To enable magnetic resonance (MR)-only radiotherapy and facilitate modelling of radiation attenuation in humans, synthetic CT (sCT) images need to be generated. Considering the application of ...MR-guided radiotherapy and online adaptive replanning, sCT generation should occur within minutes. This work aims at assessing whether an existing deep learning network can rapidly generate sCT images for accurate MR-based dose calculations in the entire pelvis. A study was conducted on data of 91 patients with prostate (59), rectal (18) and cervical (14) cancer who underwent external beam radiotherapy acquiring both CT and MRI for patients' simulation. Dixon reconstructed water, fat and in-phase images obtained from a conventional dual gradient-recalled echo sequence were used to generate sCT images. A conditional generative adversarial network (cGAN) was trained in a paired fashion on 2D transverse slices of 32 prostate cancer patients. The trained network was tested on the remaining patients to generate sCT images. For 30 patients in the test set, dose recalculations of the clinical plan were performed on sCT images. Dose distributions were evaluated comparing voxel-based dose differences, gamma and dose-volume histogram (DVH) analysis. The sCT generation required 5.6 s and 21 s for a single patient volume on a GPU and CPU, respectively. On average, sCT images resulted in a higher dose to the target of maximum 0.3%. The average gamma pass rates using the 3%, 3 mm and 2%, 2 mm criteria were above 97 and 91%, respectively, for all volumes of interests considered. All DVH points calculated on sCT differed less than ±2.5% from the corresponding points on CT. Results suggest that accurate MR-based dose calculation using sCT images generated with a cGAN trained on prostate cancer patients is feasible for the entire pelvis. The sCT generation was sufficiently fast for integration in an MR-guided radiotherapy workflow.
•The Elekta Unity MR-linac adaptive radiotherapy concept is explained.•The adapt to shape and adapt to position workflows are compared.•Different methods for dose re-calculation and optimization are ...discussed.•Full online re-planning is the most robust adaptive planning method for the Unity.•Faster methods are available, but should be dosimetrically explored per use case.
The promise of the MR-linac is that one can visualize all anatomical changes during the course of radiotherapy and hence adapt the treatment plan in order to always have the optimal treatment. Yet, there is a trade-off to be made between the time spent for adapting the treatment plan against the dosimetric gain. In this work, the various daily plan adaptation methods will be presented and applied on a variety of tumour sites. The aim is to provide an insight in the behavior of the state-of-the-art 1.5 T MRI guided on-line adaptive radiotherapy methods.
To explore the different available plan adaptation workflows and methods, we have simulated online plan adaptation for five cases with varying levels of inter-fraction motion, regions of interest and target sizes: prostate, rectum, esophagus and lymph node oligometastases (single and multiple target). The plans were evaluated based on the clinical dose constraints and the optimization time was measured.
The time needed for plan adaptation ranged between 17 and 485 s. More advanced plan adaptation methods generally resulted in more plans that met the clinical dose criteria. Violations were often caused by insufficient PTV coverage or, for the multiple lymph node case, a too high dose to OAR in the vicinity of the PTV. With full online replanning it was possible to create plans that met all clinical dose constraints for all cases.
Daily full online replanning is the most robust adaptive planning method for Unity. It is feasible for specific sites in clinically acceptable times. Faster methods are available, but before applying these, the specific use cases should be explored dosimetrically.
Rectal cancer treatment is associated with substantial short- and longer-term morbidity that may affect patients' ability to work.
We evaluated patient-reported work ability during the first 2 years ...after rectal cancer diagnosis, relative to the Dutch general population. Also, we assessed the association between clinical factors and work ability.
This is a prospective cohort study.
This study was conducted at the Radiation-Oncology Department of a tertiary center.
Patients with rectal cancer, <67 years of age, and treated with curative intent were selected.
Work ability was assessed with the Work Ability Index before the start of treatment (baseline) and at 3, 6, 12, 18, and 24 months after. The Work Ability Index scores of patients with paid employment were compared with the scores of matched population controls. Mixed models were used to estimate the impact of clinical factors on work ability.
