The effect of radiation treatment of solid tumors on neutrophil infiltration and function: a systematic review.

Radiotherapy (RT) initiates a local and systemic immune response which can induce anti-tumor immunity and improve immunotherapy efficacy. Neutrophils are among the first immune cells that infiltrate tumors after RT and are suggested to be essential for the initial anti-tumor immune response. However, neutrophils in tumors are associated with poor outcomes and RT induced neutrophil infiltration could also change the composition of the tumor microenvironment (TME) in favor of tumor progression. To improve RT efficacy for cancer patients it is important to understand the interplay between RT and neutrophils. Here, we review the literature on how RT affects the infiltration and function of neutrophils in the TME of solid tumors, using both patients studies and preclinical murine in vivo models. In general, it was found that neutrophil levels increase and reach maximal levels in the first days after RT and can remain elevated up to three weeks. Most studies report an immunosuppressive role of neutrophils in the TME after RT, caused by upregulated expression of neutrophil indoleamine 2,3-dioxygenase 1 (IDO1) and arginase 1 (ARG1), as well as neutrophil extracellular trap (NET) formation. RT was also associated with increased reactive oxygen species (ROS) production by neutrophils, which can both improve and inhibit anti-tumor immunity. In addition, multiple murine models showed improved RT efficacy when depleting neutrophils, suggesting that neutrophils have a pro-tumor phenotype after RT. We conclude that the role of neutrophils should not be overlooked when developing RT strategies and requires further investigation in specific tumor types. In addition, neutrophils can possibly be exploited to enhance RT efficacy by combining RT with neutrophil-targeting therapies.

Recurrent disease detection after resection of pancreatic ductal adenocarcinoma using a recurrence-focused surveillance strategy (RADAR-PANC): protocol of an international randomized controlled trial according to the Trials within Cohorts design.

BACKGROUND: Disease recurrence remains one of the biggest concerns in patients after resection of pancreatic ductal adenocarcinoma (PDAC). Despite (neo)adjuvant systemic therapy, most patients experience local and/or distant PDAC recurrence within 2 years. High-level evidence regarding the benefits of recurrence-focused surveillance after PDAC resection is missing, and the impact of early detection and treatment of recurrence on survival and quality of life is unknown. In most European countries, recurrence-focused follow-up after surgery for PDAC is currently lacking. Consequently, guidelines regarding postoperative surveillance are based on expert opinion and other low-level evidence. The recent emergence of more potent local and systemic treatment options for PDAC recurrence has increased interest in early diagnosis. To determine whether early detection and treatment of recurrence can lead to improved survival and quality of life, we designed an international randomized trial. METHODS: This randomized controlled trial is nested within an existing prospective cohort in pancreatic cancer centers in the Netherlands (Dutch Pancreatic Cancer Project; PACAP) and the United Kingdom (UK) (Pancreas Cancer: Observations of Practice and survival; PACOPS) according to the "Trials within Cohorts" (TwiCs) design. All PACAP/PACOPS participants with a macroscopically radical resection (R0-R1) of histologically confirmed PDAC, who provided informed consent for TwiCs and participation in quality of life questionnaires, are included. Participants randomized to the intervention arm are offered recurrence-focused surveillance, existing of clinical evaluation, serum cancer antigen (CA) 19-9 testing, and contrast-enhanced computed tomography (CT) of chest and abdomen every three months during the first 2 years after surgery. Participants in the control arm of the study will undergo non-standardized clinical follow-up, generally consisting of clinical follow-up with imaging and serum tumor marker testing only in case of onset of symptoms, according to local practice in the participating hospital. The primary endpoint is overall survival. Secondary endpoints include quality of life, patterns of recurrence, compliance to and costs of recurrence-focused follow-up, and the impact on recurrence-focused treatment. DISCUSSION: The RADAR-PANC trial will be the first randomized controlled trial to generate high level evidence for the current clinical equipoise regarding the value of recurrence-focused postoperative surveillance with serial tumor marker testing and routine imaging in patients after PDAC resection. The Trials within Cohort design allows us to study the acceptability of recurrence-focused surveillance among cohort participants and increases the generalizability of findings to the general population. While it is strongly encouraged to offer all trial participants treatment at time of recurrence diagnosis, type and timing of treatment will be determined through shared decision-making. This might reduce the potential survival benefits of recurrence-focused surveillance, although insights into the impact on patients' quality of life will be obtained. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04875325 . Registered on May 6, 2021.

