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).

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.

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.

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.

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).

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).

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.

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.

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.

Detecting Interval Distant Metastases With 18F-FDG PET/CT After Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Cancer.

PURPOSE: Patients with esophageal cancer can develop distant metastases between the start of neoadjuvant chemoradiotherapy (nCRT) and planned surgery (ie, interval distant metastases). 18F-FDG PET/CT restaging after nCRT detects interval distant metastases in ~8% of patients. This study aimed to identify patients for whom 18F-FDG PET/CT restaging after nCRT could be omitted using an existing prediction model predicting for interval distant metastases or by using clinical stage groups. PATIENTS AND METHODS: Patients with locally advanced esophageal cancer who underwent baseline and restaging 18F-FDG PET/CT, nCRT, and were planned for esophagectomy between 2017 and 2021 were eligible for inclusion in this retrospective study. The primary outcome was the existing model's external performance (ie, discrimination and calibration) for predicting interval distant metastases. The existing model predictors included tumor length, cN status, squamous cell carcinoma histology, and baseline SUVmax. The secondary outcome determined the clinical stage groups (AJCC/UICC eighth edition) for adenocarcinoma and squamous cell carcinoma for which the incidence of interval distant metastases was <10%. RESULTS: In total, 127 patients were included, of whom 17 patients developed interval distant metastases (13%; 95% confidence interval [CI], 8%-21%) and 9 patients were deemed to have false-positive lesions on 18F-FDG PET/CT (7%; 95% CI, 2%-11%). Applying the existing model to this cohort yielded a discriminatory c-statistic of 0.56 (95% CI, 0.40-0.72). The calibration of the existing model was poor (ie, mostly underestimating the actual risk). The incidence of true-positive versus false-positive interval distant metastases for patients with clinical stage II disease was 5% versus 0%; clinical stage III, 14% versus 8%; and clinical stage IVa, 22% versus 9%. CONCLUSIONS: The existing prediction model cannot reliably identify patients at risk for developing interval distant metastases after nCRT for esophageal cancer. Omission of 18F-FDG PET/CT restaging after nCRT could be considered in patients with clinical stage II esophageal cancer.

Intrafraction pancreatic tumor motion patterns during ungated magnetic resonance guided radiotherapy with an abdominal corset.

BACKGROUND: Stereotactic body radiotherapy (SBRT) has been shown to be a promising therapy for unresectable pancreatic tumors. However, intrafraction motion, caused by respiratory motion and organ drift, is one of the main concerns for efficient dose delivery in ungated upper abdominal radiotherapy. The aim of this study was to analyze the intrafraction gross tumor volume (GTV) motion in a clinical cohort. MATERIALS AND METHODS: We included 13 patients that underwent online adaptive magnetic resonance (MR)-guided SBRT for malignancies in the pancreatic region (5 × 8 Gy). An abdominal corset was fitted in order to reduce the abdominal respiratory motion. Coronal and sagittal cine magnetic resonance images of the tumor region were made at 2 Hz during the entire beam-on time of each fraction. We used deformable image registration to obtain GTV motion profiles in all three directions, which were subsequently high-pass and low-pass filtered to isolate the motion caused by respiratory motion and baseline drift, respectively. RESULTS: The mean (SD) respiratory amplitudes were 4.2 (1.9) mm cranio-caudal (CC), 2.3 (1.1) mm ventral-dorsal (AP) and 1.4 (0.6) mm left-right (LR), with low variability within patients. The mean (SD) maximum baseline drifts were 1.2 (1.1) mm CC, 0.5 (0.4) mm AP and 0.5 (0.3) mm LR. The mean (SD) minimum baseline drifts were -0.7 (0.5) mm CC, -0.6 (0.5) mm AP and -0.5 (0.4) mm LR. CONCLUSION: Overall tumor motion during treatment was small and interfractionally stable. These findings show that high-precision ungated MR-guided SBRT is feasible with an abdominal corset.

Detection, Treatment, and Survival of Pancreatic Cancer Recurrence in the Netherlands: A Nationwide Analysis.

