this work was to investigate the ability of machine learning models to use treatment plan dosimetry for prediction of clinician approval of treatment plans (no further planning needed) for left-sided whole breast radiation therapy with boost. Methods and Materials: Investigated plans were generated to deliver a dose of 40.05 Gy to the whole breast in 15 fractions over 3 weeks, with the tumor bed simultaneously boosted to 48 Gy. In addition to the manually generated clinical plan of each of the 120 patients from a single institution, an automatically generated plan was included for each patient to enhance the number of study plans to 240. In random order, the treating clinician retrospectively scored all 240 plans as (1) approved without further planning to seek improvement or (2) further planning needed, while being blind for type of plan generation (manual or automated). In total, 2 × 5 classifiers were trained and evaluated for ability to correctly predict the clinician's plan evaluations: random forest (RF) and constrained logistic regression (LR) classifiers, each trained for 5 different sets of dosimetric plan parameters (feature sets [FS]). Importances of included features for predictions were investigated to better understand clinicians' choices. Results: Although all 240 plans were in principle clinically acceptable for the clinician, only for 71.5% was no further planning required. For the most extensive FS, accuracy, area under the receiver operating characteristic curve, and Cohen's κ for generated RF/LR models for prediction of approval without further planning were 87.2 ± 2.0/86.7 ± 2.2, 0.80 ± 0.03/0.86 ± 0.02, and 0.63 ± 0.05/0.69 ± 0.04, respectively. In contrast to LR, RF performance was independent of the applied FS. For both RF and LR, whole breast excluding boost PTV (PTV40.05Gy) was the most important structure for predictions, with importance factors of 44.6% and 43%, respectively, dose recieved by 95% volume of PTV40.05 (D95%) as the most important parameter in most cases. Conclusions: The investigated use of machine learning to predict clinician approval of treatment plans is highly promising. Including nondosimetric parameters could further increase classifiers' performances. The tool could become useful for aiding treatment planners in generating plans with a high probability of being directly approved by the treating clinician.

Per-fraction planning to enhance optimization degrees of freedom compared to the conventional single-plan approach.

Objective. In conventional radiotherapy, a single treatment plan is generated pre-treatment, and delivered in daily fractions. In this study, we propose to generate different treatment plans for all fractions ('Per-fraction' planning) to reduce cumulative organs at risk (OAR) doses. Per-fraction planning was compared to the 'Conventional' single-plan approach for non-coplanar 4 × 9.5 Gy prostate stereotactic body radiation therapy (SBRT).Approach. An in-house application for fully automated, non-coplanar multi-criterial treatment planning with integrated beam angle and fluence optimization was used for plan generations. For the Conventional approach, a single 12-beam non-coplanar IMRT plan with individualized beam angles was generated for each of the 20 included patients. In Per-fraction planning, four fraction plans were generated for each patient. For each fraction, a different set of patient-specific 12-beam configurations could be automatically selected. Per-fraction plans were sequentially generated by adding dose to already generated fraction plan(s). For each fraction, the cumulative- and fraction dose were simultaneously optimized, allowing some minor constraint violations in fraction doses, but not in cumulative.Main results. In the Per-fraction approach, on average 32.9 ± 3.1 [29;39] unique beams per patient were used. PTV doses in the separate Per-fraction plans were acceptable and highly similar to those in Conventional plans, while also fulfilling all OAR hard constraints. When comparing total cumulative doses, Per-fraction planning showed improved bladder sparing for all patients with reductions in Dmean of 22.6% (p= 0.0001) and in D1cc of 2.0% (p= 0.0001), reductions in patient volumes receiving 30% and 50% of the prescribed dose of 54.7% and 6.3%, respectively, and a 3.1% lower rectum Dmean (p= 0.007). Rectum D1cc was 4.1% higher (p= 0.0001) and Urethra dose was similar.Significance. In this proof-of-concept paper, Per-fraction planning resulted in several dose improvements in healthy tissues compared to the Conventional single-plan approach, for similar PTV dose. By keeping the number of beams per fraction the same as in Conventional planning, reported dosimetric improvements could be obtained without increase in fraction durations. Further research is needed to explore the full potential of the Per-fraction planning approach.