Do dental implants facilitate bone invasion in patients with oral squamous cell carcinoma? A case series.

Osseointegrated dental implants in the vicinity of oral squamous cell carcinoma (OSCC) will become more common given the increasing popularity of dental implants. Reports and studies of OSCC around dental implants are rare, as is the topic of how to handle OSCC surgically when implants are in contact with the tumour. In view of this uncertainty, a histological study was performed to assess tumour behaviour around implants. The aim was to determine whether an implant facilitates inward growth of the tumour and how this should be taken into account during staging and treatment planning. A total of 20 specimens were collected. The implants were macroscopically in contact with OSCC in 13 of the 20 specimens. Histologically, tumour tissue near the implant was indeed confirmed in nine of these cases. In seven cases, tumour invasion had led to resorption of the underlying jaw bone; tumour between the bone-implant interface was identified in only two of these cases, but without downward growth along the implant. In conclusion, no proof was found to confirm that the bone-implant interface is a preferred route for invasion. Therefore, dental implants in the vicinity of OSCC should not influence staging and treatment planning in this regard.

A nationwide randomized controlled trial on additional treatment for isolated local pancreatic cancer recurrence using stereotactic body radiation therapy (ARCADE).

BACKGROUND: Disease recurrence is the main cause of mortality after resection of pancreatic ductal adenocarcinoma (PDAC). In 20-30% of resected patients, isolated local PDAC recurrence occurs. Retrospective studies have suggested that stereotactic body radiation therapy (SBRT) might lead to improved local control in these patients, potentially having a beneficial effect on both survival and quality of life. The "nationwide randomized controlled trial on additional treatment for isolated local pancreatic cancer recurrence using stereotactic body radiation therapy" (ARCADE) will investigate the value of SBRT in addition to standard of care in patients with isolated local PDAC recurrence compared to standard of care alone, regarding both survival and quality of life outcomes. METHODS: The ARCADE trial is nested within a prospective cohort (Dutch Pancreatic Cancer Project; PACAP) according to the 'Trials within Cohorts' design. All PACAP participants with isolated local PDAC recurrence after primary resection who provided informed consent for being randomized in future studies are eligible. Patients will be randomized for local therapy (5 fractions of 8 Gy SBRT) in addition to standard of care or standard of care alone. In total, 174 patients will be included. The main study endpoint is survival after recurrence. The most important secondary endpoint is quality of life. DISCUSSION: It is hypothesized that additional SBRT, compared to standard of care alone, improves survival and quality of life in patients with isolated local recurrence after PDAC resection. TRIAL REGISTRATION: ClinicalTrials.gov registration NCT04881487 . Registered on May 11, 2021.

Clinical implementation and feasibility of long-course fractionated MR-guided chemoradiotherapy for patients with esophageal cancer: An R-IDEAL stage 1b/2a evaluation of technical innovation.