Of the 230 eligible patients, 172 (75%) had paid employment. Work ability decreased at 3 and 6 months compared with baseline. At 12 months, work ability recovered to baseline level but remained significantly lower than in population controls up to 24 months. Fifty-four percent reported 100 to 365 days of sick leave during the first 12 months of treatment versus 2% in the general population. At 24 months, 32% needed substantial adaptations in work activities, worked reduced hours, or were unable to work due to the disease versus 6% in the general population. Female sex, multiple comorbidities, oligometastatic disease, chemoradiation, and abdominoperineal resection were associated with lower work ability.
The study was limited by a decrease in questionnaire response rate from 83% to 64% over time.
Patient-reported work ability deteriorates during rectal cancer treatment. Within 24 months after diagnosis, work ability returns to pretreatment level but remains lower than that of the general population. See Video Abstract at http://links.lww.com/DCR/B175. CAPACIDAD DE TRABAJO REPORTADO POR PACIENTES DURANTE LOS PRIMEROS DOS AÑOS DESPUÉS DEL DIAGNÓSTICO DE CÁNCER RECTAL: El tratamiento del cáncer rectal se asocia con una morbilidad significante a corto y largo plazo que puede afectar la capacidad de trabajo de pacientes.Evaluamos la capacidad de trabajo reportado por pacientes durante los primeros dos años después del diagnóstico de cáncer rectal, en relación con la población general holandesa. Además, evaluamos la asociación entre los factores clínicos y capacidad para trabajar.Estudio de cohorte prospectivo.Este estudio se realizó en el Departamento de Radiación Oncológica de en un centro de referencia de tercer nivel.Se seleccionaron pacientes con cáncer rectal, <67 años de edad, y tratados con intención curativa.La capacidad de trabajo se evaluó con el índice de capacidad de trabajo antes del inicio del tratamiento (línea de base) y a los 3, 6, 12, 18 y 24 meses después. Los puntajes de capacidad laboral de los pacientes con empleo remunerado se compararon con los puntajes de los controles de población pareados. Se utilizaron modelos mixtos para estimar el impacto de los factores clínicos en la capacidad laboral.De los 230 pacientes elegibles, 172 (75%) tenían empleo remunerado. La capacidad de trabajo disminuyó a los 3 y 6 meses en comparación con la línea de base. A los 12 meses, la capacidad de trabajo se recuperó al nivel de referencia, pero se mantuvo significativamente más baja que en los controles de la población hasta 24 meses. Durante los primeros 12 meses, el 54% reportó 100-365 días de baja por enfermedad versus el 2% en la población general. A los 24 meses, el 32% necesitaba adaptaciones sustanciales en las actividades laborales, trabajó horas reducidas o no pudo trabajar debido a la enfermedad frente al 6% en la población general. El sexo femenino, las comorbilidades múltiples, la enfermedad oligometastásica, la quimiorradiación y la resección abdominoperineal se asociaron con una menor capacidad de trabajo.El estudio estuvo limitado por una disminución en la tasa de respuesta al cuestionario del 83% al 64% a lo largo plazo.La capacidad laboral informada por el paciente se deteriora durante el tratamiento del cáncer rectal. Dentro de los 24 meses posteriores al diagnóstico, la capacidad laboral vuelve al nivel de pretratamiento, pero sigue siendo inferior a la de la población general. Consulte Video Resumen en http://links.lww.com/DCR/B175. (Traducción-Dr. Adrian Ortega).
To enable magnetic resonance imaging (MRI)-guided radiotherapy with real-time adaptation, motion must be quickly estimated with low latency. The motion estimate is used to adapt the radiation beam to ...the current anatomy, yielding a more conformal dose distribution. As the MR acquisition is the largest component of latency, deep learning (DL) may reduce the total latency by enabling much higher undersampling factors compared to conventional reconstruction and motion estimation methods. The benefit of DL on image reconstruction and motion estimation was investigated for obtaining accurate deformation vector fields (DVFs) with high temporal resolution and minimal latency. 2D cine MRI acquired at 1.5 T from 135 abdominal cancer patients were retrospectively included in this study. Undersampled radial golden angle acquisitions were retrospectively simulated. DVFs were computed using different combinations of conventional- and DL-based methods for image reconstruction and motion estimation, allowing a comparison of four approaches to achieve real-time motion estimation. The four approaches were evaluated based on the end-point-error and root-mean-square error compared to a ground-truth optical flow estimate on fully-sampled images, the structural similarity (SSIM) after registration and time necessary to acquire k-space, reconstruct an image and estimate motion. The lowest DVF error and highest SSIM were obtained using conventional methods up to R≤10. For undersampling factors R>10, the lowest DVF error and highest SSIM were obtained using conventional image reconstruction and DL-based motion estimation. We have found that, with this combination, accurate DVFs can be obtained up to R=25 with an average root-mean-square error up to 1 millimeter and an SSIM greater than 0.8 after registration, taking 60 milliseconds. High-quality 2D DVFs from highly undersampled k-space can be obtained with a high temporal resolution with conventional image reconstruction and a deep learning-based motion estimation approach for real-time adaptive MRI-guided radiotherapy.