Patient anatomy-specific trade-offs between sub-clinical disease coverage and normal tissue dose reduction in head-and-neck cancer.

PURPOSE: Risk of subclinical disease decreases with increasing distance from the GTV in head- and-neck squamous cell carcinoma (HNSCC). Depending on individual patient anatomy, OAR sparing could be improved by reducing target coverage in regions with low risk of subclinical spread. Using automated multi-criteria optimization, we investigate patient-specific optimal trade-offs between target periphery coverage and OAR sparing. METHODS: VMAT plans for 39 HNSCC patients were retrospectively created following our clinical three-target-level protocol: high-risk (PTV1), intermediate-risk (PTV2, 5 mm expansion from PTV1), and elective (PTV3). A baseline plan fulfilling clinical constraints (D 99 % ≥95 % for all PTVs) was compared to three plans with reduced PTV2 coverage (goals: PTV2 D 99 % ≥90 % or 85 %, or no PTV2) at the outer edge of PTV2. Plans were compared on PTV D 99 %, OAR D mean, and NTCP (xerostomia/dysphagia). RESULTS: Trade-offs between PTV2 coverage and OAR doses varied considerably between patients. For plans with PTV2 D 99 % -goal 90 %, median PTV2 D 99 % was 91.5 % resulting in xerostomia (≥grade 4) and dysphagia (≥grade 2) NTCP decrease of median [maximum] 1.9 % [5.3 %] and 1.1 % [4.1 %], respectively, compared to nominal PTV2 D 99 % -goal 95 %. For PTV2 D 99 % -goal 85 % median PTV D 99 % was 87 % with NTCP improvements of 4.6 % [9.9 %] and 1.5 % [5.4 %]. For no-margin plans, PTV2 D 99 % decreased to 83.3 % with NTCP reductions of 5.1 % [10.2 %] and 1.4 % [6.1 %]. CONCLUSION: Clinically relevant, patient-specific reductions in OARs and NTCP were observed at limited cost in target under-coverage at the outermost PTV edge. Given the observed inter-patient variations, individual evaluation is warranted to determine whether trade- offs would benefit a specific patient.

Patient selection, inter-fraction plan robustness and reduction of toxicity risk with deep inspiration breath hold in intensity-modulated radiotherapy of locally advanced non-small cell lung cancer.

Background: State-of-the-art radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC) is performed with intensity-modulation during free breathing (FB). Previous studies have found encouraging geometric reproducibility and patient compliance of deep inspiration breath hold (DIBH) radiotherapy for LA-NSCLC patients. However, dosimetric comparisons of DIBH with FB are sparse, and DIBH is not routinely used for this patient group. The objective of this simulation study was therefore to compare DIBH and FB in a prospective cohort of LA-NSCLC patients treated with intensity-modulated radiotherapy (IMRT). Methods: For 38 LA-NSCLC patients, 4DCTs and DIBH CTs were acquired for treatment planning and during the first and third week of radiotherapy treatment. Using automated planning, one FB and one DIBH IMRT plan were generated for each patient. FB and DIBH was compared in terms of dosimetric parameters and NTCP. The treatment plans were recalculated on the repeat CTs to evaluate robustness. Correlations between ΔNTCPs and patient characteristics that could potentially predict the benefit of DIBH were explored. Results: DIBH reduced the median Dmean to the lungs and heart by 1.4 Gy and 1.1 Gy, respectively. This translated into reductions in NTCP for radiation pneumonitis grade ≥2 from 20.3% to 18.3%, and for 2-year mortality from 51.4% to 50.3%. The organ at risk sparing with DIBH remained significant in week 1 and week 3 of treatment, and the robustness of the target coverage was similar for FB and DIBH. While the risk of radiation pneumonitis was consistently reduced with DIBH regardless of patient characteristics, the ability to reduce the risk of 2-year mortality was evident among patients with upper and left lower lobe tumors but not right lower lobe tumors. Conclusion: Compared to FB, DIBH allowed for smaller target volumes and similar target coverage. DIBH reduced the lung and heart dose, as well as the risk of radiation pneumonitis and 2-year mortality, for 92% and 74% of LA-NSCLC patients, respectively. However, the advantages varied considerably between patients, and the ability to reduce the risk of 2-year mortality was dependent on tumor location. Evaluation of repeat CTs showed similar robustness of the dose distributions with each technique.

