Treatment planning for MR-guided SBRT of pancreatic tumors on a 1.5 T MR-Linac: A global consensus protocol.

Background and purpose: Treatment planning for MR-guided stereotactic body radiotherapy (SBRT) for pancreatic tumors can be challenging, leading to a wide variation of protocols and practices. This study aimed to harmonize treatment planning by developing a consensus planning protocol for MR-guided pancreas SBRT on a 1.5 T MR-Linac. Materials and methods: A consortium was founded of thirteen centers that treat pancreatic tumors on a 1.5 T MR-Linac. A phased planning exercise was conducted in which centers iteratively created treatment plans for two cases of pancreatic cancer. Each phase was followed by a meeting where the instructions for the next phase were determined. After three phases, a consensus protocol was reached. Results: In the benchmarking phase (phase I), substantial variation between the SBRT protocols became apparent (for example, the gross tumor volume (GTV) D99% ranged between 36.8 - 53.7 Gy for case 1, 22.6 - 35.5 Gy for case 2). The next phase involved planning according to the same basic dosimetric objectives, constraints, and planning margins (phase II), which led to a large degree of harmonization (GTV D99% range: 47.9-53.6 Gy for case 1, 33.9-36.6 Gy for case 2). In phase III, the final consensus protocol was formulated in a treatment planning system template and again used for treatment planning. This not only resulted in further dosimetric harmonization (GTV D99% range: 48.2-50.9 Gy for case 1, 33.5-36.0 Gy for case 2) but also in less variation of estimated treatment delivery times. Conclusion: A global consensus protocol has been developed for treatment planning for MR-guided pancreatic SBRT on a 1.5 T MR-Linac. Aside from harmonizing the large variation in the current clinical practice, this protocol can provide a starting point for centers that are planning to treat pancreatic tumors on MR-Linac systems.

Predicting Long-term Disease-free Survival After Resection of Pancreatic Ductal Adenocarcinoma: A Nationwide Cohort Study.

OBJECTIVE: To develop a prediction model for long-term (≥5 years) disease-free survival (DFS) after the resection of pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Despite high recurrence rates, ~10% of patients have long-term DFS after PDAC resection. A model to predict long-term DFS may aid individualized prognostication and shared decision-making. METHODS: This nationwide cohort study included all consecutive patients who underwent PDAC resection in the Netherlands (2014-2016). The best-performing prognostic model was selected by Cox-proportional hazard analysis and Akaike's Information Criterion, presented by hazard ratios (HRs) with 95% confidence intervals (CIs). Internal validation was performed, and discrimination and calibration indices were assessed. RESULTS: In all, 836 patients with a median follow-up of 67 months (interquartile range 51-79) were analyzed. Long-term DFS was seen in 118 patients (14%). Factors predictive of long-term DFS were low preoperative carbohydrate antigen 19-9 (logarithmic; HR 1.21; 95% CI 1.10-1.32), no vascular resection (HR 1.33; 95% CI 1.12-1.58), T1 or T2 tumor stage (HR 1.52; 95% CI 1.14-2.04, and HR 1.17; 95% CI 0.98-1.39, respectively), well/moderate tumor differentiation (HR 1.44; 95% CI 1.22-1.68), absence of perineural and lymphovascular invasion (HR 1.42; 95% CI 1.11-1.81 and HR 1.14; 95% CI 0.96-1.36, respectively), N0 or N1 nodal status (HR 1.92; 95% CI 1.54-2.40, and HR 1.33; 95% CI 1.11-1.60, respectively), R0 resection margin status (HR 1.25; 95% CI 1.07-1.46), no major complications (HR 1.14; 95% CI 0.97-1.35) and adjuvant chemotherapy (HR 1.74; 95% CI 1.47-2.06). Moderate performance (concordance index 0.68) with adequate calibration (slope 0.99) was achieved. CONCLUSIONS: The developed prediction model, readily available at www.pancreascalculator.com, can be used to estimate the probability of long-term DFS after resection of pancreatic ductal adenocarcinoma.

The effect of surface roughening on the success of orthodontic mini-implants: A systematic review and meta-analysis.

