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... Show moreIntroduction 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. Show less
Purpose: Current delineation of the gross tumor volume (GTV) in esophageal cancer relies on computed tomography (CT) and combination with F-18-fluorodeoxyglucose (FDG) positron emission tomography ... Show morePurpose: Current delineation of the gross tumor volume (GTV) in esophageal cancer relies on computed tomography (CT) and combination with F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET). There is increasing interest in integrating magnetic resonance imaging (MRI) in radiation treatment, which can potentially obviate CT- or FDG-PET/CT-based delineation. The aim of this study is to evaluate the feasibility of target delineation on T2-weighted (T2W) MRI and T2W including diffusion-weighted MRI (T2W + DW-MRI) compared with current-practice FDG-PET/CT.Methods: Ten observers delineated primary esophageal tumor GTVs of 6 patients on FDG-PET/ CT, T2W-MRI, and T2W DW-MRI. GTVs, generalized conformity indices, in-slice delineation variation (root mean square), and standard deviations in the position of the most cranial and caudal delineated slice were calculated.Results: Delineations on MRI showed smaller GTVs compared with FDG-PET/CT-based delineations. The main variation was seen at the cranial and caudal border. No differences were observed in conformity indices (FDG-PET/CT, 0.68; T2W-MRI, 0.66; T2W + DW-MRI, 0.68) and in-slice variation (root mean square, 0.13 cm on FDG-PET/CT; 0.10 cm on T2W-MRI; 0.14 cm on T2W + DW-MRI). In the 2 tumors involving the gastroesophageal junction, addition of DW-MRI to T2W-MRI significantly decreased caudal border variation.Conclusions: MRI-based target delineation of the esophageal tumor is feasible with interobserver variability comparable to that with FDG-PET/CT, despite limited experience with delineation on MRI. Most variation was seen at cranial-caudal borders, and addition of DW-MRI to T2W-MRI may reduce caudal delineation variation of gastroesophageal junction tumors. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. Show less
Background and purposeAccurate delineation of the primary tumour is vital to the success of radiotherapy and even more important for successful boost strategies, aiming for improved local control... Show moreBackground and purposeAccurate delineation of the primary tumour is vital to the success of radiotherapy and even more important for successful boost strategies, aiming for improved local control in oesophageal cancer patients. Therefore, the aim was to assess delineation variability of the gross tumour volume (GTV) between CT and combined PET-CT in oesophageal cancer patients in a multi-institutional study.Materials and methodsTwenty observers from 14 institutes delineated the primary tumour of 6 cases on CT and PET-CT fusion. The delineated volumes, generalized conformity index (CIgen) and standard deviation (SD) in position of the most cranial/caudal slice over the observers were evaluated. For the central delineated region, perpendicular distance between median surface GTV and each individual GTV was evaluated as in-slice SD.ResultsAfter addition of PET, mean GTVs were significantly smaller in 3 cases and larger in 1 case. No difference in CIgen was observed (average 0.67 on CT, 0.69 on PET-CT). On CT cranial-caudal delineation variation ranged between 0.2 and 1.5 cm SD versus 0.2 and 1.3 cm SD on PET-CT. After addition of PET, the cranial and caudal variation was significantly reduced in 1 and 2 cases, respectively. The in-slice SD was on average 0.16 cm in both phases.ConclusionIn some cases considerable GTV delineation variability was observed at the cranial-caudal border. PET significantly influenced the delineated volume in four out of six cases, however its impact on observer variation was limited. Show less
An organized layer of connective tissue coursing from aorta to esophagus was recently discovered in the mediastinum. The relations with other peri-esophageal fascias have not been described and it... Show moreAn organized layer of connective tissue coursing from aorta to esophagus was recently discovered in the mediastinum. The relations with other peri-esophageal fascias have not been described and it is unclear whether this layer can be visualized by non-invasive imaging. This study aimed to provide a comprehensive description of the peri-esophageal fascias and determine whether the connective tissue layer between aorta and esophagus can be visualized by magnetic resonance imaging (MRI). First, T2-weighted MRI scanning of the thoracic region of a human cadaver was performed, followed by histological examination of transverse sections of the peri-esophageal tissue between the thyroid gland and the diaphragm. Secondly, pretreatment motion-triggered MRI scans were prospectively obtained from 34 patients with esophageal cancer and independently assessed by two radiologists for the presence and location of the connective tissue layer coursing from aorta to esophagus. A layer of connective tissue coursing from the anterior aspect of the descending aorta to the left lateral aspect of the esophagus, with a thin extension coursing to the right pleural reflection, was visualized exvivo in the cadaver on MR images, macroscopic tissue sections, and after histologic staining, as well as on invivo MR images. The layer connecting esophagus and aorta was named aorto-esophageal ligament' and the layer connecting aorta to the right pleural reflection aorto-pleural ligament'. These connective tissue layers divides the posterior