Automated multi-criterial planning with beam angle optimization to establish non-coplanar VMAT class solutions for nasopharyngeal carcinoma.

PURPOSE: Complexity in selecting optimal non-coplanar beam setups and prolonged delivery times may hamper the use of non-coplanar treatments for nasopharyngeal carcinoma (NPC). Automated multi-criterial planning with integrated beam angle optimization was used to define non-coplanar VMAT class solutions (CSs), each consisting of a coplanar arc and additional 1 or 2 fixed, non-coplanar partial arcs. METHODS: Automated planning was used to generate a coplanar VMAT plan with 5 complementary computer-optimized non-coplanar IMRT beams (VMAT+5) for each of the 20 included patients. Subsequently, the frequency distribution of the 100 patient-specific non-coplanar IMRT beam directions was used to select non-coplanar arcs for supplementing coplanar VMAT. A second investigated CS with only one non-coplanar arc consisted of coplanar VMAT plus a partial arc at 90° couch angle (VMATCS90). Plans generated with the two VMATCSs were compared to coplanar VMAT. RESULTS: VMAT+5 analysis resulted in VMATCS60: two partial non-coplanar arcs at couch angles 60° and -60° to complement coplanar VMAT. Compared to coplanar VMAT, the non-coplanar VMATCS60 and VMATCS90 yielded substantial average dose reductions in OARs associated with xerostomia and dysphagia, i.e., parotids, submandibular glands, oral cavity and swallowing muscles (p < 0.05) for the same PTV coverage and without violating hard constraints. Impact of non-coplanar treatment and superiority of either VMACS60 and VMATCS90 was highly patient dependent. CONCLUSIONS: Compared to coplanar VMAT, dose to OARs was substantially reduced with a CS with one or two non-coplanar arcs. Preferences for coplanar or one or two additional arcs are highly patient-specific, balancing plan quality and treatment time.

Chemical vs. Enzymatic Refining to Produce Peanut Oil for Edible Use or to Obtain a Sustainable and Cost-Effective Protector for Stored Grains against Sitophilus zeamais (Coleoptera: Curculionidae).

Among the various existing techniques, enzymatic degumming represents a process that is establishing itself as a valid alternative to the more classic chemical processes. Moreover, vegetable oils of various origins have been gaining more consideration as sustainable and affordable protectants for cereals and pulses against the attack of several insect pests. Sitophilus zeamais (Motschulsky) (Coleoptera: Curculionidae) is one of the key pests of cereal crops in the field and in stored and processed cereal products. Based on these highlighted issues, the overall aim of this research was twofold: (i) firstly, the effectiveness of the enzymatic degumming process was evaluated through the use of three different enzymes in order to verify the possible industrial application within the SALOV company as an alternative to the conventional chemical process; (ii) in a second phase, the possible use of the innovative refined oils was explored for sustainable stored grain protection towards S. zeamais. The results obtained confirm the strong possibility of applying the enzymatic process, which is innovative and, in a chemical way, more sustainable than the classical one. Regarding the toxicity towards S. zeamais, the crude peanut oil and the chemically refined peanut oil had lower LC50 values (1.836 and 1.372 g kg-1, respectively) than the oils rectified through enzymatic degumming (LC50 from 2.453 to 4.076 g kg-1), and, therefore, they can be suggested as sustainable stored grain protectants.