INTRODUCTION: Orthodontic mini-implants are a widely accepted treatment modality in orthodontics; however, the failure rate is moderately high. Surface roughening is the golden standard in conventional oral implantology, and this may prove beneficial for orthodontic mini-implants as well. The objective of this systematic review is to assess the effect of surface roughening on the success rate of orthodontic mini-implants in both adolescent and adult patients undergoing orthodontic treatment. METHODS: Randomized studies comparing the success of surface-roughened and smooth, machined-surface orthodontic mini-implants were included. A literature search was conducted for 6 electronic databases (Pubmed/Medline, Embase, Cochrane, CINAHL, Web of Science, and Scopus), Clinical trial registry (https://www. CLINICALTRIALS: gov), and grey literature (Google Scholar). A manual search of the reference lists of included studies was performed. Two authors independently performed the screening, data extraction, risk of bias, and quality assessments. The risk of bias was assessed with the Cochrane risk-of-bias 2.0 Tool. Data were synthesized using a random effect model meta-analysis presented as a forest plot. The certainty in the body of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation tool. RESULTS: A total of 4226 unique records were screened, and 6 of these were included in the quantitative analysis. Four additional articles were selected for a secondary outcome. A total of 364 orthodontic mini-implants were included in the primary outcome analysis. There was no statistically significant effect of surface roughening on the success of orthodontic mini-implants (odds ratio = 0.63 favoring roughened orthodontic mini-implants; 95% confidence interval, 0.35-1.14). The secondary outcome (ie, the overall failure rate of roughened orthodontic mini-implants) was 6% based on studies with high heterogeneity. Limitations of this study were the risk of bias, study imprecision, and possible publication bias, leading to a very low certainty in the body of evidence. CONCLUSIONS: There is very low-quality evidence that there is no statistically significant effect of surface roughening on the success of orthodontic mini-implants in humans. The overall failure rate of surface-roughened orthodontic mini-implants was 6%. FUNDING: No funding was received for this review. REGISTRATION: This study was preregistered in the Prospective Register of Systematic Reviews (CRD42022371830).

Gating and intrafraction drift correction on a 1.5 T MR-Linac: Clinical dosimetric benefits for upper abdominal tumors.

This work reports on the first seven patients treated with gating and baseline drift correction on the high-field MR-Linac system. Dosimetric analysis showed that the active motion management system improved congruence to the planned dose, efficiently mitigating detrimental effects of intrafraction motion in the upper abdomen.

A robust semi-automatic delineation workflow using denoised diffusion weighted magnetic resonance imaging for response assessment of patients with esophageal cancer treated with neoadjuvant chemoradiotherapy.

Background and Purpose: Diffusion weighted magnetic resonance imaging (DW-MRI) can be prognostic for response to neoadjuvant chemotherapy (nCRT) in patients with esophageal cancer. However, manual tumor delineation is labor intensive and subjective. Furthermore, noise in DW-MRI images will propagate into the corresponding apparent diffusion coefficient (ADC) signal. In this study a workflow is investigated that combines a denoising algorithm with semi-automatic segmentation for quantifying ADC changes. Materials and Methods: Twenty patients with esophageal cancer who underwent nCRT before esophagectomy were included. One baseline and five weekly DW-MRI scans were acquired for every patient during nCRT. A self-supervised learning denoising algorithm, Patch2Self, was used to denoise the DWI-MRI images. A semi-automatic delineation workflow (SADW) was next developed and compared with a manually adjusted workflow (MAW). The agreement between workflows was determined using the Dice coefficients and Brand Altman plots. The prognostic value of ADCmean increases (%/week) for pathologic complete response (pCR) was assessed using c-statistics. Results: The median Dice coefficient between the SADW and MAW was 0.64 (interquartile range 0.20). For the MAW, the c-statistic for predicting pCR was 0.80 (95% confidence interval (CI):0.56-1.00). The SADW showed a c-statistic of 0.84 (95%CI:0.63-1.00) after denoising. No statistically significant differences in c-statistics were observed between the workflows or after applying denoising. Conclusions: The SADW resulted in non-inferior prognostic value for pCR compared to the more laborious MAW, allowing broad scale applications. The effect of denoising on the prognostic value for pCR needs to be investigated in larger cohorts.

Clinical outcomes after online adaptive MR-guided stereotactic body radiotherapy for pancreatic tumors on a 1.5 T MR-linac.