Purpose: This R-Ideal stage 1b/2a study describes the workflow and feasibility of long-course fractionated online adaptive MR-guided chemoradiotherapy with reduced CTV-to-PTV margins on the 1.5T MR-Linac for patients with esophageal cancer. Methods: Patients with esophageal cancer scheduled to undergo chemoradiation were treated on a 1.5T MR-Linac. Daily MR-images were acquired for online contour adaptation and replanning. Contours were manually adapted to match the daily anatomy and an isotropic CTV-to-PTV margin of 6 mm was applied. Time was recorded for all individual steps in the workflow. Feasibility and patient tolerability were defined as on-table time of ≤60 min and completion of >95% of the fractions on the MR-Linac, respectively. Positioning verification and post-treatment MRIs were retrospectively analyzed and dosimetric parameters were compared to standard non-adaptive conventional treatment plans. Results: Nine patients with esophageal cancer were treated with chemoradiation; eight patients received 41.4 Gy in 23 fractions and one received 50.4 Gy in 28 fractions. Four patients received all planned fractions on the MR-Linac, whereas for two patients >5% of fractions were rescheduled to a conventional linac for reasons of discomfort. A total of 183 (86%) of 212 scheduled fractions were successfully delivered on the MR-Linac. Three fractions ended prematurely due to technical issues and 26 fractions were rescheduled on a conventional linac due to MR-Linac downtime (n = 10), logistical reasons (n = 3) or discomfort (n = 13).The median time per fraction was 53 min (IQR = 3 min). Daily adapted MR-Linac plans had similar target coverage, whereas dose to the organs-at-risk was significantly reduced compared to conventional treatment (26% and 12% reduction in mean lung and heart dose, respectively). Conclusion: Daily online adaptive fractionated chemoradiotherapy with reduced PTV margins is moderately feasible for esophageal cancer and results in better sparing of heart and lungs. Future studies should focus on further optimization and acceleration of the current workflow.

[Reconstruction after facial trauma with dento-alveolar injury]. / Reconstructie na aangezichtstrauma met dentoalveolair letsel.

While abroad, a healthy 36-year-old woman slammed head-on into a rock wall at high speed, resulting in significant facial trauma. The initial trauma care and first aid took place abroad. In the Netherlands, the woman was referred to the Department of Oral and Maxillofacial Surgery (OMFS) for reconstruction of her face and alveolar processes, gingiva and dentition. In view of the seriousness of the injuries, a 3D treatment plan was drawn up in a multidisciplinary collaboration with an OMF surgeon, an implantologist, dentist and dental technician. By making a digital setup of both the top and bottom front in advance, it was possible to work predictably. The first step consisted of bone augmentation by means of an iliac crest graft to reconstruct the major bone defects of the superior and inferior alveolar processes. Implants were then placed in the upper and lower jaws in the ideal position for the suprastructure by means of drill jigs. Within 10 months after the trauma, the implant bridges could be placed on individual zirconia frameworks to optimally restore oral function and aesthetics, completing the reconstruction.

CTV-to-PTV margin assessment for esophageal cancer radiotherapy based on an accumulated dose analysis.

PURPOSE: This study aimed to assess the smallest clinical target volume (CTV) to planned target volume (PTV) margins for esophageal cancer radiotherapy using daily online registration to the bony anatomy that yield full dosimetric coverage over the course of treatment. METHODS: 29 esophageal cancer patients underwent six T2-weighted MRI scans at weekly intervals. An online bone-match image-guided radiotherapy treatment of five fractions was simulated for each patient. Multiple conformal treatment plans with increasing margins around the CTV were created for each patient. Then, the dose was warped to obtain an accumulated dose per simulated fraction. Full target coverage by 95% of the prescribed dose was assessed as a function of margin expansion in six directions. If target coverage in a single direction was accomplished, then the respective margin remained fixed for the subsequent dose plans. Margins in uncovered directions were increased in a new dose plan until full target coverage was achieved. RESULTS: The smallest set of CTV-to-PTV margins that yielded full dosimetric CTV coverage was 8 mm in posterior and right direction, 9 mm in anterior and cranial direction and 10 mm in left and caudal direction for 27 out of 29 patients. In two patients the curvature of the esophagus considerably changed between fractions, which required a 17 and 23 mm margin in right direction. CONCLUSION: Accumulated dose analysis revealed that CTV-to-PTV treatment margins of 8, 9 and 10 mm in posterior & right, anterior & cranial and left & caudal direction, respectively, are sufficient to account for interfraction tumor variations over the course of treatment when applying a daily online bone match. However, two patients with extreme esophageal interfraction motion were insufficiently covered with these margins and were identified as patients requiring replanning to achieve full target coverage.

