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Background and Purpose: This study assessed the treatment time of online adaptive (i.e. Adapt-to-Shape, ATS) and virtual couch shift (i.e. Adapt-to-Position, ATP) magnetic resonance guided radiotherapy (MRgRT) on a 1.5 Tesla MR-Linac. Additionally, the transition from a radiation oncologists (RO)-led to a radiation therapist (RTT)-led workflow, and the presence of a learning curve were assessed., Materials and Methods: This study was conducted utilizing the prospective Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-Linac study (MOMENTUM, NCT04075305). Mean (±standard deviation) online adaptation time and total treatment time were collected from MR-Linac log files. Learning and proficiency phases were defined using a cumulative sum (CUSUM) analysis. Independent T-tests were performed. A p-value < 0.01 was considered statistically significant., Results: In total, 4942 fractions of 645 patients were included. Mean total treatment time was 39 (±7), 15 (±2), 34 (±8), 41 (±11), and 40 (±7) minutes for ATS-treated prostate cancer, ATP-treated prostate cancer, ATS-treated pelvic lymph node metstasis (LNM), ATS-treated abdominal LNM and ATS-treated rectal cancer, respectively. Mean online adaptation time of RO-led and RTT-led treatment was 28 (±6) and 25 (±6) minutes (p < 0.001) for ATS-treated prostate cancer. No significant differences in the remaining subgroups were found. In subgroups with a learning curve, mean online adaptation time of learning and proficiency phase were 30 (±6) and 26 (±5) minutes (p < 0.001) for ATS-treated prostate cancer, 27 (±8) and 19 (±7) minutes for pelvic LNM (p < 0.001), and 29 (±7) and 25 (±7) minutes (p < 0.001) for rectal cancer, respectively., Conclusion: The transition from RO-led to RTT-led workflows did not significantly increase total treatment time. The online adaptation time reduced after a learning curve for ATS-treated prostate cancer, pelvic LNM and rectal cancer. Keywords ; MRgRT, MR-Linac, time, prostate cancer, oligolymphnode metastasis, rectal cancer., (© 2024 The Authors.)

Introduction: Adjuvant chemotherapy improves survival in patients with resected pancreatic ductal adenocarcinoma (PDAC). The decision to initiate chemotherapy involves both patient and physician factors, decision-specific criteria, and contextual considerations. This study aimed to assess medical oncologists' views on adjuvant chemotherapy following pancreatic resection for PDAC., Methods: An online survey and case vignette study were distributed to medical oncologists via the Dutch Pancreatic Cancer Group (DPCG), International Hepato-Pancreato-Biliary Association (IHPBA) and related networks., Results: A total of 91 oncologists from 14 countries participated, 46 % of whom treated more than 40 new PDAC patients annually, with a median experience of 15 years. Significant discrepancies were noted in their recommendations for adjuvant chemotherapy across case vignettes. In patients over 70, 17 % advised against chemotherapy, while 31 % said age was not a factor. Oncologists with less than 10 years of experience and those in non-academic settings were less likely to recommend adjuvant therapy. While 87 % agreed mFOLFIRINOX is the preferred adjuvant treatment, consensus on individual cases was lacking. The recommended interval between surgery and chemotherapy ranged from 3 to 26 weeks, with varying reasons for withholding treatment, primarily due to postoperative recovery and performance status., Conclusions: Our study revealed substantial variation among oncologists in counseling on adjuvant chemotherapy after PDAC resection. This emphasizes the need for more patient involvement in decision-making and improving shared decision-making., Competing Interests: Conflict of interest JdV has served as a consultant for Amgen, AstraZeneca, MSD, Pierre Fabre, and Servier, and has received institutional research funding from Servier. All outside the submitted work. The other authors have no conflicts., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective : The estimand framework offers a structured approach to define the treatment effect to be estimated in a clinical study. Defining the estimand upfront helps formulating the research question and informs study design, data collection and statistical analysis methods. Since the Trials within Cohorts (TwiCs) design has unique characteristics, the objective of this study is to describe considerations and provide guidance for formulating estimands for TwiCs studies. Methods : The key attributes of an estimand are the target population, treatments that are compared, the endpoint, intercurrent events and their handling, and the population-level summary measure. The estimand framework was applied retrospectively to two TwiCs studies: the SPONGE and UMBRELLA Fit trial. The aim is to demonstrate how the estimand framework can be implemented in TwiCs studies, thereby focusing on considerations relevant for defining the estimand. Three estimands were defined for both studies. For the SPONGE trial, estimators were derived. Results : Intercurrent events considered