Introduction: Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is a promising treatment modality for pancreatic cancer and is being employed by an increasing number of centers worldwide. However, clinical outcomes have only been reported on a small scale, often from single institutes and in the context of clinical trials, in which strict patient selection might limit generalizability of outcomes. This study presents clinical outcomes of a large, international cohort of patients with (peri)pancreatic tumors treated with online adaptive MRgRT. Methods: We evaluated clinical outcomes and treatment details of patients with (peri)pancreatic tumors treated on a 1.5 Tesla (T) MR-linac in two large-volume treatment centers participating in the prospective MOMENTUM cohort (NCT04075305). Treatments were evaluated through schematics, dosage, delivery strategies, and success rates. Acute toxicity was assessed until 3 months after MRgRT started, and late toxicity from 3-12 months of follow-up (FU). The EORTC QLQ-C30 questionnaire was used to evaluate the quality of life (QoL) at baseline and 3 months of FU. Furthermore, we used the Kaplan-Meier analysis to calculate the cumulative overall survival. Results: A total of 80 patients were assessed with a median FU of 8 months (range 1-39 months). There were 34 patients who had an unresectable primary tumor or were medically inoperable, 29 who had an isolated local recurrence, and 17 who had an oligometastasis. A total of 357 of the 358 fractions from all hypofractionated schemes were delivered as planned. Grade 3-4 acute toxicity occurred in 3 of 59 patients (5%) with hypofractionated MRgRT and grade 3-4 late toxicity in 5 of 41 patients (12%). Six patients died within 3 months after MRgRT; in one of these patients, RT attribution could not be ruled out as cause of death. The QLQ-C30 global health status remained stable from baseline to 3 months FU (70.5 at baseline, median change of +2.7 [P = 0.5]). The 1-year cumulative overall survival for the entire cohort was 67%, and that for the primary tumor group was 66%. Conclusion: Online adaptive MRgRT for (peri)pancreatic tumors on a 1.5 T MR-Linac could be delivered as planned, with low numbers of missed fractions. In addition, treatments were associated with limited grade 3-4 toxicity and a stable QoL at 3 months of FU.

Five years clinical outcome of maxillary mini dental implant overdenture treatment: A prospective multicenter clinical cohort study.

BACKGROUND: The long-term clinical outcome of mini dental implants (MDIs) to support an overdenture is underreported especially in severely atrophic maxillae and when installed flaplessly. PURPOSE: The current report is a 5-years follow-up of the previously published 2- and 3-years clinical outcome of MDIs supporting a maxillary overdenture in narrow alveolar ridges. MDI survival, marginal bone level, peri-implant health, technical complications, and oral health related quality of life (OHIP) and respective changes over time are reported. MATERIALS AND METHODS: Subjects aged 50 years or older, in need of improvement of maxillary denture retention, were included. The MDIs were 2.4 mm diameter one-piece tapered implants, Class 4 pure Titanium, and lengths 10 or 11.5 mm. Under local anesthesia, 5-6 MDIs were placed in atrophic maxillae with a free-handed flapless approach. One week postoperative the denture was adapted with a retentive soft reliner. The final prosthetic connection was established after 6 months with a metal-reinforced horse-shoe denture. Clinical outcome after 5 years was assessed with probing pocket depts (PPD), bleeding on probing (BoP), and additional cone beam computed tomography (CBCT) MDI bone level measurements were performed. Oral Health-Related Quality of Life (OHRQoL) investigated with OHIP-14 was assessed preoperative, during provisional loading, and after final prosthetic connection up to 5 years. RESULTS: Initially, 31 patients (14 females and 17 males) with mean age 62.30 underwent treatment. In the provisional loading interval, 16 patients encountered 32/185 MDIs failures, resulting in a failure of 17.3%; 170 MDIs were functionally loaded in 29 patients. Additionally, 14 implants were lost in three patients, all of whom had had already previous failures. Reimplantation of 17 MDIs were performed during the provisional loading and 2 MDI after functional loading. After 5 years, the absolute implant failure rate was 46/204 (22.5%), corresponding to a cumulative failure rate of 23.2%. Prosthetic failure was observed in four patients due to implant loss and in two patients related to excessive one-piece implant ball attachment wear, making the 5-years prosthetic success 80.0%. The mean PPD and absence/presence of BoP for 149 implants at 5 years was 4.3 and 0.2 mm, respectively. Average mesial-distal-vestibular-palatal bone loss in the interval 2-5 years was 0.08 mm. No statistically significant difference in marginal MDI bone loss between male or female (p = 0.835), smoking and nonsmoking (p = 0.666) was observed. The five-years total measured CBCT interdental bone level (mesial and distal) correlates with the 5-years PPD (Pearson 0.434; p = 0.01). After 5 years, OHRQoL with the treatment procedure was assessed in 27/31 participants. Decreasing mean total OHIP-14 scores with improved OHRQoL, was observed in 27/31 participants, with values of 21.3 at baseline to 15.6 at the time of provisional loading which significantly (p = 0.006) decrease to 7.3 at the final prosthetic connection. The next 3-5 years further decrease was observed with 6.5 and 4.96, respectively. CONCLUSIONS: Maxillary MDIs for overdentures are an accessible and acceptable treatment option. Although after 5 years between one fifth and one fourth of the MDIs were lost, prosthetic success remains 80.0% and high OHRQoL could be achieved.