Immediate implant placement in edentulous oral cancer patients: a long-term retrospective analysis of 207 patients.

Although the functional benefits of implants in the rehabilitation of edentulous cancer patients are well-known, most studies report on postponed implant placement. The outcome of immediate implant placement regarding successful rehabilitation, implant loading and survival is unclear. Two hundred and seven edentulous oral cancer patients that received implants during ablative surgery at the Radboud University Medical Centre between 2000 and 2011 were included. Data regarding the oncological treatment, implant placement, follow-up and prosthodontic rehabilitation were recorded retrospectively with a follow-up period of 5-17 years. Functioning implant-retained dentures were made in 73.9% of the patients. Of the surviving patients, 81.9% had functioning dentures after 2 years and 86.3% after 10 years. Patients with ASA score 1 and younger patients were rehabilitated more frequently. The median time of functioning denture placement was 336 days after surgery, with a negative influence of postoperative radiotherapy. Implant survival was 90.7%, and was lower when the implant was placed in a jaw involved in the tumour. Immediate implant placement during oral cancer surgery led to a high number of edentulous patients rehabilitated with implant-retained dentures, which are placed at an early time.

Vertical bone augmentation and regular implants versus short implants in the vertically deficient posterior mandible: a systematic review and meta-analysis of randomized studies.

The aim of this study was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the outcomes of short dental implants (≤7mm) versus vertical bone augmentation followed by regular dental implants (>7mm) in the deficient posterior mandible. In total, eight RCTs (six using interpositional sandwich grafting and two using a guided bone regeneration technique) were reported in 17 articles at different time points. In the meta-analysis of the sandwich group, the relative risk (RR) for implant loss at 1year was in favour of short implants (RR 0.41, P=0.02), while no significant difference was found at 3 years (RR 0.65, P=0.43), 5 years (RR 1.08, P=0.86), or 8 years (RR 1.53, P=0.52). The risk of complications was in favour of short implants (RR 0.34, P=0.0002), as was the mean difference in marginal bone resorption after 1 year (-0.09mm, P=0.17), 3 years (-0.32mm, P<0.00001), 5 years (-0.65mm, P<0.00001), and 8 years (-0.88, P<0.00001). The mean residual osseointegration length of the implants was between 2.94mm and 4.44mm in the short implants group and between 7.97mm and 8.62mm in the regular implants group after 5 years. In conclusion, in the deficient atrophic posterior mandible, short implants and regular implants demonstrate comparable outcomes within the first 5 years. Patients who are fit for surgery should be informed about the risks and benefits of both options.

Salvage Robot-Assisted Minimally Invasive Esophagectomy (RAMIE) for T4b Esophageal Cancer After Definitive Chemoradiotherapy.

BACKGROUND: Patients  with esophageal cancer  that invades adjacent structures (cT4b) are precluded from surgery and usually treated with definitive chemoradiotherapy (dCRT). dCRT might result in sufficient downstaging to enable a radical resection, possibly improving survival. This study aimed to assess the perioperative and oncologic outcomes of a salvage robot-assisted minimally invasive esophagectomy (RAMIE) in patients with cT4b esophageal cancer after dCRT. METHODS: Between June 2012 and November 2019, patients who underwent a RAMIE with a gastric conduit reconstruction after completion of dCRT for cT4b esophageal carcinoma were identified from a prospectively maintained surgical database at the University Medical Center Utrecht. RESULTS: In total, 24 patients with a histopathologically confirmed T4b adenocarcinoma or squamous cell carcinoma of the esophagus were included. The adjacent organs involved were the tracheobronchial tree (67%), aorta (21%) or both (13%). No conversions or major intraoperative complications were observed. A radical resection was achieved in 22 patients (92%), and a pathologic complete response was observed in 13 (54%) patients. Postoperative grade 2 or higher complications occurred in 20 patients (83%). The disease-free survival at 24 months was 68% for the patients in whom a radical resection was achieved. CONCLUSION: In patients with cT4b esophageal cancer treated with dCRT followed by a salvage RAMIE, a radical resection rate of 92% was achieved, with acceptable complications and promising survival rates. These results demonstrate the feasibility of a curative surgical treatment for patients with initially irresectable esophageal cancer but underscore the importance of a proper preoperative patient selection.