OBJECTIVE: To evaluate whether detection of recurrent pancreatic ductal adenocarcinoma (PDAC) in an early, asymptomatic stage increases the number of patients receiving additional treatment, subsequently improving survival. SUMMARY OF BACKGROUND DATA: International guidelines disagree on the value of standardized postoperative surveillance for early detection and treatment of PDAC recurrence. METHODS: A nationwide, observational cohort study was performed including all patients who underwent PDAC resection (2014-2016). Prospective baseline and perioperative data were retrieved from the Dutch Pancreatic Cancer Audit. Data on follow-up, treatment, and survival were collected retrospectively. Overall survival (OS) was evaluated using multivariable Cox regression analysis, before and after propensity-score matching, stratified for patients with symptomatic and asymptomatic recurrence. RESULTS: Eight hundred thirty-six patients with a median follow-up of 37 months (interquartile range 30-48) were analyzed. Of those, 670 patients (80%) developed PDAC recurrence after a median follow-up of 10 months (interquartile range 5-17). Additional treatment was performed in 159/511 patients (31%) with symptomatic recurrence versus 77/159 (48%) asymptomatic patients (P < 0.001). After propensity-score matching on lymph node ratio, adjuvant therapy, disease-free survival, and recurrence site, additional treatment was independently associated with improved OS for both symptomatic patients [hazard ratio 0.53 (95% confidence interval 0.42-0.67); P < 0.001] and asymptomatic patients [hazard ratio 0.45 (95% confidence interval 0.29-0.70); P < 0.001]. CONCLUSIONS: Additional treatment of PDAC recurrence was independently associated with improved OS, with asymptomatic patients having a higher probability to receive recurrence treatment. Therefore, standardized postoperative surveillance aiming to detect PDAC recurrence before the onset of symptoms has the potential to improve survival. This provides a rationale for prospective studies on standardized surveillance after PDAC resection.

The Presence of Metastatic Thoracic Duct Lymph Nodes in Western Esophageal Cancer Patients: A Multinational Observational Study.

BACKGROUND: The thoracic lymphadenectomy during an esophagectomy for esophageal cancer includes resection of the thoracic duct (TD) compartment containing the TD lymph nodes (TDLNs). The role of TD compartment resection is still a topic of debate since metastatic TDLNs have only been demonstrated in squamous cell carcinomas in Eastern esophageal cancer patients. Therefore, the aim of this study was to assess the presence and metastatic involvement of TDLNs in a Western population, in which adenocarcinoma is the predominant type of esophageal cancer. METHODS: From July 2017 to May 2020, all consecutive patients undergoing an open or robot-assisted transthoracic esophagectomy with concurrent lymphadenectomy and resection of the TD compartment in the University Medical Center Utrecht in Utrecht, the Netherlands, and the Città della Salute e della Scienza University Hospital in Turin, Italy, were included. The TD compartment was resected en bloc and was separated in the operation room by the operating surgeon after which it was macroscopically and microscopically assessed for (metastatic) TDLNs by the pathologist. RESULTS: A total of 117 patients with an adenocarcinoma (73%) or squamous cell carcinoma (27%) of the esophagus were included. In 61 (52%) patients, TDLNs were found, containing metastasis in 9 (15%) patients. No major complications related to TD compartment resection were observed. CONCLUSIONS: This study demonstrates the presence of metastatic TDLNs in adenocarcinomas of the esophagus. This result provides a valid argument to routinely extend the thoracic lymphadenectomy with resection of the TD compartment during an esophagectomy for esophageal cancer.

Online adaptive MR-guided stereotactic radiotherapy for unresectable malignancies in the upper abdomen using a 1.5T MR-linac.