Precision radiotherapy using MR-linac for pancreatic neuroendocrine tumors in MEN1 patients (PRIME): a protocol for a phase I-II trial, and systematic review on available evidence for radiotherapy of pNETs.

Background: Surgical resection is the standard of care for the treatment of pancreatic neuro-endocrine tumors (pNETs) in patients with Multiple Endocrine Neoplasia Type 1 (MEN1). However, surgery can cause significant short- and long-term morbidity. Magnetic resonance-guided radiotherapy (MRgRT) is a potential effective treatment with little side effects. With traditional radiotherapy techniques, irradiation of pancreatic tumors to high dose levels was hampered by poor visibility of the tumor during treatment. MRgRT uses onboard MRI to guide the treatment, thereby enabling delivery of ablative irradiation doses to the tumor, while sparing surrounding tissues. In this study, we describe results from a systematic review assessing efficacy of radiotherapy in pNET and present the protocol of the PRIME study. Methods: PubMed, Embase and Cochrane Library were searched for articles assessing efficacy and side effects of radiotherapy for the treatment of pNETs. Risk of bias was assessed using the ROBINS-I Risk of Bias Tool for observational studies. Descriptive statistics were used to describe results of included trials. Results: Four studies comprising of 33 patients treated by conventional radiotherapy were included. Despite the heterogeneity of studies, radiotherapy appeared to be effective for the treatment of pNETs with most patients responding (45.5%) or stabilizing (42.4%) in tumor size. Conclusion and trial design: Due to the limited literature available and concerns about damage to surrounding tissue, conventional radiotherapy is currently little used for pNETs. The PRIME study is a phase I-II trial with a single arm prospective cohort study design, investigating the efficacy of MRgRT in MEN1 patients with pNET. MEN1 patients with growing pNETs with a size between 1.0 and 3.0 cm without malignant features are eligible for inclusion. Patients are treated with 40 Gy in 5 fractions on the pNET, using online adaptive MRgRT on a 1.5T MR-linac. The primary endpoint is the change in tumor size at MRI 12 months follow-up. Secondary endpoints include radiotoxicity, quality of life, endocrine and exocrine pancreas function, resection rate, metastatic free and overall survival. When MRgRT is found effective with low radiotoxicity, it could reduce the need for surgery for pNET and preserve quality of life. Systematic Review Registration: PROSPERO https://clinicaltrials.gov/, (CRD42022325542).

Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial.

INTRODUCTION: Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ preservation following short-course radiotherapy (SCRT, 25 Gy in five fractions) and a prolonged interval (4-8 weeks) to response evaluation. The organ preservation rate could potentially be increased by dose-escalated radiotherapy. Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is anticipated to reduce radiation-induced toxicity and enable radiotherapy dose escalation. This trial aims to establish the maximum tolerated dose (MTD) of dose-escalated SCRT using online adaptive MRgRT. METHODS AND ANALYSIS: The preRADAR is a multicentre phase I trial with a 6+3 dose-escalation design. Patients with intermediate-risk rectal cancer (cT3c-d(MRF-)N1M0 or cT1-3(MRF-)N1M0) interested in organ preservation are eligible. Patients are treated with a radiotherapy boost of 2×5 Gy (level 0), 3×5 Gy (level 1), 4×5 Gy (level 2) or 5×5 Gy (level 3) on the gross tumour volume in the week following standard SCRT using online adaptive MRgRT. The trial starts on dose level 1. The primary endpoint is the MTD based on the incidence of dose-limiting toxicity (DLT) per dose level. DLT is a composite of maximum one in nine severe radiation-induced toxicities and maximum one in three severe postoperative complications, in patients treated with TME or local excision within 26 weeks following start of treatment. Secondary endpoints include the organ preservation rate, non-DLT, oncological outcomes, patient-reported QoL and functional outcomes up to 2 years following start of treatment. Imaging and laboratory biomarkers are explored for early response prediction. ETHICS AND DISSEMINATION: The trial protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht. The primary and secondary trial results will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: WHO International Clinical Trials Registry (NL8997; https://trialsearch.who.int).