Motherhood in Alternative Detention Conditions: A Preliminary Case-Control Study.

Many women in detention are mothers and often the sole caregivers of their children. Italy, as most European countries, allows mothers to keep their children with them in detention, with the aim of preserving the fundamental bond between mother and child. Since prison does not seem to provide a good environment for the child's growth, there are different alternative residential solutions, such as Group Homes. The aim of this preliminary study was to explore the differences between mothers living in detention through alternative measures with their children and mothers who are not detained regarding parenting stress, child behavior from the parent's perspective, and maternal attachment. Twelve mothers were enrolled in this study, divided equally between the detained and the control groups. Both groups' participants completed a three-questionnaire battery in order to assess parenting stress, child's behavior, and maternal attachment. The analyses of variance showed significant differences between the two groups, with the detained group reporting higher scores than the control group in almost all the subscales of parenting stress. The results highlighted that imprisoned mothers might experience more stress than the general population. There is a need to design intervention programs to support parenting in detention.

Enhancing Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer Patients with iCE, a Novel System for Automated Multi-Criterial Treatment Planning Including Beam Angle Optimization.

In this study, the novel iCE radiotherapy treatment planning system (TPS) for automated multi-criterial planning with integrated beam angle optimization (BAO) was developed, and applied to optimize organ at risk (OAR) sparing and systematically investigate the impact of beam angles on radiotherapy dose in locally advanced non-small cell lung cancer (LA-NSCLC). iCE consists of an in-house, sophisticated multi-criterial optimizer with integrated BAO, coupled to a broadly used commercial TPS. The in-house optimizer performs fluence map optimization to automatically generate an intensity-modulated radiotherapy (IMRT) plan with optimal beam angles for each patient. The obtained angles and dose-volume histograms are then used to automatically generate the final deliverable plan with the commercial TPS. For the majority of 26 LA-NSCLC patients, iCE achieved improved heart and esophagus sparing compared to the manually created clinical plans, with significant reductions in the median heart Dmean (8.1 vs. 9.0 Gy, p = 0.02) and esophagus Dmean (18.5 vs. 20.3 Gy, p = 0.02), and reductions of up to 6.7 Gy and 5.8 Gy for individual patients. iCE was superior to automated planning using manually selected beam angles. Differences in the OAR doses of iCE plans with 6 beams compared to 4 and 8 beams were statistically significant overall, but highly patient-specific. In conclusion, automated planning with integrated BAO can further enhance and individualize radiotherapy for LA-NSCLC.

MR-Linac Radiotherapy - The Beam Angle Selection Problem.

BACKGROUND: With the large-scale introduction of volumetric modulated arc therapy (VMAT), selection of optimal beam angles for coplanar static-beam IMRT has increasingly become obsolete. Due to unavailability of VMAT in current MR-linacs, the problem has re-gained importance. An application for automated IMRT treatment planning with integrated, patient-specific computer-optimization of beam angles (BAO) was used to systematically investigate computer-aided generation of beam angle class solutions (CS) for replacement of computationally expensive patient-specific BAO. Rectal cancer was used as a model case. MATERIALS AND METHODS: 23 patients treated at a Unity MR-linac were included. BAOx plans (x=7-12 beams) were generated for all patients. Analyses of BAO12 plans resulted in CSx class solutions. BAOx plans, CSx plans, and plans with equi-angular setups (EQUIx, x=9-56) were mutually compared. RESULTS: For x>7, plan quality for CSx and BAOx was highly similar, while both were superior to EQUIx. E.g. with CS9, bowel/bladder Dmean reduced by 22% [11%, 38%] compared to EQUI9 (p<0.001). For equal plan quality, the number of EQUI beams had to be doubled compared to BAO and CS. CONCLUSIONS: Computer-generated beam angle CS could replace individualized BAO without loss in plan quality, while reducing planning complexity and calculation times, and resulting in a simpler clinical workflow. CS and BAO largely outperformed equi-angular treatment. With the developed CS, time consuming beam angle re-optimization in daily adaptive MR-linac treatment could be avoided. Further systematic research on computerized development of beam angle class solutions for MR-linac treatment planning is warranted.

