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Background: In patients diagnosed with rectal cancer, dose escalation is currently being investigated in a large number of studies. Since there is little known on gross tumor volume (GTV) inter-fraction motion for rectal cancer, a wide variety in margins is used. Purpose of this study is to quantify GTV inter-fraction motion statistics on different timescales and to give estimates of planning target volume (PTV) margins. Material and methods: Thirty-two patients, diagnosed with rectal cancer, were included. To investigate motion from week-to-week, 16 patients underwent a pretreatment and five weekly MRIs, prior to a radiotherapy (RT) fraction of the chemoradiotherapy treatment. To investigate motion from day-to-day, the remaining 16 patients underwent five daily MRIs before each fraction in one week of RT. GTV was delineated on all scans according to guidelines. Scans were aligned on bony anatomy with the first MRI. For both datasets separately, GTV inter-fraction motion was determined based on center-of-gravity displacement. Therefrom, systematic and random errors were determined in left/right (LR), anterior/posterior and cranial/caudal (CC) direction. PTV margin estimates were calculated and evaluated on GTV coverage. Results: Systematic and random errors were found in the range of 2.3-4.8 mm and 1.5-3.3 mm from week-to-week, and 1.8-4.5 mm and 1.8-4.0 mm from day-to-day, respectively. On both timescales, similar motion patterns were found; the most motion was observed in CC whilst the least motion was observed in LR. On the week-to-week data more systematic and less random motion was observed compared to the day-to-day data. Overall, only slight differences in margin estimates were found. Derived PTV margin estimates were found to give adequate GTV coverage. Conclusion: GTV inter-fraction motion, on a week-to-week and day-to-day timescale, can be accounted for using motion statistics presented in this study. [ABSTRACT FROM AUTHOR]

Background and Objective: The Trials within Cohorts design aims to reduce recruitment difficulties and disappointment bias in pragmatic trials. On cohort enrollment, broad informed consent for randomization is asked, after which cohort participants can be randomized to interventions or serve as controls without further notification. We evaluated patients' recollection, understanding, and acceptance of broad consent in a clinical oncology setting., Methods: We surveyed 610 patients with cancer participating in ongoing TwiCs; 482 patients (79%) responded, of which 312 patients shortly after cohort enrollment, 108 patients after randomization to an intervention (12-18 months after cohort enrollment), and a random sample of 62 cohort participants who had not been selected for interventions (1-6 months after cohort enrollment)., Results: Shortly after providing cohort consent, 76% of patients (238/312) adequately remembered whether they had given broad consent for randomization. Of patients randomly offered interventions, 76% (82/108) remembered giving broad consent for randomization; 41% (44/108) understood they were randomly selected, 44% (48/108) were not interested in selection procedures, and 10% (11/108) did not understand selection was random. Among patients not selected for interventions, 42% (26/62) understood selection was random; 89% felt neutral regarding the scenario of "not being selected for an intervention while your data were being used in comparison with patients receiving interventions," 10% felt reassured (6/62) and 2% scared/insecure (2/62)., Conclusion: Patients adequately remember giving broad consent for randomization shortly after cohort enrollment and after being offered an intervention, but recollection is lower in those never selected for interventions. Patients are acceptant of serving as control without further notifications., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Pathologic complete tumor response after chemoradiation in patients with locally advanced rectal cancer (LARC) is associated with a favorable prognosis and allows organ-sparing treatment strategies. In the RECTAL-BOOST trial, we aimed to investigate the effect of an external radiation boost to the tumor before chemoradiation on pathologic or sustained clinical complete tumor response in LARC., Methods and Materials: This multicenter, nonblinded, phase 2 randomized controlled trial followed the trials-within-cohorts design, which is a pragmatic trial design allowing cohort participants to be randomized for an experimental intervention. Patients in the intervention group are offered the intervention (and can either accept or refuse this), whereas patients in the control group are not notified about the randomization. Participants of a colorectal cancer cohort referred for chemoradiation of LARC to either of 2 radiation therapy centers were eligible. Patients were randomized to no boost or an external radiation boost (5 × 3 Gy) without concurrent chemotherapy, directly followed by standard pelvic chemoradiation (25 × 2 Gy with concurrent capecitabine). The primary outcome was pathologic complete response (ie, ypT0N0) in patients with planned surgery at 12 weeks, or, as surrogate for pathologic complete response, a 2-year sustained clinical complete response for patients treated with an organ preservation strategy. Analyses were intention to treat. The study was registered with ClinicalTrials.gov, number NCT01951521., Results: Between September 2014 and July 2018, 128 patients were randomized. Fifty-one of the 64 (79.7%) patients in the intervention group accepted and received a boost. Compared with the control group, fewer patients in the intervention group had a cT4 stage and a low rectal tumor (31.3% vs 17.2% and 56.3% vs 45.3%, respectively), and more patients had a cN2 stage (59.4% vs 70.3%, respectively). Rate of pathologic or sustained clinical complete tumor response was similar between the groups: 23 of 64 (35.9%; 95% confidence interval [CI], 24.3-48.9) in the intervention group versus 24 of 64 (37.5%; 95% CI, 25.7-50.5) in the control group (odds ratio [OR] = 0.94; 95% CI, 0.46-1.92). Near-complete or complete tumor regression was more common in the intervention group (34 of 49; 69.4%) than in the control group (24 of 53; 45.3%; (OR = 2.74, 95% CI 1.21-6.18). Grade ≥3 acute toxicity was comparable: 6 of 64 (9.4%) in the intervention group versus 5 of 64 (7.8%) in the control group (OR = 1.22; 95% CI, 0.35-4.22)., Conclusions: Dose escalation with an external radiation therapy boost to the tumor before neoadjuvant chemoradiation did not increase the pathologic or sustained clinical complete tumor response rate in LARC., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The trials within cohorts (TwiCs) design aims to improve recruitment efficiency. We conducted the first TwiCs in radiation oncology and described efficiency of the design and generalizability of the results., Study Design and Setting: In two radiotherapy centers, patients with rectal cancer were asked to participate in a prospective cohort study and to provide broad consent for randomization and patient-reported outcomes (PROs). Consenting patients who met the trial criteria were randomized directly after cohort enrollment. The intervention arm was offered a radiotherapy boost. We evaluated acceptance rate, its impact on sample size, and compared clinical characteristics between trial participants and patients of the Dutch national cancer registry., Results: 128 of the 200 eligible patients (64%) were randomized. Sixty-two patients did not consent (in time) to cohort participation, to broad randomization, or to PROs. Of the 64 patients in the intervention arm, 52 (81%) accepted the intervention. During the trial, the acceptance rate dropped temporarily, after which sample size was adapted. Trial patients were comparable in age, comorbidity, and disease stage to the national rectal cancer population., Conclusions: The TwiCs design is feasible, allows enrollment of a high proportion of randomizable patients, with positive impact on trial efficiency and generalizability of results in a clinical oncology setting., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: As result of the aging population and increasing rectal cancer incidence, more older patients undergo treatment for rectal cancer. This study compares treatment course, postoperative complications, and quality of life (QOL) between older and younger patients with rectal cancer and evaluates the impact of postoperative complications on QOL in the elderly., Materials and Methods: Patients with rectal cancer participating in a prospective colorectal cancer cohort and referred for radiotherapy between 2013 and 2016 were included. QOL was assessed with the cancer questionnaire of the European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30) before treatment and at three, six, and twelve months. Outcomes were compared between older patients (≥70years) and younger patients (<70years) and stratified by presence of postoperative complications., Results: In total, 115 (33%) older patients and 230 (67%) younger patients were included. Compared to younger patients, older patients underwent significantly more often short-course radiation with delayed surgery (6.1% and 19.1% respectively) and less often chemoradiation (62.6% and 39.1% respectively), and were more likely to undergo a Hartmann procedure with permanent stoma (3.5% and 13.0% respectively) instead of sphincter-sparing surgery (43.9% and 29.6% respectively). Postoperative complication rates were similar (38.5% in older patients versus 34.7% in younger patients). Older patients had worse physical functioning at six and twelve months after diagnosis compared to younger patients. Presence of postoperative complications had a significant stronger impact on physical- and role functioning in older patients., Conclusion: Older patients undergo more often a tailored treatment approach for rectal cancer than younger patients. With this tailored approach, similar postoperative complication rates and QOL are achieved. However, postoperative complications have a larger negative impact on physical- and role functioning in older patients which indicates a need for better prediction of postoperative complications in the elderly., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Reduction of motion uncertainty by applying adaptive radiotherapy strategies depends largely on the temporal behavior of this motion. To fully optimize adaptive strategies, insight into target motion is needed. The purpose of this study was to analyze stability and evolution in time of motion uncertainty of both the gross tumor volume (GTV) and clinical target volume (CTV) for patients with rectal cancer. We scanned 16 patients daily during one week, on a 1.5 T MRI scanner in treatment position, prior to each radiotherapy fraction. Single slice sagittal cine MRIs were made at the beginning, middle, and end of each scan session, for one minute at 2 Hz temporal resolution. GTV and CTV motion were determined by registering a delineated reference frame to time-points later in time. The 95th percentile of observed motion (dist95%) was taken as a measure of motion. The stability of motion in time was evaluated within each cine-MRI separately. The evolution of motion was investigated between the reference frame and the cine-MRIs of a single scan session and between the reference frame and the cine-MRIs of several days later in the course of treatment. This observed motion was then converted into a PTV-margin estimate. Within a one minute cine-MRI scan, motion was found to be stable and small. Independent of the time-point within the scan session, the average dist95% remains below 3.6 mm and 2.3 mm for CTV and GTV, respectively 90% of the time. We found similar motion over time intervals from 18 min to 4 days. When reducing the time interval from 18 min to 1 min, a large reduction in motion uncertainty is observed. A reduction in motion uncertainty, and thus the PTV-margin estimate, of 71% and 75% for CTV and tumor was observed, respectively. Time intervals of 15 and 30 s yield no further reduction in motion uncertainty compared to a 1 min time interval.