Supporting consumers' informed food choices: Sources, channels, and use of information.

Information about food is available from several sources using a variety of communication channels. Following an overview of the different types on food information, the most important source/channel combinations are discussed. The key steps in processing the information toward making a food choice are discussed: consumer's exposure to such information, the attention the consumer pays to it, the understanding and/or liking of the information, as well as the importance of motivation, knowledge, and trust. To support consumers in making informed food choices, it is recommended to ensure that food information is easy to understand and targeted to consumers with a specific need or interest, align the information on the food label with the communication about the food elsewhere ("off label"), provide (non-expert) influencers with transparent information to enable an increase in the trustworthiness of their communications on the web in on social media. Furthermore, increase cooperation between authorities and food producers to create standards that fulfill the legal requirements and are feasible as label elements. Improving food literacy among consumers by including it in formal education would provide consumers with better nutrition knowledge and skills to interpret food-related information in a manner that supports informed choices.

Feasibility of online radial magnetic resonance imaging for adaptive radiotherapy of pancreatic tumors.

Background and purpose: Online adaptive magnetic resonance (MR)-guided treatment planning for pancreatic tumors on 1.5T systems typically employs Cartesian 3D T 2w magnetic resonance imaging (MRI). The main disadvantage of this sequence is that respiratory motion results in substantial blurring in the abdomen, which can hamper delineation accuracy. This study investigated the use of two motion-robust radial MRI sequences as main delineation scan for pancreatic MR-guided radiotherapy. Materials and methods: Twelve patients with pancreatic tumors were imaged with a 3D T 2w scan, a Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction (PROPELLER) scan (partially overlapping strips), and a 3D Vane scan (stack-of-stars), on a 1.5T MR-Linac under abdominal compression. The scans were assessed by three radiation oncologists for their suitability for online adaptive delineation. A quantitative comparison was made for gradient entropy and the effect of motion on apparent target position. Results: The PROPELLER scans were selected as first preference in 56% of the cases, the 3D T 2w in 42% and the 3D Vane in 3%. PROPELLER scans sometimes contained a large interslice variation which would have compromised delineation. Gradient entropy was significantly higher in 3D T 2w patient scans. The apparent target position was more sensitive to motion amplitude in the PROPELLER scans, but substantial offsets did not occur under 10 mm peak-to-peak. Conclusion: PROPELLER MRI may be a superior imaging sequence for pancreatic MRgRT compared to standard Cartesian sequences. The large interslice variation should be mitigated through further sequence optimization before PROPELLER can be adopted for online treatment adaptation.

Factors Associated with Esthetic Outcomes of Flapless Immediate Placed and Loaded Implants in the Maxillary Incisor Region-Three-Year Results of a Prospective Case Series.

Flapless immediate implant placement and provisionalization (FIIPP) is often associated with an increased risk of buccal soft-tissue recession. This study aims to assess the 3-year esthetic outcome. In 100 consecutive patients, one maxillary incisor, with or without a pre-extraction buccal bone defect (≤5 mm), was replaced by an implant installed in a maximal palatal position (buccal gap ≥2 mm). The created gaps were filled with bovine bone substitute. Patient satisfaction (PS), pink esthetic scores (PES/modPES), and white esthetic score (WES) were calculated at different time points. A multilevel regression analysis (MRA) was performed to analyze which factors may be associated with the esthetics. After three years, PS scored 8.9 ± 0.84 on a scale of 10 (n = 83), and the soft-tissue esthetics were high (PES = 12.2; modPES = 8.5), as was the WES (8.2), showing no decrease from one year. Buccal bone defect size and smoking could not be associated with the soft-tissue outcome; however, implant location, gap size, and emergence profiles could. Performing FIIPP, the final crown (WES) scored highest when it was cemented, the soft tissue (PES/modPES) in central-incisor positions, and all (WES/PES/modPES) with concave emergence profiles.