mediastinum in an anterior compartment containing the esophagus, (carinal) lymph nodes and vagus nerve, and a posterior compartment, containing the azygos vein, thoracic duct and occasionally lymph nodes. The anterior compartment was named peri-esophageal compartment' and the posterior compartment para-aortic compartment'. The connective tissue layers superior to the aortic arch and at the diaphragm corresponded with the currently available anatomic descriptions. This study confirms the existence of the previously described connective tissue layer coursing from aorta to esophagus, challenging the long-standing paradigm that no such structure exists. A comprehensive, detailed description of the peri-esophageal fascias is provided and, furthermore, it is shown that the connective tissue layer coursing from aorta to esophagus can be visualized invivo by MRI. Show less
Purpose: To explore and evaluate the potential value of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for the prediction of pathologic response to neoadjuvant chemoradiotherapy ... Show morePurpose: To explore and evaluate the potential value of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for the prediction of pathologic response to neoadjuvant chemoradiotherapy (nCRT) in oesophageal cancer.Material and methods: Twenty-six patients underwent DCE-MRI before, during (week 2-3) and after nCRT, but before surgery (pre/per/post, respectively). Histopathologic tumour regression grade (TRG) was assessed after oesophagectomy. Tumour area-under-the-concentration time curve (AUC), time-to peak (TTP) and slope were calculated. The ability of these DCE-parameters to distinguish good responders (GR, TRG 1-2) from poor responders (noGR, TRG >= 3), and pathologic complete responders (pCR) from no-pCR was assessed.Results: Twelve patients (48%) showed GR of which 8 patients (32%) pCR. Analysis of AUC change throughout treatment, AUC(per-pre), was most predictive for GR, at a threshold of 22.7% resulting in a sensitivity of 92%, specificity of 77%, PPV of 79%, and a NPV of .91%. AUC(post-pre) was most predictive for pCR, at a threshold of -24.6% resulting in a sensitivity of 83%, specificity of 88%, PPV of 71%, and a NPV of 93%. TTP and slope were not associated with pathologic response.Conclusions: This study demonstrates that changes in AUC throughout treatment are promising for prediction of histopathologic response to nCRT for oesophageal cancer. (C) 2016 Elsevier Ireland Ltd. All rights reserved. Show less
Purpose: To explore the value of diffusion-weighted magnetic resonance imaging (DW-MRI) for the prediction of pathologic response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer... Show morePurpose: To explore the value of diffusion-weighted magnetic resonance imaging (DW-MRI) for the prediction of pathologic response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer.Material and methods: In 20 patients receiving nCRT for esophageal cancer DW-MRI scanning was performed before nCRT, after 8-13 fractions, and before surgery. The median tumor apparent diffusion coefficient (ADC) was determined at these three time points. The predictive potential of initial tumor ADC, and change in ADC (Delta ADC) during and after treatment for pathologic complete response (pathCR) and good response were assessed. Good response was defined as pathCR or near-pathCR (tumor regression grade [TRG] 1 or 2).Results: A pathCR after nCRT was found in 4 of 20 patients (20%), and 8 patients (40%) showed a good response to nCRT. The Delta ADC(during) was significantly higher in pathCR vs. non-pathCR patients (34.6% +/- 10.7% [mean +/- SD] vs. 14.0% +/- 13.1%, p = 0.016), as well as in good vs. poor responders (30.5% +/- 8.3% vs. 9.5% +/- 12.5%, p = 0.002). The Delta ADC(during) was predictive of residual cancer at a threshold of 29% (sensitivity of 100%, specificity of 75%, PPV of 94%, and NPV of 100%), and for poor pathologic response at a threshold of 21% (sensitivity of 82%, specificity of 100%, PPV of 100%, and NPV of 80%).Conclusions: In this exploratory study, the treatment-induced change in ADC during the first 2-3 weeks of nCRT for esophageal cancer seemed highly predictive of histopathologic response. Larger series are warranted to verify these results. (C) 2015 Elsevier Ireland Ltd. All rights reserved. Show less
Integrated 2-[F-18]-fluoro-2-deoxy-D-glucose (FOG) PET/CT and magnetic resonance imaging (MRI) with functional features of diffusion-weighted imaging (DWI) are advancing imaging technologies that... Show moreIntegrated 2-[F-18]-fluoro-2-deoxy-D-glucose (FOG) PET/CT and magnetic resonance imaging (MRI) with functional features of diffusion-weighted imaging (DWI) are advancing imaging technologies that have current and future potential to overcome important limitations of conventional staging methods in the management of patients with oesophageal cancer. PET/CT has emerged as an important part of the standard work-up of patients with oesophageal cancer. Besides its important ability to detect unsuspected metastatic disease, PET/CT may be useful in the assessment of treatment response, radiation treatment planning, and detection of recurrent disease. In addition, high-resolution T2-weighted MRI and DWI have potential complementary roles. Recent improvements in MRI protocols and techniques have resulted in better imaging quality with the potential to bring improvement in staging, radiation treatment planning, and the assessment of treatment response. Optimal use and understanding of PET/CT and MRI in oesophageal cancer will contribute to the impact of these advancing technologies in tailoring treatment to the individual patient and achieving best possible outcomes. In this article, we graphically outline the current and potential future roles of PET/CT and MRI in the multidisciplinary management of oesophageal cancer. (C) 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. Show less