Does hyperbaric oxygen therapy play a role in the management of osteoradionecrosis? A survey of Dutch oral and maxillofacial surgeons.

For decades, hyperbaric oxygen (HBO) has often been part of the treatment of osteoradionecrosis (ORN), despite controversy in the literature about its efficacy. An online survey was conducted to investigate the use of HBO in the treatment of ORN by Dutch oral and maxillofacial surgeons and to assess their perception of its efficacy. Of the 53 Dutch oral and maxillofacial surgery units contacted, 49 (92%) replied. Thirty-five were not head and neck cancer (HNC) units or preferred partner (PP-HNC) units recognized by the Dutch Head and Neck Association. All HNC and PP-HNC units (group 1) treated ORN patients, compared to only 12 (34%) of the non-HNC units (group 2). The average number of ORN patients seen and treated was higher in group 1. The units in group 1 more often referred patients for HBO therapy (HBOT) than those in group 2 (93% vs 84%). The efficacy of HBOT in curing ORN, rated on a scale of 1 to 5 points, was 3.7 in group 1 and 3.2 in group 2. This survey shows a trend towards centralization of ORN care to more experienced units. These units tend to use HBOT in curing ORN.

[Factors contributing to a delay in the diagnostic process in oral cancer]. / Factoren die bijdragen aan het delay in het diagnostisch proces van een mondholtetumor.

In patients with a new squamous cell carcinoma in the oral cavity, factors were investigated that determine the time interval between the occurrence of the first symptoms, the diagnosis and the start of treatment. Status research was conducted on 87 patients who were diagnosed in 2017 at the department of Oral and Maxillofacial Surgery at the Radboud university medical centre (Radboudumc), Nijmegen, the Netherlands. Patients were asked about the length of time between the appearance of the first symptoms and their visit to the dentist or general practioner. Especially patients who were not registered with a dentist waited on average 2 months longer, the most important reasons being that they thought it would solve itself and treatment anxiety. It was concluded that in the case of a squamous cell carcinoma, patients who are not registered with a dentist, are more often toothless and present later with a larger tumour than patients registered with a dentist. Training on recognising the first symptoms of squamous cell carcinomas in the oral cavity should be intensified among dentists and also general practitioners, dental hygienists and dental prosthetic technicians.

3-Dimensional target coverage assessment for MRI guided esophageal cancer radiotherapy.

PURPOSE: This study aimed to quantify the coverage probability for esophageal cancer radiotherapy as a function of a preset margin for online MR-guided and (CB)CT-guided radiotherapy. METHODS: Thirty esophageal cancer patients underwent six T2-weighted MRI scans, 1 prior to treatment and 5 during neoadjuvant chemoradiotherapy at weekly intervals. Gross tumor volume (GTV) and clinical target volume (CTV) were delineated on each individual scan. Follow-up scans were rigidly aligned to the bony anatomy and to the clinical target volume itself, mimicking two online set-up correction strategies: a conventional CBCT-guided set-up and a MR-guided set-up, respectively. Geometric coverage probability of the propagated CTVs was assessed for both set-up strategies by expanding the reference CTV with an isotropic margin varying from 0 mm to 15 mm with an increment of 1 mm. RESULTS: A margin of 10 mm could resolve the interfractional changes for 118 out of the 132 (89%) analyzed fractions when applying a bone-match registration, whereas the CTV was adequately covered in 123 (93%) fractions when the registration was directly performed at the CTV itself (soft-tissue registration). Closer analyses revealed that target coverage violation predominantly occurred for distal tumors near the junction and into the cardia. CONCLUSION: Online MR-guided soft-tissue registration protocols exhibited modest improvements of the geometric target coverage probability as compared to online CBCT-guided bone match protocols. Therefore, highly conformal target irradiation using online MR-guidance can only be achieved by implementing on-table adaptive workflows where new treatment plans are daily generated based on the anatomy of the day.