Intraoral scanning of the edentulous jaw without additional markers: An in vivo validation study on scanning precision and registration of an intraoral scan with a cone-beam computed tomography scan.

Purpose: A fully digital approach to oral prosthodontic rehabilitation requires the possibility of combining (i.e., registering) digital documentation from different sources. This becomes more complex in an edentulous jaw, as fixed dental markers to perform reliable registration are lacking. This validation study aimed to evaluate the reproducibility of 1) intraoral scanning and 2) soft tissue-based registration of an intraoral scan with a cone-beam computed tomography (CBCT) scan for a fully edentulous upper jaw. Materials and Methods: Two observers independently performed intraoral scans of the upper jaw in 14 fully edentulous patients. The palatal vault of both surface models was aligned, and the inter-observer variability was assessed by calculating the mean inter-surface distance at the level of the alveolar crest. Additionally, a CBCT scan of all patients was obtained and a soft tissue surface model was generated using patient-specific gray values. This CBCT soft tissue model was registered with the intraoral scans of both observers, and the intraclass correlation coefficient (ICC) was calculated to evaluate the reproducibility of the registration method. Results: The mean inter-observer deviation when performing an intraoral scan of the fully edentulous upper jaw was 0.10 ± 0.09 mm. The inter-observer agreement for the soft tissue-based registration method was excellent (ICC=0.94; 95% confidence interval, 0.81-0.98). Conclusion: Even when teeth are lacking, intraoral scanning of the jaw and soft tissue-based registration of an intraoral scan with a CBCT scan can be performed with a high degree of precision.

Intrafraction motion analysis in online adaptive radiotherapy for esophageal cancer.

Intrafraction motion during magnetic resonance (MR)-guided dose delivery of esophageal cancer tumors was retrospectively analyzed. Deformable image registration of cine-MR series resulted in gross tumor volume motion profiles in all directions, which were subsequently filtered to isolate respiratory and drift motion. A large variability in intrafraction motion patterns was observed between patients. Median 95% peak-to-peak motion was 7.7 (3.7 - 18.3) mm, 2.1 (0.7 - 5.7) mm and 2.4 (0.5 - 5.6) mm in cranio-caudal, left-right and anterior-posterior directions, relatively. Furthermore, intrafraction drift was generally modest (<5mm). A patient specific approach could lead to very small margins (<3mm) for most patients.

Feasibility of delivered dose reconstruction for MR-guided SBRT of pancreatic tumors with fast, real-time 3D cine MRI.

BACKGROUND AND PURPOSE: In MR-guided SBRT of pancreatic cancer, intrafraction motion is typically monitored with (interleaved) 2D cine MRI. However, tumor surroundings are often not fully captured in these images, and motion might be distorted by through-plane movement. In this study, the feasibility of highly accelerated 3D cine MRI to reconstruct the delivered dose during MR-guided SBRT was assessed. MATERIALS AND METHODS: A 3D cine MRI sequence was developed for fast, time-resolved 4D imaging, featuring a low spatial resolution that allows for rapid volumetric imaging at 430 ms. The 3D cines were acquired during the entire beam-on time of 23 fractions of online adaptive MR-guided SBRT for pancreatic tumors on a 1.5 T MR-Linac. A 3D deformation vector field (DVF) was extracted for every cine dynamic using deformable image registration. Next, these DVFs were used to warp the partial dose delivered in the time interval between consecutive cine acquisitions. The warped dose plans were summed to obtain a total delivered dose. The delivered dose was also calculated under various motion correction strategies. Key DVH parameters of the GTV, duodenum, small bowel and stomach were extracted from the delivered dose and compared to the planned dose. The uncertainty of the calculated DVFs was determined with the inverse consistency error (ICE) in the high-dose regions. RESULTS: The mean (SD) relative (ratio delivered/planned) D99% of the GTV was 0.94 (0.06), and the mean (SD) relative D0.5cc of the duodenum, small bowel, and stomach were respectively 0.98 (0.04), 1.00 (0.07), and 0.98 (0.06). In the fractions with the lowest delivered tumor coverage, it was found that significant lateral drifts had occurred. The DVFs used for dose warping had a low uncertainty with a mean (SD) ICE of 0.65 (0.07) mm. CONCLUSION: We employed a fast, real-time 3D cine MRI sequence for dose reconstruction in the upper abdomen, and demonstrated that accurate DVFs, acquired directly from these images, can be used for dose warping. The reconstructed delivered dose showed only a modest degradation of tumor coverage, mostly attainable to baseline drifts. This emphasizes the need for motion monitoring and development of intrafraction treatment adaptation solutions, such as baseline drift corrections.