Variations in Head and Neck Treatment Plan Quality Assessment Among Radiation Oncologists and Medical Physicists in a Single Radiotherapy Department.

BACKGROUND: Agreement between planners and treating radiation oncologists (ROs) on plan quality criteria is essential for consistent planning. Differences between ROs and planning medical physicists (MPs) in perceived quality of head and neck cancer plans were assessed. MATERIALS AND METHODS: Five ROs and four MPs scored 65 plans for in total 15 patients. For each patient, the clinical (CLIN) plan and two or four alternative plans, generated with automated multi-criteria optimization (MCO), were included. There was always one MCO plan aiming at maximally adhering to clinical plan requirements, while the other MCO plans had a lower aimed quality. Scores were given as follows: 1-7 and 1-2, not acceptable; 3-5, acceptable if further planning would not resolve perceived weaknesses; and 6-7, straightway acceptable. One MP and one RO repeated plan scoring for intra-observer variation assessment. RESULTS: For the 36 unique observer pairs, the median percentage of plans for which the two observers agreed on a plan score (100% = 65 plans) was 27.7% [6.2, 40.0]. In the repeat scoring, agreements between first and second scoring were 52.3% and 40.0%, respectively. With a binary division between unacceptable (scores 1 and 2) and acceptable (3-7) plans, the median inter-observer agreement percentage was 78.5% [63.1, 86.2], while intra-observer agreements were 96.9% and 86.2%. There were no differences in observed agreements between RO-RO, MP-MP, and RO-MP pairs. Agreements for the highest-quality, automatically generated MCO plans were higher than for the CLIN plans. CONCLUSIONS: Inter-observer differences in plan quality scores were substantial and could result in inconsistencies in generated treatment plans. Agreements among ROs were not better than between ROs and MPs, despite large differences in training and clinical role. High-quality automatically generated plans showed the best score agreements.

Fully automated treatment planning for MLC-based robotic radiotherapy.

PURPOSE: To propose and validate a fully automated multicriterial treatment planning solution for a CyberKnife® equipped with an InCiseTM 2 multileaf collimator. METHODS: The AUTO BAO plans are generated using fully automated prioritized multicriterial optimization (AUTO MCO) of pencil-beam fluence maps with integrated noncoplanar beam angle optimization (BAO), followed by MLC segment generation. Both the AUTO MCO and segmentation algorithms have been developed in-house. AUTO MCO generates for each patient a single, high-quality Pareto-optimal IMRT plan. The segmentation algorithm then accurately mimics the AUTO MCO 3D dose distribution, while considering all candidate beams simultaneously, rather than replicating the fluence maps. Pencil-beams, segment dose depositions, and final dose calculations are performed with a stand-alone version of the clinical dose calculation engine. For validation, AUTO BAO plans were generated for 33 prostate SBRT patients and compared to reference plans (REF) that were manually generated with the commercial treatment planning system (TPS), in absence of time pressure. REF plans were also compared to AUTO RB plans, for which fluence map optimization was performed for the beam angle configuration used in the REF plan, and the segmentation could use all these beams or only a subset, depending on the dosimetry. RESULTS: AUTO BAO plans were clinically acceptable and dosimetrically similar to REF plans, but had on average reduced numbers of beams ((beams in AUTO BAO)/(beams in REF) (relative improvement): 24.7/48.3 (-49%)), segments (59.5/98.9 (-40%)), and delivery times (17.1/22.3 min. (-23%)). Dosimetry of AUTO RB and REF were also similar, but AUTO RB used on average fewer beams (38.0/48.3 (-21%)) and had on average shorter delivery times (18.6/22.3 min. (-17%)). Delivered Monitor Units (MU) were similar for all three planning approaches. CONCLUSIONS: A new, vendor-independent optimization workflow for fully automated generation of deliverable high-quality CyberKnife® plans was proposed, including BAO. Compared to manual planning with the commercial TPS, fraction delivery times were reduced by 5.3 min. (-23%) due to large reductions in beam and segment numbers.