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.
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.
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.
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.
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.
International guidelines disagree on the value of standardized postoperative surveillance for early detection and treatment of PDAC recurrence.
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.
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.
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.
•Delivered dose reconstruction with fast 3D cine MRI for MR-guided pancreas SBRT.•Intrafraction motion only modestly impacted the delivered dose.•Decreased tumor coverage was mostly attributable to ...significant baseline shifts.•These drifts could be accurately captured by the 3D cine MRI.•Simple baseline shifts could mitigate the dosimetric impact of these drifts.
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.
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.
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.
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.
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.
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.
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.
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.
Abstract
Background
Previous randomized trials found that a prolonged interval between short-course radiotherapy (SCRT, 25 Gy in 5 fractions) and surgery for rectal cancer (4–8 weeks, SCRT-delay) ...results in a lower postoperative complication rate and a higher pCR rate than SCRT and surgery within a week (SCRT-direct surgery). This study sought to confirm these results in a Dutch national database.
Methods
Patients with intermediate-risk rectal cancer (T3(mesorectal fascia (MRF)–) N0 M0 and T1–3(MRF–) N1 M0) treated with either SCRT-delay (4–12 weeks) or SCRT-direct surgery in 2018–2021 were selected from a Dutch national colorectal cancer database. Confounders were adjusted for using inverse probability of treatment weighting (IPTW). The primary endpoint was the 90-day postoperative complication rate. Secondary endpoints included the pCR rate. Endpoints were compared using log-binomial and Poisson regression.
Results
Some 664 patients were included in the SCRT-direct surgery and 238 in the SCRT-delay group. After IPTW, the 90-day postoperative complication rate was comparable after SCRT-direct surgery and SCRT-delay (40.1 versus 42.3 per cent; risk ratio (RR) 1.1, 95 per cent c.i. 0.9 to 1.3). A pCR occurred more often after SCRT-delay than SCRT-direct surgery (10.7 versus 0.4 per cent; RR 39, 11 to 139).
Conclusion
There was no difference in surgical complication rates between SCRT-delay and SCRT-direct, but SCRT-delay was associated with more patients having a pCR.
Recent randomized trials have shown that a prolonged interval between short-course radiotherapy (SCRT, 25 Gy in 5 fractions) and surgery for rectal cancer (4–8 weeks, SCRT-delay) results in a lower postoperative complication rate and a higher pCR rate than SCRT and surgery within a week (SCRT-direct surgery). This study compared the 90-day postoperative complication rate and pCR rate between SCRT-delay and SCRT-direct surgery using Dutch nationwide real-world data. An advantage in terms of postoperative complications could not be confirmed after SCRT-delay compared with SCRT-direct surgery, but the increased pCR rate after SCRT-delay was confirmed.
To evaluate patients’ experience of having served as controls without a notification at the time of randomization in the context of the trial within cohorts (TwiCs) design.
Patients were asked for ...their opinion on having served as controls in TwiCs, before and after having been provided the trial results. Patients had provided broad consent to randomization at cohort entry and had served as controls in one of two TwiCs (an exercise program after breast cancer treatment or radiotherapy dose-escalation for rectal cancer).
Two to 6 years after cohort entry, 15% (n = 16) of all patients remembered having provided broad consent to randomization. Before disclosure of trial results, 47% (n = 52) of patients thought positively, 45% (n = 50) neutrally, and 2% (n = 2) negatively of having served as controls in one of the two trials. Seventeen percent (n = 18) of patients were positive, 65% (n = 71) neutral, and 11% (n = 12) negative about not having been notified when serving as controls. The survey results were comparable after disclosure of trial results.
These results support the use of the TwiCs design with the staged-informed consent procedure. Keeping patients engaged and aware of the consents provided might further improve patients’ experience of serving as controls in TwiCs.
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