Purpose: To quantify the movement of esophageal tumors noninvasively on cine-magnetic resonance imaging (MRI) by use of a semiautomatic method to visualize tumor movement directly throughout... Show morePurpose: To quantify the movement of esophageal tumors noninvasively on cine-magnetic resonance imaging (MRI) by use of a semiautomatic method to visualize tumor movement directly throughout multiple breathing cycles.Methods and Materials: Thirty-six patients with esophageal tumors underwent MRI. Tumors were located in the upper (8), middle (7), and lower (21) esophagus. Cine-MR images were collected in the coronal and sagittal plane during 60 seconds at a rate of 2 Hz. An adaptive correlation filter was used to automatically track a previously marked reference point. Tumor movement was measured in the craniocaudal (CC), left-right (LR), and anteroposterior (AP) directions and its relationship along the longitudinal axis of the esophagus was investigated.Results: Tumor registration within the individual images was typically done at a millisecond time scale. The mean (SD) peak-to-peak displacements in the CC, AP, and LR directions were 13.3 (5.2) mm, 4.9 (2.5) mm, and 2.7 (1.2) mm, respectively. The bandwidth to cover 95% of excursions from the mean position (c95) was also calculated to exclude outliers caused by sporadic movements. The mean (SD) c95 values were 10.1 (3.8) mm, 3.7 (1.9) mm, and 2.0 (0.9) mm in the CC, AP, and LR dimensions. The end-exhale phase provided a stable position in the respiratory cycle, compared with more variety in the end-inhale phase. Furthermore, lower tumors showed more movement than did higher tumors in the CC and AP directions.Conclusions: Intrafraction tumor movement was highly variable between patients. Tumor position proved the most stable during the respiratory cycle in the end-exhale phase. A better understanding of tumor motion makes it possible to individualize radiation delivery strategies accordingly. Cine-MRI is a successful noninvasive modality to analyze motion for this purpose in the future. (C) 2014 Elsevier Inc. Show less
To outline the current role and future potential of magnetic resonance imaging (MRI) in the management of oesophageal cancer regarding T-staging, N-staging, tumour delineation for radiotherapy (RT)... Show moreTo outline the current role and future potential of magnetic resonance imaging (MRI) in the management of oesophageal cancer regarding T-staging, N-staging, tumour delineation for radiotherapy (RT) and treatment response assessment.PubMed, Embase and the Cochrane library were searched identifying all articles related to the use of MRI in oesophageal cancer. Data regarding the value of MRI in the areas of interest were extracted in order to calculate sensitivity, specificity, predictive values and accuracy for group-related outcome measures.Although historically poor, recent improvements in MRI protocols and techniques have resulted in better imaging quality and the valuable addition of functional information. In recent studies, similar or even better results have been achieved using optimised MRI compared with other imaging strategies for T- and N-staging. No studies clearly report on the role of MRI in oesophageal tumour delineation and real-time guidance for RT so far. Recent pilot studies showed that functional MRI might be capable of predicting pathological response to treatment and patient prognosis.In the near future MRI has the potential to bring improvement in staging, tumour delineation and real-time guidance for RT and assessment of treatment response, thereby complementing the limitations of currently used imaging strategies.aEuro cent MRI's role in oesophageal cancer has been somewhat limited to date.aEuro cent However MRI's ability to depict oesophageal cancer is continuously improving.aEuro cent Optimising TN-staging, radiotherapy planning and response assessment ultimately improves individualised cancer care.aEuro cent MRI potentially complements the limitations of other imaging strategies regarding these points. Show less
Neumann, H.; Neurath, M.F.; Vieth, M.; Lever, F.M.; Meijer, G.J.; Lips, I.M.; ... ; Umar, A. 2013
This paper reporting on techniques for esophageal evaluation and imaging and drugs for esophageal disease includes commentaries on endoscopy techniques including dye-based high-resolution and dye... Show moreThis paper reporting on techniques for esophageal evaluation and imaging and drugs for esophageal disease includes commentaries on endoscopy techniques including dye-based high-resolution and dye-less high-definition endoscopy; the shift from CT to MRI guidance in tumor delineation for radiation therapy; the role of functional lumen imaging in measuring esophageal distensibility; electrical stimulation of the lower esophageal sphincter (LES) as an alternative to fundoduplication for treatment of gastroesophageal reflux disease (GERD); the morphological findings of reflux esophagitis and esophageal dysmotility on double-contrast esophagography; the value of videofluoroscopy in assessing protecting mechanisms in patients with chronic reflux or swallowing disorders; targeting visceral hypersensitivity in the treatment of refractory GERD; and the symptoms and treatments of nighttime reflux and nocturnal acid breakthrough (NAB). Show less