Risk Factors for Tumor Positive Resection Margins After Neoadjuvant Chemoradiotherapy for Esophageal Cancer: Results From the Dutch Upper GI Cancer Audit: A Nationwide Population-Based Study.

OBJECTIVE: To identify risk factors for tumor positive resection margins after neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy for esophageal cancer. SUMMARY BACKGROUND DATA: Esophagectomy after nCRT is associated with tumor positive resection margins in 4% to 9% of patients. This study evaluates potential risk factors for positive resection margins after nCRT followed by esophagectomy. METHODS: All patients who underwent an elective esophagectomy following nCRT in 2011 to 2017 in the Netherlands were included. A multivariable logistic regression was performed to assess the association between potential risk factors and tumor positive resection margins. RESULTS: In total, 3900 patients were included. Tumor positive resection margins were observed in 150 (4%) patients. Risk factors for tumor positive resection margins included tumor length (in centimeters, OR: 1.1, 95% CI: 1.0-1.1), cT4-stage (OR: 3.0, 95% CI: 1.2-6.7), and an Ivor Lewis esophagectomy (OR: 1.6, 95% CI: 1.0-2.6). Predictors associated with a lower risk of tumor positive resection margins were squamous cell carcinoma (OR: 0.4, 95% CI: 0.2-0.7), distal tumors (OR: 0.5, 95% CI: 0.3-1.0), minimally invasive surgery (OR: 0.6, 95% CI: 0.4-0.9), and a hospital volume of >60 esophagectomies per year (OR: 0.6, 95% CI: 0.4-1.0). CONCLUSIONS: In this nationwide cohort study, tumor and surgical related factors (tumor length, histology, cT-stage, tumor location, surgical procedure, surgical approach, hospital volume) were identified as risk factors for tumor positive resection margins after nCRT for esophageal cancer. These results can be used to improve the radical resection rate by careful selection of patients and surgical approach and are a plea for centralization of esophageal cancer care.

Intraoral Scanning as an Alternative to Evaluate the Accuracy of Dental Implant Placements in Partially Edentate Situations: A Prospective Clinical Case Series.

(1) Background: For years, Cone-Beam Computed Tomography's (CBCT) have been the golden standard to evaluate implant placement accuracy. By validating Intraoral Scans (IOS) as an alternative to determine implant placement accuracy, a second CBCT could be avoided. (2) Methods: Using dynamic guided implant surgery, 23 implants were placed in 16 partially edentate patients. Preoperatively, both CBCT and IOS (Trios® 3) were obtained and subsequently imported into DTX Studio™ planning software to determine the ideal implant location. A CBCT scan and an IOS including scan abutments were acquired immediately after placement. Both postoperative CBCT and postoperative IOS were used to compare the achieved implant position with the planned implant position and were projected and analyzed using the Implant Position Orthogonal Projection (IPOP) method. (3) Results: Mean differences between the CBCT and IOS methods on the mesio−distal plane were 0.09 mm (p = 0.419) at the tip, 0.01 mm (p = 0.910) at the shoulder, −0.55° (p = 0.273) in angulation, and 0.2 mm (p = 0.280) in implant depth. Mean differences between both methods on the bucco-lingual/bucco-palatal plane were 0.25 mm (p = 0.000) at the tip, 0.12 mm (p = 0.011) at the shoulder, −0.81° (p = 0.002) in angulation, and 0.17 mm (p = 0.372) in implant depth. A statistical analysis was performed using a paired t-test. All mesiodistal deviations between the two methods showed no significant differences (p > 0.05). Buccolingual/buccopalatal deviations showed no significant difference in implant depth deviation. However, significant differences were found at the tip, shoulder, and angulation (p < 0.05). These values are of minimal clinical significance. (4) Conclusions: This study supports the hypothesis that a postoperative IOS is a valid alternative for determining implant placement accuracy.

Histomorphometric Analysis of Flaplessly Placed and Early Loaded One-Piece Mini Dental Implants in Overdenture Patients.