On the Importance of Individualized, Non-Coplanar Beam Configurations in Mediastinal Lymphoma Radiotherapy, Optimized With Automated Planning.

BACKGROUND AND PURPOSE: Literature is non-conclusive regarding selection of beam configurations in radiotherapy for mediastinal lymphoma (ML) radiotherapy, and published studies are based on manual planning with its inherent limitations. In this study, coplanar and non-coplanar beam configurations were systematically compared, using a large number of automatically generated plans. MATERIAL AND METHODS: An autoplanning workflow, including beam configuration optimization, was configured for young female ML patients. For each of 25 patients, 24 plans with different beam configurations were generated with autoplanning: 11 coplanar CP_x plans and 11 non-coplanar NCP_x plans with x = 5 to 15 IMRT beams with computer-optimized, patient-specific configurations, and the coplanar VMAT and non-coplanar Butterfly VMAT (B-VMAT) beam angle class solutions (600 plans in total). RESULTS: Autoplans compared favorably with manually generated, clinically delivered plans, ensuring that beam configuration comparisons were performed with high quality plans. There was no beam configuration approach that was best for all patients and all plan parameters. Overall there was a clear tendency towards higher plan quality with non-coplanar configurations (NCP_x≥12 and B-VMAT). NCP_x≥12 produced highly conformal plans with on average reduced high doses in lungs and patient and also a reduced heart Dmean, while B-VMAT resulted in reduced low-dose spread in lungs and left breast. CONCLUSIONS: Non-coplanar beam configurations were favorable for young female mediastinal lymphoma patients, with patient-specific and plan-parameter-dependent dosimetric advantages of NCP_x≥12 and B-VMAT. Individualization of beam configuration approach, considering also the faster delivery of B-VMAT vs. NCP_x≥12, can importantly improve the treatments.

Complementing Prostate SBRT VMAT With a Two-Beam Non-Coplanar IMRT Class Solution to Enhance Rectum and Bladder Sparing With Minimum Increase in Treatment Time.