to occur exclusively or more frequently in TwiCs studies compared to conventional randomized trials included intervention refusal after randomization, misalignment of timing of routine cohort measurements and the intervention period, and participants in the control arm initiating treatments similar to the studied intervention. Considerations for handling refusal after randomization related to decisions on whether the target population should include all eligible participants or the subpopulation that would accept (or undergo) the intervention when offered. Considerations for handling treatment initiation in the control arm and misalignments of timing related to decisions on whether such events should be considered part of treatment policy or whether interest is in a hypothetical scenario where such events do not occur. Conclusion : The TwiCs study design has unique features that pose specific considerations when formulating an estimand. The examples in this study can provide guidance in the definition of estimands in future TwiCs studies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background and Purpose: This study assessed quality of life (QoL) and clinical outcomes in rectal cancer patients treated with magnetic resonance (MR) guided short-course radiation therapy (SCRT) on a 1.5 Tesla (T) MR-Linac during the first 12 months after treatment., Materials and Methods: Rectal cancer patients treated with 25 Gy SCRT in five fractions with curative intent in the Netherlands (2019-2022) were identified in MOMENTUM (NCT04075305). Toxicity (CTCAE v5) and QoL (EORTC QLQ-C30 and -CR29) was primarily analyzed in patients without metastatic disease (M0) and no other therapies after SCRT. Patients who underwent tumor resection were censored from surgery. A generalized linear mixed-model was used to investigate clinically meaningful (≥10) and significant (P < 0.05) QoL changes. Clinical and pathological complete response (cCR and pCR) rates were calculated in patients in whom response was documented., Results: A total of 172 patients were included, of whom 112 patients were primarily analyzed. Acute and late radiation-induced high-grade toxicity were reported in one patient, respectively. CCR was observed in 8/64 patients (13 %), 14/37 patients (38 %) and 13/16 patients (91 %) at three, six and twelve months; pCR was observed in 3/69 (4 %) patients. After 12 months, diarrhea (mean difference [MD] -17.4 [95 % confidence interval [CI] -31.2 to -3.7]), blood and mucus in stool (MD -31.1 [95 % CI -46.4 to -15.8]), and anxiety (MD -22.4 [95 % CI -34.0 to -10.9]) were improved., Conclusion: High-field MR-guided SCRT for the treatment of patients with rectal cancer is associated with improved disease-related symptom management and functioning one year after treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background and Purpose: Online adaptive MR-guided radiotherapy (MRgRT) is a relatively new form of radiotherapy treatment, delivered using a MR-Linac. It is unknown what patients expect from this treatment and whether these expectations are met. This study evaluates whether patients' pre-treatment expectations of MRgRT are met and reports patients' on-table experience on a 1.5 T MR-Linac., Materials and Methods: All patients treated on the MR-Linac from November 2020 until April 2021, were eligible for inclusion. Patient expectation and experience were captured through questionnaires before, during, and three months after treatment. The on-table experience questionnaire included patient' physical and psychological coping. Patient-expected side effects, participation in daily and social activity, disease outcome and, disease related symptoms were compared to post-treatment experience., Results: We included 113 patients who were primarily male (n = 100, 89 %), with a median age of 69 years (range 52-90). For on-table experience, ninety percent of patients (strongly) agreed to feeling calm during their treatment. Six and eight percent of patients found the treatment position or bed uncomfortable respectively. Twenty-eight percent of patients felt tingling sensations during treatment. After treatment, 79 % of patients' expectations were met. Most patients experienced an (better than) expected level of side effects (75 %), participation in daily- (83 %) and social activity (86 %) and symptoms (78 %). However, 33 % expected more treatment efficacy than experienced., Conclusion: Treatment on the 1.5 T MR-Linac is well tolerated and meets patient expectations. Despite the fact that some patients expected greater treatment efficacy and the frequent occurrence of tingling sensations during treatment, most patient experiences were comparable or better than previously expected., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background/objectives: Pancreatic exocrine insufficiency (PEI) is a common complication following pancreatoduodenectomy (PD) leading to malnutrition. The course of PEI and related symptoms and vitamin deficiencies is unknown. This study aimed to assess the (long-term) incidence of PEI and vitamin deficiencies after PD., Methods: A bi-centre prospective