Mini dental implants (MDIs) are an affordable alternative for overdentures in medically compromised patients with reduced bone volume. This human study reports the histomorphometric analysis of early loaded and flaplessly placed tapered, one-piece MDIs (ILZ, Southern Implants; Sa: 1.5 µm) after 7 to 11 months in function. Patients agreed to have an additional MDI placed and removed for evaluation. MDI stability was assessed via Periotest prior to implant removal. Histologic sections of four mandibular and three maxillary MDIs with surrounding bone were processed, and the bone-to-implant contact (BIC) was analyzed. At retrieval, the MDIs were in function for more than 6 months, were clinically healthy, and had mean probing pocket depths of 1.4 mm and 1.6 mm in the maxilla and mandible, respectively. Periotest values were < 5.5, indicating clinical stability. Most of the screw threads were filled with bone and revealed an intimate BIC, without any signs of intervening fibrous tissue layer. In both arches, the mean BIC was 68.5%. Large osteocytes could be identified in the calcified tissue, indicative of mature peri-implant bone. It can be concluded that MDIs, when loaded within 2 weeks in either arch, provide proper clinical stability and high BIC after 6 months.

Fully digital workflow for producing implant-supported overdentures milled from PMMA on titanium bars using PEEK as the female part/sliding mechanism in three clinical visits: A case report.

PURPOSE: To prove that a fully digital workflow, even for registration of the maxillomandibular relationship, can be employed to produce implant-supported overdentures and demonstrate that CAD/CAM techniques can be used to mill permanent implant-supported overdentures from polymethylmethacrylate discs, using polyetheretherketone as the sliding mechanism. MATERIALS AND METHODS: An edentulous 64-year-old woman received six implants in the maxilla after a bone augmentation procedure and two implants in the mandible. Five months after implant placement, intraoral scans were taken of her original complete dentures, of each prosthesis individually, and of both in centric relation, and another was taken of both edentulous arches, including the scan bodies. Along with facial photographs, sufficient digital data were gathered to design and mill titanium bars, polyetheretherketone female parts and a trial implant-supported overdenture. The tooth positions and colour were discussed with the patient using Smile Design software (3Shape, Copenhagen, Denmark). In the second session, the bars and trial implant-supported overdenture were inserted and checked, and in the third session, the final implant-supported overdentures were inserted. RESULTS: The milled titanium bar exhibited a passive fit, as did the implant-supported overdentures. After 1 year, no prosthetic complications were noted; the measured pockets were all less than 4 mm in depth. On a visual analogue scale from 0 to 10, with 0 being the worst and 10 being the best, the patient awarded a score of 9 for her satisfaction with the implant-supported overdentures. CONCLUSION: A fully digital workflow enables the production of robust wear-resistant implant-supported overdentures milled from polymethylmethacrylate, using polyetheretherketone female parts as the sliding mechanism, in just three clinical sessions.

Dosimetric impact of intrafraction motion under abdominal compression during MR-guided SBRT for (Peri-) pancreatic tumors.

Objective. Intrafraction motion is a major concern for the safety and effectiveness of high dose stereotactic body radiotherapy (SBRT) in the upper abdomen. In this study, the impact of the intrafraction motion on the delivered dose was assessed in a patient group that underwent MR-guided radiotherapy for upper abdominal malignancies with an abdominal corset.Approach. Fast online 2D cine MRI was used to extract tumor motion during beam-on time. These tumor motion profiles were combined with linac log files to reconstruct the delivered dose in 89 fractions of MR-guided SBRT in twenty patients. Aside the measured tumor motion, motion profiles were also simulated for a wide range of respiratory amplitudes and drifts, and their subsequent dosimetric impact was calculated in every fraction.Main results. The average (SD)D99%of the gross tumor volume (GTV), relative to the plannedD99%, was 0.98 (0.03). The average (SD) relativeD0.5ccof the duodenum, small bowel and stomach was 0.99 (0.03), 1.00 (0.03), and 0.97 (0.05), respectively. No correlation of respiratory amplitude with dosimetric impact was observed. Fractions with larger baseline drifts generally led to a larger uncertainty of dosimetric impact on the GTV and organs at risk (OAR). The simulations yielded that the delivered dose is highly dependent on the direction of on baseline drift. Especially in anatomies where the OARs are closely abutting the GTV, even modestLRorAPdrifts can lead to substantial deviations from the planned dose.Significance. The vast majority of the fractions was only modestly impacted by intrafraction motion, increasing our confidence that MR-guided SBRT with abdominal compression can be safely executed for patients with abdominal tumors, without the use of gating or tracking strategies.