Autologous versus prosthetic nasal and auricular reconstruction - patient, professional and layperson perceptions.

The aim of this study was to retrospectively evaluate the perceptions of aesthetic outcome following the autologous and prosthetic reconstruction of nasal and auricular defects among patients, professionals (oral and maxillofacial surgeons and ear, nose and throat surgeons) and people unfamiliar with reconstructive surgery. The influence of anatomical subunits on the overall perception of nasal and auricular reconstructions was also determined. A total of 119 patients treated for nasal and auricular defects between 1997 and 2016, with a minimum follow-up period of 6 months, were selected, and photographs of 77 of these patients (65%) were presented in a digital survey and reviewed using a standardized questionnaire. No clinically relevant correlations were found between the age or gender of patients (as well as those of the respondents) and their scores. Prosthetic reconstructions of nasal and auricular defects were considered advantageous over autologous reconstructions in terms of the subjective aesthetic outcome in the view of the professionals, in particular oral and maxillofacial surgeons; however, the patients judged both techniques to be equally effective in terms of aesthetics. No anatomical subunits were found to have a significant impact on the overall match of a nasal or auricular reconstruction with the patient's face.

[Antibiotic prophylaxis and (pre-)dental implant surgery]. / AB-profylaxe en (pre)implantologische chirurgie.

Recent literature indicates that in a healthy patient, who has sufficient bone volume to allow implant placement, it is justified to refrain from prophylactic administration of antibiotics. The patient should, however, rinse with chlorhexidine digluconate 1 day prior to treatment and at least 1 week postoperatively. In the case of an immune-compromised patient, a single antibiotic gift is indicated 1 hour before the procedure (2 grams of amoxicillin orally or 2 grams of cefazoline intravenously). In the case of a healthy patient, antibiotic (AB) prophylaxis is also indicated if autologous bone, a bone filler or membranes are applied. Although AB prophylaxis is not necessary when harvesting extraoral bone grafts, it is indicated because the harvested bone is applied intraorally in the same treatment session. The question whether postoperative administration of antibiotics is still needed remains open.

Reliability and accuracy of cone beam computed tomography versus conventional multidetector computed tomography for image-guided craniofacial implant planning: An in vitro study.

PURPOSE: To assess the reliability and accuracy of linear measurements on three-dimensional (3D) cross-sectional images, both acquired with cone beam computed tomography (CBCT) and multi-detector row CT (MDCT). Bone thickness was evaluated with regard to image-guided planning of craniofacial implant surgery. MATERIALS AND METHODS: Five dry human skulls were used. Cuts were made with a circular bone saw at the ideal implant positions in the nasal, orbital, and temporal regions prior to acquisition of CBCT and MDCT scans. After imaging examination, bone width was assessed by three independent observers using a caliper and defined as a reference. In the next step, cross-sectional images of the regions with the aforementioned cuts were reconstructed from 3D virtual models generated from the digital DICOM datasets with the use of 3D image-based planning software. Subsequently, linear measurements were performed. The systematic difference and interobserver and intraobserver variation of MDCT and CBCT linear measurements were compared with the physical measurements at different locations in the nasal, orbital, and temporal region, respectively. Also, the potential influence of different gray-level values was investigated. The quantitative accuracy of distance measurements was performed using a two-way analysis of variance (ANOVA) and variance component analyses. Only differences with P values < .05 were considered significant. RESULTS: All radiologic measurements showed a significant overestimation of the bony dimensions, reaching more than the used voxel sizes of 0.3 mm for CBCT and 0.5 mm for MDCT. For CBCT, an average measurement bias of 0.39 to 0.53 mm and for MDCT of 0.57 to 0.59 mm was found. MDCT images showed less interobserver variation in linear measurements on cross-sectional images from 3D virtual models compared with CBCT images. Contrast settings statistically significantly influenced linear measurements of bone width for CBCT images (P < .0015) and interobserver variation on MDCT imaging (P < .029). CONCLUSION: Both CBCT images (KaVo 3D eXam Imaging System) and MDCT images (Aquilion ONE, Toshiba) showed a highly consistent submillimeter overestimation of the anatomical truth in assessing bone thickness of nasal, orbital, and temporal regions of ex vivo specimens. When using CBCT and MDCT images for presurgical assessment, one should be aware of the overestimation of the cortical bone thickness.