PURPOSE: Enhance rectum and bladder sparing in prostate SBRT with minimum increase in treatment time by complementing dual-arc coplanar VMAT with a two-beam non-coplanar IMRT class solution (CS). METHODS: For twenty patients, an optimizer for automated multi-criterial planning with integrated beam angle optimization (BAO) was used to generate dual-arc VMAT plans, supplemented with five non-coplanar IMRT beams with individually optimized orientations (VMAT+5). In all plan generations, reduction of high rectum dose had the highest priority after obtaining adequate PTV coverage. A CS with two most preferred directions in VMAT+5 and largest rectum dose reductions compared to dual-arc VMAT was then selected to define VMAT+CS. VMAT+CS was compared with automatically generated i) dual-arc coplanar VMAT plans (VMAT), ii) VMAT+5 plans, and iii) IMRT plans with 30 patient-specific non-coplanar beam orientations (30-NCP). Plans were generated for a 4 x 9.5 Gy fractionation scheme. Differences in PTV doses, healthy tissue sparing, and computation and treatment delivery times were quantified. RESULTS: For equal PTV coverage, VMAT+CS, consisting of dual-arc VMAT supplemented with two fixed, non-coplanar IMRT beams with fixed Gantry/Couch angles of 65°/30° and 295°/-30°, significantly reduced OAR doses and the dose bath, compared to dual-arc VMAT. Mean relative differences in rectum Dmean, D1cc, V40GyEq and V60GyEq were 19.4 ± 10.6%, 4.2 ± 2.7%, 34.9 ± 20.3%, and 39.7 ± 23.2%, respectively (all p<0.001). There was no difference in bladder D1cc, while bladder Dmean reduced by 17.9 ± 11.0% (p<0.001). Also, the clinically evaluated urethra D5%, D10%, and D50% showed small, but statistically significant improvements. All patient VX with X = 2, 5, 10, 20, and 30 Gy were reduced with VMAT+CS, with a maximum relative reduction for V10Gy of 19.0 ± 7.3% (p<0.001). Total delivery times with VMAT+CS only increased by 1.9 ± 0.7 min compared to VMAT (9.1 ± 0.7 min). The dosimetric quality of VMAT+CS plans was equivalent to VMAT+5, while optimization times were reduced by a factor of 25 due to avoidance of individualized BAO. Compared to VMAT+CS, the 30-NCP plans were only favorable in terms of dose bath, at the cost of much enhanced optimization and delivery times. CONCLUSIONS: The proposed two-beam non-coplanar class solution to complement coplanar dual-arc VMAT resulted in substantial plan quality improvements for OARs (especially rectum) and reduced irradiated patient volumes with minor increases in treatment delivery times.

Pre-clinical validation of a novel system for fully-automated treatment planning.

INTRODUCTION: Many approaches for automated treatment planning (autoplanning) have been proposed and investigated. Autoplanning can enhance plan quality compared to 'manual' trial-and-error planning, and decrease routine planning workload. A few approaches have been implemented in commercial treatment planning systems (TPSs). We performed a pre-clinical validation of a new system ('NovelATP') that is based on fully-automated multi-criterial optimization (MCO). The aim of NovelATP is to automatically generate for each patient a single high-quality, Pareto-optimal plan without manual Pareto navigation. MATERIAL AND METHODS: Validation was performed by generating VMAT/IMRT plans for conventional treatment of prostate cancer (101 pts), prostate SBRT (20 pts), bilateral head-and-neck cancer (50 pts) and rectal cancer treated at an MR-Linac (23 pts). NovelATP autoplans were compared to plans that were generated with our in-house autoplanning system. In many previous validation studies, the latter system consistently showed enhanced plan quality when compared to manual planning. RESULTS: Dosimetrical differences between NovelATP and benchmark plans were on average small and presumably not clinically relevant, pointing at high NovelATP dosimetric plan quality. MUs were 11-19% higher with NovelATP. NovelATP delivery times were up to 12% longer. Overall, there was a slight disadvantage for NovelATP regarding gamma analyses. Calculation times for NovelATP plans were between 29  and 151 min with no overall differences with the benchmark plans. CONCLUSION: The new autoplanning system was able to produce high-quality plans for four highly different planning protocols/treatment sites with a total of 194 patients investigated.

Therapeutic alliance is associated to treatment adherence in children with juvenile idiopathic arthritis.

OBJECTIVES: Therapeutic alliance (TA) is the agreement between caregiver and patient during the care process. Therapeutic adherence is a major issue for the management of Juvenile Idiopathic Arthritis (JIA) requiring child's strong ability to follow treatments. The aim of this study was to evaluate the relationship between TA and adherence in patients with JIA. METHODS: Observational, cross-sectional, multicenter study. Children, with JIA, aged 8-16, were included. Children, parents and physicians completed the Helping Alliance Questionnaire (HAQ-CP) for assessing TA. Adherence was measured using the Child/Parent Adherence Report Questionnaire (CARQ & PARQ). Demographic data, disease characteristics, current treatments and social environment were collected. The univariate relationship between TA and adherence, was studied by Pearson correlation coefficient. The multivariate analysis used a multiple linear regression model. RESULTS: A total of 119 patients were included: 68.9% girls, mean age (SD) 12.4 (2.9) years, disease duration 73.1 (48.2) months. JIA was in remission (52%), in low activity (32%) and active (16%). TA scores were high (≥80/100) for children, parents and physicians. HAQCP was highly correlated with CARQ (r=0.31; P<0.001) PARQ (r=0.37; P<0.001). In univariate analysis, disease activity (P<0.05), place of residence (P<0.01) and family status (P<0.01) were associated with child's TA. In multivariate analysis, only the place of residence (P<0.001) and the family status (P<0.05) remained associated with TA. CONCLUSION: TA strongly influences therapeutic adherence and therefore may be important for treatment effectiveness.