observational cohort study was performed, including patients who underwent PD for mainly pancreatic and periampullary (pre)malignancies (2014-2018). Two cohorts were formed to evaluate short and long-term results. Patients were followed for 18 months and clinical symptoms were evaluated by questionnaire. PEI was based on faecal elastase-1 (FE-1) levels and/or clinical symptoms., Results: In total, 95 patients were included. After three months, all but three patients had developed PEI and 27/29 (93%) patients of whom stool samples were available showed abnormal FE-1 levels, which did not improve during follow-up. After six months, all patients had developed PEI. During follow-up, symptoms resolved in 35%-70% of patients. Vitamin D and K deficiencies were observed in 48%-79% of patients, depending on the moment of follow-up; 0%-50% of the patients with deficiencies received vitamin supplementation., Discussion: This prospective study found a high incidence of PEI after PD with persisting symptoms in one-to two thirds of all patients. Limited attention was paid to vitamin deficiencies. Improved screening and treatment strategies for PEI and vitamins need to be designed., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: First, this study aimed to assess the prognostic value of different definitions for resection margin status on disease-free survival (DFS) and overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC). Second, preoperative predictors of direct margin involvement were identified., Materials and Methods: This nationwide observational cohort study included all patients who underwent upfront PDAC resection (2014-2016), as registered in the prospective Dutch Pancreatic Cancer Audit. Patients were subdivided into three groups: R0 (≥1 mm margin clearance), R1 (<1 mm margin clearance) or R1 (direct margin involvement). Survival was compared using multivariable Cox regression analysis. Logistic regression with baseline variables was performed to identify preoperative predictors of R1 (direct)., Results: 595 patients with a median OS of 18 months (IQR 10-32 months) months were analysed. R0 (≥1 mm) was achieved in 277 patients (47%), R1 (<1 mm) in 146 patients (24%) and R1 (direct) in 172 patients (29%). R1 (direct) was associated with a worse OS, as compared with both R0 (≥1 mm) (hazard ratio (HR) 1.35 [95% and confidence interval (CI) 1.08-1.70); P < 0.01) and R1 (<1 mm) (HR 1.29 [95%CI 1.01-1.67]; P < 0.05). No OS difference was found between R0 (≥1 mm) and R1 (<1 mm) (HR 1.05 [95% CI 0.82-1.34]; P = 0.71). Preoperative predictors associated with an increased risk of R1 (direct) included age, male sex, performance score 2-4, and venous or arterial tumour involvement., Conclusion: Resection margin clearance of <1 mm, but without direct margin involvement, does not affect survival, as compared with a margin clearance of ≥1 mm. Given that any vascular tumour involvement on preoperative imaging was associated with an increased risk of R1 (direct) resection with upfront surgery, neoadjuvant therapy might be considered in these patients., Competing Interests: Declaration of competing interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2020. Published by Elsevier Ltd.)

Background: The aim of this study is to collect the best available evidence for diagnostic modalities, frequency, and duration of surveillance after resection for pancreatic ductal adenocarcinoma (PDAC)., Methods: PDAC guidelines published after 2015 were collected. Furthermore, a systematic search of the literature on postoperative surveillance was performed in PubMed and Embase from 2000 to 2019. Articles comparing different diagnostic modalities and frequencies of postoperative surveillance in PDAC patients with regard to survival, quality of life, morbidity and cost-effectiveness were selected., Results: The literature search resulted in 570 articles. A total of seven guidelines and twelve original clinical studies were eventually evaluated. PDAC guidelines increasingly recommend a combination of tumor marker testing and computed tomography (CT) imaging every three to six months during the first two years after resection. These guidelines are, however, based on expert opinion and other low-level evidence. Prospective studies comparing different surveillance strategies are lacking. According to recent studies, surveillance with tumor markers and imaging at regular intervals results in the detection of PDAC recurrence before the onset of symptoms and more frequent administration of further therapy, such as chemotherapy or radiotherapy., Conclusion: Current evidence for recurrence-focused surveillance after PDAC resection is limited and contradictory. Consequently, recommendations on surveillance are conflicting. To define the clinical merit of recurrence-focused surveillance, patients who are most likely to benefit from early detection and treatment of PDAC recurrence need to be identified. To this purpose, well-designed prospective studies are needed, accounting for both economical and psychosocial implications of surveillance., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)