BACKGROUND: Introduction of online adaptive MR-guided radiotherapy enables stereotactic body radiation therapy (SBRT) of upper abdominal tumors. This study aimed to evaluate the feasibility of MR-guided SBRT on a 1.5 T MR-linac in patients with unresectable upper abdominal malignancies. MATERIAL AND METHODS: Patients treated at the UMC Utrecht (April 2019 to December 2020) were identified in the prospective 'Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-linac' (MOMENTUM) study. Feasibility of treatment was arbitrarily defined as an on-table time interval of ≤60 min for >75% of delivered fractions and completion of >95% of fractions as scheduled, reflecting patient tolerability. Acute treatment-related toxicity was assessed at 3 months of follow-up and graded according to the National Cancer Institute Common Terminology Criteria of Adverse Events version 5.0. RESULTS: Twenty-five consecutive patients with a median follow-up time of 8 (range 4-23) months were treated with 35 Gray (n = 4) and 40 Gray (n = 21) in five fractions over 2 weeks. For all fractions, contours were adapted based on the daily anatomy and delivered within 47 min/fraction (range 30-74). In 98/117 fractions (84%), adapted treatment was completed within 1 h. All patients received the scheduled irradiation dose as planned. No acute grade 3 toxicity or higher was reported. Treatment resulted in pain alleviation in 11/13 patients. DISCUSSION: Online adaptive MR-guided SBRT on a 1.5 T MR-linac is feasible and well-tolerated in patients with unresectable upper abdominal malignancies. Dose escalation studies, followed by comparative studies, are needed to determine the optimal radiation dose for irradiation of upper abdominal malignancies.

Combined effect of undersized surgical technique and axial compression on the primary implant stability and host bone architecture.

AIM: The aim of this study was to investigate the combined effect of the lateral-compression of host-bone (undersized-osteotomy-preparation) and axial-compression of host-bone (not drilling the full length of the implant) on the primary-implant-stability and the host-bone-architecture. MATERIALS AND METHODS: In this experimental-study, 44 dental implants (diameter-4.2 mm; length-10 mm; Dyna®) were installed in the femoral-condyles of four cadaver-goats using four different surgical approaches (11 implant/surgical approach; n = 11). Approach-1: Standard preparation according to the manufacturer's guidelines. The bone-cavity was prepared up to 10 mm in depth and 4 mm in diameter. Approach-2: Preparation up to 8 mm in depth and 4 mm in diameter. Approach-3: Preparation up to 10 mm in depth. Approach-4: The bone-cavity was prepared up to 8 mm in depth and 3.6 mm in diameter. Insertion torque (n = 11), removal torque (n = 7) and % bone-implant contact (n = 4) measurements were recorded. Bone architecture was assessed by micro-computer tomography and histological analysis (n = 4). RESULTS: For approaches 2, 3, and 4 (P < .05), insertion-torque values were significantly higher as compared to approach 1. Regarding the bone-implant-contact percentage (%BIC), approach 3 and 4 were significantly higher compared to approach 1 and 2 (P<.05). For approach 2, the %bone volume (%BV) was significantly higher as compared to approach 1 (P<.05) for the most the inner zone of host bone in proximity of the implant. CONCLUSION: Lateral and axial compression improved the primary-implant-stability and therefore this new surgical-technique should be considered as an alternative approach especially for placing implants in low-density bone. Nevertheless, additional in vivo studies should be performed.

Planning target volume margin assessment for online adaptive MR-guided dose-escalation in rectal cancer on a 1.5 T MR-Linac.

PURPOSE: This study assessed the margins needed to cover tumor intrafraction motion during an MR-guided radiotherapy (MRgRT) dose-escalation strategy in intermediate risk rectal cancer. METHODS: Fifteen patients with rectal cancer were treated with neoadjuvant short-course radiotherapy, 5x5 Gy, according to an online adaptive workflow on a 1.5 T MR-linac. Per patient, 26 3D T2 weighted MRIs were made; one reference scan preceding treatment and five scans per treatment fraction. The primary tumor was delineated on each scan as gross tumor volume (GTV). Target coverage margins were assessed by isotropically expanding the reference GTV until more than 95% of the voxels of the sequential GTVs were covered. A margin with a coverage probability threshold of 90% was defined as adequate. Intra- and interfraction margins to cope with the movement of the GTV in the period between scans were calculated to indicate the target volume margins. Furthermore, the margin needed to cover GTV movement was calculated for different time intervals. RESULTS: The required margins to cover inter- and intrafraction GTV motion were 17 mm and 6 mm, respectively. Analysis based on time intervals between scans showed smaller margins were needed for adequate GTV coverage as time intervals became shorter, with a 4 mm margin required for a procedure of 15 min or less. CONCLUSION: The shorter the treatment time, the smaller the margins needed to cover for the GTV movement during an online adaptive MRgRT dose-escalation strategy for intermediate risk rectal cancer. When time intervals between replanning and the end of dose delivery could be reduced to 15 min, a 4 mm margin would allow adequate target coverage.