Largely reduced OAR doses, and planning and delivery times for challenging robotic SBRT cases, obtained with a novel optimizer.

Recently, VOLO™ was introduced as a new optimizer for CyberKnife® planning. In this study, we investigated possibilities to improve treatment plans for MLC-based prostate SBRT with enhanced peripheral zone dose while sparing the urethra, and central lung tumors, compared to existing Sequential Optimization (SO). The primary focus was on reducing OAR doses. For 25 prostate and 25 lung patients treated with SO plans, replanning with VOLO™ was performed with the same planning constraints. For equal PTV coverage, almost all OAR plan parameters were improved with VOLO™. For prostate patients, mean rectum and bladder doses were reduced by 34.2% (P < 0.001) and 23.5% (P < 0.001), with reductions in D0.03cc of 3.9%, 11.0% and 3.1% for rectum, mucosa and bladder (all P ≤ 0.01). Urethra D5% and D10% were 3.8% and 3.0% lower (P ≤ 0.002). For lung patients, esophagus, main bronchus, trachea, and spinal cord D0.03cc was reduced by 18.9%, 11.1%, 16.1%, and 13.2%, respectively (all P ≤ 0.01). Apart from the dosimetric advantages of VOLO™ planning, average reductions in MU, numbers of beams and nodes for prostate/lung were 48.7/32.8%, 26.5/7.9% and 13.4/7.9%, respectively (P ≤ 0.003). VOLO™ also resulted in reduced delivery times with mean/max reductions of: 27/43% (prostate) and 15/41% (lung), P  < 0.001. Planning times reduced from 6 h to 1.1 h and from 3 h to 1.7 h for prostate and lung, respectively. The new VOLO™ planning was highly superior to SO planning in terms of dosimetric plan quality, and planning and delivery times.

Radiotherapy Treatment plannINg study Guidelines (RATING): A framework for setting up and reporting on scientific treatment planning studies.

Radiotherapy treatment planning studies contribute significantly  to advances and improvements in radiation treatment of cancer patients. They are a pivotal step to support and facilitate the introduction of novel techniques into clinical practice, or as a first step before clinical trials can be carried out. There have been numerous examples published in the literature that demonstrated the feasibility of such techniques as IMRT, VMAT, IMPT, or that compared different treatment methods (e.g. non-coplanar vs coplanar treatment), or investigated planning approaches (e.g. automated planning). However, for a planning study to generate trustworthy new knowledge and give confidence in applying its findings, then its design, execution and reporting all need to meet high scientific standards. This paper provides a 'quality framework' of recommendations and guidelines that can contribute to the quality of planning studies and resulting publications. Throughout the text, questions are posed and, if applicable to a specific study and if met, they can be answered positively in the provided 'RATING' score sheet. A normalised weighted-sum score can then be calculated from the answers as a quality indicator. The score sheet can also be used to suggest how the quality might be improved, e.g. by focussing on questions with high weight, or by encouraging consideration of aspects given insufficient attention. Whilst the overall aim of this framework and scoring system is to improve the scientific quality of treatment planning studies and papers, it might also be used by reviewers and journal editors to help to evaluate scientific manuscripts reporting planning studies.