Reliability and accuracy of skin-supported surgical templates for computer-planned craniofacial implant placement, a comparison between surgical templates: With and without bony fixation.

INTRODUCTION: The purpose is to determine the accuracy of guided implant placement in the orbital, nasal, and auricular region using computer-aided designed stereolithographic skin-supported surgical templates with and without bone fixation pins. MATERIALS AND METHODS: Preoperatively, cone-beam CT (CBCT) and multiple detector computed tomography (MDCT) scans were acquired from 10 cadaver heads, followed by virtual planning of implants in the orbital margin, auricular region and nasal floor. Surgical skin-supported templates were digitally designed to allow flapless implant placement. Fixation pins were used for stabilization comprising half of all templates in predetermined bone areas. The accuracy of the surgical templates was validated by comparing the achieved implant location to its virtual planned implant position by calculating the linear and angular deviations. RESULTS: Surgical templates with the use of bone fixation pins produced statistically significant greater implant deviations as compared to the non-fixated surgical templates. CONCLUSION: The results of this study indicate that significant deviation has to be taken into account when placing cranio-maxillofacial implants using skin-supported surgical templates. Surprisingly, the use of bone-fixated pins worsened the accuracy.

Diagnostic performance of MRI for assessment of response to neoadjuvant chemoradiotherapy in oesophageal cancer.

BACKGROUND: Patients with a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer may benefit from non-surgical management. The aim of this study was to determine the diagnostic performance of visual response assessment of the primary tumour after nCRT on T2-weighted (T2W) and diffusion-weighted (DW) MRI. METHODS: Patients with locally advanced oesophageal cancer who underwent T2W- and DW-MRI (1·5 T) before and after nCRT in two hospitals, between July 2013 and September 2017, were included in this prospective study. Three radiologists evaluated T2W images retrospectively using a five-point score for the assessment of residual tumour in a blinded manner and immediately rescored after adding DW-MRI. Histopathology of the resection specimen was used as the reference standard; ypT0 represented a pCR. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve (AUC) and interobserver agreement were calculated. RESULTS: Twelve of 51 patients (24 per cent) had a pCR. The sensitivity and specificity of T2W-MRI for detection of residual tumour ranged from 90 to 100 and 8 to 25 per cent respectively. Respective values for T2W + DW-MRI were 90-97 and 42-50 per cent. AUCs for the three readers were 0·65, 0·66 and 0·68 on T2W-MRI, and 0·71, 0·70 and 0·70 on T2W + DW-MRI (P = 0·441, P = 0·611 and P = 0·828 for readers 1, 2 and 3 respectively). The κ value for interobserver agreement improved from 0·24-0·55 on T2W-MRI to 0·55-0·71 with DW-MRI. CONCLUSION: Preoperative assessment of residual tumour on MRI after nCRT for oesophageal cancer is feasible with high sensitivity, reflecting a low chance of missing residual tumour. However, the specificity was low; this results in overstaging of complete responders as having residual tumour and, consequently, overtreatment.