Magnetic Resonance Guided Radiation Therapy for Pancreatic Adenocarcinoma, Advantages, Challenges, Current Approaches, and Future Directions.

INTRODUCTION: Pancreatic adenocarcinoma (PAC) has some of the worst treatment outcomes for any solid tumor. PAC creates substantial difficulty for effective treatment with traditional RT delivery strategies primarily secondary to its location and limited visualization using CT. Several of these challenges are uniquely addressed with MR-guided RT. We sought to summarize and place into context the currently available literature on MR-guided RT specifically for PAC. METHODS: A literature search was conducted to identify manuscript publications since September 2014 that specifically used MR-guided RT for the treatment of PAC. Clinical outcomes of these series are summarized, discussed, and placed into the context of the existing pancreatic literature. Multiple international experts were involved to optimally contextualize these publications. RESULTS: Over 300 manuscripts were reviewed. A total of 6 clinical outcomes publications were identified that have treated patients with PAC using MR guidance. Successes, challenges, and future directions for this technology are evident in these publications. MR-guided RT holds theoretical promise for the treatment of patients with PAC. As with any new technology, immediate or dramatic clinical improvements associated with its use will take time and experience. There remain no prospective trials, currently publications are limited to small retrospective experiences. The current level of evidence for MR guidance in PAC is low and requires significant expansion. Future directions and ongoing studies that are currently open and accruing are identified and reviewed. CONCLUSIONS: The potential promise of MR-guided RT for PAC is highlighted, the challenges associated with this novel therapeutic intervention are also reviewed. Outcomes are very early, and will require continued and long term follow up. MR-guided RT should not be viewed in the same fashion as a novel chemotherapeutic agent for which dosing, administration, and toxicity has been established in earlier phase studies. Instead, it should be viewed as a novel procedural intervention which must be robustly tested, refined and practiced before definitive conclusions on the potential benefits or detriments can be determined. The future of MR-guided RT for PAC is highly promising and the potential implications on PAC are substantial.

Review of MR-Guided Radiotherapy for Esophageal Cancer.

In this review, we outline the potential benefits and the future role of MRI and MR-guided radiotherapy (MRgRT) in the management of esophageal cancer. Although not currently used in most clinical practice settings, MRI is a useful non-invasive imaging modality that provides excellent soft tissue contrast and the ability to visualize cancer physiology. Chemoradiation therapy with or without surgery is essential for the management of locally advanced esophageal cancer. MRI can help stage esophageal cancer, delineate the gross tumor volume (GTV), and assess the response to chemoradiotherapy. Integrated MRgRT systems can help overcome the challenge of esophageal motion due to respiratory motion by using real-time imaging and tumor tracking with respiratory gating. With daily on-table MRI, shifts in tumor position and tumor regression can be taken into account for online-adaptation. The combination of accurate GTV visualization, respiratory gating, and online adaptive planning, allows for tighter treatment volumes and improved sparing of the surrounding normal organs. This could lead to a reduction in radiotherapy induced cardiac toxicity, pneumonitis and post-operative complications. Tumor physiology as seen on diffusion weighted imaging or dynamic contrast enhancement can help individualize treatments based on the response to chemoradiotherapy. Patients with a complete response on MRI can be considered for organ preservation while patients with no response can be offered an earlier resection. In patients with a partial response to chemoradiotherapy, areas of residual cancer can be targeted for dose escalation. The tighter and more accurate targeting enabled with MRgRT may enable hypofractionated treatment schedules.